1 00:00:10,603 --> 00:00:12,238 >> I WANTED TO WELCOME ALL OF 2 00:00:12,238 --> 00:00:14,140 YOU HERE AND OPENING REMARKS 3 00:00:14,140 --> 00:00:18,611 WILL BE GIVEN BY DR. WALTER 4 00:00:18,611 --> 00:00:20,413 KOROSHETZ WHO IS THE DIRECTOR OF 5 00:00:20,413 --> 00:00:23,349 THE NATIONAL INSTITUTES OF 6 00:00:23,349 --> 00:00:24,451 NEUROLOGICAL DISORDERS AND 7 00:00:24,451 --> 00:00:30,290 STROKE AND HAS BEEN A STAUNCH 8 00:00:30,290 --> 00:00:31,925 SUPPORTER IN ME/CFS OVER THE 9 00:00:31,925 --> 00:00:33,293 YEARS AND WITHOUT HIS HELP THIS 10 00:00:33,293 --> 00:00:34,627 WOULD NOT BE POSSIBLE AT ALL. 11 00:00:34,627 --> 00:00:35,695 THANK YOU, DR. KOROSHETZ FOR 12 00:00:35,695 --> 00:00:46,139 COMING AND ADDRESSING US. 13 00:00:50,632 --> 00:00:53,868 >> THANKS, EVERYONE WHO'S HERE AND LISTENING IN. 14 00:00:53,868 --> 00:00:58,573 I'M THE DIRECTOR OF NNDS AND WE 15 00:00:58,573 --> 00:01:01,976 HAVE BEEN WORKING WITH OUR OTHER 16 00:01:01,976 --> 00:01:04,512 INSTITUTES PRIMARILY NIAID AND 17 00:01:04,512 --> 00:01:06,915 FOR A NUMBER OF DECADES AND 18 00:01:06,915 --> 00:01:10,218 TRYING TO UNDERSTAND THE BIOLOGY 19 00:01:10,218 --> 00:01:12,186 AND THEN IN ME/CFS AND TRYING TO 20 00:01:12,186 --> 00:01:13,254 DEVELOP TREATMENTS. 21 00:01:13,254 --> 00:01:15,757 I THINK WE ALL SHARE IN THE 22 00:01:15,757 --> 00:01:17,292 GENERAL FRUSTRATION AROUND THE 23 00:01:17,292 --> 00:01:20,495 WORLD THAT THIS IS GOING WAY TOO 24 00:01:20,495 --> 00:01:20,728 SLOW. 25 00:01:20,728 --> 00:01:21,429 THERE'S TOO MUCH SUFFERING GOING 26 00:01:21,429 --> 00:01:24,565 ON AND WE DON'T HAVE ANSWERS FOR 27 00:01:24,565 --> 00:01:27,135 PEOPLE AND SO I'M REALLY PROUD 28 00:01:27,135 --> 00:01:31,673 OF THE WORK DONE HERE BY BRIAN 29 00:01:31,673 --> 00:01:36,744 WALITT AND ABBY NATH AND TRYING 30 00:01:36,744 --> 00:01:40,181 TO LOOK AT PEOPLE WHO HAVE 31 00:01:40,181 --> 00:01:41,249 ME/CFS USING RESOURCES HERE THAT 32 00:01:41,249 --> 00:01:42,617 ARE UNIQUE AND THEY TOOK 33 00:01:42,617 --> 00:01:47,622 ADVANTAGE OF THAT AND I HOPE 34 00:01:47,622 --> 00:01:48,890 THAT FOLKS CAN GET A SENSE OF 35 00:01:48,890 --> 00:01:50,858 WHAT THEY FOUND AND TRY TO PUT 36 00:01:50,858 --> 00:01:52,427 THEM IN THE RIGHT CONTEXT. 37 00:01:52,427 --> 00:01:55,296 I WOULD SAY THAT THIS ARTICLE 38 00:01:55,296 --> 00:01:58,833 THAT CAME OUT SAYING THAT WE 39 00:01:58,833 --> 00:02:01,269 FINALLY KNOW WHAT DRIVES CHRONIC 40 00:02:01,269 --> 00:02:03,538 FATIGUE ALONG COVID IS PROBABLY 41 00:02:03,538 --> 00:02:04,739 AN OVERSTATEMENT. 42 00:02:04,739 --> 00:02:07,408 YOU COULD BET HEAVILY IT'S AN 43 00:02:07,408 --> 00:02:07,742 OVERSTATEMENT. 44 00:02:07,742 --> 00:02:09,210 I THINK THE THINGS YOU'LL BE 45 00:02:09,210 --> 00:02:10,345 HEARING ABOUT TODAY AND THE 46 00:02:10,345 --> 00:02:12,714 SMALL NUMBER OF PATIENTS ARE 47 00:02:12,714 --> 00:02:15,917 VERY INTRIGUING. 48 00:02:15,917 --> 00:02:18,319 THEY'VE BEEN CLEARLY RIGOROUSLY 49 00:02:18,319 --> 00:02:20,521 STUDIED AND THE DATA IS AS 50 00:02:20,521 --> 00:02:21,756 PRISTINE AS YOU CAN GET BUT 51 00:02:21,756 --> 00:02:22,991 THERE'S LOTS OF QUESTION ARE 52 00:02:22,991 --> 00:02:24,459 GOING IT ARISE FROM THIS AND HOW 53 00:02:24,459 --> 00:02:26,027 IT ALL PANS OUT IN THE END I 54 00:02:26,027 --> 00:02:27,562 THINK IS WHAT WE HOPE WILL 55 00:02:27,562 --> 00:02:29,130 STIMULATE RESEARCH AROUND THE 56 00:02:29,130 --> 00:02:30,965 COUNTRY AND AROUND THE WORLD TO 57 00:02:30,965 --> 00:02:32,600 GET AT THE BOTTOM OF THIS 58 00:02:32,600 --> 00:02:34,669 PROBLEM. 59 00:02:34,669 --> 00:02:36,270 THERE IS A LOT MORE INTEREST IN 60 00:02:36,270 --> 00:02:38,506 THE PROBLEM NOW AND PROBABLY A 61 00:02:38,506 --> 00:02:43,478 LOT THAT COMES FROM THE FACT 62 00:02:43,478 --> 00:02:45,613 THAT ME/CFS IS A MAJOR CHRONIC 63 00:02:45,613 --> 00:02:47,915 ILLNESS THAT OCCURS AFTER COVID 64 00:02:47,915 --> 00:02:50,318 INFECTIONS WHICH OCCURRED IN 65 00:02:50,318 --> 00:02:52,153 MILLIONS IN HUNDREDS OF MILLIONS 66 00:02:52,153 --> 00:02:53,721 OF PEOPLE AROUND THE WORLD. 67 00:02:53,721 --> 00:02:57,025 SO THE PROBLEM HAS JUST BEEN 68 00:02:57,025 --> 00:02:58,860 MAGNIFYFIDE AND UNFORTUNATELY 69 00:02:58,860 --> 00:03:01,295 OUR IGNORANCE IS ALSO MAGNIFIED. 70 00:03:01,295 --> 00:03:06,567 THERE WAS A NATIONAL ACADEMY A 71 00:03:06,567 --> 00:03:08,669 REPORT ON ASSOCIATION OF CHRONIC 72 00:03:08,669 --> 00:03:08,936 ILLNESSES. 73 00:03:08,936 --> 00:03:11,406 THE HOPE IS IT WILL GAFF VANNIZE 74 00:03:11,406 --> 00:03:13,775 THE SCIENTIFIC COMMUNITY 75 00:03:13,775 --> 00:03:14,942 RETICENT TO STUDY ME/CFS TO MAKE 76 00:03:14,942 --> 00:03:17,345 A DIFFERENCE. 77 00:03:17,345 --> 00:03:19,614 ALSO, I'D SAY THAT WE'RE GOING 78 00:03:19,614 --> 00:03:22,350 TO BE TALKING IN NEUROLOGICAL 79 00:03:22,350 --> 00:03:23,484 TERMS A LOT OF THE TIME HERE AND 80 00:03:23,484 --> 00:03:25,620 SO I THINK THAT MAY BE SOMETHING 81 00:03:25,620 --> 00:03:29,424 NEW TO PEOPLE. 82 00:03:29,424 --> 00:03:30,725 AND I'LL TALK ABOUT TERMINOLOGY 83 00:03:30,725 --> 00:03:34,962 IN A SECOND BUT JUST TO SAY THAT 84 00:03:34,962 --> 00:03:39,534 THE BIOLOGY OF FATIGUE IS POORLY 85 00:03:39,534 --> 00:03:43,204 UNDERSTAND AS A GENERAL CONCEPT 86 00:03:43,204 --> 00:03:44,238 AND INHERENTLY IN IMPORTANT IN 87 00:03:44,238 --> 00:03:46,074 EVERYTHING WE DO IN EVERY 88 00:03:46,074 --> 00:03:47,075 SECOND, EVERY MICROSECOND 89 00:03:47,075 --> 00:03:48,709 THERE'S A CALCULATION GOING ON 90 00:03:48,709 --> 00:03:51,646 IN OUR BRAIN ON WHAT IS THE 91 00:03:51,646 --> 00:03:53,214 REWARD EFFORT MATCH AND TRYING 92 00:03:53,214 --> 00:03:54,482 TO UNDERSTAND THE BIOLOGY OF 93 00:03:54,482 --> 00:03:59,620 FATIGUE WHICH OCCURS CAN IN SO 94 00:03:59,620 --> 00:04:00,755 MANY CONDITIONS WAS THE SUBJECT 95 00:04:00,755 --> 00:04:05,259 OF A GROUP COMING FROM THE 96 00:04:05,259 --> 00:04:06,694 BLUEPRINT AND PUBLISHED THIS 97 00:04:06,694 --> 00:04:07,962 PAPER IN GROUP RESEARCH SOCIETY. 98 00:04:07,962 --> 00:04:11,232 THERE'S CLEARLY AS I MENTIONED A 99 00:04:11,232 --> 00:04:14,769 BIGGER EMPHASIS IN THE PROBLEM 100 00:04:14,769 --> 00:04:16,737 GIVEN THE COVID PANDEMIC AND 101 00:04:16,737 --> 00:04:18,439 ME/CFS COMING ON AS A CHRONIC 102 00:04:18,439 --> 00:04:24,679 COMPLICATION OF COVID. 103 00:04:24,679 --> 00:04:26,614 THERE'S WORK GOING ON TO UNRAVEL 104 00:04:26,614 --> 00:04:28,583 THE TWO CONDITIONS 105 00:04:28,583 --> 00:04:28,950 SIMULTANEOUSLY. 106 00:04:28,950 --> 00:04:31,719 THERE MAY BE SOME DIFFERENCES 107 00:04:31,719 --> 00:04:34,555 BUT WE PERSPECTIVE THERE'S WAY 108 00:04:34,555 --> 00:04:37,158 MORE IN COMMON THAN DIFFERENCES. 109 00:04:37,158 --> 00:04:42,563 OF NOTE THE NINDS HAS BEEN 110 00:04:42,563 --> 00:04:45,800 WORKING TO DEVELOP A RESEARCH 111 00:04:45,800 --> 00:04:47,201 ROAD MAP FOR ME/CFS RESEARCH 112 00:04:47,201 --> 00:04:50,605 THAT WE HOPE WILL ALSO BE ABLE 113 00:04:50,605 --> 00:04:52,340 TO GIVE SOME GUIDANCE TO 114 00:04:52,340 --> 00:04:53,875 SCIENTISTS AROUND THE WORLD ON 115 00:04:53,875 --> 00:04:55,576 WHAT THE CURRENT STATE OF 116 00:04:55,576 --> 00:04:58,045 AFFAIRS ARE AND WHAT THINGS LOOK 117 00:04:58,045 --> 00:04:59,213 LIKE THEY'RE WORTH MOVING INTO. 118 00:04:59,213 --> 00:05:00,882 I WOULD SAY A LOT OF THE RESULTS 119 00:05:00,882 --> 00:05:03,017 YOU'LL HEAR ABOUT TODAY CAME OUT 120 00:05:03,017 --> 00:05:05,887 AFTER THAT SO THESE ARE GOING TO 121 00:05:05,887 --> 00:05:07,989 BE WHAT YOU'LL HEAR ABOUT IS 122 00:05:07,989 --> 00:05:09,690 ADDITIONAL STUFF. 123 00:05:09,690 --> 00:05:13,661 I WANTED TO SAY THAT THE EFFORT 124 00:05:13,661 --> 00:05:16,731 HERE AVI NATH AND BRIAN WALITT 125 00:05:16,731 --> 00:05:18,966 HAVE BEEN WORK ON IS LOOKING AT 126 00:05:18,966 --> 00:05:20,501 THE GENERAL PROBLEM. 127 00:05:20,501 --> 00:05:22,470 YOU'LL HEAR ABOUT THE ME/CFS 128 00:05:22,470 --> 00:05:24,105 STUDY AND STUDIED LONG COVID 129 00:05:24,105 --> 00:05:28,176 PATIENTS WITH SIMILAR TESTING 130 00:05:28,176 --> 00:05:29,610 AND TO BE ABLE TO COMPARE 131 00:05:29,610 --> 00:05:32,713 RESULTS AND ALSO HAVE PROJECT 132 00:05:32,713 --> 00:05:35,850 GOING ON ONE THE VETERANS 133 00:05:35,850 --> 00:05:38,853 ADMINISTRATION WHERE THERE'S 134 00:05:38,853 --> 00:05:41,455 SIGNIFICANT OVERLAP IN ISSUES. 135 00:05:41,455 --> 00:05:44,725 THE ROAD MAP WILL BE PRESENTED 136 00:05:44,725 --> 00:05:48,496 AT OUR COUNCIL DURING THE OPEN 137 00:05:48,496 --> 00:05:49,964 SESSION OF OUR NINDS SESSION. 138 00:05:49,964 --> 00:05:52,633 PEOPLE, PLEASE ZOOM IN FOR THAT. 139 00:05:52,633 --> 00:05:54,335 THEY'RE LOOKING AT A BUNCH OF 140 00:05:54,335 --> 00:05:56,604 DIFFERENT SYSTEMS AND DATA 141 00:05:56,604 --> 00:05:58,472 COMING OUT OF ALL COUNTRIES, 142 00:05:58,472 --> 00:06:01,475 DIFFERENT TYPES OF LABS AND 143 00:06:01,475 --> 00:06:03,744 TRYING TO SYNTHESIZE BEST THEY 144 00:06:03,744 --> 00:06:03,911 CAN. 145 00:06:03,911 --> 00:06:05,980 BUT PUTTING IT ALL TOGETHER HAS 146 00:06:05,980 --> 00:06:07,448 BEEN A PROBLEM. 147 00:06:07,448 --> 00:06:08,749 HOPEFULLY THIS WILL STIMULATE 148 00:06:08,749 --> 00:06:11,686 MORE WORK IN THE AREA. 149 00:06:11,686 --> 00:06:13,921 THEY LOOKED AT MULTIPLE WEBINAR 150 00:06:13,921 --> 00:06:15,523 TO DEVELOP THE ROAD MAP AND ALL 151 00:06:15,523 --> 00:06:16,524 THESE DIFFERENT SYSTEMS AND CAME 152 00:06:16,524 --> 00:06:20,728 UP WITH TARGETS TO LOOK AT AS 153 00:06:20,728 --> 00:06:22,063 POTENTIAL DRIVERS. 154 00:06:22,063 --> 00:06:23,631 IN TERMS OF COVID, I HAVE HERE A 155 00:06:23,631 --> 00:06:23,931 SLIDE. 156 00:06:23,931 --> 00:06:26,133 THIS IS THE REPORT OF THE 157 00:06:26,133 --> 00:06:27,468 SYMPTOMS THAT ARE ASSOCIATED 158 00:06:27,468 --> 00:06:29,971 WITH LONG COVID COMING OUT VERY 159 00:06:29,971 --> 00:06:31,639 EARLY AFTER THE PANDEMIC OR 160 00:06:31,639 --> 00:06:33,007 ACTUALLY DURING THE PANDEMIC. 161 00:06:33,007 --> 00:06:36,310 AND YOU CAN SEE HOW IN YELLOW 162 00:06:36,310 --> 00:06:40,715 WHAT THE OVERLAP IS MANY OF THE 163 00:06:40,715 --> 00:06:44,418 SYSTEMS IN ME/CFS AND ACTUALLY 164 00:06:44,418 --> 00:06:46,954 POST EXERTION MALAISE IS THE 165 00:06:46,954 --> 00:06:48,222 SYMPTOM THAT IS THE MOST 166 00:06:48,222 --> 00:06:49,190 SPECIFIC FOR LONG COVID. 167 00:06:49,190 --> 00:06:54,395 THERE'S A LOT OF OVERLAP HERE. 168 00:06:54,395 --> 00:06:55,830 THE RECOVER INITIATIVE WHICH IS 169 00:06:55,830 --> 00:06:58,633 WELL FINANCED TO STUDY PEOPLE 170 00:06:58,633 --> 00:07:03,170 WITH LONG COVID, WE'RE TRYING TO 171 00:07:03,170 --> 00:07:05,172 UNDERSTAND THE PATHOBIOLOGY IN 172 00:07:05,172 --> 00:07:05,740 CLINICAL TRIALS. 173 00:07:05,740 --> 00:07:08,776 WE DON'T HAVE A LOT OF CLUES AS 174 00:07:08,776 --> 00:07:10,411 TO WHAT'S CAUSING IT YET BUT 175 00:07:10,411 --> 00:07:12,413 FOLLOWING UP ON THE PARTIAL 176 00:07:12,413 --> 00:07:16,717 CLUES WE HAVE AND TRYING TO TRY 177 00:07:16,717 --> 00:07:20,688 DIFFERENT SYMPTOMATIC THERAPIES 178 00:07:20,688 --> 00:07:23,190 WOULD BE TRIED IN PEOPLE WITH 179 00:07:23,190 --> 00:07:24,659 ME/CFS AND WORK GOING ON HERE 180 00:07:24,659 --> 00:07:26,093 AND MORE IMPORTANT THAN ANYTHING 181 00:07:26,093 --> 00:07:28,663 IS THERE'S THOUSANDS OF PEOPLE 182 00:07:28,663 --> 00:07:29,497 WORKING ON THIS PROBLEM. 183 00:07:29,497 --> 00:07:32,600 AND WHAT WE NEED TO DO IS TO 184 00:07:32,600 --> 00:07:34,568 HAVE THESE FOLKS REALIZE THE 185 00:07:34,568 --> 00:07:35,803 COMMONALITIES BETWEEN THESE IT 186 00:07:35,803 --> 00:07:37,305 DIFFERENT CONDITIONS AS DR. NATH 187 00:07:37,305 --> 00:07:40,708 AND HIS TEAM HAVE ALL ALONG. 188 00:07:40,708 --> 00:07:41,709 THAT WOULD BE GREAT MOVING IN 189 00:07:41,709 --> 00:07:48,949 THE FUTURE TO HAVE THIS ARMY 190 00:07:48,949 --> 00:07:51,052 WORK ING ON THE PROBLEMS MOST 191 00:07:51,052 --> 00:07:52,820 IMPORTANT TO PEOPLE WITH ME/CFS. 192 00:07:52,820 --> 00:07:56,724 I WANT TO SPEND TIME ON HOW 193 00:07:56,724 --> 00:07:59,226 NEUROLOGISTS THINK. 194 00:07:59,226 --> 00:08:01,362 WE'RE ALL PECULIAR PEOPLE YOU'LL 195 00:08:01,362 --> 00:08:02,229 FIND OUT MORE TODAY. 196 00:08:02,229 --> 00:08:03,331 WITH TRY TO THINK HOW THE BRAIN 197 00:08:03,331 --> 00:08:05,032 WORKS. 198 00:08:05,032 --> 00:08:07,168 AND THERE'S A NEUROLOGY TO 199 00:08:07,168 --> 00:08:07,468 EVERYTHING. 200 00:08:07,468 --> 00:08:11,138 THERE'S A NEUROLOGY TO WHY THIS 201 00:08:11,138 --> 00:08:12,807 GUY HERE IS MOVING HIS LEGS BACK 202 00:08:12,807 --> 00:08:15,142 AND FORTH AND WHY I JUST SMILED. 203 00:08:15,142 --> 00:08:17,845 IT'S EVERYTHING WE DO IS THROUGH 204 00:08:17,845 --> 00:08:26,220 THESE SECTOR CIRCUITS IN THE 205 00:08:26,220 --> 00:08:28,723 BRAIN AND THE CIRCUITS ARE NOT 206 00:08:28,723 --> 00:08:29,924 FUNCTIONAL IN ME/CFS AND TRYING 207 00:08:29,924 --> 00:08:31,125 TO FIND OUT THE PROBLEM AND THIS 208 00:08:31,125 --> 00:08:33,494 IS AN AREA SO PRIMITIVE TO ANY 209 00:08:33,494 --> 00:08:36,731 ORGANISM BUT SO UNDER STUDIED. 210 00:08:36,731 --> 00:08:44,705 WE WHY WE EAT, DON'T EAT AND 211 00:08:44,705 --> 00:08:47,775 FEEL SATIATY AND MAKING AN 212 00:08:47,775 --> 00:08:50,544 EFFORT TO DO SOMETHING IS AS 213 00:08:50,544 --> 00:08:51,278 PRIMITIVE AS EATING. 214 00:08:51,278 --> 00:08:53,247 THERE'S CIRCUITS IN THE BRAIN 215 00:08:53,247 --> 00:08:56,350 THAT ARE DEVOTED TO EVERYTHING 216 00:08:56,350 --> 00:08:57,785 WE DO INCLUDING THE DECISION TO 217 00:08:57,785 --> 00:09:00,721 MAKE AN EFFORT ON ANYTHING THAT 218 00:09:00,721 --> 00:09:00,921 WE DO. 219 00:09:00,921 --> 00:09:03,057 EVERYTHING. 220 00:09:03,057 --> 00:09:07,161 NOW, THE PROBLEM IS THE WORD 221 00:09:07,161 --> 00:09:08,796 EFFORT HAS CONNOTATIONS IN THE 222 00:09:08,796 --> 00:09:11,332 LATE PRESS THAT DON'T APPLY TO 223 00:09:11,332 --> 00:09:11,766 WHAT WE'RE DOING AS 224 00:09:11,766 --> 00:09:13,434 NEUROLOGISTS. 225 00:09:13,434 --> 00:09:14,635 WHAT WE'RE TRYING TO THINK ABOUT 226 00:09:14,635 --> 00:09:18,038 IS HOW THE BRAIN IS MAKE THIS 227 00:09:18,038 --> 00:09:21,008 DECISION, WHAT AM I GOING TO DO 228 00:09:21,008 --> 00:09:23,010 ON A MICROSECOND LEVEL. 229 00:09:23,010 --> 00:09:24,678 IT'S NOT LIKE I'M GOING TO TRY 230 00:09:24,678 --> 00:09:25,946 TO MAKE AN EFFORT OR NOT. 231 00:09:25,946 --> 00:09:28,649 THIS IS GOING ON IN YOUR BRAIN 232 00:09:28,649 --> 00:09:30,584 CONSTANTLY AND YOU DON'T EVEN 233 00:09:30,584 --> 00:09:32,086 KNOW WHAT'S GOING ON. 234 00:09:32,086 --> 00:09:34,155 IT'S NOT IN YOUR CONSCIOUSNESS. 235 00:09:34,155 --> 00:09:38,025 COULDN'T THINK EVERY MOTION YOU 236 00:09:38,025 --> 00:09:39,593 DO AND DECIDE IN A DELIBERATE 237 00:09:39,593 --> 00:09:41,462 WAY AM I GOING MAKE THAT MOTION. 238 00:09:41,462 --> 00:09:44,165 YOU COULD MAKE 100 A DAY AND I'M 239 00:09:44,165 --> 00:09:45,900 MAKE 300 IN THREE SECONDS. 240 00:09:45,900 --> 00:09:48,903 SO THEN THE QUESTION IS WHAT IS 241 00:09:48,903 --> 00:09:51,705 FATIGUE. 242 00:09:51,705 --> 00:09:55,843 ONE THINK ABOUT DIFFERENT WAYS 243 00:09:55,843 --> 00:09:57,244 AND I'M NOT AN EXPERT BUT 244 00:09:57,244 --> 00:09:58,379 DR. HALLETT IS AN EXPERT AND 245 00:09:58,379 --> 00:09:59,013 HE'LL TALK LATER. 246 00:09:59,013 --> 00:10:00,714 THE BRAIN IS TRYING TO MAKE A 247 00:10:00,714 --> 00:10:02,650 DECISION IN A SIMPLISTIC WAY IS 248 00:10:02,650 --> 00:10:07,087 I'M GOING TO DO X FOR REWARD Y. 249 00:10:07,087 --> 00:10:07,922 THAT'S EVERY SINGLE ACTION. 250 00:10:07,922 --> 00:10:10,057 YOUR BRAIN IS MAKING THAT 251 00:10:10,057 --> 00:10:12,159 COMPLICATION SO YOU HAVE TO IT 252 00:10:12,159 --> 00:10:14,061 MAKE SOME ESTIMATION OF WHAT THE 253 00:10:14,061 --> 00:10:15,563 WORK OR THE EFFORT IS AND THEN 254 00:10:15,563 --> 00:10:17,298 YOU MAKE SOME ESTIMATION OF WHAT 255 00:10:17,298 --> 00:10:18,632 THE REWARD IS AND YOUR BRAIN IS 256 00:10:18,632 --> 00:10:22,436 DOING THAT ALL THE TIME. 257 00:10:22,436 --> 00:10:24,138 AND THEN FATIGUE, THERE'S A REAL 258 00:10:24,138 --> 00:10:24,705 PROBLEM THERE. 259 00:10:24,705 --> 00:10:27,007 WE'RE NOT SURE WHAT THE PROBLEM 260 00:10:27,007 --> 00:10:28,075 IS. 261 00:10:28,075 --> 00:10:29,844 IT COULD BE YOU'RE 262 00:10:29,844 --> 00:10:31,345 OVERESTIMATING THE EFFORT OR 263 00:10:31,345 --> 00:10:32,813 COULD BE THAT YOU'RE NOT GETTING 264 00:10:32,813 --> 00:10:35,382 THE REWARD SIGNAL FOR THE 265 00:10:35,382 --> 00:10:35,649 EFFORT. 266 00:10:35,649 --> 00:10:38,385 BUT THAT IS A COMPUTATIONAL 267 00:10:38,385 --> 00:10:39,753 PROBLEM IN YOUR BRAIN. 268 00:10:39,753 --> 00:10:41,755 AND PEOPLE -- IT'S IMPORTANT FOR 269 00:10:41,755 --> 00:10:42,923 PEOPLE TO UNDERSTAND THIS HAS 270 00:10:42,923 --> 00:10:43,824 NOTHING TO DO WITH THEY DON'T 271 00:10:43,824 --> 00:10:45,159 WANT TO MAKE AN EFFORT. 272 00:10:45,159 --> 00:10:47,294 IT HAS NOTHING TO DO ONE THAT. 273 00:10:47,294 --> 00:10:47,862 IT'S COMPLETELY SEPARATE. 274 00:10:47,862 --> 00:10:49,563 IT'S HOW YOUR BRAIN IS MAKING 275 00:10:49,563 --> 00:10:53,133 THESE COMPUTATIONS. 276 00:10:53,133 --> 00:10:54,468 JUST AN EXAMPLE. 277 00:10:54,468 --> 00:10:56,971 IF YOU LOOK AT MUSCLE FATIGUE. 278 00:10:56,971 --> 00:10:59,273 HERE'S SOMETHING SIMPLE AND 279 00:10:59,273 --> 00:11:00,708 NOTHING DO WITH ANY ME/CFS IT'S 280 00:11:00,708 --> 00:11:02,943 ABOUT FATIGUE. 281 00:11:02,943 --> 00:11:06,247 WHEN YOU TRY TO MAKE 282 00:11:06,247 --> 00:11:09,383 CONTRACTIONS AGAINST A FORCE 283 00:11:09,383 --> 00:11:13,454 EVENTUALLY YOU'LL FATIGUE AND 284 00:11:13,454 --> 00:11:14,889 WHAT HAPPENS IS -- WHAT YOU SEE 285 00:11:14,889 --> 00:11:16,023 HERE IS THE FORCE STARTS TO DROP 286 00:11:16,023 --> 00:11:19,460 OFF AFTER YOU DO IT 100 TIMES 287 00:11:19,460 --> 00:11:21,595 AND THE INTERESTING THING IS YOU 288 00:11:21,595 --> 00:11:23,397 WOULD SAY OKAY THE MUSCLE CAN'T 289 00:11:23,397 --> 00:11:24,431 DO IT ANYMORE. 290 00:11:24,431 --> 00:11:25,566 NOT TRUE. 291 00:11:25,566 --> 00:11:26,400 WHEN YOU STIMULATE THE NERVE YOU 292 00:11:26,400 --> 00:11:29,703 GET THE CONTRACTION TO COME 293 00:11:29,703 --> 00:11:30,271 BACK. 294 00:11:30,271 --> 00:11:32,706 SO THERE'S SOMETHING IN THE 295 00:11:32,706 --> 00:11:35,075 CENTRAL NERVOUS SYSTEM THAT IS 296 00:11:35,075 --> 00:11:38,779 TELLING THE NERVES I DON'T WANT 297 00:11:38,779 --> 00:11:40,381 TO DO THIS ANYMORE. 298 00:11:40,381 --> 00:11:41,515 YOU STOP FIRING. 299 00:11:41,515 --> 00:11:42,917 THERE'S NOTHING WRONG WITH THE 300 00:11:42,917 --> 00:11:44,418 MUSCLE -- WELL, THE MUSCLE'S 301 00:11:44,418 --> 00:11:46,787 TIRED I CAN'T GET TO WHERE IT 302 00:11:46,787 --> 00:11:47,888 WAS BEFORE BUT LOOK AT THE 303 00:11:47,888 --> 00:11:50,457 DIFFERENCE WHEN YOU STIMULATE 304 00:11:50,457 --> 00:11:51,025 DIRECTLY. 305 00:11:51,025 --> 00:11:54,628 THAT IS ONE SENSE OF FATIGUE 306 00:11:54,628 --> 00:12:00,734 THAT IS EVIDENCE COMING FROM A 307 00:12:00,734 --> 00:12:02,403 CENTRAL CONTROLLER. 308 00:12:02,403 --> 00:12:03,971 THAT'S ABOUT WHAT WE'RE TRYING 309 00:12:03,971 --> 00:12:05,139 TO UNDERSTAND IN ME/CFS, WHERE'S 310 00:12:05,139 --> 00:12:07,241 THE CENTRAL CONTROLLER AND 311 00:12:07,241 --> 00:12:07,975 WHAT'S WRONG IN IT. 312 00:12:07,975 --> 00:12:12,379 THERE'S LOTS OF THINGS TO CAUSE 313 00:12:12,379 --> 00:12:13,781 YOU FATIGUE. 314 00:12:13,781 --> 00:12:15,349 WE KNOW A LOT OF THE LIST OF THE 315 00:12:15,349 --> 00:12:18,018 PROBLEMS AND INJECT YOU WITH 316 00:12:18,018 --> 00:12:19,453 SOMETHING FOR FATIGUE BUT WHERE 317 00:12:19,453 --> 00:12:21,388 IN THE BRAIN THAT'S HAPPENING IS 318 00:12:21,388 --> 00:12:23,624 THE QUESTION AND WHY PEOPLE WITH 319 00:12:23,624 --> 00:12:27,895 ME/CFS IS THERE THAT RESET, THAT 320 00:12:27,895 --> 00:12:36,737 BALANCE BEING WHY'S IT ABNORMAL 321 00:12:36,737 --> 00:12:39,273 I WANT PEOPLE TO PUT THEIR LAY 322 00:12:39,273 --> 00:12:40,107 TERMINOLOGY AND THE SCIENCE WILL 323 00:12:40,107 --> 00:12:44,578 GIVE THE ANSWERS. 324 00:12:44,578 --> 00:12:46,647 ONCE WE UNDERSTAND WHAT'S GOING 325 00:12:46,647 --> 00:12:48,382 ON IN THE BRAIN AND WHERE IT'S 326 00:12:48,382 --> 00:12:51,218 OCCURRING YOU CAN MODULATE 327 00:12:51,218 --> 00:12:51,485 CIRCUITS. 328 00:12:51,485 --> 00:12:54,655 PEOPLE WITH SEVERE CHRONIC PAIN 329 00:12:54,655 --> 00:12:56,490 STIMULATE A CERTAIN AREA, IT 330 00:12:56,490 --> 00:12:57,057 GOES AWAY. 331 00:12:57,057 --> 00:12:58,926 PEOPLE WITH DEPRESSION, CLOSE TO 332 00:12:58,926 --> 00:13:01,195 SUICIDE, YOU TURN ON THE 333 00:13:01,195 --> 00:13:02,596 STIMULATOR IT GOES AWAY. 334 00:13:02,596 --> 00:13:04,398 THERE'S REAL PROMISE IN 335 00:13:04,398 --> 00:13:05,833 UNDERSTANDING WHAT'S WRONG WITH 336 00:13:05,833 --> 00:13:07,267 THE CIRCUITS AND WHAT YOU'LL 337 00:13:07,267 --> 00:13:08,769 HEAR ABOUT TODAY FROM DR. NATH 338 00:13:08,769 --> 00:13:12,740 AND THE TEAM AND HOPEFULLY THIS 339 00:13:12,740 --> 00:13:16,744 MOVES US A STEP FURTHER TO 340 00:13:16,744 --> 00:13:20,648 BETTER UNDERSTAND AN GET US TO 341 00:13:20,648 --> 00:13:22,116 TREATMENT FOR ME/CFS. 342 00:13:22,116 --> 00:13:23,283 I APPRECIATE THE TREMENDOUS 343 00:13:23,283 --> 00:13:24,752 AMOUNT OF WORK THAT'S DIDN'T 344 00:13:24,752 --> 00:13:27,488 DONE AND CREDIT TO AVI AN HIS 345 00:13:27,488 --> 00:13:30,324 TEAM TO MAKE THIS PUBLIC AND 346 00:13:30,324 --> 00:13:31,592 EXPLAIN IT IN THE BEST WAY 347 00:13:31,592 --> 00:13:32,760 POSSIBLE TO THE WORLD SO THANKS 348 00:13:32,760 --> 00:13:41,268 VERY MUCH. 349 00:13:41,268 --> 00:13:44,838 >> THANK YOU, DR. KOROSHETZ THAT 350 00:13:44,838 --> 00:13:47,808 WAS AN ELEGANT DESCRIPTION. 351 00:13:47,808 --> 00:13:49,677 BETTER THAN I COULD HAVE 352 00:13:49,677 --> 00:13:50,811 EXPLAINED IT MYSELF. 353 00:13:50,811 --> 00:13:52,680 SO I'M JUST GOING TO GIVE A FEW 354 00:13:52,680 --> 00:13:54,948 OPENING REMARKS TO PUT THIS IN 355 00:13:54,948 --> 00:13:55,215 CONTEXT. 356 00:13:55,215 --> 00:14:00,754 THE FIRST THING I WANT TO DO IS 357 00:14:00,754 --> 00:14:02,790 TELL WHERE YOU ALL THIS RESEARCH 358 00:14:02,790 --> 00:14:03,757 TAKES PLACE. 359 00:14:03,757 --> 00:14:05,292 SO YOU'RE IN BILLING 10 RIGHT 360 00:14:05,292 --> 00:14:07,895 NOW AND THE THREE BUILDINGS ARE 361 00:14:07,895 --> 00:14:09,063 THE CLINICAL RESEARCH CENTER. 362 00:14:09,063 --> 00:14:10,431 THAT'S WHERE ALL THE PATIENTS 363 00:14:10,431 --> 00:14:11,031 CAME. 364 00:14:11,031 --> 00:14:14,902 IT'S THE LARGEST RESEARCH 365 00:14:14,902 --> 00:14:17,938 HOSPITAL IN THE WORLD BUT YET 366 00:14:17,938 --> 00:14:20,274 IT'S BUILT AS A 200 BED HOSPITAL 367 00:14:20,274 --> 00:14:24,044 AND ONLY 90 OCCUPIED AT THE 368 00:14:24,044 --> 00:14:24,411 MOMENT. 369 00:14:24,411 --> 00:14:27,548 ALL THE LARGE FOR RESEARCH AND 370 00:14:27,548 --> 00:14:31,618 SMALL IN CONTEXT. 371 00:14:31,618 --> 00:14:36,724 IT GIVES US THE ABILITY TO STUDY 372 00:14:36,724 --> 00:14:39,460 PATIENTS IN A WAY YOU REALLY 373 00:14:39,460 --> 00:14:40,027 COULDN'T OTHERWISE. 374 00:14:40,027 --> 00:14:43,363 IT PROVIDES THE EASE OF BEING 375 00:14:43,363 --> 00:14:45,132 ABLE TO SEE PATIENTS AND DO 376 00:14:45,132 --> 00:14:46,433 RESEARCH IN THE SAME PLACE. 377 00:14:46,433 --> 00:14:48,435 DON'T HAVE TO GET IN YOUR CAR TO 378 00:14:48,435 --> 00:14:49,269 GO SOME PLACE. 379 00:14:49,269 --> 00:14:52,206 I WANT TO THANK A LOT OF PEOPLE 380 00:14:52,206 --> 00:14:56,210 WHO MADE THIS POSSIBLE. 381 00:14:56,210 --> 00:14:58,679 AND FIRST OF ALL I WANTED TO 382 00:14:58,679 --> 00:15:00,347 THANK THE STUDY PARTICIPANTS 383 00:15:00,347 --> 00:15:01,482 BECAUSE THEY REALLY SPENT A LOT 384 00:15:01,482 --> 00:15:03,484 OF TIME AND EFFORT COMING HERE 385 00:15:03,484 --> 00:15:05,319 AND KNOWING THAT THERE'S NO 386 00:15:05,319 --> 00:15:06,019 TANGIBLE BENEFIT TO THIS MANY AT 387 00:15:06,019 --> 00:15:10,257 THE END OF THIS STUDY. 388 00:15:10,257 --> 00:15:13,427 BUT YET WE PROBED THEM AND DID 389 00:15:13,427 --> 00:15:15,863 ALL KINDS OF TESTS TO THEM AND 390 00:15:15,863 --> 00:15:17,998 TOOK BLOOD AND SPINAL FLUID AND 391 00:15:17,998 --> 00:15:19,533 IMAGING AND ALL KINDS OF THINGS 392 00:15:19,533 --> 00:15:21,101 AND THEY WENT THROUGH ALL OF IT. 393 00:15:21,101 --> 00:15:22,269 THEY WERE HERE FOR A WEEK AND 394 00:15:22,269 --> 00:15:24,938 THEN TWO WEEKS. 395 00:15:24,938 --> 00:15:27,508 SO WE'RE EXTREMELY GRATEFUL TO 396 00:15:27,508 --> 00:15:28,809 THEM BECAUSE WITHOUT THEIR 397 00:15:28,809 --> 00:15:30,177 VOLUNTEERING THIS WOULD NOT BE 398 00:15:30,177 --> 00:15:30,477 POSSIBLE. 399 00:15:30,477 --> 00:15:34,481 THE STUDY PARTICIPANTS ARE NOT 400 00:15:34,481 --> 00:15:36,450 JUST PATIENTS WITH ME/CFS BUT 401 00:15:36,450 --> 00:15:37,084 HEALTHY CONTROLS WHO WENT 402 00:15:37,084 --> 00:15:38,352 THROUGH THE SAME PROCESS. 403 00:15:38,352 --> 00:15:40,754 SO THEY'RE DEFINITELY NOT 404 00:15:40,754 --> 00:15:41,922 BENEFITING IN ANY WAY BUT WERE 405 00:15:41,922 --> 00:15:43,857 WILLING TO PUT THEMSELVES 406 00:15:43,857 --> 00:15:45,292 THROUGH IT IN ORDER FOR US TO BE 407 00:15:45,292 --> 00:15:46,426 ABLE TO FIND WAYS OF STUDYING 408 00:15:46,426 --> 00:15:50,264 OTHER DISEASES. 409 00:15:50,264 --> 00:15:52,566 I HAVE TO THANK THE NIH 410 00:15:52,566 --> 00:15:54,668 LEADERSHIP START FROM FRANCIS 411 00:15:54,668 --> 00:15:57,204 COLLINS TO DR. KOROSHETZ AND 412 00:15:57,204 --> 00:15:57,538 OTHERS. 413 00:15:57,538 --> 00:16:00,374 A LOT OF THE INSTITUTES REALLY 414 00:16:00,374 --> 00:16:02,209 PARTICIPATED IN THIS STUDY AND 415 00:16:02,209 --> 00:16:05,345 WOULD NOT BE POSSIBLE UNLESS THE 416 00:16:05,345 --> 00:16:07,447 DIRECTORS OF THOSE INSTITUTES 417 00:16:07,447 --> 00:16:08,182 MADE THEIR RESOURCES AVAILABLE 418 00:16:08,182 --> 00:16:11,418 FOR THE STUDY ITSELF. 419 00:16:11,418 --> 00:16:14,421 THE STUDY STREAM CONSISTS OF 420 00:16:14,421 --> 00:16:15,923 NEARLY 75 INVESTIGATORS. 421 00:16:15,923 --> 00:16:18,125 MOST OF THEM PUT ASIDE WHAT THEY 422 00:16:18,125 --> 00:16:20,527 WERE DOING AND TOOK THIS ON TOP 423 00:16:20,527 --> 00:16:21,628 OF WHATEVER THEY WERE DOING IN 424 00:16:21,628 --> 00:16:23,397 ORDER TO CONTRIBUTE TO THE 425 00:16:23,397 --> 00:16:23,964 STUDY. 426 00:16:23,964 --> 00:16:27,634 ANYONE AND EVERYONE I ASKED TO 427 00:16:27,634 --> 00:16:28,402 HELP THEY ACTUALLY DID. 428 00:16:28,402 --> 00:16:31,505 A STUDY TEAM WAS LED BY 429 00:16:31,505 --> 00:16:34,675 DR. BRIAN WALITT AND HE HAS DONE 430 00:16:34,675 --> 00:16:37,477 A SUPERB JOB LEADING THIS ENTIRE 431 00:16:37,477 --> 00:16:37,744 STUDY. 432 00:16:37,744 --> 00:16:39,646 WITHOUT HIS HELP THIS WOULD NOT 433 00:16:39,646 --> 00:16:41,448 BE POSSIBLE. 434 00:16:41,448 --> 00:16:46,720 THEN WE HAD A TEAM OF 435 00:16:46,720 --> 00:16:48,922 ADJUDICATORS AND THEY ADJUD 436 00:16:48,922 --> 00:16:50,457 ADJUDICATED EVERY PATIENT ON THE 437 00:16:50,457 --> 00:16:53,427 STUDY THAT TEAM DID A PHENOMENAL 438 00:16:53,427 --> 00:16:55,229 JOB MAKING SURE WE WERE STUDYING 439 00:16:55,229 --> 00:16:57,397 THE RIGHT INDIVIDUALS. 440 00:16:57,397 --> 00:16:58,932 RESEARCHERS AS A MENTIONED CAME 441 00:16:58,932 --> 00:17:00,334 FROM ALL THESE VARIOUS 442 00:17:00,334 --> 00:17:02,069 INSTITUTES OVER HERE AND SOME OF 443 00:17:02,069 --> 00:17:04,972 THEM HAVE AFFILIATIONS IN OTHER 444 00:17:04,972 --> 00:17:06,340 UNIVERSITIES AND RESEARCHERS 445 00:17:06,340 --> 00:17:07,474 THAT WE COLLABORATED WITH. 446 00:17:07,474 --> 00:17:08,809 AND WE'RE GRATEFUL TO ALL OF 447 00:17:08,809 --> 00:17:10,777 THEM. 448 00:17:10,777 --> 00:17:19,286 WE HAVE TWO PANELS TODAY. 449 00:17:19,286 --> 00:17:21,688 ESTEEMED PANEL OF STUDY 450 00:17:21,688 --> 00:17:22,756 PARTICIPATED AND UME GRATE FOL 451 00:17:22,756 --> 00:17:24,758 BOTH PANELS AND YOU'LL HEAR FROM 452 00:17:24,758 --> 00:17:26,293 THEM AS WELL. 453 00:17:26,293 --> 00:17:31,498 I WANT TO THANK THE ORGANIZERS 454 00:17:31,498 --> 00:17:37,104 ESPECIALLY WARREN AND ALISSA AND 455 00:17:37,104 --> 00:17:47,648 THE OTHERS ARE HERE AND BARBARA 456 00:17:48,081 --> 00:17:49,583 AND THE AMOUNT OF WORK TO PUT 457 00:17:49,583 --> 00:17:51,852 THIS EFFORT TOGETHER AND WITHOUT 458 00:17:51,852 --> 00:17:52,719 THEIR HELP WOULD NOT BE POSSIBLE 459 00:17:52,719 --> 00:17:57,658 AT ALL. 460 00:17:57,658 --> 00:18:00,761 I WANT TO THANK FES FOR 461 00:18:00,761 --> 00:18:03,497 PROVIDING COFFEE AND SNACKS FOR 462 00:18:03,497 --> 00:18:04,364 THE MORNING. 463 00:18:04,364 --> 00:18:06,633 THE GOAL OF THE STUDY OF TODAY'S 464 00:18:06,633 --> 00:18:09,770 PRESENTATION IS TO DISCUSS THE 465 00:18:09,770 --> 00:18:11,905 FINDINGS FROM THE NIH INTRAMURAL 466 00:18:11,905 --> 00:18:15,776 RESEARCH O ON POST INFECTIOUS 467 00:18:15,776 --> 00:18:19,713 ME/CFS. 468 00:18:19,713 --> 00:18:21,148 AND WE WANT YOU TO HEAR DIRECTLY 469 00:18:21,148 --> 00:18:23,016 FROM THE RESEARCHERS AND THERE'S 470 00:18:23,016 --> 00:18:25,285 NO ONE WHO UNDERSTAND THE STUDY 471 00:18:25,285 --> 00:18:27,821 IN ITS ENTIRETY BUT WE HAVE THE 472 00:18:27,821 --> 00:18:28,989 WORLD'S EXPERTS WHO CONTRIBUTED 473 00:18:28,989 --> 00:18:29,523 TIME. 474 00:18:29,523 --> 00:18:31,792 I WANT YOU TO HEAR DIRECTLY FROM 475 00:18:31,792 --> 00:18:32,225 THEM. 476 00:18:32,225 --> 00:18:36,730 THEN WE LIKE TO DISCUSS FUTURE 477 00:18:36,730 --> 00:18:38,365 DIRECTION JUST AS DR. KOROSHETZ 478 00:18:38,365 --> 00:18:39,199 SAID IT'S A GOOD BEGINNING BUT 479 00:18:39,199 --> 00:18:41,468 NOT THE END. 480 00:18:41,468 --> 00:18:44,171 I WANT TO GIVE YOU A LITTLE HOW 481 00:18:44,171 --> 00:18:45,739 I GOT INVOLVED IN THIS THING AND 482 00:18:45,739 --> 00:18:47,908 I CALL IT THE IT TALE OF THREE 483 00:18:47,908 --> 00:18:48,275 PANDEMICS. 484 00:18:48,275 --> 00:18:51,845 MY CAREER STARTED WENL THE HIV 485 00:18:51,845 --> 00:18:54,581 PANDEMIC IN THE '80s AND I 486 00:18:54,581 --> 00:18:56,750 LEARNED A LOT ABOUT INFECTIONS 487 00:18:56,750 --> 00:18:58,752 DUE TO THE BRAIN THROUGH DECADES 488 00:18:58,752 --> 00:19:00,988 OF RESEARCH STUDYING HIV 489 00:19:00,988 --> 00:19:01,455 INFECTION. 490 00:19:01,455 --> 00:19:03,890 THE INTRAMURAL STUDY START AT 491 00:19:03,890 --> 00:19:11,732 THE TIME I WAS INVOLVED IN THE 492 00:19:11,732 --> 00:19:12,099 EBOLA PANDEMIC. 493 00:19:12,099 --> 00:19:15,335 THE EARLY TELECONFERENCES I TOOK 494 00:19:15,335 --> 00:19:16,903 IN LIBERIA FOR ME/CFS. 495 00:19:16,903 --> 00:19:19,306 THAT'S HOW THIS ACTUALLY 496 00:19:19,306 --> 00:19:19,606 STARTED. 497 00:19:19,606 --> 00:19:22,442 THEN A STUDY ENDED WITH THE 498 00:19:22,442 --> 00:19:23,176 COVID PANDEMIC. 499 00:19:23,176 --> 00:19:25,645 SOMEWHAT ABRUPTLY BECAUSE WE 500 00:19:25,645 --> 00:19:27,581 COULDN'T BRING PATIENTS IN ANY 501 00:19:27,581 --> 00:19:27,881 LONGER. 502 00:19:27,881 --> 00:19:29,850 THE STUDY WAS SANDWICHED BETWEEN 503 00:19:29,850 --> 00:19:31,251 TWO PANDEMICS BUT WE LEARNED A 504 00:19:31,251 --> 00:19:33,820 LOT FROM ALL THREE OF THEM. 505 00:19:33,820 --> 00:19:37,090 AND THEY HAVE SIMILAR THINGS. 506 00:19:37,090 --> 00:19:39,793 FOR EXAMPLE, IT WITH THE EBOLA 507 00:19:39,793 --> 00:19:43,897 PANDEMIC WE REALIZED THERE'S A 508 00:19:43,897 --> 00:19:45,465 POST-EBOLA SYNDROME THAT LOOKS 509 00:19:45,465 --> 00:19:48,035 SIMILAR TO ME/CFS AND WITH THE 510 00:19:48,035 --> 00:19:49,603 SARS COV2 PANDEMIC WE REALIZED 511 00:19:49,603 --> 00:20:00,147 THERE'S A LONG COVID WHICH ALSO 512 00:20:00,747 --> 00:20:01,014 OV 513 00:20:01,014 --> 00:20:02,149 OVERLAPS WITH ME/CFS. 514 00:20:02,149 --> 00:20:04,017 WHAT IS INTERESTING AS THEY'RE 515 00:20:04,017 --> 00:20:08,255 ALL POST INFECTION SYNDROMES AND 516 00:20:08,255 --> 00:20:09,356 OVERLAP TREMENDOUSLY WITH ONE 517 00:20:09,356 --> 00:20:10,023 ANOTHER. 518 00:20:10,023 --> 00:20:13,360 WHAT IS FASCINATING IS THAT WITH 519 00:20:13,360 --> 00:20:18,665 THE AIDS PATIENTS THEY HAVE 520 00:20:18,665 --> 00:20:21,501 PERSISTENT VIRAL RESERVOIRS. 521 00:20:21,501 --> 00:20:22,769 THEY'RE PROTEINS ARE ALWAYS 522 00:20:22,769 --> 00:20:27,007 BEING PRODUCED BUT NOT PRODUCE 523 00:20:27,007 --> 00:20:29,943 THE CFS SYNDROME SO JUST 524 00:20:29,943 --> 00:20:31,344 PERSISTENT INFECTION ALONE IS 525 00:20:31,344 --> 00:20:33,280 NOT SUFFICIENT TO EXPLAIN THIS 526 00:20:33,280 --> 00:20:33,480 THING. 527 00:20:33,480 --> 00:20:36,750 WHAT IS INTERESTING IS THE ROUTE 528 00:20:36,750 --> 00:20:38,385 OF INFECTION IS QUITE DIFFERENT. 529 00:20:38,385 --> 00:20:40,087 SO IF YOU LOOK AT POST EBOLA 530 00:20:40,087 --> 00:20:43,924 SYNDROME AND IT'S LARGELY A 531 00:20:43,924 --> 00:20:48,728 GASTROINTESTINAL IN INFECTION 532 00:20:48,728 --> 00:20:56,736 AND ME/CFS COULD BE 533 00:20:56,736 --> 00:20:59,439 GASTROINTESTINAL OR OTHER AND 534 00:20:59,439 --> 00:21:04,711 THESE ARE QUESTIONS UNANSWERED. 535 00:21:04,711 --> 00:21:07,380 WHAT YOU'LL HEAR TODAY IS A 536 00:21:07,380 --> 00:21:09,282 DESCRIPTION OF FINDINGS RELATED 537 00:21:09,282 --> 00:21:10,717 TO EACH OF THESE DIFFERENT 538 00:21:10,717 --> 00:21:12,519 BUCKETS WE PUT TOGETHER HERE AND 539 00:21:12,519 --> 00:21:15,388 IN OUR PAPER WE PROPOSED A 540 00:21:15,388 --> 00:21:15,689 HYPOTHESIS. 541 00:21:15,689 --> 00:21:17,224 IT'S IMPORTANT TO SAY WE DON'T 542 00:21:17,224 --> 00:21:18,325 REALLY KNOW THE PATHWAY. 543 00:21:18,325 --> 00:21:21,228 IT'S A CROSS-SECTIONAL STUDY BUT 544 00:21:21,228 --> 00:21:26,032 WE'VE PROPOSED A PATHWAY. 545 00:21:26,032 --> 00:21:28,435 AND SO ALL THE RESEARCHERS WILL 546 00:21:28,435 --> 00:21:30,303 DISCUSS VARIOUS ASPECTS OF THIS 547 00:21:30,303 --> 00:21:31,438 THAT THEY ARE EXPERTS ON. 548 00:21:31,438 --> 00:21:33,974 I'M NOT GOING TO GO THROUGH THIS 549 00:21:33,974 --> 00:21:35,242 ENTIRETY BECAUSE I FIGURE IT 550 00:21:35,242 --> 00:21:36,743 WILL BE DISCUSSED IN MORE DETAIL 551 00:21:36,743 --> 00:21:41,281 LATER ON TODAY. 552 00:21:41,281 --> 00:21:44,351 SO THE AGENDA FOR TODAY IS THAT 553 00:21:44,351 --> 00:21:46,520 YOU'LL HEAR A DESCRIPTION OF THE 554 00:21:46,520 --> 00:21:48,121 STUDY ITSELF. 555 00:21:48,121 --> 00:21:51,224 WE THEN DIVIDED INTO THREE MAJOR 556 00:21:51,224 --> 00:21:51,525 BUCKETS. 557 00:21:51,525 --> 00:21:55,061 ONE IS ON IMMUNOLOGY AND OMICS. 558 00:21:55,061 --> 00:21:57,330 THE SECOND IS ON NEUROPHYSIOLOGY 559 00:21:57,330 --> 00:22:00,000 AND THE BIO ENERGETICS AND 560 00:22:00,000 --> 00:22:00,800 LASTLY YOU'LL HEAR SOMETHING 561 00:22:00,800 --> 00:22:02,903 ABOUT THE DATA MANAGEMENT AND 562 00:22:02,903 --> 00:22:05,438 SHARING BECAUSE THAT ITSELF WAS 563 00:22:05,438 --> 00:22:07,140 A HUGE MASSIVE UNDERTAKING AND 564 00:22:07,140 --> 00:22:09,276 THEN WE HAVE TWO PANELS AND THEN 565 00:22:09,276 --> 00:22:11,278 WE'LL WELCOME QUESTIONS AND 566 00:22:11,278 --> 00:22:13,513 MULTIPLE PLACES WHERE THERE'LL 567 00:22:13,513 --> 00:22:14,281 BE OPPORTUNITY FOR DISCUSSION 568 00:22:14,281 --> 00:22:15,148 AND ENCOURAGE YOU TO ASK US 569 00:22:15,148 --> 00:22:18,785 QUESTIONS. 570 00:22:18,785 --> 00:22:23,757 SO THIS IS MY LAST SLIDE. 571 00:22:23,757 --> 00:22:28,161 AND HERE I WANTED TO DIRECTLY 572 00:22:28,161 --> 00:22:28,929 ADDRESS THE ME/CFS COMMUNITY. 573 00:22:28,929 --> 00:22:32,699 I WANT YOU TO KNOW THAT AS 574 00:22:32,699 --> 00:22:33,700 PHYSICIANS AND RESEARCHERS, 575 00:22:33,700 --> 00:22:35,702 WE'RE DEEPLY COMMITTED AND HAVE 576 00:22:35,702 --> 00:22:37,971 A STRONG CONVICTION TO TREATING 577 00:22:37,971 --> 00:22:40,407 THIS ILLNESS AND FINDING CURES 578 00:22:40,407 --> 00:22:41,675 FOR THE DISEASE. 579 00:22:41,675 --> 00:22:43,043 WE'RE YOUR PARTNERS AND WE HAVE 580 00:22:43,043 --> 00:22:45,378 THE SAME SHARED GOALS AND I 581 00:22:45,378 --> 00:22:47,214 THINK THAT'S IMPORTANT FOR YOU 582 00:22:47,214 --> 00:22:48,515 TO REAL. 583 00:22:48,515 --> 00:22:50,217 AND AS SHOWN HERE IF WE WALK 584 00:22:50,217 --> 00:22:52,085 TOGETHER I THINK WE CAN ACHIEVE 585 00:22:52,085 --> 00:22:54,654 THE INSURMOUNTABLE. 586 00:22:54,654 --> 00:22:56,823 BUT AS IN ANY PARTNERSHIP, 587 00:22:56,823 --> 00:22:57,891 HEALTHY CRITICISM AND RESPECT 588 00:22:57,891 --> 00:22:59,593 FOR ONE ANOTHER WILL HELP US 589 00:22:59,593 --> 00:23:00,760 GROW BECAUSE WE'RE REALLY ON THE 590 00:23:00,760 --> 00:23:02,729 SAME SIDE. 591 00:23:02,729 --> 00:23:06,299 ALL THE SAME, WHEN YOU DOUBT OUR 592 00:23:06,299 --> 00:23:08,568 INTENTIONS AND PICK APART EVERY 593 00:23:08,568 --> 00:23:11,137 SINGLE WORD, YOU ALSO TEAR US A 594 00:23:11,137 --> 00:23:11,571 PART. 595 00:23:11,571 --> 00:23:14,574 IT CAUSES PAIN AND SUFFERING ON 596 00:23:14,574 --> 00:23:16,076 BOTH SIDES AND DEMORALIZES US 597 00:23:16,076 --> 00:23:19,279 AND SHATTERS OUR GOALS. 598 00:23:19,279 --> 00:23:25,652 SO YOU HAVE A PHENOMENAL TEAM 599 00:23:25,652 --> 00:23:28,021 WHO DEVOTED TIME AND EFFORT TO 600 00:23:28,021 --> 00:23:30,190 UNDERSTAND THE FUNDAMENTAL BASIS 601 00:23:30,190 --> 00:23:30,790 OF ME/CFS. 602 00:23:30,790 --> 00:23:31,791 THEY'RE THE WORLD'S EXPERTS IN 603 00:23:31,791 --> 00:23:33,426 THE FIELD AND TOOK ON THIS 604 00:23:33,426 --> 00:23:34,127 PROJECT ON TOP OF EVERYTHING 605 00:23:34,127 --> 00:23:36,429 ELSE THEY WERE DOING. 606 00:23:36,429 --> 00:23:38,999 WHEN WE ASK THEM TO LEND THEIR 607 00:23:38,999 --> 00:23:40,767 EXPERTISE TO THE PROJECT, EACH 608 00:23:40,767 --> 00:23:44,437 ONE OF THEM SAID YES AND THEY 609 00:23:44,437 --> 00:23:44,704 DELIVERED. 610 00:23:44,704 --> 00:23:46,640 SO IS TOGETHER I THINK WE CAN 611 00:23:46,640 --> 00:23:48,241 REALLY MAKE A HUGE DIFFERENCE IN 612 00:23:48,241 --> 00:23:51,077 THIS DISEASE BUT IT'S IMPORTANT 613 00:23:51,077 --> 00:23:52,545 THAT WE WORK TOGETHER AND NOT 614 00:23:52,545 --> 00:23:58,218 AGAINST ONE ANOTHER. 615 00:23:58,218 --> 00:23:59,786 I THINK THIS IS ALSO AN 616 00:23:59,786 --> 00:24:03,156 OPPORTUNITY TO DISCUSS OUR 617 00:24:03,156 --> 00:24:04,758 FINDINGS AND I URGE YOU TO NOT 618 00:24:04,758 --> 00:24:06,326 MISS THE OPPORTUNITY TO THANK 619 00:24:06,326 --> 00:24:08,928 THESE RESEARCHERS WHEN YOU GET A 620 00:24:08,928 --> 00:24:10,730 CHANCE. 621 00:24:10,730 --> 00:24:12,866 THESE RESEARCHERS ARE SHINING 622 00:24:12,866 --> 00:24:14,668 THE LIGHT ON THE PATH WE NEED TO 623 00:24:14,668 --> 00:24:16,136 FOLLOW AND HOLDING HANDS 624 00:24:16,136 --> 00:24:18,138 TOGETHER WE'LL FIND TREATMENTS 625 00:24:18,138 --> 00:24:20,507 AND CURES WE DESPERATELY NEED. 626 00:24:20,507 --> 00:24:22,676 SO I'LL STOP HERE AND GOING TO 627 00:24:22,676 --> 00:24:25,078 HAND IT OVER TO DR. BRIAN WALITT 628 00:24:25,078 --> 00:24:27,647 WHO IS GOING TO DESCRIBE THE 629 00:24:27,647 --> 00:24:30,950 CLINICAL COHORT AND THE 630 00:24:30,950 --> 00:24:31,785 PROTOCOL. 631 00:24:31,785 --> 00:24:37,857 DR. WALITT IS A RHEUMATOLOGIST 632 00:24:37,857 --> 00:24:40,727 BY TRAINING AND HE SPECIALIZED 633 00:24:40,727 --> 00:24:45,265 IN FIBFIBROMYALGIA BEFORE HE CA 634 00:24:45,265 --> 00:24:48,401 TO NIH AND HE CAME AND 635 00:24:48,401 --> 00:24:49,703 VOLUNTEERED TO HELP ME PUT THE 636 00:24:49,703 --> 00:24:54,240 STUDY TOGETHER AND HE'S DONE AN 637 00:24:54,240 --> 00:24:58,211 ABSOLUTELY PHENOMENAL JOB AND AN 638 00:24:58,211 --> 00:24:59,946 ASTUTE PHYSICIAN AND VERY 639 00:24:59,946 --> 00:25:00,180 CAREFUL. 640 00:25:00,180 --> 00:25:02,349 HE WENT THROUGH RECORDS OF ALL 641 00:25:02,349 --> 00:25:04,317 THE PATIENTS THAT CAME THROUGH 642 00:25:04,317 --> 00:25:05,919 HELPED IDENTIFY THE PATIENTS, 643 00:25:05,919 --> 00:25:07,320 EXAMINED THEM ON WEEKENDS AND 644 00:25:07,320 --> 00:25:09,456 DAYS AND NEWTS, WHATEVER IT TOOK 645 00:25:09,456 --> 00:25:11,224 TO MAKE SURE THAT EVERY ASPECT 646 00:25:11,224 --> 00:25:14,394 OF THE STUDY WORKED OUT WELL. 647 00:25:14,394 --> 00:25:16,996 WITHOUT HIS HELP THIS WOULD NOT 648 00:25:16,996 --> 00:25:18,398 BE POSSIBLE. 649 00:25:18,398 --> 00:25:20,500 DR. WALITT, I'LL LED YOU 650 00:25:20,500 --> 00:25:21,101 DESCRIBE THE OVERVIEW OF THE 651 00:25:21,101 --> 00:25:31,211 STUDY. 652 00:25:33,580 --> 00:25:33,780 ♪ 653 00:25:33,780 --> 00:25:33,947 OF 654 00:25:33,947 --> 00:25:34,714 >> THANK YOU ALL FOR COME 655 00:25:36,116 --> 00:25:37,951 THANK YOU ALL FOR COMING TODAY 656 00:25:37,951 --> 00:25:40,754 AND FOR YOUR KIND WORDS AVI AND 657 00:25:40,754 --> 00:25:41,888 HERE WE ARE. 658 00:25:41,888 --> 00:25:43,590 SO I'M GOING TO TAKE TIME NOW TO 659 00:25:43,590 --> 00:25:45,291 DESCRIBE THE COHORT OF PATIENTS 660 00:25:45,291 --> 00:25:46,760 THAT WERE RECRUITED IN THE 661 00:25:46,760 --> 00:25:48,728 PROTOCOL WE PUT TOGETHER TO 662 00:25:48,728 --> 00:25:52,399 STUDY. 663 00:25:52,399 --> 00:25:56,736 SO AS MENTIONED IT WAS ANNOUNCED 664 00:25:56,736 --> 00:26:00,807 WE WERE GOING STUDY CHRONIC 665 00:26:00,807 --> 00:26:03,510 FATIGUE SYNDROME AROUND 2015, 666 00:26:03,510 --> 00:26:04,744 HERE WE ARE IN 2024 I'M HERE TO 667 00:26:04,744 --> 00:26:06,212 PRESENT THE RESULT ARE TO YOU. 668 00:26:06,212 --> 00:26:08,581 THIS IS A HAPPY MOMENT FOR ME TO 669 00:26:08,581 --> 00:26:10,750 BE ABLE SO THE YOU ALL THIS WORK 670 00:26:10,750 --> 00:26:13,686 WE DID. 671 00:26:13,686 --> 00:26:21,127 SO, SOMEONE HAS TO EXPLAIN WHAT 672 00:26:21,127 --> 00:26:26,266 MIALGIC CHRONIC FATIGUE SYNDROME 673 00:26:26,266 --> 00:26:27,534 IT'S DIAGNOSIS CLINICAL. 674 00:26:27,534 --> 00:26:31,805 HERE'S THE IOM, THE INSTITUTE OF 675 00:26:31,805 --> 00:26:32,939 MEDICINE CRITERIA A SUBSTANTIAL 676 00:26:32,939 --> 00:26:34,707 DECREASE IN FUNCTION OVER SIX 677 00:26:34,707 --> 00:26:37,210 MONTHS IN TIME. 678 00:26:37,210 --> 00:26:39,779 THE SYMPTOMS OF POST EXERTIONAL 679 00:26:39,779 --> 00:26:44,751 MALAISE AND UNREFRESHING SLEEP 680 00:26:44,751 --> 00:26:47,787 AND ORTHOSTATIC INTOLERANCE. 681 00:26:47,787 --> 00:26:50,723 ON THE RIGHT IS A PICTURE A 682 00:26:50,723 --> 00:26:52,125 PARTICIPANT DREW TO TRY TO 683 00:26:52,125 --> 00:26:53,560 VISUALIZE THE SYMPTOMS SHE HAS. 684 00:26:53,560 --> 00:26:57,931 YOU CAN SEE THE VARIOUS WAYS SHE 685 00:26:57,931 --> 00:26:59,532 SUFFERS FROM HER ME/CFS. 686 00:26:59,532 --> 00:27:02,202 MUSCLE ACHES, FEELINGS OF FLU, 687 00:27:02,202 --> 00:27:04,370 HEADACHES, SENSITIVITY TO LIGHT, 688 00:27:04,370 --> 00:27:07,607 THE SENSATION OF BRAIN FOG AND 689 00:27:07,607 --> 00:27:08,208 DIFFICULTY FOCUSSING. 690 00:27:08,208 --> 00:27:11,344 WHAT IT MIGHT FEEL LIKE TO HAVE 691 00:27:11,344 --> 00:27:11,778 UNREFRESHING SLEEP. 692 00:27:11,778 --> 00:27:15,448 SHE HAD NAUSEA AND THE IDEA OF 693 00:27:15,448 --> 00:27:18,885 DIZZINESS AND THE BLACK HOLE 694 00:27:18,885 --> 00:27:22,422 THAT IS THE FEELING OF 695 00:27:22,422 --> 00:27:23,423 POST-EXERTIONAL MALAISE AND 696 00:27:23,423 --> 00:27:24,958 THERE'LL BE MORE ON WHAT THAT IS 697 00:27:24,958 --> 00:27:26,092 IN THE PRESENTATION. 698 00:27:26,092 --> 00:27:27,727 WE PUT TOGETHER THE PROTOCOL. 699 00:27:27,727 --> 00:27:30,530 WHEN EVERYTHING GOT STARTED WE 700 00:27:30,530 --> 00:27:33,099 HAD TO GO AS FAST AS POSSIBLE 701 00:27:33,099 --> 00:27:34,267 AND WERE ABLE TO WRITE A 702 00:27:34,267 --> 00:27:35,768 PROTOCOL IN ABOUT A MONTH'S TIME 703 00:27:35,768 --> 00:27:37,370 TO GIVE TO THE IRB. 704 00:27:37,370 --> 00:27:38,905 IT WENT UNDER A FAIR BIT OF 705 00:27:38,905 --> 00:27:40,740 AMENDMENT OVER TIME TO GET IT 706 00:27:40,740 --> 00:27:43,743 INTO ITS FINAL FORM BUT WE MOVED 707 00:27:43,743 --> 00:27:46,479 AS FAST AS POSSIBLE TO GET THIS 708 00:27:46,479 --> 00:27:48,748 PROTOCOL STARTED. 709 00:27:48,748 --> 00:27:50,850 THE HYPOTHESIS WAS 710 00:27:50,850 --> 00:27:52,118 POST-INFECTIOUS ME/CFS WAS 711 00:27:52,118 --> 00:27:54,554 TRIGGERED BY INFECTIOUS ILLNESS 712 00:27:54,554 --> 00:27:56,122 THAT RESULTED IN IMMUNE MEDIATED 713 00:27:56,122 --> 00:27:56,689 BRAIN DYSFUNCTION. 714 00:27:56,689 --> 00:28:02,929 TO DO THIS WE WANTED TO CONDUCT 715 00:28:02,929 --> 00:28:04,197 A STUDY DEEPLY PHENOTYPE 716 00:28:04,197 --> 00:28:07,367 PARTICIPANT TO DEFINE ITS PATH 717 00:28:07,367 --> 00:28:08,768 YO PHYSIOLOGY. 718 00:28:08,768 --> 00:28:08,935 SO WHAT 719 00:28:10,703 --> 00:28:11,004 PATHOPHYSIOLOGY. 720 00:28:11,004 --> 00:28:12,772 WHAT IS DEEP PHENOTYPING? 721 00:28:12,772 --> 00:28:14,440 I PROVIDED A REFERENCE FOR THOSE 722 00:28:14,440 --> 00:28:16,175 LOOKING TO DIVE DEEPER. 723 00:28:16,175 --> 00:28:19,012 THE PRECISE AND COMPREHENSIVE 724 00:28:19,012 --> 00:28:20,280 ANALYSIS OF PHENOTYPIC 725 00:28:20,280 --> 00:28:22,015 ABNORMALITIES WHERE THE 726 00:28:22,015 --> 00:28:22,982 INDIVIDUAL COMPONENTS OF 727 00:28:22,982 --> 00:28:23,550 PHENOTYPE ARE OBSERVED AND 728 00:28:23,550 --> 00:28:27,153 DESCRIBED. 729 00:28:27,153 --> 00:28:28,755 MEASURE EVERYTHING POSSIBLE TO 730 00:28:28,755 --> 00:28:32,392 FIRST ALL THE DIFFERENT ASPECTS 731 00:28:32,392 --> 00:28:32,692 OF A PERSON. 732 00:28:32,692 --> 00:28:37,196 AND TO DO THIS THIS IS A LIST OF 733 00:28:37,196 --> 00:28:38,631 MOST THE PHENOTYPING MEASURES WE 734 00:28:38,631 --> 00:28:38,965 MADE. 735 00:28:38,965 --> 00:28:41,534 SOME ARE THINGS THAT CLINICIANS 736 00:28:41,534 --> 00:28:45,872 DO LIKE HISTORIES AND PHYSICAL 737 00:28:45,872 --> 00:28:46,072 EXAMS. 738 00:28:46,072 --> 00:28:49,442 SOME ARE MEASUREMENTS OF 739 00:28:49,442 --> 00:28:51,844 PEOPLE'S BEHAVIOR, HOW THEY EAT 740 00:28:51,844 --> 00:28:55,548 AND SLEEP AND MEASURES OF 741 00:28:55,548 --> 00:29:00,720 PHYSIOLOGY SUCH AS THEIR SLEEP 742 00:29:00,720 --> 00:29:07,961 POLY SOMNOGRAMS AND MEASURES OF 743 00:29:07,961 --> 00:29:09,796 BLOOD AND CEREBRAL SPINAL FLUID 744 00:29:09,796 --> 00:29:10,229 AND SO FORTH. 745 00:29:10,229 --> 00:29:13,499 THIS WAYS STUDY AND MOST STUDIES 746 00:29:13,499 --> 00:29:16,336 PEOPLE THINK ABOUT IS TO TEST 747 00:29:16,336 --> 00:29:16,636 HYPOTHESIS. 748 00:29:16,636 --> 00:29:19,305 THIS TRYING TO GENERATE A NEW 749 00:29:19,305 --> 00:29:20,740 HYPOTHESIS TO GIVE US DIRECTION 750 00:29:20,740 --> 00:29:24,310 TO MOVE FORWARD IN THE FUTURE. 751 00:29:24,310 --> 00:29:26,446 AND FOR US OUR MISSION WAS TO 752 00:29:26,446 --> 00:29:27,981 EXPLORE THE POSSIBLE 753 00:29:27,981 --> 00:29:29,682 RELATIONSHIPS BETWEEN THE STUDY 754 00:29:29,682 --> 00:29:32,752 MEASUREMENTS WITHOUT PRIOR 755 00:29:32,752 --> 00:29:33,386 ASSUMPTIONS TO WHAT THOSE MIGHT 756 00:29:33,386 --> 00:29:37,090 MEAN. 757 00:29:37,090 --> 00:29:38,658 SO PARTICIPANT SELECTION WAS AN 758 00:29:38,658 --> 00:29:39,826 IMPORTANT PIECE OF THE PUZZLE 759 00:29:39,826 --> 00:29:40,627 FOR THE STUDY. 760 00:29:40,627 --> 00:29:42,695 WE WANTED TO MAKE SURE EVERYBODY 761 00:29:42,695 --> 00:29:45,231 HAD A WELL DOCUMENTED INFECTION. 762 00:29:45,231 --> 00:29:47,066 THIS REQUIRED US TO LOOK THROUGH 763 00:29:47,066 --> 00:29:49,469 LOTS OF MEDICAL RECORDS TO MAKE 764 00:29:49,469 --> 00:29:51,771 SURE THE PATIENTS HAD NORMAL 765 00:29:51,771 --> 00:29:54,607 HEALTH PRIOR TO INFECTION AND 766 00:29:54,607 --> 00:29:58,711 DEMONSTRATE THESE PEOPLE WHO 767 00:29:58,711 --> 00:29:59,846 WERE OSTENSIBLY HEALTHY 768 00:29:59,846 --> 00:30:00,747 DEVELOPED ME/CFS FOLLOWING THE 769 00:30:00,747 --> 00:30:02,115 DOCUMENTED INFECTION. 770 00:30:02,115 --> 00:30:03,116 WE FELT THIS WAS IMPORTANT 771 00:30:03,116 --> 00:30:04,751 BECAUSE AT THE END OF THE DAY IF 772 00:30:04,751 --> 00:30:06,819 YOU LOOK AT THE CAUSE OF ME/CFS 773 00:30:06,819 --> 00:30:09,088 IN THE COHORT IT'S AN INFECTION. 774 00:30:09,088 --> 00:30:10,156 THESE PEOPLE ALL HAD UNINFECTION 775 00:30:10,156 --> 00:30:12,091 THAT CAUSED THEIR ME/CFS. 776 00:30:12,091 --> 00:30:14,394 -- HAD AN INFECTION THAT CAUSED 777 00:30:14,394 --> 00:30:15,228 THEIR ME/CFS. 778 00:30:15,228 --> 00:30:17,163 WE BROUGHT THEM TO CAMPUS TO DO 779 00:30:17,163 --> 00:30:20,333 DETAILED SCREENING FOR MEDICAL 780 00:30:20,333 --> 00:30:22,301 AND PSYCHIATRIC FACTORS. 781 00:30:22,301 --> 00:30:26,039 WE DID A DETAILED IN PERSON 782 00:30:26,039 --> 00:30:28,441 MEDICAL AND PSYCHIATRIC 783 00:30:28,441 --> 00:30:29,976 EVALUATIONS WE'LL TALK ABOUT IN 784 00:30:29,976 --> 00:30:31,444 A MINUTE AND FURTHER WE REALIZED 785 00:30:31,444 --> 00:30:34,280 IN MEDICINE, NOT EVERYTHING IS 786 00:30:34,280 --> 00:30:35,248 EVIDENT AT THE TIME WHEN YOU 787 00:30:35,248 --> 00:30:36,249 EVALUATE SOMEBODY. 788 00:30:36,249 --> 00:30:37,650 SO WE KNEW WE'D HAVE TO STAY IN 789 00:30:37,650 --> 00:30:38,918 TOUCH OVER THE COURSE OF THE 790 00:30:38,918 --> 00:30:41,220 STUDY TO SEE IF THINGS CHANGED, 791 00:30:41,220 --> 00:30:42,355 IF THAT WOULD CHANGE HOW WE 792 00:30:42,355 --> 00:30:43,890 LOOKED AT OUR PARTICIPANTS. 793 00:30:43,890 --> 00:30:45,658 SO THE FOLLOW UP WAS VERY 794 00:30:45,658 --> 00:30:46,793 IMPORTANT IN HELPING US 795 00:30:46,793 --> 00:30:49,762 UNDERSTAND THE TRAJECTORY OF 796 00:30:49,762 --> 00:30:50,663 THESE PARTICIPANTS. 797 00:30:50,663 --> 00:30:52,465 LASTLY, WE DIDN'T WANT TO TAKE 798 00:30:52,465 --> 00:30:55,168 IT UPON OURSELVES TO DECIDE WHAT 799 00:30:55,168 --> 00:30:57,437 THE PROPER CASE IS. 800 00:30:57,437 --> 00:30:59,605 WE WERE NEW IN THE FIELD AS OUR 801 00:30:59,605 --> 00:31:02,308 FIRST EFFORT AS A TEAM TO STUDY 802 00:31:02,308 --> 00:31:03,710 ME/CFS SO WE WORKED WITH EFFORTS 803 00:31:03,710 --> 00:31:06,245 THAT WERE CLINICAL EXPERTS THAT 804 00:31:06,245 --> 00:31:08,014 WERE WELL RENOWN IN THE FIELD TO 805 00:31:08,014 --> 00:31:12,518 HELP REVIEW EACH OF THE CASES. 806 00:31:12,518 --> 00:31:13,953 MAKE SURE THEY MEET ME/CFS 807 00:31:13,953 --> 00:31:16,789 CRITERIA AND ALL THE ADJUDICA 808 00:31:16,789 --> 00:31:22,762 ADJUDICATORS HAD TO AGREE THIS 809 00:31:22,762 --> 00:31:25,631 WAS A GOOD CASE AND ANYONE COULD 810 00:31:25,631 --> 00:31:26,065 VETO. 811 00:31:26,065 --> 00:31:27,233 WE FELT OUR CAUSE SELECTION 812 00:31:27,233 --> 00:31:27,867 PROCESS WAS STRONG. 813 00:31:27,867 --> 00:31:33,172 THIS IS AN OVERVIEW OF THE 814 00:31:33,172 --> 00:31:35,274 RECRUITMENT. 815 00:31:35,274 --> 00:31:45,785 WHILE WE WERE OPEN WE HAD 484 816 00:31:48,654 --> 00:31:53,092 INQUIRIES AND WOUND UP WITH THIS 817 00:31:53,092 --> 00:31:54,360 AND THE SARS COV2 PANDEMIC SHUT 818 00:31:54,360 --> 00:31:55,394 DOWN OPERATIONS WE WOULD HAVE 819 00:31:55,394 --> 00:31:56,896 CONTINUED TO RECRUIT IF WE COULD 820 00:31:56,896 --> 00:32:01,601 HAVE BUT WITH THE UNCERTAINTY OF 821 00:32:01,601 --> 00:32:02,869 THE PANDEMIC AND THE CLINICAL 822 00:32:02,869 --> 00:32:05,138 CENTER CLOSED TWO YEARS IT WAS 823 00:32:05,138 --> 00:32:08,307 FELT WE SHOULD SHUT DOWN OUR 824 00:32:08,307 --> 00:32:09,675 RECRUITMENT AND MOVE INTO OUR 825 00:32:09,675 --> 00:32:12,512 ANALYSIS AS FAST AS POSSIBLE. 826 00:32:12,512 --> 00:32:16,949 SO OF THE 484 PARTICIPANTS THAT 827 00:32:16,949 --> 00:32:19,218 INQUIRED, 267 WERE SCREENED OUT 828 00:32:19,218 --> 00:32:20,386 INITIALLY AND ON THE RIGHT SIDE 829 00:32:20,386 --> 00:32:22,488 IS I PROVIDE SOME REASONS WHY 830 00:32:22,488 --> 00:32:24,724 PEOPLE WERE SCREENED OUT ON THE 831 00:32:24,724 --> 00:32:26,893 TELEPHONE SCREENING. 832 00:32:26,893 --> 00:32:29,328 I PERSONALLY INTERVIEWED AND 833 00:32:29,328 --> 00:32:32,598 REVIEWED THE RECORDS OF 217 834 00:32:32,598 --> 00:32:33,166 INDIVIDUALS. 835 00:32:33,166 --> 00:32:34,634 OF THOSE 146 PEOPLE WERE 836 00:32:34,634 --> 00:32:35,768 SCREENED OUT AND YOU CAN SEE 837 00:32:35,768 --> 00:32:37,036 SOME REASONS WHY THEY SCREENED 838 00:32:37,036 --> 00:32:37,203 OUT. 839 00:32:37,203 --> 00:32:39,939 AND 44 PEOPLE UNFORTUNATELY WERE 840 00:32:39,939 --> 00:32:41,240 STUCK IN LIMBO THAT HAPPENED 841 00:32:41,240 --> 00:32:42,108 BECAUSE OF THE PANDEMIC AND 842 00:32:42,108 --> 00:32:44,944 NEVER GOT TO FINISH THE REVIEW 843 00:32:44,944 --> 00:32:47,580 PROCESS. 844 00:32:47,580 --> 00:32:48,948 OF THE PEOPLE THAT MADE IT 845 00:32:48,948 --> 00:32:50,349 THROUGH THE SECOND SET OF 846 00:32:50,349 --> 00:32:53,085 SCREENING, 25 HEALTHY VOLUNTEERS 847 00:32:53,085 --> 00:32:54,787 AND 27 ME/CFS PARTICIPANTS CAME 848 00:32:54,787 --> 00:32:55,221 TO CAMPUS. 849 00:32:55,221 --> 00:32:56,889 AND YOU CAN SORT OF SEE HERE ON 850 00:32:56,889 --> 00:32:59,926 THE RIGHT THE HEALTHY 851 00:32:59,926 --> 00:33:01,327 VOLUNTEERS. 852 00:33:01,327 --> 00:33:03,329 NOT EVERYBODY WHO THINK THEY'RE 853 00:33:03,329 --> 00:33:04,730 HEALTHY ARE HEALTHY AND FOUR OF 854 00:33:04,730 --> 00:33:07,300 THE HEALTHY VOLUNTEERS WERE 855 00:33:07,300 --> 00:33:08,768 FOUND TO HAVE MEDICAL ISSUES 856 00:33:08,768 --> 00:33:10,570 THAT WERE EXCLUSIONARY ON THEIR 857 00:33:10,570 --> 00:33:12,738 EVALUATION AND ONE HEALTHY 858 00:33:12,738 --> 00:33:14,173 VOLUNTEER WITHDREW LEAVING US 859 00:33:14,173 --> 00:33:15,842 WITH 21 HEALTHY VOLUNTEERS. 860 00:33:15,842 --> 00:33:18,377 IT'S WORTHY TO NOTE THE 861 00:33:18,377 --> 00:33:20,112 VOLUNTEERISM OF FAMILY IS ALWAYS 862 00:33:20,112 --> 00:33:25,484 SOMETHING SPECIAL AND TWO OF THE 863 00:33:25,484 --> 00:33:26,786 HEALTHY VOLUNTEERS WERE FAMILY 864 00:33:26,786 --> 00:33:29,222 MEMBERS OF THE PARTICIPANTS. 865 00:33:29,222 --> 00:33:31,224 OF OUR 27 ME/CFS PARTICIPANT 866 00:33:31,224 --> 00:33:36,729 CAME TO CAMPUS, ALL OF THEM 867 00:33:36,729 --> 00:33:41,734 WOULD HAVE MET ME/CFS CRITERIA 868 00:33:41,734 --> 00:33:44,103 MEASURED THAT WAY BUT TWO 869 00:33:44,103 --> 00:33:46,138 WITHDREW AND FOUR WERE INCLUDE 870 00:33:46,138 --> 00:33:47,206 ON OUR EVALUATION BECAUSE ONE 871 00:33:47,206 --> 00:33:52,945 WAS FOUND TO HAVE A RARE CANCER, 872 00:33:52,945 --> 00:33:55,748 D 873 00:33:55,748 --> 00:34:00,720 DES 874 00:34:00,720 --> 00:34:02,188 DESMOPLASTIC CARCINOMA AND SOME 875 00:34:02,188 --> 00:34:04,056 WERE ADJUDICATED OUT ON REVIEW 876 00:34:04,056 --> 00:34:05,324 BECAUSE THEY'RE CASES DIDN'T 877 00:34:05,324 --> 00:34:11,430 MEET OUR HIGH THRESHOLD FOR 878 00:34:11,430 --> 00:34:15,835 DEMONSTRATING INFECTIOUS 879 00:34:15,835 --> 00:34:16,836 CAUSALITY LEAVING US WITH 17 880 00:34:16,836 --> 00:34:17,136 CASES. 881 00:34:17,136 --> 00:34:19,538 WHAT INFECTIONS DID THESE HAVE. 882 00:34:19,538 --> 00:34:22,541 10 HAD UPPER RESPIRATORY TRACT 883 00:34:22,541 --> 00:34:26,646 INFECTIONS, THREE WERE ACUTE 884 00:34:26,646 --> 00:34:35,488 EBBSTEIN VIRAL INFECTION AND 885 00:34:35,488 --> 00:34:41,861 SOME WERE RELATED TO OTHER IN 886 00:34:41,861 --> 00:34:42,194 F 887 00:34:42,194 --> 00:34:42,495 INFECTIONS. 888 00:34:42,495 --> 00:34:44,997 WE HAVE HEALTHY VOLUNTEERS 889 00:34:44,997 --> 00:34:51,971 UNBLUE AND ME/CFS IN REDDISH 890 00:34:51,971 --> 00:34:52,204 SHADES. 891 00:34:52,204 --> 00:34:55,341 ON AVERAGE PEOPLE WERE MATCHED 892 00:34:55,341 --> 00:34:57,810 AND MID AGED IN THEIR LATE 30s, 893 00:34:57,810 --> 00:34:58,778 EARLY 40s. 894 00:34:58,778 --> 00:35:01,647 WE MATCHED REASONABLY WELL ON 895 00:35:01,647 --> 00:35:04,717 BIRTH SEX WITH 48% OF THE 896 00:35:04,717 --> 00:35:09,188 HEALTHY VOLUNTEERS BEING MEN AND 897 00:35:09,188 --> 00:35:16,429 41% OF THE ME/CFS BEING MEN AND 898 00:35:16,429 --> 00:35:18,965 IT SKEWED TOWARDS CAUCASIAN AND 899 00:35:18,965 --> 00:35:22,268 WELL EDUCATED AND BODY MASS 900 00:35:22,268 --> 00:35:25,538 INDEX WAS MATCHED AND THE ME/CFS 901 00:35:25,538 --> 00:35:26,672 PARTICIPANTS WERE PRETTY 902 00:35:26,672 --> 00:35:28,808 DISABLED BY THEIR SYMPTOMS. 903 00:35:28,808 --> 00:35:34,981 ALL THE PARTICIPANTS MET THE 904 00:35:34,981 --> 00:35:45,524 2015 CRITERIA AND 53% MET OTHER 905 00:35:46,859 --> 00:35:49,829 CRITERIA CAN AND PATIENTS CAME 906 00:35:49,829 --> 00:35:51,263 TO CAMPUS FOR THEIR INITIAL 907 00:35:51,263 --> 00:35:51,564 EVALUATION. 908 00:35:51,564 --> 00:35:54,967 THIS IS WHERE WE DID THE BULK OF 909 00:35:54,967 --> 00:35:55,668 THESE PHENOTYPING MEASURES. 910 00:35:55,668 --> 00:35:57,436 HERE'S A SAMPLE OF THE CALENDAR 911 00:35:57,436 --> 00:35:59,372 A PARTICIPANT WOULD GET PRIOR TO 912 00:35:59,372 --> 00:36:00,740 COMING TO CAMPUS. 913 00:36:00,740 --> 00:36:03,642 IT WAS A VIGOROUS AFFAIR AND A 914 00:36:03,642 --> 00:36:05,311 LOT OF OUR EFFORTS AS A TEAM 915 00:36:05,311 --> 00:36:07,880 WERE TO HELP PEOPLE NAVIGATE ALL 916 00:36:07,880 --> 00:36:10,082 THE DIFFERENT TESTS AND TIMING 917 00:36:10,082 --> 00:36:13,786 AND TO ENSURE THEY HAD REST TO 918 00:36:13,786 --> 00:36:15,554 RECUPERATE AND HELP CHEERLEAD 919 00:36:15,554 --> 00:36:16,655 THEM THROUGH THIS GAUNTLET OF 920 00:36:16,655 --> 00:36:19,859 RESEARCH WE PUT THEM THROUGH. 921 00:36:19,859 --> 00:36:21,193 YOU CAN SORT OF SEE IN THE 922 00:36:21,193 --> 00:36:22,995 CALENDAR WE HAD TO ENSURE FOR 923 00:36:22,995 --> 00:36:25,231 OURSELVES WE HAD TO MAKE SURE 924 00:36:25,231 --> 00:36:26,799 THERE WAS BREAKFAST AND LUNCH 925 00:36:26,799 --> 00:36:27,833 AND TIME OUT TO REST. 926 00:36:27,833 --> 00:36:29,402 WE HAD TO BUILD THAT IN THEIR 927 00:36:29,402 --> 00:36:32,071 COLORS TO MAKE SURE THEY CAN 928 00:36:32,071 --> 00:36:32,772 MAKE IT THROUGH THE IT RESEARCH 929 00:36:32,772 --> 00:36:40,913 PROTOCOL. 930 00:36:40,913 --> 00:36:44,316 OFF 931 00:36:44,316 --> 00:36:47,853 AFTER THE EVALUATION WE SENT 932 00:36:47,853 --> 00:36:49,422 ADJUDICATION PAMPHLETS TO OUR 933 00:36:49,422 --> 00:36:51,557 PANEL AND ALL THE MEDICAL 934 00:36:51,557 --> 00:36:53,692 TESTING AND HISTORY AND I WROTE 935 00:36:53,692 --> 00:36:54,827 NARRATIVES ON EACH OF THE 936 00:36:54,827 --> 00:36:56,228 PARTICIPANTS TO MAKE SURE I 937 00:36:56,228 --> 00:36:57,930 CAPTURED THEIR STORY CORRECTLY 938 00:36:57,930 --> 00:36:58,964 AND EVERY PARTICIPANT REVIEWED 939 00:36:58,964 --> 00:37:01,934 THEIR STORY AND SIGNED OFF ON IT 940 00:37:01,934 --> 00:37:05,638 PRIOR TO THE ADJUDICATION. 941 00:37:05,638 --> 00:37:11,844 THE PANEL OF EXPERTS IN 942 00:37:11,844 --> 00:37:12,778 DEPARTMENTALLY REVIEWED THESE 943 00:37:12,778 --> 00:37:17,450 AND EACH MADE THEIR INDEPENDENT 944 00:37:17,450 --> 00:37:17,750 DECISIONS. 945 00:37:17,750 --> 00:37:19,151 IT WASN'T GROUP THINK. 946 00:37:19,151 --> 00:37:20,719 IF THEY UNANIMOUSLY AGREED, A 947 00:37:20,719 --> 00:37:23,722 PERSON WAS INVITED BACK OR 948 00:37:23,722 --> 00:37:25,291 CONSIDERED A CASE FOR ANALYSIS 949 00:37:25,291 --> 00:37:26,826 AND IF THERE WAS AN AGREEMENT WE 950 00:37:26,826 --> 00:37:28,394 HAD THE PANEL MEET TO DISCUSS 951 00:37:28,394 --> 00:37:33,232 THE CASE TO SEE IF WE COULD GET 952 00:37:33,232 --> 00:37:40,039 TO UNANIMITY AND THANK YOU TO 953 00:37:40,039 --> 00:37:42,908 THE DEBATERS. 954 00:37:42,908 --> 00:37:44,043 [LISTING NAMES] 955 00:37:44,043 --> 00:37:45,177 AFTER THAT THEY WERE BROUGHT 956 00:37:45,177 --> 00:37:47,880 BACK FOR A SECOND VISIT TO HAVE 957 00:37:47,880 --> 00:37:50,282 AN EXERCISE STRESS TEST IT 958 00:37:50,282 --> 00:37:53,853 PERFORMED AND THIS IT WAS A CPAC 959 00:37:53,853 --> 00:37:55,955 FOLLOWED BY 72 HOURS OF 960 00:37:55,955 --> 00:37:58,958 MEASUREMENT TO UNDERSTAND THE 961 00:37:58,958 --> 00:38:00,659 BIOLOGY OF POST EXERTION 962 00:38:00,659 --> 00:38:00,893 MALAISE. 963 00:38:00,893 --> 00:38:02,228 HERE'S SOME MEASURES WE PUT 964 00:38:02,228 --> 00:38:05,931 TOGETHER AND PICTURE OF OUR 965 00:38:05,931 --> 00:38:07,099 PARTICIPANTS PERFORMING THE 966 00:38:07,099 --> 00:38:07,500 THIS. 967 00:38:07,500 --> 00:38:10,936 AND BESIDES THE C PET THERE WERE 968 00:38:10,936 --> 00:38:14,907 MEASURES OF THEIR BIO ENERGETICS 969 00:38:14,907 --> 00:38:17,610 USING A METABOLIC CHAMBER AND 970 00:38:17,610 --> 00:38:22,014 STOOL AND SALIVA AND THERE WAS A 971 00:38:22,014 --> 00:38:23,582 LUMBAR PUNCTURE AND 972 00:38:23,582 --> 00:38:25,284 NEUROCOGNITIVE TESTING AND OTHER 973 00:38:25,284 --> 00:38:25,851 NEUROLOGICAL TESTS. 974 00:38:25,851 --> 00:38:30,689 HERE'S AN EXAMPLE OF THEIR 975 00:38:30,689 --> 00:38:31,123 SCHEDULE. 976 00:38:31,123 --> 00:38:34,093 THE NICE THING IS THERE'S EIGHT 977 00:38:34,093 --> 00:38:35,394 OF REST AFTER THE C PET. 978 00:38:35,394 --> 00:38:38,497 IT WAS REALLY IMPORTANT TO US 979 00:38:38,497 --> 00:38:39,932 WITH ALL THE PARTICIPANTS WENT 980 00:38:39,932 --> 00:38:43,502 THROUGH THAT WE TRIED TO MAKE IT 981 00:38:43,502 --> 00:38:46,071 POSSIBLE THAT TO GET THROUGH THE 982 00:38:46,071 --> 00:38:48,007 PROCEDURING AND DO OUR MOST NOT 983 00:38:48,007 --> 00:38:58,317 TO INJURY ANYBODY. 984 00:38:59,652 --> 00:39:03,689 ON PHYSICAL EXAMPLE THERE WERE 985 00:39:03,689 --> 00:39:10,362 FINDINGS AND TWO PATIENTS WITH 986 00:39:10,362 --> 00:39:12,932 MOBILITY AND ONE PARTICIPANT HAD 987 00:39:12,932 --> 00:39:18,037 A SMALL NEUROPATHY AND ONE HAD 988 00:39:18,037 --> 00:39:20,439 RESIDUAL WEAKNESS FROM THEIR 989 00:39:20,439 --> 00:39:24,009 HERPES ZOSTER INFECTION AND ONE 990 00:39:24,009 --> 00:39:26,679 HAD WE THOUGHT HAD A DISORDER 991 00:39:26,679 --> 00:39:28,147 AND CLINICALLY THERE WAS NOT A 992 00:39:28,147 --> 00:39:30,149 LOT OF PATHOLOGY WE FOUND. 993 00:39:30,149 --> 00:39:32,718 THERE WAS SOME MILD SLEEP APNEA 994 00:39:32,718 --> 00:39:34,253 AND LIMB DISORDERS. 995 00:39:34,253 --> 00:39:35,688 ANY PARTICIPANT WE FOUND TO HAVE 996 00:39:35,688 --> 00:39:40,359 SLEEP APNEA WE GAVE THEM A 997 00:39:40,359 --> 00:39:42,494 SIX-WEEK TRIAL OF C PAP TO SEE 998 00:39:42,494 --> 00:39:44,730 IF IT MADE A DIFFERENCE AND IT 999 00:39:44,730 --> 00:39:47,466 DIDN'T CHANGE ANYBODY IN A 1000 00:39:47,466 --> 00:39:49,335 PROFOUND WAY. 1001 00:39:49,335 --> 00:39:52,304 BRAIN MRI THERE WAS LESIONS IN 1002 00:39:52,304 --> 00:39:56,275 FIVE HEALTHY VOLUNTEERS AND THE 1003 00:39:56,275 --> 00:39:58,277 PARTICIPANTS. 1004 00:39:58,277 --> 00:39:59,578 ON THE CLINICAL LABORATORY 1005 00:39:59,578 --> 00:40:00,746 EVALUATION THERE WASN'T TOO MUCH 1006 00:40:00,746 --> 00:40:01,113 DIFFERENCE. 1007 00:40:01,113 --> 00:40:03,382 WE DID A BROAD PANEL OF 1008 00:40:03,382 --> 00:40:04,717 HEMATOLOGY AND CHEMISTRY AND 1009 00:40:04,717 --> 00:40:06,085 IMMUNOLOGY AND VIROLOGY AND 1010 00:40:06,085 --> 00:40:12,358 HEAVY METALS ANALYSIS. 1011 00:40:12,358 --> 00:40:14,660 ON PSYCHOLOGICAL EVALUATION THE 1012 00:40:14,660 --> 00:40:15,928 PARTICIPANTS WERE MORE OFTEN 1013 00:40:15,928 --> 00:40:17,763 DEPRESSED THAN ANXIOUS BUT NOT 1014 00:40:17,763 --> 00:40:18,097 SEVERELY SO. 1015 00:40:18,097 --> 00:40:21,333 THIS SHOWED YOU SOME OF THOSE 1016 00:40:21,333 --> 00:40:21,734 DIFFERENCES. 1017 00:40:21,734 --> 00:40:24,136 AND WHEN PEOPLE DID HAVE ISSUES 1018 00:40:24,136 --> 00:40:28,140 THEY WERE MILD. 1019 00:40:28,140 --> 00:40:29,308 AND NOT THAT DIFFERENT THE 1020 00:40:29,308 --> 00:40:30,909 HEALTHY VOLUNTEERS AND WE'LL 1021 00:40:30,909 --> 00:40:32,978 SHOW THAT YOU THAT ON THE NEXT 1022 00:40:32,978 --> 00:40:33,412 SLIDE. 1023 00:40:33,412 --> 00:40:34,246 HERE IS SYMPTOM REPORTING. 1024 00:40:34,246 --> 00:40:37,249 ON THE LEFT IS ALL THE DIFFERENT 1025 00:40:37,249 --> 00:40:37,850 MEASURES WE TOOK. 1026 00:40:37,850 --> 00:40:42,821 IT'S QUITE AN IMPRESSIVE LIST 1027 00:40:42,821 --> 00:40:45,357 BUT YOU SEE THE P VALUES FOR ALL 1028 00:40:45,357 --> 00:40:47,192 THESE THINGS ARE HIGHLY 1029 00:40:47,192 --> 00:40:47,493 SUBSTANTIAL. 1030 00:40:47,493 --> 00:40:51,196 IN GENERAL ON MOST SYSTEM 1031 00:40:51,196 --> 00:40:52,798 MEASURES PEOPLE WITH PI AND CFS 1032 00:40:52,798 --> 00:40:54,867 WERE TWO STANDARD DEVIATIONS 1033 00:40:54,867 --> 00:40:57,436 WORSE THAN WHAT WE CONSIDERED 1034 00:40:57,436 --> 00:40:58,871 NORMAL IN THE POPULATION. 1035 00:40:58,871 --> 00:41:00,005 ON THE RIGHT SIDE TO GIVE A 1036 00:41:00,005 --> 00:41:03,542 SENSE OF THE DIFFERENCES BETWEEN 1037 00:41:03,542 --> 00:41:04,743 HEALTHY VOLUNTEERS AND ME/CFS 1038 00:41:04,743 --> 00:41:05,077 PARTICIPANTS. 1039 00:41:05,077 --> 00:41:12,184 BLUE AND RED YOU CAN SEE FOR 1040 00:41:12,184 --> 00:41:15,788 FATI 1041 00:41:15,788 --> 00:41:16,622 FATIGUE THEY'RE QUITE DIFFERENT 1042 00:41:16,622 --> 00:41:18,057 AND FAR ENDS OF THE SPECTRUM AND 1043 00:41:18,057 --> 00:41:22,361 SEEMS TO BE THE MOST PROFOUND 1044 00:41:22,361 --> 00:41:28,467 DIFFERENCESTOWN -- DIFFERENCES 1045 00:41:28,467 --> 00:41:30,202 BETWEEN THE GROUPS AND THERE'S 1046 00:41:30,202 --> 00:41:33,272 MORE SYMPTOMS IN TERMS OF THE 1047 00:41:33,272 --> 00:41:34,707 PHQ15 A MEASURE OF MULTIPLE 1048 00:41:34,707 --> 00:41:36,275 SYMPTOMS, AGAIN YOU SEE THE 1049 00:41:36,275 --> 00:41:37,976 PARTICIPANTS HAD MANY MANY MORE 1050 00:41:37,976 --> 00:41:42,681 SYMPTOMS THAN THE HEALTHY 1051 00:41:42,681 --> 00:41:43,382 VOLUNTEERS. 1052 00:41:43,382 --> 00:41:44,750 THE MEASURE OF SUBJECTIVE 1053 00:41:44,750 --> 00:41:46,251 COGNITION AND AGAIN YOU CAN SEE 1054 00:41:46,251 --> 00:41:47,419 THERE'S A DIFFERENCE BETWEEN THE 1055 00:41:47,419 --> 00:41:53,926 GROUPS BUT NOT PROFOUNDLY SO. 1056 00:41:53,926 --> 00:41:56,595 WITH THAT I'D LIKE TO THANK ALL 1057 00:41:56,595 --> 00:42:00,733 THE TEAM WE CALL 3D19 THAT 1058 00:42:00,733 --> 00:42:06,004 DIRECTLY WORK MYTH WITH ME AND 1059 00:42:06,004 --> 00:42:12,311 THAT WORK WITH THE PATIENTS. 1060 00:42:12,311 --> 00:42:15,080 [LISTING NAMES]YTH WITH ME AND 1061 00:42:15,080 --> 00:42:15,647 THAT WORK WITH THE PATIENTS. 1062 00:42:15,647 --> 00:42:16,281 [LISTING NAMES]TH WITH ME AND 1063 00:42:16,281 --> 00:42:16,849 THAT WORK WITH THE PATIENTS. 1064 00:42:16,849 --> 00:42:17,449 [LISTING NAMES]H WITH ME AND 1065 00:42:17,449 --> 00:42:18,016 THAT WORK WITH THE PATIENTS. 1066 00:42:18,016 --> 00:42:18,684 [LISTING NAMES] WITH ME AND THT 1067 00:42:18,684 --> 00:42:19,184 WORK WITH THE PATIENTS. 1068 00:42:19,184 --> 00:42:19,818 [LISTING NAMES]WITH ME AND THAT 1069 00:42:19,818 --> 00:42:20,319 WORK WITH THE PATIENTS. 1070 00:42:20,319 --> 00:42:23,088 [LISTING NAMES] 1071 00:42:23,088 --> 00:42:23,589 AND THANK YOU FOR YOUR 1072 00:42:23,589 --> 00:42:33,766 ATTENTION. 1073 00:42:36,201 --> 00:42:38,537 >> NOW WE'RE GOING MOVE INTO 1074 00:42:38,537 --> 00:42:40,739 FIRST GROUP AND THAT IS ON THE 1075 00:42:40,739 --> 00:42:44,543 IMMUNOLOGY AND OMICS. 1076 00:42:44,543 --> 00:42:47,946 I HAVE A COUPLE INTRODUCTORY 1077 00:42:47,946 --> 00:42:48,180 SLIDES. 1078 00:42:48,180 --> 00:42:51,784 HERE WE HAVE THREE SESSIONS. 1079 00:42:51,784 --> 00:42:56,722 THE FIRST WILL BE ON AMINO 1080 00:42:56,722 --> 00:43:03,729 PHENOTYPING LED BY STEVE 1081 00:43:03,729 --> 00:43:11,136 DICKERSON AND YOSHIMI AND THE 1082 00:43:11,136 --> 00:43:13,238 GUT MICROBIOME BY JOHN AND 1083 00:43:13,238 --> 00:43:13,572 OMICS. 1084 00:43:13,572 --> 00:43:16,108 I SHOWED THE SLIDE PREVIOUSLY. 1085 00:43:16,108 --> 00:43:20,712 IN THIS SLIDE HERE IN THIS TALK 1086 00:43:20,712 --> 00:43:22,781 WE'LL BE FOCUSSING PRIMARILY ON 1087 00:43:22,781 --> 00:43:23,816 THESE TWO ASPECT. 1088 00:43:23,816 --> 00:43:26,051 ALL OF OUR PATIENTS HAD AN 1089 00:43:26,051 --> 00:43:28,187 INFECTION SO HOW DOES THE 1090 00:43:28,187 --> 00:43:29,054 INFECTION AFFECT THE IMMUNE 1091 00:43:29,054 --> 00:43:32,724 SYSTEM AND HOW DOES IT AFFECT 1092 00:43:32,724 --> 00:43:33,325 THE MICROBIOME. 1093 00:43:33,325 --> 00:43:37,729 AND THEN FROM THERE HOW DOES IT 1094 00:43:37,729 --> 00:43:41,266 REALLY AFFECT THE AFFERENT PART 1095 00:43:41,266 --> 00:43:42,968 OF THE NERVOUS SYSTEM WHICH IS 1096 00:43:42,968 --> 00:43:48,106 HOW DOES THE IMMUNE SYSTEM 1097 00:43:48,106 --> 00:43:49,675 AFFECT THE BRAIN AS WELL AS THE 1098 00:43:49,675 --> 00:43:52,744 CHANGES IN METABOLITES AND THE 1099 00:43:52,744 --> 00:43:53,078 MICROBIOME. 1100 00:43:53,078 --> 00:43:58,650 WE'RE GOING TO FOCUS ON THAT 1101 00:43:58,650 --> 00:43:59,151 ASPECT. 1102 00:43:59,151 --> 00:44:02,921 AND THIS SLIDE BRIAN JUST SHOWED 1103 00:44:02,921 --> 00:44:04,623 ARE THE VARIOUS TESTINGS DONE ON 1104 00:44:04,623 --> 00:44:07,025 THE PATIENTS AND ON THIS SECTION 1105 00:44:07,025 --> 00:44:11,997 OF THE TALK YOU'LL HEAR ABOUT 1106 00:44:11,997 --> 00:44:17,536 ALL THE OMICS DONE ON THE BLOOD 1107 00:44:17,536 --> 00:44:21,273 LOOKING AT THE PROTEIN, LIPIDS 1108 00:44:21,273 --> 00:44:22,808 AND HERE WE'VE LISTED EACH OF 1109 00:44:22,808 --> 00:44:24,443 THE INSTITUTES THAT CONTRIBUTED 1110 00:44:24,443 --> 00:44:27,079 TO IT AND THE RESEARCHERS WHO 1111 00:44:27,079 --> 00:44:32,718 MAKE MAJOR CONTRIBUTION TO EACH 1112 00:44:32,718 --> 00:44:36,889 ONE OF THEM AND SO NOW THE FIRST 1113 00:44:36,889 --> 00:44:42,361 PRESENTATION WILL BE MADE BY 1114 00:44:42,361 --> 00:44:46,865 YOSHIMI AND YOSHIMI YAKAHATA 1115 00:44:46,865 --> 00:44:48,734 RECEIVED HER Ph.D. IN JAPAN AND 1116 00:44:48,734 --> 00:44:51,670 HER POST-DOCTORAL TRAINING WAS 1117 00:44:51,670 --> 00:44:53,572 AT UNIVERSITY OF NEBRASKA AS 1118 00:44:53,572 --> 00:44:55,541 WELL AS THE VIRAL IMMUNOLOGY 1119 00:44:55,541 --> 00:44:57,643 SECTION AT NINDS. 1120 00:44:57,643 --> 00:44:59,645 SHE'S CURRENTLY A STAFF 1121 00:44:59,645 --> 00:45:02,514 SCIENTIST AND WORKS RESEARCH 1122 00:45:02,514 --> 00:45:04,049 STUDIES RELATED TO ME/CFS IMMUNE 1123 00:45:04,049 --> 00:45:04,716 RESPONSES. 1124 00:45:04,716 --> 00:45:08,754 SHE STUDIES A VARIETY OF 1125 00:45:08,754 --> 00:45:11,557 NEUROLOGICAL DISEASES INCLUDING 1126 00:45:11,557 --> 00:45:14,560 HDLD1 AND A LOT OF WORK ON 1127 00:45:14,560 --> 00:45:16,128 MULTIPLE SCLEROSIS AND HAS BEEN 1128 00:45:16,128 --> 00:45:17,129 INTERESTED IN THE IMMUNE CHANGES 1129 00:45:17,129 --> 00:45:20,566 AND CHRONIC VIRAL INFECTIONS AS 1130 00:45:20,566 --> 00:45:21,199 WELL AS INFLAMMATORY DISEASES 1131 00:45:21,199 --> 00:45:24,503 AND WILL TALK ABOUT THE WORK 1132 00:45:24,503 --> 00:45:34,736 SHE'S DONE ON ME/CFS. 1133 00:45:34,736 --> 00:45:36,338 >> THANK YOU FOR THE 1134 00:45:36,338 --> 00:45:36,671 INTRODUCTION. 1135 00:45:36,671 --> 00:45:39,841 I'D LIKE TO PRESENT OUR 1136 00:45:39,841 --> 00:45:43,578 PHENOTYPING IN ME/CFS USING FLOW 1137 00:45:43,578 --> 00:45:47,449 SIGHT CYTOMETRY. 1138 00:45:47,449 --> 00:45:49,484 IT'S A DISEASE IMPAIRING. 1139 00:45:49,484 --> 00:45:51,786 THE MECHANISM IS STILL NOT FULLY 1140 00:45:51,786 --> 00:45:58,793 UNDERSTOOD YET. 1141 00:45:58,793 --> 00:46:03,999 HOWEVER, IT HAS BEEN FREQUENTLY 1142 00:46:03,999 --> 00:46:13,341 DESCRIBED INCLUDING -- AUTO 1143 00:46:13,341 --> 00:46:15,043 IMMUNITY AND T CELL METABOLISM 1144 00:46:15,043 --> 00:46:16,311 AND SO ON. 1145 00:46:16,311 --> 00:46:20,181 IN ADDITION THE DISEASE ONSET OF 1146 00:46:20,181 --> 00:46:22,584 ME/CFS IS OFTEN REPORTED TO BE 1147 00:46:22,584 --> 00:46:25,720 TREAT THE BY INFECTION AND THE 1148 00:46:25,720 --> 00:46:27,856 LINK BETWEEN INFECTION AND 1149 00:46:27,856 --> 00:46:31,960 MEDIATED DISEASE IS WELL 1150 00:46:31,960 --> 00:46:42,170 ESTABLISHED. 1151 00:46:52,180 --> 00:47:01,656 IN THIS STUDY WE COLLECTED BLOOD 1152 00:47:01,656 --> 00:47:04,659 AND CFS IN SUBJECTS WITH ME/CFS 1153 00:47:04,659 --> 00:47:12,968 AND THE CONTROL TO ANALYZE THIS 1154 00:47:12,968 --> 00:47:19,641 IMMUNOLOGY MARKER USING MULTIPLE 1155 00:47:19,641 --> 00:47:22,077 FLOW CYTOMETRY AND THE MARKERS 1156 00:47:22,077 --> 00:47:24,312 AND FIND THE LYMPHOCYTE AND 1157 00:47:24,312 --> 00:47:25,914 SUBSET AND ACTIVATION AND 1158 00:47:25,914 --> 00:47:30,986 EXERTION. 1159 00:47:30,986 --> 00:47:32,721 OVER ALL THERE WAS NO 1160 00:47:32,721 --> 00:47:34,689 SIGNIFICANT GROUP DIFFERENCES IN 1161 00:47:34,689 --> 00:47:37,659 PRESENTATION OF MAJOR LEUKOCYTE 1162 00:47:37,659 --> 00:47:41,396 INCLUDING T CELL, CD4 AND CD 8 1163 00:47:41,396 --> 00:47:48,403 AND B CELL AND K CELL AND 1164 00:47:48,403 --> 00:47:48,937 MONOC 1165 00:47:48,937 --> 00:47:49,204 MONOCYTE. 1166 00:47:49,204 --> 00:47:50,472 ALSO THE COUNTS WERE IN THE 1167 00:47:50,472 --> 00:47:51,773 NORMAL RANGE. 1168 00:47:51,773 --> 00:47:55,677 I'D LIKE TO SHOW SOME DIFFERENCE 1169 00:47:55,677 --> 00:48:05,253 AND THE SUBSET B CELL AND CD 8. 1170 00:48:05,253 --> 00:48:07,255 SO THESE ARE ANTIBODIES THAT 1171 00:48:07,255 --> 00:48:09,691 PLAY AN IMPORTANT ROLE OF THE 1172 00:48:09,691 --> 00:48:11,526 CONTROL IN INFECTION IN THE 1173 00:48:11,526 --> 00:48:12,360 ME/CFS AND THE ANTIBODY 1174 00:48:12,360 --> 00:48:13,995 PRODUCTION HAS BEEN ASSOCIATED 1175 00:48:13,995 --> 00:48:20,535 WITH BOTH PROTECTIVE AND 1176 00:48:20,535 --> 00:48:23,772 PATHOGENIC FRACTION IN 1177 00:48:23,772 --> 00:48:25,673 NEUROINFLAMMATORY DISEASE AND 1178 00:48:25,673 --> 00:48:28,176 THIS SHOWS THE DISEASE. 1179 00:48:28,176 --> 00:48:34,115 IMAGINE DATA SUGGESTS THAT 1180 00:48:34,115 --> 00:48:37,385 MULTIPLE STEP SUCH AS SET POINT 1181 00:48:37,385 --> 00:48:39,754 DEFECT ON B CELL AND AFFECT OF T 1182 00:48:39,754 --> 00:48:43,258 CELL HELP AND ALSO THE B CELL 1183 00:48:43,258 --> 00:48:45,660 ACTIVATION BRINGS OUT THE T CELL 1184 00:48:45,660 --> 00:48:47,362 HELP MIGHT MEDIATE SEVERAL 1185 00:48:47,362 --> 00:48:53,201 NEUROLOGICAL DISEASE. 1186 00:48:53,201 --> 00:49:01,142 IN THE RESULT GROUP OF PI CFS 1187 00:49:01,142 --> 00:49:06,915 SHOWS A SUBSET INCLUDING 1188 00:49:06,915 --> 00:49:08,983 INCREASE OF B CELL AND ALSO 1189 00:49:08,983 --> 00:49:09,684 DECREASE OF MEMORY TYPE OF B 1190 00:49:09,684 --> 00:49:14,656 CELL. 1191 00:49:14,656 --> 00:49:15,924 IN PI-ME/CFS COMPARED TO HEALTHY 1192 00:49:15,924 --> 00:49:24,899 VOLUNTEER. 1193 00:49:24,899 --> 00:49:27,469 UNFORTUNATELY, TO THE LOW NUMBER 1194 00:49:27,469 --> 00:49:30,038 IN THE CFS WE WERE ABLE TO 1195 00:49:30,038 --> 00:49:33,908 ANALYZE THE SUBSET ONLY TWO 1196 00:49:33,908 --> 00:49:38,580 SUBJECT WITH ME/CFS. 1197 00:49:38,580 --> 00:49:47,222 IN THE PATIENT ANTIBODY 1198 00:49:47,222 --> 00:49:51,659 PRODUCTION WERE DETECTED OVER 1199 00:49:51,659 --> 00:49:52,193 THE ME/CFS. 1200 00:49:52,193 --> 00:49:57,031 SO NEXT WE MOVED TO THE CD 8D 1201 00:49:57,031 --> 00:49:58,633 CELL. 1202 00:49:58,633 --> 00:50:01,469 IT PLAYS A CRUCIAL ROLE AGAINST 1203 00:50:01,469 --> 00:50:01,736 INFECTION. 1204 00:50:01,736 --> 00:50:06,441 AFTER ENCOUNTERING ANTIGEN 1205 00:50:06,441 --> 00:50:11,112 STIMULATION, CD T CELL ACTIVATED 1206 00:50:11,112 --> 00:50:15,984 AND DIFFERENTIATED TO THE TARGET 1207 00:50:15,984 --> 00:50:21,389 CELL CYTOTOXIC FATIGUE AND 1208 00:50:21,389 --> 00:50:25,360 EXPOSURE OF THE ANTIGEN OR 1209 00:50:25,360 --> 00:50:31,766 INFECTION CD 8 T CELL WERE 1210 00:50:31,766 --> 00:50:34,302 EXHAUSTED AND PRESENTED 1211 00:50:34,302 --> 00:50:36,838 PROLIFERATION OF CYTOKINE 1212 00:50:36,838 --> 00:50:37,138 PRODUCTION. 1213 00:50:37,138 --> 00:50:40,441 THIS REGULATED THE CD 8 T CELL 1214 00:50:40,441 --> 00:50:43,778 WITH DAMAGE ON THE OTHER CELL IN 1215 00:50:43,778 --> 00:50:46,681 THE CFS. 1216 00:50:46,681 --> 00:50:49,918 IN CD 8D CELL INCREASED 1217 00:50:49,918 --> 00:50:55,757 FREQUENCY OF THE POSITIVE CD 1218 00:50:55,757 --> 00:50:59,761 WERE DETECTED IN THE PI ME/CFS 1219 00:50:59,761 --> 00:51:00,328 PATIENT. 1220 00:51:00,328 --> 00:51:03,131 ALSO, THE DECREASED FREQUENCY OF 1221 00:51:03,131 --> 00:51:07,769 CD 2 TO POSITIVE CD 8 POSITIVE 1222 00:51:07,769 --> 00:51:11,673 CELLS WERE DETECTED COMPARED TO 1223 00:51:11,673 --> 00:51:17,412 HEALTHY VOLUNTEER. 1224 00:51:17,412 --> 00:51:21,649 SO PD 1 AND CD 26 DESCRIBED AS 1225 00:51:21,649 --> 00:51:24,319 THE IMMUNOCHECK MOLECULES TO 1226 00:51:24,319 --> 00:51:25,920 REGULATE T CELL ACTIVATION. 1227 00:51:25,920 --> 00:51:28,756 PD 1 INHIBIT T CELL ACTIVATION 1228 00:51:28,756 --> 00:51:32,193 THROUGH THE INTERACTION WITH THE 1229 00:51:32,193 --> 00:51:35,597 LIGAND PD 81 AND REPORT THE T 1230 00:51:35,597 --> 00:51:37,165 CELL ACTIVATION THROUGH 1231 00:51:37,165 --> 00:51:40,735 INTERRUPTION WITH THE LIGAND CD 1232 00:51:40,735 --> 00:51:41,269 155. 1233 00:51:41,269 --> 00:51:44,038 PD 1 IS ALSO REPORTED TO 1234 00:51:44,038 --> 00:51:48,409 DIRECTLY INHIBIT THE 1235 00:51:48,409 --> 00:51:51,813 PHOSPHORYLATION OF CD 226 IN THE 1236 00:51:51,813 --> 00:51:52,947 DOMAIN. 1237 00:51:52,947 --> 00:51:54,449 IN CHRONIC VIRAL INFECTION SUCH 1238 00:51:54,449 --> 00:52:01,055 AS HIV IT HAS BEEN REPORTED 1239 00:52:01,055 --> 00:52:05,360 ANTIGEN SPECIFIC CD 8 T CELL 1240 00:52:05,360 --> 00:52:10,431 DECREASED CD 2 ON THE CD 8 T 1241 00:52:10,431 --> 00:52:10,999 CELL. 1242 00:52:10,999 --> 00:52:11,799 THERE IS ARE SIGNIFICANT 1243 00:52:11,799 --> 00:52:15,770 DIFFERENCE OF THE SUBSET OF PI 1244 00:52:15,770 --> 00:52:18,806 ME/CFS BY GENDER. 1245 00:52:18,806 --> 00:52:25,680 IN MALE PI ME/CFS SHOW INCREASED 1246 00:52:25,680 --> 00:52:33,354 FREQUENCY OF CXCR5 AND THE 1247 00:52:33,354 --> 00:52:37,325 POSITIVE CD 8 CELL ARE ON THE 1248 00:52:37,325 --> 00:52:41,296 HAVE TOXIC REACTION ONE THE 1249 00:52:41,296 --> 00:52:43,765 VIRUS AND CONTROL ANTIBODY 1250 00:52:43,765 --> 00:52:44,832 PRODUCTION. 1251 00:52:44,832 --> 00:52:48,136 IN FEMALE, PI ME/CFS SHOWED AN 1252 00:52:48,136 --> 00:52:51,005 INCREASE FREQUENCY OF NAIVE CD 8 1253 00:52:51,005 --> 00:52:51,506 T CELL. 1254 00:52:51,506 --> 00:52:54,375 THIS RESULT MAY SUPPORT THE 1255 00:52:54,375 --> 00:52:56,644 GENDER SPECIFIC ORIENTATION IN 1256 00:52:56,644 --> 00:53:00,648 THE CD OF THE PI ME/CFS. 1257 00:53:00,648 --> 00:53:05,453 SO THE CONCLUSION, TO PI ME/CFS 1258 00:53:05,453 --> 00:53:11,459 HAS A DISEASE SPECIFIC 1259 00:53:11,459 --> 00:53:13,027 IMMUNOSIGNATURE INCLUDING THE B 1260 00:53:13,027 --> 00:53:15,697 CELL PHENOTYPE AND THE T CELL 1261 00:53:15,697 --> 00:53:18,299 EXERTION AND ACTIVATION AND ALSO 1262 00:53:18,299 --> 00:53:21,536 THE SPECIFIC DIFFERENCE OF THE 1263 00:53:21,536 --> 00:53:23,771 PI ME/CFS PATIENT. 1264 00:53:23,771 --> 00:53:34,248 THANK YOU FOR THE ATTENTION. 1265 00:53:35,249 --> 00:53:42,323 >> NEXT YOU'LL HEAR FROM 1266 00:53:42,323 --> 00:53:50,031 DR. JOHN McKCULLOCH AND LOOKS A 1267 00:53:50,031 --> 00:53:53,835 PROJECTS STUDYING THE ROLE OF 1268 00:53:53,835 --> 00:53:57,305 MICROBIOME ON HUMAN HEALTH 1269 00:53:57,305 --> 00:53:57,939 PARTICULARLY CANCER AND 1270 00:53:57,939 --> 00:54:01,142 INTERESTED IN DISCOVERING NOVEL 1271 00:54:01,142 --> 00:54:02,176 APPROACHES FOR ANALYZE 1272 00:54:02,176 --> 00:54:05,646 MICROBIOME DATA AND OFFERED A 1273 00:54:05,646 --> 00:54:06,514 SOFTWARE PACKAGE ON MICROBIOME 1274 00:54:06,514 --> 00:54:07,815 ANALYSIS AND WILL TALK ABOUT THE 1275 00:54:07,815 --> 00:54:09,817 WORK HE'S DONE ON THE GUT 1276 00:54:09,817 --> 00:54:16,190 MICROBIOME AND ME/CFS PATIENTS. 1277 00:54:16,190 --> 00:54:17,625 >> GOOD MORNING. 1278 00:54:17,625 --> 00:54:19,026 TODAY I'LL TALK ABOUT THE 1279 00:54:19,026 --> 00:54:20,895 MICROBIOME ASPECT OF THE STUDY. 1280 00:54:20,895 --> 00:54:22,864 WHAT WE DID AND WHY WE DID IT 1281 00:54:22,864 --> 00:54:25,266 AND WHAT WE FOUND AND THE NEXT 1282 00:54:25,266 --> 00:54:26,000 STEPS WILL BE. 1283 00:54:26,000 --> 00:54:29,704 SO THERE'S MORE THAN MEETS THE 1284 00:54:29,704 --> 00:54:35,676 EYE REGARDING LIFE WHEN WE LOOK 1285 00:54:35,676 --> 00:54:38,212 AT A HUMAN BEING AND ALL 1286 00:54:38,212 --> 00:54:43,184 SURFACES OF THE BODY AND THE 1287 00:54:43,184 --> 00:54:43,818 GASTROINTESTINAL TRACT THERE'S A 1288 00:54:43,818 --> 00:54:49,257 THRIVING COMMUNITY OF ORGANISMS 1289 00:54:49,257 --> 00:54:51,826 THAT HAVE A MUTUALLY BENEFICIAL 1290 00:54:51,826 --> 00:54:54,429 RELATIONSHIP TO US, THEIR HOST. 1291 00:54:54,429 --> 00:54:57,732 NOW, THE STRUCTURE OF AN 1292 00:54:57,732 --> 00:54:59,867 INDIVIDUAL'S MICROBIOME IS NOT 1293 00:54:59,867 --> 00:55:01,269 STATIC THROUGHOUT LIFE. 1294 00:55:01,269 --> 00:55:04,806 SO AS TIME GOES ON, THIS 1295 00:55:04,806 --> 00:55:06,374 MICROBIOME THE COMPOSITION MAY 1296 00:55:06,374 --> 00:55:08,810 CHANGE AND IS HIGHLY INFLUENCED 1297 00:55:08,810 --> 00:55:13,648 BY A PANOPLY OF FACTORS SUCH AS 1298 00:55:13,648 --> 00:55:18,619 DIET, AGE, GEOGRAPHICAL LOCATION 1299 00:55:18,619 --> 00:55:21,189 AND WHAT FAMILY MEMBERS YOU ARE 1300 00:55:21,189 --> 00:55:22,723 CONTACT WITH AND PET ETCETERA. 1301 00:55:22,723 --> 00:55:25,293 WHAT CAN HAPPEN IS YOU CAN GET A 1302 00:55:25,293 --> 00:55:27,762 CONDITION CALLED DYSBIOSIS WHICH 1303 00:55:27,762 --> 00:55:38,272 IS OPPOSED TO UBIOSIS AND THE 1304 00:55:40,408 --> 00:55:40,975 COMPOSITION OF THE MICROBIOME 1305 00:55:40,975 --> 00:55:45,246 AND THAT HINDERS OR ABROGATES 1306 00:55:45,246 --> 00:55:47,782 THE MUTUALLY BENEFICIAL 1307 00:55:47,782 --> 00:55:49,484 RELATIONSHIP BETWEEN THE 1308 00:55:49,484 --> 00:55:50,485 MICROBIOME AND THE HOST. 1309 00:55:50,485 --> 00:55:57,725 THIS CAN OR CANNOT BE REVERSED. 1310 00:55:57,725 --> 00:56:00,995 GUT MICROBIOME THE FU HAVE AN 1311 00:56:00,995 --> 00:56:03,831 UNHEALTHY OR THIS UNSTABLE 1312 00:56:03,831 --> 00:56:04,966 DYSBIOTIC GUT MICROBIOME IT'S 1313 00:56:04,966 --> 00:56:07,702 BEEN SHOWN TO CONTRIBUTE TO THE 1314 00:56:07,702 --> 00:56:09,403 PATHOGENESIS OF SEVERAL 1315 00:56:09,403 --> 00:56:11,405 METABOLIC DISORDERS AND EVEN 1316 00:56:11,405 --> 00:56:13,241 MENTAL ILLNESSES. 1317 00:56:13,241 --> 00:56:15,409 WELL, HOW DO YOU GAUGE WHAT'S IN 1318 00:56:15,409 --> 00:56:16,410 THE MICROBIOME? 1319 00:56:16,410 --> 00:56:17,645 ONCE YOU HAVE MICROBIOME 1320 00:56:17,645 --> 00:56:21,949 SAMPLES, HOW DO YOU ANALYZE AND 1321 00:56:21,949 --> 00:56:24,886 SEE WHAT'S IN THE MICROBIOME OF 1322 00:56:24,886 --> 00:56:25,219 INDIVIDUALS? 1323 00:56:25,219 --> 00:56:26,587 SO THE FIRST STAGE IS TO ANALYZE 1324 00:56:26,587 --> 00:56:28,456 THE CHARACTERISTICS WITHIN EACH 1325 00:56:28,456 --> 00:56:28,723 SAMPLE. 1326 00:56:28,723 --> 00:56:33,995 SO WITHIN A SAMPLE OF THE GUT 1327 00:56:33,995 --> 00:56:35,429 MICROBIOME CAN BE A STOOL SAMPLE 1328 00:56:35,429 --> 00:56:37,532 WHICH WILL BE REFLECTIVE OF THE 1329 00:56:37,532 --> 00:56:39,267 COMMUNITY THAT IS CURRENTLY AT 1330 00:56:39,267 --> 00:56:43,671 THE TIME OF COLLECTION OF SAMPLE 1331 00:56:43,671 --> 00:56:46,374 AND IN THE GUT MICROBIOME OF THE 1332 00:56:46,374 --> 00:56:51,779 INDIVIDUAL WHO IS SUPPLYING THAT 1333 00:56:51,779 --> 00:56:52,179 SAMPLE. 1334 00:56:52,179 --> 00:56:54,615 AND TOTAL DNA IS EXTRACTED FROM 1335 00:56:54,615 --> 00:56:56,250 FECAL SAMPLE AND WHAT THE 1336 00:56:56,250 --> 00:56:57,885 COMMUNITY IS BASED ON THE 1337 00:56:57,885 --> 00:56:59,787 DIFFERENT KINDS OF DNA WE FIND 1338 00:56:59,787 --> 00:57:01,455 IN THE SAMPLE. 1339 00:57:01,455 --> 00:57:05,560 NOW, ONE OF THE CHALLENGES FOR 1340 00:57:05,560 --> 00:57:09,697 THIS ANALYSIS IS THAT THE DNA 1341 00:57:09,697 --> 00:57:13,100 SEQUENCE IS OBTAINED FROM THE 1342 00:57:13,100 --> 00:57:14,969 CURRENTLY AVAILABLE DEEP 1343 00:57:14,969 --> 00:57:17,371 SEQUENCES. 1344 00:57:17,371 --> 00:57:23,010 THEY'RE IN VERY SMALL SIZES. 1345 00:57:23,010 --> 00:57:25,646 SO IT'S MUCH LIKE A THE SEQUENCE 1346 00:57:25,646 --> 00:57:27,582 WILL GIVE YOU MILLIONS AND 1347 00:57:27,582 --> 00:57:29,050 MILLIONS OF READS WHICH ARE 1348 00:57:29,050 --> 00:57:31,786 SHORT READS AND THAT REPRESENTS 1349 00:57:31,786 --> 00:57:37,992 ABOUT 0.01 PERFORMANCE A VIRAL 1350 00:57:37,992 --> 00:57:40,261 GENOME AND THEY'RE JUMBLED UP 1351 00:57:40,261 --> 00:57:44,098 VOW TO UNJUMBLE IN A VALID WAY 1352 00:57:44,098 --> 00:57:47,368 IN ORDER TO GAUGE WHAT THE 1353 00:57:47,368 --> 00:57:50,304 TAXONOMIC COMMUNITY IS WITHIN 1354 00:57:50,304 --> 00:57:52,506 THE MICROBIOME SAMPLE. 1355 00:57:52,506 --> 00:57:55,810 ONE COULD MAP THE READS TO KNOWN 1356 00:57:55,810 --> 00:57:57,178 GENOMES BUT THE APPROACHED WE 1357 00:57:57,178 --> 00:58:01,749 USED WAS TO ASSEMBLE THE REGION 1358 00:58:01,749 --> 00:58:03,818 TO LARGER SECTIONS MUCH LIKE YOU 1359 00:58:03,818 --> 00:58:11,726 WILL DO ONE A JIGSAW PUZZLE AND 1360 00:58:11,726 --> 00:58:14,295 NOT DONE BY HAND BUT TRIED AND 1361 00:58:14,295 --> 00:58:16,964 TESTED SOFTWARE. 1362 00:58:16,964 --> 00:58:25,206 THEN YOU CLASSIFY TAXONOMICALLY 1363 00:58:25,206 --> 00:58:31,045 THE SECTIONS AND WHAT SAMPLE DO 1364 00:58:31,045 --> 00:58:32,446 THESE WHAT COMPOSE THE 1365 00:58:32,446 --> 00:58:33,214 MICROBIOME. 1366 00:58:33,214 --> 00:58:35,850 THIS WAS DONE BY US USING A 1367 00:58:35,850 --> 00:58:40,988 COMPREHENSIVE SOFTWARE PACK AND 1368 00:58:40,988 --> 00:58:42,123 WE DEVELOPED OURSELVES AND IT'S 1369 00:58:42,123 --> 00:58:46,661 A TRIED AND TESTED METHOD. 1370 00:58:46,661 --> 00:58:49,664 NOW, THE MICROBIAL SPECIES YOU 1371 00:58:49,664 --> 00:58:53,200 CLASSIFY AND QUANTIFY THEM AND 1372 00:58:53,200 --> 00:58:54,769 THEN THAT'S THE SECOND PHASE OF 1373 00:58:54,769 --> 00:58:55,770 THE ANALYSIS. 1374 00:58:55,770 --> 00:58:56,771 HAVE ALL THE INFORMATION WITHIN 1375 00:58:56,771 --> 00:58:57,371 EACH SAMPLE. 1376 00:58:57,371 --> 00:59:00,341 NOW YOU HAVE TO COMPARE BETWEEN 1377 00:59:00,341 --> 00:59:02,209 SAMPLES AND HOW DO YOU DO THAT? 1378 00:59:02,209 --> 00:59:07,014 WHAT KINDS OF THINGS ARE WE 1379 00:59:07,014 --> 00:59:10,751 LOOKING FOR WHEN YOU GAUGE THE 1380 00:59:10,751 --> 00:59:11,052 MICROBIOME. 1381 00:59:11,052 --> 00:59:13,554 ONE IS ALPHA DIVERSITY AND ONE 1382 00:59:13,554 --> 00:59:15,690 IS BETA DIVERSITY. 1383 00:59:15,690 --> 00:59:17,825 YOU'RE GAUGING THE DIVERSITY AND 1384 00:59:17,825 --> 00:59:22,363 HOW MANY THINGS YOU FIND IN EACH 1385 00:59:22,363 --> 00:59:25,766 SAMPLE AND WHAT IS THEIR SHARE 1386 00:59:25,766 --> 00:59:26,300 OF THE DISTRIBUTION. 1387 00:59:26,300 --> 00:59:31,806 AND UNEVEN DISTRIBUTION AND IN 1388 00:59:31,806 --> 00:59:35,776 THE EXAMPLE I'M GIVING HERE 1389 00:59:35,776 --> 00:59:40,347 IMAGINE FOUR IMAGINARY SAMPLES 1390 00:59:40,347 --> 00:59:44,318 AND I'M REPRESENTING DIFFERENT 1391 00:59:44,318 --> 00:59:45,252 MICROBIAL CELLS AND DIFFERENT 1392 00:59:45,252 --> 00:59:46,020 COLORS REPRESENT DIFFERENT 1393 00:59:46,020 --> 00:59:46,687 SPECIES. 1394 00:59:46,687 --> 00:59:51,092 YOU CAN SEE ALL HAVE THE SAME 1395 00:59:51,092 --> 00:59:53,094 NUMBER OF INDIVIDUAL CELLS BUT 1396 00:59:53,094 --> 00:59:54,829 THE PROPORTIONS CAN BE 1397 00:59:54,829 --> 00:59:55,429 DIFFERENT. 1398 00:59:55,429 --> 00:59:58,532 SO IN SAMPLE A YOU'VE GOT 15 1399 00:59:58,532 --> 01:00:00,067 SPECIES WITH UNEVEN DISTRIBUTION 1400 01:00:00,067 --> 01:00:02,837 AND DOMINATION OF SOME SPECIES 1401 01:00:02,837 --> 01:00:07,007 AT HIGH LEVELS AND FEW AT LOWER 1402 01:00:07,007 --> 01:00:07,241 LEVELS. 1403 01:00:07,241 --> 01:00:09,477 SAMPLES B AND C HAVE SIX SPECIES 1404 01:00:09,477 --> 01:00:11,579 BUT ONE HAS AN EVEN 1405 01:00:11,579 --> 01:00:11,912 DISTRIBUTION. 1406 01:00:11,912 --> 01:00:15,282 SO 16% OF EACH SPECIES IN SAMPLE 1407 01:00:15,282 --> 01:00:17,852 B WHEREAS IN SAMPLE C HAVE YOU 1408 01:00:17,852 --> 01:00:19,286 DOMINATION OF BASICALLY TWO 1409 01:00:19,286 --> 01:00:21,689 SPECIES IN THE WHOLE OF THE 1410 01:00:21,689 --> 01:00:23,390 SAMPLE AND SPECIES D YOU'VE GOT 1411 01:00:23,390 --> 01:00:24,792 10. 1412 01:00:24,792 --> 01:00:27,228 BUT WHEN YOU LOOK AT DIVERSITY 1413 01:00:27,228 --> 01:00:28,395 IF YOU'RE GOING IT GAUGE WHICH 1414 01:00:28,395 --> 01:00:30,498 TWO SAMPLES ARE MOST SIMILAR ONE 1415 01:00:30,498 --> 01:00:34,335 CAN SAY SAMPLES B AND D THOUGH 1416 01:00:34,335 --> 01:00:35,803 THEY HAVE DIFFERENT OVER ALL 1417 01:00:35,803 --> 01:00:38,305 NUMBER OF SPECIES THEY'RE 1418 01:00:38,305 --> 01:00:39,039 PROPORTIONATELY SIMILAR TO EACH 1419 01:00:39,039 --> 01:00:39,340 OTHER. 1420 01:00:39,340 --> 01:00:43,410 IT'S GOT THE SAME PROPORTION OF 1421 01:00:43,410 --> 01:00:44,345 SIMILAR SHARES OF THE SAME KIND 1422 01:00:44,345 --> 01:00:50,985 OF TAXA. 1423 01:00:50,985 --> 01:00:55,122 GIVEN ALL THE EXPLANATION LET'S 1424 01:00:55,122 --> 01:00:55,656 LOOK AT THE RESULT. 1425 01:00:55,656 --> 01:00:57,658 WHEN WE LOOK AT DIVERSITY WITHIN 1426 01:00:57,658 --> 01:00:59,293 THE SAMPLE AND THE FROM THE 1427 01:00:59,293 --> 01:01:02,396 RESULTS OBTAINED IN THE STUDY 1428 01:01:02,396 --> 01:01:06,901 THERE WAS A STATISTICALLY 1429 01:01:06,901 --> 01:01:08,369 DIFFERENCE IN THE NUMBER OF 1430 01:01:08,369 --> 01:01:10,471 SPECIES THE CFS SAMPLES HAVING A 1431 01:01:10,471 --> 01:01:12,873 NUMBER OF OBSERVED FEATURES AS 1432 01:01:12,873 --> 01:01:15,276 COMPARED TO THE HEALTHY 1433 01:01:15,276 --> 01:01:15,543 CONTROLS. 1434 01:01:15,543 --> 01:01:20,147 BUT WHEN WE MEASURE THE 1435 01:01:20,147 --> 01:01:23,717 DIVERSITY WITH THE INDEX THE 1436 01:01:23,717 --> 01:01:26,120 MEASURE OF THE EFFECTED NUMBER 1437 01:01:26,120 --> 01:01:27,221 OF PARTIES YOU'RE WEIGHTING AND 1438 01:01:27,221 --> 01:01:30,124 GIVING MORE VALUE TO SPECIES 1439 01:01:30,124 --> 01:01:32,426 WHICH REPRESENT A HIGHER 1440 01:01:32,426 --> 01:01:34,929 PROPORTION OF YOUR SAMPLE THEN 1441 01:01:34,929 --> 01:01:37,198 IS NO REAL STATISTICAL 1442 01:01:37,198 --> 01:01:39,800 DIFFERENCE BETWEEN THE NUMBER OF 1443 01:01:39,800 --> 01:01:43,170 EFFECTIVE PARTIES AND NUMBER OF 1444 01:01:43,170 --> 01:01:44,471 SPECIES BETWEEN THE SAMPLES FROM 1445 01:01:44,471 --> 01:01:48,742 HEALTHY VOLUNTEERS AND THOSE 1446 01:01:48,742 --> 01:01:53,080 FROM CFS. 1447 01:01:53,080 --> 01:01:56,483 THIS SUGGESTS THAT MOST THE 1448 01:01:56,483 --> 01:02:00,521 DIFFERENCE WE SEE IS IN LOW 1449 01:02:00,521 --> 01:02:01,956 LEVEL AND SPECIES WHICH ARE AT 1450 01:02:01,956 --> 01:02:05,359 LOW ROWS OF ABUNDANCE. 1451 01:02:05,359 --> 01:02:07,795 MOVING FROM RICHNESS TO 1452 01:02:07,795 --> 01:02:10,197 TAXONOMIC COMPOSITION OF SAMPLES 1453 01:02:10,197 --> 01:02:11,632 ONE CAN GET A VISUAL 1454 01:02:11,632 --> 01:02:14,168 REPRESENTATION HOW SIMILAR OR 1455 01:02:14,168 --> 01:02:16,437 NOT THE COMPOSITION OF TWO 1456 01:02:16,437 --> 01:02:19,540 SAMPLES ARE TWO EACH OTHER BY 1457 01:02:19,540 --> 01:02:21,008 ALGORITHMS REDUCED THE 1458 01:02:21,008 --> 01:02:24,144 DIMENSIONALITY SUCH AS PCLA OR 1459 01:02:24,144 --> 01:02:25,246 UMAC. 1460 01:02:25,246 --> 01:02:26,413 WE DID SEVERAL. 1461 01:02:26,413 --> 01:02:29,750 THE ONE I'M SHOWING IS UMAC. 1462 01:02:29,750 --> 01:02:32,786 YOU CAN INTERPRET THIS AS EACH 1463 01:02:32,786 --> 01:02:35,489 DOT IN THE PLOT AS REPRESENTING 1464 01:02:35,489 --> 01:02:38,359 AN INDIVIDUAL SAMPLE AND THE 1465 01:02:38,359 --> 01:02:40,928 FURTHER APART TWO DOTS ARE FROM 1466 01:02:40,928 --> 01:02:42,329 EACH OTHER THAT MEANS THEY ARE 1467 01:02:42,329 --> 01:02:42,963 MORE DIFFERENT IN TERMS OF THEIR 1468 01:02:42,963 --> 01:02:49,336 COMPOSITION. 1469 01:02:49,336 --> 01:02:51,572 HERE WE SEE SAMPLES IN CFS CASES 1470 01:02:51,572 --> 01:02:54,575 IN RED AND HEALTHY VOLUNTEERS IN 1471 01:02:54,575 --> 01:02:56,510 BLUE AND THE MEAN POSITION OF 1472 01:02:56,510 --> 01:02:59,780 ALL SAMPLES WITHIN EACH GROUP IS 1473 01:02:59,780 --> 01:03:01,949 THE BIG DOTS. 1474 01:03:01,949 --> 01:03:04,652 YOU CAN SEE AN EVIDENT 1475 01:03:04,652 --> 01:03:05,519 SEPARATION AND THAT'S VISUAL. 1476 01:03:05,519 --> 01:03:11,091 WE ALSO DID A STATISTICAL TEST 1477 01:03:11,091 --> 01:03:14,495 PERMUTATION MULT VAREIALITY 1478 01:03:14,495 --> 01:03:17,298 ANALYSIS APPLIED TO THE SAMPLE 1479 01:03:17,298 --> 01:03:18,599 DISTANCE MATRIX AND SHOWS THE 1480 01:03:18,599 --> 01:03:20,534 DIFFERENCE BETWEEN THE GROUPS 1481 01:03:20,534 --> 01:03:23,871 AND SAMPLES CONTAINED WITHIN 1482 01:03:23,871 --> 01:03:27,141 OOCH GROUP IS STATISTICALLY 1483 01:03:27,141 --> 01:03:27,441 SIGNIFICANT. 1484 01:03:27,441 --> 01:03:29,810 AS EXPECTED VARIANCE IN THE 1485 01:03:29,810 --> 01:03:31,312 STRUCTURE OF THE MICROBIOME 1486 01:03:31,312 --> 01:03:36,216 INDEPENDENT OF DISEASE STALTUS. 1487 01:03:36,216 --> 01:03:39,820 YOU CAN SEE SOME ME/CFS SAMPLES 1488 01:03:39,820 --> 01:03:41,789 DONE THERE WHICH ARE CLOSER TO 1489 01:03:41,789 --> 01:03:47,795 HEALTHY VOLUNTEER SAMPLES. 1490 01:03:47,795 --> 01:03:50,531 OVERALL THE CENTROIDS ARE 1491 01:03:50,531 --> 01:03:52,433 SEPARATED AND THAT DIFFERENCE IS 1492 01:03:52,433 --> 01:03:53,434 STATISTICALLY SIGNIFICANT. 1493 01:03:53,434 --> 01:03:57,972 WELL, WHEN WE LOOK AT WHAT ARE 1494 01:03:57,972 --> 01:04:00,274 THE MICROBIAL SPECIES EITHER 1495 01:04:00,274 --> 01:04:03,544 ENRICHED OR DEPLETED, THERE ARE 1496 01:04:03,544 --> 01:04:05,512 IN THE ORDER OF 200 DIFFERENT 1497 01:04:05,512 --> 01:04:07,381 SPECIES WE FOUND OVER ALL IN 1498 01:04:07,381 --> 01:04:08,215 SAMPLES. 1499 01:04:08,215 --> 01:04:10,784 IF WE LOOK AT WHICH ONES ARE 1500 01:04:10,784 --> 01:04:14,521 INCREASED IN HEALTHY DONORS AND 1501 01:04:14,521 --> 01:04:18,325 WHICH ONES ARE INCREASED IN 1502 01:04:18,325 --> 01:04:19,793 ME/CFS SAMPLES WE FIND THERE ARE 1503 01:04:19,793 --> 01:04:21,729 ABOUT 25 DIFFERENT SPECIES WHICH 1504 01:04:21,729 --> 01:04:23,597 ARE ENRICHED IN EITHER GROUP. 1505 01:04:23,597 --> 01:04:26,734 AND BY MEANING ENRICHED I MEAN 1506 01:04:26,734 --> 01:04:28,569 STATISTICALLY SIGNIFICANTLY 1507 01:04:28,569 --> 01:04:30,004 DIFFERENT AND AT LEAST A TWO 1508 01:04:30,004 --> 01:04:31,405 FOLD INCREASE. 1509 01:04:31,405 --> 01:04:33,107 TWICE AS MUCH IN TERMS OF 1510 01:04:33,107 --> 01:04:35,776 PROPORTION IN ONE GROUP RATHER 1511 01:04:35,776 --> 01:04:39,146 THAN THE OTHER. 1512 01:04:39,146 --> 01:04:41,382 THEY ALL HAPPEN TO BE BACTERIA. 1513 01:04:41,382 --> 01:04:45,919 THOUGH WE LOOKED AT VIRUSES, 1514 01:04:45,919 --> 01:04:48,756 FUNGI AND OTHERS AND THE 25 1515 01:04:48,756 --> 01:04:51,191 WHICH WERE UP OR DOWN OR HAPPEN 1516 01:04:51,191 --> 01:04:51,792 TO BE BACTERIA. 1517 01:04:51,792 --> 01:04:54,328 I'M NOT GOING TO GO THROUGH ALL 1518 01:04:54,328 --> 01:04:56,530 OF THEM BUT SUFFICE TO SAY 1519 01:04:56,530 --> 01:04:59,533 SEVERAL SPECIES ESPECIALLY THOSE 1520 01:04:59,533 --> 01:05:01,135 ENRICHED IN THE CFS SAMPLES WERE 1521 01:05:01,135 --> 01:05:02,536 ALSO FOUND TO BE ENRICHED IN 1522 01:05:02,536 --> 01:05:08,409 OTHER STUDIES. 1523 01:05:08,409 --> 01:05:10,244 THAT CONFIRMS THOUGH IT'S NOT 1524 01:05:10,244 --> 01:05:14,548 EXACTLY THE SAME SPECIES OVER 1525 01:05:14,548 --> 01:05:16,183 ALL IT CONFIRMS PREVIOUS STUDIES 1526 01:05:16,183 --> 01:05:21,055 THAT INCLUDE THE MICROBIOME AND 1527 01:05:21,055 --> 01:05:22,322 PART OF GROUPS AND THAT'S NOT 1528 01:05:22,322 --> 01:05:22,923 WHERE IT ENDS. 1529 01:05:22,923 --> 01:05:24,525 THIS IS JUST THE BEGINNING. 1530 01:05:24,525 --> 01:05:26,560 THERE'S MORE THAT CAN BE DONE 1531 01:05:26,560 --> 01:05:27,728 WITH THIS DATA. 1532 01:05:27,728 --> 01:05:31,131 THE GERMS PACKAGE WE USED 1533 01:05:31,131 --> 01:05:36,670 OUTPUTS NOT ONLY TO TAXONOMIC 1534 01:05:36,670 --> 01:05:39,807 DATA BUT INDEPENDENT BIOLOGICAL 1535 01:05:39,807 --> 01:05:41,708 FUNCTION GAUGED FROM THE 1536 01:05:41,708 --> 01:05:43,811 PREDICTED PROTEOME FUNCTION 1537 01:05:43,811 --> 01:05:48,916 INDEPENDENT OF TAX IT -- 1538 01:05:48,916 --> 01:05:50,484 TAXONOMY AND A SECOND PAPER 1539 01:05:50,484 --> 01:05:52,453 FOCUSSING ON THE GUT MICROBIOME 1540 01:05:52,453 --> 01:05:57,591 RESULTS OF THIS COHORT. 1541 01:05:57,591 --> 01:05:59,793 WHICH WILL CORRELATE TO THE 1542 01:05:59,793 --> 01:06:01,595 MICROBIOME AND ITS FUNCTIONS TO 1543 01:06:01,595 --> 01:06:10,270 ALL THESE OTHER CLINICAL DATA. 1544 01:06:10,270 --> 01:06:12,673 ALSO, RICHARD RODRIGUEZ IS 1545 01:06:12,673 --> 01:06:14,608 HELPING BUILD A TRANS KINGDOM 1546 01:06:14,608 --> 01:06:16,210 NETWORK WITH THE INTENT OF 1547 01:06:16,210 --> 01:06:17,611 IDENTIFYING WHAT THE 1548 01:06:17,611 --> 01:06:19,046 RELATIONSHIPS ARE BETWEEN THESE 1549 01:06:19,046 --> 01:06:19,780 DIFFERENT CLINICAL DATA SETS AND 1550 01:06:19,780 --> 01:06:22,616 THE OMICS. 1551 01:06:22,616 --> 01:06:29,857 SO THIS MAY NOT BE A APPARENT 1552 01:06:29,857 --> 01:06:31,792 AND SEEING HOW DATA CONNECT TO 1553 01:06:31,792 --> 01:06:34,561 EACH OTHER BECAUSE YOU CAN 1554 01:06:34,561 --> 01:06:35,796 INFERENCE THE GUT MICROBIOME AND 1555 01:06:35,796 --> 01:06:38,632 FIRE THE DIETARY INTAKE AND THE 1556 01:06:38,632 --> 01:06:39,800 MICROBIOME WILL INFLUENCE THE 1557 01:06:39,800 --> 01:06:41,935 IMMUNE SYSTEM OR GUT-BRAIN AXIS 1558 01:06:41,935 --> 01:06:43,270 AND SO ON AND SO FORTH. 1559 01:06:43,270 --> 01:06:45,939 WARE TRYING TO FORMALIZE AND 1560 01:06:45,939 --> 01:06:47,508 FIND OUT WHAT THE DIRECTIONALITY 1561 01:06:47,508 --> 01:06:49,910 IS OR ABOUT WHAT THE IMPORTANCE 1562 01:06:49,910 --> 01:06:50,644 ASSOCIATIONS ARE. 1563 01:06:50,644 --> 01:06:54,915 WITH THIS I'D LIKE TO THANK 1564 01:06:54,915 --> 01:06:56,717 EVERYONE AT NINDS AND ESPECIALLY 1565 01:06:56,717 --> 01:07:00,888 AT THE GENETICS CORE FOR 1566 01:07:00,888 --> 01:07:04,858 SEQUENCING THE SAMPLES TO 1567 01:07:04,858 --> 01:07:06,460 RICHARD RODRIGUEZ AND MANY IN 1568 01:07:06,460 --> 01:07:09,263 THE LAB FOR HELPFUL INSIGHTS 1569 01:07:09,263 --> 01:07:09,997 REGARDING THE MICROBIOME OF THIS 1570 01:07:09,997 --> 01:07:14,635 PROJECT AND ESPECIALLY TO 1571 01:07:14,635 --> 01:07:22,910 DR. WALITT AND CARLOTTA AND 1572 01:07:22,910 --> 01:07:23,777 SCRUTINIZING THE DATA AND IT'S 1573 01:07:23,777 --> 01:07:24,144 BEEN A PLEASURE. 1574 01:07:24,144 --> 01:07:34,488 THANK YOU VERY MUCH. 1575 01:07:47,134 --> 01:07:49,636 >> I'LL BE TALKING ABOUT THE 1576 01:07:49,636 --> 01:07:50,704 VARIOUS OMIC PACKAGE WE LOOKED 1577 01:07:50,704 --> 01:07:51,805 AT AND THE DATA THERE. 1578 01:07:51,805 --> 01:07:54,074 WHAT DO I MEAN BY OMICS? 1579 01:07:54,074 --> 01:07:56,076 IT'S THE COLLECTIVE 1580 01:07:56,076 --> 01:07:57,477 CHARACTERIZATION AND 1581 01:07:57,477 --> 01:07:59,379 QUANTIFICATION OF POOLS OF 1582 01:07:59,379 --> 01:08:05,852 BIOLOGIC MOLECULES THAT FORM THE 1583 01:08:05,852 --> 01:08:09,690 DIYNAMICS OF AN ORGANISM OR 1584 01:08:09,690 --> 01:08:11,792 TRYING TO MEASURE EVERYTHING YOU 1585 01:08:11,792 --> 01:08:12,092 CAN. 1586 01:08:12,092 --> 01:08:14,161 THERE'S DIFFERENT OMICS ONE CAN 1587 01:08:14,161 --> 01:08:14,428 MEASURE. 1588 01:08:14,428 --> 01:08:15,796 THERE'S SUCH MAJOR CATEGORIES 1589 01:08:15,796 --> 01:08:17,698 FROM GENOMICS AND THE 1590 01:08:17,698 --> 01:08:22,636 METABOLOMICS AND PROTEOMICS AND 1591 01:08:22,636 --> 01:08:27,774 TRANSCRIPTOMICS AND IN TODAY'S 1592 01:08:27,774 --> 01:08:29,009 LECTURE I'LL FOCUS ON THESE 1593 01:08:29,009 --> 01:08:31,612 THREE WITH A DASH OF LIPID OMIC. 1594 01:08:31,612 --> 01:08:33,580 WHAT CAN YOU DO WITH OMICS? 1595 01:08:33,580 --> 01:08:35,582 THERE'S A NUMBER OF THINGS. 1596 01:08:35,582 --> 01:08:37,985 FIRST YOU CAN IDENTIFY MOLECULES 1597 01:08:37,985 --> 01:08:39,886 DIFFERENT BETWEEN GROUPS AND YOU 1598 01:08:39,886 --> 01:08:42,990 MEASURE THE INDIVIDUAL MOLECULES 1599 01:08:42,990 --> 01:08:45,559 AND COMPARE TO SEE IF THEY'RE 1600 01:08:45,559 --> 01:08:45,826 DIFFERENT. 1601 01:08:45,826 --> 01:08:48,528 YOU CAN THEN SEE HOW THE 1602 01:08:48,528 --> 01:08:49,296 DIFFERENCES RELATE BY PLACING 1603 01:08:49,296 --> 01:08:52,499 THEM INTO BIOLOGIC NETWORK AND 1604 01:08:52,499 --> 01:08:55,569 ANALYZING THE NETWORKS AND ARE 1605 01:08:55,569 --> 01:08:57,638 THE DIFFERENTLY EXPRESSED 1606 01:08:57,638 --> 01:08:58,038 MOLECULES RELATED. 1607 01:08:58,038 --> 01:08:59,773 IF THEY ARE IT SEEMS TO MAKE 1608 01:08:59,773 --> 01:09:00,674 THEM MORE SIGNIFICANT. 1609 01:09:00,674 --> 01:09:05,879 THEN THERE'S THE CONCEPT OF 1610 01:09:05,879 --> 01:09:06,780 CONSILIENCE DAVID GOLDSTEIN TOLD 1611 01:09:06,780 --> 01:09:08,715 ME ABOUT AT THE BEGINNING MUCH 1612 01:09:08,715 --> 01:09:09,583 THIS. 1613 01:09:09,583 --> 01:09:11,785 THE IDEA CAN USE MULTIPLE TYPES 1614 01:09:11,785 --> 01:09:13,420 OF KNOWLEDGE TO REACH NEW 1615 01:09:13,420 --> 01:09:13,720 CONCLUSIONS. 1616 01:09:13,720 --> 01:09:21,028 AND IN OUR OMICS IF WE USE AND 1617 01:09:21,028 --> 01:09:23,096 LOOK AT MULTIPLE OMICS 1618 01:09:23,096 --> 01:09:28,902 TECHNIQUES MERGE TO A SIMILAR 1619 01:09:28,902 --> 01:09:30,771 CONCLUSION ACROSS THE BIO 1620 01:09:30,771 --> 01:09:31,004 FLUIDS? 1621 01:09:31,004 --> 01:09:33,040 WITH THAT INFORMATION WE HOPE TO 1622 01:09:33,040 --> 01:09:34,608 POINT THE WAY FORWARD FOR TWO 1623 01:09:34,608 --> 01:09:35,309 THINGS. 1624 01:09:35,309 --> 01:09:39,780 ONE IS HOW CAN WE IDENTIFY NEW 1625 01:09:39,780 --> 01:09:41,548 BIO MARKERS TO DIFFERENTIATE 1626 01:09:41,548 --> 01:09:42,716 PERSONS WITH ME/CFS FROM THOSE 1627 01:09:42,716 --> 01:09:44,384 WHO DON'T HAVE IT AND TO HELP 1628 01:09:44,384 --> 01:09:51,258 IDENTIFY THERAPEUTIC TARGETS. 1629 01:09:51,258 --> 01:09:54,394 IN THE STUDY WE LOOKED AT 1630 01:09:54,394 --> 01:09:56,096 PROTEOMICS AND GOT 1300 PROTEINS 1631 01:09:56,096 --> 01:09:59,232 AND LIPID OMICS AND DIFFERENT 1632 01:09:59,232 --> 01:10:02,669 CATEGORIES AND LOOKED AT 1633 01:10:02,669 --> 01:10:05,205 PERIPHERAL MONONUCLEAR CELLS AND 1634 01:10:05,205 --> 01:10:08,675 LOOKED AT 18,000 TRANSCRIPT AND 1635 01:10:08,675 --> 01:10:12,979 1300 PROTEINS AND 444 1636 01:10:12,979 --> 01:10:15,282 METABOLITES IN THE MUSCLE 1637 01:10:15,282 --> 01:10:18,985 SAMPLES ABOUT 11,000 RNA 1638 01:10:18,985 --> 01:10:22,089 TRANSCRIPTS AND AS YOU HEARD 1639 01:10:22,089 --> 01:10:24,091 EARLIER FROM THE MICROBIOME 1640 01:10:24,091 --> 01:10:30,230 ABOUT 10,000 TAXOMICS WERE 1641 01:10:30,230 --> 01:10:30,530 IDENTIFIED. 1642 01:10:30,530 --> 01:10:33,033 WHEN HAVE YOU SO MANY SAMPLES 1643 01:10:33,033 --> 01:10:34,334 YOU HAVE TO CHOOSE TOOLS 1644 01:10:34,334 --> 01:10:38,672 EFFECTIVE AT ANALYZING THE DATA 1645 01:10:38,672 --> 01:10:41,308 AND THESE ARE PRINCIPLE 1646 01:10:41,308 --> 01:10:43,610 COMPONENT ANALYSIS AND THESE 1647 01:10:43,610 --> 01:10:44,644 REALLY ARE STATISTICS OF 1648 01:10:44,644 --> 01:10:49,449 BIOMARKER DISCOVERY. 1649 01:10:49,449 --> 01:10:54,721 WHAT ARE THESE TECHNIQUES LINEAR 1650 01:10:54,721 --> 01:10:56,690 REDUCTIONALITY TECHNIQUES USED 1651 01:10:56,690 --> 01:10:58,925 WHERE THE FEATURES OUT NUMBER 1652 01:10:58,925 --> 01:10:59,359 THE SAMPLES. 1653 01:10:59,359 --> 01:11:02,329 IT FITS THE DATA INTO LINES 1654 01:11:02,329 --> 01:11:06,933 ACROSS EACH OF THE DIFFERENT 1655 01:11:06,933 --> 01:11:07,901 COMPONENTS WHILE LOSING AS 1656 01:11:07,901 --> 01:11:08,668 LITTLE AS THE INFORMATION AS 1657 01:11:08,668 --> 01:11:10,737 POSSIBLE AND IT'S KNOWN AS 1658 01:11:10,737 --> 01:11:12,439 VARIANTS IN THE ANALYSES. 1659 01:11:12,439 --> 01:11:15,776 AND THEN YOU CAN USE THE 1660 01:11:15,776 --> 01:11:17,844 INFORMATION FOR EACH INDIVIDUAL 1661 01:11:17,844 --> 01:11:19,546 POINT AND SEE IF THERE'S FACTORS 1662 01:11:19,546 --> 01:11:20,180 THAT CAN SEPARATE ONE GROUP FROM 1663 01:11:20,180 --> 01:11:30,357 THE OTHER. 1664 01:11:30,590 --> 01:11:32,659 YOU CAN SEE A SET OF DOTS THAT 1665 01:11:32,659 --> 01:11:34,094 REPRESENT TWO GROUPS. 1666 01:11:34,094 --> 01:11:36,329 IF YOU TOOK ALL THE INFORMATION 1667 01:11:36,329 --> 01:11:37,798 AND PLOTTED IT TO A CERTAIN 1668 01:11:37,798 --> 01:11:40,200 POINT YOU WOULD END UP WITH 1669 01:11:40,200 --> 01:11:41,201 REDUCING A LARGE AMOUNT OF 1670 01:11:41,201 --> 01:11:42,302 INFORMATION TO A SINGLE POINT. 1671 01:11:42,302 --> 01:11:45,172 AND THEN YOU CAN SEE HOW DISTANT 1672 01:11:45,172 --> 01:11:46,339 OR DIFFERENT THE POINTS ARE FROM 1673 01:11:46,339 --> 01:11:47,607 EACH OTHER. 1674 01:11:47,607 --> 01:11:49,443 WHEN YOU USE A PRINCIPLE 1675 01:11:49,443 --> 01:11:54,147 COMPONENTS ANALYSIS OF PCA YOU 1676 01:11:54,147 --> 01:11:55,549 ANALYZE IT IN AN UNSUPERVISED 1677 01:11:55,549 --> 01:11:57,517 FASHION USING THE DATA ITSELF TO 1678 01:11:57,517 --> 01:11:58,585 FIND DIFFERENCES. 1679 01:11:58,585 --> 01:12:02,756 IN THIS CASE IMAGINE THE DATA 1680 01:12:02,756 --> 01:12:05,125 LOOKED LIKE ALL BLACK DOTS TO 1681 01:12:05,125 --> 01:12:07,794 YOU VERSUS PURPLE AND GREEN. 1682 01:12:07,794 --> 01:12:10,497 IF YOU LOOKED AT JUST THE 1683 01:12:10,497 --> 01:12:12,299 SCATTERING OF THE DOTS YOU'D 1684 01:12:12,299 --> 01:12:13,500 CHOOSE THE PURPLE ARROW AS THE 1685 01:12:13,500 --> 01:12:18,705 WAY TO DISCRIMINATE THE DATA. 1686 01:12:18,705 --> 01:12:29,249 HOWEVER, A PLS-DA ALLOWS US TO 1687 01:12:31,852 --> 01:12:32,552 CHOOSE DIRECTIONALITY AND 1688 01:12:32,552 --> 01:12:34,087 THERE'S PURPLE AND GREEN DATA 1689 01:12:34,087 --> 01:12:35,789 YOU WOULD CHOOSE A DIFFERENT 1690 01:12:35,789 --> 01:12:38,492 DIRECTION TO ANALYZE THE DATA. 1691 01:12:38,492 --> 01:12:40,827 SO PCA IS MUCH BETTER FOR 1692 01:12:40,827 --> 01:12:43,597 ANALYZE LINEAR RELATIONSHIPS 1693 01:12:43,597 --> 01:12:47,601 UNDATA WHILE PLS-DA IS SUPERIOR 1694 01:12:47,601 --> 01:12:49,436 FOR ANALYZING COST OF DATA AND 1695 01:12:49,436 --> 01:12:51,438 WE USE BOTH IN OUR ANALYSIS. 1696 01:12:51,438 --> 01:12:54,374 WE APPLY IT TO ME/CFS AND WE'LL 1697 01:12:54,374 --> 01:12:57,811 START WITH OUR PERIPHERAL BLOOD 1698 01:12:57,811 --> 01:12:59,546 MONONUCLEAR CELL RNA SEQUENCING. 1699 01:12:59,546 --> 01:13:02,883 WHEN YOU LOOK ON THE LEFT YOU 1700 01:13:02,883 --> 01:13:03,850 SEE DIFFERENT DOTS THAT DON'T 1701 01:13:03,850 --> 01:13:06,086 DISTINGUISH EACH OTHER FROM 1702 01:13:06,086 --> 01:13:06,386 THEMSELVES. 1703 01:13:06,386 --> 01:13:09,256 THE GREEN CFS AND THE RED 1704 01:13:09,256 --> 01:13:11,525 CONTROL DOTS SORT OF OVERLAP AND 1705 01:13:11,525 --> 01:13:14,861 THERE'S REALLY NO SEPARATION IN 1706 01:13:14,861 --> 01:13:18,598 THE GROUPS. 1707 01:13:18,598 --> 01:13:20,867 HOWEVER WHEN WE ANALYZE THE DATA 1708 01:13:20,867 --> 01:13:22,002 AND DIFFERENCE BETWEEN GROUPS WE 1709 01:13:22,002 --> 01:13:25,138 SEE SEPARATION ON THE RIGHT AND 1710 01:13:25,138 --> 01:13:26,873 THIS ANALYSIS SUGGESTS THAT 1711 01:13:26,873 --> 01:13:28,275 THERE'S SOMETHING THAT'S ABLE TO 1712 01:13:28,275 --> 01:13:29,809 BE SEPARATING IN THE DATA AND WE 1713 01:13:29,809 --> 01:13:35,649 NEEDED TO DIG FURTHER. 1714 01:13:35,649 --> 01:13:39,019 I WANT TO THANK THOSE WHO DID 1715 01:13:39,019 --> 01:13:42,489 MOST THIS WORK. 1716 01:13:42,489 --> 01:13:44,491 AS WE LOOKED AT ALL THE DATA 1717 01:13:44,491 --> 01:13:47,227 AGAIN THINK OF DEMOGRAPHICS, WE 1718 01:13:47,227 --> 01:13:49,029 SEPARATED BY BIRTH SEX AND HERE 1719 01:13:49,029 --> 01:13:53,033 IN PC4 YOU CAN SEE SEPARATE MALE 1720 01:13:53,033 --> 01:13:55,802 AND FEMALE MEN BEING GREEN AND 1721 01:13:55,802 --> 01:13:57,203 WOMEN BEING RED, THE GROUPS DO 1722 01:13:57,203 --> 01:13:58,972 SEPARATE. 1723 01:13:58,972 --> 01:14:01,141 SO THIS IS SUGGESTING TO US THAT 1724 01:14:01,141 --> 01:14:03,543 BIRTH SEX WAS HAVING AN IMPACT 1725 01:14:03,543 --> 01:14:04,377 ON OUR GENE EXPRESSION ANALYSIS 1726 01:14:04,377 --> 01:14:07,948 AND WAS CONFOUNDING OUR ANALYSIS 1727 01:14:07,948 --> 01:14:08,949 OF THE SAMPLES. 1728 01:14:08,949 --> 01:14:11,217 SO WE MIGHT DO BETTER IF WE 1729 01:14:11,217 --> 01:14:12,953 SEPARATED MEN FROM WOMEN AND 1730 01:14:12,953 --> 01:14:13,620 REANALYZE THE DATA. 1731 01:14:13,620 --> 01:14:14,988 THIS IS WHAT IT LOOKS LIKE WHEN 1732 01:14:14,988 --> 01:14:16,623 YOU DO THAT. 1733 01:14:16,623 --> 01:14:18,892 ON THE LEFT YOU CAN SEE THE MALE 1734 01:14:18,892 --> 01:14:22,128 DATA AND YOU CAN SEE THERE'S A 1735 01:14:22,128 --> 01:14:24,998 CLEAR SEPARATION ON THE PCA 1736 01:14:24,998 --> 01:14:28,702 BETWEEN THE HEALTHY VOLUNTEERS 1737 01:14:28,702 --> 01:14:29,836 AND PI ME/CFS MEN. 1738 01:14:29,836 --> 01:14:31,271 IN THE MIDDLE IS WHAT HAPPENS 1739 01:14:31,271 --> 01:14:33,139 WHEN YOU DO IT WITH FEMALE DATA. 1740 01:14:33,139 --> 01:14:35,075 AGAIN YOU SEE THIS ENORMOUS 1741 01:14:35,075 --> 01:14:35,375 SEPARATION. 1742 01:14:35,375 --> 01:14:37,110 SOUM HOW WHEN WE REDUCE THE 1743 01:14:37,110 --> 01:14:42,349 NUMBER OF SAMPLES WE SEE 1744 01:14:42,349 --> 01:14:45,218 SEPARATION POWER OF SEX ON OUR 1745 01:14:45,218 --> 01:14:45,685 ANALYSIS. 1746 01:14:45,685 --> 01:14:47,787 AND WHAT'S LABELLED C HERE IS A 1747 01:14:47,787 --> 01:14:51,725 VEN DIAGRAM AND OF THE 1748 01:14:51,725 --> 01:14:53,460 DIFFERENTIALLY EXPRESSED GENES 1749 01:14:53,460 --> 01:14:55,328 IN BOTH THE GROUPS AND MEN AND 1750 01:14:55,328 --> 01:14:57,430 WOMEN ONLY 34 WERE THE SAME. 1751 01:14:57,430 --> 01:15:00,567 AND GIVES A SENSE OF HOW 1752 01:15:00,567 --> 01:15:02,569 DIFFERENT THE PBMCs WERE 1753 01:15:02,569 --> 01:15:09,809 BEHAVING BY SEX. 1754 01:15:09,809 --> 01:15:11,778 WHEN BIRTH SEX WERE CONSIDERED 1755 01:15:11,778 --> 01:15:12,412 WE WERE ABLE TO DISCRIMINATE 1756 01:15:12,412 --> 01:15:18,618 FROM THE HEALTHY VOLUNTEERS. 1757 01:15:18,618 --> 01:15:20,520 I'M SHOWING THE DATA THAT SHOWS 1758 01:15:20,520 --> 01:15:30,263 IT'S MOSTLY RELATED TO THE TLR9 1759 01:15:30,263 --> 01:15:31,297 PROTEIN-PROTEIN INTERACTOME IN 1760 01:15:31,297 --> 01:15:34,034 MEN AND IT'S CONSISTENT WITH THE 1761 01:15:34,034 --> 01:15:37,537 EXPANSION OF THE CELLS AND 1762 01:15:37,537 --> 01:15:38,805 DECREASED SWITCHED B CELL IN 1763 01:15:38,805 --> 01:15:39,873 FLOW CYTOMETRY WE PRESENTED 1764 01:15:39,873 --> 01:15:43,043 EARLIER AND THIS IS CONSISTENT 1765 01:15:43,043 --> 01:15:43,943 WITH THE OBSERVATION. 1766 01:15:43,943 --> 01:15:46,079 WHAT ARE WE SEEING IN THE WOMEN? 1767 01:15:46,079 --> 01:15:50,917 HERE WE SEE CYTOKINE CHANGES AND 1768 01:15:50,917 --> 01:15:52,919 PROCESSES AND B CELL BEING UP 1769 01:15:52,919 --> 01:15:53,887 REGULATED. 1770 01:15:53,887 --> 01:15:55,789 AND THIS AGAIN IS ALSO 1771 01:15:55,789 --> 01:15:57,190 CONSISTENT WITH EXPANSION OF 1772 01:15:57,190 --> 01:15:59,793 NAIVE B CELLS AND DECREASED 1773 01:15:59,793 --> 01:16:00,727 MEMORY B CELLS. 1774 01:16:00,727 --> 01:16:03,163 SO THIS SUGGESTS MORE THAN ONE 1775 01:16:03,163 --> 01:16:07,133 WAY TO GET TO THE IMMUNOLOGICAL 1776 01:16:07,133 --> 01:16:08,835 PHENOTYPE WE'RE WERE GETTING TO 1777 01:16:08,835 --> 01:16:11,805 EARLIER THERE MAY BE TWO IMMUNE 1778 01:16:11,805 --> 01:16:20,914 RESPONSES. 1779 01:16:20,914 --> 01:16:22,615 THAT'S AN INTERESTING PATTERN 1780 01:16:22,615 --> 01:16:27,187 BUT THIS IS LOOKING AT THE 1781 01:16:27,187 --> 01:16:33,193 PLASMA PROTEOMICS YOU SEE THE 1782 01:16:33,193 --> 01:16:33,460 ANALYSIS. 1783 01:16:33,460 --> 01:16:36,696 THIS IS THE CENTER FOR HUMAN 1784 01:16:36,696 --> 01:16:39,399 IMMUNOLOGY WHO DID THIS WORK AND 1785 01:16:39,399 --> 01:16:43,103 YOU GET A LITTLE BIT OF SPRAYING 1786 01:16:43,103 --> 01:16:45,672 SEPARATION BUT NOTHING REALLY 1787 01:16:45,672 --> 01:16:45,939 WONDERFUL. 1788 01:16:45,939 --> 01:16:47,774 WHEN WE SEPARATE BY MEN AND 1789 01:16:47,774 --> 01:16:50,643 WOMEN WOW, THAT'S A LOT OF 1790 01:16:50,643 --> 01:16:51,077 SEPARATION. 1791 01:16:51,077 --> 01:16:52,912 IT SEEMED TO BE PLAYING A ROLE 1792 01:16:52,912 --> 01:16:53,913 HERE. 1793 01:16:53,913 --> 01:16:54,614 UNFORTUNATELY YOU WOULD LOOK 1794 01:16:54,614 --> 01:16:56,082 CLOSELY AND SEE THE VARIANCES 1795 01:16:56,082 --> 01:16:59,786 THAT ARE EXPLAINED BY THE 1796 01:16:59,786 --> 01:17:03,056 DIFFERENCES ARE SMALL AND SO 1797 01:17:03,056 --> 01:17:05,558 THIS DOESN'T EXPLAIN A LOT OF 1798 01:17:05,558 --> 01:17:10,563 THE DIFFERENCE IN PROTEOMICS. 1799 01:17:10,563 --> 01:17:14,434 WHEN WE LOOK AT CEREBRAL SPINAL 1800 01:17:14,434 --> 01:17:16,569 FLUID AND YOU SEE THE PROFOUND 1801 01:17:16,569 --> 01:17:16,870 SEPARATION. 1802 01:17:16,870 --> 01:17:18,505 SO BIRTH SEX AGAIN HAS AN IMPACT 1803 01:17:18,505 --> 01:17:22,776 ON THE PROTEOMICS OF BLOOD AND 1804 01:17:22,776 --> 01:17:25,945 CEREBRAL SPINAL FLOOD BUT 1805 01:17:25,945 --> 01:17:27,313 PROTEOMICS ON AVERAGE BEHAVE 1806 01:17:27,313 --> 01:17:30,183 POORLY BY THE LOW VARIANCES 1807 01:17:30,183 --> 01:17:30,884 EXPLAINED. 1808 01:17:30,884 --> 01:17:33,286 HOW ABOUT IN THE MUSCLE? 1809 01:17:33,286 --> 01:17:35,288 HERE WE'RE LOOKING AT MUSCLE DNA 1810 01:17:35,288 --> 01:17:35,588 SEQUENCING. 1811 01:17:35,588 --> 01:17:37,423 ON THE LEFT IS ALL PARTICIPANTS 1812 01:17:37,423 --> 01:17:39,793 AND YOU DON'T SEE VERY MUCH 1813 01:17:39,793 --> 01:17:40,093 SEPARATION. 1814 01:17:40,093 --> 01:17:41,828 WILL THE ME SEPARATE BY BIRTH 1815 01:17:41,828 --> 01:17:42,328 SEX. 1816 01:17:42,328 --> 01:17:43,530 SEE AGAIN WONDERFUL SEPARATION 1817 01:17:43,530 --> 01:17:45,298 IN MEN AND WOMEN. 1818 01:17:45,298 --> 01:17:48,234 SO IT CAN AGAIN DISCRIMINATION 1819 01:17:48,234 --> 01:17:49,669 WHEN YOU CONSIDER BIRTH SEX. 1820 01:17:49,669 --> 01:17:57,310 THIS DATA THANK YOU TO DIAGO AND 1821 01:17:57,310 --> 01:17:58,878 OTHERS FOR PROVIDING THE DATA TO 1822 01:17:58,878 --> 01:17:59,045 US. 1823 01:17:59,045 --> 01:18:06,019 WHAT IS DIFFERENT IN THE MEN? 1824 01:18:06,019 --> 01:18:10,557 HERE YOU SEE PROCESSING AND BETA 1825 01:18:10,557 --> 01:18:12,458 OXIDATION NETWORK AND DOWN 1826 01:18:12,458 --> 01:18:13,026 REGULATION IN MITOCHONDRIAL 1827 01:18:13,026 --> 01:18:17,797 PROCESS. 1828 01:18:17,797 --> 01:18:22,635 IN THE WOMEN YOU SEE 1829 01:18:22,635 --> 01:18:25,505 UPREGULATION AND DOWN REGULATION 1830 01:18:25,505 --> 01:18:27,407 FATTY OXIDATION MITOCHONDRIAL 1831 01:18:27,407 --> 01:18:28,208 PROCESSING. 1832 01:18:28,208 --> 01:18:32,912 I'LL HAVE THAT LIPID OMICS. 1833 01:18:32,912 --> 01:18:34,714 AGAIN, THANK YOU FOR PROVIDING 1834 01:18:34,714 --> 01:18:36,883 US THE DATA AND YOU SEE THE 1835 01:18:36,883 --> 01:18:39,319 PATTERNS IN ALL PARTICIPANTS YOU 1836 01:18:39,319 --> 01:18:42,422 SEE POOR SPRAYING BUT WHEN YOU 1837 01:18:42,422 --> 01:18:45,391 SEPARATE BY BIRTH SEX YOU GET 1838 01:18:45,391 --> 01:18:49,796 NICE SEPARATION IN BOTH. 1839 01:18:49,796 --> 01:18:53,499 HOW ABOUT CEREBRAL SPINAL FLUID 1840 01:18:53,499 --> 01:18:54,100 METABOLOMIC. 1841 01:18:54,100 --> 01:18:55,935 YOU SEE POOR SEPARATION WITH ALL 1842 01:18:55,935 --> 01:18:57,904 COMERS. 1843 01:18:57,904 --> 01:19:00,907 BUT WHEN WE APPLY KSLDA WITH THE 1844 01:19:00,907 --> 01:19:02,041 DIFFERENTIAL EXPRESSION OF GENES 1845 01:19:02,041 --> 01:19:03,476 HERE'S THE FIRST TIME AT LOOKING 1846 01:19:03,476 --> 01:19:06,746 AT ALL COMERS WHERE YOU SEE 1847 01:19:06,746 --> 01:19:07,580 SEPARATION. 1848 01:19:07,580 --> 01:19:10,316 OF ALL THE BIO FLUIDS WE TESTED 1849 01:19:10,316 --> 01:19:15,388 ONLY THE CFS METABOLOMICS 1850 01:19:15,388 --> 01:19:16,723 SEPARATED BY DIAGNOSTIC GROUP. 1851 01:19:16,723 --> 01:19:20,393 AND IT EXPLAINS A FAIR BIT OF 1852 01:19:20,393 --> 01:19:21,694 THE VARIANTS THAT 35% OF THE 1853 01:19:21,694 --> 01:19:27,066 VARIANT. 1854 01:19:27,066 --> 01:19:31,771 EXACTLY WHAT IS DIFFERENT? 1855 01:19:31,771 --> 01:19:35,642 THERE'S GLUTAMATE, POLY AMMIN 1856 01:19:35,642 --> 01:19:39,178 PATHWAYS AND TCA PATHWAY 1857 01:19:39,178 --> 01:19:39,479 METABOLITES. 1858 01:19:39,479 --> 01:19:41,180 AND THESE IF YOU FOLLOW THE 1859 01:19:41,180 --> 01:19:43,116 LITERATURE SHE'S COME UP AGAIN 1860 01:19:43,116 --> 01:19:43,483 AND AGAIN 1861 01:19:43,483 --> 01:19:47,420 THESE COME UP AGAIN AND AGAIN 1862 01:19:47,420 --> 01:19:49,255 NOT ONLY IN THE CFS LITERATURE 1863 01:19:49,255 --> 01:19:50,223 BUT IN THE LONG COVID. 1864 01:19:50,223 --> 01:19:53,960 THESE DIFFERENCE ALL PARTS OF 1865 01:19:53,960 --> 01:19:55,361 SEVERAL PATHWAYS. 1866 01:19:55,361 --> 01:19:58,932 THE ARGININE PATHWAY AND THE 1867 01:19:58,932 --> 01:19:59,832 METABOLIC PATHWAY AND BRANCH 1868 01:19:59,832 --> 01:20:02,902 CHAIN AMINO ACID PATHWAYS THAT 1869 01:20:02,902 --> 01:20:07,173 ARE ALL FUNDAMENTAL IN CELL 1870 01:20:07,173 --> 01:20:07,473 REGULATION. 1871 01:20:07,473 --> 01:20:11,744 SO HOW ABOUT BIRTH SEX AND CFS 1872 01:20:11,744 --> 01:20:12,078 METABOLOMICS? 1873 01:20:12,078 --> 01:20:15,982 WHEN WE LOOK AT MEN AND WOMEN, 1874 01:20:15,982 --> 01:20:19,786 WHEN WE APPLY THE PLSDA WE 1875 01:20:19,786 --> 01:20:26,526 IMPROVE THE PERFORMANCE AT 1876 01:20:26,526 --> 01:20:30,063 SEPARATION AND IN MEN IT'S 1877 01:20:30,063 --> 01:20:31,364 RELATED TO TRYPTOPHAN AND 1878 01:20:31,364 --> 01:20:34,033 SEROTONIN SIGNALLING 1879 01:20:34,033 --> 01:20:35,635 DIFFERENCES. 1880 01:20:35,635 --> 01:20:40,606 IT MAY PROVOKE MEMORIES OF A 1881 01:20:40,606 --> 01:20:43,309 PAPER OF SEROTONIN REDUCTION IN 1882 01:20:43,309 --> 01:20:43,776 LONG COVID. 1883 01:20:43,776 --> 01:20:46,579 WHAT SHOULD YOU TAKE HOME FROM 1884 01:20:46,579 --> 01:20:47,447 THIS? 1885 01:20:47,447 --> 01:20:49,749 BIRTH SIX IS MECHANICALLY 1886 01:20:49,749 --> 01:20:52,185 RELEVANT IN ME/CFS. 1887 01:20:52,185 --> 01:20:53,853 DISCRIMINATIVE POWER INCREASES 1888 01:20:53,853 --> 01:20:55,989 DESPITE A DECREASE IN SAMPLE 1889 01:20:55,989 --> 01:20:57,991 SIZE. 1890 01:20:57,991 --> 01:21:01,094 THIS IS SEEN IN GENE EXPRESSION 1891 01:21:01,094 --> 01:21:03,363 AND IMMUNE CELLS AND PROTEINS 1892 01:21:03,363 --> 01:21:05,498 AND BLOOD AND CEREBRAL FINAL 1893 01:21:05,498 --> 01:21:10,336 FLUID AND IN LIPIDS IN THE BLOOD 1894 01:21:10,336 --> 01:21:13,906 AND MOLECULES IN THE SPINAL 1895 01:21:13,906 --> 01:21:14,107 FLUID. 1896 01:21:14,107 --> 01:21:15,775 EVERYWHERE WE LOOKED WE FOUND 1897 01:21:15,775 --> 01:21:17,844 THIS AND SEEMS TO BE PROFOUND 1898 01:21:17,844 --> 01:21:19,278 IMPORTANCE IN UNDERSTANDING THE 1899 01:21:19,278 --> 01:21:20,279 NATURE OF THE ME/CFS. 1900 01:21:20,279 --> 01:21:26,452 OF ALL THE BIO FLUIDS WE TESTED 1901 01:21:26,452 --> 01:21:29,956 CEREBRAL FINAL FLUID AND 1902 01:21:29,956 --> 01:21:31,791 METABOLOMICS WAS THE BEST AT 1903 01:21:31,791 --> 01:21:35,795 DISCRIMING THIS AND TO ME IT 1904 01:21:35,795 --> 01:21:38,331 SUGGESTS THE CENTRAL NERVOUS 1905 01:21:38,331 --> 01:21:42,602 SYSTEM IS THE PLACE DIVERGENT 1906 01:21:42,602 --> 01:21:43,603 MECHANISMS UNIFY IN THE PATHWAY 1907 01:21:43,603 --> 01:21:45,505 OF ME/CFS AND OF COURSE THESE 1908 01:21:45,505 --> 01:21:47,874 FINDINGS HAVE IMPORTANT 1909 01:21:47,874 --> 01:21:51,177 RAMIFICATIONS ON FUTURE 1910 01:21:51,177 --> 01:21:51,644 BIOMARKER DEVELOPMENT. 1911 01:21:51,644 --> 01:21:52,879 LIKED TO THANK EVERYBODY 1912 01:21:52,879 --> 01:21:55,281 INVOLVED WITH THE PROJECT. 1913 01:21:55,281 --> 01:21:58,117 AVI NATH AND CORY JOHNSON WITH 1914 01:21:58,117 --> 01:22:04,390 THE WORK AND EXTRA SHOUT OUT TO 1915 01:22:04,390 --> 01:22:07,760 THOSE WHOSE INSIGHT THE PERSON 1916 01:22:07,760 --> 01:22:11,898 WHO DISCOVERED THE BIRTH SEM 1917 01:22:11,898 --> 01:22:12,598 DIFFER -- 1918 01:22:12,598 --> 01:22:15,868 SEX DIFFERENCES IN THE OMICS AND 1919 01:22:15,868 --> 01:22:18,304 I'D LIKE TO THANK DIAGO AND 1920 01:22:18,304 --> 01:22:26,145 KATHY AND ALL THE MEMBERS OF CHI 1921 01:22:26,145 --> 01:22:27,213 AND ALL THE HELP IN GETTING THE 1922 01:22:27,213 --> 01:22:27,547 ANALYSIS DONE. 1923 01:22:27,547 --> 01:22:37,890 THANK YOU VERY MUCH. 1924 01:22:38,558 --> 01:22:42,228 >> I'M GOING TO SUMMARIZE THE 1925 01:22:42,228 --> 01:22:43,796 KEY FEATURES FROM THE SESSION. 1926 01:22:43,796 --> 01:22:46,732 FIRST IS THE IMMUNOLOGY. 1927 01:22:46,732 --> 01:22:50,303 I THINK AS YOU HEARD, THE KEY 1928 01:22:50,303 --> 01:22:53,973 DEFECT IS INABILITY OF THESE 1929 01:22:53,973 --> 01:22:55,908 PATIENTS TO SWITCH B CELLS FROM 1930 01:22:55,908 --> 01:22:58,277 IGM TO IGG. 1931 01:22:58,277 --> 01:23:03,549 THAT IS -- THAT CAN EXPLAIN ALL 1932 01:23:03,549 --> 01:23:07,653 THE POOR IMMUNE RESPONSE TO 1933 01:23:07,653 --> 01:23:08,087 MICROBIAL ANTIGENS. 1934 01:23:08,087 --> 01:23:11,791 THIS IF HAVE YOU PERSISTENT OR 1935 01:23:11,791 --> 01:23:13,192 MICROBIAL ANTIGEN AND I PUT A 1936 01:23:13,192 --> 01:23:14,594 QUESTION MARK BECAUSE WE DIDN'T 1937 01:23:14,594 --> 01:23:15,461 REALLY DEMONSTRATE THE PRESENCE 1938 01:23:15,461 --> 01:23:15,795 OF IT. 1939 01:23:15,795 --> 01:23:18,664 IT'S A HYPOTHESIS. 1940 01:23:18,664 --> 01:23:21,300 ABOUT WHAT IT WILL LEAD TO THEN 1941 01:23:21,300 --> 01:23:22,635 IS T CELL EXHAUSTION BECAUSE THE 1942 01:23:22,635 --> 01:23:25,138 B CELLS AREN'T ABLE TO SWITCH 1943 01:23:25,138 --> 01:23:28,841 AND THE T CELLS ARE TRYING TO O 1944 01:23:28,841 --> 01:23:30,676 DO THEIR JOB BUT REALLY CANNOT 1945 01:23:30,676 --> 01:23:33,946 DO IT AND GET ACTIVATED AND THEN 1946 01:23:33,946 --> 01:23:37,216 GET EXHAUSTED AND THEN YOU'RE 1947 01:23:37,216 --> 01:23:39,452 JUST LEFT WITH THE INNATE PNEUM 1948 01:23:39,452 --> 01:23:41,654 SYSTEM IS A BAD WAY OF TRYING TO 1949 01:23:41,654 --> 01:23:44,490 GENERATE ANY MICROBE. 1950 01:23:44,490 --> 01:23:50,730 IT'S NON SPECIFIC ACTIVATION OF 1951 01:23:50,730 --> 01:23:55,268 MACROPHAGES AND MICROGLIAL CELLS 1952 01:23:55,268 --> 01:23:56,435 THAT CAUSE DAMAGE. 1953 01:23:56,435 --> 01:24:03,476 IT CAN ALL BE EXPLAINED BY ONE 1954 01:24:03,476 --> 01:24:07,180 ABNORMALITY. 1955 01:24:07,180 --> 01:24:09,081 NONETHELESS YOU CAN PROBABLY 1956 01:24:09,081 --> 01:24:19,525 TARGET THINGS ALONG THAT CHAIN. 1957 01:24:19,525 --> 01:24:23,029 WHILE THERE WAS NO SPOKING GUN, 1958 01:24:23,029 --> 01:24:25,431 PER SE, WE DIDN'T REALLY FIND 1959 01:24:25,431 --> 01:24:31,170 MUCH ALPHA DIVERSITY BUT THERE 1960 01:24:31,170 --> 01:24:32,138 WAS BETA DIVERSITY. 1961 01:24:32,138 --> 01:24:35,775 AND HE POINTED OUT MULTIPLE 1962 01:24:35,775 --> 01:24:43,616 DIFFERENT TYPES OF TAXONOMIC 1963 01:24:43,616 --> 01:24:45,084 TYPES OF BACTERIA WERE AFFECTED 1964 01:24:45,084 --> 01:24:47,753 AND ONE IS BUTYRATE PRODUCING 1965 01:24:47,753 --> 01:24:49,655 BACTERIA BEING DECREASED. 1966 01:24:49,655 --> 01:24:51,324 I THINK IT'S IMPORTANT BECAUSE 1967 01:24:51,324 --> 01:24:52,625 IN THE SPINAL FLUID OF THE 1968 01:24:52,625 --> 01:24:54,460 PATIENTS THEY WERE DECREASED 1969 01:24:54,460 --> 01:24:56,062 LEVELS OF BUTYRATE. 1970 01:24:56,062 --> 01:24:57,463 BUTYRATE IS NOT PRODUCED IN THE 1971 01:24:57,463 --> 01:24:59,765 HUMAN BODY. 1972 01:24:59,765 --> 01:25:01,901 THE ONLY SOURCE IS THE 1973 01:25:01,901 --> 01:25:02,268 MICROBIOME. 1974 01:25:02,268 --> 01:25:05,671 THE FACT THE LEVELS ARE 1975 01:25:05,671 --> 01:25:07,506 DECREASED TELLS YOU THERE'S 1976 01:25:07,506 --> 01:25:08,941 SOMETHING WRONG WITH THE 1977 01:25:08,941 --> 01:25:09,475 MICROBIOME ITSELF. 1978 01:25:09,475 --> 01:25:11,777 SO THEN THE OMICS STUDY I THINK 1979 01:25:11,777 --> 01:25:15,081 THERE'S TWO THINGS I LIKE TO 1980 01:25:15,081 --> 01:25:16,048 POINT OUT. 1981 01:25:16,048 --> 01:25:18,784 ONE IS THAT WE'RE ALL INTERESTED 1982 01:25:18,784 --> 01:25:20,253 IN BIOMARKERS. 1983 01:25:20,253 --> 01:25:25,891 AND THE BEST DIFFERENTIATING 1984 01:25:25,891 --> 01:25:27,159 FEATURE WE FOUND BETWEEN ME/CFS 1985 01:25:27,159 --> 01:25:33,699 AND THE HEALTHY VOL UNTIRES -- 1986 01:25:33,699 --> 01:25:35,401 VOLUNTEERS WAS THE METABOLOMICS 1987 01:25:35,401 --> 01:25:38,971 AND THERE'S NOT A SINGLE 1988 01:25:38,971 --> 01:25:41,374 MOLECULE I CAN POINT TO BUT IT'S 1989 01:25:41,374 --> 01:25:44,110 TELLING YOU IRRESPECTIVE OF 1990 01:25:44,110 --> 01:25:45,211 MALE, FEMALE YOU, CAN SEPARATE 1991 01:25:45,211 --> 01:25:47,346 THE GROUPS WHEN YOU LOOK AT THE 1992 01:25:47,346 --> 01:25:48,014 METABOLOME AND SPINAL FLUID. 1993 01:25:48,014 --> 01:25:51,350 I THINK WE NEED TO DIG DEEPER 1994 01:25:51,350 --> 01:25:51,751 IN. 1995 01:25:51,751 --> 01:25:53,753 PROBLEMS ACCESS TO SPINAL FLUID 1996 01:25:53,753 --> 01:25:55,187 HAS BEEN POOR BUT IT'S CRITICAL 1997 01:25:55,187 --> 01:25:56,956 IF YOU WANT TO STUDY 1998 01:25:56,956 --> 01:25:57,723 NEUROLOGICAL DISEASE YOU HAVE TO 1999 01:25:57,723 --> 01:26:06,565 HAVE ACCESS TO THE SPINAL CORD. 2000 01:26:06,565 --> 01:26:09,969 AND WE'VE SHOWN MULTIPLE SEX 2001 01:26:09,969 --> 01:26:10,970 DIFFERENCES. 2002 01:26:10,970 --> 01:26:11,771 IF YOU'RE GOING TO DESIGN 2003 01:26:11,771 --> 01:26:14,340 VARIOUS KINDS OF INTERVENTIONS 2004 01:26:14,340 --> 01:26:15,508 TAKING INTO CONSIDERATION WHO 2005 01:26:15,508 --> 01:26:16,142 YOU'RE TREATING IS ABSOLUTELY 2006 01:26:16,142 --> 01:26:23,082 CRITICAL. 2007 01:26:23,082 --> 01:26:24,317 I'M GOING TO END THE SESSION 2008 01:26:24,317 --> 01:26:25,751 HERE AND WE'LL HAVE A FEW 2009 01:26:25,751 --> 01:26:26,352 MINUTES FOR DISCUSSION. 2010 01:26:26,352 --> 01:26:27,853 I'LL OPEN IT UP FOR DISCUSSION 2011 01:26:27,853 --> 01:26:32,425 HERE. 2012 01:26:32,425 --> 01:26:38,030 ANY QUESTIONS FROM THE AUDIENCE 2013 01:26:38,030 --> 01:26:42,535 WE'LL BE HAPPY TO TAKE THEM? 2014 01:26:42,535 --> 01:26:53,045 ANY QUESTIONS ONLINE AND YOU 2015 01:26:54,547 --> 01:26:55,214 CAN COME UP. 2016 01:26:55,214 --> 01:27:00,152 >> MY QUESTION IS A GENERAL ONE 2017 01:27:00,152 --> 01:27:01,587 WHERE YOU HAVE A SMALL GROUP OF 2018 01:27:01,587 --> 01:27:03,055 CONTROLS AND PATIENTS THE 2019 01:27:03,055 --> 01:27:05,558 QUESTION IS WHETHER DIFFERENCES 2020 01:27:05,558 --> 01:27:08,127 YOU SEE HOW THEY WOULD STACK UP 2021 01:27:08,127 --> 01:27:09,995 IF YOU HAD A LARGER CONTROL 2022 01:27:09,995 --> 01:27:10,296 GROUP. 2023 01:27:10,296 --> 01:27:13,399 ALL IN ALL PEOPLE IN THE WORLD 2024 01:27:13,399 --> 01:27:15,868 AND YOU LOOK AT THEM SO OF 2025 01:27:15,868 --> 01:27:18,404 COURSE THAT'S NOT POSSIBLE IN 2026 01:27:18,404 --> 01:27:21,407 MANY OF THESE TESTS BUT ABOUT 2027 01:27:21,407 --> 01:27:22,541 THE MICROBIOME WHETHER THEY 2028 01:27:22,541 --> 01:27:24,610 COULD LOOK AT OTHER DATA THEY 2029 01:27:24,610 --> 01:27:26,045 HAVE FROM FOLKS AND SEE -- 2030 01:27:26,045 --> 01:27:27,380 >> THAT'S A GOOD QUESTION. 2031 01:27:27,380 --> 01:27:29,448 WE DIDN'T SHOW YOU -- THAT'S 2032 01:27:29,448 --> 01:27:31,784 TRUE EVEN FOR THE IMMUNOLOGY 2033 01:27:31,784 --> 01:27:34,253 HERE STEVE JACOBSON HAS THE 2034 01:27:34,253 --> 01:27:37,857 MULTIPLE SCLEROSIS AND THE OTHER 2035 01:27:37,857 --> 01:27:38,124 DISEASES. 2036 01:27:38,124 --> 01:27:39,792 WE CAN QUICKLY LOOK AT THAT AND 2037 01:27:39,792 --> 01:27:40,860 THEY'VE DONE SOME ANALYSIS. 2038 01:27:40,860 --> 01:27:43,696 WE DIDN'T REALLY PRESENT IT HERE 2039 01:27:43,696 --> 01:27:44,463 AND THAT'S AVAILABLE. 2040 01:27:44,463 --> 01:27:47,767 JOHN, DO YOU WANT TO ADDRESS IT 2041 01:27:47,767 --> 01:27:52,805 WITH REGARD TO THE MICROBIOME? 2042 01:27:52,805 --> 01:27:54,907 YOU CAN TAKE THE MICROPHONE OR 2043 01:27:54,907 --> 01:27:55,741 COME UP HERE SO PEOPLE ONLINE 2044 01:27:55,741 --> 01:27:59,044 CAN SEE YOU. 2045 01:27:59,044 --> 01:28:02,615 >> SO THE ISSUE WITH MICROBIOME 2046 01:28:02,615 --> 01:28:04,316 IS IT'S A MOVING GOALPOST 2047 01:28:04,316 --> 01:28:05,317 BECAUSE IT'S NOT STATIC. 2048 01:28:05,317 --> 01:28:08,554 TODAY I DID NOT GO TO McDONALDS 2049 01:28:08,554 --> 01:28:11,557 BUT MAY GO ON TUESDAY AND OTHER 2050 01:28:11,557 --> 01:28:13,526 FAST FOOD PLACES ARE AVAILABLE 2051 01:28:13,526 --> 01:28:15,494 AND THESE SMALL CHANGES, THESE 2052 01:28:15,494 --> 01:28:18,297 SMALL INTERVENTIONS DO CHANGE MY 2053 01:28:18,297 --> 01:28:19,532 MICROBIOME ALL THE TIME. 2054 01:28:19,532 --> 01:28:22,835 WHO HAVE I BEEN IN CONTACT WITH, 2055 01:28:22,835 --> 01:28:26,672 DID I TAKE ANTIBIOTICS AND THE 2056 01:28:26,672 --> 01:28:33,512 CHALLENGE IS IN SMALL COHORTS 2057 01:28:33,512 --> 01:28:35,448 THE STARTING POINT THERE'S NO 2058 01:28:35,448 --> 01:28:36,081 GOLD STANDARD FOR COMPARISON, 2059 01:28:36,081 --> 01:28:46,158 YES. 2060 01:28:53,132 --> 01:28:54,066 ABSOLUTELY. 2061 01:28:54,066 --> 01:28:54,667 RIGHT. 2062 01:28:54,667 --> 01:28:57,503 INDEED -- BUT ONE OF THE THINGS 2063 01:28:57,503 --> 01:29:00,206 THAT CAN BE DONE IS TO LOOK AT 2064 01:29:00,206 --> 01:29:03,175 ALL SAMPLES TOGETHER INCREASE 2065 01:29:03,175 --> 01:29:07,012 SAMPLE SIZE AND ALSO LOOK AT 2066 01:29:07,012 --> 01:29:08,347 MULTIPLE SAMPLES FROM THE SAME 2067 01:29:08,347 --> 01:29:10,583 PATIENT FOR A LONG TIME AND THEN 2068 01:29:10,583 --> 01:29:12,485 SEE BECAUSE IT'S LIKE IN A 2069 01:29:12,485 --> 01:29:12,718 MOVIE. 2070 01:29:12,718 --> 01:29:23,262 SO IF YOU LOOK AT THE ORDINATION 2071 01:29:23,829 --> 01:29:26,499 PLOT IT'S HOW MUCH THEY GIGGLE 2072 01:29:26,499 --> 01:29:28,200 IN THE CONTEXT OF OTHERS. 2073 01:29:28,200 --> 01:29:38,744 >> I LIKE THE CONCEPT OF GIGGLE. 2074 01:29:43,649 --> 01:29:49,555 >> HI, I'D LIKE TO TAKE -- 2075 01:29:49,555 --> 01:29:50,689 >> IDENTIFY YOURSELF. 2076 01:29:50,689 --> 01:29:55,094 >> I'M DR. LOMEN A PATIENT WITH 2077 01:29:55,094 --> 01:29:57,530 ME AND HAVE DONE RESEARCH 2078 01:29:57,530 --> 01:30:03,669 INFORMALLY ON THIS. 2079 01:30:03,669 --> 01:30:07,039 THE CARDINAL SYMPTOM WAS POST 2080 01:30:07,039 --> 01:30:07,773 EXERTIONAL MALAISE. 2081 01:30:07,773 --> 01:30:11,777 HOW DO THE RESULTS YOU'VE JUST 2082 01:30:11,777 --> 01:30:16,982 SHOWED US FIT IN TO EXPLAINING 2083 01:30:16,982 --> 01:30:17,149 PEM? 2084 01:30:17,149 --> 01:30:17,683 THANK YOU. 2085 01:30:17,683 --> 01:30:19,118 >> I THINK THAT WILL BE 2086 01:30:19,118 --> 01:30:19,718 DISCUSSED FURTHER. 2087 01:30:19,718 --> 01:30:25,291 BRIAN, DO YOU WANT TO TAKE THAT 2088 01:30:25,291 --> 01:30:26,692 NOW OR LATER? 2089 01:30:26,692 --> 01:30:30,062 WHY DON'T WE TAKE PART OF IT NOW 2090 01:30:30,062 --> 01:30:31,363 AND DISCUSS IN MORE DETAIL 2091 01:30:31,363 --> 01:30:31,564 LATER. 2092 01:30:31,564 --> 01:30:35,768 >> AS WE TALKED ABOUT THE DESIGN 2093 01:30:35,768 --> 01:30:39,204 OF THE STUDY, POST EXERTIONAL 2094 01:30:39,204 --> 01:30:40,306 MALAISE WAS REQUIRED AS A SYSTEM 2095 01:30:40,306 --> 01:30:42,608 SO EVERYBODY HAD TO HAVE POST 2096 01:30:42,608 --> 01:30:43,008 EXERTION MALAISE. 2097 01:30:43,008 --> 01:30:47,279 SO IF YOU'RE LOOKING 2098 01:30:47,279 --> 01:30:48,280 CROSS-SECTIONALLY EVERY PERSON 2099 01:30:48,280 --> 01:30:50,115 HAD POST EXERTIONAL MALAISE AND 2100 01:30:50,115 --> 01:30:51,116 MEASURED THANE FOUR DIFFERENT 2101 01:30:51,116 --> 01:30:54,553 WAYS AND WE'LL TALK ABOUT SOME 2102 01:30:54,553 --> 01:30:58,657 OF THAT IN THE BIOENERGETICS 2103 01:30:58,657 --> 01:31:00,526 TALKED AND BARBARA STUSSMAN AND 2104 01:31:00,526 --> 01:31:03,095 OUR QUALITATIVE RESEARCHER HAD 2105 01:31:03,095 --> 01:31:05,331 FOCUS GROUPS AND WE HAD 2106 01:31:05,331 --> 01:31:05,998 DEVELOPED A PARTICULAR 2107 01:31:05,998 --> 01:31:08,901 INSTRUMENT FOR MEASURING 2108 01:31:08,901 --> 01:31:09,535 EXCHANGE IN POST EXERTIONAL 2109 01:31:09,535 --> 01:31:10,769 MALAISE OVER TIME. 2110 01:31:10,769 --> 01:31:16,742 YOU HAD TO HAVE IT TO COME AND 2111 01:31:16,742 --> 01:31:19,778 THE C PET WAS TO INDUCE POST 2112 01:31:19,778 --> 01:31:20,980 EXERTIONAL MALAISE WHILE WE 2113 01:31:20,980 --> 01:31:22,114 WATCHED. 2114 01:31:22,114 --> 01:31:23,849 THAT HASN'T BEEN FULLY STUDIED 2115 01:31:23,849 --> 01:31:25,451 AND OUR TEAM IS STILL WORK ON 2116 01:31:25,451 --> 01:31:27,553 THAT AND ONGOING DIRECTIONS BUT 2117 01:31:27,553 --> 01:31:30,956 WE USED THE C PET TO INDUCE POST 2118 01:31:30,956 --> 01:31:36,328 EXERTIONAL MALAISE IN FRONT OF 2119 01:31:36,328 --> 01:31:39,231 US AND MEASURE THAT PHENOMENA IN 2120 01:31:39,231 --> 01:31:44,436 MULTIPLE WAYS AS IT WAS 2121 01:31:44,436 --> 01:31:44,703 UNFOLDING. 2122 01:31:44,703 --> 01:31:47,439 >> THE PATHOPHYSIOLOGY. 2123 01:31:47,439 --> 01:31:49,141 >> THAT'S A TOUGH QUESTION 2124 01:31:49,141 --> 01:31:50,142 BECAUSE WE DON'T QUITE 2125 01:31:50,142 --> 01:31:52,277 UNDERSTAND THE PATHOPHYSIOLOGY 2126 01:31:52,277 --> 01:31:54,279 OF POST O EXERTIONAL MALAISE. 2127 01:31:54,279 --> 01:31:55,681 WE KNOW IT'S AN ENTRY CRITERIA 2128 01:31:55,681 --> 01:31:57,583 SO EVERYBODY HAS TO HAVE IT 2129 01:31:57,583 --> 01:32:03,589 WHICH MEANS ALL THESE THINGS -- 2130 01:32:03,589 --> 01:32:06,925 WHATEVER CORRELATES WITH 2131 01:32:06,925 --> 01:32:08,360 POST-EXERTIONAL MALAISE AND ONE 2132 01:32:08,360 --> 01:32:11,764 PHYSIOLOGY IS A QUESTION WE 2133 01:32:11,764 --> 01:32:15,601 CAN'T ANSWER. 2134 01:32:15,601 --> 01:32:22,007 >> GOOD MORNING. 2135 01:32:22,007 --> 01:32:31,116 I'M A PHYSICIAN FROM NIAID A 2136 01:32:31,116 --> 01:32:31,850 RHEUMATOLOGIST THEN WORK YOU'VE 2137 01:32:31,850 --> 01:32:35,788 DONE IS SOMETHING TO ADMIRE AND 2138 01:32:35,788 --> 01:32:36,088 RECOGNIZED. 2139 01:32:36,088 --> 01:32:41,760 WHAT ARE THE POTENTIAL EXPANSION 2140 01:32:41,760 --> 01:32:43,462 OF THIS INTO PIS BECAUSE MOST 2141 01:32:43,462 --> 01:32:45,030 ARE ADULTS SO ANY THOUGHTS ABOUT 2142 01:32:45,030 --> 01:32:47,766 THAT AND FUTURE ENDEAVORS IN 2143 01:32:47,766 --> 01:32:50,736 THAT AREA? 2144 01:32:50,736 --> 01:32:52,371 >> THAT'S A POTENTIAL POPULATION 2145 01:32:52,371 --> 01:32:57,576 AND CONDUCTING RESEARCH ON 2146 01:32:57,576 --> 01:32:58,711 CHILDREN IS VERY HARD BECAUSE IF 2147 01:32:58,711 --> 01:33:00,946 YOU WANT TO PUT THEM IN THE 2148 01:33:00,946 --> 01:33:01,880 HOSPITAL FOR WEEKS AND PUTTING 2149 01:33:01,880 --> 01:33:04,783 SPINAL TAPS ON CHILDREN IS NOT 2150 01:33:04,783 --> 01:33:06,919 EASY. 2151 01:33:06,919 --> 01:33:07,619 YOU HAVE TO ANESTHETIZE THEM. 2152 01:33:07,619 --> 01:33:08,787 IT'S A MASSIVE UNDERTAKING. 2153 01:33:08,787 --> 01:33:13,759 WE HOPE WHAT WE LEARN CAN BE 2154 01:33:13,759 --> 01:33:15,761 APPLIED TO CHILDREN IN SOME 2155 01:33:15,761 --> 01:33:17,463 MANNER AND TEST IN A SMALLER 2156 01:33:17,463 --> 01:33:22,167 COHORT AND NOT HAVE TO PUT THEM 2157 01:33:22,167 --> 01:33:25,270 THROUGH SUCH A HUGE BATTERY OF 2158 01:33:25,270 --> 01:33:25,771 INVESTIGATIONS BUT THE 2159 01:33:25,771 --> 01:33:31,677 POPULATION NEEDS TO BE STUDIES. 2160 01:33:31,677 --> 01:33:34,079 >> I'M PAUL WONG AT NIH. 2161 01:33:34,079 --> 01:33:35,781 I WANTED TO THROW OUT A QUICK 2162 01:33:35,781 --> 01:33:43,655 QUESTION. 2163 01:33:43,655 --> 01:33:46,525 THE B CELL DIFFERENTIATION IS A 2164 01:33:46,525 --> 01:33:47,092 PROBLEM. 2165 01:33:47,092 --> 01:33:48,160 IN THE ME/CFS POPULATION ARE 2166 01:33:48,160 --> 01:33:53,832 THERE PROBLEMS WITH REPORTS OF 2167 01:33:53,832 --> 01:34:04,276 ADAPTIVE IMMUNE PROBLEMS? 2168 01:34:19,391 --> 01:34:23,295 >> IT DOESN'T LEAD TO IMMUNE 2169 01:34:23,295 --> 01:34:25,230 DEFICIENCY. 2170 01:34:25,230 --> 01:34:27,699 >> JOE LANSET. 2171 01:34:27,699 --> 01:34:28,567 I'M A PATIENT. 2172 01:34:28,567 --> 01:34:31,770 YOU MENTIONED BUTYRATE AS A 2173 01:34:31,770 --> 01:34:32,404 SIGNAL FOR MICROBIOME 2174 01:34:32,404 --> 01:34:35,240 DYSFUNCTION IS THAT WHAT YOU 2175 01:34:35,240 --> 01:34:37,643 FIND IN CFS OR A LESS INVASIVE 2176 01:34:37,643 --> 01:34:40,679 WAY AS A CLINICAL TEST FOR 2177 01:34:40,679 --> 01:34:42,281 MICROBIOME DYSFUNCTION? 2178 01:34:42,281 --> 01:34:44,650 >> I'M SURE YOU COULD PROBABLY 2179 01:34:44,650 --> 01:34:47,352 MEASURE BUTYRATE AT MANY LEVELS. 2180 01:34:47,352 --> 01:34:49,621 IT'S AN HBLC METHOD SHOULD BE 2181 01:34:49,621 --> 01:34:51,190 ABLE TO PICK IT UP AND PEOPLE 2182 01:34:51,190 --> 01:34:53,058 CAN DEVELOP IT IF THEY DON'T 2183 01:34:53,058 --> 01:34:53,458 EXIST ALREADY. 2184 01:34:53,458 --> 01:34:55,761 I DON'T THINK THAT'S GOING TO BE 2185 01:34:55,761 --> 01:35:06,138 DIAGNOSTIC OF ME/CFS. 2186 01:35:15,981 --> 01:35:22,054 WE WERE SURPRISED YOU CAN SHOW 2187 01:35:22,054 --> 01:35:32,264 DIFFERENCES. 2188 01:35:45,878 --> 01:35:46,945 AND MODULATE DNA EXPRESSION AND 2189 01:35:46,945 --> 01:35:51,516 PLAYS A ROLE AND QUITE IN 2190 01:35:51,516 --> 01:35:55,487 INTRIGUING BUT DON'T THINK ONE 2191 01:35:55,487 --> 01:35:56,121 MOLECULE ALONE WILL EXPLAIN THE 2192 01:35:56,121 --> 01:36:06,265 DISEASE. 2193 01:36:36,428 --> 01:36:46,538 [OFF-MIC] 2194 01:37:11,663 --> 01:37:21,773 [OFF-MIC] 2195 01:37:47,866 --> 01:37:57,976 [OFF-MIC] 2196 01:38:05,417 --> 01:38:05,784 >> THANKS. 2197 01:38:05,784 --> 01:38:11,323 LET ME RE -- REPEAT WHAT HE 2198 01:38:11,323 --> 01:38:11,590 SAID. 2199 01:38:11,590 --> 01:38:14,159 THE BUTYRATE ITSELF CAN AFFECT 2200 01:38:14,159 --> 01:38:15,794 THE GUT INTEGRITY SO THINGS CAN 2201 01:38:15,794 --> 01:38:19,431 MOVE FROM THE GUT INTO THE 2202 01:38:19,431 --> 01:38:20,565 BLOODSTREAM AND THAT COULD HAVE 2203 01:38:20,565 --> 01:38:21,566 A CASCADE OF EVENTS. 2204 01:38:21,566 --> 01:38:24,436 THE SECOND THING HE MENTIONED 2205 01:38:24,436 --> 01:38:26,972 WAS THE INNATE IMMUNE RESPONSES 2206 01:38:26,972 --> 01:38:27,806 MAY BE CRITICAL BECAUSE YOU SEE 2207 01:38:27,806 --> 01:38:30,509 STIMULATION OF THOSE AND THE 2208 01:38:30,509 --> 01:38:33,211 THIRD THING HE MENTIONED IS POST 2209 01:38:33,211 --> 01:38:34,980 EXERTIONAL MALAISE DOESN'T START 2210 01:38:34,980 --> 01:38:37,349 IMMEDIATELY BUT AFTER THE 2211 01:38:37,349 --> 01:38:37,616 EXERTION. 2212 01:38:37,616 --> 01:38:39,484 THE GAP IS INTERESTING AND SOME 2213 01:38:39,484 --> 01:38:41,887 THING IS HAPPENING DURING THAT 2214 01:38:41,887 --> 01:38:42,554 PIEFRD OF TIME IN ORDER TO LEAD 2215 01:38:42,554 --> 01:38:44,289 TO THAT AND THOSE ARE IMPORTANT 2216 01:38:44,289 --> 01:38:46,024 POINTS OF FURTHER DISCUSSION. 2217 01:38:46,024 --> 01:38:48,693 THANK YOU VERY MUCH. 2218 01:38:48,693 --> 01:38:51,430 >> WE HAN ONE QUESTION FROM OUR 2219 01:38:51,430 --> 01:38:52,431 VIRTUAL AUDIENCE. 2220 01:38:52,431 --> 01:38:54,966 WOULD DIETARY SUPPLEMENT OF 2221 01:38:54,966 --> 01:38:57,702 BUTYRATE POTENTIALLY HELP THESE 2222 01:38:57,702 --> 01:38:57,969 PATIENTS? 2223 01:38:57,969 --> 01:38:59,805 >> JOHN, DO YOU WANT TO TAKE 2224 01:38:59,805 --> 01:39:07,012 THAT ONE? 2225 01:39:07,012 --> 01:39:08,346 >> I DON'T KNOW BUT IT MIGHT. 2226 01:39:08,346 --> 01:39:10,749 THE THING IS THAT BUTYRATE 2227 01:39:10,749 --> 01:39:14,319 PRODUCTION WHEN YOU HAVE IT FROM 2228 01:39:14,319 --> 01:39:17,722 A MICROBIOME STANDPOINT IT'S 2229 01:39:17,722 --> 01:39:19,024 CONTINUALLY PRODUCING BUTYRATE. 2230 01:39:19,024 --> 01:39:19,724 IF YOU SUPPLEMENTING I DON'T 2231 01:39:19,724 --> 01:39:23,462 KNOW IF THAT WILL BE THE SAME. 2232 01:39:23,462 --> 01:39:25,730 THE ABSORPTION MAY BE IN A 2233 01:39:25,730 --> 01:39:26,398 DIFFERENT PLACE. 2234 01:39:26,398 --> 01:39:31,636 HAVE YOU GUT MICROBIOME IN 2235 01:39:31,636 --> 01:39:39,478 DIFFERENT SECTIONS OF YOUR 2236 01:39:39,478 --> 01:39:40,078 GASTROINTESTINAL TRACT AND I 2237 01:39:40,078 --> 01:39:46,485 DON'T KNOW IF YOU GIVE IT ORALLY 2238 01:39:46,485 --> 01:39:49,054 IT WILL HAVE THE SAME EFFECT. 2239 01:39:49,054 --> 01:39:51,890 THERE'S NOT ENOUGH BUTYRATE 2240 01:39:51,890 --> 01:39:52,557 CAUSING IT. 2241 01:39:52,557 --> 01:39:55,794 IT'S LIKE MOLES IN A SWISS 2242 01:39:55,794 --> 01:39:57,996 CHEESE IT'S AN ADDED AFFECT THAT 2243 01:39:57,996 --> 01:39:59,798 MAY CONTRIBUTE TO THE OVER ALL 2244 01:39:59,798 --> 01:40:04,970 APPEARANCE OF THE SYMPTOMS. 2245 01:40:04,970 --> 01:40:07,205 CERTAINLY IT'S WORTH LOOKING AT 2246 01:40:07,205 --> 01:40:09,908 BUT AGAIN WE NEED LARGER SAMPLE 2247 01:40:09,908 --> 01:40:10,242 SIZES. 2248 01:40:10,242 --> 01:40:14,613 IF BUTYRATE IS BEING PRODUCED 2249 01:40:14,613 --> 01:40:15,847 CONSTANTLY OR NOT SO THERE YOU 2250 01:40:15,847 --> 01:40:16,148 GO. 2251 01:40:16,148 --> 01:40:21,753 THAT'S WHAT I THINK. 2252 01:40:21,753 --> 01:40:24,589 >> WOULD BUTYRATE SURVIVE 2253 01:40:24,589 --> 01:40:24,856 DIGESTION? 2254 01:40:24,856 --> 01:40:26,825 >> IT SHOULD BECAUSE IT'S A 2255 01:40:26,825 --> 01:40:32,831 SMALL CHAIN FATTY ACID JUST FOUR 2256 01:40:32,831 --> 01:40:35,233 CARBONS AND A COH. 2257 01:40:35,233 --> 01:40:38,637 I DON'T SEE IT BEING DIGESTED BY 2258 01:40:38,637 --> 01:40:41,640 ANY PEPTIDE OR BY ANY ENZYME. 2259 01:40:41,640 --> 01:40:43,808 >> THE THING IS THAT THERE'S SO 2260 01:40:43,808 --> 01:40:44,643 MANY CHANGES. 2261 01:40:44,643 --> 01:40:47,612 I LIKE YOUR ANALOGY OF THE SWISS 2262 01:40:47,612 --> 01:40:49,181 CHEESE YOU PLUG ONE HOLE BUT 2263 01:40:49,181 --> 01:40:50,015 STILL HAVE OTHERS. 2264 01:40:50,015 --> 01:40:53,752 >> ALL THE HOLES HAVE TO ALIGN. 2265 01:40:53,752 --> 01:40:55,987 >> ALL RIGHT. 2266 01:40:55,987 --> 01:41:01,629 GOOD. 2267 01:41:01,629 --> 01:41:03,030 ANY OTHER? 2268 01:41:03,030 --> 01:41:05,132 IF NOT LET'S TAKE A PAUL BREAK. 2269 01:41:05,132 --> 01:41:17,052 WE HAVE 15 MINUTES. 2270 01:41:17,052 --> 01:41:28,690 >> WE'LL GET STARTED. 2271 01:41:28,690 --> 01:41:32,093 DR. HALLETT RECENTLY RETIRED BUT 2272 01:41:32,093 --> 01:41:33,728 WAS AN NIH DISTINGUISHED 2273 01:41:33,728 --> 01:41:37,365 INVESTIGATOR AND CHIEF OF THE 2274 01:41:37,365 --> 01:41:37,999 MORT CONTROL SEC AT THE 2275 01:41:37,999 --> 01:41:41,602 INSTITUTE OF NEUROLOGICAL 2276 01:41:41,602 --> 01:41:44,305 DISORDERS AND STROKES AND WAS 2277 01:41:44,305 --> 01:41:50,144 THE CLINICAL DIRECTOR OF THIS 2278 01:41:50,144 --> 01:41:53,448 INSTITUTE AND ALSO THE PAST 2279 01:41:53,448 --> 01:41:54,015 PRESIDENT OF THE MOVEMENT 2280 01:41:54,015 --> 01:41:56,984 DISORDER SOCIETY AND PAST EDITOR 2281 01:41:56,984 --> 01:41:59,821 AND CHIEF OF NEURO PHYSIOLOGY 2282 01:41:59,821 --> 01:42:01,556 AND RECEIVED MANY AWARDS FOR THE 2283 01:42:01,556 --> 01:42:03,424 WORK HE'S DONE AND IS THE 2284 01:42:03,424 --> 01:42:06,160 WORLD'S EXPERT WHEN IT COMES TO 2285 01:42:06,160 --> 01:42:10,832 PRINCIPLES OF MOTOR CONTROL AND 2286 01:42:10,832 --> 01:42:11,933 PATHOPHYSIOLOGY OF MOVEMENT 2287 01:42:11,933 --> 01:42:14,168 DISORDERS. 2288 01:42:14,168 --> 01:42:14,469 DR. HALLETT. 2289 01:42:14,469 --> 01:42:24,612 THANK YOU. 2290 01:42:24,612 --> 01:42:25,713 >> THANK YOU. 2291 01:42:25,713 --> 01:42:30,151 IT'S A PLEASURE TO PRESENT THE 2292 01:42:30,151 --> 01:42:33,054 RESU 2293 01:42:33,054 --> 01:42:33,287 RESULTS. 2294 01:42:33,287 --> 01:42:34,956 AND TO POINT OUT EVERYONE IS 2295 01:42:34,956 --> 01:42:36,290 CLEAR IN TERMS OF INFORMATION 2296 01:42:36,290 --> 01:42:37,959 ANY PARTICULAR DISEASE AND THAT 2297 01:42:37,959 --> 01:42:43,197 IS THE PHENOTYPE THAT WE'RE 2298 01:42:43,197 --> 01:42:44,098 TRYING TO UNDERSTAND HERE ONE 2299 01:42:44,098 --> 01:42:48,069 STARTS WITH THE ETIOLOGY AND THE 2300 01:42:48,069 --> 01:42:49,337 UNDERLYING CAUSES. 2301 01:42:49,337 --> 01:42:51,038 THOSE WHICH WE JUST HEARD ABOUT 2302 01:42:51,038 --> 01:42:52,607 IN THE LAST PRESENTATION SOMEHOW 2303 01:42:52,607 --> 01:42:54,976 LEAD TO THE PATHOPHYSIOLOGY OF 2304 01:42:54,976 --> 01:42:56,344 THE DISORDER WHICH WIRE GOING TO 2305 01:42:56,344 --> 01:43:01,015 BE TALKING ABOUT IN WHICH 2306 01:43:01,015 --> 01:43:02,150 DRDR 2307 01:43:02,150 --> 01:43:04,385 DR. KOROSHETZ WAS TALKING ABOUT 2308 01:43:04,385 --> 01:43:06,954 ALSO AND THE PATHOPHYSIOLOGY 2309 01:43:06,954 --> 01:43:10,391 LEADS TO THE PHENOTYPE WHICH 2310 01:43:10,391 --> 01:43:16,531 WILL BE OF THE DECREASED OR IN 2311 01:43:16,531 --> 01:43:17,465 THE AMOUNT OF FATIGUE. 2312 01:43:17,465 --> 01:43:20,034 TO GO BACK TO THIS PARTICULAR 2313 01:43:20,034 --> 01:43:21,736 DIAGRAM, AS YOU HEARD WE WERE 2314 01:43:21,736 --> 01:43:23,471 TALKING ABOUT THE FIRST TWO 2315 01:43:23,471 --> 01:43:24,005 COLUMNS IN THE FIRST 2316 01:43:24,005 --> 01:43:24,338 PRESENTATION. 2317 01:43:24,338 --> 01:43:29,677 NOW WE'RE GOING TO BE TALKING 2318 01:43:29,677 --> 01:43:33,414 ABOUT THE NEXT TWO AND A HALF TO 2319 01:43:33,414 --> 01:43:41,522 LEARN HOW POTENTIALLY THOSE ET 2320 01:43:41,522 --> 01:43:43,357 YO LOGICAL FACTORS LEAD TO THE 2321 01:43:43,357 --> 01:43:44,392 IDENTIFICATION OF WHERE FATIGUE 2322 01:43:44,392 --> 01:43:54,602 MIGHT ARISE. 2323 01:43:55,670 --> 01:43:57,438 THESE ARE THE SUBSET OF WHAT 2324 01:43:57,438 --> 01:43:59,140 WE'LL BE STRIKE NOW AND THE 2325 01:43:59,140 --> 01:44:02,410 OUTLINE OF WHAT YOU'LL BE 2326 01:44:02,410 --> 01:44:05,580 HEARING ABOUT. 2327 01:44:05,580 --> 01:44:07,849 REPETITIVE SUB MAXIMAL EXERCISE 2328 01:44:07,849 --> 01:44:10,117 IS A GOOD WAY AND TYPICAL WAY OF 2329 01:44:10,117 --> 01:44:15,823 ANALYZING MOTOR FATIGUE. 2330 01:44:15,823 --> 01:44:18,059 AND ONE CAN UNDERSTAND IT BY 2331 01:44:18,059 --> 01:44:20,561 LOOKING AT ELEMENTS OF WHERE THE 2332 01:44:20,561 --> 01:44:22,230 FATIGUE COMES FROM. 2333 01:44:22,230 --> 01:44:25,733 DOES IT COME FROM THE PERIPHERAL 2334 01:44:25,733 --> 01:44:27,635 ASPECT OF THE NEURAL MUSCULAR 2335 01:44:27,635 --> 01:44:29,570 SYSTEM OR THE MOTOR CORTEX OR 2336 01:44:29,570 --> 01:44:32,139 THE DRIVERS OF THE MOTOR CORTEX 2337 01:44:32,139 --> 01:44:34,141 WHERE ONE WOULD DESCRIBE IT AS 2338 01:44:34,141 --> 01:44:35,743 CENTRAL FATIGUE. 2339 01:44:35,743 --> 01:44:36,844 DR. KOROSHETZ GAVE AN 2340 01:44:36,844 --> 01:44:38,546 INTRODUCTION TO THAT. 2341 01:44:38,546 --> 01:44:41,983 YOU'LL HEAR FROM PATRICK BEDARD 2342 01:44:41,983 --> 01:44:43,684 WHO IS A NEUROSCIENTIST WHO HAS 2343 01:44:43,684 --> 01:44:45,219 BEEN WORKING SPECIFICALLY ON 2344 01:44:45,219 --> 01:44:46,354 THIS PROJECT FOR A NUMBER OF 2345 01:44:46,354 --> 01:44:51,759 YEARS NOW. 2346 01:44:51,759 --> 01:44:55,897 AND DR. HOROWITZ A NEUROIMAGER 2347 01:44:55,897 --> 01:44:56,931 WHO HAS BEEN A COLLEAGUE IN THE 2348 01:44:56,931 --> 01:44:58,165 MOTOR CONTROL SECTION FOR MANY 2349 01:44:58,165 --> 01:45:08,276 YEARS. 2350 01:45:08,476 --> 01:45:10,878 THE NEXT YOU'LL HEAR FROM DAVID 2351 01:45:10,878 --> 01:45:12,113 GOLDSTEIN HE'S A SENIOR 2352 01:45:12,113 --> 01:45:13,681 SCIENTIST WHO HAS BEEN AT NIH 2353 01:45:13,681 --> 01:45:18,185 MANY YEARS AND MADE MANY 2354 01:45:18,185 --> 01:45:21,355 IMPORTANT S ON THE AUTONOMIC 2355 01:45:21,355 --> 01:45:24,592 SURFACE SYSTEM AND HEAR MORE 2356 01:45:24,592 --> 01:45:28,329 FROM MARK LEVIN A CARDIOLOGIST 2357 01:45:28,329 --> 01:45:30,164 AND REPRESENTING NHLBI IN THE 2358 01:45:30,164 --> 01:45:32,066 MULTI-INSTITUTE PROJECT. 2359 01:45:32,066 --> 01:45:36,137 THE HEART IS A MAJOR TARGET FOR 2360 01:45:36,137 --> 01:45:38,573 THE AUTONOMIC NERVOUS SYSTEM AND 2361 01:45:38,573 --> 01:45:39,840 IMPORTANT TO UNDERSTAND. 2362 01:45:39,840 --> 01:45:41,042 NEUROCOGNITIVE ISSUES ARE ALSO 2363 01:45:41,042 --> 01:45:42,977 IMPORTANT. 2364 01:45:42,977 --> 01:45:47,848 JOSEPH SNOW IS A SENIOR 2365 01:45:47,848 --> 01:45:49,784 NEUROPSYCHOLOGIST AT NIH WITH 2366 01:45:49,784 --> 01:45:51,886 MANY EXPERIENCE AND HAS DONE 2367 01:45:51,886 --> 01:45:56,324 COMPREHENSIVE STUDIES YOU'LL 2368 01:45:56,324 --> 01:46:00,595 MARE ABOUT AND A POST-DOCTORAL 2369 01:46:00,595 --> 01:46:03,864 FELLOW WAS WORKING AT NIHM AND 2370 01:46:03,864 --> 01:46:06,734 NOW AT NINDS TO CONTINUE HIS 2371 01:46:06,734 --> 01:46:08,002 STUDIES OF EFFORT IN RELATION TO 2372 01:46:08,002 --> 01:46:13,975 THE WAY HE BRAIN IS ORGANIZED. 2373 01:46:13,975 --> 01:46:16,243 EFFORT IS ONE OF THE DRIVERS OF 2374 01:46:16,243 --> 01:46:18,079 THE MOTOR CORTEX, DECISION 2375 01:46:18,079 --> 01:46:20,715 MAKING AND REWARD VERSUS EFFORT 2376 01:46:20,715 --> 01:46:22,083 DR. KOROSHETZ INTRODUCED EARLIER 2377 01:46:22,083 --> 01:46:26,153 BUT YOU'LL BE HEARING ABOUT THAT 2378 01:46:26,153 --> 01:46:28,356 LATER. 2379 01:46:28,356 --> 01:46:30,157 SO I'M NOT GOING TO MAKE 2380 01:46:30,157 --> 01:46:31,659 INDIVIDUAL INTRODUCTIONS OF THE 2381 01:46:31,659 --> 01:46:31,892 PEOPLE. 2382 01:46:31,892 --> 01:46:32,526 WE ALREADY SAID A LITTLE BIT 2383 01:46:32,526 --> 01:46:35,162 ABOUT THEM AND GOING TO GO 2384 01:46:35,162 --> 01:46:37,164 THROUGH THIS AS INFORMATION ONE 2385 01:46:37,164 --> 01:46:39,000 TOPIC AFTER THE NEXT. 2386 01:46:39,000 --> 01:46:41,869 WE'LL LEAD ON NEXT TO OR FIRST 2387 01:46:41,869 --> 01:46:45,539 AND THIS IS PATRICK BEDARD WHO 2388 01:46:45,539 --> 01:46:52,513 WILL TALK ABOUT ASPECTS OF 2389 01:46:52,513 --> 01:46:53,080 TRANSCRANIAL MAGNETIC 2390 01:46:53,080 --> 01:46:53,681 STIMULATION UNDERSTANDING THE 2391 01:46:53,681 --> 01:47:01,055 NATURE OF FATIGUE. 2392 01:47:01,055 --> 01:47:04,191 >> HELLO, EVERYONE. 2393 01:47:04,191 --> 01:47:05,459 IN ORDER TO MAKE HOMES THE BRAIN 2394 01:47:05,459 --> 01:47:09,463 AND IN PARTICULAR THE MOTOR 2395 01:47:09,463 --> 01:47:09,997 CORTEX SEEN AS THE GREEN 2396 01:47:09,997 --> 01:47:20,141 STRIP -- WILL GENERATE MOTOR 2397 01:47:20,141 --> 01:47:20,708 COMMANDS AND ACTIVATE THE 2398 01:47:20,708 --> 01:47:22,143 MUSCLES AND WE'LL HAVE MOVEMENT. 2399 01:47:22,143 --> 01:47:26,113 IF WE REPEAT THESE HOMES WITH 2400 01:47:26,113 --> 01:47:27,214 ENOUGH INTENSITY IT WILL CAUSE 2401 01:47:27,214 --> 01:47:27,915 FATIGUE. 2402 01:47:27,915 --> 01:47:29,950 WE CAN ASK THE QUESTION WHETHER 2403 01:47:29,950 --> 01:47:31,619 FATIGUE IS REPRESENTED IN THE 2404 01:47:31,619 --> 01:47:33,087 BRAIN OR IN THE PERIPHERY? 2405 01:47:33,087 --> 01:47:39,593 IS IT CENTRAL OR PERIPHERAL? 2406 01:47:39,593 --> 01:47:41,629 THE GOAL IS TO EVALUATE THE 2407 01:47:41,629 --> 01:47:43,297 MOTOR CORTEX EXCITABILITY OR THE 2408 01:47:43,297 --> 01:47:44,999 AMOUNT OF AVAILABLE RESOURCES TO 2409 01:47:44,999 --> 01:47:49,537 MAKE MOVEMENTS. 2410 01:47:49,537 --> 01:47:55,376 TO DO THAT WE APPLIED THE PULSE 2411 01:47:55,376 --> 01:47:58,779 THE TRANS CRANIAL MAGNETIC 2412 01:47:58,779 --> 01:48:01,482 STIMULATION OR TMS OVER THE 2413 01:48:01,482 --> 01:48:02,817 PRIMARY MOTOR CORTEX TO GENERATE 2414 01:48:02,817 --> 01:48:04,452 MOVEMENTS AND WE GENERATE THEM 2415 01:48:04,452 --> 01:48:07,755 IN THE RIGHT THUMB SHOWN IN THE 2416 01:48:07,755 --> 01:48:09,323 PICTURE AT THE BOTTOM RIGHT. 2417 01:48:09,323 --> 01:48:14,862 HERE THE INTENSITY OR AMPLITUDE 2418 01:48:14,862 --> 01:48:16,330 IS AN INDICATION OF HOW MUCH 2419 01:48:16,330 --> 01:48:18,199 EXCITABILITY IS IN THE PRIMARY 2420 01:48:18,199 --> 01:48:18,733 MOTOR CORTEX. 2421 01:48:18,733 --> 01:48:20,835 WHAT WE SHOULD EXPECT TO FIND IS 2422 01:48:20,835 --> 01:48:22,436 WITH CENTRAL FATIGUE WE SHOULD 2423 01:48:22,436 --> 01:48:25,639 SEE A REDUCTION OF THE RESPONSE. 2424 01:48:25,639 --> 01:48:26,841 THERE'S LESS RESOURCES FOR 2425 01:48:26,841 --> 01:48:30,144 PRIMARY MOTOR CORTEX TO DRIVE 2426 01:48:30,144 --> 01:48:31,378 MOVEMENTS. 2427 01:48:31,378 --> 01:48:34,749 FOR PERIPHERAL FATIGUE, THE GOAL 2428 01:48:34,749 --> 01:48:38,085 IS TO EVALUATE THE MUSCLE 2429 01:48:38,085 --> 01:48:39,453 FATIGUING TEST. 2430 01:48:39,453 --> 01:48:42,156 A KEY FEATURE IS A SHIFT IN THE 2431 01:48:42,156 --> 01:48:43,624 MUSCLE ACTIVITY TOWARDS THE LOW 2432 01:48:43,624 --> 01:48:48,129 FREQUENCY COMPONENTS. 2433 01:48:48,129 --> 01:48:50,131 ONE WAY TO MEASURE THAT SWING 2434 01:48:50,131 --> 01:48:52,099 THE INDEX. 2435 01:48:52,099 --> 01:48:53,968 THIS IS THE METRIC WE WILL USE. 2436 01:48:53,968 --> 01:48:56,103 WE SHOULD EXPECT TO FIND WITH 2437 01:48:56,103 --> 01:48:59,306 PERIPHERAL FATIGUE WE SHOULD SEE 2438 01:48:59,306 --> 01:49:04,545 AN INCREASE IN THE MUTUAL INDEX 2439 01:49:04,545 --> 01:49:05,479 AND RESOURCES AVAILABLE. 2440 01:49:05,479 --> 01:49:07,314 TO INDUCE FATIGUE WE DESIGNED A 2441 01:49:07,314 --> 01:49:09,016 TASK IN WHICH PARTICIPANTS HAD 2442 01:49:09,016 --> 01:49:12,019 TO CONTROL THE GREEN BAR ON THE 2443 01:49:12,019 --> 01:49:15,890 LEFT MOVING IT UP AND DOWN BY 2444 01:49:15,890 --> 01:49:16,590 SQUEEZING THE DEVICE SHOWN ON 2445 01:49:16,590 --> 01:49:16,891 THE RIGHT. 2446 01:49:16,891 --> 01:49:18,726 WHAT THEY HAVE TO DO IS TO 2447 01:49:18,726 --> 01:49:20,995 REMAIN LEVEL WITH THE RED BAR 2448 01:49:20,995 --> 01:49:25,099 WHICH WAS SET AT 50% OF THE 2449 01:49:25,099 --> 01:49:25,966 MAXIMUM FORCE A PARTICIPANT 2450 01:49:25,966 --> 01:49:29,236 COULD DO ALSO KNOWN AS THE 2451 01:49:29,236 --> 01:49:30,104 MAXIMUM VOLUNTARY COUNTER 2452 01:49:30,104 --> 01:49:30,571 ACTION. 2453 01:49:30,571 --> 01:49:32,106 WE DID THIS TASK FOR BLOCKS OF 2454 01:49:32,106 --> 01:49:35,042 30 SECONDS INTERSPACED WITH 2455 01:49:35,042 --> 01:49:38,145 BLOCKS OF REST OF ALSO 30 2456 01:49:38,145 --> 01:49:41,182 SECONDS AND THEY DID THESE 2457 01:49:41,182 --> 01:49:42,483 BLOCKS IN MANY OF THESE BLOCKS. 2458 01:49:42,483 --> 01:49:46,487 THE RESULTS HAVE SHOWN THERE WAS 2459 01:49:46,487 --> 01:49:48,422 NO DIFFERENCE IN THE MAXIMUM 2460 01:49:48,422 --> 01:49:49,156 VOLUNTARY CONTRACTION BETWEEN 2461 01:49:49,156 --> 01:49:49,723 THE GROUPS. 2462 01:49:49,723 --> 01:49:51,025 HERE IN BLUE YOU SEE THE 2463 01:49:51,025 --> 01:49:54,161 CONTROLS AND IN RED IS THE CFS 2464 01:49:54,161 --> 01:49:55,529 GROUP. 2465 01:49:55,529 --> 01:49:57,832 BUT DURING THE TASK IT BECAME 2466 01:49:57,832 --> 01:50:00,100 DIFFICULT FOR THE PARTICIPANTS 2467 01:50:00,100 --> 01:50:02,169 OF THE ME/CFS TO MAINTAIN AND 2468 01:50:02,169 --> 01:50:05,840 GENERATE ENOUGH FORCE TO 2469 01:50:05,840 --> 01:50:08,142 MAINTAIN MATCH THE DEMANDS OF 2470 01:50:08,142 --> 01:50:09,210 THE TASK. 2471 01:50:09,210 --> 01:50:10,811 THEY CANNOT GENERATE ENOUGH 2472 01:50:10,811 --> 01:50:11,946 FORCE AND THE CONTROLS WE'RE 2473 01:50:11,946 --> 01:50:14,014 AUTOMOBILE TO STAY LEVEL WITH 2474 01:50:14,014 --> 01:50:17,051 THE DEMANDS OF THE TASK. 2475 01:50:17,051 --> 01:50:20,721 CONCERNING CENTRAL FATIGUE OR 2476 01:50:20,721 --> 01:50:24,124 THE MUSCLE RESPONSE TO THE TMS 2477 01:50:24,124 --> 01:50:25,559 STIMULATION AS EXPECTED IN THE 2478 01:50:25,559 --> 01:50:27,394 CONTROLS IN BLUE WE SAW A 2479 01:50:27,394 --> 01:50:29,396 DECREASE IN THE RESPONSE BECAUSE 2480 01:50:29,396 --> 01:50:31,232 THE MOTOR CORTEX BECAME LESS 2481 01:50:31,232 --> 01:50:32,967 EXCITABLE DUE TO FATIGUE. 2482 01:50:32,967 --> 01:50:35,269 IN REVERSE WE SAW AN INCREASE IN 2483 01:50:35,269 --> 01:50:35,936 THE RESPONSE. 2484 01:50:35,936 --> 01:50:36,971 INDICATING THERE WAS STILL 2485 01:50:36,971 --> 01:50:38,138 RESOURCES AVAILABLE TO PRODUCE 2486 01:50:38,138 --> 01:50:42,343 MOVEMENT. 2487 01:50:42,343 --> 01:50:45,212 CONCERNING PERIPHERAL FATIGUE OR 2488 01:50:45,212 --> 01:50:46,447 THE MUSCLE RESPONSE DURING THE 2489 01:50:46,447 --> 01:50:49,016 TASK WE SAW THE CONTROLS REMAIN 2490 01:50:49,016 --> 01:50:50,150 STABLE OR THERE WAS A SLIGHT 2491 01:50:50,150 --> 01:50:53,687 INCREASE BUT THERE WAS A SHARP 2492 01:50:53,687 --> 01:50:55,589 DECREASE FOR THE ME/CFS GROUP 2493 01:50:55,589 --> 01:50:59,827 INDICATING NO SHIFT TOWARDS THE 2494 01:50:59,827 --> 01:51:01,528 LOW FREQUENCIES AND WERE STILL 2495 01:51:01,528 --> 01:51:02,162 REMAINING RESOURCES IN THE 2496 01:51:02,162 --> 01:51:09,670 MUSCLES TO GENERATE MOVEMENT. 2497 01:51:09,670 --> 01:51:14,141 SO IN CONCLUSION WE STARTED THE 2498 01:51:14,141 --> 01:51:16,477 MOTOR NETWORK IN GENERAL 2499 01:51:16,477 --> 01:51:17,311 REMAINED EXCITABLE FOR THE 2500 01:51:17,311 --> 01:51:18,512 ME/CFS AND REMAINING RESOURCES 2501 01:51:18,512 --> 01:51:21,081 AND WE SAW THE SAME THING NOR 2502 01:51:21,081 --> 01:51:24,985 MUSCLES. 2503 01:51:24,985 --> 01:51:27,688 THIS SUGGESTS THERE WAS ALSO 2504 01:51:27,688 --> 01:51:30,157 DRIVING FORCE FROM THE MOTOR 2505 01:51:30,157 --> 01:51:39,800 NETWORK. 2506 01:51:39,800 --> 01:51:40,935 >> GOOD MORNING. 2507 01:51:40,935 --> 01:51:45,739 MY NAME IS SILVINA HOROVITZ AND 2508 01:51:45,739 --> 01:51:51,078 TALK ABOUT THE YIELD FROM FMRI. 2509 01:51:51,078 --> 01:51:54,148 AS DR. BEDARD TOLD US, FATIGUE 2510 01:51:54,148 --> 01:51:55,849 SEEMS TO BE CENTRAL. 2511 01:51:55,849 --> 01:51:57,885 WE DIDN'T FIND PERIPHERAL 2512 01:51:57,885 --> 01:52:00,254 EFFECTS. 2513 01:52:00,254 --> 01:52:02,156 SO WE WANT TO UNDERSTAND WHY. 2514 01:52:02,156 --> 01:52:06,160 FOR THIS WE WANT TO OBSERVE HOW 2515 01:52:06,160 --> 01:52:08,495 THE BRAIN AREAS ENGAGE OR 2516 01:52:08,495 --> 01:52:10,164 DISENGAGE AS THE PROCESS OF 2517 01:52:10,164 --> 01:52:17,905 FATIGUE IS HAPPENING. 2518 01:52:17,905 --> 01:52:21,175 FOR FUNCTIONAL fMRI A SCANNER 2519 01:52:21,175 --> 01:52:22,876 YOU CAN USE FOR OTHER RESONANCE 2520 01:52:22,876 --> 01:52:25,579 STUDIES AND HAS THE ABILITY TO 2521 01:52:25,579 --> 01:52:28,716 FOLLOW NEURAL ACTIVITY. 2522 01:52:28,716 --> 01:52:31,552 SO IF THE NEURONS ARE ACTIVATED 2523 01:52:31,552 --> 01:52:32,186 THEY'LL NEED SUPPLIES. 2524 01:52:32,186 --> 01:52:34,288 THE SUPPLIES WILL COME THROUGH 2525 01:52:34,288 --> 01:52:38,158 THE OXYGEN AND THE BLOOD WILL 2526 01:52:38,158 --> 01:52:44,198 BECOME THE OXYGENATOR AND 2527 01:52:44,198 --> 01:52:46,166 THEY'RE DIFFERENT AND THEREFORE 2528 01:52:46,166 --> 01:52:48,769 THE SCANNER CAN HAVE ALTERATIONS 2529 01:52:48,769 --> 01:52:50,637 AND THAT WILL BECOME THE SIGNAL 2530 01:52:50,637 --> 01:52:55,342 AS YOU CAN SEE IN THE FIGURE IN 2531 01:52:55,342 --> 01:52:57,644 THE FAR LEFT OF YOU. 2532 01:52:57,644 --> 01:52:59,913 AND THAT IS A MAP OF THE AREAS 2533 01:52:59,913 --> 01:53:10,591 THAT PARTICIPATED IN THE TASK. 2534 01:53:10,591 --> 01:53:12,092 FOR THIS WE DON'T HAVE AN 2535 01:53:12,092 --> 01:53:13,694 ABSOLUTE MEASURE OR THE SIGNAL 2536 01:53:13,694 --> 01:53:16,797 WILL TELL EXACTLY A NUMBER BUT 2537 01:53:16,797 --> 01:53:18,298 RATHER THE DIFFERENCE BETWEEN 2538 01:53:18,298 --> 01:53:20,467 TWO DIFFERENT CONDITIONS. 2539 01:53:20,467 --> 01:53:24,738 SO IN A BLOOD DESIGN AS SHOWN IN 2540 01:53:24,738 --> 01:53:27,007 THE TOP YOU HAVE REST AND TASK 2541 01:53:27,007 --> 01:53:29,043 OR ACTIVITY AND THAT WILL BE OUR 2542 01:53:29,043 --> 01:53:31,412 COMPARING AND WHAT IS IMPORTANT 2543 01:53:31,412 --> 01:53:34,681 TO NOTE IS THAT BECAUSE IT'S A 2544 01:53:34,681 --> 01:53:37,084 RELATIVE DIFFERENCE BETWEEN THE 2545 01:53:37,084 --> 01:53:39,553 CONDITIONS THE VALUE WE ARE 2546 01:53:39,553 --> 01:53:41,655 SEEING COULD BE A CHANGE IN 2547 01:53:41,655 --> 01:53:45,292 ACTIVATION OR CHANGE IN THE 2548 01:53:45,292 --> 01:53:48,762 CONDITION THAT WE CALL REST. 2549 01:53:48,762 --> 01:53:51,231 SO FOR OUR STUDY WE USED THE 2550 01:53:51,231 --> 01:53:53,300 SAME PARADIGM DESCRIBED BY 2551 01:53:53,300 --> 01:53:57,271 DR. BEDARD WHERE WE USE THE REST 2552 01:53:57,271 --> 01:54:02,142 AS RELAXING THE HAND AND THE 2553 01:54:02,142 --> 01:54:04,044 BLOCK TASK WAS THE FORCE USING 2554 01:54:04,044 --> 01:54:07,114 USED BEFORE AND ASKING THE 2555 01:54:07,114 --> 01:54:08,515 SUBJECTS TO MAINTAIN THAT RED 2556 01:54:08,515 --> 01:54:13,120 BAR THAT WILL BE AT THE 50% OF 2557 01:54:13,120 --> 01:54:13,754 THE MAXIMUM CONSTRUCTION THAT 2558 01:54:13,754 --> 01:54:15,522 THEY COULD DO. 2559 01:54:15,522 --> 01:54:18,358 THE TWO QUESTIONS THAT WE WANTED 2560 01:54:18,358 --> 01:54:20,661 TO ANSWER NOW WITHIN THE BRAIN 2561 01:54:20,661 --> 01:54:22,162 IS WHETHER THE DEFICITS COME 2562 01:54:22,162 --> 01:54:25,332 FROM THE MOTOR NETWORK OR THE 2563 01:54:25,332 --> 01:54:28,302 CHANGES IN FATIGUE COME 2564 01:54:28,302 --> 01:54:31,271 SOMEWHERE ELSEWHERE WHAT IS 2565 01:54:31,271 --> 01:54:33,340 HAPPENING IN THE WHOLE BRAIN 2566 01:54:33,340 --> 01:54:37,678 BECAUSE MOTOR CORTEX IS OUR 2567 01:54:37,678 --> 01:54:39,980 OBVIOUS PLACE TO LOOK FOR MOTOR 2568 01:54:39,980 --> 01:54:41,448 TASK BUT THE BRAIN ACTS AS A 2569 01:54:41,448 --> 01:54:43,517 NETWORK AND MORE INTEGRATED. 2570 01:54:43,517 --> 01:54:47,721 SO THE RESULTS WE HAVE ARE 2571 01:54:47,721 --> 01:54:50,157 SIMILAR AGAIN IN THE TASK TO 2572 01:54:50,157 --> 01:54:54,061 WHAT WAS FOUND IN THE EXPERIMENT 2573 01:54:54,061 --> 01:54:56,763 WITH TMS AND EDG. 2574 01:54:56,763 --> 01:54:58,899 THE NUMBER OF BLOCKS THE 2575 01:54:58,899 --> 01:55:02,136 CONTROLS DID IS HY THAN THE 2576 01:55:02,136 --> 01:55:04,738 NUMBER OF BLOCKS OF THE PATIENTS 2577 01:55:04,738 --> 01:55:06,006 WITH ME/CFS. 2578 01:55:06,006 --> 01:55:08,275 PATIENTS WERE ABLE TO PERFORM 2579 01:55:08,275 --> 01:55:09,676 HOWEVER, EVERYBODY DOES DID THE 2580 01:55:09,676 --> 01:55:12,546 TASK AND WHEN WE LOOKED AT THE 2581 01:55:12,546 --> 01:55:14,982 MORT TASK ACTIVATION WE CAN SEE 2582 01:55:14,982 --> 01:55:18,285 BOTH HAVE ACTIVITY IN THE MOTOR 2583 01:55:18,285 --> 01:55:21,655 CORTEX AND INDEED WITH DON'T SEE 2584 01:55:21,655 --> 01:55:23,624 IN THAT NETWORK A SIGNIFICANT 2585 01:55:23,624 --> 01:55:26,126 DIFFERENCE WHEN WE COMPARE THE 2586 01:55:26,126 --> 01:55:28,762 SIGNALS. 2587 01:55:28,762 --> 01:55:31,331 WHEN WE LOOK AT THE WHOLE BRAIN 2588 01:55:31,331 --> 01:55:34,134 ANALYSIS WE DO FIND DIFFERENCES. 2589 01:55:34,134 --> 01:55:36,403 HERE WE NEED DO THE ANALYSIS 2590 01:55:36,403 --> 01:55:36,904 SLIGHTLY DIFFERENT. 2591 01:55:36,904 --> 01:55:39,373 FOR THIS PART OF THE ANALYSIS WE 2592 01:55:39,373 --> 01:55:44,111 DIVIDED THE 16 BLOCKS THAT 2593 01:55:44,111 --> 01:55:47,781 SUBJECTS DID IN FOUR CHUNKS. 2594 01:55:47,781 --> 01:55:51,218 WE COMPARED HOW THE SIGNAL 2595 01:55:51,218 --> 01:55:55,622 EVOLVED OVER TIME AND CROSS 2596 01:55:55,622 --> 01:55:56,089 GROUPS. 2597 01:55:56,089 --> 01:55:59,359 WE FIND A DIFFERENCE IN THIS 2598 01:55:59,359 --> 01:56:03,630 AREA THAT IS THE TEMPORAL 2599 01:56:03,630 --> 01:56:06,200 PARIETAL JUNCTION AND THE 2600 01:56:06,200 --> 01:56:09,736 PARIETAL LOBULE AND THEY'RE 2601 01:56:09,736 --> 01:56:11,405 ASSOCIATED WITH MOTOR 2602 01:56:11,405 --> 01:56:12,406 INTEGRATION INCLUDING MOTOR 2603 01:56:12,406 --> 01:56:12,639 CONTROL. 2604 01:56:12,639 --> 01:56:14,708 WE FIND AT THE BEGINNING OF 2605 01:56:14,708 --> 01:56:16,276 ACTIVATION OF THE TRIAL THE 2606 01:56:16,276 --> 01:56:19,079 FIRST FOUR BLOCKS THERE WAS NO 2607 01:56:19,079 --> 01:56:19,947 GROUP DIFFERENCE IN THE WAY THAT 2608 01:56:19,947 --> 01:56:21,949 THESE AREAS WERE ENGAGED. 2609 01:56:21,949 --> 01:56:23,116 BUT AS WE PROGRESSED IN THE 2610 01:56:23,116 --> 01:56:24,918 BLOCKS AND CAN SEE THE 2611 01:56:24,918 --> 01:56:27,120 DIFFERENCE IN BEHAVIOR, WE CAN 2612 01:56:27,120 --> 01:56:28,689 ALSO OBSERVE IN THE BLUE LINE 2613 01:56:28,689 --> 01:56:30,324 THE SIGNAL INCREASED UP TO THE 2614 01:56:30,324 --> 01:56:36,029 POINT OF FATIGUE AND GOES DOWN. 2615 01:56:36,029 --> 01:56:39,333 HOWEVER, IN THE FES GROUP THE 2616 01:56:39,333 --> 01:56:39,866 SIGNAL CONTINUOUSLY SHOWS 2617 01:56:39,866 --> 01:56:42,135 DECREASE. 2618 01:56:42,135 --> 01:56:45,439 SO IN SUMMARY WE CAN SAY THE 2619 01:56:45,439 --> 01:56:50,143 MOTOR NETWORK ENGAGEMENT SHOWS 2620 01:56:50,143 --> 01:56:51,078 SIMILAR PATTERNS FOR BOTH 2621 01:56:51,078 --> 01:56:51,378 GROUPS. 2622 01:56:51,378 --> 01:56:53,247 THIS SUGGESTS IT'S NOTE CAUSE OF 2623 01:56:53,247 --> 01:56:54,815 THE FATIGUE AND WHEN WE LOOK AT 2624 01:56:54,815 --> 01:56:59,786 THE WHOLE BRAIN LABEL THE AREAS 2625 01:56:59,786 --> 01:57:02,155 THAT SHOW DIFFERENCES THE 2626 01:57:02,155 --> 01:57:04,491 TEMPORAL PARIETAL JUNCTION AND 2627 01:57:04,491 --> 01:57:07,461 LOBE WHERE AREAS OF HIGH ORDE 2628 01:57:07,461 --> 01:57:09,463 INTEGRATION AND SHOW THE 2629 01:57:09,463 --> 01:57:12,165 DIFFERENCE AND THIS COULD 2630 01:57:12,165 --> 01:57:14,134 INDICATE SOME DECREASED MOTOR 2631 01:57:14,134 --> 01:57:18,171 CONTROL SIGNALLING OR CHANGES IN 2632 01:57:18,171 --> 01:57:28,515 THE MOTOR MATCHING. 2633 01:57:36,123 --> 01:57:43,130 NOW DR. GOLDSTEIN. 2634 01:57:43,130 --> 01:57:45,565 >> I'M DAVE GOLDSTEIN. 2635 01:57:45,565 --> 01:57:49,002 I DIRECT THE AUTONOMIC MEDICINE 2636 01:57:49,002 --> 01:57:50,137 SECTION IN THE NEURAL CLINICAL 2637 01:57:50,137 --> 01:57:50,537 SCIENCES PROGRAM. 2638 01:57:50,537 --> 01:57:55,976 TODAY I'LL BE TALKING ABOUT THE 2639 01:57:55,976 --> 01:58:00,814 AUTONOMIC AND CAT COAL MINNER 2640 01:58:00,814 --> 01:58:01,448 GIC IN THE ME/CFS COMPARED TO 2641 01:58:01,448 --> 01:58:11,758 THIL KOL UNVEERZ. 2642 01:58:14,061 --> 01:58:17,264 IT'S NOT ONE THING AND IN TERMS 2643 01:58:17,264 --> 01:58:22,169 OF ENTERIC AND PARASYMPATHETIC 2644 01:58:22,169 --> 01:58:29,076 SYMPTOM AND SYMPATHETIC NERVOUS 2645 01:58:29,076 --> 01:58:29,376 SYSTEM. 2646 01:58:29,376 --> 01:58:31,144 IT WAS FOUND THERE ARE SPECIFIC 2647 01:58:31,144 --> 01:58:33,680 MEM CAL MESSENGERS ASSOCIATED 2648 01:58:33,680 --> 01:58:37,184 WITH THE DIFFERENT COMPONENTS OF 2649 01:58:37,184 --> 01:58:42,589 THE AUTONOMIC NERVOUS SYSTEM AND 2650 01:58:42,589 --> 01:58:46,159 ACETYLCHOLINE NOT ONLY THE CH 2651 01:58:46,159 --> 01:58:49,129 CHEMICAL MESSENGER OF THE SYSTEM 2652 01:58:49,129 --> 01:58:59,539 WHICH MEDIATED SWEATING. 2653 01:59:04,544 --> 01:59:07,214 AND THEY DEFINE THE ADRENAL 2654 01:59:07,214 --> 01:59:10,450 SYSTEM AS A MONOLITHIC EMERGENCY 2655 01:59:10,450 --> 01:59:12,753 SYSTEM TO MAINTAIN HOMEOSTASIS. 2656 01:59:12,753 --> 01:59:19,025 A WORD HE COINED IN EMERGENCIES. 2657 01:59:19,025 --> 01:59:20,127 ACTUALLY, THREES DIFFERENT 2658 01:59:20,127 --> 01:59:21,795 COMPONENTS AND ARE REGULATED 2659 01:59:21,795 --> 01:59:24,731 DIFFERENTLY AS I'LL GET INTO IN 2660 01:59:24,731 --> 01:59:25,298 A LITTLE BIT. 2661 01:59:25,298 --> 01:59:33,006 THE CHEMICAL MESSENGER OF THE 2662 01:59:33,006 --> 01:59:33,807 SYMPATHETIC ANNIVERSARY SYSTEM 2663 01:59:33,807 --> 01:59:37,944 IN CARDIOVASCULAR SECTION IS NOR 2664 01:59:37,944 --> 01:59:42,182 EPINEPHRINE AND EPINEPHRINE IS 2665 01:59:42,182 --> 01:59:46,920 THE MAIN RECENTER OF THE 2666 01:59:46,920 --> 01:59:47,754 NEUROENDOCRINE SYSTEM. 2667 01:59:47,754 --> 01:59:50,524 ONE OF THE KEY AUTONOMIC 2668 01:59:50,524 --> 01:59:52,159 FUNCTION TEST THAT'S DONE IS 2669 01:59:52,159 --> 01:59:53,293 TILT TABLE TESTING. 2670 01:59:53,293 --> 01:59:56,563 THIS IS BECAUSE WHEN A PERSON IS 2671 01:59:56,563 --> 02:00:00,167 TILTED UP THERE'S A DECREASE IN 2672 02:00:00,167 --> 02:00:01,401 RETURN TO THE HEART AND YOU'RE 2673 02:00:01,401 --> 02:00:04,404 EXAMINING THE ABILITY TO COUNTER 2674 02:00:04,404 --> 02:00:07,707 THAT DECREASE IN VENOUS RETURN 2675 02:00:07,707 --> 02:00:10,343 BY A VARIETY OF COMPENSATORY 2676 02:00:10,343 --> 02:00:11,511 HOMEOSTATIC PROCESSES. 2677 02:00:11,511 --> 02:00:16,750 THIS SHOWS THE ARRANGEMENT AT 2678 02:00:16,750 --> 02:00:18,785 THE TIME OF THE AUTONOMIC 2679 02:00:18,785 --> 02:00:21,855 FUNCTION TESTING. 2680 02:00:21,855 --> 02:00:25,725 IT STARTED WITH THE VALSALVIN 2681 02:00:25,725 --> 02:00:26,860 MANEUVER AND WON'T GO IN THE 2682 02:00:26,860 --> 02:00:28,929 RESULTS OF THAT AND FOCUS ON 2683 02:00:28,929 --> 02:00:30,864 WHAT HAPPENED DURING HEAD UP, 2684 02:00:30,864 --> 02:00:34,034 TILT TABLE TESTING FOR UP TO 40 2685 02:00:34,034 --> 02:00:44,177 MINUTES. 2686 02:00:49,816 --> 02:00:52,619 HERE'S SOME OF THE PHYSIOLOGICAL 2687 02:00:52,619 --> 02:00:56,456 DATA AS THE CONVENTION FOR OTHER 2688 02:00:56,456 --> 02:00:59,960 TALKS HE WILL THE VOLUNTEERS IN 2689 02:00:59,960 --> 02:01:01,761 BLUE AND ME/CFS GROUP IN RED. 2690 02:01:01,761 --> 02:01:06,166 HEART RATE INCREASED IN BOTH 2691 02:01:06,166 --> 02:01:08,101 GROUPS WITH INCREASE 2692 02:01:08,101 --> 02:01:09,402 IDENTICALLY. 2693 02:01:09,402 --> 02:01:11,671 FINGER SYSTOLIC BLOOD PRESSURE 2694 02:01:11,671 --> 02:01:12,939 WENT UP IN BOTH GROUPS. 2695 02:01:12,939 --> 02:01:15,642 KIND OF AN INTERESTING 2696 02:01:15,642 --> 02:01:16,209 PHENOMENON. 2697 02:01:16,209 --> 02:01:18,211 YOU WOULD THINK BLOOD PRESSURE 2698 02:01:18,211 --> 02:01:21,915 SHOULDN'T GO UP WITH TILTING BUT 2699 02:01:21,915 --> 02:01:24,184 THAT'S WHAT WAS FOUND. 2700 02:01:24,184 --> 02:01:27,053 STROKE VOLUME WENT DOWN IN BOTH 2701 02:01:27,053 --> 02:01:27,888 GROUPS. 2702 02:01:27,888 --> 02:01:32,392 THIS IS STROKE VOLUME ESTIMATED 2703 02:01:32,392 --> 02:01:33,960 BY APPLYING AN ALGORITHM CALLED 2704 02:01:33,960 --> 02:01:38,164 BEAT SCOPE TO THE FINGER CUFF 2705 02:01:38,164 --> 02:01:48,542 BLOOD PRESSURE SIGNAL. 2706 02:01:55,515 --> 02:02:00,987 THERE'S AN INCREASE IN STROKE 2707 02:02:00,987 --> 02:02:02,155 VOLUME IN THE CHRONIC FATIGUE 2708 02:02:02,155 --> 02:02:12,332 PATIENTS. 2709 02:02:13,466 --> 02:02:18,104 IN TERMS OF CATECHOLAMINES 2710 02:02:18,104 --> 02:02:19,205 NOREPINEPHRINE WENT UP AND 2711 02:02:19,205 --> 02:02:24,344 STAYED UP DURING TILTING BUT 2712 02:02:24,344 --> 02:02:25,612 GROUPS DID NOT DIFFER. 2713 02:02:25,612 --> 02:02:28,014 WHEN IT COUPLES TO EPINEPHRINE 2714 02:02:28,014 --> 02:02:32,152 THIS WAS AN INCREASE IN 2715 02:02:32,152 --> 02:02:33,053 EPINEPHRINE IN THE GROUPS TENDED 2716 02:02:33,053 --> 02:02:33,987 TO DIFFER. 2717 02:02:33,987 --> 02:02:39,392 YOU CAN SEE BASED ON THE 2718 02:02:39,392 --> 02:02:42,462 INDIVIDUAL RESULTS HERE THAT 2719 02:02:42,462 --> 02:02:46,166 SOME OF THE ME/CFS PATIENTS HAD 2720 02:02:46,166 --> 02:02:48,501 LARGE EPINEPHRINE RESPONSES AND 2721 02:02:48,501 --> 02:02:49,135 THAT EXPLAINS THE INCREASE IN 2722 02:02:49,135 --> 02:02:52,072 THE MEAN VALUES. 2723 02:02:52,072 --> 02:02:52,539 BUT THERE'S A LOT OF 2724 02:02:52,539 --> 02:03:02,182 VARIABILITY. 2725 02:03:02,182 --> 02:03:04,050 TO SUMMARIZE THE TILT FINDING 2726 02:03:04,050 --> 02:03:12,959 THERE WAS NO ORTHOSTATIC BY THE 2727 02:03:12,959 --> 02:03:14,127 FINGER CUFFING IN EITHER GROUP 2728 02:03:14,127 --> 02:03:22,068 AND THERE WAS NO INCREASE IN THE 2729 02:03:22,068 --> 02:03:27,007 FREQUENCY OF POSTURAL 2730 02:03:27,007 --> 02:03:28,608 TACHYCARDIA SYNDROME BY THE 2731 02:03:28,608 --> 02:03:29,776 HEART RATE RESPONSE TO THE 2732 02:03:29,776 --> 02:03:30,010 TILTING. 2733 02:03:30,010 --> 02:03:31,011 THE DIFFERENCE YOU SEE IS NOT 2734 02:03:31,011 --> 02:03:39,719 STATISTICALLY SIGNIFICANT. 2735 02:03:39,719 --> 02:03:45,258 THE GROUPS DID NOT DIFFER IN 2736 02:03:45,258 --> 02:03:50,096 SUDDEN HYPERTENSION CALLED 2737 02:03:50,096 --> 02:03:53,967 NEURALLY MEDIATED HYPOTENSION 2738 02:03:53,967 --> 02:04:04,444 AND NO DIFFERENCE IN PRE -- 2739 02:04:08,515 --> 02:04:10,717 PRESINCOPY AND NAUSEA. 2740 02:04:10,717 --> 02:04:12,986 THIS IS A SCHEME THAT SHOWS THE 2741 02:04:12,986 --> 02:04:20,560 SOURCES OF DIFFERENT LEVELS OF 2742 02:04:20,560 --> 02:04:31,071 CATTICOLS IN THE SPINAL FLUID. 2743 02:04:32,138 --> 02:04:42,582 THIS IS INDUCED BY THIROSINE 2744 02:04:46,252 --> 02:04:49,389 CONVERTED TO NOREPINEPHRINE. 2745 02:04:49,389 --> 02:04:51,725 MAIN MEASURE OF NOREPINEPHRINE 2746 02:04:51,725 --> 02:04:55,395 SCORES IS DHPG. 2747 02:04:55,395 --> 02:04:59,666 THE MAIN NEURONAL METABOLITE OF 2748 02:04:59,666 --> 02:05:01,067 NOR EPINEPHRINE. 2749 02:05:01,067 --> 02:05:04,471 THE MAIN STORES ISN'T DOPAMINE 2750 02:05:04,471 --> 02:05:09,909 IT'S DOPAC ACID THE MAIN 2751 02:05:09,909 --> 02:05:20,453 NEURONAL METABOLITE OF DOPAMINE. 2752 02:05:25,492 --> 02:05:28,361 THE CATECHOLAMINE DECREASED IN 2753 02:05:28,361 --> 02:05:30,163 THE ME/CFS GROUP COMPARED TO 2754 02:05:30,163 --> 02:05:33,933 HEALTHY VOLUNTEERED AND NOTABLY, 2755 02:05:33,933 --> 02:05:38,171 DHGP THE METABOLITE OF 2756 02:05:38,171 --> 02:05:40,507 NOREPINEPHRINE WAS QUITE 2757 02:05:40,507 --> 02:05:51,017 DECREASED IN THE ME/CFS GROUP. 2758 02:05:51,351 --> 02:05:55,255 WE DID NOT FIND EVIDENCE FOR 2759 02:05:55,255 --> 02:05:56,523 ORTHOSTATIC HYPERTENSION IN 2760 02:05:56,523 --> 02:05:57,090 ME/CFS. 2761 02:05:57,090 --> 02:05:58,558 THERE WERE NON SIGNIFICANT 2762 02:05:58,558 --> 02:06:01,194 DIFFERENCES IN TACHYCARDIA 2763 02:06:01,194 --> 02:06:04,030 SYNDROME DEFINED ENTIRELY BY A 2764 02:06:04,030 --> 02:06:07,167 HEART RATE AND THERE WAS NO 2765 02:06:07,167 --> 02:06:10,170 DIFFERENCE BETWEEN THE GROUPS 2766 02:06:10,170 --> 02:06:15,441 WITH SUDDEN HYPOTENSION WAS VASO 2767 02:06:15,441 --> 02:06:18,845 CONSTRICTION IN THE ME/CFS GROUP 2768 02:06:18,845 --> 02:06:21,748 AND PLASMA NOREPINEPHRINE DURING 2769 02:06:21,748 --> 02:06:25,084 REST AND INCREASED NORMALLY 2770 02:06:25,084 --> 02:06:28,621 WHEREAS THERE WAS A SUGGESTION 2771 02:06:28,621 --> 02:06:33,493 THAT SOME OF THE ME/CFS GROUP 2772 02:06:33,493 --> 02:06:35,895 HAD LARGE RESPONSE TO TILT BUT 2773 02:06:35,895 --> 02:06:38,164 THE BALANCE AND THE LARGER 2774 02:06:38,164 --> 02:06:45,505 INCREASE IN SYMPATHETIC 2775 02:06:45,505 --> 02:06:54,280 AGINERGIC ACTIVITY AND THE 2776 02:06:54,280 --> 02:06:58,184 CATECHOL RESPONSE SUGGESTS BIO 2777 02:06:58,184 --> 02:06:59,686 SYNTHESIS RESULTING IN DECREASED 2778 02:06:59,686 --> 02:07:02,188 NOREPINEPHRINE STORES. 2779 02:07:02,188 --> 02:07:12,365 THANK YOU. 2780 02:07:23,509 --> 02:07:23,877 >> HI. 2781 02:07:23,877 --> 02:07:28,014 I'M MARK LEVIN A CARDIOLOGIST AT 2782 02:07:28,014 --> 02:07:31,417 NHLBI AS DR. HALLETT MENTIONED. 2783 02:07:31,417 --> 02:07:38,258 I STUDY ARRHYTHMIA AND SUDDEN 2784 02:07:38,258 --> 02:07:40,226 CARDIAC DEATH AND I STUDY THE 2785 02:07:40,226 --> 02:07:41,060 AUTONOMIC SYSTEM AND WHAT I'LL 2786 02:07:41,060 --> 02:07:42,195 TALK ABOUT TODAY. 2787 02:07:42,195 --> 02:07:45,832 THE HEART IS A PUMP COORDINATE 2788 02:07:45,832 --> 02:07:47,300 THE CARDIAC INDUCTION SYSTEM AND 2789 02:07:47,300 --> 02:07:50,470 IT'S PICTURED IN THE CARTOON. 2790 02:07:50,470 --> 02:07:53,306 NORMAL BEATS CONDUCTED PROPERLY 2791 02:07:53,306 --> 02:07:55,575 WHICH MEANS THOSE BEATS 2792 02:07:55,575 --> 02:07:57,410 INITIATED IN THE SINUS NODE AND 2793 02:07:57,410 --> 02:07:58,678 PROGRESS TO THE AV NODE 2794 02:07:58,678 --> 02:08:00,246 THROUGHOUT THE REST OF THE HEART 2795 02:08:00,246 --> 02:08:02,849 ARE CONSIDERED NORMAL BEATS. 2796 02:08:02,849 --> 02:08:06,185 AND THE ELECTRICAL ACTIVITY THAT 2797 02:08:06,185 --> 02:08:08,655 PROCEEDS THROUGH THE HEART CAN 2798 02:08:08,655 --> 02:08:11,224 BE GRAPHED LIKE THE PICTURE HERE 2799 02:08:11,224 --> 02:08:14,594 AND ONE CAN NAME COMPONENTS OR 2800 02:08:14,594 --> 02:08:16,462 COMPLEXES IN THAT GRAPH SO 2801 02:08:16,462 --> 02:08:19,799 THERE'S THE PWAVE, THERE'S THE 2802 02:08:19,799 --> 02:08:22,435 QRS COMPLEX AND WHEN WE TALK 2803 02:08:22,435 --> 02:08:23,770 ABOUT THE DISTANCE BETWEEN TWO 2804 02:08:23,770 --> 02:08:26,572 QRS COMPLEXES WE TALK ABOUT THE 2805 02:08:26,572 --> 02:08:28,408 R INTERVAL. 2806 02:08:28,408 --> 02:08:29,976 WHEN THOSE BEATS AREN'T NORMAL 2807 02:08:29,976 --> 02:08:31,711 BEATS MEANING PROPERLY CONDUCTED 2808 02:08:31,711 --> 02:08:35,548 THROUGH THE CONDUCTION SYSTEM WE 2809 02:08:35,548 --> 02:08:38,952 CAN REFER TO THEM AS AN INTERVAL 2810 02:08:38,952 --> 02:08:42,789 WHICH IS AN ABBREVIATION YOU'LL 2811 02:08:42,789 --> 02:08:44,757 SEE IN THE REST OF TALK. 2812 02:08:44,757 --> 02:08:46,826 IT INVOLVES COMPARING NORMAL 2813 02:08:46,826 --> 02:08:50,596 BEATS MATHEMATICALLY DO QUANTIFY 2814 02:08:50,596 --> 02:08:51,898 AUTONOMIC SYSTEM ACTIVITY. 2815 02:08:51,898 --> 02:08:53,833 THIS ANALYSIS ASSUMES TIME 2816 02:08:53,833 --> 02:08:55,001 DIFFERENCES BETWEEN DIFFERENT 2817 02:08:55,001 --> 02:08:58,104 NORMAL BEATS ARE ATTRIBUTABLE TO 2818 02:08:58,104 --> 02:09:02,175 DIFFERENCES IN AUTONOMIC NERVOUS 2819 02:09:02,175 --> 02:09:04,277 SYSTEM ACTIVITY AND CAN BE 2820 02:09:04,277 --> 02:09:06,179 FURTHER BROKEN DOWN TO 2821 02:09:06,179 --> 02:09:08,348 SYMPATHETIC AND PARASYMPATHETIC 2822 02:09:08,348 --> 02:09:10,183 ACTIVITY AND THOSE ELEMENTS CAN 2823 02:09:10,183 --> 02:09:13,886 BE QUANTIFIED WITH HEART RATE 2824 02:09:13,886 --> 02:09:15,755 VARIABILITY, PARASYMPATHETIC 2825 02:09:15,755 --> 02:09:17,890 MEASURES ARE PRETTY WELL AGREED 2826 02:09:17,890 --> 02:09:19,592 UPON AND AGREED THE SYMPATHETIC 2827 02:09:19,592 --> 02:09:25,598 MEASURES ARE NOT GREAT. 2828 02:09:25,598 --> 02:09:27,066 SOME TYPES OF MATHEMATICAL 2829 02:09:27,066 --> 02:09:27,767 APPROACHES YOU CAN TAKE ARE 2830 02:09:27,767 --> 02:09:29,602 PICTURED HERE. 2831 02:09:29,602 --> 02:09:33,973 THOSE INCLUDE THE TIME DOMAIN 2832 02:09:33,973 --> 02:09:36,309 WHICH INVOLVE STRAIGHTFORWARD 2833 02:09:36,309 --> 02:09:37,510 STANDARD DEVIATION OF THE 2834 02:09:37,510 --> 02:09:39,946 INTERVALS, FREQUENCY DOMAIN 2835 02:09:39,946 --> 02:09:43,649 WHICH ASSUMES THAT A WAVE FORM 2836 02:09:43,649 --> 02:09:46,219 CAN BE DE COMPOSED INTO 2837 02:09:46,219 --> 02:09:52,792 COMPOSITE SIGN WAVES AS SHOWN 2838 02:09:52,792 --> 02:10:00,733 HERE USING FFT TRANSFORMATION 2839 02:10:00,733 --> 02:10:03,970 AND COULD BE FURTHER QUANTIFIED 2840 02:10:03,970 --> 02:10:05,071 AND COMPARED USING SPECTRAL 2841 02:10:05,071 --> 02:10:09,442 POWER UP ANALYSIS AS SHOWN HERE. 2842 02:10:09,442 --> 02:10:10,977 FINALLY THERE'S WHAT'S CALLED 2843 02:10:10,977 --> 02:10:13,112 NON-LINEAR APPROACHES WHICH ARE 2844 02:10:13,112 --> 02:10:14,180 HIGHER ORDER MATHEMATICAL 2845 02:10:14,180 --> 02:10:16,916 ANALYSIS WHICH ASSUME NO 2846 02:10:16,916 --> 02:10:18,217 PREDICTABLE PROPORTIONAL 2847 02:10:18,217 --> 02:10:19,919 RELATIONSHIP AND ONE OF THOSE 2848 02:10:19,919 --> 02:10:28,261 TYPES OF ANALYSES ARE PICTURED 2849 02:10:28,261 --> 02:10:32,698 HERE WHICH INVOLVES GRAPHING THE 2850 02:10:32,698 --> 02:10:39,806 INTERVAL AS THE SUBSEQUENT RR 2851 02:10:39,806 --> 02:10:41,541 INTERVAL AND THIS INVOLVES THE 2852 02:10:41,541 --> 02:10:42,809 SD1 INTERVAL. 2853 02:10:42,809 --> 02:10:45,912 WE DID OUR ANALYSIS BASED ON 2854 02:10:45,912 --> 02:10:48,347 CONSENSUS GUIDELINES AND YOU CAN 2855 02:10:48,347 --> 02:10:50,883 SEE THE REFERENCES FOR THOSE 2856 02:10:50,883 --> 02:10:58,691 GUIDELINES HERE. 2857 02:10:58,691 --> 02:11:00,059 IN DOING THESE ANALYSIS HEART 2858 02:11:00,059 --> 02:11:03,563 RATE AS A SURROGATE OF 2859 02:11:03,563 --> 02:11:04,130 SYMPATHETIC ACTIVITY. 2860 02:11:04,130 --> 02:11:05,731 WHILE THERE WAS NO STATISTICALLY 2861 02:11:05,731 --> 02:11:07,900 SIGNIFICANT DIFFERENCE WE FOUND 2862 02:11:07,900 --> 02:11:11,170 A TREND TOWARDS SIGNIFICANCE IN 2863 02:11:11,170 --> 02:11:14,974 THAT THEIR HEART RATES IN ME/CFS 2864 02:11:14,974 --> 02:11:16,809 SUBJECTS LOOKED LIKE IT MIGHT BE 2865 02:11:16,809 --> 02:11:26,452 GREATER THAN THAT OF CONTROLS. 2866 02:11:26,452 --> 02:11:29,856 WITH RESPECT TO PARASYMPATHETIC 2867 02:11:29,856 --> 02:11:34,160 ACTIVITY WE USED SEVERAL TIME 2868 02:11:34,160 --> 02:11:36,529 DETAIN MARKERS AND WE FOUND 2869 02:11:36,529 --> 02:11:38,965 ME/CFS SUBJECTS HAD DIMINISHED 2870 02:11:38,965 --> 02:11:46,172 VALUES IN BOTH OF THESE 2871 02:11:46,172 --> 02:11:46,572 PARAMETERS. 2872 02:11:46,572 --> 02:11:49,075 SIMILARLY WITH RESPECT TO 2873 02:11:49,075 --> 02:11:51,077 FREQUENCY DOMAIN ANALYSIS WE 2874 02:11:51,077 --> 02:11:51,644 FOUND HIGH FREQUENCY POWER 2875 02:11:51,644 --> 02:11:56,749 DIMINISHED IN ME/CFS SUBJECTS 2876 02:11:56,749 --> 02:11:59,218 COMPARED TO CONTROLS AND FOUND 2877 02:11:59,218 --> 02:12:02,088 THE SAME THING IN SD 1 IN 2878 02:12:02,088 --> 02:12:07,560 SUBJECTS COMPARED TO CONTROLS. 2879 02:12:07,560 --> 02:12:10,563 WE FOUND COMPOSITE MEASURES THAT 2880 02:12:10,563 --> 02:12:11,998 MEASURE OVER ALL HEART RATE 2881 02:12:11,998 --> 02:12:14,167 VARIABILITY AND THOSE INCLUDE 2882 02:12:14,167 --> 02:12:18,304 SDNN INDEX AND SD 1. 2883 02:12:18,304 --> 02:12:20,806 WE FOUND BOTH DIMINISHED 2884 02:12:20,806 --> 02:12:21,807 COMPARED TO CONTROLS AS WELL. 2885 02:12:21,807 --> 02:12:24,343 IN CONCLUSION, HEART RATE 2886 02:12:24,343 --> 02:12:26,179 VARIABILITY ASSESSED FROM 24 2887 02:12:26,179 --> 02:12:29,248 HOURS AMBULATORY ECGs SUGGEST 2888 02:12:29,248 --> 02:12:31,751 THAT ME/CFS SUBJECT HAVE 2889 02:12:31,751 --> 02:12:37,290 DECREASED PAIR TRA -- 2890 02:12:37,290 --> 02:12:39,258 PARASYMPATHETIC ACTIVITY AND 2891 02:12:39,258 --> 02:12:39,559 SD1. 2892 02:12:39,559 --> 02:12:41,994 THERE'S A SUGGESTION THAT 2893 02:12:41,994 --> 02:12:43,729 INCREASED HEART RATE IN ME/CFS 2894 02:12:43,729 --> 02:12:46,098 SUBJECTS COMPARED TO CONTROLS 2895 02:12:46,098 --> 02:12:49,502 MIGHT SUBJECT INCREASED 2896 02:12:49,502 --> 02:12:50,937 SYMPATHETIC ACTIVITY AND FINALLY 2897 02:12:50,937 --> 02:12:54,106 ME/CFS SUBJECTS HAVE DECREASED 2898 02:12:54,106 --> 02:12:55,741 OVER ALL HEART RATE VARIABILITY 2899 02:12:55,741 --> 02:12:58,344 AS COMPARED TO CONTROLS WITH 2900 02:12:58,344 --> 02:13:01,280 RESPECT TO SD NNI AND SD 1. 2901 02:13:01,280 --> 02:13:11,591 THANKS VERY MUCH. 2902 02:13:18,998 --> 02:13:20,233 >> HELLO, EVERYBODY. 2903 02:13:20,233 --> 02:13:23,936 MY NAME IS JOSEPH SNOW. 2904 02:13:23,936 --> 02:13:26,072 I'M AN INTRAMURAL CLINICAL 2905 02:13:26,072 --> 02:13:36,582 NEURAL PSYCHOLOGIST IN NIMHD. 2906 02:13:38,084 --> 02:13:41,487 WE PERFORM COGNITIVE TESTS 2907 02:13:41,487 --> 02:13:43,556 BECAUSE OF COMPLAINTS OF 2908 02:13:43,556 --> 02:13:45,124 COGNITIVE DIFFICULTY OR BRAIN 2909 02:13:45,124 --> 02:13:46,292 FOG DESCRIBED AS A CORE SYMPTOM 2910 02:13:46,292 --> 02:13:49,395 IN ME/CFS. 2911 02:13:49,395 --> 02:13:54,800 IN ADDITION COGNITIVE EXERTION 2912 02:13:54,800 --> 02:13:56,802 TRIGGERS POST EXERTIONAL MALAISE 2913 02:13:56,802 --> 02:13:58,170 AND FOUND COGNITIVE DEFICITS IN 2914 02:13:58,170 --> 02:14:08,314 ME/CFS. 2915 02:14:11,651 --> 02:14:14,153 THE GOALS WERE TO USE STANDARD 2916 02:14:14,153 --> 02:14:16,555 PSYCH METRIC METHODS TO EVALUATE 2917 02:14:16,555 --> 02:14:20,526 COGNITIVE FUNCTIONING IN ME/CFS 2918 02:14:20,526 --> 02:14:23,562 AND EVALUATE THEIR SUBJECTIVE 2919 02:14:23,562 --> 02:14:29,135 COMPLAINTS OF ME/CFS FOL 2920 02:14:29,135 --> 02:14:30,636 UNTEARS. 2921 02:14:30,636 --> 02:14:32,605 SO A VALID NEUROCOGNITIVE 2922 02:14:32,605 --> 02:14:33,339 EVALUATION HAS SEVERAL 2923 02:14:33,339 --> 02:14:33,906 REQUIREMENTS. 2924 02:14:33,906 --> 02:14:36,609 THERE NEEDS TO BE STANDARD 2925 02:14:36,609 --> 02:14:38,010 ADMINISTRATION THAT IS AN 2926 02:14:38,010 --> 02:14:39,045 EXAMINER MUST FOLLOW THE SAME 2927 02:14:39,045 --> 02:14:42,548 RULES FOR ALL RESPONDENTS. 2928 02:14:42,548 --> 02:14:44,550 THERE MUST BE OPTIMAL ENGAGEMENT 2929 02:14:44,550 --> 02:14:46,552 AND NEEDS TO BE OBJECTIVE 2930 02:14:46,552 --> 02:14:47,553 SCORING ALL TRAINED EVALUATORS 2931 02:14:47,553 --> 02:14:51,390 YIELD THE SAME RESULTS WITHIN A 2932 02:14:51,390 --> 02:14:54,393 MARGIN OF ERROR AND NORMATIVE 2933 02:14:54,393 --> 02:14:55,428 COMPARISON. 2934 02:14:55,428 --> 02:14:57,096 TESTEES COMPARED TO OTHERS 2935 02:14:57,096 --> 02:14:58,197 SIMILAR TO THEM SUCH AS IN TERMS 2936 02:14:58,197 --> 02:15:03,636 OF THEIR AGE AND EDUCATION. 2937 02:15:03,636 --> 02:15:06,172 AS PART OF OUR BATTERY WE 2938 02:15:06,172 --> 02:15:07,573 ADMINISTERED DIFFERENT TYPES OF 2939 02:15:07,573 --> 02:15:08,607 MEASURES. 2940 02:15:08,607 --> 02:15:11,544 SO-CALLED SUBJECTIVE MEASURES 2941 02:15:11,544 --> 02:15:16,415 SUCH AS ASKING TESTEES TO RATE 2942 02:15:16,415 --> 02:15:20,419 THEIR OWN SYMPTOMS OF 2943 02:15:20,419 --> 02:15:23,255 DEPRESSION, SYMPTOMS OF ANXIETY 2944 02:15:23,255 --> 02:15:24,957 OR THEIR COGNITIVE SYMPTOMS OR 2945 02:15:24,957 --> 02:15:26,158 THEIR OWN LEVEL OF TASK 2946 02:15:26,158 --> 02:15:31,364 ENGAGEMENT. 2947 02:15:31,364 --> 02:15:33,432 WE ALSO INCLUDED PERFORMANCE 2948 02:15:33,432 --> 02:15:36,535 VALIDITY TESTS WHICH ARE 2949 02:15:36,535 --> 02:15:37,336 QUANTITATIVE MEASURES TO 2950 02:15:37,336 --> 02:15:39,004 DETERMINE IF THERE IS AN 2951 02:15:39,004 --> 02:15:43,809 ACCEPTABLE LEVEL OF TASK 2952 02:15:43,809 --> 02:15:44,877 ENGAGEMENT AND THERE BE ASSIST 2953 02:15:44,877 --> 02:15:45,611 IN DETERMINING IF THE EVALUATION 2954 02:15:45,611 --> 02:15:49,548 ITSELF WAS VALID. 2955 02:15:49,548 --> 02:15:50,983 HERE ARE SOME SAMPLE 2956 02:15:50,983 --> 02:15:54,387 NEUROCOGNITIVE TESTS. 2957 02:15:54,387 --> 02:15:58,157 ON THE LEFT, WE HAVE A TASK 2958 02:15:58,157 --> 02:16:01,060 WHERE A LIST OF WORDS IS READ TO 2959 02:16:01,060 --> 02:16:03,362 THE VOLUNTEER SEVERAL TIMES AND 2960 02:16:03,362 --> 02:16:04,930 A NUMBER OF WORDS RECALL ON THE 2961 02:16:04,930 --> 02:16:05,898 TRIAL IS RECORDED AS WELL AS 2962 02:16:05,898 --> 02:16:08,033 FOLLOWING THE DELAY. 2963 02:16:08,033 --> 02:16:11,170 IN THE MIDDLE PANEL WE HAVE A 2964 02:16:11,170 --> 02:16:12,171 DESIGN LEARNING TASK, SEVERAL 2965 02:16:12,171 --> 02:16:14,473 TRIALS ARE PRESENTED AND THE 2966 02:16:14,473 --> 02:16:17,109 VOLUNTEER HAS TO RECALL THE 2967 02:16:17,109 --> 02:16:17,777 DESIGNS AFTER EACH PRESENTATION 2968 02:16:17,777 --> 02:16:20,179 AND FOLLOWING A DELAY. 2969 02:16:20,179 --> 02:16:23,282 ON THE RIGHT IS A CARD SORTING 2970 02:16:23,282 --> 02:16:24,984 TASK USED TO ASSESS EXECUTIVE 2971 02:16:24,984 --> 02:16:25,284 FUNCTIONING. 2972 02:16:25,284 --> 02:16:28,120 AND WE DID A WHOLE BUNCH OF 2973 02:16:28,120 --> 02:16:28,320 TESTS. 2974 02:16:28,320 --> 02:16:34,160 SOME ADDITIONAL TESTS WOULD BE 2975 02:16:34,160 --> 02:16:36,929 ASKING VOLUNTEERS TO GENERATE 2976 02:16:36,929 --> 02:16:39,565 THEIR WORDS TO CUE OR ASKING 2977 02:16:39,565 --> 02:16:41,367 THEM TO RAPIDLY PLACE PEGS IN 2978 02:16:41,367 --> 02:16:44,003 SLOTTED HOLES OR TO DO OTHER 2979 02:16:44,003 --> 02:16:46,205 TASK LIKE MENTAL ARITHMETIC OR A 2980 02:16:46,205 --> 02:16:51,310 CODING TASK. 2981 02:16:51,310 --> 02:16:53,712 SO THE DATA IS COLLECTED SUCH AS 2982 02:16:53,712 --> 02:16:57,550 A NUMBER OF ERRORS AND RAW 2983 02:16:57,550 --> 02:16:57,817 SCORES. 2984 02:16:57,817 --> 02:17:00,419 TIME TO COMPLETION AND THEN WE 2985 02:17:00,419 --> 02:17:02,555 ALSO COMPUTE THROUGH THE 2986 02:17:02,555 --> 02:17:04,089 NORMATIVE PROCESS WHERE ALL 2987 02:17:04,089 --> 02:17:05,724 SCORES ARE CONVERTED TO SCALE 2988 02:17:05,724 --> 02:17:07,927 SCORES AND T SCORES AND STANDARD 2989 02:17:07,927 --> 02:17:08,160 SCORES. 2990 02:17:08,160 --> 02:17:09,361 EACH HAS ITS OWN MEAN AND 2991 02:17:09,361 --> 02:17:13,766 STANDARD DEVIATION. 2992 02:17:13,766 --> 02:17:17,403 TO SUMMARIZE WE COLLECT SEVERAL 2993 02:17:17,403 --> 02:17:22,174 TYPES OF DATA CLUTH SUBJECTIVE 2994 02:17:22,174 --> 02:17:24,844 MEASURES, PERFORMANCE VALIDITY 2995 02:17:24,844 --> 02:17:29,715 AND PERFORMANCE BASED MEASURES 2996 02:17:29,715 --> 02:17:31,617 THE NEUROCOGNITIVE DATA PROPER. 2997 02:17:31,617 --> 02:17:33,219 ONE SUBJECT MEASURE IS THE MASS 2998 02:17:33,219 --> 02:17:34,153 CUE. 2999 02:17:34,153 --> 02:17:36,655 AS THEY MULTIPLE ABILITY 3000 02:17:36,655 --> 02:17:38,457 SELF-REPORT QUESTIONNAIRE AND ON 3001 02:17:38,457 --> 02:17:43,762 THIS FOR THIS QUESTIONNAIRE WE 3002 02:17:43,762 --> 02:17:45,464 ASKED VOLUNTEERS THE ME/CFS 3003 02:17:45,464 --> 02:17:46,165 PARTICIPANTS AND CONTROLS 3004 02:17:46,165 --> 02:17:47,766 QUESTIONS ABOUT THEIR CURRENT 3005 02:17:47,766 --> 02:17:50,035 LANGUAGE, ATTENTION, VERBAL 3006 02:17:50,035 --> 02:17:53,806 MEMORY VISUAL MEMORY AND 3007 02:17:53,806 --> 02:17:56,842 PERCEPTION, ETCETERA. 3008 02:17:56,842 --> 02:17:58,611 WE FOUND INDIVIDUALS IN THE RED 3009 02:17:58,611 --> 02:18:00,546 DESCRIBE MORE PROBLEMS IN EACH 3010 02:18:00,546 --> 02:18:02,147 OF THESE CATEGORIES THAN THE 3011 02:18:02,147 --> 02:18:07,620 CONTROLS. 3012 02:18:07,620 --> 02:18:08,554 THEN WE ALSO MEASURE DEPRESSION. 3013 02:18:08,554 --> 02:18:15,895 THIS WAS MENTIONED EARLIER. 3014 02:18:15,895 --> 02:18:21,300 WE FOUND VOLUNTEERS DESCRIBE 3015 02:18:21,300 --> 02:18:22,868 MORE ANXIETY THAN CONTROLS BUT 3016 02:18:22,868 --> 02:18:23,869 NOT VERY ELEVATED EITHER OF 3017 02:18:23,869 --> 02:18:25,738 THEM. 3018 02:18:25,738 --> 02:18:28,274 WE ALSO USED SOMETHING CALLED 3019 02:18:28,274 --> 02:18:30,676 VISUAL ANALOG SCALES TO HAVE OUR 3020 02:18:30,676 --> 02:18:33,512 PARTICIPANTS SELF-RATE THEIR 3021 02:18:33,512 --> 02:18:35,648 MENTAL FATIGUE AND PHYSICAL 3022 02:18:35,648 --> 02:18:38,951 FATIGUE AND ENGAGEMENT AND THE 3023 02:18:38,951 --> 02:18:40,553 TASK AND FATIGUE APPEARS TO GO 3024 02:18:40,553 --> 02:18:45,057 UP ACROSS TIME FOR EVERYBODY. 3025 02:18:45,057 --> 02:18:47,760 THE ME/CFS VOLUNTEERS HAVE MORE 3026 02:18:47,760 --> 02:18:50,029 SELF-REPORTED MENTAL AND 3027 02:18:50,029 --> 02:18:51,430 PHYSICAL FATIGUE PRIOR TO AND 3028 02:18:51,430 --> 02:18:52,031 DURING TESTING. 3029 02:18:52,031 --> 02:18:54,433 WE DO MULTIPLE MEASURES ACROSS 3030 02:18:54,433 --> 02:18:54,633 TIME. 3031 02:18:54,633 --> 02:18:57,136 BUT BOTH THE ME/CFS AND CONTROL 3032 02:18:57,136 --> 02:18:59,572 GROUPS ENDURE SELF-REPORTED 3033 02:18:59,572 --> 02:19:00,739 FATIGUE AT AN EQUAL RATE ACROSS 3034 02:19:00,739 --> 02:19:02,841 THE TESTING SESSION SO WE DIDN'T 3035 02:19:02,841 --> 02:19:05,978 SEE A DIVERGENCE OF THE TWO 3036 02:19:05,978 --> 02:19:10,816 LINES. 3037 02:19:10,816 --> 02:19:13,085 IN TERMS OF PERFORMANCE VALIDITY 3038 02:19:13,085 --> 02:19:16,622 TEST DESIGN TO ENSURE ADEQUATE 3039 02:19:16,622 --> 02:19:18,624 TASK ENGAGEMENT THERE WAS NO 3040 02:19:18,624 --> 02:19:20,159 DIFFERENCE BETWEEN ME/CFS AND 3041 02:19:20,159 --> 02:19:21,026 HEALTHY VOLUNTEERS. 3042 02:19:21,026 --> 02:19:23,295 SO INDIVIDUALS WITH ME/CFS DO 3043 02:19:23,295 --> 02:19:27,700 NOT APPEAR TO BE UNENGAGED IN 3044 02:19:27,700 --> 02:19:30,002 DOING WELL ON THE NEUROCOGNITIVE 3045 02:19:30,002 --> 02:19:34,173 TESTS. 3046 02:19:34,173 --> 02:19:36,542 IN TERMS OF PERFORMANCE ON 3047 02:19:36,542 --> 02:19:37,843 NEUROCOGNITIVE MEASURES THE LAB 3048 02:19:37,843 --> 02:19:39,578 MEASURES THAT HAVE BEEN WELL 3049 02:19:39,578 --> 02:19:44,917 VALIDATED AND USED FOR DECADES, 3050 02:19:44,917 --> 02:19:46,685 WE FOUND ME/CFS VOLUNTEERS 3051 02:19:46,685 --> 02:19:47,786 PERFORMED IN THE AVERAGE RANGE 3052 02:19:47,786 --> 02:19:50,155 AND THE YELLOW LINE ATTEMPTS TO 3053 02:19:50,155 --> 02:19:54,093 DEPICT THAT FOR EACH OF THE 3054 02:19:54,093 --> 02:19:58,964 CATEGORIES OF TESTS. 3055 02:19:58,964 --> 02:20:01,166 THE PERFORMANCE OF ME/CFS 3056 02:20:01,166 --> 02:20:02,101 ACCORDING TO OUR STATISTICAL 3057 02:20:02,101 --> 02:20:03,068 METHODS DOES NOT DIFFER FROM OUR 3058 02:20:03,068 --> 02:20:08,974 CONTROL VOLUNTEERS. 3059 02:20:08,974 --> 02:20:11,944 TO SUMMARIZE, ME/CFS VOLUNTEERS 3060 02:20:11,944 --> 02:20:14,179 HAVE A SATISFACTORY LEVEL OF 3061 02:20:14,179 --> 02:20:16,949 TASK ENGAGEMENT. 3062 02:20:16,949 --> 02:20:21,487 ME/CFS VOLUNTEERS DO NOT HAVE 3063 02:20:21,487 --> 02:20:22,121 INVALID TASK PERFORMANCE. 3064 02:20:22,121 --> 02:20:24,323 ME/CFS VOLUNTEERS HAVE MORE 3065 02:20:24,323 --> 02:20:26,892 SELF-REPORTED DEFICITS IN 3066 02:20:26,892 --> 02:20:29,028 ATTENTION, VERBAL MEMORY, VISUAL 3067 02:20:29,028 --> 02:20:30,162 SPATIAL LANGUAGE AND VISUAL 3068 02:20:30,162 --> 02:20:33,832 MEMORY. 3069 02:20:33,832 --> 02:20:37,169 ME/CFS VOLUNTEERS HAVE 3070 02:20:37,169 --> 02:20:38,404 SIGNIFICANTLY MORE SELF-REPORTED 3071 02:20:38,404 --> 02:20:43,108 DEPRESSION AND ANXIETY SYMPTOMS. 3072 02:20:43,108 --> 02:20:45,244 ME/CFS VOLUNTEERS HAVE MORE 3073 02:20:45,244 --> 02:20:46,645 SELF-REPORTED MENTAL AND 3074 02:20:46,645 --> 02:20:47,946 PHYSICAL FATIGUE PRIOR TO AND 3075 02:20:47,946 --> 02:20:51,483 DURING THE TESTING BATTERY BUT 3076 02:20:51,483 --> 02:20:54,153 BOTH ME/CFS AND CONTROL GROUPS 3077 02:20:54,153 --> 02:20:55,921 ENDURE SELF-REPORTED FATIGUE AT 3078 02:20:55,921 --> 02:20:58,157 AN EQUAL RATE ACROSS THE TESTING 3079 02:20:58,157 --> 02:20:58,457 SESSION. 3080 02:20:58,457 --> 02:21:01,026 FINALLY, DESPITE THOSE FINDINGS, 3081 02:21:01,026 --> 02:21:02,995 ME/CFS VOLUNTEERS PERFORM 3082 02:21:02,995 --> 02:21:05,164 NORMALLY ON STANDARDIZED 3083 02:21:05,164 --> 02:21:07,266 MEASURES OF COGNITION AND 3084 02:21:07,266 --> 02:21:08,100 PERFORMANCE COULD NOT BE 3085 02:21:08,100 --> 02:21:10,169 DISTINGUISHED FROM THAT OF 3086 02:21:10,169 --> 02:21:10,436 CONTROLS. 3087 02:21:10,436 --> 02:21:20,612 THANK YOU. 3088 02:21:24,516 --> 02:21:24,817 HELLO. 3089 02:21:24,817 --> 02:21:28,887 MY NAME IS NICK MADIAN AND TALK 3090 02:21:28,887 --> 02:21:31,323 ABOUT OUR FINDINGS TO EFFORT AND 3091 02:21:31,323 --> 02:21:32,591 HOW EFFORT CAN BE THOUGHT OF AS 3092 02:21:32,591 --> 02:21:36,128 A FEELING AND NOT JUST AN 3093 02:21:36,128 --> 02:21:36,528 ACTION. 3094 02:21:36,528 --> 02:21:37,596 WHY WE FEEL EFFORT, 3095 02:21:37,596 --> 02:21:39,431 EFFORT COUNTING AND PREFERENCE 3096 02:21:39,431 --> 02:21:41,400 AND THE EFFORT EXPENDITURE FOR 3097 02:21:41,400 --> 02:21:45,270 REWARDS TASK OR EFERT AND HOW 3098 02:21:45,270 --> 02:21:55,647 IT'S INPRESTERPRETED. 3099 02:21:55,647 --> 02:21:58,083 PEOPLE USE EFFORT AS AN ACTION 3100 02:21:58,083 --> 02:21:59,218 UNDER CONSCIOUS CONTROL. 3101 02:21:59,218 --> 02:22:03,989 MERRIAM WEBSTER'S CALLS IT A 3102 02:22:03,989 --> 02:22:05,157 CONSCIOUS EXERTION OF POWER BUT 3103 02:22:05,157 --> 02:22:07,159 THE COMMON DEFINITION MAY NOT BE 3104 02:22:07,159 --> 02:22:08,060 ENTIRELY ACCURATE. 3105 02:22:08,060 --> 02:22:09,561 WE NOW KNOW EFFORT CAN BE 3106 02:22:09,561 --> 02:22:11,964 THOUGHT OF NOT ONLY AS AN ACTION 3107 02:22:11,964 --> 02:22:15,534 BUT AAS A FEELING WE GET WHEN WE 3108 02:22:15,534 --> 02:22:17,069 TAKE ACTION. 3109 02:22:17,069 --> 02:22:20,672 IN THE 1900s RESEARCHERS FOUND 3110 02:22:20,672 --> 02:22:22,908 SOMETHING DIFFICULT AND 3111 02:22:22,908 --> 02:22:24,510 AGREEABLE ABOUT CERTAIN TYPES OF 3112 02:22:24,510 --> 02:22:25,344 WORK. 3113 02:22:25,344 --> 02:22:26,779 THIS FEELING IS ANYWHERE IN OUR 3114 02:22:26,779 --> 02:22:28,046 DAILY LIVES. 3115 02:22:28,046 --> 02:22:31,049 WE FEEL IT WHEN WE WALK UP A 3116 02:22:31,049 --> 02:22:32,651 FLIGHT OF STAIRS OR CARRY 3117 02:22:32,651 --> 02:22:34,887 SOMETHING HEAVY OR PICK 3118 02:22:34,887 --> 02:22:35,320 SOMETHING UP. 3119 02:22:35,320 --> 02:22:36,488 IT'S THE FEELING OF EFFORT FOR 3120 02:22:36,488 --> 02:22:37,422 THE SENSE OF EFFORT. 3121 02:22:37,422 --> 02:22:40,292 THIS FEELING IS UNPLEASANT AND 3122 02:22:40,292 --> 02:22:40,559 AVERSIVE. 3123 02:22:40,559 --> 02:22:42,294 AND IT GETS STRONGER AND MORE 3124 02:22:42,294 --> 02:22:46,165 UNPLEASANT THE MORE ENERGY THE 3125 02:22:46,165 --> 02:22:47,099 WORK REQUIRES. 3126 02:22:47,099 --> 02:22:48,467 WE ALSO KNOW THE EXERCISE OF 3127 02:22:48,467 --> 02:22:53,472 EFFORT IS NOT ENTIRELY OR EVEN 3128 02:22:53,472 --> 02:22:55,941 MOSTLY CONSCIOUS DESPITE WHAT 3129 02:22:55,941 --> 02:22:58,177 MERRIAM WEBSTER SAID WHEN IT 3130 02:22:58,177 --> 02:23:02,714 GETS TO BE TOO MUCH THE BRAIN 3131 02:23:02,714 --> 02:23:04,716 WILL BACK OFFER AND IT CAN 3132 02:23:04,716 --> 02:23:06,485 CHANGE BASED ON CONTEXT EVEN IF 3133 02:23:06,485 --> 02:23:10,155 THE EFFORT EXERTED STAYS THE 3134 02:23:10,155 --> 02:23:19,531 SPAM WHEN SPENDING NERG ENERGY 3135 02:23:19,531 --> 02:23:22,434 CAN CHANGE AND THE MORE FATIGUE 3136 02:23:22,434 --> 02:23:28,073 THE MORE UNPLEASANT CHANGE CAN 3137 02:23:28,073 --> 02:23:29,741 BE AND THE BRAIN MUST ACCOUNT 3138 02:23:29,741 --> 02:23:30,909 FOR ENERGY SPENT AND REWARDS TO 3139 02:23:30,909 --> 02:23:32,744 BE GAINED AND THE PUNISHMENTS TO 3140 02:23:32,744 --> 02:23:34,179 BE AVOID FOR SPENDING THAT 3141 02:23:34,179 --> 02:23:34,613 ENERGY. 3142 02:23:34,613 --> 02:23:36,615 FURTHERMORE THE, SYSTEMS MUST BE 3143 02:23:36,615 --> 02:23:38,150 ABLE TO COMPUTE SOME RATIO OF 3144 02:23:38,150 --> 02:23:39,852 COST TO BENEFITS. 3145 02:23:39,852 --> 02:23:41,420 THE RESULTS OF WHICH INFLUENCE 3146 02:23:41,420 --> 02:23:42,588 HOW THE EFFORT FEELS. 3147 02:23:42,588 --> 02:23:45,157 WE CAN THINK OF THIS OF BEING A 3148 02:23:45,157 --> 02:23:46,291 BIT LIKE THE SYSTEM ON WHICH 3149 02:23:46,291 --> 02:23:48,260 SIDE OF THE SCALE IS HEAVIER OR 3150 02:23:48,260 --> 02:23:49,528 WHETHER THE SOLUTION TO AN 3151 02:23:49,528 --> 02:23:50,863 EQUATION IS POSITIVE OR 3152 02:23:50,863 --> 02:23:51,663 NEGATIVE. 3153 02:23:51,663 --> 02:23:53,498 THE PROCESS BY WHICH THE BRAIN 3154 02:23:53,498 --> 02:23:55,701 FIGURES OUT THE COST BENEFIT 3155 02:23:55,701 --> 02:23:56,668 RATIO EFFORT DISCOUNTING. 3156 02:23:56,668 --> 02:23:58,770 THERE'S ONE MORE LAYER OF 3157 02:23:58,770 --> 02:23:59,471 COMPLICATION TO THE PROCESS. 3158 02:23:59,471 --> 02:24:01,907 THE WEIGHTS GIVEN TO THE ENERGY 3159 02:24:01,907 --> 02:24:04,877 COSTS OBTAINED REWARDS AND 3160 02:24:04,877 --> 02:24:06,011 AVOIDED PUNISHMENT SEEM TO 3161 02:24:06,011 --> 02:24:08,080 DIFFER ON A PERSON TO PERSON OR 3162 02:24:08,080 --> 02:24:09,748 BRAIN TO BRAIN BASIS. 3163 02:24:09,748 --> 02:24:12,050 TO THE SAME ENERGY COST AND 3164 02:24:12,050 --> 02:24:16,121 COULDN'T TEXT TWO BRAINS CAN 3165 02:24:16,121 --> 02:24:17,256 ASSIGN TWO WEIGHTS MEANING THE 3166 02:24:17,256 --> 02:24:18,457 FEELING OF EFFORT CAN BE 3167 02:24:18,457 --> 02:24:19,691 DIFFERENT FOR DIFFERENT PEOPLE. 3168 02:24:19,691 --> 02:24:21,526 THE SAME BRAIN MAY ASSIGN 3169 02:24:21,526 --> 02:24:22,961 DIFFERENT WEIGHTS AT DIFFERENT 3170 02:24:22,961 --> 02:24:23,662 POINTS IN TIME. 3171 02:24:23,662 --> 02:24:26,632 FOR EXAMPLE, WHEN ONE IS JUST 3172 02:24:26,632 --> 02:24:30,168 STARTING A TASK VERSUS WHEN ONE 3173 02:24:30,168 --> 02:24:35,607 IS FATIGUED AND THE DIFFERENCE 3174 02:24:35,607 --> 02:24:39,778 IN WEIGHTING MAY BE FATIGUE SELF 3175 02:24:39,778 --> 02:24:41,313 IT SELF AND THOUGHT TO BE IN THE 3176 02:24:41,313 --> 02:24:42,814 EVALUATION NETWORK. 3177 02:24:42,814 --> 02:24:44,416 ANOTHER REGION OF THE BRAIN IS 3178 02:24:44,416 --> 02:24:46,151 THE A TINY REGION IN THE BRAIN 3179 02:24:46,151 --> 02:24:53,992 STEM WHICH PRODUCES THE 3180 02:24:53,992 --> 02:24:56,094 NEUROTRANSMITTER NOREPINEPHRINE 3181 02:24:56,094 --> 02:24:57,796 AND CONNECTED TO SEVERAL BRAIN 3182 02:24:57,796 --> 02:24:58,530 REGIONS IN THE EVALUATION 3183 02:24:58,530 --> 02:24:59,231 NETWORK. 3184 02:24:59,231 --> 02:25:00,832 THE FUNCTIONING OF THESE BRAIN 3185 02:25:00,832 --> 02:25:06,171 REGIONS DOES NOT APPEAR TO BE 3186 02:25:06,171 --> 02:25:07,673 UNDER CONSCIOUS CONTROL. 3187 02:25:07,673 --> 02:25:12,311 THE WEIGHTS ARE WIRED 3188 02:25:12,311 --> 02:25:13,845 DIFFERENTLY RESULTING IN 3189 02:25:13,845 --> 02:25:14,980 DIFFERENT PEOPLE FEELING THE 3190 02:25:14,980 --> 02:25:17,416 EFFORT IN DIFFERENT WAYS. 3191 02:25:17,416 --> 02:25:18,116 THE INTERINDIVIDUAL VARIABILITY 3192 02:25:18,116 --> 02:25:22,154 THROUGH THE PROCESS IS CALLED 3193 02:25:22,154 --> 02:25:23,789 EFFORT PREFERENCE. 3194 02:25:23,789 --> 02:25:26,158 SOME AVAILABILITY IS DIFFERENT 3195 02:25:26,158 --> 02:25:27,626 AND HYPOTHETICAL PEOPLE A AND B 3196 02:25:27,626 --> 02:25:30,062 ASKED TO DO THE SAME EXERCISE, 3197 02:25:30,062 --> 02:25:32,798 20 PUSH-UPS FOR THE SAME REWARD, 3198 02:25:32,798 --> 02:25:33,065 $20. 3199 02:25:33,065 --> 02:25:34,800 PERSON A'S EVALUATION MAY ASSIGN 3200 02:25:34,800 --> 02:25:36,768 LARGE WEIGHT TO ENERGY COSTS AND 3201 02:25:36,768 --> 02:25:38,603 SMALL WEIGHT TO REWARD BENEFITS. 3202 02:25:38,603 --> 02:25:40,172 WE BELIEVE THIS PERSON WOULD 3203 02:25:40,172 --> 02:25:44,276 FEEL EFFORT FROM THE PUSHUPS AND 3204 02:25:44,276 --> 02:25:46,278 LESS LIKELY TO ACCEPT THE OFFER. 3205 02:25:46,278 --> 02:25:48,714 IN CONTRAST WE HAVE PERSON B 3206 02:25:48,714 --> 02:25:50,983 WHOSE EVALUATION NETWORK MAY 3207 02:25:50,983 --> 02:25:52,818 ASSIGN SMALLER WEIGHTS TO THE 3208 02:25:52,818 --> 02:25:53,986 COST AND LARGER WEIGHT TO 3209 02:25:53,986 --> 02:25:55,253 BENEFIT AND MAKE THEM MORE 3210 02:25:55,253 --> 02:25:57,556 WILLING TO ACCEPT THE OFFER. 3211 02:25:57,556 --> 02:25:59,524 THOUGH DIFFERENT BOTH ARE 3212 02:25:59,524 --> 02:26:00,659 EXAMPLES OF HEALTHY EVALUATION 3213 02:26:00,659 --> 02:26:02,160 OF NETWORK FUNCTIONING. 3214 02:26:02,160 --> 02:26:04,529 SOMETIMES THE NETWORK DOES NOT 3215 02:26:04,529 --> 02:26:05,630 FUNCTION PROPERLY. 3216 02:26:05,630 --> 02:26:06,898 CERTAIN NEUROLOGICAL DISEASES 3217 02:26:06,898 --> 02:26:08,900 CAN DISRUPT OR DAMAGE THE 3218 02:26:08,900 --> 02:26:10,168 EVALUATION NETWORK AFFECTING THE 3219 02:26:10,168 --> 02:26:11,636 EFFORT DISCOUNTING PROCESS AND 3220 02:26:11,636 --> 02:26:13,071 CHANGING THE WAY EFFORT IS 3221 02:26:13,071 --> 02:26:14,306 EXPERIENCED. 3222 02:26:14,306 --> 02:26:17,709 DISEASES LIKE PARKINSON'S OR 3223 02:26:17,709 --> 02:26:20,245 FRONTO TEMPORAL DEMENTIA AND 3224 02:26:20,245 --> 02:26:21,680 STROKES AND BRAIN DAMAGE FOUND 3225 02:26:21,680 --> 02:26:23,548 TO DAMAGE BRAIN REGIONS 3226 02:26:23,548 --> 02:26:24,983 AFFECTING EFFORT DISCOUNTING AND 3227 02:26:24,983 --> 02:26:26,151 PREFERENCE AND THE FEELING OF 3228 02:26:26,151 --> 02:26:27,252 EFFORT ITSELF. 3229 02:26:27,252 --> 02:26:29,921 WE WONDERED WHETHER SOMETHING 3230 02:26:29,921 --> 02:26:30,822 SIMILAR MAY HAVE HAPPENED TO 3231 02:26:30,822 --> 02:26:31,957 PEOPLE WITH ME/CFS. 3232 02:26:31,957 --> 02:26:33,625 TO TEST WHETHER THERE WERE 3233 02:26:33,625 --> 02:26:35,894 BEHAVIORAL SIGNS OF DISRUPTED 3234 02:26:35,894 --> 02:26:38,497 EFFORT DISCOUNTING IN PEOPLE 3235 02:26:38,497 --> 02:26:40,766 WITH ME/CFS WE HAD A TASK. 3236 02:26:40,766 --> 02:26:45,337 THIS IS A WELL VALIDATED TASK TO 3237 02:26:45,337 --> 02:26:46,571 QUANTIFY DISCOUNTING AND IT'S 3238 02:26:46,571 --> 02:26:49,708 BEEN USED TO STUDY EFFORT IN 3239 02:26:49,708 --> 02:26:50,709 SEVERAL NEUROLOGICAL DISORDERS 3240 02:26:50,709 --> 02:26:52,411 AND REQUIRES PARTICIPANTS TO 3241 02:26:52,411 --> 02:26:54,112 PERFORM TRIALS CONSISTING OF 3242 02:26:54,112 --> 02:26:56,248 BUTTON PRESSING SUB TASKS WITH 3243 02:26:56,248 --> 02:26:57,983 TWO DIFFICULTY LEVELS. 3244 02:26:57,983 --> 02:26:59,017 PARTICIPANTS SELECT THE 3245 02:26:59,017 --> 02:27:00,886 DIFFICULTY LEVELS BASED ON THE 3246 02:27:00,886 --> 02:27:01,787 REWARD AT STAKE WHICH VARIES 3247 02:27:01,787 --> 02:27:02,687 FROM TRIAL TO TRIAL. 3248 02:27:02,687 --> 02:27:05,357 EACH TRIAL BEGINS WITH THE 5 3249 02:27:05,357 --> 02:27:06,925 SECOND CHOICE PERIOD IN WHICH 3250 02:27:06,925 --> 02:27:08,493 PARTICIPANTS ARE PRESENTED WITH 3251 02:27:08,493 --> 02:27:11,163 INFORMATION WITH THE REWARD 3252 02:27:11,163 --> 02:27:12,798 MAGNITUDE AND THE PROBABILITY OF 3253 02:27:12,798 --> 02:27:14,733 RECEIVING REWARD FOR THE TRIAL. 3254 02:27:14,733 --> 02:27:18,203 AFTER CHOOSING THE HARD OR EASY 3255 02:27:18,203 --> 02:27:22,707 SUB TASK PARTICIPANTS MAKE RAPID 3256 02:27:22,707 --> 02:27:24,843 BUTTON TASK AND RECEIVE FEEDBACK 3257 02:27:24,843 --> 02:27:27,446 AND TOLD WHETHER THEY RECEIVED 3258 02:27:27,446 --> 02:27:29,381 REWARD BASED ON THE REWARD 3259 02:27:29,381 --> 02:27:32,084 PROBABILITY AND WHETHER THEY 3260 02:27:32,084 --> 02:27:33,952 COMPLETE THE TASK. 3261 02:27:33,952 --> 02:27:37,089 ALL TOGETHER IT RUNS 15 MINUTES. 3262 02:27:37,089 --> 02:27:40,826 THE EEFRT CAN BE INTERPRETED. 3263 02:27:40,826 --> 02:27:44,296 THE LEFT DEPICTS HOW TWO PEOPLE 3264 02:27:44,296 --> 02:27:45,764 IN THE PURPLE AND TEAL LINES 3265 02:27:45,764 --> 02:27:49,601 WILL RESPOND AS REWARD 3266 02:27:49,601 --> 02:27:49,868 INCREASES. 3267 02:27:49,868 --> 02:27:51,870 BOTH ASSIGN EQUAL WEIGHTS 3268 02:27:51,870 --> 02:27:54,139 INITIALLY AND START AT THE SAME 3269 02:27:54,139 --> 02:27:54,339 POINT. 3270 02:27:54,339 --> 02:27:57,275 THE PURPOSE WEIGHS REWARDS AND 3271 02:27:57,275 --> 02:28:01,213 WILL ENGAGE MORE OFTEN WHEN MORE 3272 02:28:01,213 --> 02:28:04,516 REWARD IS OFFERED. 3273 02:28:04,516 --> 02:28:10,489 THE PERSON IN TEAL DOESN'T SEE A 3274 02:28:10,489 --> 02:28:10,822 DIFFERENCE. 3275 02:28:10,822 --> 02:28:13,391 AND THE IT PERSON IN PURPLE 3276 02:28:13,391 --> 02:28:16,461 WEIGHS ENERGY COSTS LESS HEAVILY 3277 02:28:16,461 --> 02:28:19,030 THAN THE PERSON IN TEAL THUS 3278 02:28:19,030 --> 02:28:21,433 ENGAGE IN THE HARD TASK MORE 3279 02:28:21,433 --> 02:28:23,902 OFTEN AND THE LINES START AT 3280 02:28:23,902 --> 02:28:24,569 DIFFERENT POINTS. 3281 02:28:24,569 --> 02:28:28,840 BOTH PEOPLE ASSIGN EQUAL WEIGHT 3282 02:28:28,840 --> 02:28:30,275 INITIALLY BUT ONLY THE PERSON IN 3283 02:28:30,275 --> 02:28:33,512 TEAL GETS FATIGUED AND THE 3284 02:28:33,512 --> 02:28:36,248 PERSON IN PURPLE IS IMMUNE AND 3285 02:28:36,248 --> 02:28:41,186 WE FOUND FOR THE SAME LEVELS 3286 02:28:41,186 --> 02:28:43,388 ME/CFS ARE LESS LIKELY TO 3287 02:28:43,388 --> 02:28:46,158 PARTICIPATE THAN HEALTHY 3288 02:28:46,158 --> 02:28:46,925 CONTROLS. 3289 02:28:46,925 --> 02:28:48,927 SOMETHING ABOUT THE EFFORT 3290 02:28:48,927 --> 02:28:51,163 DISCOUNTING PROCESS IS ALTERED 3291 02:28:51,163 --> 02:28:53,565 IN PEOPLE WITH ME/CFS THIS IS 3292 02:28:53,565 --> 02:28:54,900 THE GAP AT BLEW LINE FOR THE 3293 02:28:54,900 --> 02:28:56,301 HEALTHY CONTROLS AND RED LINE 3294 02:28:56,301 --> 02:28:57,736 FOR THE PEOPLE WITH ME/CFS. 3295 02:28:57,736 --> 02:29:00,105 HOWEVER, WE DID NOT SEE AN 3296 02:29:00,105 --> 02:29:02,340 INDICATION REWARD WEIGHTING WAS 3297 02:29:02,340 --> 02:29:03,308 DIFFERENT BETWEEN GROUPS. 3298 02:29:03,308 --> 02:29:05,944 BOTH GROUPS ENGAGE AS REWARDS 3299 02:29:05,944 --> 02:29:06,511 WENT UP. 3300 02:29:06,511 --> 02:29:10,515 WE ALSO INVESTIGATED WHETHER THE 3301 02:29:10,515 --> 02:29:14,653 PEOPLE WITH ME/CFS PREFERS 3302 02:29:14,653 --> 02:29:15,420 CHANGE AND WHETHER THEY TOO 3303 02:29:15,420 --> 02:29:15,921 TEGED FASTER. 3304 02:29:15,921 --> 02:29:18,223 WE DID NOT SEE AN INDICATION OF 3305 02:29:18,223 --> 02:29:20,025 THIS IN OUR DATA. 3306 02:29:20,025 --> 02:29:22,027 THE PROBABILITY OF ENGAGING WITH 3307 02:29:22,027 --> 02:29:23,862 THE HARD TASK DECLINES AT 3308 02:29:23,862 --> 02:29:24,996 APPROXIMATELY THE SAME RATE FOR 3309 02:29:24,996 --> 02:29:26,865 BOTH GROUPS BUT SAW A DIFFERENCE 3310 02:29:26,865 --> 02:29:29,000 AT BASELINE INDICATING 3311 02:29:29,000 --> 02:29:30,168 DIFFERENCES IN EFFORT 3312 02:29:30,168 --> 02:29:31,703 DISCOUNTING. 3313 02:29:31,703 --> 02:29:34,139 IMPORTANTLY, WE ALSO FOUND A 3314 02:29:34,139 --> 02:29:35,340 STRONG POSITIVE CORRELATION 3315 02:29:35,340 --> 02:29:37,142 BETWEEN THE NEUROTRANSMITTER AND 3316 02:29:37,142 --> 02:29:39,945 THE PROPORTION OF HEART TRIALS 3317 02:29:39,945 --> 02:29:41,980 CHOSEN IN THE PEOPLE WITH 3318 02:29:41,980 --> 02:29:42,247 ME/CFS. 3319 02:29:42,247 --> 02:29:45,750 THIS SUGGESTS THE UNDER PINNING 3320 02:29:45,750 --> 02:29:46,785 INVOLVING THE SMALL PART OF THE 3321 02:29:46,785 --> 02:29:49,487 BRAIN FOR EFFORT DISCOUNTING IN 3322 02:29:49,487 --> 02:29:51,356 PEOPLE WITH ME/CFS. 3323 02:29:51,356 --> 02:29:53,225 NOTABLY, EFFORT HAS BEEN STUDIED 3324 02:29:53,225 --> 02:30:00,131 IN PARK PARKINSON'S DISEASE AND 3325 02:30:00,131 --> 02:30:01,566 FINDING LOOK SIMILAR. 3326 02:30:01,566 --> 02:30:03,268 PEOPLE WITH PARKINSON'S DISEASE 3327 02:30:03,268 --> 02:30:06,171 DOES NOT ENGAGE WITH THE 3328 02:30:06,171 --> 02:30:10,141 PHYSICAL TASK AS HEALTHY 3329 02:30:10,141 --> 02:30:10,408 CONTROLS. 3330 02:30:10,408 --> 02:30:12,510 THIS IS A TASK WHERE THE PEOPLE 3331 02:30:12,510 --> 02:30:16,481 WITH THE DISEASE AND HEALTHY 3332 02:30:16,481 --> 02:30:17,482 VOLUNTEERS COULD PERFORM EQUALLY 3333 02:30:17,482 --> 02:30:19,384 WELL AND THIS WAS NOT ASSOCIATED 3334 02:30:19,384 --> 02:30:20,885 WITH THE DISEASE. 3335 02:30:20,885 --> 02:30:23,388 ONCE GIVEN MEDICATIONS THAT 3336 02:30:23,388 --> 02:30:25,624 INCREASE THE NEUROTRANSMITTER 3337 02:30:25,624 --> 02:30:27,325 DOPAMINE THE PEOPLE WITH 3338 02:30:27,325 --> 02:30:29,294 PARKINSON'S DISEASE ENGAGED WITH 3339 02:30:29,294 --> 02:30:31,596 THE PHYSICAL TASK MORE READILY 3340 02:30:31,596 --> 02:30:34,165 FOR THE SAME CONTROLS AS THE 3341 02:30:34,165 --> 02:30:34,699 INCENTIVES. 3342 02:30:34,699 --> 02:30:36,835 INCREASING DOPAMINE CHANGE THE 3343 02:30:36,835 --> 02:30:41,806 EFFORT DISCOUNTING PROCESS AND 3344 02:30:41,806 --> 02:30:42,774 IT'S NOT A CONSCIOUS CHOICE. 3345 02:30:42,774 --> 02:30:45,677 TO CONCLUDE IT APPEARS PEOPLE 3346 02:30:45,677 --> 02:30:47,212 WITH ME/CFS EXPERIENCE SOME 3347 02:30:47,212 --> 02:30:48,947 ALTERATION OR DISRUPTION OF 3348 02:30:48,947 --> 02:30:50,448 EFFORT DISCOUNT WHICH LEADS TO 3349 02:30:50,448 --> 02:30:51,449 ALTERED EFFORT PREFERENCE. 3350 02:30:51,449 --> 02:30:55,654 THIS APPEARS TO BE RELATED TO 3351 02:30:55,654 --> 02:30:57,622 THE TRANSMITTER NOREPINEPHRINE 3352 02:30:57,622 --> 02:30:59,858 AND IT MAY BE THE CASE AND 3353 02:30:59,858 --> 02:31:01,993 EFFORT DISCOUNTING ARE RELATED 3354 02:31:01,993 --> 02:31:04,729 TO THE POST EXERTIONAL MALAISE. 3355 02:31:04,729 --> 02:31:06,398 FURTHER RESEARCH ON EVALUATION 3356 02:31:06,398 --> 02:31:07,832 NETWORK DAMAGE OR DYSFUNCTION AS 3357 02:31:07,832 --> 02:31:10,101 A POSSIBLE CONTRIBUTOR TO THE 3358 02:31:10,101 --> 02:31:11,970 SYMPTOMS IS ALSO WARRANTED. 3359 02:31:11,970 --> 02:31:12,971 A CLOSER INVESTIGATION 3360 02:31:12,971 --> 02:31:14,139 EVALUATION NETWORK FUNCTIONING 3361 02:31:14,139 --> 02:31:18,376 IN PEOPLE WITH ME/CFS IS ALREADY 3362 02:31:18,376 --> 02:31:28,553 UNDERWAY. 3363 02:31:30,655 --> 02:31:31,589 >> I HOPE YOU UNDERSTAND ALL THE 3364 02:31:31,589 --> 02:31:33,625 THINGS PRESENTED BY THE TEAM. 3365 02:31:33,625 --> 02:31:37,295 THEY DID A GOOD JOB IN GIVING 3366 02:31:37,295 --> 02:31:37,962 THANK YOU IMPORTANT DATA AND NOW 3367 02:31:37,962 --> 02:31:41,232 MY JOB IS TO TRY TO SYNTHESIZE 3368 02:31:41,232 --> 02:31:42,167 IT A LITTLE BIT BETTER PERHAPS 3369 02:31:42,167 --> 02:31:47,772 FOUR TO UNDERSTAND HOW WE THINK 3370 02:31:47,772 --> 02:31:53,345 ABOUT IT AT THE PRESENT POINT. 3371 02:31:53,345 --> 02:31:54,746 THERE'S FATIGUE OF CONTINUING 3372 02:31:54,746 --> 02:31:58,917 MUSCLE CAN CONTRACTS. 3373 02:31:58,917 --> 02:32:01,820 PATIENTS HAVE INDEED MUSCULAR 3374 02:32:01,820 --> 02:32:04,289 FATIGUE. 3375 02:32:04,289 --> 02:32:07,826 AND THE QUESTION IS WHERE DOES 3376 02:32:07,826 --> 02:32:09,861 THIS FATIGUE OF MOTOR 3377 02:32:09,861 --> 02:32:12,263 PERFORMANCE COME FROM? 3378 02:32:12,263 --> 02:32:17,068 AS WE'RE TALKING ABOUT IT FROM 3379 02:32:17,068 --> 02:32:22,140 THE CENTRAL OR PERIPHERAL 3380 02:32:22,140 --> 02:32:25,844 NERVOUS SYSTEM AND HEARD ABOUT 3381 02:32:25,844 --> 02:32:27,879 THE ORIGIN WANT TO HEAR ABOUT IT 3382 02:32:27,879 --> 02:32:31,616 IN THIS PARTICULAR STUDY. 3383 02:32:31,616 --> 02:32:32,450 THERE'S ATROPHY IN THE PATIENTS 3384 02:32:32,450 --> 02:32:34,586 THAT IS SOME BUT THE CRITICAL 3385 02:32:34,586 --> 02:32:37,689 FINDING IS THERE WAS NO INCREASE 3386 02:32:37,689 --> 02:32:39,491 IN THE SLOPE OF THE INDEX WHICH 3387 02:32:39,491 --> 02:32:42,160 COMES ABOUT IF THERE IS FATIGUE 3388 02:32:42,160 --> 02:32:46,664 IN THE MUSCLE. 3389 02:32:46,664 --> 02:32:48,633 LET ME DESCRIBE ENERGY 3390 02:32:48,633 --> 02:32:51,102 METABOLISM IN THE MUSCLE. 3391 02:32:51,102 --> 02:32:54,105 IN ORDER TO PRODUCE ATP WHICH IS 3392 02:32:54,105 --> 02:32:57,342 ENERGY, YOU NEED TO HAVE A 3393 02:32:57,342 --> 02:33:00,311 SUBSTRATE SUCH AS GLUCOSE AND 3394 02:33:00,311 --> 02:33:04,315 YOU CAN THEN METABOLIZE THAT 3395 02:33:04,315 --> 02:33:07,852 POTENTIALLY WITH OXYGEN. 3396 02:33:07,852 --> 02:33:15,293 AND YOU GREAT BY THE PROCESS OF 3397 02:33:15,293 --> 02:33:16,461 GLYCOLYSIS THE SUBSTRATE 3398 02:33:16,461 --> 02:33:19,697 UTILIZED AND IF YOU HAVE OXYGEN 3399 02:33:19,697 --> 02:33:25,503 LY , YOU CAN PRODUCE A LOT OF 3400 02:33:25,503 --> 02:33:25,670 ATP. 3401 02:33:25,670 --> 02:33:26,604 PEOPLE PREFER TO USE THAT 3402 02:33:26,604 --> 02:33:29,207 PATHWAY AS LONG AS TAY CAN. 3403 02:33:29,207 --> 02:33:33,611 IF YOU RUN OUT OF THE ABILITY TO 3404 02:33:33,611 --> 02:33:35,780 USE OXYGEN BECAUSE YOU'RE 3405 02:33:35,780 --> 02:33:37,715 FATIGUING THE MUSCLE, THEN 3406 02:33:37,715 --> 02:33:39,984 YOU'LL SWITCH TO AN ANAEROBIC 3407 02:33:39,984 --> 02:33:42,287 MECHANISM IN WHICH YOU PRODUCE 3408 02:33:42,287 --> 02:33:42,587 LACTATE. 3409 02:33:42,587 --> 02:33:49,994 AND LACTATE IS WHAT IS THE 3410 02:33:49,994 --> 02:33:57,068 DRIVER OF THE DIMITROF INDEX AND 3411 02:33:57,068 --> 02:34:02,040 YOU'RE NOT SWITCHING TO ANROBIC 3412 02:34:02,040 --> 02:34:04,342 METABOLISM AND STILL PERFORMING 3413 02:34:04,342 --> 02:34:06,211 AEROBICALLY AND THERE'S STILL 3414 02:34:06,211 --> 02:34:07,779 RESOURCES AVAILABLE TO THE 3415 02:34:07,779 --> 02:34:08,413 PATIENT AS FAR AS THE MUSCLE IS 3416 02:34:08,413 --> 02:34:11,850 CONCERN CANNED. 3417 02:34:11,850 --> 02:34:12,584 -- CONCERNED. 3418 02:34:12,584 --> 02:34:14,752 IT DOESN'T APPEAR TO BE DUE TO A 3419 02:34:14,752 --> 02:34:15,720 PROBLEM IN THE MUSCLE IT'S NOT 3420 02:34:15,720 --> 02:34:17,989 DUE TO PERIPHERAL AND THEN THE 3421 02:34:17,989 --> 02:34:20,391 QUESTION WAS IS IT DUE TO A 3422 02:34:20,391 --> 02:34:22,160 PROBLEM IN THE MOTOR CORTEX 3423 02:34:22,160 --> 02:34:25,497 WHICH IS THE DIRECT DRIVER FROM 3424 02:34:25,497 --> 02:34:26,531 THE CENTRAL NERVOUS SYSTEM TO 3425 02:34:26,531 --> 02:34:27,365 THE MUSCLE. 3426 02:34:27,365 --> 02:34:31,936 AND YOU HEARD THERE WAS NO 3427 02:34:31,936 --> 02:34:34,072 ABNORMALITY IN THE POTENTIALS 3428 02:34:34,072 --> 02:34:35,773 WHICH IS A MEASURE OF THE 3429 02:34:35,773 --> 02:34:38,243 DRIVING FROM THE MOTOR CORTEX TO 3430 02:34:38,243 --> 02:34:39,611 THE MUSCLE. 3431 02:34:39,611 --> 02:34:42,146 THERE WAS NO EVIDENCE THE MOTOR 3432 02:34:42,146 --> 02:34:45,850 CORTEX ITSELF WAS PROBLEMATIC 3433 02:34:45,850 --> 02:34:50,121 AND YOU SAW IN THE NEUROIMAGING 3434 02:34:50,121 --> 02:34:52,624 RESULTS PRESENTED THAT WHEN THE 3435 02:34:52,624 --> 02:34:56,127 MOTOR CORTEX IS ITSELF WERE 3436 02:34:56,127 --> 02:34:58,162 COMPARED THERE WAS NO DIFFERENCE 3437 02:34:58,162 --> 02:35:01,332 BETWEEN THE GROUPS. 3438 02:35:01,332 --> 02:35:03,902 SO THERE'S NO EVIDENCE THE MOTOR 3439 02:35:03,902 --> 02:35:06,137 CORTEX OR DIRECT DRIVERS OF 3440 02:35:06,137 --> 02:35:08,206 MOVEMENT ARE ABNORMAL. 3441 02:35:08,206 --> 02:35:14,012 NOW, THIS IS AGAIN A SIMPLE 3442 02:35:14,012 --> 02:35:16,414 DIAGRAM OF THE WAY THAT THE 3443 02:35:16,414 --> 02:35:22,587 SYSTEM IS ORGANIZE O D AND SOME 3444 02:35:22,587 --> 02:35:26,090 ASSOCIATED REGIONS SUCH AS THE 3445 02:35:26,090 --> 02:35:27,725 SUPPLEMENTARY AREA BUT THE MOTOR 3446 02:35:27,725 --> 02:35:30,128 CORTEX GETS DRIVEN BY VARIOUS 3447 02:35:30,128 --> 02:35:32,363 FACTORS THROUGH THE REST OF THE 3448 02:35:32,363 --> 02:35:32,931 BRAIN. 3449 02:35:32,931 --> 02:35:34,365 THAT'S WHY THE MOTOR CORTEX DOES 3450 02:35:34,365 --> 02:35:35,767 WHAT IT DOES. 3451 02:35:35,767 --> 02:35:39,437 IT HAS TO GET THE DRIVING 3452 02:35:39,437 --> 02:35:42,540 FACTORS TO ACTUALLY DECIDE TO 3453 02:35:42,540 --> 02:35:45,476 MAKE THESE DIFFERENT MOVEMENTS. 3454 02:35:45,476 --> 02:35:47,178 SO THERE APPEARS TO BE THEN A 3455 02:35:47,178 --> 02:35:50,782 PROBLEM WITH CENTRAL FATIGUE NOT 3456 02:35:50,782 --> 02:35:53,251 ARRIVING FROM THE MOTOR CORTEX 3457 02:35:53,251 --> 02:35:54,352 BUT ARISING FROM THE DRIVERS OF 3458 02:35:54,352 --> 02:35:57,522 THIS. 3459 02:35:57,522 --> 02:35:58,957 NOW, I THINK IN TRYING TO 3460 02:35:58,957 --> 02:36:02,093 UNDERSTAND THAT, THAT'S WHERE WE 3461 02:36:02,093 --> 02:36:05,330 COME TO A VERY INTERESTING 3462 02:36:05,330 --> 02:36:10,134 CORRELATION IN RELATION TO THE 3463 02:36:10,134 --> 02:36:15,139 DEFICIENCY OF CATECHOLAMINE AND 3464 02:36:15,139 --> 02:36:16,474 NOREPINEPHRINE HAS BEEN AFFECTED 3465 02:36:16,474 --> 02:36:20,011 AND YOU HEARD ABOUT SEROTONIN AS 3466 02:36:20,011 --> 02:36:21,412 BEING A POTENTIAL PROBLEM. 3467 02:36:21,412 --> 02:36:23,448 THERE ARE A NUMBER OF THESE 3468 02:36:23,448 --> 02:36:27,685 CATECHOLAMINES IN THE BRAIN. 3469 02:36:27,685 --> 02:36:31,089 WE SEE THIS MANIFESTATION IN 3470 02:36:31,089 --> 02:36:33,091 DEFICIENT OUGHT NOTTIC CONTROL 3471 02:36:33,091 --> 02:36:34,258 OF BLOOD PRESSURE IN THE HEART 3472 02:36:34,258 --> 02:36:38,162 AND IT MAY ALSO AFFECT BRAIN 3473 02:36:38,162 --> 02:36:40,098 METABOLISM DIRECTLY. 3474 02:36:40,098 --> 02:36:43,301 I THINK THESE FINDINGS IN THE 3475 02:36:43,301 --> 02:36:45,036 AUTONOMIC SYSTEM GIVE US A 3476 02:36:45,036 --> 02:36:51,209 MARKER TO AN EXTENT OF WHAT'S 3477 02:36:51,209 --> 02:36:55,146 GOING ON IN THE INFERENCE 3478 02:36:55,146 --> 02:36:55,413 SYSTEM. 3479 02:36:55,413 --> 02:37:02,153 WE HAVE ALL THESE 3480 02:37:02,153 --> 02:37:05,857 NEUROTRANSMI 3481 02:37:05,857 --> 02:37:06,858 NEUROTRANSMI 3482 02:37:06,858 --> 02:37:16,734 NEUROTRANSMITTERS CHOLAMINER 3483 02:37:16,734 --> 02:37:20,438 GIC SYSTEMS AND HAVE NEUROTRANS 3484 02:37:20,438 --> 02:37:21,639 MITTERS EVERYWHERE AND THIS IS A 3485 02:37:21,639 --> 02:37:27,045 BLOWUP OF THE REGION AND YOU 3486 02:37:27,045 --> 02:37:32,517 HEARD ABOUT THE SOURCE IN THE 3487 02:37:32,517 --> 02:37:36,621 LOC 3488 02:37:36,621 --> 02:37:37,088 LOCUS GIVING ENERGY. 3489 02:37:37,088 --> 02:37:38,556 ENERGY IS ALSO NEEDED TO FUNG IN 3490 02:37:38,556 --> 02:37:42,026 THE BRAIN. 3491 02:37:42,026 --> 02:37:44,328 IT'S NOT ONLY IN THE MUSCLE AND 3492 02:37:44,328 --> 02:37:45,630 ENERGY METABOLISM IS A LITTLE 3493 02:37:45,630 --> 02:37:47,331 BIT DIFFERENT IN THE BRAIN AS IT 3494 02:37:47,331 --> 02:37:49,500 IS IN THE MUSCLE GENERALLY WE 3495 02:37:49,500 --> 02:37:51,335 HAVE OXYGEN MOST OF THE TIME BUT 3496 02:37:51,335 --> 02:37:56,407 STILL IT'S IMPORTANT TO HAVE A 3497 02:37:56,407 --> 02:37:59,410 SUBSTRATE SUCH AS GLUCOSE AND 3498 02:37:59,410 --> 02:38:05,283 YOU HAVE TO PRODUCE PIRUVATE. 3499 02:38:05,283 --> 02:38:08,086 IT TURNS OUT NEURONS LIKE TO 3500 02:38:08,086 --> 02:38:09,654 HAVE LACTATE WHEN THEY HAVE TO 3501 02:38:09,654 --> 02:38:10,154 FIRE QUICKLY. 3502 02:38:10,154 --> 02:38:12,623 IT'S AN IMPORTANT SUBSTRATE IN 3503 02:38:12,623 --> 02:38:16,327 THE BRAIN COMING FROM GLUCOSE IN 3504 02:38:16,327 --> 02:38:17,895 THE LONG RUN BUT THE SHORT RUN 3505 02:38:17,895 --> 02:38:18,463 YOU CAN JUST HAVE LACTATE 3506 02:38:18,463 --> 02:38:24,736 ITSELF. 3507 02:38:24,736 --> 02:38:26,604 NOW LACTATE IN THE BRAIN IS 3508 02:38:26,604 --> 02:38:28,272 SUPPORTED BY THE GLIAL CELLS. 3509 02:38:28,272 --> 02:38:31,509 THE ASTROCYTES IN THE BRAIN 3510 02:38:31,509 --> 02:38:33,544 SUPPLY NEURONS WITH A LOT OF THE 3511 02:38:33,544 --> 02:38:38,149 LACTATE THAT THEY USE WHEN THEY 3512 02:38:38,149 --> 02:38:38,683 NEED IT. 3513 02:38:38,683 --> 02:38:40,418 NOW, ONE OF THE OTHER 3514 02:38:40,418 --> 02:38:42,353 INTERESTING FEATURES IT TURNS 3515 02:38:42,353 --> 02:38:46,357 OUT IS THAT NOREPINEPHRINE IS AN 3516 02:38:46,357 --> 02:38:51,896 IMPORTANT NEUROTRANSMITTER THAT 3517 02:38:51,896 --> 02:38:54,165 HELPS THE ASTROCYTE TRANSMIT 3518 02:38:54,165 --> 02:38:57,568 LACTATE TO THE NEURON. 3519 02:38:57,568 --> 02:39:00,271 WE SEE THE ABNORMALITY OF 3520 02:39:00,271 --> 02:39:02,140 NOREPINEPHRINE THAT IS PRESENT 3521 02:39:02,140 --> 02:39:02,974 THERE. 3522 02:39:02,974 --> 02:39:07,612 NOREPINEPHRINE IS HELPING THE 3523 02:39:07,612 --> 02:39:09,113 ASTROCYTE SUPPLY NOREPINEPHRINE 3524 02:39:09,113 --> 02:39:10,648 TO THE NEURONS AND THEREFORE 3525 02:39:10,648 --> 02:39:15,653 THERE COULD WELL BE AN ENERGY 3526 02:39:15,653 --> 02:39:18,222 PROBLEM WITH THIS FUNCTION 3527 02:39:18,222 --> 02:39:24,295 WITHIN THE BRAIN. 3528 02:39:24,295 --> 02:39:26,230 WE HAVE ALL THESE DRIVERS AND WE 3529 02:39:26,230 --> 02:39:34,705 SEE A SPECIFIC DRIVER THAT IS 3530 02:39:34,705 --> 02:39:36,541 DIMINISHED WHEN WE LOOK AT THE 3531 02:39:36,541 --> 02:39:38,242 WHOLE BRAIN IMAGINING AND IT'S A 3532 02:39:38,242 --> 02:39:41,212 DECLINE IN THE ACTIVITY OF THE 3533 02:39:41,212 --> 02:39:44,649 RIGHT TEMPORAL PARIETAL JUNCTION 3534 02:39:44,649 --> 02:39:46,818 AND NEARBY PARIETAL LOBE. 3535 02:39:46,818 --> 02:39:52,456 THESE REGIONS AS SHE NOTED ARE 3536 02:39:52,456 --> 02:39:55,159 IMPORTANT FOR SENSORY MOTOR 3537 02:39:55,159 --> 02:39:55,626 INTEGRATION. 3538 02:39:55,626 --> 02:39:57,862 BOTH THE SENSE OF FEELING ABOUT 3539 02:39:57,862 --> 02:39:59,463 MOVEMENT AND THE INTERPRETATION 3540 02:39:59,463 --> 02:40:02,433 OF MOVEMENT AND ALSO DRIVING OF 3541 02:40:02,433 --> 02:40:04,135 MOVEMENT. 3542 02:40:04,135 --> 02:40:05,970 THAT'S PART OF THEIR ROLE AND 3543 02:40:05,970 --> 02:40:07,605 THEY CAN ALSO PLAY A ROLE 3544 02:40:07,605 --> 02:40:09,540 PRESUMABLY IN COGNITION AND 3545 02:40:09,540 --> 02:40:16,647 OTHER ASPECTS AS WELL. 3546 02:40:16,647 --> 02:40:22,053 SO THERE APPEARS TO BE A DECLINE 3547 02:40:22,053 --> 02:40:23,721 OF ENERGY FOR THAT EFFORT I 3548 02:40:23,721 --> 02:40:24,488 POINT THE OUT. 3549 02:40:24,488 --> 02:40:26,991 THIS PRESUMABLY IS EXPERIENCED 3550 02:40:26,991 --> 02:40:33,865 AS CENTRAL FATIGUE. 3551 02:40:33,865 --> 02:40:37,134 SO WHAT WE UNDERSTAND THEN IS WE 3552 02:40:37,134 --> 02:40:46,277 HEARD ABOUT THE ETTIO -- 3553 02:40:46,277 --> 02:40:49,780 ETIOLOGICAL SYSTEMS WHICH WILL 3554 02:40:49,780 --> 02:40:51,949 THEN POTENTIALLY INFLUENCE THE 3555 02:40:51,949 --> 02:40:55,353 HYPOTHALAMUS AND BRAIN STEM TO 3556 02:40:55,353 --> 02:40:56,888 REDUCE THE NEUROTRANSMITTERS. 3557 02:40:56,888 --> 02:41:01,993 THEY THEN INFLUENCE OTHER PARTS 3558 02:41:01,993 --> 02:41:05,730 OF THE BRAIN THAT WILL GIVE RISE 3559 02:41:05,730 --> 02:41:07,865 TO THE DIFFERENT SYMPTOMS WE'VE 3560 02:41:07,865 --> 02:41:09,567 BEEN TALKING ABOUT AND 3561 02:41:09,567 --> 02:41:14,705 EMPHASIZED HERE PARTICULARLY 3562 02:41:14,705 --> 02:41:17,642 DECREASED MOTOR CONTROL. 3563 02:41:17,642 --> 02:41:20,778 AND THESE SYSTEMS WILL DRIVE THE 3564 02:41:20,778 --> 02:41:22,747 CARDIO RESPIRATORY SYSTEM AND 3565 02:41:22,747 --> 02:41:25,016 YOU'LL HEAR MORE ABOUT THAT IN 3566 02:41:25,016 --> 02:41:29,320 THE NEXT SERIES BUT FOR THE 3567 02:41:29,320 --> 02:41:30,955 MOMENT WE'LL STOP HERE WITH THIS 3568 02:41:30,955 --> 02:41:37,295 PARTICULAR PART OF THE 3569 02:41:37,295 --> 02:41:38,029 PATHOPHYSIOLOGY THAT'S THEN OF 3570 02:41:38,029 --> 02:41:38,996 OUR PRESENTATION AND WE'LL BE 3571 02:41:38,996 --> 02:41:40,831 HAPPY TO DEAL WITH QUESTIONS AND 3572 02:41:40,831 --> 02:41:43,834 PERHAPS THE PANELISTS WHO MADE 3573 02:41:43,834 --> 02:41:45,136 PRESENTATIONS CAN COME DOWN SO 3574 02:41:45,136 --> 02:41:47,271 WE CAN ANSWER THE QUESTIONS 3575 02:41:47,271 --> 02:41:50,174 ANYONE MIGHT HAVE FOR US SO 3576 02:41:50,174 --> 02:42:00,351 THANK YOU. 3577 02:42:19,236 --> 02:42:21,405 >> MY NAME IS DR. LOMEN. 3578 02:42:21,405 --> 02:42:22,540 I'M A PATIENT. 3579 02:42:22,540 --> 02:42:26,110 ALSO HAVE DONE IN FORMAL 3580 02:42:26,110 --> 02:42:26,377 RESEARCH. 3581 02:42:26,377 --> 02:42:30,181 I WOULD LIKE TO DIRECT THIS 3582 02:42:30,181 --> 02:42:32,650 QUESTION TO DR. SNOW AND MADIAN. 3583 02:42:32,650 --> 02:42:36,654 WHEN YOU STUDY THE SUBJECTS, FOR 3584 02:42:36,654 --> 02:42:41,025 INSTANCE, WHEN YOU WERE DOING 3585 02:42:41,025 --> 02:42:42,426 THE NEUROCOGNITIVE STUDIES DID 3586 02:42:42,426 --> 02:42:46,163 YOU ALSO CORRELATE THAT TO 3587 02:42:46,163 --> 02:42:56,640 WHETHER THE PATIENTS WERE 3588 02:42:56,874 --> 02:42:58,075 SYMPTOMATIC WITH THEIR BRAIN FOG 3589 02:42:58,075 --> 02:42:59,543 AND IT COMES AND GOES. 3590 02:42:59,543 --> 02:43:00,778 SAME WITH MUSCLES. 3591 02:43:00,778 --> 02:43:02,079 DID YOU LOOK AT THE FINDINGS OF 3592 02:43:02,079 --> 02:43:07,218 THE MUSCLES WHEN THE PATIENTS 3593 02:43:07,218 --> 02:43:09,153 WERE EXPERIENCING THEIR PEM. 3594 02:43:09,153 --> 02:43:09,420 THANK YOU. 3595 02:43:09,420 --> 02:43:15,326 >> GOOD QUESTION. 3596 02:43:15,326 --> 02:43:18,262 PERHAPS THE QUESTION SHOULD BE 3597 02:43:18,262 --> 02:43:23,000 IN THE MICROPHONE. 3598 02:43:23,000 --> 02:43:23,968 DR. SNOW. 3599 02:43:23,968 --> 02:43:29,106 >> CORRELATION AS A STATISTICAL 3600 02:43:29,106 --> 02:43:31,642 TE 3601 02:43:31,642 --> 02:43:32,076 TERM, NO. 3602 02:43:32,076 --> 02:43:35,346 BUT I PRESENTED THE VISUAL 3603 02:43:35,346 --> 02:43:37,281 ANALOG SCALES AND PEOPLE DOES 3604 02:43:37,281 --> 02:43:42,319 ENDURE DURING OUR SESSION THEY 3605 02:43:42,319 --> 02:43:45,189 WERE FATIGUED AND WERE HAVING 3606 02:43:45,189 --> 02:43:46,857 PROBLEMS PHYSICAL AND MENTAL 3607 02:43:46,857 --> 02:43:47,858 FATIGUE AT THE TIME. 3608 02:43:47,858 --> 02:43:51,695 THAT WOULD INDICATE THAT THERE 3609 02:43:51,695 --> 02:43:54,298 WAS SOME AND IT WENT UP AS THE 3610 02:43:54,298 --> 02:43:57,234 SESSION PROGRESSED. 3611 02:43:57,234 --> 02:44:00,805 I WON'T SAY THAT WE WERE ABLE TO 3612 02:44:00,805 --> 02:44:02,673 NECESSARY CAPTURE THEM WHILE 3613 02:44:02,673 --> 02:44:06,243 THEY WERE HAVING BRAIN FOG LIKE 3614 02:44:06,243 --> 02:44:08,179 WE DIDN'T -- I'M NOT SURE AND 3615 02:44:08,179 --> 02:44:10,414 BRIAN, DID YOU WANT TO SAY 3616 02:44:10,414 --> 02:44:20,591 SOMETHING? 3617 02:44:37,441 --> 02:44:39,477 >> THERE MAY BE ANOTHER WAY TO 3618 02:44:39,477 --> 02:44:41,112 ANSWER THE QUESTION AND IN THE 3619 02:44:41,112 --> 02:44:44,014 POPULATION YOU SAW HOW MANY HAD 3620 02:44:44,014 --> 02:44:49,186 COMPLAINTS OF NEUROCOGNITIVE 3621 02:44:49,186 --> 02:44:50,020 DYSFUNCTION? 3622 02:44:50,020 --> 02:44:50,888 >> ALL THEM. 3623 02:44:50,888 --> 02:45:00,397 >> 100% HAD BRAIN FOG THAI WERE 3624 02:45:00,397 --> 02:45:02,166 COMPLAINING ABOUT. 3625 02:45:02,166 --> 02:45:05,069 >> SIMILAR QUESTION OF THE 3626 02:45:05,069 --> 02:45:05,302 MUSCLE. 3627 02:45:05,302 --> 02:45:08,506 AT THAT STAGE OF BEING TESTED, 3628 02:45:08,506 --> 02:45:12,943 WERE THEY AT THE BASELINE OR DID 3629 02:45:12,943 --> 02:45:17,181 YOU FEEL THEY WERE ALREADY 3630 02:45:17,181 --> 02:45:19,884 COMPLAINING OF MUSCLE FATIGUE. 3631 02:45:19,884 --> 02:45:21,886 THAT WAS A SYMPTOM THEY HAD 3632 02:45:21,886 --> 02:45:22,620 ORDINARILY. 3633 02:45:22,620 --> 02:45:25,422 >> AT THE BEGINNING OF THE 3634 02:45:25,422 --> 02:45:29,727 MEASUREMENT BOTH GROUPS WERE THE 3635 02:45:29,727 --> 02:45:33,097 SAME LEVEL BUT BUT IN TIME THE 3636 02:45:33,097 --> 02:45:39,336 RESPONSES CHANGED. 3637 02:45:39,336 --> 02:45:42,640 >> WE TALKING OVER A DAY? 3638 02:45:42,640 --> 02:45:52,750 WE DIDN'T DO THAT MEASUREMENT. 3639 02:45:52,750 --> 02:46:00,558 >> GREAT. 3640 02:46:00,558 --> 02:46:02,159 >> HI THERE AGAIN. 3641 02:46:02,159 --> 02:46:05,062 SO OVER THE COURSE OF ALL OF 3642 02:46:05,062 --> 02:46:08,499 THESE TASKS, WE WERE PERFORMING 3643 02:46:08,499 --> 02:46:10,167 VISUAL ANALOG SCALE SO 3644 02:46:10,167 --> 02:46:12,303 FUNCTIONAL MRI AND TMS BEGINNING 3645 02:46:12,303 --> 02:46:14,538 IN THE MIDDLE AND END WE WERE 3646 02:46:14,538 --> 02:46:17,474 WATCHING THE PROGRESSION OF 3647 02:46:17,474 --> 02:46:18,209 THEIR SYSTEMS SEEING IF THEY 3648 02:46:18,209 --> 02:46:26,183 WERE CHANGING WITH THE TASK AND 3649 02:46:26,183 --> 02:46:29,587 IN GENERAL A HIGH FATIGUE OR 3650 02:46:29,587 --> 02:46:30,688 SYMPTOMOLOGY AND WHEN HAVE YOU 3651 02:46:30,688 --> 02:46:31,989 PARTICIPANTS TELL YOU ABOUT 3652 02:46:31,989 --> 02:46:34,191 THEIR EXPERIENCES, MANY SAID 3653 02:46:34,191 --> 02:46:36,527 THEY WERE PEM MOST OF THE 3654 02:46:36,527 --> 02:46:38,162 EVALUATION WHEN YOU ASKED THEM 3655 02:46:38,162 --> 02:46:42,166 DIRECTLY. 3656 02:46:42,166 --> 02:46:44,335 WE ALSO MEASURED QUESTIONS 3657 02:46:44,335 --> 02:46:46,770 THROUGHOUT THE WEEK AND THEY 3658 02:46:46,770 --> 02:46:50,207 ALWAYS HAD HIGH LEVELS OF BOTH 3659 02:46:50,207 --> 02:46:58,716 PHYSICAL AND COGNITIVE. 3660 02:46:58,716 --> 02:47:00,584 >> THERE'S A QUESTION FOR 3661 02:47:00,584 --> 02:47:02,553 PATRICK AND MAYBE OTHERS AS WELL 3662 02:47:02,553 --> 02:47:05,656 BUT SO THIS MOTOR CORTEX M1 I 3663 02:47:05,656 --> 02:47:10,928 DON'T KNOW MUCH ABOUT THIS TMS 3664 02:47:10,928 --> 02:47:13,097 STIMULATION BUT IS THERE A 3665 02:47:13,097 --> 02:47:15,199 POSSIBILITY THEY COULD FATIGUE 3666 02:47:15,199 --> 02:47:18,802 OF THE BRAIN SAY SECONDARY TO 3667 02:47:18,802 --> 02:47:21,205 MITOCHONDRIAL DISORDER? 3668 02:47:21,205 --> 02:47:25,175 MY INTEREST IS IN MITOCHONDRIA 3669 02:47:25,175 --> 02:47:27,478 AND WONDERING IF IN PRIMARY 3670 02:47:27,478 --> 02:47:30,180 MITOCHONDRIAL DISEASES WHERE 3671 02:47:30,180 --> 02:47:32,483 THERE'S SIMILAR FINDINGS 3672 02:47:32,483 --> 02:47:34,184 OBSERVED IN THIS TESTING, TMS 3673 02:47:34,184 --> 02:47:37,254 MOSTLY. 3674 02:47:37,254 --> 02:47:38,155 >> RIGHT. 3675 02:47:38,155 --> 02:47:41,392 MOTOR CORTEX METABOLISM WAS 3676 02:47:41,392 --> 02:47:42,092 NORMAL AT BASELINE. 3677 02:47:42,092 --> 02:47:44,795 THERE WASN'T ANY CHANGE IN THE 3678 02:47:44,795 --> 02:47:46,096 WAY THAT MOTOR CORTEX WAS 3679 02:47:46,096 --> 02:47:48,766 FUNCTIONING AND AS YOU SAW WITH 3680 02:47:48,766 --> 02:47:50,167 THE IMAGING, IT FUNCTIONED 3681 02:47:50,167 --> 02:47:54,171 NORMALLY IN TERMS OF GOING UP 3682 02:47:54,171 --> 02:47:57,007 WITH THE EXERCISE. 3683 02:47:57,007 --> 02:48:01,145 THE MOTOR CORTEX METABOLISM WAS 3684 02:48:01,145 --> 02:48:03,881 NORMAL AND CHANGED NORMALLY WITH 3685 02:48:03,881 --> 02:48:05,282 EXERCISE. 3686 02:48:05,282 --> 02:48:08,118 THERE WAS NO EVIDENCE OF 3687 02:48:08,118 --> 02:48:10,254 ABNORMALITY OF THE MOTOR CORTEX. 3688 02:48:10,254 --> 02:48:13,724 THE ABNORMALITY WAS IN A 3689 02:48:13,724 --> 02:48:14,291 DIFFERENT PART OF THE BRAIN. 3690 02:48:14,291 --> 02:48:15,793 AND THAT AS I WAS POINTING OUT 3691 02:48:15,793 --> 02:48:20,798 COULD BE DUE TO A METABOLIC 3692 02:48:20,798 --> 02:48:21,098 ABNORMALITY. 3693 02:48:21,098 --> 02:48:24,168 >> I GUESS I'M TRYING TO PUT IT 3694 02:48:24,168 --> 02:48:31,208 ALL TOGETHER LIKE WITH DAVID'S 3695 02:48:31,208 --> 02:48:33,210 FINDING WITH THE METABOLISM ALL 3696 02:48:33,210 --> 02:48:36,547 REQUIRE THE MITOCHONDRIA AND SO 3697 02:48:36,547 --> 02:48:37,815 IF THERE'S DYSFUNCTION YOU COULD 3698 02:48:37,815 --> 02:48:38,549 KIND OF PUT ALL THIS TOGETHER IN 3699 02:48:38,549 --> 02:48:41,552 THE BRAIN. 3700 02:48:41,552 --> 02:48:44,388 >> QUESTION, THAT IS SORT OF THE 3701 02:48:44,388 --> 02:48:45,122 WAY WE WERE DOING IT. 3702 02:48:45,122 --> 02:48:47,091 >> TWO QUESTIONS. 3703 02:48:47,091 --> 02:48:50,160 ONE IS WAS THERE A CORRELATION 3704 02:48:50,160 --> 02:48:56,734 BETWEEN ANXIETY AND LEVELS OF 3705 02:48:56,734 --> 02:48:59,336 CATECHOLAMINE AND THERE WAS ANY 3706 02:48:59,336 --> 02:49:03,140 REFERENCE TO NUCLEUS CIRCUMBENS 3707 02:49:03,140 --> 02:49:04,141 AND WONDER IF THERE'S SOMETHING 3708 02:49:04,141 --> 02:49:06,076 YOU COULDN'T SEE OR THERE WAS NO 3709 02:49:06,076 --> 02:49:06,410 ABNORMALITIES. 3710 02:49:06,410 --> 02:49:13,484 THANK YOU. 3711 02:49:13,484 --> 02:49:19,857 >> THAT DID NOT SHOW DIFFERENCE 3712 02:49:19,857 --> 02:49:20,991 BETWEEN GROUPS AND THE OVER 3713 02:49:20,991 --> 02:49:24,194 QUESTION ABOUT CORRELATION 3714 02:49:24,194 --> 02:49:28,031 BETWEEN ANXIETY, THESE ARE WE 3715 02:49:28,031 --> 02:49:29,900 DID MANY CORRELATIONS ACROSS 3716 02:49:29,900 --> 02:49:30,334 DIFFERENT THINGS. 3717 02:49:30,334 --> 02:49:32,002 I DON'T RECALL WHETHER WE DID 3718 02:49:32,002 --> 02:49:33,604 THAT PARTICULAR CORRELATION OR 3719 02:49:33,604 --> 02:49:33,871 NOT. 3720 02:49:33,871 --> 02:49:34,538 BRIAN, DO YOU RECALL WHETHER 3721 02:49:34,538 --> 02:49:44,782 THAT WAS DONE? 3722 02:49:58,262 --> 02:50:00,631 >> NOREPINEPHRINE IS WORTH 3723 02:50:00,631 --> 02:50:01,899 LOOKING AT. 3724 02:50:01,899 --> 02:50:03,200 IF WE DID IT WE DON'T RECALL WE 3725 02:50:03,200 --> 02:50:13,477 DID IT. 3726 02:50:13,477 --> 02:50:15,712 THAT IS EASY ENOUGH TO CHECK. 3727 02:50:15,712 --> 02:50:17,247 >> WE HAVE QUESTIONS FROM THE 3728 02:50:17,247 --> 02:50:19,116 VIRTUAL AUDIENCE. 3729 02:50:19,116 --> 02:50:21,919 CREATORS OF THE EEFRT STATE THE 3730 02:50:21,919 --> 02:50:24,488 DATA IS NOT VALID IF 3731 02:50:24,488 --> 02:50:26,523 PARTICIPANTS ARE NOT ABLE TO 3732 02:50:26,523 --> 02:50:28,325 CONSISTENTLY COMPLETE THE TASK. 3733 02:50:28,325 --> 02:50:31,028 WHY DID YOU PROCEED WITH THE 3734 02:50:31,028 --> 02:50:32,663 DATA AS EVIDENCE OF IMPAIRED 3735 02:50:32,663 --> 02:50:35,199 PREFERENCE WHEN THE DATA APPEARS 3736 02:50:35,199 --> 02:50:38,869 TO BE INVALID ACCORDING TO THE 3737 02:50:38,869 --> 02:50:39,870 GUIDELINES SET BY THE TEST 3738 02:50:39,870 --> 02:50:40,170 VALIDATERS. 3739 02:50:40,170 --> 02:50:44,842 >> FIRST I WANT TO EXPRESS MY 3740 02:50:44,842 --> 02:50:47,377 THANKS FOR THE QUESTION AND I 3741 02:50:47,377 --> 02:50:49,079 WAS INFORMED THE QUESTION HAD 3742 02:50:49,079 --> 02:50:51,114 BEEN RAISED AND WANTED TO FIELD 3743 02:50:51,114 --> 02:50:52,649 IT BECAUSE I HAD DONE WORK WITH 3744 02:50:52,649 --> 02:50:54,384 THIS TASK AND SIMILAR TASKS. 3745 02:50:54,384 --> 02:50:57,221 I'M FAMILIAR WITH THE ORIGINAL 3746 02:50:57,221 --> 02:50:58,755 PUBLICATION THE QUESTION 3747 02:50:58,755 --> 02:50:59,756 MENTIONED AND NEVERTHELESS I 3748 02:50:59,756 --> 02:51:01,492 STILL REALLY WANTED TO MAKE SURE 3749 02:51:01,492 --> 02:51:04,595 I DID MY DUE DILIGENCE SO SPENT 3750 02:51:04,595 --> 02:51:06,163 A SIGNIFICANT OF TIME BEFORE THE 3751 02:51:06,163 --> 02:51:07,698 MEETING REVIEWING THE 3752 02:51:07,698 --> 02:51:08,499 PUBLICATION IN QUESTION CLOSELY 3753 02:51:08,499 --> 02:51:11,602 TO MAKE SURE I'M REPRESENTING IT 3754 02:51:11,602 --> 02:51:11,902 ACCURATELY. 3755 02:51:11,902 --> 02:51:14,872 WA THE PAPER DESCRIBES IS THAT 3756 02:51:14,872 --> 02:51:17,574 EEFRT WAS DESCRIBED TO THE 3757 02:51:17,574 --> 02:51:18,976 SAMPLE OF PATIENTS USED IN THE 3758 02:51:18,976 --> 02:51:19,676 ORIGINAL STUDY COULD 3759 02:51:19,676 --> 02:51:21,211 CONSISTENTLY COMPLETE THE TASK. 3760 02:51:21,211 --> 02:51:22,379 THIS DOES NOT MEAN THAT EVERYONE 3761 02:51:22,379 --> 02:51:26,216 WHO TAKES THE TASK MUST BE ABLE 3762 02:51:26,216 --> 02:51:28,051 TO COMPLETE WITHOUT ISSUE FOR 3763 02:51:28,051 --> 02:51:28,919 THE ADMINISTRATION OR DATA TO BE 3764 02:51:28,919 --> 02:51:33,624 VALID OR INTERPRETABLE. 3765 02:51:33,624 --> 02:51:35,192 IT SEEMS THAT THE CREATORS 3766 02:51:35,192 --> 02:51:36,894 WANTED TO ENSURE THAT IN GENERAL 3767 02:51:36,894 --> 02:51:38,028 AS MANY PEOPLE AS POSSIBLE WOULD 3768 02:51:38,028 --> 02:51:40,864 BE ABLE TO COMPLETE THE TASK BUT 3769 02:51:40,864 --> 02:51:42,499 WITHOUT COMPRISING THE TASK 3770 02:51:42,499 --> 02:51:46,003 ABILITY TO CHALLENGE. 3771 02:51:46,003 --> 02:51:49,006 FURTHERMORE, I THINK IT BEARS 3772 02:51:49,006 --> 02:51:50,941 MENTIONING THOUGH ME/CFS 3773 02:51:50,941 --> 02:51:51,608 PARTICIPANTS DOES NOT COMPLETE 3774 02:51:51,608 --> 02:51:52,809 IT AT THE SAME RATE IN THE 3775 02:51:52,809 --> 02:51:55,245 ORIGINAL STUDY, OR AT THE SAME 3776 02:51:55,245 --> 02:51:56,880 RATE AS OUR HEALTHY CONTROLS 3777 02:51:56,880 --> 02:51:59,216 THEY STILL COMPLETE THE TASK THE 3778 02:51:59,216 --> 02:52:06,156 LARGE MARJORITY OF THE TIME AND 3779 02:52:06,156 --> 02:52:09,159 TO CONSISTENTLY COMPLETE THE 3780 02:52:09,159 --> 02:52:11,728 TASK IS NOT NECESSARY FOR THE 3781 02:52:11,728 --> 02:52:12,996 VALID AND BELIEVE THE TEST IS 3782 02:52:12,996 --> 02:52:15,599 VALID AND INTERPRETABLE AS A 3783 02:52:15,599 --> 02:52:19,303 MEASURE OF EFFORT DISCOUNTING. 3784 02:52:19,303 --> 02:52:19,970 >> THANKS. 3785 02:52:19,970 --> 02:52:22,673 >> WE HAD ANOTHER QUESTION. 3786 02:52:22,673 --> 02:52:24,508 WHAT IS YOUR RATIONALE FOR 3787 02:52:24,508 --> 02:52:26,710 REFRAMING THE EEFRT AS A MEASURE 3788 02:52:26,710 --> 02:52:28,478 OF EFFORT PREFERENCE RATHER THAN 3789 02:52:28,478 --> 02:52:30,180 USING AN ESTABLISHED 3790 02:52:30,180 --> 02:52:31,081 INTERPRETATION? 3791 02:52:31,081 --> 02:52:34,251 >> WE HAD HEARD ABOUT THIS 3792 02:52:34,251 --> 02:52:38,355 BEFORE SO BRIAN WILL ANSWER THIS 3793 02:52:38,355 --> 02:52:38,655 QUESTION. 3794 02:52:38,655 --> 02:52:41,758 >> THE ANSWER IS PRETTY SIMPLE. 3795 02:52:41,758 --> 02:52:45,862 I THINK NICK DID A WONDERFUL JOB 3796 02:52:45,862 --> 02:52:52,369 TALKING ABOUT WHAT EEFRT FOR US 3797 02:52:52,369 --> 02:52:54,171 AND THE UNCONSCIOUS TASK. 3798 02:52:54,171 --> 02:52:56,707 IT'S TYPICALLY FRAMED AS REWARD 3799 02:52:56,707 --> 02:52:58,075 MOTIVATION AND EFFORT ALLOCATION 3800 02:52:58,075 --> 02:53:00,944 OR EFFORT-BASED DECISION MAKING. 3801 02:53:00,944 --> 02:53:03,280 THESE TERMS EFFORT ALLOCATION 3802 02:53:03,280 --> 02:53:06,183 AND EFFORT-BASED DECISION MAKING 3803 02:53:06,183 --> 02:53:12,723 FRAME TASK PERFORMANCE AS A 3804 02:53:12,723 --> 02:53:14,157 VOLITION ACTION AND MEASURE THE 3805 02:53:14,157 --> 02:53:15,892 CONSCIOUS AND UNCONSCIOUS 3806 02:53:15,892 --> 02:53:17,728 ASPECTS AND THE MOMENT TO MOMENT 3807 02:53:17,728 --> 02:53:19,429 CHOICES DURING THE EFFORT TEST. 3808 02:53:19,429 --> 02:53:22,099 >> I THINK WE'RE RUNNING A 3809 02:53:22,099 --> 02:53:23,667 LITTLE BIT BEHIND SO WE HAVE ONE 3810 02:53:23,667 --> 02:53:24,534 MORE QUESTION. 3811 02:53:24,534 --> 02:53:26,670 IT SEEMS NOTABLE YOUR STUDY 3812 02:53:26,670 --> 02:53:27,838 FOUND NO EVIDENCE FOR POTS IN 3813 02:53:27,838 --> 02:53:31,241 THE SAMPLE AS IT APPEARS TO BE 3814 02:53:31,241 --> 02:53:33,510 PREVALENT CLINICALLY. 3815 02:53:33,510 --> 02:53:35,245 CAN YOU SAY MORE ABOUT THE 3816 02:53:35,245 --> 02:53:37,347 SEEMING DICHOTOMY? 3817 02:53:37,347 --> 02:53:38,348 >> I DIDN'T UNDERSTAND THE 3818 02:53:38,348 --> 02:53:38,915 QUESTION. 3819 02:53:38,915 --> 02:53:40,751 >> THE QUESTION, IT SEEMS 3820 02:53:40,751 --> 02:53:43,587 NOTABLE YOUR STUDY FOUND NO 3821 02:53:43,587 --> 02:53:47,491 EVIDENCE FOR POTS IN THE SAMPLE 3822 02:53:47,491 --> 02:53:49,426 AS IT APPEARS TO BE PREVALENT 3823 02:53:49,426 --> 02:53:51,361 CAN YOU SAY MORE ABOUT THE 3824 02:53:51,361 --> 02:54:01,538 DICHOTOMY. 3825 02:54:03,040 --> 02:54:13,517 >> OTHER GROUPS POTS IS VERY -- 3826 02:54:21,658 --> 02:54:24,127 THE FACTS ARE THE FACTS. 3827 02:54:24,127 --> 02:54:26,229 IT'S A SMALL STUDY BUT MAINLY A 3828 02:54:26,229 --> 02:54:36,640 MATTER OF REFERRAL BIAS. 3829 02:54:38,008 --> 02:54:39,476 THERE'S INTO REFERRAL BIAS BUT 3830 02:54:39,476 --> 02:54:44,948 WITH OTHER GROUPS WHEN THEY'RE 3831 02:54:44,948 --> 02:54:54,458 ASKED HOW FREQUENT IS POTS IN 3832 02:54:54,458 --> 02:54:56,960 CHRONIC FATIGUE SYNDROME IT'S 3833 02:54:56,960 --> 02:54:57,594 VERY COMMON. 3834 02:54:57,594 --> 02:55:03,934 I THINK TO AN IMPORTANT EXTENT 3835 02:55:03,934 --> 02:55:07,504 THE REFERRAL BIAS CAN RESULT IN 3836 02:55:07,504 --> 02:55:10,507 OVER ESTIMATION OF THE FREQUENCY 3837 02:55:10,507 --> 02:55:14,177 OF POTS IN THE ME/CFS 3838 02:55:14,177 --> 02:55:14,911 POPULATION. 3839 02:55:14,911 --> 02:55:16,947 >> LET ME ADD ONE MORE THING TO 3840 02:55:16,947 --> 02:55:19,349 IT THAT IS IN THE NEXT SESSION I 3841 02:55:19,349 --> 02:55:21,618 THINK YOU'LL HEAR LATE ABOUT 3842 02:55:21,618 --> 02:55:26,990 AUTONOMIC DYSFUNCTION AND I 3843 02:55:26,990 --> 02:55:32,562 THINK THERE IS ENOUGH AUTONOMIC 3844 02:55:32,562 --> 02:55:41,505 DYSFUNCTION SUGGESTING DYSAUTO 3845 02:55:41,505 --> 02:55:44,207 NOMIA AND A LARGE COHORT HAD 3846 02:55:44,207 --> 02:55:44,407 POTS. 3847 02:55:44,407 --> 02:55:46,176 WHAT MAKES IT DIFFERENCE IS NOT 3848 02:55:46,176 --> 02:55:48,578 THE PARTICIPANTS DIDN'T HAVE 3849 02:55:48,578 --> 02:55:50,180 POTS BUT THE HEALTHY VOLUNTEERS 3850 02:55:50,180 --> 02:55:57,454 DID ALSO. 3851 02:55:57,454 --> 02:56:01,525 THEY HAD CRITERIA AND WE HAD 3852 02:56:01,525 --> 02:56:03,260 HEALTHY VOLUNTEERS AND MAYBE 3853 02:56:03,260 --> 02:56:06,830 POTS IN CHRONICALLY ASYMPTOMATIC 3854 02:56:06,830 --> 02:56:10,100 PEOPLE IS MORE THAN PEOPLE REELS 3855 02:56:10,100 --> 02:56:13,069 AND NOT THE PATIENTS DIDN'T HAVE 3856 02:56:13,069 --> 02:56:14,171 POTS, BUT THE HEALTHY VOLUNTEERS 3857 02:56:14,171 --> 02:56:22,746 DID. 3858 02:56:22,746 --> 02:56:23,880 THANK YOU. 3859 02:56:23,880 --> 02:56:26,583 >> MAYBE WE CAN NOW END THE 3860 02:56:26,583 --> 02:56:28,985 SESSION AND THEN COME BACK AFTER 3861 02:56:28,985 --> 02:56:33,123 LUNCH AND SO IT'S 12:17, AND 3862 02:56:33,123 --> 02:56:34,324 LET'S GIVE YOU A ROUND OF 3863 02:56:34,324 --> 02:56:44,501 APPLAUSE. 3864 02:56:49,105 --> 02:56:51,074 LUNCH IS SCHEDULED TO 12:45 AND 3865 02:56:51,074 --> 02:56:52,876 MAYBE WE CAN COME BACK AT 1:00. 3866 02:56:52,876 --> 02:56:53,376 LET'S COME BACK AT 1:00. 3867 02:56:53,376 --> 02:56:54,110 3868 02:56:59,874 --> 02:57:03,177 >> THE NEXT IS ON BIOENERGIES 3869 02:57:03,177 --> 02:57:06,080 LED BY THE CO-DIRECTOR OF THE 3870 02:57:06,080 --> 02:57:07,948 METABOLIC CLINICAL RESEARCH UNIT 3871 02:57:07,948 --> 02:57:09,884 ALSO CHIEF OF THE ENERGY 3872 02:57:09,884 --> 02:57:10,618 METABOLISM SECTION AND DIRECTOR 3873 02:57:10,618 --> 02:57:13,721 OF THE HEALTH ENERGY AND BODY 3874 02:57:13,721 --> 02:57:15,155 WEIGHT REACTION CORE. 3875 02:57:15,155 --> 02:57:21,996 HIS GROUP DEVELOPED TECHNIQUES 3876 02:57:21,996 --> 02:57:25,966 USED TO MEASURE THE RATE OF 3877 02:57:25,966 --> 02:57:27,067 EXPENDITURE ON MINUTE BY MINUTE 3878 02:57:27,067 --> 02:57:37,478 LEVEL FOR HOURS OR DAYS. 3879 02:57:43,083 --> 02:57:47,955 AND MEASURE ENERGY, METABOLISM 3880 02:57:47,955 --> 02:57:49,957 AND RESPONSES AND LED THE 3881 02:57:49,957 --> 02:57:51,859 STUDIES ON ME/CFS AND WE LOOK 3882 02:57:51,859 --> 02:57:53,127 FORWARD TO HEARING FROM HIM AND 3883 02:57:53,127 --> 02:57:55,963 HIS GROUP. 3884 02:57:55,963 --> 02:58:02,369 THANK YOU. 3885 02:58:02,369 --> 02:58:06,507 I HAVE THE PLEASURE AND HORN TO 3886 02:58:06,507 --> 02:58:08,809 INTRODUCE SOME SPEAKERS FIRST 3887 02:58:08,809 --> 02:58:10,477 THE CONCEPT OF BIO ENERGETICS. 3888 02:58:10,477 --> 02:58:13,881 YOU MAY HAVE HEARD SOME TERMS 3889 02:58:13,881 --> 02:58:15,950 AND PARTICULARLY ENERGY SO IN 3890 02:58:15,950 --> 02:58:26,493 OUR VIEW, ENERGY IS THIS IS AN 3891 02:58:28,996 --> 02:58:31,365 INTERESTING SYSTEM. 3892 02:58:31,365 --> 02:58:35,970 NEVERTHELESS, YOU'LL SEE THIS 3893 02:58:35,970 --> 02:58:39,773 PERSON ON THE RIGHT AND WE TALK 3894 02:58:39,773 --> 02:58:41,041 ABOUT ENERGY AND THE CALORIES IN 3895 02:58:41,041 --> 02:58:43,978 OR OUT AND IT COULD BE DIRECTLY 3896 02:58:43,978 --> 02:58:47,715 MEASURED BY HEAT OR IN OUR CASE 3897 02:58:47,715 --> 02:58:49,483 INDIRECTLY THAT WOULD MEASURE 3898 02:58:49,483 --> 02:58:54,121 THE CARBON DIOXIDE PRODUCTION 3899 02:58:54,121 --> 02:58:57,124 AND CONSUMPTION AND HEAR FROM 3900 02:58:57,124 --> 02:58:59,660 THE WHOLE ROOM SETTING AS WELL 3901 02:58:59,660 --> 02:59:01,528 AS EXERCISE SETTING WHERE YOU 3902 02:59:01,528 --> 02:59:02,096 WEAR A MASK. 3903 02:59:02,096 --> 02:59:05,099 THIS ENERGY ESPECIALLY IN THE 3904 02:59:05,099 --> 02:59:09,336 DIET ON THESE CHEMICAL ENERGY, 3905 02:59:09,336 --> 02:59:12,940 CARBOHYDRATE, FATS AND OTHERS IS 3906 02:59:12,940 --> 02:59:15,576 CONVERTED TO ATP. 3907 02:59:15,576 --> 02:59:17,444 WE CAN MEASURE THAT AND WE'LL 3908 02:59:17,444 --> 02:59:21,148 INTRODUCE TO YOU MEASURES OF 3909 02:59:21,148 --> 02:59:25,152 INTAKE AND THE CAR MACRO ENERGY 3910 02:59:25,152 --> 02:59:27,955 AND HOW WE COLLECT THE 3911 02:59:27,955 --> 02:59:35,095 EXPENDITURE AND REPRESENTED 3912 02:59:35,095 --> 02:59:38,065 METABOLISM AND MEASURE THE BODY 3913 02:59:38,065 --> 02:59:39,933 COMPOSITION THE FAT STORAGE. 3914 02:59:39,933 --> 02:59:42,036 ANYWHERE IN THE SYSTEM IF THEY 3915 02:59:42,036 --> 02:59:43,470 PROBLEMS WE MAY SEE THE 3916 02:59:43,470 --> 02:59:43,771 SIGNATURES. 3917 02:59:43,771 --> 02:59:46,874 WE'VE EXPERIENCED WITH PATIENTS 3918 02:59:46,874 --> 02:59:49,777 WITH CHRONIC DISEASES SUCH AS 3919 02:59:49,777 --> 02:59:51,945 KIDNEY AND CARDIOVASCULAR 3920 02:59:51,945 --> 02:59:56,984 DISEASE AND THYROID, DIABETES, 3921 02:59:56,984 --> 02:59:57,851 NEUROMUSCULAR DISEASE SHOWING 3922 02:59:57,851 --> 02:59:59,420 VARIOUS BIO ENERGETIC 3923 02:59:59,420 --> 02:59:59,720 SIGNATURES. 3924 02:59:59,720 --> 03:00:01,388 BY IDENTIFYING THEM WE CAN 3925 03:00:01,388 --> 03:00:04,792 REVIEW THE MECHANISM OF 3926 03:00:04,792 --> 03:00:05,526 PATHOPHYSIOLOGY AND THAT'S OUR 3927 03:00:05,526 --> 03:00:06,093 RATIONALE OF STUDYING THIS 3928 03:00:06,093 --> 03:00:12,199 GROUP. 3929 03:00:12,199 --> 03:00:15,035 AS SHOWN IT'S STEP WISE PROCESS 3930 03:00:15,035 --> 03:00:18,439 IN DEEP PHENOTYPING AND EXERCISE 3931 03:00:18,439 --> 03:00:19,006 STRESS TEST. 3932 03:00:19,006 --> 03:00:21,875 LIKE OTHER WE'LL TAKE DIFFERENT 3933 03:00:21,875 --> 03:00:23,744 PIECES AND YOU'LL FIRST HEAR 3934 03:00:23,744 --> 03:00:26,447 FROM BARBARA STUSSMAN ON THE 3935 03:00:26,447 --> 03:00:29,716 POST EXERTION MALAISE. 3936 03:00:29,716 --> 03:00:31,518 THIS IS THE LAST SESSION YOU'LL 3937 03:00:31,518 --> 03:00:33,387 HEAR THE BEST PART. 3938 03:00:33,387 --> 03:00:35,255 BARBARA WILL PRESENT THAT AND 3939 03:00:35,255 --> 03:00:39,960 SHANNA WITH HER COLLABORATION 3940 03:00:39,960 --> 03:00:43,630 WITH SARA TURNER THE DIETARY 3941 03:00:43,630 --> 03:00:47,468 EVALUATIONS AND MY LAB WILL 3942 03:00:47,468 --> 03:00:50,471 PRESENT THE BODY COMPOSITION 3943 03:00:50,471 --> 03:00:56,710 DATA BODY FAT AND LEAN MASS 3944 03:00:56,710 --> 03:00:59,713 DISTRIBUTION AND WEARABLE 3945 03:00:59,713 --> 03:01:06,286 EXCELOMETER DATA AND -- 3946 03:01:06,286 --> 03:01:08,522 ACCELOMETER DATA AND HEAR ABOUT 3947 03:01:08,522 --> 03:01:14,094 THE EXERCISE TEST ITSELF. 3948 03:01:14,094 --> 03:01:24,238 THIS IS THE TESTS AND LISA WILL 3949 03:01:24,238 --> 03:01:26,573 BE DOING THE TALKING AND PRESENT 3950 03:01:26,573 --> 03:01:30,110 THE WHOLE BODY EXPENDITURE DATA. 3951 03:01:30,110 --> 03:01:31,578 LAST BUT NOT LEAST WE'LL HEAR 3952 03:01:31,578 --> 03:01:35,883 FROM PAUL WONG TAKING THE MUSCLE 3953 03:01:35,883 --> 03:01:41,355 SAMPLES AND LOOKING AT THE MACRO 3954 03:01:41,355 --> 03:01:47,961 LEFT AND STRESS AND 3955 03:01:47,961 --> 03:01:51,064 MITOCHONDRIAL FUNCTION AND 3956 03:01:51,064 --> 03:01:53,100 PIECES IN THE MEASUREMENT. 3957 03:01:53,100 --> 03:01:55,936 ARE THERE PHENOTYPIC SIGNATURES 3958 03:01:55,936 --> 03:01:59,940 AND BALANCE MEASURES AND WITH 3959 03:01:59,940 --> 03:02:02,643 THE EXERCISE CHALLENGE ARE THIS 3960 03:02:02,643 --> 03:02:06,780 UNIQUE CHANGES. 3961 03:02:06,780 --> 03:02:13,387 WITH THAT SAID, BARBARA. 3962 03:02:13,387 --> 03:02:17,925 >> THANK YOU, DR. CHEN. 3963 03:02:17,925 --> 03:02:19,493 I'LL GIVE AN OVERVIEW OF OUR 3964 03:02:19,493 --> 03:02:20,928 RESEARCH IN TWO PAPERS. 3965 03:02:20,928 --> 03:02:22,896 THE FIRST CONDUCTED TO LEARN 3966 03:02:22,896 --> 03:02:24,865 MORE ABOUT PEM AND INFORM THE 3967 03:02:24,865 --> 03:02:26,433 STUDY PROCEDURES IN THE MAIN 3968 03:02:26,433 --> 03:02:26,934 STUDY. 3969 03:02:26,934 --> 03:02:30,270 THE SECOND PAPER DESCRIBES OUR 3970 03:02:30,270 --> 03:02:32,139 MIX METHODS SYSTEM TO ASSESS PEM 3971 03:02:32,139 --> 03:02:35,809 AT A SINGULAR TIME POINT. 3972 03:02:35,809 --> 03:02:38,111 WHAT IS POST EXERTIONAL MALAISE? 3973 03:02:38,111 --> 03:02:40,714 ACCORDING TO THE INSTITUTE OF 3974 03:02:40,714 --> 03:02:42,216 MEDICINE REPORT ON ME/CFS THEY 3975 03:02:42,216 --> 03:02:43,650 DESCRIBED IT AS A WORSENING OF 3976 03:02:43,650 --> 03:02:49,022 SYSTEMS AFTER PHYSICAL, MENTAL 3977 03:02:49,022 --> 03:02:51,625 OR EMOTIONAL EXERTION THAT WOULD 3978 03:02:51,625 --> 03:02:52,793 NOT HAVE CAUSED A PROBLEM BEFORE 3979 03:02:52,793 --> 03:02:55,963 THE ILLNESS AND PUT THE PATIENT 3980 03:02:55,963 --> 03:02:58,732 IN RELAPSE THAT LAST LONGER THE 3981 03:02:58,732 --> 03:02:59,967 SYMPTOMS GET WORSE AFTER THE 3982 03:02:59,967 --> 03:03:02,703 EXPOSURE AND CAN LAST FOR DAYS 3983 03:03:02,703 --> 03:03:09,710 OR WEEKS. 3984 03:03:09,710 --> 03:03:11,945 WE DISCUSSED HOW TO BEST USE 3985 03:03:11,945 --> 03:03:13,380 QUALITATIVE METHODS TO STUDY 3986 03:03:13,380 --> 03:03:13,814 PEM. 3987 03:03:13,814 --> 03:03:15,782 AT THAT TIME IT WAS NOT WELL 3988 03:03:15,782 --> 03:03:18,218 STUDIED AND THERE WERE NO 3989 03:03:18,218 --> 03:03:18,685 VALIDATED MEASURES. 3990 03:03:18,685 --> 03:03:20,320 THAT'S HOW TO HE FOCUS GROUP 3991 03:03:20,320 --> 03:03:21,622 STUDY WAS INITIATED. 3992 03:03:21,622 --> 03:03:23,957 I WANT TO ACKNOWLEDGE MY 3993 03:03:23,957 --> 03:03:26,760 CO-AUTHORS HERE. 3994 03:03:26,760 --> 03:03:28,462 THE OBJECTIVES WERE TO INFORM 3995 03:03:28,462 --> 03:03:30,163 THE STUDY DESIGN OF THE MAIN 3996 03:03:30,163 --> 03:03:30,430 STUDY. 3997 03:03:30,430 --> 03:03:32,733 SPECIFICALLY WE WANTED TO 3998 03:03:32,733 --> 03:03:34,701 DETERMINE INDIVIDUAL PEM 3999 03:03:34,701 --> 03:03:36,837 SYMPTOMS TO QUANTIFY AND THE 4000 03:03:36,837 --> 03:03:38,805 SPECIFIC TIME POINTS FOR 4001 03:03:38,805 --> 03:03:41,842 ASSESSING PEM BEFORE AND AFTER 4002 03:03:41,842 --> 03:03:43,110 THE C PET. 4003 03:03:43,110 --> 03:03:46,380 WE CHOSE FOCUS GROUPS AS WAS 4004 03:03:46,380 --> 03:03:49,082 POST EXERCISAL MALAISE AND TOPIC 4005 03:03:49,082 --> 03:03:49,283 AREAS. 4006 03:03:49,283 --> 03:03:54,054 WE HAD 43 FROM NOVEMBER 2016 TO 4007 03:03:54,054 --> 03:03:57,057 AUGUST 2019 RANGING FROM AN HOUR 4008 03:03:57,057 --> 03:03:58,725 40 MINUTES TO TWO HOURS. 4009 03:03:58,725 --> 03:04:00,894 THEY WERE CONDUCTED OVER THE 4010 03:04:00,894 --> 03:04:02,496 PHONE TO ALLOW PARTICIPATION 4011 03:04:02,496 --> 03:04:03,664 FROM PEOPLE WHO COULD NOT 4012 03:04:03,664 --> 03:04:14,107 OTHERWISE TRAVEL EASILY. 4013 03:04:14,107 --> 03:04:15,942 PEM IS TRIGGERED BY COGNITIVE 4014 03:04:15,942 --> 03:04:20,847 EFFORT, PHYSICAL ACTIVITY AND 4015 03:04:20,847 --> 03:04:24,217 EMOTIONAL TRIGGERS. 4016 03:04:24,217 --> 03:04:26,186 SEE EXAMPLES ON THE SLIDE. 4017 03:04:26,186 --> 03:04:28,755 THE WORD CLOUD SHOWS PEM 4018 03:04:28,755 --> 03:04:30,324 SYMPTOMS AFTER C PET REPORTED BY 4019 03:04:30,324 --> 03:04:31,892 THE PARTICIPANTS THE SIZE OF THE 4020 03:04:31,892 --> 03:04:33,894 WORDS ARE PROPORTIONAL TO THE 4021 03:04:33,894 --> 03:04:34,995 FREQUENCY OF THE SYMPTOM 4022 03:04:34,995 --> 03:04:35,295 REPORTED. 4023 03:04:35,295 --> 03:04:38,265 YOU CAN SEE THERE WERE A WIDE 4024 03:04:38,265 --> 03:04:38,999 RANGE OF SYMPTOMS. 4025 03:04:38,999 --> 03:04:41,535 THERE WERE THREE CORE SYMPTOMS 4026 03:04:41,535 --> 03:04:46,940 MENTIONED BY VIRTUALLY EVERY , 4027 03:04:46,940 --> 03:04:49,509 EXHAUSTION, DIFFICULTY THINKING 4028 03:04:49,509 --> 03:04:50,277 AND MUSCULAR COMPLAINTS. 4029 03:04:50,277 --> 03:04:54,081 WE CHARTED THE ONSET PEAK AND 4030 03:04:54,081 --> 03:04:56,216 RECOVERY AFTER C PET. 4031 03:04:56,216 --> 03:04:58,185 PARTICIPANTS SAID THAT OCCURRED 4032 03:04:58,185 --> 03:04:59,586 FROM IMMEDIATELY TO 48 HOURS 4033 03:04:59,586 --> 03:05:00,754 FOLLOWING THE C PET. 4034 03:05:00,754 --> 03:05:02,889 THE PEAK RANGE FROM IMMEDIATELY 4035 03:05:02,889 --> 03:05:03,924 TO A WEEK FOLLOWING. 4036 03:05:03,924 --> 03:05:07,761 PARTICIPANTS SAID THEY RETURN 4037 03:05:07,761 --> 03:05:10,864 ARE ED FROM THEIR PRELEVEL TO 4038 03:05:10,864 --> 03:05:14,134 SOME REPORTING THEY NEVER FULLY 4039 03:05:14,134 --> 03:05:14,401 RECOVERED. 4040 03:05:14,401 --> 03:05:15,936 SOME PARTICIPANTS REPORTED A 4041 03:05:15,936 --> 03:05:19,206 LONGER RECOVERY AFTER THE TWO 4042 03:05:19,206 --> 03:05:22,409 DAY VERSUS ONE-DAY C PET. 4043 03:05:22,409 --> 03:05:23,944 THERE WERE SEVERAL IMPLICATIONS. 4044 03:05:23,944 --> 03:05:26,346 WE DEVELOPED OUR OWN SYSTEM FOR 4045 03:05:26,346 --> 03:05:27,914 ASSESSING PEM THAT WE USED IN 4046 03:05:27,914 --> 03:05:32,452 THE MAIN STUDY QUALITATIVE 4047 03:05:32,452 --> 03:05:34,621 INTERVIEWS BEFORE AND AFTER C 4048 03:05:34,621 --> 03:05:36,423 PET ALONG WITH THE VISUAL ANALOG 4049 03:05:36,423 --> 03:05:38,558 SCALES MENTIONED THIS MORNING. 4050 03:05:38,558 --> 03:05:41,261 DURING THE INTERVIEWS WE ASKED 4051 03:05:41,261 --> 03:05:44,030 EVERY PATIENT HOW THEY WERE 4052 03:05:44,030 --> 03:05:46,967 FEELING FIGURATIVELY, 4053 03:05:46,967 --> 03:05:49,836 COGNITIVELY AND EMOTIONALLY AND 4054 03:05:49,836 --> 03:05:51,371 MOST BOTHERSOME SYMPTOMS AND 4055 03:05:51,371 --> 03:05:53,240 SOME HAD A MORE DIFFICULT 4056 03:05:53,240 --> 03:05:55,075 RECOVERY AFTER THE TWO DAY THAN 4057 03:05:55,075 --> 03:05:57,110 ONE DAY C PET AND THEY DESCRIBED 4058 03:05:57,110 --> 03:05:58,211 THE SEVERITY OF THE SYMPTOMS 4059 03:05:58,211 --> 03:06:00,947 FOLLOWING THE C PET AND THE 4060 03:06:00,947 --> 03:06:02,182 DIFFICULTY OF THE TRAVEL 4061 03:06:02,182 --> 03:06:03,984 REQUIRED WE ALLOWED ALL PATIENT 4062 03:06:03,984 --> 03:06:08,155 TO REST TWO DAYS AT THE CLINICAL 4063 03:06:08,155 --> 03:06:10,390 CENTER TO REDUCE POTENTIAL HARM. 4064 03:06:10,390 --> 03:06:12,626 NOW I'LL TALK ABOUT OUR SECOND 4065 03:06:12,626 --> 03:06:14,294 PAPER WHICH WAS PUBLISHED IN 4066 03:06:14,294 --> 03:06:16,997 FEBRUARY THIS YEAR DETAILING AND 4067 03:06:16,997 --> 03:06:19,132 VALIDATING OUR SYSTEM FOR 4068 03:06:19,132 --> 03:06:20,834 ASSESSING PEM AFTER C PET. 4069 03:06:20,834 --> 03:06:23,970 I'D LIKE TO ACKNOWLEDGE MY 4070 03:06:23,970 --> 03:06:25,939 CO-AUTHORS HERE. 4071 03:06:25,939 --> 03:06:28,508 WE ANALYZED TRANSCRIPTS FROM 4072 03:06:28,508 --> 03:06:30,076 INTERVIEWS AND CONDUCTED THE 4073 03:06:30,076 --> 03:06:31,878 INTERVIEWS AT SIX TIME POINTS 4074 03:06:31,878 --> 03:06:33,814 BEFORE AND AFTER C PET WHICH 4075 03:06:33,814 --> 03:06:38,418 GENERATED HUNDREDS OF PAGES OF 4076 03:06:38,418 --> 03:06:39,886 TRANSCRIPTS PER EACH 4077 03:06:39,886 --> 03:06:40,587 PARTICIPANT. 4078 03:06:40,587 --> 03:06:41,855 FOUR RESEARCHERS READ THEM AND 4079 03:06:41,855 --> 03:06:45,826 PLOT THE TRAJECTORY OF PEM AND 4080 03:06:45,826 --> 03:06:47,127 PEAK AND MOST BOTHERSOME 4081 03:06:47,127 --> 03:06:47,394 SYSTEMS. 4082 03:06:47,394 --> 03:06:53,233 WE ACHIEVED 100% CON CENSUS AND 4083 03:06:53,233 --> 03:06:59,306 HAVING IN DEPTH DISCUSSION TO 4084 03:06:59,306 --> 03:07:07,614 ADJUDICATE DISAGREEMENTS. 4085 03:07:07,614 --> 03:07:09,182 IF HE PATIENT STARTED WORSE 4086 03:07:09,182 --> 03:07:10,317 BEFORE THE BASELINE AND PEAKED 4087 03:07:10,317 --> 03:07:12,219 AT 24 HOURS AND STARTED TO GET 4088 03:07:12,219 --> 03:07:13,153 BETTER. 4089 03:07:13,153 --> 03:07:15,856 THE RED DOTTED LINE SERVED AS A 4090 03:07:15,856 --> 03:07:18,458 BENCHMARK REPRESENTING A SEVERE 4091 03:07:18,458 --> 03:07:19,960 EPISODE OF PEM THE PATIENT 4092 03:07:19,960 --> 03:07:22,562 PREVIOUSLY EXPERIENCED IN THEIR 4093 03:07:22,562 --> 03:07:23,263 DAILY LIFE. 4094 03:07:23,263 --> 03:07:25,799 TO MEET THE THRESHOLD THE 4095 03:07:25,799 --> 03:07:28,001 PREVALUE AND PEAK RATING OF AT 4096 03:07:28,001 --> 03:07:30,504 LEAST 3 WAS REQUIRED. 4097 03:07:30,504 --> 03:07:35,942 3 WAS CHOSEN BECAUSE IT WAS 4098 03:07:35,942 --> 03:07:39,446 CLINICALLY NONE EXPERIENCED PEM 4099 03:07:39,446 --> 03:07:43,183 AND ALL THE ME/CFS S EXPERIENCED 4100 03:07:43,183 --> 03:07:43,350 PEM. 4101 03:07:43,350 --> 03:07:47,954 NEXT WE OVERLAID THE PEM DATA 4102 03:07:47,954 --> 03:07:49,956 WITH THE VISUAL SCALES AND THEY 4103 03:07:49,956 --> 03:07:52,692 PROVIDE A CONTINUUM FROM NOT AT 4104 03:07:52,692 --> 03:07:54,160 ALL TO MOST EXTREME. 4105 03:07:54,160 --> 03:07:55,929 PATIENTS MARK THE SYMPTOMS ON 4106 03:07:55,929 --> 03:07:57,564 THE CONTINUUM. 4107 03:07:57,564 --> 03:08:01,635 VISUAL ANALOG SCALES WERE DONE 4108 03:08:01,635 --> 03:08:04,638 AT THE INTERVIEWS AND CREATED A 4109 03:08:04,638 --> 03:08:05,305 COMPOSITE VAS THAT COMBINE 12 OF 4110 03:08:05,305 --> 03:08:08,475 THE INDIVIDUAL SYMPTOMS. 4111 03:08:08,475 --> 03:08:10,744 THIS SHOWS ONE PATIENT AS AN 4112 03:08:10,744 --> 03:08:11,211 EXAMPLE. 4113 03:08:11,211 --> 03:08:15,148 THE FATIGUE VAS IN BLACK AND 4114 03:08:15,148 --> 03:08:16,883 COMPOSITE VAS IN PURPLE REMAIN 4115 03:08:16,883 --> 03:08:19,019 FLAT AND THE PEM RATING IN BLUE 4116 03:08:19,019 --> 03:08:23,690 SHOWS MORE GRANULARITY. 4117 03:08:23,690 --> 03:08:25,425 THIS TABLE SHOWS CORRELATIONS 4118 03:08:25,425 --> 03:08:27,327 BETWEEN PEM INTERVIEW RATING AND 4119 03:08:27,327 --> 03:08:27,827 VAS SCALES. 4120 03:08:27,827 --> 03:08:29,663 IN THE INTEREST OF TIME I WON'T 4121 03:08:29,663 --> 03:08:30,931 GO THROUGH THE WHOLE TABLE BUT 4122 03:08:30,931 --> 03:08:33,767 THE MAIN POINT IS WHEN WE 4123 03:08:33,767 --> 03:08:37,470 SINGLED OUT THE ME/CFS PATIENTS 4124 03:08:37,470 --> 03:08:39,205 MOST BOTHERSOME SYSTEMS THE 4125 03:08:39,205 --> 03:08:42,475 MEASURES WERE STRONGER AT ALL 4126 03:08:42,475 --> 03:08:45,011 THREE DATA POINTS. 4127 03:08:45,011 --> 03:08:49,583 PRE-C PET AND CHANGE FROM PRE-C 4128 03:08:49,583 --> 03:08:54,721 PET TO CHANGE AND THIS IS THE 4129 03:08:54,721 --> 03:08:55,422 MOST BOTHERSOME SYSTEM OF 4130 03:08:55,422 --> 03:08:56,823 ME/CFS. 4131 03:08:56,823 --> 03:08:59,225 IMPLICATIONS FROM OUR MIXED 4132 03:08:59,225 --> 03:09:00,594 METHODS STUDY THAT USING OUR 4133 03:09:00,594 --> 03:09:01,928 NOVEL ASSESSMENT TOOL ALL 4134 03:09:01,928 --> 03:09:03,997 PATIENTS WERE DETERMINED TO HAVE 4135 03:09:03,997 --> 03:09:06,933 PEM FOLLOWING THE C PET. 4136 03:09:06,933 --> 03:09:09,402 DUE TO THE WIDE BREADTH OF 4137 03:09:09,402 --> 03:09:11,871 SYSTEM THE ABILITY TO SYNTHESIZE 4138 03:09:11,871 --> 03:09:14,307 MULTIPLE SYSTEMS INTO A SIMPLE 4139 03:09:14,307 --> 03:09:15,609 HOLISTIC EXPERIENCE WORKS BETTER 4140 03:09:15,609 --> 03:09:17,744 THAN LOOKING AT SINGULAR 4141 03:09:17,744 --> 03:09:19,946 INDIVIDUAL SYMPTOMS. 4142 03:09:19,946 --> 03:09:20,847 ISOLATING THE MOST BOTHER SYSTEM 4143 03:09:20,847 --> 03:09:23,116 SYMPTOMS SEEMED TO IMPROVE THE 4144 03:09:23,116 --> 03:09:23,750 PERFORMS OF THE VAS SCALES. 4145 03:09:23,750 --> 03:09:28,989 THE MIXED METHOD APPROACH HAS 4146 03:09:28,989 --> 03:09:30,824 PROMISE FOR RESEARCHERS TO USE 4147 03:09:30,824 --> 03:09:32,759 AND CURRENTLY OF USING THE 4148 03:09:32,759 --> 03:09:33,693 SYSTEM IN OUR COVID PATIENTS. 4149 03:09:33,693 --> 03:09:43,870 THANK YOU. 4150 03:09:50,343 --> 03:09:51,544 >> GOOD AFTERNOON, EVERYONE. 4151 03:09:51,544 --> 03:09:54,014 I'LL BE TALKING US THROUGH THE 4152 03:09:54,014 --> 03:09:55,715 CHALLENGE DONE AS PART OF THE 4153 03:09:55,715 --> 03:09:56,282 STUDY. 4154 03:09:56,282 --> 03:09:59,386 YOU MAY HAVE HEARD IT REFERRED 4155 03:09:59,386 --> 03:10:04,958 TO AS STRESS TEST OR CARDIO 4156 03:10:04,958 --> 03:10:08,928 PULMONARY TEST OR C PET FOR 4157 03:10:08,928 --> 03:10:09,262 SHORT. 4158 03:10:09,262 --> 03:10:13,033 SUBJECTS ARE REQUESTED TO CYCLE 4159 03:10:13,033 --> 03:10:15,435 AT A REQUESTED CADENCE AND 4160 03:10:15,435 --> 03:10:18,905 DURING THIS TIME INTENSITY IS 4161 03:10:18,905 --> 03:10:19,873 INCREASED OVER TIME. 4162 03:10:19,873 --> 03:10:21,141 THE EXERCISE TASK IS STOPPED 4163 03:10:21,141 --> 03:10:23,143 WHEN PARTICIPANTS ARE NO LONGER 4164 03:10:23,143 --> 03:10:28,882 ABLE TO MAINTAIN A SET CADENCE. 4165 03:10:28,882 --> 03:10:32,452 AS SEEN IN THE IMAGE, THERE IS 4166 03:10:32,452 --> 03:10:35,121 SEVERAL NON-BASIC PHYSIOLOGICAL 4167 03:10:35,121 --> 03:10:36,856 MEASURES TAKEN DURING THIS TASK. 4168 03:10:36,856 --> 03:10:39,959 FOR INSTANCE, YOU HAVE GAS 4169 03:10:39,959 --> 03:10:41,828 EXCHANGE THAT IS MEASURED 4170 03:10:41,828 --> 03:10:51,871 MEASURING OXYGEN AND CO2 AND 4171 03:10:51,871 --> 03:11:02,182 OXYGEN SATURATION. 4172 03:11:33,646 --> 03:11:38,818 ALL OF THIS IS CAPTURED THROUGH 4173 03:11:38,818 --> 03:11:49,362 THE CPET ASSESSMENT AND STIM -- 4174 03:12:02,208 --> 03:12:02,842 STIMULIZING MEASUREMENTS AND 4175 03:12:02,842 --> 03:12:05,145 THESE WERE BASED OFF PREDICTED 4176 03:12:05,145 --> 03:12:06,146 FITNESS. 4177 03:12:06,146 --> 03:12:09,983 SO BECAUSE WE KNOW THAT PIMES 4178 03:12:09,983 --> 03:12:11,217 PARTICIPANT HAVE A LOWER 4179 03:12:11,217 --> 03:12:13,653 CAPACITY THEY WERE GIVEN A 15 4180 03:12:13,653 --> 03:12:15,822 WATT PER MINUTE INCREMENT. 4181 03:12:15,822 --> 03:12:21,628 FOR HEALTHY THEY COULD HAVE A 15 4182 03:12:21,628 --> 03:12:24,297 OR 20 WATT INCREMENT INSTEAD. 4183 03:12:24,297 --> 03:12:26,499 TO HIGHLIGHT THAT AGAIN THE 4184 03:12:26,499 --> 03:12:27,467 LEVEL OR INCREASE IN THE WORK 4185 03:12:27,467 --> 03:12:31,638 RATE WAS RELATED TO TRYING TO 4186 03:12:31,638 --> 03:12:35,942 OPTIMIZE 8 TO 12 DURATION FOR 4187 03:12:35,942 --> 03:12:46,219 NEARLY EVERYONE. 4188 03:13:24,557 --> 03:13:29,429 THAT'S REPORTED AS PEAK VO2 AND 4189 03:13:29,429 --> 03:13:31,931 HAVE DISASSOCIATED WORK RATE 4190 03:13:31,931 --> 03:13:40,840 SHOWN AS PEAK. 4191 03:13:40,840 --> 03:13:45,845 AND WE HAVE CO2 AND DETERMINE 4192 03:13:45,845 --> 03:13:46,813 THE AT FOR SHORT. 4193 03:13:46,813 --> 03:13:51,351 SO THE A.T. IS A POINT SHOWN 4194 03:13:51,351 --> 03:13:53,653 HERE IN THIS FIGURE WHERE 4195 03:13:53,653 --> 03:13:55,889 FATIGUE IS IMMINENT. 4196 03:13:55,889 --> 03:14:00,193 ACTIVITIES BELOW THIS A.T. LEVEL 4197 03:14:00,193 --> 03:14:02,462 ARE THEORETICALLY ACTIVITIES YOU 4198 03:14:02,462 --> 03:14:05,565 CAN SUSTAIN WITHOUT IN OCCURRING 4199 03:14:05,565 --> 03:14:07,433 FATIGUE AND IF YOU CAN DO THEM 4200 03:14:07,433 --> 03:14:09,736 ABOVE A.T. THAT'S WHEN FATIGUE 4201 03:14:09,736 --> 03:14:11,938 WOULD DEVELOP. 4202 03:14:11,938 --> 03:14:15,875 OTHER MEASURES TAKING DURING THE 4203 03:14:15,875 --> 03:14:18,645 CPET TEST LOOK AT HEART RATE AND 4204 03:14:18,645 --> 03:14:23,082 THERE'S A STEADY INCREASE 4205 03:14:23,082 --> 03:14:24,617 TOWARDS PEAK AS EXERCISE 4206 03:14:24,617 --> 03:14:25,919 INCREASES OR WORK RATE 4207 03:14:25,919 --> 03:14:26,185 INCREASES. 4208 03:14:26,185 --> 03:14:27,921 WE TOOK MEASURES AT THE LOCAL 4209 03:14:27,921 --> 03:14:29,756 MUSCLE LEVEL. 4210 03:14:29,756 --> 03:14:31,891 HERE WE'RE LOOKING AT MUSCLE 4211 03:14:31,891 --> 03:14:32,392 OXYGEN SATURATION. 4212 03:14:32,392 --> 03:14:36,296 YOU SEE A SLIGHT DECLINE OR 4213 03:14:36,296 --> 03:14:37,563 DECLINE THAT'S HAPPENING BECAUSE 4214 03:14:37,563 --> 03:14:42,035 OF THE MUSCLE IS EXTRACTING 4215 03:14:42,035 --> 03:14:45,972 OXYGEN FROM THE MICROVASCULATURE 4216 03:14:45,972 --> 03:14:48,141 AS EXERCISE PROGRESSES. 4217 03:14:48,141 --> 03:14:49,809 TURNING OUR ATTENTION TO THE 4218 03:14:49,809 --> 03:14:50,043 RESULTS. 4219 03:14:50,043 --> 03:14:53,546 WE'RE LOOKING AT RESPIRATORY 4220 03:14:53,546 --> 03:14:57,183 EXCHANGE RATIO OR RER FOR SHORT. 4221 03:14:57,183 --> 03:15:01,888 THAT'S THE RATIO OF CO2, 2OT. 4222 03:15:01,888 --> 03:15:04,290 YOU CAN SOMETIMES USE THE RER TO 4223 03:15:04,290 --> 03:15:07,927 REFLECT WHETHER GAVE IT A GOOD 4224 03:15:07,927 --> 03:15:15,969 ATTEMPT ON THE EXERCISE TASK. 4225 03:15:15,969 --> 03:15:18,104 ALMOST EVERYONE HAD A GREATER 4226 03:15:18,104 --> 03:15:23,376 SCORE THAN 1.1 AND PEAK 4227 03:15:23,376 --> 03:15:25,111 PERFORMANCE WAS ACHIEVED IN BOTH 4228 03:15:25,111 --> 03:15:25,345 GROUPS. 4229 03:15:25,345 --> 03:15:29,782 THOSE WHO TRENDED TOWARDS A 4230 03:15:29,782 --> 03:15:34,620 LOWER PEAK POWER IN THE 4231 03:15:34,620 --> 03:15:38,891 PARTICIPANTS LOWER PEAK VO 2 4232 03:15:38,891 --> 03:15:40,159 VERSUS HEALTHY VOLUNTEERS AND 4233 03:15:40,159 --> 03:15:44,998 WHEN YOU LOOK AT PEAK VO2 AS A 4234 03:15:44,998 --> 03:15:47,667 PERCENTAGE OFF SEX, AGE AND 4235 03:15:47,667 --> 03:15:51,070 WEIGHT THE MAJORITY AT THESE 4236 03:15:51,070 --> 03:15:52,939 ALMOST ALL BUT ONE PARTICIPANTS 4237 03:15:52,939 --> 03:15:56,075 WAS LESS THAN 84% OF PREDICTED 4238 03:15:56,075 --> 03:15:59,479 VO2 CONVERSELY IN THE HEALTHY 4239 03:15:59,479 --> 03:16:03,750 VOLUNTEERS THE MAJORITY OF 4240 03:16:03,750 --> 03:16:06,586 PARTICIPANTS WERE OVER 84% OF 4241 03:16:06,586 --> 03:16:09,722 PREDICTED PEAK VO2. 4242 03:16:09,722 --> 03:16:11,724 IT'S A LOWER CAPACITY OBSERVED 4243 03:16:11,724 --> 03:16:16,062 AT PEAK AND THE ANAEROBIC 4244 03:16:16,062 --> 03:16:18,531 THRESHOLD IN TERMS OF HEALTHY 4245 03:16:18,531 --> 03:16:18,831 VOLUNTEERS. 4246 03:16:18,831 --> 03:16:20,533 LET'S LOOK AT PRACTICAL TERMS. 4247 03:16:20,533 --> 03:16:23,936 THIS IS SHOWING THE METABOLIC 4248 03:16:23,936 --> 03:16:27,140 EQUIVALENT OF TASK WHERE ONE IS 4249 03:16:27,140 --> 03:16:27,774 ENERGY REQUIREMENT JUST TO SIT 4250 03:16:27,774 --> 03:16:33,179 QUIETLY HERE. 4251 03:16:33,179 --> 03:16:34,380 ALONG THE RIGHT YOU'LL SEE 4252 03:16:34,380 --> 03:16:38,885 DIFFERENT COMMON ACTIVITIES AND 4253 03:16:38,885 --> 03:16:40,887 THE ASSOCIATED VALUES. 4254 03:16:40,887 --> 03:16:43,723 CARING A 15 POUND LOAD IS 5 4255 03:16:43,723 --> 03:16:44,323 MEANING FIVE TIMES THE ENERGY 4256 03:16:44,323 --> 03:16:53,800 REQUIREMENT THAN AT REST. 4257 03:16:53,800 --> 03:16:57,403 ALSO, DOWN HERE IT'S WHERE YOUR 4258 03:16:57,403 --> 03:16:59,238 DAILY ACTIVITIES OF DAILY LIVING 4259 03:16:59,238 --> 03:17:00,206 WOULD RESIDE. 4260 03:17:00,206 --> 03:17:02,809 THESE ARE TALKING ABOUT BASIC 4261 03:17:02,809 --> 03:17:03,976 SELF-CARE OF FEEDING, GROOMING, 4262 03:17:03,976 --> 03:17:14,153 DRESSING. 4263 03:17:23,996 --> 03:17:27,934 THIS IS CLEANING, COOKING AND 4264 03:17:27,934 --> 03:17:29,268 DAILY ACTIVITY. 4265 03:17:29,268 --> 03:17:31,938 HAVE YOU HERE ON THE RIGHT THE 4266 03:17:31,938 --> 03:17:34,907 PEAK EXERCISE BUT WHAT WE'RE 4267 03:17:34,907 --> 03:17:39,946 SEEING AS A GROUP IS HAVE YOU 4268 03:17:39,946 --> 03:17:41,013 ME/CFS PARTICIPANTS HAVING LOWER 4269 03:17:41,013 --> 03:17:44,183 AT A.T. AND PEAK EXERCISE. 4270 03:17:44,183 --> 03:17:46,752 FOR SHE'S INDIVIDUALS SHOWN 4271 03:17:46,752 --> 03:17:49,555 BELOW THE LEVEL FOR A.T. 4272 03:17:49,555 --> 03:17:51,390 PERFORMING INSTRUMENTAL 4273 03:17:51,390 --> 03:17:52,692 ACTIVITIES OF DAILY LIVING WILL 4274 03:17:52,692 --> 03:17:53,126 BE DIFFICULT. 4275 03:17:53,126 --> 03:17:55,928 COMPOUND THAT IF THEY WERE ALSO 4276 03:17:55,928 --> 03:17:58,431 HAVING A MET LEVEL OF LESS THAN 4277 03:17:58,431 --> 03:18:06,205 5 AT PEAK EXERCISE. 4278 03:18:06,205 --> 03:18:07,673 KNOWING IT'S UP TO SIX FOR 4279 03:18:07,673 --> 03:18:10,343 MODERATE ACTIVITIES SEE AROUND 4280 03:18:10,343 --> 03:18:13,312 WHAT IS STILL TERM THERE'S A 4281 03:18:13,312 --> 03:18:15,014 FAIR AMOUNT OF PARTICIPANTS THAT 4282 03:18:15,014 --> 03:18:25,525 WOULD BE AT THEIR PEAK LIMITS. 4283 03:19:13,839 --> 03:19:16,475 THERE WAS A HEART RATE RESPONSE 4284 03:19:16,475 --> 03:19:18,444 IN THE ME/CFS PARTICIPANTS BUT 4285 03:19:18,444 --> 03:19:19,946 NOT AMONG THE HEALTHY 4286 03:19:19,946 --> 03:19:25,885 VOLUNTEERS. 4287 03:19:25,885 --> 03:19:28,487 TO WRAP UP IN TERMS OF 4288 03:19:28,487 --> 03:19:31,524 AMBULATORY EFFICIENCY HOW WELL 4289 03:19:31,524 --> 03:19:33,092 THE LUNGS FUNCTIONED TO EXPEL 4290 03:19:33,092 --> 03:19:34,660 CO2 THERE WAS NO REAL DIFFERENCE 4291 03:19:34,660 --> 03:19:36,629 BETWEEN THE GROUPS AND 4292 03:19:36,629 --> 03:19:38,631 MECHANICAL EFFICIENCY AND 4293 03:19:38,631 --> 03:19:42,335 SIMILAR BETWEEN THE GROUPS AND 4294 03:19:42,335 --> 03:19:43,936 THE MICROVASCULATURE LOOKING AT 4295 03:19:43,936 --> 03:19:46,505 THE MUSCLE OXYGEN SATURATION AND 4296 03:19:46,505 --> 03:19:48,641 THERE WAS NO REAL DIFFERENCE 4297 03:19:48,641 --> 03:19:50,710 BETWEEN THE GROUPS AND THERE WAS 4298 03:19:50,710 --> 03:19:55,147 A LOT OF VARIABILITY. 4299 03:19:55,147 --> 03:19:55,948 SIMILAR EFFICIENCY AS WELL AS 4300 03:19:55,948 --> 03:19:58,517 MUSCLE TISSUE OXYGEN WERE FOUND 4301 03:19:58,517 --> 03:19:58,951 BETWEEN THE GROUPS. 4302 03:19:58,951 --> 03:20:09,128 THANK YOU. 4303 03:20:16,636 --> 03:20:27,079 >> I'M SHANNA YANG AM AND WE 4304 03:20:31,651 --> 03:20:32,818 LOOKED AT THE LITERATURE AND NOT 4305 03:20:32,818 --> 03:20:35,554 SUPER SURPRISINGLY THERE WASN'T 4306 03:20:35,554 --> 03:20:39,492 A WHOLE LOT OUT THERE DESCRIBING 4307 03:20:39,492 --> 03:20:40,526 DIET IN THE POPULATION BUT MIXED 4308 03:20:40,526 --> 03:20:42,228 REPORTS IN WHAT WAS OUT THERE. 4309 03:20:42,228 --> 03:20:44,630 SOME MENTIONED FREQUENT 4310 03:20:44,630 --> 03:20:47,166 AVOIDANCE OF DIETARY ITEMS OR 4311 03:20:47,166 --> 03:20:49,201 FOOD GROUPS INCLUDING DAIRY, 4312 03:20:49,201 --> 03:20:55,775 GLUTEN, SUGAR WHICH WE HEARD 4313 03:20:55,775 --> 03:20:59,111 ANECDOTALLY AND OTHER STUDIES 4314 03:20:59,111 --> 03:21:01,981 FOUND NUTRIENT INTAKE WAS NOT 4315 03:21:01,981 --> 03:21:05,418 DIFFERENT BETWEEN HEALTHY V 4316 03:21:05,418 --> 03:21:08,087 VOLUNTEERS AND THE REGULAR 4317 03:21:08,087 --> 03:21:08,387 POPULATION. 4318 03:21:08,387 --> 03:21:10,656 THE MIXED RESULTS LED US TO 4319 03:21:10,656 --> 03:21:16,095 THINK TO LOOK FURTHER IN THIS. 4320 03:21:16,095 --> 03:21:19,765 THE OTHER REASON IS THERE'S 4321 03:21:19,765 --> 03:21:20,599 INTERESTING INTERVENTION AND IN 4322 03:21:20,599 --> 03:21:23,736 2017 A REVIEW ARTICLE MENTIONED 4323 03:21:23,736 --> 03:21:24,470 DIFFERENT INTERVENTION TRIALS 4324 03:21:24,470 --> 03:21:27,940 LOOKING AT DIET MOSTLY FOCUSSED 4325 03:21:27,940 --> 03:21:30,142 ON SUPPLEMENTS AND DIETS LIKE 4326 03:21:30,142 --> 03:21:31,277 LOW SUGAR AND LOW YEAST DIET. 4327 03:21:31,277 --> 03:21:32,845 BECAUSE OF THIS ANOTHER REASON 4328 03:21:32,845 --> 03:21:33,846 WE THOUGHT I WAS IMPORTANT TO 4329 03:21:33,846 --> 03:21:37,683 QUANTIFY DIET. 4330 03:21:37,683 --> 03:21:39,218 WE USED TWO DIFFERENT TOOLS. 4331 03:21:39,218 --> 03:21:41,787 THE FIRST IS THE DIET HISTORY 4332 03:21:41,787 --> 03:21:43,789 QUESTIONNAIRE DHQ2. 4333 03:21:43,789 --> 03:21:46,058 A COMPREHENSIVE FOOD FREQUENCY 4334 03:21:46,058 --> 03:21:47,626 QUESTIONNAIRE THAT COVERS 4335 03:21:47,626 --> 03:21:49,228 DIETARY HABITS OVER A LONG TERM 4336 03:21:49,228 --> 03:21:51,197 PERIOD IN THIS CASE IN THE PAST 4337 03:21:51,197 --> 03:21:53,165 YEAR AND 134 FOOD ITEMS. 4338 03:21:53,165 --> 03:21:54,800 IT'S USED TO ASSESS TYPICAL 4339 03:21:54,800 --> 03:21:58,437 NUTRIENT INTAKE OVER THE PAST 4340 03:21:58,437 --> 03:21:59,939 YEAR AND DOES QUANTIFY PORTION 4341 03:21:59,939 --> 03:22:02,274 SIZE AS WELL AND WEB BASED AND 4342 03:22:02,274 --> 03:22:03,542 SELF-ADMINISTERED AND COMPLETED 4343 03:22:03,542 --> 03:22:05,144 FROM ALL PARTICIPANTS AT THEIR 4344 03:22:05,144 --> 03:22:05,845 FIRST VISIT. 4345 03:22:05,845 --> 03:22:07,947 THIS PROVIDED A GENERAL 4346 03:22:07,947 --> 03:22:10,783 ASSESSMENT OF DIETARY PATTERNS 4347 03:22:10,783 --> 03:22:16,355 OVER A LONG-TERM PERIOD OF TIME. 4348 03:22:16,355 --> 03:22:19,892 THESE ARE SCREEN SHOTS OF THE 4349 03:22:19,892 --> 03:22:20,493 QUESTIONNAIRE. 4350 03:22:20,493 --> 03:22:23,596 IT ASKS ABOUT ALL THESE FOODS 4351 03:22:23,596 --> 03:22:27,867 AND IT GOES ON TO ASK IN FURTHER 4352 03:22:27,867 --> 03:22:30,302 DETAIL AND WHAT'S YOUR PORTION 4353 03:22:30,302 --> 03:22:31,137 SIDE ETCETERA. 4354 03:22:31,137 --> 03:22:33,873 IT'S VERY COMPREHENSIVE. 4355 03:22:33,873 --> 03:22:35,741 THE SECOND TOOL WERE FOOD 4356 03:22:35,741 --> 03:22:36,942 RECORDS AND ASKED EACH 4357 03:22:36,942 --> 03:22:39,111 PARTICIPANT TO KEEP A SEVEN DAY 4358 03:22:39,111 --> 03:22:40,880 FOOD RECORD FOR THE WEEK PRIOR 4359 03:22:40,880 --> 03:22:42,548 TO THEIR VISIT AT THE CENTER 4360 03:22:42,548 --> 03:22:46,886 THIS COVERED THE SAME PERIOD. 4361 03:22:46,886 --> 03:22:50,189 WE REVIEWED THIS FOOD REPORT FOR 4362 03:22:50,189 --> 03:22:53,325 ACCURACY AND COMPLETENESS AND 4363 03:22:53,325 --> 03:22:55,027 VERIFIED BRAND NAMES, COOKING, 4364 03:22:55,027 --> 03:22:59,165 METHODS, AMOUNTS, ETCETERA AND 4365 03:22:59,165 --> 03:23:01,600 PROBED FOR MISSING OR FORGOTTEN 4366 03:23:01,600 --> 03:23:04,003 ITEMS AND CODED THE INFORMATION 4367 03:23:04,003 --> 03:23:07,273 INTO A SOFTWARE CALLED NUTRITION 4368 03:23:07,273 --> 03:23:09,108 SYSTEM DATA FOR RESEARCH TO 4369 03:23:09,108 --> 03:23:11,076 QUANTIFY INTAKE DOWN TO THE 4370 03:23:11,076 --> 03:23:13,813 NUTRIENT LEVEL. 4371 03:23:13,813 --> 03:23:16,982 THIS PROVIDES GRANULAR DATA RICH 4372 03:23:16,982 --> 03:23:19,652 IN DETAIL AND PRECISION BUT ONLY 4373 03:23:19,652 --> 03:23:21,954 COVERS A SHORT TERM PERIOD AND 4374 03:23:21,954 --> 03:23:23,355 DOESN'T LOOK AS MUCH AS THE 4375 03:23:23,355 --> 03:23:24,089 PATTERNS AS MUCH AS THE PRECISE 4376 03:23:24,089 --> 03:23:33,999 DETAIL. 4377 03:23:33,999 --> 03:23:36,869 FROM BOTH SCHOOLS WE DIDN'T SEE 4378 03:23:36,869 --> 03:23:39,939 MUCH DIFFERENCE BETWEEN HEALTHY 4379 03:23:39,939 --> 03:23:42,374 VOLUNTEERS AND ME/CFS 4380 03:23:42,374 --> 03:23:42,741 PARTICIPANTS. 4381 03:23:42,741 --> 03:23:45,411 THERE WAS NO DIFFERENCE IN 4382 03:23:45,411 --> 03:23:47,980 ENERGY ACROSS THE BOARD. 4383 03:23:47,980 --> 03:23:50,382 THE ONLY MACRO NUTRIENTS LOOKING 4384 03:23:50,382 --> 03:23:53,118 AT CARBOHYDRATE, FAT, PROTEIN, 4385 03:23:53,118 --> 03:23:54,820 ALCOHOL WE DID FIND A DIFFERENCE 4386 03:23:54,820 --> 03:23:59,091 IN WAS SATURATED FAT WHERE WE 4387 03:23:59,091 --> 03:24:04,029 SAW THE PERCENT OF CALORIES WAS 4388 03:24:04,029 --> 03:24:07,900 HIGHER IN PI ME/CFS AND FIBER 4389 03:24:07,900 --> 03:24:11,203 WAS SLIGHTLY HIGHER IN OUR 4390 03:24:11,203 --> 03:24:15,908 HEALTHY VOLUNTEERS. 4391 03:24:15,908 --> 03:24:18,244 MOVING TO THE MICRONUTRIENTS 4392 03:24:18,244 --> 03:24:22,248 LOOKING AT ONLY DIETARY INTAKE 4393 03:24:22,248 --> 03:24:23,249 AND DOES NOT INCLUDE 4394 03:24:23,249 --> 03:24:23,616 SUPPLEMENTATION. 4395 03:24:23,616 --> 03:24:26,385 WE DIDN'T SEE MUCH DIFFERENCE IN 4396 03:24:26,385 --> 03:24:30,923 TERMS OF INTAKE. 4397 03:24:30,923 --> 03:24:38,330 THE ONLY DIFFERENT WAS IN TERMS 4398 03:24:38,330 --> 03:24:41,166 OF FOLATE WITH HEALTHY 4399 03:24:41,166 --> 03:24:43,135 VOLUNTEERS TAKING MORE. 4400 03:24:43,135 --> 03:24:44,870 DURING THE SECOND VISIT WE 4401 03:24:44,870 --> 03:24:46,839 CONTROLLED DIET FOR PART OF THE 4402 03:24:46,839 --> 03:24:47,873 STUDY. 4403 03:24:47,873 --> 03:24:50,242 THEY WERE NO LONGER EATING THEIR 4404 03:24:50,242 --> 03:24:51,677 TYPICAL DIET BUT WHAT WAS 4405 03:24:51,677 --> 03:24:52,878 PROVIDED TO THEM AND TWO REASONS 4406 03:24:52,878 --> 03:24:54,413 WE DID THIS. 4407 03:24:54,413 --> 03:24:57,516 THE FIRST WAS AS YOU ALREADY 4408 03:24:57,516 --> 03:24:59,251 HEARD WHOLE BODY ENERGY 4409 03:24:59,251 --> 03:25:01,220 METABOLISM ANALYZED IN 4410 03:25:01,220 --> 03:25:01,954 RESPIRATORY CHAMBERS. 4411 03:25:01,954 --> 03:25:05,291 WHEN WE LOOK AT ENERGY OUT WE 4412 03:25:05,291 --> 03:25:07,993 FEED TO BE ABLE TO QUANTIFY 4413 03:25:07,993 --> 03:25:10,029 ENERGY IN PRECISELY. 4414 03:25:10,029 --> 03:25:12,431 WE NEED TO KNOW PRECISELY WHAT 4415 03:25:12,431 --> 03:25:12,998 PREME EATING. 4416 03:25:12,998 --> 03:25:15,301 WE CONTROLLED THEIR DIET DURING 4417 03:25:15,301 --> 03:25:17,169 THE PERIOD OF TIME WHILE THEY 4418 03:25:17,169 --> 03:25:18,704 WERE IN THE RESPIRATORY 4419 03:25:18,704 --> 03:25:19,004 CHAMBERS. 4420 03:25:19,004 --> 03:25:22,575 AND IT'S IMPORTANT TO CONTROL 4421 03:25:22,575 --> 03:25:25,144 DIET TO ISOLATE INDIVIDUAL 4422 03:25:25,144 --> 03:25:29,081 FACTORS AND KNOW IT'S SOMETHING 4423 03:25:29,081 --> 03:25:31,216 RELATED TO THE INDIVIDUAL 4424 03:25:31,216 --> 03:25:32,651 METABOLISM VERSUS SOMEONE EATING 4425 03:25:32,651 --> 03:25:35,354 HIGH CARB OR FAT OR A DIFFERENCE 4426 03:25:35,354 --> 03:25:41,760 LIKE THAT. 4427 03:25:41,760 --> 03:25:43,462 THAT'S ONE OF OUR COOKS 4428 03:25:43,462 --> 03:25:46,999 PREPARING A METABOLIC DIET HOW 4429 03:25:46,999 --> 03:25:48,434 WE CONTROLLED WHILE METABOLISM 4430 03:25:48,434 --> 03:25:49,168 WAS BEING ASSESSED. 4431 03:25:49,168 --> 03:25:52,137 WE PROVIDED A DIET CONTROLLED IN 4432 03:25:52,137 --> 03:25:54,540 DIFFERENT NUTRIENTS. 4433 03:25:54,540 --> 03:25:55,874 EVERY FOOD AND BEVERAGE WAS 4434 03:25:55,874 --> 03:25:57,409 WEIGHED OUT TO THE EXACT GRAM. 4435 03:25:57,409 --> 03:25:59,878 AS PLANNED THE DIETS WERE 4436 03:25:59,878 --> 03:26:00,946 CONTROLLED FOR ENERGY. 4437 03:26:00,946 --> 03:26:05,384 THE ENERGY WAS CALCULATED TO 4438 03:26:05,384 --> 03:26:06,518 MEET INDIVIDUALIZED ENERGY NEEDS 4439 03:26:06,518 --> 03:26:08,487 USING STANDARD ACTIVITY FACTOR 4440 03:26:08,487 --> 03:26:11,023 AND MACRO NUTRIENTS WERE 4441 03:26:11,023 --> 03:26:11,757 STANDARDIZED ACROSS ALL 4442 03:26:11,757 --> 03:26:13,325 PARTICIPANTS WITH 30% OF ENERGY 4443 03:26:13,325 --> 03:26:16,328 FROM FAT AND 15% FROM PROTEIN 4444 03:26:16,328 --> 03:26:18,297 AND 55% FROM CARBOHYDRATE. 4445 03:26:18,297 --> 03:26:20,499 PARTICIPANTS WERE ASKED TO 4446 03:26:20,499 --> 03:26:22,601 CONSUME THE DIET IN ENTIRETY AND 4447 03:26:22,601 --> 03:26:25,104 ANY REFUSED ITEMS OR UNABLE TO 4448 03:26:25,104 --> 03:26:28,807 FINISH WERE WEIGHED BACK TO 4449 03:26:28,807 --> 03:26:29,675 CALCULATE THE CONSUMED DIET DATA 4450 03:26:29,675 --> 03:26:31,543 TO TAKE INTO ACCOUNT AND YOU'LL 4451 03:26:31,543 --> 03:26:33,345 HEAR MORE WHEN YOU HEAR ABOUT 4452 03:26:33,345 --> 03:26:34,947 THE RESULTS OF THAT RESPIRATORY 4453 03:26:34,947 --> 03:26:35,447 CHAMBER. 4454 03:26:35,447 --> 03:26:45,591 THANKS. 4455 03:26:53,198 --> 03:27:02,341 >> GOOD AFTERNOON. 4456 03:27:02,341 --> 03:27:07,913 MY NAME IS SAM LOVE 4457 03:27:10,849 --> 03:27:14,920 SAM LAMUNION AND WE LOOK AT 4458 03:27:14,920 --> 03:27:17,322 BONE, LEAN AND FAT MASSES. 4459 03:27:17,322 --> 03:27:24,163 AND YOU MIGHT WONDER HOW DOES IT 4460 03:27:24,163 --> 03:27:26,298 RELATE AND FAT FREE PASS 4461 03:27:26,298 --> 03:27:29,468 ACCOUNTS FOR 70% AND 80% OF 4462 03:27:29,468 --> 03:27:31,870 RESTING ENERGY EXPENDITURE AND 4463 03:27:31,870 --> 03:27:33,839 YOU CAN SEE ON THE FIGURE ON THE 4464 03:27:33,839 --> 03:27:41,814 RIGHT RESTING EXPENDITURE IS 60% 4465 03:27:41,814 --> 03:27:44,583 TO 70% BUT IT VARIES BY 4466 03:27:44,583 --> 03:27:44,883 INDIVIDUAL. 4467 03:27:44,883 --> 03:27:47,052 HOW DO WE MEASURE THIS? 4468 03:27:47,052 --> 03:27:51,957 YOU'LL SEE THE SCANNER WHICH WE 4469 03:27:51,957 --> 03:27:56,462 USED IN THE METABOLIC SUITE AND 4470 03:27:56,462 --> 03:27:59,565 DUEL ENERGY OR DEXA FOR SHORT 4471 03:27:59,565 --> 03:28:03,001 AND PATIENTS COMPLETED A WHOLE 4472 03:28:03,001 --> 03:28:04,536 BODY DEXA SCAN AT THE DEEP 4473 03:28:04,536 --> 03:28:05,537 PHENOTYPING VISIT. 4474 03:28:05,537 --> 03:28:07,973 AND WE'RE ABLE TO GET OUTPUT ON 4475 03:28:07,973 --> 03:28:11,944 WHOLE BODY AND REGIONAL 4476 03:28:11,944 --> 03:28:13,645 COMPOSITION OF FAT MASS, LEAN 4477 03:28:13,645 --> 03:28:15,981 MASS AND ESTIMATED VISCERAL FAT 4478 03:28:15,981 --> 03:28:18,617 AROUND THE VITAL ORGANS. 4479 03:28:18,617 --> 03:28:22,888 OUR QUESTION WAS WHAT DOES BODY 4480 03:28:22,888 --> 03:28:23,622 COMPOSITION LOOK LIKE IN PI 4481 03:28:23,622 --> 03:28:25,724 ME/CFS COMPARED TO HEALTHY 4482 03:28:25,724 --> 03:28:26,024 VOLUNTEERS. 4483 03:28:26,024 --> 03:28:27,392 YOU SEE THE IMAGE NOT FROM 4484 03:28:27,392 --> 03:28:29,261 ANYONE IN THE STUDY BUT TO GIVE 4485 03:28:29,261 --> 03:28:32,131 AN IDEA OF WHAT THE IMAGE OUTPUT 4486 03:28:32,131 --> 03:28:32,831 LOOKS LUKE. 4487 03:28:32,831 --> 03:28:35,234 WHAT WE FOUND WAS BODY 4488 03:28:35,234 --> 03:28:37,703 COMPOSITION WAS NORMAL OR AT 4489 03:28:37,703 --> 03:28:39,204 LEAST NOT DIFFERENT FROM THE 4490 03:28:39,204 --> 03:28:40,806 THEY WILL HI VOLUNTEERS THAT 4491 03:28:40,806 --> 03:28:41,807 PARTICIPATED IN THE STUDY. 4492 03:28:41,807 --> 03:28:45,210 YOU'LL SEE IN ALL THE PANELS 4493 03:28:45,210 --> 03:28:46,745 LEAN BODY MASS WAS NOT 4494 03:28:46,745 --> 03:28:47,346 DIFFERENT. 4495 03:28:47,346 --> 03:28:48,614 THERE WERE NO STATISTICAL 4496 03:28:48,614 --> 03:28:49,615 DIFFERENCES FOR ALL THE MEASURES 4497 03:28:49,615 --> 03:28:53,652 FOR LEAN BODY MASS AND FAT MASS 4498 03:28:53,652 --> 03:28:57,422 AND BODY FAT PERCENTAGE AND 4499 03:28:57,422 --> 03:29:00,959 VISCERAL FAT MASS ESTIMATE AND 4500 03:29:00,959 --> 03:29:02,694 DOMINANT ARM LEAN MASS AND LEGS 4501 03:29:02,694 --> 03:29:03,462 LEAN MASS. 4502 03:29:03,462 --> 03:29:07,299 WITHIN BOTH GROUPS THE HEALTHY 4503 03:29:07,299 --> 03:29:08,834 VOLUNTEERS AND PI ME/CFS YOU SEE 4504 03:29:08,834 --> 03:29:11,103 INDIVIDUAL DIFFERENCES. 4505 03:29:11,103 --> 03:29:12,704 WE SEE THIS IN THE POPULATION WE 4506 03:29:12,704 --> 03:29:17,676 SEE LOTS OF PATIENTS WITH 4507 03:29:17,676 --> 03:29:23,682 DIFFERENT CHRONIC DISEASES AND 4508 03:29:23,682 --> 03:29:25,584 IT'S EQUIVALENT TO VARIABILITY 4509 03:29:25,584 --> 03:29:26,084 ACROSS INDIVIDUALS. 4510 03:29:26,084 --> 03:29:29,855 THE NEXT PART WHAT IS THE 4511 03:29:29,855 --> 03:29:33,292 RELATIONSHIP BETWEEN ENERGY AND 4512 03:29:33,292 --> 03:29:35,127 ENERGY EXPENDITURE AND THE TOP 4513 03:29:35,127 --> 03:29:37,429 PART OF THE FIGURE IS PHYSICAL 4514 03:29:37,429 --> 03:29:38,764 ACTIVITY AND ENERGY EXPENDITURE 4515 03:29:38,764 --> 03:29:41,867 AND HOW DOES THAT RELATE TO 4516 03:29:41,867 --> 03:29:44,536 TOTAL ENERGY EXPENDITURE. 4517 03:29:44,536 --> 03:29:46,338 WITH DEFECTIVE FEEDING YOU'LL 4518 03:29:46,338 --> 03:29:48,941 HEAR ABOUT MOMENTARILY THE LAST 4519 03:29:48,941 --> 03:29:50,943 PART FOR ENERGY EXPENDITURE 4520 03:29:50,943 --> 03:29:53,712 MAKES UP 15% TO 20% OF TOTAL 4521 03:29:53,712 --> 03:29:54,947 DAILY EXPENDITURE. 4522 03:29:54,947 --> 03:29:55,881 THERE'S HIGH INDIVIDUAL 4523 03:29:55,881 --> 03:29:57,749 VARIATION DAY TO DAY AND ACROSS 4524 03:29:57,749 --> 03:29:58,317 INDIVIDUALS. 4525 03:29:58,317 --> 03:30:00,586 THIS COULD BE ESTIMATE FROM 4526 03:30:00,586 --> 03:30:01,587 VARIABLE DEVICE DATA. 4527 03:30:01,587 --> 03:30:05,724 AND YOU SEE THE FIGURE SPLIT IN 4528 03:30:05,724 --> 03:30:07,960 TWO CATEGORIES, ENERGIZE 4529 03:30:07,960 --> 03:30:11,730 EXPENDITURE GOING WALK OR RUN OR 4530 03:30:11,730 --> 03:30:13,966 SOME ACTIVITY OR NON-EXERCISE 4531 03:30:13,966 --> 03:30:18,070 AND THERMO GENESIS OR INCIDENTAL 4532 03:30:18,070 --> 03:30:22,341 ACTIVITIES OF DAILY ACTIVITY. 4533 03:30:22,341 --> 03:30:23,909 THINGS YOU DO TRANSPORTATION AND 4534 03:30:23,909 --> 03:30:25,911 THAT SORT OF THING. 4535 03:30:25,911 --> 03:30:34,253 THAT CAN BE MEASURED WITH 4536 03:30:34,253 --> 03:30:35,554 ACCELER OM TRY. 4537 03:30:35,554 --> 03:30:39,091 WE DID SAYS FREE LIVING OR 4538 03:30:39,091 --> 03:30:40,392 HABITUAL BEHAVIOR BETWEEN VISITS 4539 03:30:40,392 --> 03:30:45,364 ALIGNED WITH THE OUT PATIENT 4540 03:30:45,364 --> 03:30:47,633 DIET FOOD RECORDS AND WAS IT 4541 03:30:47,633 --> 03:30:52,771 DIFFERENT FROM HEALTHY 4542 03:30:52,771 --> 03:30:53,205 VOLUNTEERS? 4543 03:30:53,205 --> 03:30:58,510 WE USED A SMALL PORTABLE DEVICE 4544 03:30:58,510 --> 03:30:59,811 RECORDED LOCALLY ON THE DEVICE 4545 03:30:59,811 --> 03:31:02,147 AND THIS IS AMERICA MOVEMENT IN 4546 03:31:02,147 --> 03:31:04,683 THREE PLANES AND NO OTHER 4547 03:31:04,683 --> 03:31:06,585 PHYSIOLOGICAL OUTCOMES, JUST 4548 03:31:06,585 --> 03:31:07,419 MOVEMENT. 4549 03:31:07,419 --> 03:31:09,821 WE COLLECTED RAW AT 80 HERTZ AND 4550 03:31:09,821 --> 03:31:11,890 LATER COLLAPSED TO ONE MINUTE IN 4551 03:31:11,890 --> 03:31:22,167 ACTIVITY COUNTS. 4552 03:31:23,168 --> 03:31:27,072 AND THIS WAS STANDARDIZED SO 4553 03:31:27,072 --> 03:31:29,741 PEOPLE WHO DIDN'T WEAR IT AS 4554 03:31:29,741 --> 03:31:31,176 MUCH AS GOT NOT INCLUDED IN THE 4555 03:31:31,176 --> 03:31:31,443 ANALYSES. 4556 03:31:31,443 --> 03:31:34,846 WE USED THE VALIDATED CUT POINT 4557 03:31:34,846 --> 03:31:36,982 FOR ESTIMATING MODERATE TO 4558 03:31:36,982 --> 03:31:40,552 VOIG VIGOROUS ACTIVITY. 4559 03:31:40,552 --> 03:31:43,956 WE'LL LOOK AT MEAN TOTAL STEPS 4560 03:31:43,956 --> 03:31:46,858 PER DAY AND THE PI ME/CFS TOOK 4561 03:31:46,858 --> 03:31:47,826 SIGNIFICANTLY FEWER STEPS 4562 03:31:47,826 --> 03:31:50,228 COMPARED TO HEALTHY VOLUNTEERS. 4563 03:31:50,228 --> 03:31:53,799 IN THE MIDDLE IS THE MAGNITUDE, 4564 03:31:53,799 --> 03:31:55,067 TOTAL ACTIVITY COUNTS AND THE 4565 03:31:55,067 --> 03:31:57,202 SQUARE ROOT OF THE SUM OF THE 4566 03:31:57,202 --> 03:31:57,469 SQUARES. 4567 03:31:57,469 --> 03:31:59,071 DON'T WORRY ABOUT THE MATH. 4568 03:31:59,071 --> 03:32:00,739 IT'S SUMMARY MEASURE OF THE 4569 03:32:00,739 --> 03:32:01,907 NUMBER OF COUNTS PER DAY SO THIS 4570 03:32:01,907 --> 03:32:06,411 IS AN INTEGRATED SUMMARIZED 4571 03:32:06,411 --> 03:32:07,179 METRICS. 4572 03:32:07,179 --> 03:32:08,714 MORE COUNTS TRANSLATES TO MORE 4573 03:32:08,714 --> 03:32:08,981 MOVEMENT. 4574 03:32:08,981 --> 03:32:11,917 ANOTHER VOLUME MEASURE AND SAW 4575 03:32:11,917 --> 03:32:14,019 THE PI ME/CFS GROUP HAD LESS 4576 03:32:14,019 --> 03:32:16,288 TOTAL MOVEMENT PER DAY FOR THIS 4577 03:32:16,288 --> 03:32:20,225 MEASURE AND LASTLY FOR INTENSITY 4578 03:32:20,225 --> 03:32:23,962 MEASURE DR. CHEN HIGHLIGHTED, 4579 03:32:23,962 --> 03:32:29,968 MODERATE INTENSITY ACTIVITY IS 4580 03:32:29,968 --> 03:32:33,038 ASSESSED AND STARTING AT 3 4581 03:32:33,038 --> 03:32:34,439 MOBILE EQUIVALENTS OF TASKS AND 4582 03:32:34,439 --> 03:32:37,142 A CUT POINT FOR EVERYBODY OR 4583 03:32:37,142 --> 03:32:38,977 ADULTS AND WE SAW THE PI ME/CFS 4584 03:32:38,977 --> 03:32:41,980 GROUP DID ACCUMULATE OR ENGAGE 4585 03:32:41,980 --> 03:32:44,983 IN SIGNIFICANTLY LESS MODERATE 4586 03:32:44,983 --> 03:32:47,119 INTENSITY PHYSICAL ACTIVITY ON A 4587 03:32:47,119 --> 03:32:48,553 DAILY BASIS AND AS HIGHLIGHTED 4588 03:32:48,553 --> 03:32:51,923 WITHIN EACH GROUP WE SAW 4589 03:32:51,923 --> 03:32:53,658 VARIABILITY AND THIS DOES AGAIN 4590 03:32:53,658 --> 03:32:55,627 VARIES WITH INDIVIDUAL DAY TO 4591 03:32:55,627 --> 03:32:56,661 DAY AND WITHIN INDIVIDUALS 4592 03:32:56,661 --> 03:32:57,362 WITHIN THE GROUP. 4593 03:32:57,362 --> 03:33:01,800 WITH THAT I'LL TURN IT OVER TO 4594 03:33:01,800 --> 03:33:09,307 DR. BRYCHTA. 4595 03:33:09,307 --> 03:33:11,476 >> I'M A STAFF SCIENTIST AT 4596 03:33:11,476 --> 03:33:13,245 NIDDK AND I'LL TALK ABOUT OUR 4597 03:33:13,245 --> 03:33:18,050 MEASUREMENTS OF WHOLE BODY 4598 03:33:18,050 --> 03:33:19,217 ENERGY EXPENDITURE. 4599 03:33:19,217 --> 03:33:24,389 A LITTLE DIAGRAM WHAT WE USED TO 4600 03:33:24,389 --> 03:33:26,358 USE TO MEASURE THIS RESPIRATORY 4601 03:33:26,358 --> 03:33:32,531 CHAMBER OR METABOLIC CHAMBER. 4602 03:33:32,531 --> 03:33:34,933 WE SEE IN THE WHITE IS THE ROOM 4603 03:33:34,933 --> 03:33:36,134 AND YELLOW IS AIR BUFFER AROUND 4604 03:33:36,134 --> 03:33:38,737 THE ROOM A CORRIDOR AROUND THE 4605 03:33:38,737 --> 03:33:39,004 ROOM. 4606 03:33:39,004 --> 03:33:43,008 AND FRESH AIR CAN GO IN THE ROOM 4607 03:33:43,008 --> 03:33:44,209 THROUGH A SMALL PORTAL. 4608 03:33:44,209 --> 03:33:50,115 AND THE REST OF ROOM IS SEALED. 4609 03:33:50,115 --> 03:33:51,850 PEOPLE STAY IN THE ROOM AND 4610 03:33:51,850 --> 03:33:53,385 CHANGE THE COMPOSITION OF THE 4611 03:33:53,385 --> 03:33:56,855 AIR BY CONSUMING OXYGEN AND 4612 03:33:56,855 --> 03:33:57,956 PRODUCING CARBON DIOXIDE. 4613 03:33:57,956 --> 03:34:00,625 WE PULL AIR OUT OF THE ROOM SO 4614 03:34:00,625 --> 03:34:03,061 THERE'S A ONE-WAY FLOW OF AIR 4615 03:34:03,061 --> 03:34:05,797 AND MEASURE THE FLOW OF AIR OUT 4616 03:34:05,797 --> 03:34:07,365 OF THE ROOM AND SAMPLE THE 4617 03:34:07,365 --> 03:34:10,902 COMPOSITION OF THE AIR USING AN 4618 03:34:10,902 --> 03:34:13,138 OXYGEN AND CO2 ANALYZER TO 4619 03:34:13,138 --> 03:34:15,407 MEASURE THE CONCENTRATION OVER 4620 03:34:15,407 --> 03:34:17,142 TIME AND COMPARE WHAT'S GOING ON 4621 03:34:17,142 --> 03:34:19,144 INSIDE OF THE ROOM GETTING 4622 03:34:19,144 --> 03:34:20,846 CHANGED BY THE SUBJECT TO WHAT'S 4623 03:34:20,846 --> 03:34:23,381 GOING IN TO THE ROOM IN THE 4624 03:34:23,381 --> 03:34:25,784 FRESH AIR, THE COMPOSITION OF 4625 03:34:25,784 --> 03:34:27,552 THE OXYGEN AND CO2 WHICH IN THE 4626 03:34:27,552 --> 03:34:34,359 FRESH AIR IS PRETTY STABLE. 4627 03:34:34,359 --> 03:34:39,464 NOW, HERE IS AN EXAMPLE OF OUR 4628 03:34:39,464 --> 03:34:44,436 METABOLIC CHAMBER AT NIDDK 4629 03:34:44,436 --> 03:34:44,703 BETHESDA. 4630 03:34:44,703 --> 03:34:52,043 PEOPLE SPENT FROM 4:00 P.M. TO 4631 03:34:52,043 --> 03:34:54,980 8:00 A.M. IN THIS STUDY AND MOST 4632 03:34:54,980 --> 03:34:56,815 SPENT FOUR TO FIVE NIGHTS IN THE 4633 03:34:56,815 --> 03:34:57,983 METABOLIC CHAMBER. 4634 03:34:57,983 --> 03:35:03,188 IT LOOKS LIKE A WALK-IN FREEZER 4635 03:35:03,188 --> 03:35:03,588 IF YOU'LL NOTICE. 4636 03:35:03,588 --> 03:35:06,992 ON THE TOP THERE'S THE SAMPLING 4637 03:35:06,992 --> 03:35:12,597 PORTS WHICH ARE METAL AND 4638 03:35:12,597 --> 03:35:14,599 THERE'S MOTION SENSORS TO TELL 4639 03:35:14,599 --> 03:35:19,004 IF PEOPLE ARE MOVING OR NOT 4640 03:35:19,004 --> 03:35:22,140 MOVING AND ASLEEP. 4641 03:35:22,140 --> 03:35:30,815 AS DR. LAMUNION POINTED OUT WE 4642 03:35:30,815 --> 03:35:33,351 CAN MEASURE THE DAILY EXPEND 4643 03:35:33,351 --> 03:35:35,954 YOU'RE USING THE DEVICE BUT THE 4644 03:35:35,954 --> 03:35:37,189 TIME CONSTRAINTS AND PEOPLE'S 4645 03:35:37,189 --> 03:35:39,958 SCHEDULE DOING THIS INTENSIVE 4646 03:35:39,958 --> 03:35:41,493 STUDY WE MEASURED THEM. 4647 03:35:41,493 --> 03:35:43,728 THESE PARTICULAR SUBJECTS FROM 4648 03:35:43,728 --> 03:35:45,897 4:00 P.M. TO 8:00 a.m. 4649 03:35:45,897 --> 03:35:47,732 WE'RE BASICALLY CONCENTRATING ON 4650 03:35:47,732 --> 03:35:49,334 MEASUREMENTS OF THEIR RESTING 4651 03:35:49,334 --> 03:35:54,973 AND SLEEPING ENERGY EXPENDITURE. 4652 03:35:54,973 --> 03:35:57,209 AND PARTICULARLY THE RESPONSE TO 4653 03:35:57,209 --> 03:35:57,809 THE CPET. 4654 03:35:57,809 --> 03:36:03,982 TO DO THAT ACROSS THE PEOPLE 4655 03:36:03,982 --> 03:36:05,517 HEALTHY VOLUNTEERS AND PATIENTS, 4656 03:36:05,517 --> 03:36:07,953 WE MINIMIZED THE VARIABILITY OF 4657 03:36:07,953 --> 03:36:09,221 THEIR ACTIVITY ENERGY 4658 03:36:09,221 --> 03:36:09,521 EXPENDITURE. 4659 03:36:09,521 --> 03:36:11,756 THEY REMAIN SEDENTARY OR ASLEEP 4660 03:36:11,756 --> 03:36:12,924 DURING THE STUDY. 4661 03:36:12,924 --> 03:36:17,162 THEY BASICALLY WHEN THEY WEREN'T 4662 03:36:17,162 --> 03:36:22,701 ASLEEP THEY WERE WATCHING TV AND 4663 03:36:22,701 --> 03:36:25,103 RELAXING AND MINIMIZED THE 4664 03:36:25,103 --> 03:36:26,705 VARIABILITY IN THERMO EFFECTIVE 4665 03:36:26,705 --> 03:36:27,973 FOOD OR ENERGY RESPONSE TO 4666 03:36:27,973 --> 03:36:30,809 BREAKING DOWN THE FOOD OF THEIR 4667 03:36:30,809 --> 03:36:31,276 DIET. 4668 03:36:31,276 --> 03:36:34,212 EACH PERSON GOT ONE MEAL IN THE 4669 03:36:34,212 --> 03:36:38,216 CHAMBER AND THE MEALS ARE 4670 03:36:38,216 --> 03:36:39,951 STANDARDIZED AND THE DIET IS 4671 03:36:39,951 --> 03:36:43,955 WEIGHT MAINTENANCE DIET FOR EACH 4672 03:36:43,955 --> 03:36:45,323 PERSON'S NEED. 4673 03:36:45,323 --> 03:36:50,328 THIS IS A 24-HOUR TRACING WHAT 4674 03:36:50,328 --> 03:36:52,297 WE SEE IN THE CHAMBER AND THIS 4675 03:36:52,297 --> 03:36:53,732 IS A PERSON FROM A DIFFERENT 4676 03:36:53,732 --> 03:36:54,899 STUDY. 4677 03:36:54,899 --> 03:36:59,938 YOU SEE THE SLEEPING ENERGY 4678 03:36:59,938 --> 03:37:03,775 EXPENDITURE HIGHLIGHTED IN RED 4679 03:37:03,775 --> 03:37:09,047 AND THIS IS THE MOST STEADY AND 4680 03:37:09,047 --> 03:37:11,916 MINUTE TO MINUTE VARIABILITY AND 4681 03:37:11,916 --> 03:37:15,453 MOST REPRODUCIBLE FROM NIGHT TO 4682 03:37:15,453 --> 03:37:18,757 NIGHT AND CORRELATED TO YOUR FAT 4683 03:37:18,757 --> 03:37:21,426 FREE MASS AND RESTING ENERGY 4684 03:37:21,426 --> 03:37:23,728 EXPENDITURE AND SLEEPING ENERGY 4685 03:37:23,728 --> 03:37:24,996 EXPENDITURE EXPLAINED BY 70% TO 4686 03:37:24,996 --> 03:37:27,966 80% OF THE VARIATION AND THAT'S 4687 03:37:27,966 --> 03:37:32,871 EXPLAINED BY YOUR FAT FREE MASS. 4688 03:37:32,871 --> 03:37:36,808 THIS IS DIFFICULT TO MEASURE YOU 4689 03:37:36,808 --> 03:37:41,680 CAN IMAGINE IF YOU'RE MEASURING 4690 03:37:41,680 --> 03:37:43,748 OXYGEN AND CO2 VIEWED TO WEAR A 4691 03:37:43,748 --> 03:37:44,349 MASK AND THAT'S DIFFICULT TO 4692 03:37:44,349 --> 03:37:49,754 SLEEP IN. 4693 03:37:49,754 --> 03:37:52,490 HERE'S WHAT WE FOUND WITH OUR 4694 03:37:52,490 --> 03:37:55,460 SLEEPING ENERGY EXPENDITURE AND 4695 03:37:55,460 --> 03:37:57,295 THIS IS AT BASELINE THE NIGHT 4696 03:37:57,295 --> 03:38:00,432 BEFORE THE CPET. 4697 03:38:00,432 --> 03:38:04,002 HERE AGAIN THE PI ME/CFS 4698 03:38:04,002 --> 03:38:06,271 PATIEPATIENT 4699 03:38:06,271 --> 03:38:09,040 S ARE IN RED AND HEALTHY 4700 03:38:09,040 --> 03:38:11,476 VOLUNTEERS IN BLUE AND MEN WILL 4701 03:38:11,476 --> 03:38:14,946 SQUARES AND WOMEN ARE CIRCLES. 4702 03:38:14,946 --> 03:38:17,749 IN GENERAL WOMEN HAVE A LOWER 4703 03:38:17,749 --> 03:38:19,317 FAT FREE MASS THAN MEN AND ON 4704 03:38:19,317 --> 03:38:20,719 THE LEFT CORNER OF THE GRAPH 4705 03:38:20,719 --> 03:38:22,454 BECAUSE WOMEN ARE GENERALLY 4706 03:38:22,454 --> 03:38:23,955 SHORTER THAN MEN SO THEY'RE 4707 03:38:23,955 --> 03:38:29,027 GOING TO HAVE LESS FAT FREE MASS 4708 03:38:29,027 --> 03:38:31,429 BUT YOU CAN SEE ACROSS THE WHOLE 4709 03:38:31,429 --> 03:38:34,065 GROUP THE FAT FREE MASS AND 4710 03:38:34,065 --> 03:38:35,100 EXPENDITURE IS HIGHLY CORRELATED 4711 03:38:35,100 --> 03:38:40,939 AND THERE'S NOT REALLY MUCH OF A 4712 03:38:40,939 --> 03:38:43,208 TREND BETWEEN THAT 4713 03:38:43,208 --> 03:38:47,312 DIFFERENTIATES THE HEALTHY 4714 03:38:47,312 --> 03:38:48,346 VOLUNTEERS AND ME/CFS 4715 03:38:48,346 --> 03:38:50,749 PARTICIPANTS AND THE R SQUARED 4716 03:38:50,749 --> 03:38:51,649 IS .78. 4717 03:38:51,649 --> 03:38:54,352 IT'S ABOUT 78% OF THE VARIATION 4718 03:38:54,352 --> 03:38:57,856 IS EXPLAINED BY THEIR FAT FREE 4719 03:38:57,856 --> 03:38:58,590 MASS. 4720 03:38:58,590 --> 03:39:03,261 WHEN YOU LOOK AT TOTAL ENERGY 4721 03:39:03,261 --> 03:39:05,463 EXPENDITURE IT'S ONLY FROM 4:00 4722 03:39:05,463 --> 03:39:07,399 P.M. TO 8:00 A.M. MOSTLY RESTING 4723 03:39:07,399 --> 03:39:10,668 AND MOST TIME IS SLEEPING BUT 4724 03:39:10,668 --> 03:39:11,970 AGAIN IT'S EXPLAINED BY ABOUT 4725 03:39:11,970 --> 03:39:15,974 75% OF THE VARIATION IS 4726 03:39:15,974 --> 03:39:18,376 EXPLAINED BY THEIR FAT FREE 4727 03:39:18,376 --> 03:39:21,446 MASS. 4728 03:39:21,446 --> 03:39:24,449 SO WHEN WE LOOK AT SHE SLEEPING 4729 03:39:24,449 --> 03:39:27,152 ENERGY EXPENDITURE FROM BEFORE 4730 03:39:27,152 --> 03:39:29,187 THE CPET TO AFTER THE NIGHT 4731 03:39:29,187 --> 03:39:35,994 AFTER THE CPET, AND THAT -- IS 4732 03:39:35,994 --> 03:39:37,529 IN THE OPEN CIRCLES AND SQUARES 4733 03:39:37,529 --> 03:39:39,964 AND A LINE CONNECTING EACH 4734 03:39:39,964 --> 03:39:42,400 PARTICIPANT TO THEIR BASELINE 4735 03:39:42,400 --> 03:39:43,935 MEASUREMENT BEFORE THE CPET TO 4736 03:39:43,935 --> 03:39:45,670 AFTER MEASUREMENT ANN CAN SEE 4737 03:39:45,670 --> 03:39:51,943 THE RED DOTTED LINE WHICH THE 4738 03:39:51,943 --> 03:39:58,016 REGRESSION OF FAT FREE FALLS ON 4739 03:39:58,016 --> 03:39:58,583 TO THE CPET. 4740 03:39:58,583 --> 03:40:09,127 THERE WASN'T MUCH OF AN EFFECT. 4741 03:40:24,943 --> 03:40:27,178 WE SEE WHERE THE REGRESSION 4742 03:40:27,178 --> 03:40:28,646 LINES OF TOTAL ENERGY 4743 03:40:28,646 --> 03:40:31,449 EXPENDITURE FALL ON ONE OF ONE 4744 03:40:31,449 --> 03:40:35,854 NORTH AND COMPARING THEMSELVES 4745 03:40:35,854 --> 03:40:37,589 WE DON'T SEE DIFFERENCE NIGHT 4746 03:40:37,589 --> 03:40:41,259 BEFORE TO AFTER THE CPET. 4747 03:40:41,259 --> 03:40:43,661 NOW THE OTHER THING WE CAN LOOK 4748 03:40:43,661 --> 03:40:45,830 AT WITH THE METABOLIC CHAMBER IS 4749 03:40:45,830 --> 03:40:47,665 CALLED THE RESPIRATORY QUOTIENT 4750 03:40:47,665 --> 03:40:54,639 OR LEE -- LISA REFERRED TO IT 4751 03:40:54,639 --> 03:40:57,041 AS THE MEASURE OF CARBON DIOXIDE 4752 03:40:57,041 --> 03:41:02,580 EXPIRED TO OXYGEN CONSUMED. 4753 03:41:02,580 --> 03:41:05,416 WHEN YOU'RE EXERCISING THIS IS A 4754 03:41:05,416 --> 03:41:07,652 MEASURE OF YOUR EFFORT OR HOW 4755 03:41:07,652 --> 03:41:09,554 MUCH YOU'RE EXPENDING AND WHEN 4756 03:41:09,554 --> 03:41:15,693 YOU'RE AT REST THIS REFLECTS 4757 03:41:15,693 --> 03:41:16,961 WHAT FUEL YOU'RE USING WHERE THE 4758 03:41:16,961 --> 03:41:18,096 MAJORITY OF YOUR ENERGY IS 4759 03:41:18,096 --> 03:41:18,696 COMING FROM. 4760 03:41:18,696 --> 03:41:23,768 A RATIO OF .7 WOULD BE PURELY 4761 03:41:23,768 --> 03:41:25,937 FAT IN THE DIET AND 1.0 WOULD BE 4762 03:41:25,937 --> 03:41:28,773 PURELY CARBOHYDRATE AND THE 4763 03:41:28,773 --> 03:41:29,908 STANDARD MIXED MEAL IS SOME 4764 03:41:29,908 --> 03:41:31,609 PLACE IN BETWEEN. 4765 03:41:31,609 --> 03:41:36,047 WE CAN SEE AT REST OR AT SLEEP 4766 03:41:36,047 --> 03:41:38,416 THERE WAS NO DIFFERENCE BETWEEN 4767 03:41:38,416 --> 03:41:39,217 THE PEOPLE COMPARED TO 4768 03:41:39,217 --> 03:41:43,421 THEMSELVES IN THEIR SLEEPING 4769 03:41:43,421 --> 03:41:45,290 RESPIRATORY QUOTIENT WHICH IS A 4770 03:41:45,290 --> 03:41:47,959 LITTLE BIT LOWER THAN THEIR 4771 03:41:47,959 --> 03:41:51,963 RESPIRATORY QUOTIENT WHILE THEY 4772 03:41:51,963 --> 03:41:54,499 WERE HAVING A MEAL. 4773 03:41:54,499 --> 03:41:57,802 THERE'S REALLY -- THERE WAS NO 4774 03:41:57,802 --> 03:41:58,970 DETECTED DIFFERENCE BETWEEN THE 4775 03:41:58,970 --> 03:42:00,738 NIGHT BEFORE AND THE NIGHT AFTER 4776 03:42:00,738 --> 03:42:03,174 THE CPET THANE MEASURE. 4777 03:42:03,174 --> 03:42:04,175 -- IN THAT MEASURE. 4778 03:42:04,175 --> 03:42:11,149 WITH THAT I'LL GIVE IT TO 4779 03:42:11,149 --> 03:42:21,326 DR. HWANG. 4780 03:42:34,973 --> 03:42:38,576 ALL RIGHT. 4781 03:42:38,576 --> 03:42:47,251 I'M PAUL HWANG AN INVESTIGATOR 4782 03:42:47,251 --> 03:42:47,819 IN NATIONAL HEART, LUNG AND 4783 03:42:47,819 --> 03:42:50,421 BLOOD INSTITUTE AND START BY 4784 03:42:50,421 --> 03:42:51,522 THANKING THE ORGANIZERS FOR 4785 03:42:51,522 --> 03:42:52,123 GIVING ME THE OPPORTUNITY TO 4786 03:42:52,123 --> 03:42:56,794 PRESENT OUR WORK. 4787 03:42:56,794 --> 03:42:59,897 WHAT I'D LIKE TO DO IS SHARE A 4788 03:42:59,897 --> 03:43:03,735 PROJECT OVER THE PAST SEVERAL 4789 03:43:03,735 --> 03:43:11,275 YEARS TRYING TO DETERMINE THE 4790 03:43:11,275 --> 03:43:12,710 MOLECULAR MECHANISM OF THE 4791 03:43:12,710 --> 03:43:20,151 MUSCLE OF PATIENTS WITH ME/CFS. 4792 03:43:20,151 --> 03:43:23,955 WE HAD REPORTED EARLY IN OUR 4793 03:43:23,955 --> 03:43:26,658 STUDIES INDIVIDUALS WITH THE 4794 03:43:26,658 --> 03:43:27,659 SYNDROME A CANCER DISORDER 4795 03:43:27,659 --> 03:43:35,933 CAUSED BY GERM LINE MUTATIONS OF 4796 03:43:35,933 --> 03:43:40,838 P53, SORRY. 4797 03:43:40,838 --> 03:43:46,544 THAT IS THE EARLY ONSET CANCER 4798 03:43:46,544 --> 03:43:48,846 DISORDER HAVE DECREASED 4799 03:43:48,846 --> 03:43:51,816 MITOCHONDRIAL DYSFUNCTION AND 4800 03:43:51,816 --> 03:43:52,417 INCREASED ENDURANCE. 4801 03:43:52,417 --> 03:43:58,189 A PATIENT HAD READ OUR WORK ON 4802 03:43:58,189 --> 03:44:00,892 THE WEB E-MAILED ME SAYING SHE 4803 03:44:00,892 --> 03:44:03,995 WAS THE EXACT OPPOSITE AND WAS 4804 03:44:03,995 --> 03:44:06,164 ALWAYS FATIGUED AND HAD TERRIBLE 4805 03:44:06,164 --> 03:44:07,198 EXERCISE ENDURANCE. 4806 03:44:07,198 --> 03:44:13,671 THIS IS THE CASE OF A 4807 03:44:13,671 --> 03:44:17,041 38-YEAR-OLD WOMAN WITH 4808 03:44:17,041 --> 03:44:17,709 LI-FRAUMENNI SYNDROME AND 4809 03:44:17,709 --> 03:44:19,944 STARTED IN HER TEEN AGE YEARS 4810 03:44:19,944 --> 03:44:24,582 AFTER SHE CONTRACTED 4811 03:44:24,582 --> 03:44:27,952 MONONUCLEOSIS AND THE FATIGUE 4812 03:44:27,952 --> 03:44:30,388 SYMPTOMS NEVER WENT AWAY AND HAD 4813 03:44:30,388 --> 03:44:35,059 EXTENSIVE CLINICAL WORKUP AND 4814 03:44:35,059 --> 03:44:35,693 MITOCHONDRIAL DISEASE EVALUATION 4815 03:44:35,693 --> 03:44:40,198 AND GENOME SEQUENCING WHICH WERE 4816 03:44:40,198 --> 03:44:43,935 ALL UNREMARKABLE AND HAD TYPICAL 4817 03:44:43,935 --> 03:44:50,141 SYMPTOMS ASSOCIATED WITH ME/CFS. 4818 03:44:50,141 --> 03:44:51,943 THERE'S BEEN MANY MECHANISMS 4819 03:44:51,943 --> 03:44:54,145 PROPOSED BUT SOME HAVE INCLUDED 4820 03:44:54,145 --> 03:44:55,947 DYSFUNCTION OF THE MITOCHONDRIA 4821 03:44:55,947 --> 03:44:59,951 BUT NO SPECIFIC MEDIATOR HAS 4822 03:44:59,951 --> 03:45:06,390 BEEN IDENTIFIED. 4823 03:45:06,390 --> 03:45:08,626 WE STUDIED PATIENTS AND NONE HAD 4824 03:45:08,626 --> 03:45:11,896 REPORTED FATIGUE SYMPTOMS AND 4825 03:45:11,896 --> 03:45:13,164 WERE INTRIGUED BY THE REPORT AND 4826 03:45:13,164 --> 03:45:14,465 DECIDED TO STUDY THE PATIENT. 4827 03:45:14,465 --> 03:45:18,936 WE INVITED HER AND SHE'S 4828 03:45:18,936 --> 03:45:23,941 INDICATED HERE AS SIBLING S1. 4829 03:45:23,941 --> 03:45:30,548 WE DID A PHOSPHORUS NONINVASIVE 4830 03:45:30,548 --> 03:45:31,549 TEST OF THE EXERCISE MUSCLE AND 4831 03:45:31,549 --> 03:45:35,653 SHOWN BY OTHER INVESTIGATORS AS 4832 03:45:35,653 --> 03:45:36,220 A MARKER OF MITOCHONDRIAL 4833 03:45:36,220 --> 03:45:40,458 DYSFUNCTION. 4834 03:45:40,458 --> 03:45:43,594 WHEN WE PERFORMED THIS TEST ON 4835 03:45:43,594 --> 03:45:47,732 THE PATIENT WE WERE AMAZED HOW 4836 03:45:47,732 --> 03:45:51,169 SLOW HER RECOVERY TIME WAS AT 80 4837 03:45:51,169 --> 03:45:55,406 SECONDS OVER TWO DIFFERENT TIME 4838 03:45:55,406 --> 03:46:00,812 PERIODS IN A SIX MONTH TIME 4839 03:46:00,812 --> 03:46:01,045 PERIOD. 4840 03:46:01,045 --> 03:46:03,848 AND WE WERE UNFORTUNATE TO 4841 03:46:03,848 --> 03:46:05,550 INVITE THE BROTHER ALSO HAD THE 4842 03:46:05,550 --> 03:46:07,351 SYNDROME BUT DIDN'T HAVE THE 4843 03:46:07,351 --> 03:46:07,785 FATIGUE SYMPTOMS. 4844 03:46:07,785 --> 03:46:10,755 HIS RECOVERY TIME WAS 30 SECONDS 4845 03:46:10,755 --> 03:46:13,958 AND THAT'S IN THE REALM OF WHAT 4846 03:46:13,958 --> 03:46:17,728 WE HAD PREVIOUSLY OBSERVED IN 4847 03:46:17,728 --> 03:46:18,963 OTHER SYMPTOMS. 4848 03:46:18,963 --> 03:46:23,267 IT'S FASTER THAN NON-CARRIERS IN 4849 03:46:23,267 --> 03:46:26,704 THE REALM OF 36 SECONDS. 4850 03:46:26,704 --> 03:46:29,941 WE OBTAINED BIOPSIES AND MADE 4851 03:46:29,941 --> 03:46:34,078 FIBROBLASTS AND DID A SIMPLE 4852 03:46:34,078 --> 03:46:36,914 EXPERIMENT LOOKING AT OXYGEN 4853 03:46:36,914 --> 03:46:39,917 FUNCTION AND THE PATIENT S1 4854 03:46:39,917 --> 03:46:44,055 OXYGEN CONSUMPTION IN THE BASAL 4855 03:46:44,055 --> 03:46:48,759 AND MAXIMAL STATE WAS 4856 03:46:48,759 --> 03:46:50,061 SIGNIFICANTLY LOWER THAN THE 4857 03:46:50,061 --> 03:46:51,062 BROTHER'S CONSUMPTION. 4858 03:46:51,062 --> 03:46:52,763 THIS WAS AN INTERESTING FINDING 4859 03:46:52,763 --> 03:46:55,967 AND WE PURSUED THIS FURTHER AND 4860 03:46:55,967 --> 03:46:57,401 BASICALLY SUMMARIZED A LARGE 4861 03:46:57,401 --> 03:47:02,974 BODY OF WORK AND WERE ABLE TO 4862 03:47:02,974 --> 03:47:05,376 IDENTIFY OF THE POTENTIAL 4863 03:47:05,376 --> 03:47:10,781 MEDIATOR OF THE MITOCHONDRIAL 4864 03:47:10,781 --> 03:47:11,082 DYSFUNCTION. 4865 03:47:11,082 --> 03:47:11,949 FINDING THIS INVOLVED TRACING 4866 03:47:11,949 --> 03:47:14,919 THIS SIGNALLING THAT WE OBSERVED 4867 03:47:14,919 --> 03:47:17,788 INVOLVING P53 PHOSPHORYLATION 4868 03:47:17,788 --> 03:47:20,291 AND P38 KINASE ACTIVATION. 4869 03:47:20,291 --> 03:47:23,728 IN RETROSPECT THE SIGNALLING 4870 03:47:23,728 --> 03:47:25,596 ABNORMALITIES WERE SECONDARY TO 4871 03:47:25,596 --> 03:47:27,965 PRIMARY DEFECT IN MITOCHONDRIAL 4872 03:47:27,965 --> 03:47:28,699 FUNG IN THE KRILZ. 4873 03:47:28,699 --> 03:47:30,001 -- CELLS. 4874 03:47:30,001 --> 03:47:34,138 WE IDENTIFIED FOR THE PROTEIN 4875 03:47:34,138 --> 03:47:37,008 FOUND AND THE GENE THAT'S 4876 03:47:37,008 --> 03:47:41,779 MUTATED IN THIS IMMUNODEFICIENCY 4877 03:47:41,779 --> 03:47:44,348 AND FAMILY GENE IN THE SYNDROME. 4878 03:47:44,348 --> 03:47:46,784 AND INTERESTINGLY WE REPORTED A 4879 03:47:46,784 --> 03:47:50,154 NUMBER OF YEARS AGO IT WAS A TOP 4880 03:47:50,154 --> 03:47:52,456 CANDIDATE GENE ASSOCIATED WITH 4881 03:47:52,456 --> 03:47:57,428 ME/CFS IN A LARGE BIO 4882 03:47:57,428 --> 03:47:58,062 INFORMATICS META-ANALYSIS BUT 4883 03:47:58,062 --> 03:47:59,931 NOT MUCH MORE HAD BEEN DONE 4884 03:47:59,931 --> 03:48:05,236 SUBSEQUENT TO THE REPORT. 4885 03:48:05,236 --> 03:48:07,939 IT WAS KNOWN TO INTERACT WITH 4886 03:48:07,939 --> 03:48:14,211 ACTIN POLYMERIZATION FOR THE 4887 03:48:14,211 --> 03:48:17,782 CYTOSKELETON OF THE CELL AND A 4888 03:48:17,782 --> 03:48:19,750 SCAFFOLDING PROTEIN FOR 4889 03:48:19,750 --> 03:48:21,152 COMPLEXES. 4890 03:48:21,152 --> 03:48:22,620 IT'S ALSO KNOWN TO INFORM CELL 4891 03:48:22,620 --> 03:48:23,955 MIGRATION AND HAS BEEN STUDIED 4892 03:48:23,955 --> 03:48:31,329 IN THE CANCER FIELD. 4893 03:48:31,329 --> 03:48:33,965 ONE EARLY EXPERIMENT WE DID WAS 4894 03:48:33,965 --> 03:48:36,400 TO DOWN REGULATE THE PROTEIN 4895 03:48:36,400 --> 03:48:37,034 LEVELS IN THE PATIENT CELLS THE 4896 03:48:37,034 --> 03:48:44,508 S 1 PATIENT CELLS USING THE RNA 4897 03:48:44,508 --> 03:48:47,078 AND FOUND SIGNIFICANT 4898 03:48:47,078 --> 03:48:49,013 IMPROVEMENT IN OXYGEN 4899 03:48:49,013 --> 03:48:51,482 CONSUMPTION WHEN WE DECREASED 4900 03:48:51,482 --> 03:48:54,018 THE LEVELS AND ASSOCIATED WAS A 4901 03:48:54,018 --> 03:48:56,487 NICE INCREASE IN THE 4902 03:48:56,487 --> 03:48:59,357 MITOCHONDRIAL COMPLEX 4 PROTEINS 4903 03:48:59,357 --> 03:49:02,560 YOU CAN SEE HERE. 4904 03:49:02,560 --> 03:49:07,331 WE ALSO DID OPPOSITE EXPERIMENT 4905 03:49:07,331 --> 03:49:11,502 OF OVEREXPRESSING THIS IN 4906 03:49:11,502 --> 03:49:12,670 MYOBLASTS AND WHEN WE 4907 03:49:12,670 --> 03:49:14,939 OVEREXPRESSED THE PROTEIN OXYGEN 4908 03:49:14,939 --> 03:49:16,907 CONSUMPTION IS DECREASED AND YOU 4909 03:49:16,907 --> 03:49:21,879 CAN SEE WHEN WE LOOK AT THE 4910 03:49:21,879 --> 03:49:23,948 DIFFERENT COMPLEXES, COMPLEX 4 4911 03:49:23,948 --> 03:49:29,420 SUB UNIT PROTEIN COX 1 SUB UNIT 4912 03:49:29,420 --> 03:49:30,855 IS DECREASED WHILE THE OTHER 4913 03:49:30,855 --> 03:49:34,458 COMPLEX 5, 3 AND 1 PROTEINS ARE 4914 03:49:34,458 --> 03:49:34,759 NOT CHANGED. 4915 03:49:34,759 --> 03:49:37,294 THE REASON FOR THIS BECOMES 4916 03:49:37,294 --> 03:49:39,930 CLEARER BASED ON FURTHER 4917 03:49:39,930 --> 03:49:41,265 MECHANISTIC STUDIES AND AGAIN TO 4918 03:49:41,265 --> 03:49:45,770 SUMMARIZE OUR WORK WE SHOWED 4919 03:49:45,770 --> 03:49:51,942 THAT THE WAS 3 PROTEIN ENRICHED 4920 03:49:51,942 --> 03:49:54,478 THE MITOCHONDRIA AND USING 4921 03:49:54,478 --> 03:49:55,746 PROXIMITY LIGATION ASSAYS 4922 03:49:55,746 --> 03:49:57,181 LOOKING AT THE INTERACTION 4923 03:49:57,181 --> 03:49:59,884 BETWEEN WAS 3 AND SOME 4924 03:49:59,884 --> 03:50:01,085 MITOCHONDRIAL RESPIRATORY 4925 03:50:01,085 --> 03:50:02,887 PROTEINS WE WERE ABLE TO SHOW 4926 03:50:02,887 --> 03:50:05,990 WAS CAN INTERACT WITH THE 4927 03:50:05,990 --> 03:50:10,828 RESPIRATORY COMPLEX 3 SUB UNIT 4928 03:50:10,828 --> 03:50:14,098 PROTEINS AND THAT WAS 3 IS OVER 4929 03:50:14,098 --> 03:50:15,933 EXPRESSED IT DISRUPTS THE 4930 03:50:15,933 --> 03:50:18,369 ASSEMBLY OF THE PROTEINS AND 4931 03:50:18,369 --> 03:50:19,970 WELL KNOWN IN THE LITERATURE 4932 03:50:19,970 --> 03:50:22,173 WHEN YOU DESTABILIZE COMPLEX 4 4933 03:50:22,173 --> 03:50:24,475 PROTEINS THEY GET DEGRADED. 4934 03:50:24,475 --> 03:50:26,477 THAT EXPLAINS WHAT WE OBSERVED 4935 03:50:26,477 --> 03:50:28,779 WITH THE PROTEIN LEVEL WHEN IT 4936 03:50:28,779 --> 03:50:31,182 EXPRESSED THE PROTEINS WITHOUT. 4937 03:50:31,182 --> 03:50:35,619 BESIDES MAKING A MOUSE MODEL 4938 03:50:35,619 --> 03:50:38,089 EVERY EXPRESSED WAS 3 AND 4939 03:50:38,089 --> 03:50:42,393 SHOWING A DECREASE IN EXERCISE 4940 03:50:42,393 --> 03:50:47,531 CAPACITY OF NICE ON TREADMILL WE 4941 03:50:47,531 --> 03:50:55,172 OBTAINED SAMPLES FROM THE STUDY 4942 03:50:55,172 --> 03:50:57,875 AND LOOKED AT WHAT WAS STORED IN 4943 03:50:57,875 --> 03:50:59,743 PATIENTS COMPARED TO HEALTHY 4944 03:50:59,743 --> 03:51:01,879 VOLUNTEERS AND OBSERVED 4945 03:51:01,879 --> 03:51:03,447 SIGNIFICANT INCREASE IN THE 4946 03:51:03,447 --> 03:51:04,582 PROTEIN LEVELS IN THE MUSCLE 4947 03:51:04,582 --> 03:51:06,417 SAMPLES OF THE PATIENTS AND THEN 4948 03:51:06,417 --> 03:51:11,555 YOU CAN SEE HERE THE INVERSE 4949 03:51:11,555 --> 03:51:13,157 RELATIONSHIP BETWEEN THE 4950 03:51:13,157 --> 03:51:15,693 EXPRESSION AND COMPLEX IN THE 4951 03:51:15,693 --> 03:51:17,394 PROTEINS FROM THE MUSCLE SUB 4952 03:51:17,394 --> 03:51:17,595 UNITS. 4953 03:51:17,595 --> 03:51:19,830 IN TERMS OF WHAT MIGHT BE 4954 03:51:19,830 --> 03:51:23,200 INCREASING THE WAS 3 PROTEIN 4955 03:51:23,200 --> 03:51:24,335 LEVELS THERE WAS EVIDENCE IN THE 4956 03:51:24,335 --> 03:51:26,070 LITERATURE E.R. STRESS IS 4957 03:51:26,070 --> 03:51:26,737 INVOLVED IN INCREASING THE 4958 03:51:26,737 --> 03:51:30,641 PROTEIN LEVELS. 4959 03:51:30,641 --> 03:51:31,942 WE LOOKED AT ONE OF THE MARKERS 4960 03:51:31,942 --> 03:51:41,886 OF THE PROTEIN MARKER COMPARED 4961 03:51:41,886 --> 03:51:50,928 TO HEALTHY VOLUNTEERS. 4962 03:51:50,928 --> 03:51:54,064 WE WERE ABLE TO TAKE THE PATIENT 4963 03:51:54,064 --> 03:51:56,500 CELL WITH CHRONIC FATIGUE AND 4964 03:51:56,500 --> 03:52:00,738 CELLS IN CULTURE AND ADD A 4965 03:52:00,738 --> 03:52:02,606 SPECIFIC STRESS INHIBITOR. 4966 03:52:02,606 --> 03:52:07,311 IT WORKS SPECIFICALLY BY 4967 03:52:07,311 --> 03:52:08,746 INHIBITING KINASE THAT IS 4968 03:52:08,746 --> 03:52:10,581 INVOLVED IN REGULATING E.R. 4969 03:52:10,581 --> 03:52:14,818 STRESS AND ABLE TO SHOW IN A 4970 03:52:14,818 --> 03:52:15,686 DRUG-DOSE DEPENDENT MANNER WE 4971 03:52:15,686 --> 03:52:18,822 ARE ABLE TO RECOVER THE 4972 03:52:18,822 --> 03:52:19,557 MITOCHONDRIAL FUNCTION OF THE 4973 03:52:19,557 --> 03:52:22,126 PATIENT'S CELLS YOU CAN SEE 4974 03:52:22,126 --> 03:52:22,359 HERE. 4975 03:52:22,359 --> 03:52:25,629 IN PARALLEL WE WERE ABLE TO SHOW 4976 03:52:25,629 --> 03:52:29,200 RECOVERY OF THE SUPER COMPLEX 3 4977 03:52:29,200 --> 03:52:31,302 DIMER AND COMPLEX 4 PROTEINS 4978 03:52:31,302 --> 03:52:33,737 WERE INCREASED AGAIN IN THE 4979 03:52:33,737 --> 03:52:36,307 PATIENT S1 CELLS BY THE ADDITION 4980 03:52:36,307 --> 03:52:39,944 OF THE DRUG THE CHEMICAL WHILE 4981 03:52:39,944 --> 03:52:42,146 THE PROTEIN LEVELS OF COMPLEX 4 4982 03:52:42,146 --> 03:52:43,280 WAS UNCHANGED. 4983 03:52:43,280 --> 03:52:44,815 AGAIN THAT SPEAKS TO WHAT I 4984 03:52:44,815 --> 03:52:46,383 SHOWED YOU EARLIER WITH THE 4985 03:52:46,383 --> 03:52:47,818 SPECIFICITY OF THE INTERACTION 4986 03:52:47,818 --> 03:52:51,222 THAT SEEMS TO BE LOCALIZED 4987 03:52:51,222 --> 03:52:52,356 COMPLEX 3 PROTEIN. 4988 03:52:52,356 --> 03:52:55,926 SO BASICALLY JUST TO SUMMARIZE I 4989 03:52:55,926 --> 03:52:58,195 HOPE I'VE SHOWED YOU PATIENT ONE 4990 03:52:58,195 --> 03:53:02,066 ME/CFS HAVE INCREASED EXPRESSION 4991 03:53:02,066 --> 03:53:05,436 OF WAS 3 IN THE SUBSET OF THE 4992 03:53:05,436 --> 03:53:09,707 PATIENT AND WAS 3 MOLECULARLY 4993 03:53:09,707 --> 03:53:12,610 DISRUPTS BY PREVENTING COMPLEX 4994 03:53:12,610 --> 03:53:15,579 FORM AND DISABLIZING COMPLEX 4 4995 03:53:15,579 --> 03:53:19,383 AND INDUCED STRESS AND 4996 03:53:19,383 --> 03:53:20,251 MITOCHONDRIAL DYSFUNCTION 4997 03:53:20,251 --> 03:53:21,151 SUGGESTING A TREATMENT STRATEGY 4998 03:53:21,151 --> 03:53:31,629 WE CAN PURSUE IN THE FUTURE. 4999 03:53:39,536 --> 03:53:42,006 >> WE TALK ABOUT BIO ENERGETICS 5000 03:53:42,006 --> 03:53:43,874 AND HEARD FROM THE DIFFERENT 5001 03:53:43,874 --> 03:53:46,844 ASPECTS BOTH IN THE SCOPE OF THE 5002 03:53:46,844 --> 03:53:47,945 WHOLE BODY AS WELL AS THE LAST 5003 03:53:47,945 --> 03:53:58,389 CASE IN THE MUSCLE CELLS. 5004 03:53:59,723 --> 03:54:02,092 YOU CAN SEE HOW WE TRY TO FIT 5005 03:54:02,092 --> 03:54:03,627 THAT IN THE LAST PART OF THE 5006 03:54:03,627 --> 03:54:03,894 FIGURE. 5007 03:54:03,894 --> 03:54:05,195 THE PERIPHERAL. 5008 03:54:05,195 --> 03:54:07,731 IT'S EVERYTHING WE STUDY IS 5009 03:54:07,731 --> 03:54:09,600 BELOW THE NECK EXCEPT YOU 5010 03:54:09,600 --> 03:54:11,302 BARBARA, YOU STUDY THE BRAIN 5011 03:54:11,302 --> 03:54:11,502 LEVEL. 5012 03:54:11,502 --> 03:54:19,410 AND IT'S REFLECTED IN THE PEM. 5013 03:54:19,410 --> 03:54:21,545 KEY QUESTION ONE IS THERE 5014 03:54:21,545 --> 03:54:23,947 PHENOTYPIC SIGNATURES IN THE 5015 03:54:23,947 --> 03:54:25,716 WHOLE BODY ENERGY BALANCE 5016 03:54:25,716 --> 03:54:27,951 MEASURES COMPARED TO THE HEALTHY 5017 03:54:27,951 --> 03:54:36,593 NORMAL CONTROLS. 5018 03:54:36,593 --> 03:54:39,930 THERE WERE NO DIFFERENCE THESE 5019 03:54:39,930 --> 03:54:42,866 AND A COUPLE OTHERS BUT SLIGHT 5020 03:54:42,866 --> 03:54:47,938 TRENDS IN LESS FIBER AND FOLATE 5021 03:54:47,938 --> 03:54:51,709 AND MORE SATURATED FAT INTAKES. 5022 03:54:51,709 --> 03:54:54,244 THERE WERE NO DETECTABLE 5023 03:54:54,244 --> 03:54:55,579 DIFFERENCES IN THE OUTPUT IN 5024 03:54:55,579 --> 03:54:59,249 TOTAL ENERGY EXPENDITURE IN 5025 03:54:59,249 --> 03:55:00,784 SLEEPING AS WELL AS THE 4:00 5026 03:55:00,784 --> 03:55:06,056 P.M. TO 8:00 A.M. AND OXIDATION 5027 03:55:06,056 --> 03:55:07,524 THERE'S COMPARABLE FATIGUE 5028 03:55:07,524 --> 03:55:11,929 GROUPS AT BASELINE AND AS WELL 5029 03:55:11,929 --> 03:55:13,597 AS AFTER ONE NIGHT AFTER THE 5030 03:55:13,597 --> 03:55:13,897 CPET. 5031 03:55:13,897 --> 03:55:15,733 THEY WENT INTO DETECTABLE 5032 03:55:15,733 --> 03:55:19,536 DIFFERENCE IN BODY COMPOSITION 5033 03:55:19,536 --> 03:55:22,573 AND BONE MASSES. 5034 03:55:22,573 --> 03:55:25,542 THE PATIENTS HAD FREE LIVING 5035 03:55:25,542 --> 03:55:29,380 PHYSICAL ACTIVITY. 5036 03:55:29,380 --> 03:55:31,548 IT CONFIRMS THE SELF-REPORTS AND 5037 03:55:31,548 --> 03:55:37,554 LITERATURE. 5038 03:55:37,554 --> 03:55:42,192 ONE THING THAT STRUCK US MOST 5039 03:55:42,192 --> 03:55:45,028 THERE'S INDIVIDUAL DIFFERENCES. 5040 03:55:45,028 --> 03:55:47,164 PARTICULARLY IN THE CPET TEST 5041 03:55:47,164 --> 03:55:49,433 YOU'VE SEEN IT'S A WIDE VARIETY 5042 03:55:49,433 --> 03:55:51,301 AND THERE ARE SOME COUPLE 5043 03:55:51,301 --> 03:55:52,636 PATIENTS THAT HAD ONE OF THE 5044 03:55:52,636 --> 03:55:58,675 HIGHER OXYGEN CAPACITIES. 5045 03:55:58,675 --> 03:56:01,512 WHEN IT COMES TO QUESTION 2, ARE 5046 03:56:01,512 --> 03:56:03,981 THERE UNIQUE CHANGES AFTER THE 5047 03:56:03,981 --> 03:56:11,488 CPET COMPARED TO THEMSELVES AS 5048 03:56:11,488 --> 03:56:13,557 WELL AS PATIENTS VERSUS CONTROL 5049 03:56:13,557 --> 03:56:16,160 AND NO DETECTABLE DIFFERENCES IN 5050 03:56:16,160 --> 03:56:21,732 THE MECHANICAL DEFICIENCY AND 5051 03:56:21,732 --> 03:56:23,600 MEASURED IN THE CPET PROCESS 5052 03:56:23,600 --> 03:56:27,871 WHETHER THERE'S LOWER PEAK VO2 5053 03:56:27,871 --> 03:56:28,839 ANROBIC THRESHOLD AND HEART RATE 5054 03:56:28,839 --> 03:56:31,542 RESPONSE DURING THE CPET AND NO 5055 03:56:31,542 --> 03:56:34,945 DE TECTABLE DIFFERENCES IN 5056 03:56:34,945 --> 03:56:35,946 SLEEPINESS EXPENDITURE OR 5057 03:56:35,946 --> 03:56:38,649 OXIDATION RATE AFTER THE CPET. 5058 03:56:38,649 --> 03:56:40,217 AGAIN, THERE WAS CONSIDERABLE 5059 03:56:40,217 --> 03:56:42,619 BETWEEN INDIVIDUAL DIFFERENCES 5060 03:56:42,619 --> 03:56:48,258 IN THE CPET AND PM PATTERNS. 5061 03:56:48,258 --> 03:56:51,862 SO OUR INTERPRETATION IS THE 5062 03:56:51,862 --> 03:56:54,698 PATIENTS WITH PI ME/CFS HAVE A 5063 03:56:54,698 --> 03:57:00,838 WIDE RANGE OF BIOENERGETIC 5064 03:57:00,838 --> 03:57:03,674 CAPACITIES WE CAN'T ASSESS THEM 5065 03:57:03,674 --> 03:57:05,375 BEFORE THE DISEASE AND CAN'T 5066 03:57:05,375 --> 03:57:08,712 TEASE OUT THE CAUSE AND WHILE 5067 03:57:08,712 --> 03:57:10,113 THE ENERGY BALANCE IS PRESERVED 5068 03:57:10,113 --> 03:57:17,721 AT TESTING IT REDUCED PEAK 5069 03:57:17,721 --> 03:57:19,756 CAPACITY SKELETAL MITOCHONDRIAL 5070 03:57:19,756 --> 03:57:23,927 DYSFUNCTION ARE EVIDENT AT LEAST 5071 03:57:23,927 --> 03:57:28,732 IN SOME PATIENTS. 5072 03:57:28,732 --> 03:57:30,567 LET ME ASK THE PANEL BACK DOWN. 5073 03:57:30,567 --> 03:57:32,736 IF YOU HAVE QUESTIONS 5074 03:57:32,736 --> 03:57:35,939 SPECIFICALLY TO THESE AREAS 5075 03:57:35,939 --> 03:57:46,450 WE'LL BE HAPPY IT ANSWER THEM. 5076 03:58:11,441 --> 03:58:19,049 >> JOE LANCET I'LL A PATIENT. 5077 03:58:19,049 --> 03:58:23,954 WHAT WOULD A VALIDATED MEASURE 5078 03:58:23,954 --> 03:58:26,723 FOR POST EXERCISAL MALAISE LOOK 5079 03:58:26,723 --> 03:58:29,626 LIKE AND WHY DOES THE CPET FOT 5080 03:58:29,626 --> 03:58:31,929 QUALIFY AS A MEASURE AS IT'S 5081 03:58:31,929 --> 03:58:32,529 CURRENTLY BEING USED FOR 5082 03:58:32,529 --> 03:58:35,933 DISABILITY EVALUATIONS. 5083 03:58:35,933 --> 03:58:46,109 THANK YOU. 5084 03:58:47,544 --> 03:58:49,646 >> THERE WERE NO VALIDATED 5085 03:58:49,646 --> 03:58:51,582 MEASURES AND NOW THERE'S 5086 03:58:51,582 --> 03:58:52,616 QUESTIONNAIRES TO ASSESS PEM BUT 5087 03:58:52,616 --> 03:58:54,885 TO MY KNOWLEDGE NO VALIDATED 5088 03:58:54,885 --> 03:58:56,720 MEASURES TO ASSESS AT POINT IN 5089 03:58:56,720 --> 03:58:59,289 TIME BEFORE AND AFTER CPET. 5090 03:58:59,289 --> 03:59:01,625 THERE'S THE VAS SCALES USED 5091 03:59:01,625 --> 03:59:03,961 TRADITIONALLY BUT HAVE NOT BEEN 5092 03:59:03,961 --> 03:59:05,862 VALIDATED FOR THAT PURPOSE BUT 5093 03:59:05,862 --> 03:59:07,264 I'LL LET DR. WALITT HAND THAT 5094 03:59:07,264 --> 03:59:07,698 WILL. 5095 03:59:07,698 --> 03:59:10,534 >> THE QUESTIONNAIRE WAS VOL 5096 03:59:10,534 --> 03:59:14,938 DATED AS AN INSTRUMENT TO 5097 03:59:14,938 --> 03:59:15,973 MEASURE THE POLL QUESTIONNAIRE 5098 03:59:15,973 --> 03:59:20,978 WAS VALIDATED EDD AS AN INSTRU 5099 03:59:20,978 --> 03:59:25,182 TO MEASURE IN A PERSON AFTER 5100 03:59:25,182 --> 03:59:25,616 STARTED. 5101 03:59:25,616 --> 03:59:27,985 THERE WASN'T ANY INSTRUMENTS 5102 03:59:27,985 --> 03:59:33,991 WHILE THEY WERE STARTING. 5103 03:59:33,991 --> 03:59:36,693 THAT WOULD BE THE GO TO AND USED 5104 03:59:36,693 --> 03:59:37,794 IN LONG COVID RESEARCH AS A 5105 03:59:37,794 --> 03:59:41,698 MEASURE OF PEM. 5106 03:59:41,698 --> 03:59:52,242 IN TERM OF THE TWO-DAY CPET IT'S 5107 03:59:55,112 --> 03:59:55,646 MEASURING FURTHER DELAYED 5108 03:59:55,646 --> 03:59:57,314 RESPONSE TO EXERCISE SOMEBODY 5109 03:59:57,314 --> 03:59:57,581 FEELS. 5110 03:59:57,581 --> 04:00:01,151 WHAT MIGHT BE PHYSIOLOGICAL 5111 04:00:01,151 --> 04:00:03,020 MEASUREMENTS ISN'T CAPTURING 5112 04:00:03,020 --> 04:00:05,255 WHAT THE EXPERIENCE OF POST 5113 04:00:05,255 --> 04:00:08,525 EXERTIONAL MALAISE IS AND IT'S 5114 04:00:08,525 --> 04:00:13,830 NOT A MEASURE OF PEM BUT CARD 5115 04:00:13,830 --> 04:00:18,769 YEAR OVER YEAR -- 5116 04:00:18,769 --> 04:00:19,369 CARDIORESPIRATORY PERFORMANCE. 5117 04:00:19,369 --> 04:00:22,739 >> ISN'T IT TRUE AFTER THE FIRST 5118 04:00:22,739 --> 04:00:26,209 CPET THESE PATIENTS ARE PRETTY 5119 04:00:26,209 --> 04:00:26,476 EXHAUSTED. 5120 04:00:26,476 --> 04:00:34,418 A SECOND DAY WOULD HAVE BEEN -- 5121 04:00:34,418 --> 04:00:36,286 >> WITH BARBARA'S INSTRUMENT 5122 04:00:36,286 --> 04:00:39,423 EVERYBODY HAD PEM AFTER ONE DAY 5123 04:00:39,423 --> 04:00:41,958 AND TWO OF DAY CPET WASN'T 5124 04:00:41,958 --> 04:00:43,260 NECESSARY TO PUT THEM -- 5125 04:00:43,260 --> 04:00:47,931 >> WOULD END UP HURTING THEM. 5126 04:00:47,931 --> 04:00:55,472 >> WE COULD HAVE. 5127 04:00:55,472 --> 04:00:59,176 >> HAVE THE FINDINGS OF WAS 3 5128 04:00:59,176 --> 04:01:03,480 AND MITOCHONDRIAL DYSFUNCTION 5129 04:01:03,480 --> 04:01:05,682 BEEN SEEN IN FIBROMYALGIA 5130 04:01:05,682 --> 04:01:07,951 PATIENT. 5131 04:01:07,951 --> 04:01:18,261 >> GREAT QUESTION. 5132 04:01:23,300 --> 04:01:25,902 FIBROMYALGIA WOULD BE GREAT TO 5133 04:01:25,902 --> 04:01:29,072 LOOK AT IN THE RUMATO LOGIC 5134 04:01:29,072 --> 04:01:30,741 DISCOVEREDS AND THEY'RE GREAT 5135 04:01:30,741 --> 04:01:32,609 THINGS TO DO AND HOPE OTHERS 5136 04:01:32,609 --> 04:01:34,177 THAT WILL HAVE READ OUR PAPER 5137 04:01:34,177 --> 04:01:39,850 THAT WILL ALSO DO THESE STUDIES. 5138 04:01:39,850 --> 04:01:42,586 >> WHAT DO THEY TELL US ABOUT 5139 04:01:42,586 --> 04:01:50,527 THE LOWERING OF ANAEROBIC 5140 04:01:50,527 --> 04:01:51,394 MEASURES IN THE SECOND DAY OF 5141 04:01:51,394 --> 04:01:52,963 THE TEST. 5142 04:01:52,963 --> 04:01:53,964 >> REPEAT THE QUESTION. 5143 04:01:53,964 --> 04:01:55,098 ON THE SECOND DAY OF CPET? 5144 04:01:55,098 --> 04:01:59,770 >> YEAH, WHAT DO THE 5145 04:01:59,770 --> 04:02:01,938 BIOENERGETIC STUDIES ABOUT THE 5146 04:02:01,938 --> 04:02:03,774 LOWERING OF THE ANAEROBIC 5147 04:02:03,774 --> 04:02:05,609 STUDIES OF THE SECOND DAY. 5148 04:02:05,609 --> 04:02:10,747 >> WE DIDN'T DO A SECOND DAY 5149 04:02:10,747 --> 04:02:11,014 CPET. 5150 04:02:11,014 --> 04:02:12,215 IT WOULD BE HARD TO SPECULATE 5151 04:02:12,215 --> 04:02:14,417 WHAT IS RELATED. 5152 04:02:14,417 --> 04:02:24,661 >> THANK YOU. 5153 04:02:25,295 --> 04:02:27,931 >> I WONDER IF YOU CAN COMMENT 5154 04:02:27,931 --> 04:02:32,335 ON CHRONOTROPIC INCONTINENCE. 5155 04:02:32,335 --> 04:02:35,038 THERE'S ONE OTHER ELEMENT I 5156 04:02:35,038 --> 04:02:36,873 WONDER IF WE HAVE EXPLANATION 5157 04:02:36,873 --> 04:02:37,974 FOR. 5158 04:02:37,974 --> 04:02:42,179 >> LISA. 5159 04:02:42,179 --> 04:02:43,947 >> FROM THE MEASUREMENTS FROM 5160 04:02:43,947 --> 04:02:46,817 THE HEART RATE AND WE WERE 5161 04:02:46,817 --> 04:02:51,922 LOOKING BASED ON THE AGE 5162 04:02:51,922 --> 04:02:53,790 PREDICTED HEART RATE PRESERVE 5163 04:02:53,790 --> 04:02:55,926 AND FIVE OF THE EIGHT SHOWED 5164 04:02:55,926 --> 04:02:58,929 THEY HAD MET THE CRITERIA AND 5165 04:02:58,929 --> 04:03:01,031 WHEN WE LOOKED ACROSS THE 5166 04:03:01,031 --> 04:03:02,032 EXERCISE DURATION OR DURING 5167 04:03:02,032 --> 04:03:05,735 EXERCISE TESTS WE COULD SEE 5168 04:03:05,735 --> 04:03:07,604 THOSE SLOPES WERE LOWERED. 5169 04:03:07,604 --> 04:03:09,539 THERE'S A LOWER HEART LATE 5170 04:03:09,539 --> 04:03:11,942 RESPONSE ACROSS THE DIFFERENT 5171 04:03:11,942 --> 04:03:15,712 WORK RATES IN ME/CFS VERSUS THE 5172 04:03:15,712 --> 04:03:17,214 HEALTHY VOLUNTEERS. 5173 04:03:17,214 --> 04:03:20,584 SO WHETHER THIS IS RELATED BACK 5174 04:03:20,584 --> 04:03:23,253 TO SOME OF THE AUTONOMIC 5175 04:03:23,253 --> 04:03:25,088 DYSFUNCTION COULD BE RELATED BUT 5176 04:03:25,088 --> 04:03:26,656 THAT'S WHAT WE'RE FINDING. 5177 04:03:26,656 --> 04:03:28,658 >> THE FINDING IS CLEAR. 5178 04:03:28,658 --> 04:03:31,928 I WONDER WHAT THE EXPLANATION 5179 04:03:31,928 --> 04:03:37,500 IS. 5180 04:03:37,500 --> 04:03:47,978 >> WHERE DOES IT COME FROM? 5181 04:03:55,919 --> 04:04:06,396 >> IT'S THOUGHT TO BE A DISA 5182 04:04:07,998 --> 04:04:08,565 DISAUT 5183 04:04:08,565 --> 04:04:18,475 DISAUTONOMIA ISN'T KICKING IN. 5184 04:04:18,475 --> 04:04:18,742 [OFF-MIC] 5185 04:04:18,742 --> 04:04:21,745 >> DO YOU WANT TO COME TO THE 5186 04:04:21,745 --> 04:04:22,045 MICROPHONE? 5187 04:04:22,045 --> 04:04:24,047 THIS IS WHY WE HAVE A WHOLE TEAM 5188 04:04:24,047 --> 04:04:30,520 OF PEOPLE HERE. 5189 04:04:30,520 --> 04:04:33,924 >> THERE IS A SYSTEMATIC 5190 04:04:33,924 --> 04:04:40,430 APPROACH TO CHRONOTROPIC 5191 04:04:40,430 --> 04:04:44,334 INCONTINENCE AND BOILS DOWN TO 5192 04:04:44,334 --> 04:04:51,141 DOSE RESPONSE WITH ISOPREL AND 5193 04:04:51,141 --> 04:04:54,711 THERE'S A CATECHOLAMINE AND YOU 5194 04:04:54,711 --> 04:04:56,279 CAN MEASURE THE INCREASE IN 5195 04:04:56,279 --> 04:05:02,953 HEART RATE FOR A GIVEN LEVEL AND 5196 04:05:02,953 --> 04:05:06,323 MORE IMPORTANTLY, THERE'S A 5197 04:05:06,323 --> 04:05:11,628 RELEASE OF NOREPINEPHRINE BY 5198 04:05:11,628 --> 04:05:15,932 STIMULATING VEGA2 RECEPTORS. 5199 04:05:15,932 --> 04:05:19,602 BY MEASURING THE RESPONSE TO 5200 04:05:19,602 --> 04:05:22,973 ISOPREL YOU CAN PINPOINT THE 5201 04:05:22,973 --> 04:05:25,809 BASIS FOR CHRONOTROPIC 5202 04:05:25,809 --> 04:05:27,944 INCONTINENCE FROM THE BASAL 5203 04:05:27,944 --> 04:05:28,712 RECEPTOR MEDIATED PROCESSES. 5204 04:05:28,712 --> 04:05:33,516 >> WHEN YOU SAY THE FINDINGS 5205 04:05:33,516 --> 04:05:35,919 DECREASE NOR EPINEPHRINE COULD 5206 04:05:35,919 --> 04:05:38,421 BE RELATED TO WHY WE'RE SEEING 5207 04:05:38,421 --> 04:05:41,224 CHRONOTROPIC INCOMPETENCE IN THE 5208 04:05:41,224 --> 04:05:42,025 INDIVIDUALS? 5209 04:05:42,025 --> 04:05:48,865 >> IT'S A MISSTATEMENT. 5210 04:05:48,865 --> 04:05:50,467 WHAT WE FOUND WAS THE SPINAL 5211 04:05:50,467 --> 04:05:56,373 FLUID, QUITE INDEPENDENT OF THE 5212 04:05:56,373 --> 04:05:58,675 NOREPINEPHRINE IN THE PLASMA AS 5213 04:05:58,675 --> 04:06:02,278 A MEASURE OF SYMPATHETIC 5214 04:06:02,278 --> 04:06:02,979 OUTFLOW. 5215 04:06:02,979 --> 04:06:05,015 IT'S A POWERFUL BLOOD BRAIN 5216 04:06:05,015 --> 04:06:10,220 BARRIER FOR CATECHOLAMINE. 5217 04:06:10,220 --> 04:06:11,955 YOU SEE VERY INDIRECTLY RELATED 5218 04:06:11,955 --> 04:06:13,656 OR NOT RELATED AT ALL TO WHAT 5219 04:06:13,656 --> 04:06:18,628 YOU SEE IN THE PERIPHERY. 5220 04:06:18,628 --> 04:06:21,765 WHAT WE FOUND IN THE PERIPHERY 5221 04:06:21,765 --> 04:06:29,272 WAS NOREPINEPHRINE WAS NORMAL. 5222 04:06:29,272 --> 04:06:31,341 IT'S SUPPOSED TO INCREASE WHEN 5223 04:06:31,341 --> 04:06:35,245 TILTED AND DID INCREASE AND 5224 04:06:35,245 --> 04:06:39,215 INCREASED NORMALLY IN THE ME/CFS 5225 04:06:39,215 --> 04:06:40,383 GROUP. 5226 04:06:40,383 --> 04:06:43,720 THERE'S THE DATA ABOUT S 5227 04:06:43,720 --> 04:06:51,494 SYMPATHETIC RESPONSES IN THE 5228 04:06:51,494 --> 04:07:01,037 STUDY ARE SAY INCONSISTENT AND 5229 04:07:01,037 --> 04:07:02,906 DIDN'T SEE A PROBLEM IN THE 5230 04:07:02,906 --> 04:07:03,139 STUDY. 5231 04:07:03,139 --> 04:07:06,576 >> HOW ABOUT THE INCREASED 5232 04:07:06,576 --> 04:07:09,846 EPINEPHRINE LEVELS IN SOME 5233 04:07:09,846 --> 04:07:11,981 PARTICIPANTS? 5234 04:07:11,981 --> 04:07:14,918 >> AS I SHOWED IN MY SLIDE AND 5235 04:07:14,918 --> 04:07:19,956 YOU GET THE CATECHOLAMINES 5236 04:07:19,956 --> 04:07:23,359 PUMPING IT'S NOT ALL TRUE. 5237 04:07:23,359 --> 04:07:26,496 ESPECIALLY IN FAINTING REACTION 5238 04:07:26,496 --> 04:07:31,968 AND IT INVOKED HYPOTENSION 5239 04:07:31,968 --> 04:07:33,703 THERE'S A DISASSOCIATION BETWEEN 5240 04:07:33,703 --> 04:07:39,809 WHAT HAPPENS TO NOREPINEPHRINE. 5241 04:07:39,809 --> 04:07:42,178 IF YOU REMEMBER THE INDIVIDUAL 5242 04:07:42,178 --> 04:07:42,645 SPAGHETTI PLOTS. 5243 04:07:42,645 --> 04:07:49,652 NOT OVER ALL IN THE GROUP. 5244 04:07:49,652 --> 04:07:51,955 YOU HAVE TO KEEP IN MIND THE 5245 04:07:51,955 --> 04:07:57,760 SYSTEM NOT ONE THING. 5246 04:07:57,760 --> 04:08:02,866 >> NOT SURE THAT ANSWERED YOUR 5247 04:08:02,866 --> 04:08:03,566 QUESTION. 5248 04:08:03,566 --> 04:08:05,435 MARK'S ASKING A CRITICAL 5249 04:08:05,435 --> 04:08:07,170 QUESTION AND LET ME ASK BY 5250 04:08:07,170 --> 04:08:11,975 BRIAN'S EARLIER REMARKS THIS IS 5251 04:08:11,975 --> 04:08:14,644 A HYPOTHESIS GENERATING STUDY 5252 04:08:14,644 --> 04:08:17,947 AND GET TO MECHANISM OF SKELETAL 5253 04:08:17,947 --> 04:08:19,949 MUSCLES. 5254 04:08:19,949 --> 04:08:25,355 WE'RE JUST GETTING STARTED. 5255 04:08:25,355 --> 04:08:29,159 WITH SAW EARLIER THE OMICS 5256 04:08:29,159 --> 04:08:34,030 ANALYSIS AND CLEAR 5257 04:08:34,030 --> 04:08:35,598 DIFFERENTIATION BETWEEN GENDERS 5258 04:08:35,598 --> 04:08:36,733 DID YOU SEE THAT WITH YOUR 5259 04:08:36,733 --> 04:08:36,966 RESULTS? 5260 04:08:36,966 --> 04:08:43,773 >> WE HAD A MIX OF SAMPLES. 5261 04:08:43,773 --> 04:08:47,243 WE DIDN'T REALLY SEE A GOOD 5262 04:08:47,243 --> 04:08:47,677 CORRELATION. 5263 04:08:47,677 --> 04:08:50,413 WE LOOKED AT 14 INDIVIDUAL 5264 04:08:50,413 --> 04:08:50,780 SAMPLES. 5265 04:08:50,780 --> 04:08:51,948 PROBABLY MORE WOMEN SAMPLES THAN 5266 04:08:51,948 --> 04:08:56,619 MEN. 5267 04:08:56,619 --> 04:08:58,922 WE DIDN'T SEE A CLEAR 5268 04:08:58,922 --> 04:09:00,657 CORRELATION AND SPECTRUM OF 5269 04:09:00,657 --> 04:09:02,725 LEVELS. 5270 04:09:02,725 --> 04:09:08,431 CAN'T COMMENT ON THAT. 5271 04:09:08,431 --> 04:09:10,567 >> I BELIEVE WE'RE RUNNING OUT 5272 04:09:10,567 --> 04:09:14,971 OF TIME. 5273 04:09:14,971 --> 04:09:19,809 THERE'S ANY OTHER QUESTIONS 5274 04:09:19,809 --> 04:09:21,511 WE'LL BE ABLE TO ADDRESS THEM 5275 04:09:21,511 --> 04:09:22,645 OVER E-MAILS. 5276 04:09:22,645 --> 04:09:24,380 >> I'M A PATIENT. 5277 04:09:24,380 --> 04:09:29,919 ANY GUESSES, DR. H WANG ON 5278 04:09:29,919 --> 04:09:31,988 WHAT'S CAUSING THE ENDO 5279 04:09:31,988 --> 04:09:34,057 RETICULUM STRESS IN THE 5280 04:09:34,057 --> 04:09:35,959 MITOCHONDRIAL DYSFUNCTION? 5281 04:09:35,959 --> 04:09:45,835 >> GREAT QUESTION. 5282 04:09:45,835 --> 04:09:50,873 THE FIBROBLAST HAS NOTHING TO 5283 04:09:50,873 --> 04:09:55,979 BIG DO WITH MUSCLE COMPARED TO 5284 04:09:55,979 --> 04:09:59,949 THE BROADER SIBLING. 5285 04:09:59,949 --> 04:10:02,819 IF I WAS TO SPECULATE THE STRESS 5286 04:10:02,819 --> 04:10:08,891 IS A RESPONSE OF NORMAL PROTEIN 5287 04:10:08,891 --> 04:10:14,130 HOMEOSTASIS AND YOU SEE WITH 5288 04:10:14,130 --> 04:10:16,966 INFECTIONS AND VIRAL INFECTIONS 5289 04:10:16,966 --> 04:10:20,903 THE VERY WELL TRIES TO SHE SUT 5290 04:10:20,903 --> 04:10:23,273 DOWN PRODUCTION OF VIRAL 5291 04:10:23,273 --> 04:10:26,075 PROTEINS AND ME/CFS IS 5292 04:10:26,075 --> 04:10:28,678 ASSOCIATED WITH A 5293 04:10:28,678 --> 04:10:31,748 POST-INFECTIOUS STATE AND IF I 5294 04:10:31,748 --> 04:10:37,320 CAN SPECULATE ABNORMAL 5295 04:10:37,320 --> 04:10:42,525 ACTIVATION AND IT WOULD BE GREAT 5296 04:10:42,525 --> 04:10:53,036 TO HAVE EXPERTS IN THE FIELD. 5297 04:10:56,039 --> 04:11:06,215 GOOD QUESTION. 5298 04:11:18,761 --> 04:11:20,029 >> I'LL TALK ABOUT DATA SHARING 5299 04:11:20,029 --> 04:11:27,704 AND ONGOING WORK TO COME. 5300 04:11:27,704 --> 04:11:30,506 ONE OF THE MOST IMPORTANT THINGS 5301 04:11:30,506 --> 04:11:35,044 WE CAN DO IS FOLLOW THE TENETS 5302 04:11:35,044 --> 04:11:36,879 OF OPEN SCIENCE AT THE 5303 04:11:36,879 --> 04:11:37,513 RECOMMENDATIONS OF OPEN SCIENCE 5304 04:11:37,513 --> 04:11:44,721 ARE HERE FOR YOU. 5305 04:11:44,721 --> 04:11:47,857 TRYING TO MAKE IT OPEN AND 5306 04:11:47,857 --> 04:11:51,060 INCLUSIVE TO PEOPLE WITHOUT SIDE 5307 04:11:51,060 --> 04:11:55,665 OF TRADITIONAL SCIENCE. 5308 04:11:55,665 --> 04:11:57,066 IT'S TO MAKE IT. 5309 04:11:57,066 --> 04:11:59,235 LY AVAILABLE AND USABLE TO 5310 04:11:59,235 --> 04:11:59,969 INCREASE SCIENTIFIC 5311 04:11:59,969 --> 04:12:01,104 COLLABORATIONS AND SHARING OF 5312 04:12:01,104 --> 04:12:03,072 INFORMATION FOR THE BENEFIT OF 5313 04:12:03,072 --> 04:12:05,608 ALL AND OPEN THE PROFESSOR OF 5314 04:12:05,608 --> 04:12:06,509 SCIENTIFIC KNOWLEDGE CREATION TO 5315 04:12:06,509 --> 04:12:07,977 EVERYBODY THAT'S INTERESTED IN 5316 04:12:07,977 --> 04:12:13,316 BEING INVOLVED. 5317 04:12:13,316 --> 04:12:16,586 THERE ARE FIVE TENETS OF OPEN 5318 04:12:16,586 --> 04:12:17,587 SCIENTIFIC KNOWLEDGE AND I'LL 5319 04:12:17,587 --> 04:12:19,956 TALK ABOUT THE ONES APPLIED TO 5320 04:12:19,956 --> 04:12:20,823 US. 5321 04:12:20,823 --> 04:12:23,993 THE FIRST BEING MAKE SCIENTIFIC 5322 04:12:23,993 --> 04:12:27,964 PUBLICATIONS AVAILABLE TO ALL. 5323 04:12:27,964 --> 04:12:29,565 MANY DON'T REALIZE THAT IT COSTS 5324 04:12:29,565 --> 04:12:33,102 A LOT OF MONEY TO MAKE A 5325 04:12:33,102 --> 04:12:35,638 SCIENTIFIC PUBLICATION WIDELY 5326 04:12:35,638 --> 04:12:36,239 AVAILABLE. 5327 04:12:36,239 --> 04:12:38,474 YOU HAVE TO BE PART OF A 5328 04:12:38,474 --> 04:12:39,942 UNIVERSITY OR HAVE A FRIEND TO 5329 04:12:39,942 --> 04:12:43,446 GET YOU A COPY OR PDF THERE 5330 04:12:43,446 --> 04:12:44,447 ANOTHER FRIEND. 5331 04:12:44,447 --> 04:12:45,281 THIS GETS IN THE WAY OF SHARING 5332 04:12:45,281 --> 04:12:50,720 OF INFORMATION. 5333 04:12:50,720 --> 04:12:53,990 WE UNDERSTOOD THAT AND MADE SURE 5334 04:12:53,990 --> 04:12:56,526 OUR PUBLICATION IS PUBLICALLY 5335 04:12:56,526 --> 04:12:58,394 AVAILABLE AND CAN GOOGLE NATURE 5336 04:12:58,394 --> 04:12:59,996 AND WALITT AND GET THE WHOLE 5337 04:12:59,996 --> 04:13:05,234 ARTICLE THAT EASILY. 5338 04:13:05,234 --> 04:13:10,907 SECOND IS TO OPEN DATA TO 5339 04:13:10,907 --> 04:13:11,240 EVERYBODY. 5340 04:13:11,240 --> 04:13:13,309 WE BENT OVER BACKWARDS TO MAKE 5341 04:13:13,309 --> 04:13:15,044 SURE OUR DATA IS AVAILABLE AND 5342 04:13:15,044 --> 04:13:16,212 THIS IS THE STATEMENT IN THE 5343 04:13:16,212 --> 04:13:18,881 PAPER ITSELF WHICH IS MULTIPLE 5344 04:13:18,881 --> 04:13:22,018 PARAGRAPHS I'LL MAKE EASIER BY 5345 04:13:22,018 --> 04:13:22,985 TALKING ABOUT THE CONTENTS ARE 5346 04:13:22,985 --> 04:13:24,987 AND WHERE TO FIND OUR DATA. 5347 04:13:24,987 --> 04:13:32,428 ALL OUR DATA IS CCBY4.0 THROUGH 5348 04:13:32,428 --> 04:13:33,229 CREATIVE COMMONS. 5349 04:13:33,229 --> 04:13:35,965 IT SAYS WHEN YOU SHARE DATA HOW 5350 04:13:35,965 --> 04:13:37,667 ARE OTHER PEOPLE ALLOWED TO USE 5351 04:13:37,667 --> 04:13:39,669 IT AND WHAT YOU NEED TO DO. 5352 04:13:39,669 --> 04:13:41,370 WITH OUR DATA EVERYONE IS FREE 5353 04:13:41,370 --> 04:13:44,474 IT SHARE IT, COPY IT, 5354 04:13:44,474 --> 04:13:47,043 REDISTRIBUTE THE MATERIAL ANYWAY 5355 04:13:47,043 --> 04:13:48,177 YOU WANT. 5356 04:13:48,177 --> 04:13:50,880 IF YOU CAN FIND COMMERCIAL 5357 04:13:50,880 --> 04:13:51,848 VALUE, HAVE FUN. 5358 04:13:51,848 --> 04:13:54,183 YOU CAN ADAPT THE DATA AND BUILD 5359 04:13:54,183 --> 04:13:55,952 ON IT EVEN IF YOU'RE LOOKING TO 5360 04:13:55,952 --> 04:13:56,586 MAKE COMMERCIAL SUCCESS THROUGH 5361 04:13:56,586 --> 04:13:59,722 THAT. 5362 04:13:59,722 --> 04:14:02,692 WE WON'T REVOKE THOSE FREEDOMS. 5363 04:14:02,692 --> 04:14:05,261 ONLY THING WE SKIN RETURN IS YOU 5364 04:14:05,261 --> 04:14:07,497 ATTRIBUTE US AS THE SOURCE OF 5365 04:14:07,497 --> 04:14:07,697 DATA. 5366 04:14:07,697 --> 04:14:10,466 IF YOU'RE GOING TO USE OUR DATA 5367 04:14:10,466 --> 04:14:11,634 JUST GIVE APPROPRIATE DATA WHERE 5368 04:14:11,634 --> 04:14:15,338 THE DATA CAME FROM. 5369 04:14:15,338 --> 04:14:19,876 OUR DATA IS MAINLY PLACED IN A 5370 04:14:19,876 --> 04:14:23,980 NEW DATABASE DEVELOPED BY NINDS 5371 04:14:23,980 --> 04:14:32,955 FOR ME/CFS RESEARCH. 5372 04:14:32,955 --> 04:14:35,958 THOUGHTS OF DIFFERENT GROUPS ARE 5373 04:14:35,958 --> 04:14:37,260 STARTING TO USE THE SECURE DATA 5374 04:14:37,260 --> 04:14:42,632 PLATFORM AND THERE'S TOOLS 5375 04:14:42,632 --> 04:14:44,200 EMBEDDED IN THE PLATFORM AND OUR 5376 04:14:44,200 --> 04:14:51,040 DATA SETS CAN BE FOUND HERE. 5377 04:14:51,040 --> 04:14:55,011 WHAT WE DID IS RECODED OUR CODED 5378 04:14:55,011 --> 04:14:57,480 DATA TO USE THE DATA IDENTITIES. 5379 04:14:57,480 --> 04:14:59,949 ALL THE DATA IDENTITIES AND THE 5380 04:14:59,949 --> 04:15:02,118 DATA SETS ARE THE SAME. 5381 04:15:02,118 --> 04:15:04,020 IF ONE WANTED TO LOOK AT THE 5382 04:15:04,020 --> 04:15:07,356 CORRELATION BETWEEN ANXIETY AND 5383 04:15:07,356 --> 04:15:08,090 NOREPINEPHRINE YOU CAN TAKE BOTH 5384 04:15:08,090 --> 04:15:10,526 DATA SETS AND DO IT ON YOUR OWN. 5385 04:15:10,526 --> 04:15:12,628 YOU DON'T NEED TO WORK THROUGH 5386 04:15:12,628 --> 04:15:14,630 US TO DO THAT. 5387 04:15:14,630 --> 04:15:17,066 WE'LL TRY TO USE THE I.D.s 5388 04:15:17,066 --> 04:15:20,036 ACROSS OUR DATA SETS EVEN ON 5389 04:15:20,036 --> 04:15:21,437 OTHER PLATFORMS. 5390 04:15:21,437 --> 04:15:22,838 IF YOU'RE INTERESTED IN LEARNING 5391 04:15:22,838 --> 04:15:23,973 MORE HERE'S THE E-MAIL AND 5392 04:15:23,973 --> 04:15:27,276 WEBSITE FOUR. 5393 04:15:27,276 --> 04:15:28,010 -- FOR YOU. 5394 04:15:28,010 --> 04:15:31,314 OUR RAW DATA IS STORED IN 5395 04:15:31,314 --> 04:15:35,518 CLASSIC RAW DATA ARCHIVES AND 5396 04:15:35,518 --> 04:15:37,119 SEQUENCE READS ARE IN SEQUENCE 5397 04:15:37,119 --> 04:15:39,121 READ ARCHIVE AND METABOLOMICS 5398 04:15:39,121 --> 04:15:41,991 DATA IS AT THE METABOLOMICS WORK 5399 04:15:41,991 --> 04:15:43,793 BENCH AND HERE'S THE INFORMATION 5400 04:15:43,793 --> 04:15:52,368 IF SOMEONE WANTS TO SEE THEM. 5401 04:15:52,368 --> 04:15:57,173 fMRI AND OTHER DATA CAN BE FOUND 5402 04:15:57,173 --> 04:16:00,443 IN THE NEWER ARCHIVE FUNDED BY 5403 04:16:00,443 --> 04:16:02,712 NINDS. 5404 04:16:02,712 --> 04:16:04,413 IT'S DEVELOPED TO HOST THIS 5405 04:16:04,413 --> 04:16:05,114 COMPLICATED TYPES OF DATA SETS. 5406 04:16:05,114 --> 04:16:07,550 IF YOU WANT TO LOOK AT OUR MRI 5407 04:16:07,550 --> 04:16:13,356 DATA THIS IS WHERE YOU WOULD GO. 5408 04:16:13,356 --> 04:16:16,492 COMING SOON WE'LL HAVE OUR EEG 5409 04:16:16,492 --> 04:16:21,631 DATA AND ACTIGRAPHY DATA IN THE 5410 04:16:21,631 --> 04:16:23,032 RESOURCE PICTURED HERE. 5411 04:16:23,032 --> 04:16:27,737 THE NSRR HOSTS A LOT OF 5412 04:16:27,737 --> 04:16:38,114 DIFFERENT POLYSOME -- 5413 04:16:48,424 --> 04:16:49,625 POLYSOMNOGRAM DATA AND I'D LIKE 5414 04:16:49,625 --> 04:16:54,463 TO TAKE A MOMENT TO THANK SAM 5415 04:16:54,463 --> 04:16:55,965 BECAUSE HE REALLY PUT EFFORT 5416 04:16:55,965 --> 04:16:57,466 REQUIRED TO GET OUR CODE 5417 04:16:57,466 --> 04:16:59,035 TOGETHER AND TO REANALYZE OUR 5418 04:16:59,035 --> 04:16:59,969 DATA TO MAKE SURE EVERYTHING WAS 5419 04:16:59,969 --> 04:17:03,606 VALID. 5420 04:17:03,606 --> 04:17:06,709 THE DATA USED IN OUR PAPER, EACH 5421 04:17:06,709 --> 04:17:08,678 OF THE FIGURES HAS ITS OWN DATA 5422 04:17:08,678 --> 04:17:10,980 FILE TO BE KERRIED. 5423 04:17:10,980 --> 04:17:12,815 -- QUERIED. 5424 04:17:12,815 --> 04:17:14,784 EACH TABLE HAS ITS OWN DATA FILE 5425 04:17:14,784 --> 04:17:15,217 TO BE QUERY. 5426 04:17:15,217 --> 04:17:16,552 YOU CAN TWO BACK AND SEE IF YOU 5427 04:17:16,552 --> 04:17:19,922 CAN PRODUCE ALL THE DATA AND THE 5428 04:17:19,922 --> 04:17:23,626 DATA FILES ARE LINKED TO THE 5429 04:17:23,626 --> 04:17:25,194 PAPER ITSELF. 5430 04:17:25,194 --> 04:17:29,899 THE GITHUB REPOSITORY YOU'LL 5431 04:17:29,899 --> 04:17:31,967 FIND THE DIFFERENT CODES IN THE 5432 04:17:31,967 --> 04:17:42,078 PAPER. 5433 04:17:52,988 --> 04:17:55,624 AND YOU CAN SEE THE CODE WITHIN 5434 04:17:55,624 --> 04:17:57,159 OUR REPOSITORY IN AN EFFORT TO 5435 04:17:57,159 --> 04:17:59,028 TRY TO MAKE IT TOTALLY 5436 04:17:59,028 --> 04:17:59,662 UNDERSTANDABLE HOW WE CAME TO 5437 04:17:59,662 --> 04:18:03,332 THESE CONCLUSIONS. 5438 04:18:03,332 --> 04:18:05,301 I'LL TAKE A MOMENT TO TALK ABOUT 5439 04:18:05,301 --> 04:18:06,569 VALUE ADDED. 5440 04:18:06,569 --> 04:18:09,405 YOU SEE THE FIRST BROAD PATHS OF 5441 04:18:09,405 --> 04:18:10,573 ALL THE DATA. 5442 04:18:10,573 --> 04:18:13,843 THE BIG FIRST PAPER BUT IT 5443 04:18:13,843 --> 04:18:17,079 DOESN'T MEAN THERE CAN'T BE MORE 5444 04:18:17,079 --> 04:18:18,514 EFFORTS OF THINGS HAPPENING. 5445 04:18:18,514 --> 04:18:21,350 THERE WERE PAPER CAME ABOUT AS 5446 04:18:21,350 --> 04:18:23,619 WE WERE TRYING TO GET THE PAPER 5447 04:18:23,619 --> 04:18:25,221 OUT THE DOOR. 5448 04:18:25,221 --> 04:18:30,159 THE PAPER ON POST-EXERTION 5449 04:18:30,159 --> 04:18:31,761 MALAISE AND WAS3 AND THERE'S 5450 04:18:31,761 --> 04:18:35,965 BEEN OTHER PAPERS WITH OUR DATA 5451 04:18:35,965 --> 04:18:38,200 AS WELL. 5452 04:18:38,200 --> 04:18:42,471 THESE THREE PAPERS AND IT'S 5453 04:18:42,471 --> 04:18:47,943 INTERESTING TO ME AS A 5454 04:18:47,943 --> 04:18:52,548 RHEUMATOLOGIST AND THERE'S EXTRA 5455 04:18:52,548 --> 04:18:56,619 DATA AND THEY CAN SERVE AS A 5456 04:18:56,619 --> 04:19:03,993 WELL CHARACTERIZED COHORT FOR 5457 04:19:03,993 --> 04:19:04,627 COMPAR 5458 04:19:04,627 --> 04:19:08,864 COMPARISON. 5459 04:19:08,864 --> 04:19:14,537 WE HAVE A CHARACTERIZATION OF 5460 04:19:14,537 --> 04:19:17,106 THE GUT MICROBIOME AND STUDY 5461 04:19:17,106 --> 04:19:18,674 POST EXERTION MALAISE MORE 5462 04:19:18,674 --> 04:19:22,511 DEEPLY AND SAMPLES COLLECTED AT 5463 04:19:22,511 --> 04:19:27,950 MULTIPLE TIME POINTS RUNNING 5464 04:19:27,950 --> 04:19:31,053 THEM THROUGH MULTIPLEX ANALYSIS. 5465 04:19:31,053 --> 04:19:32,321 THERE'S WIDE POTENTIAL FOR 5466 04:19:32,321 --> 04:19:34,223 STUDYING SLEEP DEEPLY. 5467 04:19:34,223 --> 04:19:35,958 WE ONLY TALK IN BROAD STROKES 5468 04:19:35,958 --> 04:19:37,326 ABOUT CLINICAL SLEEP DISORDERS 5469 04:19:37,326 --> 04:19:39,695 BUT WE DIDN'T DO MUCH WITH 5470 04:19:39,695 --> 04:19:41,831 LOOKING AT SLEEP 5471 04:19:41,831 --> 04:19:43,566 MICROARCHITECTURE OR CIRCADIAN 5472 04:19:43,566 --> 04:19:44,133 RHYTHM ANALYSIS. 5473 04:19:44,133 --> 04:19:46,168 SAME WITH OUR ACTIGRAPHY DATA. 5474 04:19:46,168 --> 04:19:47,937 THERE'S POTENTIAL TO STUDY THAT 5475 04:19:47,937 --> 04:19:52,107 FURTHER. 5476 04:19:52,107 --> 04:19:55,778 THE DATA ONCE AVAILABLE 5477 04:19:55,778 --> 04:19:58,080 PUBLICALLY FOR THOSE INTERESTED 5478 04:19:58,080 --> 04:20:03,752 AND WANT TO WORK WITH US WE'RE 5479 04:20:03,752 --> 04:20:06,322 HAPPY TO AND THERE'S WORK BEING 5480 04:20:06,322 --> 04:20:07,957 DEVELOPED TO LOOK AT THE 5481 04:20:07,957 --> 04:20:11,961 MULTI-MODAL NEUROIMAGING OF 5482 04:20:11,961 --> 04:20:15,698 PHYSICAL FATIGUE AND SHOWS THE 5483 04:20:15,698 --> 04:20:17,833 fMRI DATA AND BECAUSE THERE'S 5484 04:20:17,833 --> 04:20:19,969 WISE COMBINE THEM INTO UNIQUE 5485 04:20:19,969 --> 04:20:21,971 INFORMATIONS. 5486 04:20:21,971 --> 04:20:23,672 ALSO I KNOW OUR COLLEAGUES I 5487 04:20:23,672 --> 04:20:27,209 PRESENTED TODAY ARE WORKING ON 5488 04:20:27,209 --> 04:20:27,977 CONNECTIVITY ANALYSES TO 5489 04:20:27,977 --> 04:20:31,247 UNDERSTAND HOW THE 5490 04:20:31,247 --> 04:20:31,947 NEUROEPINEPHRINE RICH BRAIN 5491 04:20:31,947 --> 04:20:37,953 AREAS MAY BE PLAYING A ROLE ON 5492 04:20:37,953 --> 04:20:40,856 THE INITIAL S. 5493 04:20:40,856 --> 04:20:43,325 WE PLAN ON ADDITIONAL MODELLING. 5494 04:20:43,325 --> 04:20:47,963 WE HAVE ARE WORKING WITH THE 5495 04:20:47,963 --> 04:20:48,964 V.A. 5496 04:20:48,964 --> 04:20:51,367 WE HAVE THE FIRST V.A. 5497 04:20:51,367 --> 04:20:54,103 INTRAMURAL NIH COLLABORATION TO 5498 04:20:54,103 --> 04:20:56,272 STUDY THE DISEASE AT NIH. 5499 04:20:56,272 --> 04:20:59,808 PROJECT IN DEPTH IS THE EFFORT. 5500 04:20:59,808 --> 04:21:03,245 I'M WORKING WITH THE 5501 04:21:03,245 --> 04:21:04,013 COMPUTATIONAL BIOLOGY TEAM TO 5502 04:21:04,013 --> 04:21:08,918 USE THEIR MODELLING WORK ON OUR 5503 04:21:08,918 --> 04:21:10,252 DATA TO LOOK AT IMMUNE 5504 04:21:10,252 --> 04:21:13,889 SIGNALLING NETWORKS AND TO USE 5505 04:21:13,889 --> 04:21:15,557 THEIR DRUG TARGETS SELECTION 5506 04:21:15,557 --> 04:21:19,962 PROCESS BY CROSS REFERENCING OUR 5507 04:21:19,962 --> 04:21:29,805 NETWORK ANALYSIS WITH DATABASES. 5508 04:21:29,805 --> 04:21:31,640 LASTLY, WE HAVE METHODOLOGIES. 5509 04:21:31,640 --> 04:21:34,076 ONE OF THE BIG QUESTION PEOPLE 5510 04:21:34,076 --> 04:21:35,344 HAVE IS LONG COVID AND ME/CFS 5511 04:21:35,344 --> 04:21:35,978 THE SAME THING ARE THEY 5512 04:21:35,978 --> 04:21:41,050 DIFFERENT? 5513 04:21:41,050 --> 04:21:43,285 WHEN WE COLLECT ENOUGH SAMPLES 5514 04:21:43,285 --> 04:21:44,753 WE CAN COMPARE THE DATA ONE WILL 5515 04:21:44,753 --> 04:21:52,494 THE NEW DATA WE'RE GENERATING. 5516 04:21:52,494 --> 04:21:58,801 I WANT TO THANK EVERYBODY SOME 5517 04:21:58,801 --> 04:22:00,102 PEOPLE WHO CONTRIBUTED LARGE AND 5518 04:22:00,102 --> 04:22:04,006 SMALL OVER THE EIGHT YEAR WE DID 5519 04:22:04,006 --> 04:22:04,273 THIS WORK. 5520 04:22:04,273 --> 04:22:06,775 I WANT TO THANK ALL THE PEOPLE 5521 04:22:06,775 --> 04:22:08,777 TONE RIGHT AND THEIR 5522 04:22:08,777 --> 04:22:10,312 CONTRIBUTIONS FROM FRANCIS 5523 04:22:10,312 --> 04:22:11,780 COLLINS TO INITIATING THE 5524 04:22:11,780 --> 04:22:15,918 PROJECT AND WALTER KOROSHETZ FOR 5525 04:22:15,918 --> 04:22:18,554 SUPPORTING US AND THOSE LISTED 5526 04:22:18,554 --> 04:22:21,390 HERE AND THE PEOPLE PART OF THE 5527 04:22:21,390 --> 04:22:23,258 PROJECT THAT CAME AND GO AND 5528 04:22:23,258 --> 04:22:23,959 SORT OF WHO HAVE PASSED OVER 5529 04:22:23,959 --> 04:22:30,232 THIS TIME. 5530 04:22:30,232 --> 04:22:35,938 OUR ETERNAL GRATITUDE TO THE 5531 04:22:35,938 --> 04:22:38,073 PARTICIPANTS TOE TO TRUST US AND 5532 04:22:38,073 --> 04:22:40,542 HEALTHY VOLUNTEERS WHO DID THE 5533 04:22:40,542 --> 04:22:40,743 SAME. 5534 04:22:40,743 --> 04:22:42,811 WITH THAT, THANK YOU. 5535 04:22:42,811 --> 04:22:52,988 WE'LL MOVE ON TO OUR PANELS. 5536 04:22:52,988 --> 04:22:56,392 >> NOW WE HAVE TWO PANELS. 5537 04:22:56,392 --> 04:23:03,799 THE FIRST IS THE STUDY 5538 04:23:03,799 --> 04:23:07,903 PARTICIPANTS PANEL CHAIRED BY 5539 04:23:07,903 --> 04:23:08,303 VICKY WHITTEMORE. 5540 04:23:08,303 --> 04:23:11,206 SHE'S A NEUROSCIENTIST IN THE 5541 04:23:11,206 --> 04:23:12,775 PROGRAM AT NINDS. 5542 04:23:12,775 --> 04:23:15,244 SHE'S A PROGRAM DIRECTOR AND 5543 04:23:15,244 --> 04:23:19,014 OVERSEES THE ME/CFS PROGRAM AND 5544 04:23:19,014 --> 04:23:22,885 HAS A BROAD UNDERSTANDING OF THE 5545 04:23:22,885 --> 04:23:24,286 DISEASE AND IS GOING TO CHAIR 5546 04:23:24,286 --> 04:23:28,223 THE PATIENT PANEL. 5547 04:23:28,223 --> 04:23:36,799 THANK YOU. 5548 04:23:36,799 --> 04:23:40,069 >> IT'S MY PLEASURE TO INTRODUCE 5549 04:23:40,069 --> 04:23:45,641 THIS PANEL AND THANK ALL THE 5550 04:23:45,641 --> 04:23:50,012 INDIVIDUALS WHO VOLUNTEERED AS 5551 04:23:50,012 --> 04:23:51,947 PARTICIPANTS AND THANK THE 5552 04:23:51,947 --> 04:23:53,015 SCIENTISTS PART OF THE STUDY. 5553 04:23:53,015 --> 04:23:55,284 IT'S BEEN AMAZING TO HEAR YOUR 5554 04:23:55,284 --> 04:23:55,951 RESULTS PRESENTED HERE TODAY. 5555 04:23:55,951 --> 04:23:59,755 THANK YOU VERY MUCH. 5556 04:23:59,755 --> 04:24:01,824 TODAY YOU'LL HEAR FROM DAVID 5557 04:24:01,824 --> 04:24:06,829 RHYMER AND HIS SISTER SUE AND 5558 04:24:06,829 --> 04:24:11,100 SELLA AND SOME RECORD MESSAGES 5559 04:24:11,100 --> 04:24:19,608 AROUND WE'LL LISTEN TO THEM NOW. 5560 04:24:19,608 --> 04:24:22,845 I'M NOT SURE HOW WE GET THEM 5561 04:24:22,845 --> 04:24:32,988 PLAYING. 5562 04:24:41,997 --> 04:24:47,970 >> I HOPE TO BE ABLE TO PROVIDE 5563 04:24:47,970 --> 04:24:51,907 MORE CONTEXT I BECAME SICK 5564 04:24:51,907 --> 04:24:53,342 QUICKLY IN THE DAY AFTER 5565 04:24:53,342 --> 04:24:55,577 THANKSGIVING 2014 I CAME DOWN 5566 04:24:55,577 --> 04:24:58,981 WITH WHAT WAS DIAGNOSED AS 5567 04:24:58,981 --> 04:25:00,549 BACTERIAL BRONCHITIS. 5568 04:25:00,549 --> 04:25:02,584 THE MEDICATIONS GIVEN DID THEIR 5569 04:25:02,584 --> 04:25:05,053 JOB AND FELT BETTER IN TERMS OF 5570 04:25:05,053 --> 04:25:09,424 THE BRONCHITIS BUT I KEPT 5571 04:25:09,424 --> 04:25:12,528 GETTING WEAKER AND WEAKER AND MY 5572 04:25:12,528 --> 04:25:15,497 BODY FELL LIKE LED AND A MONTH 5573 04:25:15,497 --> 04:25:18,033 LATER I WAS IN ABLE TO GET TO 5574 04:25:18,033 --> 04:25:20,502 THE DINING ROOM TABLE AND 5575 04:25:20,502 --> 04:25:24,873 FORWARDING TO 2017, 2018 I WAS 5576 04:25:24,873 --> 04:25:27,009 STUCK IN BED AND FRUSTRATED AN 5577 04:25:27,009 --> 04:25:34,149 ANGRY AND I CHANNELLED THAT 5578 04:25:34,149 --> 04:25:36,385 ENERGY INTO FIVE CLAIM TRIALS 5579 04:25:36,385 --> 04:25:38,520 THE NIH THE MOST TAXING AND MOST 5580 04:25:38,520 --> 04:25:39,254 EFFECTIVE ONE. 5581 04:25:39,254 --> 04:25:44,793 I WAS THRILLED WHEN I WAS 5582 04:25:44,793 --> 04:25:50,332 INVITED TO PARTICIPATE AND THE 5583 04:25:50,332 --> 04:25:51,967 ENTIRE PROCESS SHOWED THEY WERE 5584 04:25:51,967 --> 04:25:59,107 THOROUGH AND CARING. 5585 04:25:59,107 --> 04:26:02,711 I WAS THERE TWO WEEKS THE FIRST 5586 04:26:02,711 --> 04:26:09,284 TIME IN 2018 AND TWO WEEKS IN 5587 04:26:09,284 --> 04:26:09,551 2019. 5588 04:26:09,551 --> 04:26:12,287 I USED MY WHEEL CARE AND 5589 04:26:12,287 --> 04:26:15,791 ASSISTANCE FROM MY HUSBAND AND 5590 04:26:15,791 --> 04:26:17,926 FRIEND HOWEVER, I WAS SO CRASHED 5591 04:26:17,926 --> 04:26:19,761 AFTER THE TEST THEY WAS ONLY 5592 04:26:19,761 --> 04:26:23,131 ABLE TO GET TO ANY KIND OF 5593 04:26:23,131 --> 04:26:24,466 TESTING ON A STRETCHER. 5594 04:26:24,466 --> 04:26:27,603 I WAS A BED PAN AND UNABLE TO DO 5595 04:26:27,603 --> 04:26:29,871 ANYTHING AND NOT EVEN ABLE TO 5596 04:26:29,871 --> 04:26:30,806 SIGN THE CONSENT FORM. 5597 04:26:30,806 --> 04:26:34,443 I THINK IT WAS BEFORE THE LONG 5598 04:26:34,443 --> 04:26:36,678 HAUL WHERE THEY NOTICED I COULD 5599 04:26:36,678 --> 04:26:39,481 NOT LIFT MY HAND AND RIGHT MY 5600 04:26:39,481 --> 04:26:41,516 OWN NAME AT THAT POINT VERY 5601 04:26:41,516 --> 04:26:42,651 WELL. 5602 04:26:42,651 --> 04:26:44,686 IT WAS VERY TOUGH. 5603 04:26:44,686 --> 04:26:50,325 IT WAS WORTH THE EFFORTS 5604 04:26:50,325 --> 04:26:51,159 ABSOLUTELY. 5605 04:26:51,159 --> 04:26:56,898 SO I ALSO REALIZED THAT THE WAY 5606 04:26:56,898 --> 04:26:59,167 I CRASH EVEN IF I WAS ABLE TO 5607 04:26:59,167 --> 04:27:00,469 SIT ON THE EXERCISE BIKE FOR THE 5608 04:27:00,469 --> 04:27:03,972 CPET FOR SOME TIME IT I WOULD 5609 04:27:03,972 --> 04:27:07,409 ABSOLUTELY BE UNABLE TO BE IN A 5610 04:27:07,409 --> 04:27:08,977 METABOLIC CHAMBER 24 HOURS 5611 04:27:08,977 --> 04:27:09,444 WITHOUT ASSISTANCE. 5612 04:27:09,444 --> 04:27:11,680 I THEREFORE WAS NOT ABLE TO 5613 04:27:11,680 --> 04:27:12,714 PARTICIPATE IN THE CPET PART BUT 5614 04:27:12,714 --> 04:27:15,384 THEY INVITED KNOW DO A MODIFIED 5615 04:27:15,384 --> 04:27:17,185 PROTOCOL SO I WAS ABLE TO GO FOR 5616 04:27:17,185 --> 04:27:21,556 A SECOND VISIT. 5617 04:27:21,556 --> 04:27:25,060 I ALWAYS FELT THE TEAM LISTENED, 5618 04:27:25,060 --> 04:27:27,329 CARED FOR ME AND WANTED TO MAKE 5619 04:27:27,329 --> 04:27:28,330 PROGRESS FOR ALL OF US. 5620 04:27:28,330 --> 04:27:30,632 ONE EXAMPLE WOULD BE WHEN I 5621 04:27:30,632 --> 04:27:31,767 ARRIVED IN THE SECOND VISIT 5622 04:27:31,767 --> 04:27:35,003 THERE WAS A NEW RULE THAT WAS 5623 04:27:35,003 --> 04:27:36,838 SUPPOSED TO BE IMPLEMENTED 5624 04:27:36,838 --> 04:27:40,008 THROUGHOUT THE ENTIRE CLINICAL 5625 04:27:40,008 --> 04:27:43,945 CENTER WE HAD TO MARCH UP PLACE 5626 04:27:43,945 --> 04:27:45,080 STANDING SHOWING OUR STABILITY 5627 04:27:45,080 --> 04:27:46,815 AND THOSE THINGS TWICE A DAY. 5628 04:27:46,815 --> 04:27:48,817 FOR ME THAT WOULD HAVE BEEN A 5629 04:27:48,817 --> 04:27:51,086 HUGE EFFORT JUST TO DEMONSTRATE 5630 04:27:51,086 --> 04:27:53,355 I WAS FAILING A LOT OF THESE 5631 04:27:53,355 --> 04:27:55,490 FUNCTIONAL TESTS. 5632 04:27:55,490 --> 04:27:58,026 I EXPRESSED MY CONCERNS TO 5633 04:27:58,026 --> 04:27:59,428 DR. WALITT AND HE IMMEDIATELY 5634 04:27:59,428 --> 04:28:02,030 WENT TO THE HIGHEST LEVEL OF THE 5635 04:28:02,030 --> 04:28:04,433 NIH TO REQUEST AN EXEMPTION SO I 5636 04:28:04,433 --> 04:28:06,435 WOULDN'T HAVE TO SPEND MY ENERGY 5637 04:28:06,435 --> 04:28:11,373 ON SHOWING I CAN'T SIT UP, STAND 5638 04:28:11,373 --> 04:28:12,607 UP, WHAFRT WAS. 5639 04:28:12,607 --> 04:28:14,976 -- WHATEVER IT WAS. 5640 04:28:14,976 --> 04:28:16,845 I FELT TAKEN SERIOUSLY AND CARED 5641 04:28:16,845 --> 04:28:18,814 FOR AND WE ALL LEARN HOW TO PACE 5642 04:28:18,814 --> 04:28:23,085 AND MAKE OUR OWN CHOICE O AND 5643 04:28:23,085 --> 04:28:24,486 WHAT TO PEND EFFORT AND ENERGY 5644 04:28:24,486 --> 04:28:26,388 ON AND I WAS DETERMINED TO PUT 5645 04:28:26,388 --> 04:28:27,956 EVERYTHING IN TEST RESULTS AND 5646 04:28:27,956 --> 04:28:30,325 NOTHING ELSE. 5647 04:28:30,325 --> 04:28:32,461 USUALLY BY THEN OF MY VISIT I 5648 04:28:32,461 --> 04:28:33,228 WAS COMPLETELY CRASHED. 5649 04:28:33,228 --> 04:28:36,331 I WOULD SAY MOST THE RESULTS 5650 04:28:36,331 --> 04:28:42,704 THEY GATHERED 279 RESULTS IN MY 5651 04:28:42,704 --> 04:28:43,138 CHART. 5652 04:28:43,138 --> 04:28:45,407 MOST PDM OR CRASH RESULTS 5653 04:28:45,407 --> 04:28:48,377 BECAUSE I WAS NOT IN GOOD SHAPE. 5654 04:28:48,377 --> 04:28:51,213 GETTING HOME WAS DIFFICULT SO MY 5655 04:28:51,213 --> 04:28:53,482 HUSBAND HAD TO DRIVE FROM 5656 04:28:53,482 --> 04:28:59,488 CHICAGO TO BETHESDA WITH 5657 04:28:59,488 --> 04:29:00,489 MATTRESS IN THE BACK OF THE VAN 5658 04:29:00,489 --> 04:29:02,791 AND I WAS WEARING A DIAPER AND 5659 04:29:02,791 --> 04:29:13,235 IT WAS PRETTY UNPLEASANT. 5660 04:29:13,802 --> 04:29:17,539 THE APPLICATION PROCESS AND 5661 04:29:17,539 --> 04:29:20,675 AFTER THE CARE TEAM SURPASSED MY 5662 04:29:20,675 --> 04:29:23,211 EXPECTATIONS AND CHECK ON HOW I 5663 04:29:23,211 --> 04:29:25,046 WAS DOING AND SHOWED THE UTMOST 5664 04:29:25,046 --> 04:29:30,352 CARE AND THOUGHTFULNESS. 5665 04:29:30,352 --> 04:29:31,920 I'M VERY GRATEFUL FOR THEIR WORK 5666 04:29:31,920 --> 04:29:35,590 AND IT WAS DIFFICULT TO PROCESS 5667 04:29:35,590 --> 04:29:37,192 THE CRITICISM I SAW AFTER THE 5668 04:29:37,192 --> 04:29:39,294 PUBLICATION OF THE RESULTS. 5669 04:29:39,294 --> 04:29:41,563 IT WAS IN SUCH CONTRAST TO MY 5670 04:29:41,563 --> 04:29:45,700 PERSONAL EXPERIENCES. 5671 04:29:45,700 --> 04:29:52,941 I HOPE THIS WAS HELPFUL TO SEE 5672 04:29:52,941 --> 04:29:54,242 HEAR FROM A PARTICIPANT WHAT 5673 04:29:54,242 --> 04:29:59,347 CONDITION THEY WERE IN AND 5674 04:29:59,347 --> 04:30:01,783 ALWAYS FELT EVERYONE IN THE TEAM 5675 04:30:01,783 --> 04:30:03,485 AND BRIAN WALITT THERE DOING A 5676 04:30:03,485 --> 04:30:06,455 LOT OF THE TESTS HIMSELF ALWAYS 5677 04:30:06,455 --> 04:30:09,191 FELT ACCESSIBLE AND WANTING TO 5678 04:30:09,191 --> 04:30:11,693 TAKE CARE OF HIS PARTICIPANTS AS 5679 04:30:11,693 --> 04:30:16,298 BEST HE POSSIBLY COULD. 5680 04:30:16,298 --> 04:30:19,768 I HOPE THIS LEADS MORE AND A 5681 04:30:19,768 --> 04:30:26,942 THANK YOU FOR LISTENING. 5682 04:30:26,942 --> 04:30:29,344 >> I'M PLEASED FOR HERE IN THE 5683 04:30:29,344 --> 04:30:30,946 NIH STUDY TO SOLVE ME/CFS. 5684 04:30:30,946 --> 04:30:33,048 ONE OF THE MOST DIFFICULT 5685 04:30:33,048 --> 04:30:34,883 DECISIONS WAS DETERMINING TO 5686 04:30:34,883 --> 04:30:37,185 LIVE A CONTRIBUTING LIFE DESPITE 5687 04:30:37,185 --> 04:30:37,886 HAVING ME/CFS. 5688 04:30:37,886 --> 04:30:41,590 PRIOR I A BUSY PERSON. 5689 04:30:41,590 --> 04:30:43,959 IT WAS NOT UNUSUAL FOR KNOW GO 5690 04:30:43,959 --> 04:30:47,262 TO WORK 60 TO 80 HOURS AND THE 5691 04:30:47,262 --> 04:30:48,964 REMAINING HOURS DOING HOUSEWORK, 5692 04:30:48,964 --> 04:30:51,266 VARIOUS ACTIVITIES AND HELPING 5693 04:30:51,266 --> 04:30:51,666 OTHERS. 5694 04:30:51,666 --> 04:30:53,101 MY MORNINGS WOULD START EARLY 5695 04:30:53,101 --> 04:30:54,703 AND GET MY HUSBAND TO WORK. 5696 04:30:54,703 --> 04:30:57,339 I LOVED MY LIFE. 5697 04:30:57,339 --> 04:31:01,209 IT WAS FULFILLING. 5698 04:31:01,209 --> 04:31:05,080 MARCH 6, 2014 MY LIFE SHIFTED I 5699 04:31:05,080 --> 04:31:06,047 COULD NOT WALK WITHOUT 5700 04:31:06,047 --> 04:31:08,750 ASSISTANCE OR CALL MY HUSBAND 5701 04:31:08,750 --> 04:31:11,753 AND COULD NOT SPEAK ABOVE A 5702 04:31:11,753 --> 04:31:14,756 SLIGHT WHISPER AND NEEDED HELP 5703 04:31:14,756 --> 04:31:16,458 TO SHOWER, BRUSH MY TEETH. 5704 04:31:16,458 --> 04:31:19,461 I SAW MYSELF STOPPED. 5705 04:31:19,461 --> 04:31:23,265 I WAS AWAKE AND TAKE A CALL IT 5706 04:31:23,265 --> 04:31:24,432 LASTED LESS THAN A MINUTE. 5707 04:31:24,432 --> 04:31:26,935 MY SWEET HUSBAND AND FAMILY 5708 04:31:26,935 --> 04:31:27,802 BECAME MY ADVOCATES. 5709 04:31:27,802 --> 04:31:30,238 MY HUSBAND, CHILDREN AND 5710 04:31:30,238 --> 04:31:32,807 DAUGHTERS AND SON IN-LAWS AND 5711 04:31:32,807 --> 04:31:34,609 EXTENDED FAMILY RALLIED AROUND. 5712 04:31:34,609 --> 04:31:37,512 I REQUIRED THAT MANY PEOPLE TO 5713 04:31:37,512 --> 04:31:37,979 HELP. 5714 04:31:37,979 --> 04:31:42,183 I FELT I HIT A WALL THAT WAS 5715 04:31:42,183 --> 04:31:42,551 INSURMOUNTABLE. 5716 04:31:42,551 --> 04:31:47,889 I HAD DAILY TASKS AND A DAUG 5717 04:31:47,889 --> 04:31:51,593 DAUGHTER-IN-LAW TO BUY ME 5718 04:31:51,593 --> 04:31:53,862 GADGETS FOR DEVICES TO KEEP IN 5719 04:31:53,862 --> 04:31:54,129 TOUCH. 5720 04:31:54,129 --> 04:31:56,531 AND VARIOUS TREATMENTS WERE 5721 04:31:56,531 --> 04:31:58,033 TRIED AND NOT PAID FOR BY 5722 04:31:58,033 --> 04:31:59,234 EXPERIENCE AND EXPENSIVE. 5723 04:31:59,234 --> 04:32:01,703 SIGNS OF CRASHES WERE OBSERVED 5724 04:32:01,703 --> 04:32:03,638 AND SHARED SO EVERYONE CAN HELP 5725 04:32:03,638 --> 04:32:05,640 ME LEARN TO MANAGE EXERTION. 5726 04:32:05,640 --> 04:32:07,642 I COULD NOT ACTIVITY PARTICIPATE 5727 04:32:07,642 --> 04:32:08,810 IN LIFE TWO YEARS. 5728 04:32:08,810 --> 04:32:12,747 MY PRACTICER HELPED ME AND IT 5729 04:32:12,747 --> 04:32:14,215 WAS ARDUOUS TO FILL OUT THE 5730 04:32:14,215 --> 04:32:17,619 PAPER AND VERIFY WHETHER I HAD 5731 04:32:17,619 --> 04:32:19,721 ME/CFS WAS A BLESSING TO BE 5732 04:32:19,721 --> 04:32:22,424 ACCEPTED AND GIVE ME A NEW SENSE 5733 04:32:22,424 --> 04:32:24,259 OF USEFULNESS. 5734 04:32:24,259 --> 04:32:27,262 UPON LEARNING I WAS ACCEPTED WE 5735 04:32:27,262 --> 04:32:28,630 BEGAN A SERIES OF PREPARATORY 5736 04:32:28,630 --> 04:32:31,800 TEST TO SEE IF I CAN WITHSTAND 5737 04:32:31,800 --> 04:32:33,568 THE TRAVEL AND MY HUSBAND BOUGHT 5738 04:32:33,568 --> 04:32:35,937 A VAN TO TOTE ME AROUND AND ONE 5739 04:32:35,937 --> 04:32:41,943 TOOK ONE TRIP 1200 MILES AND 5740 04:32:41,943 --> 04:32:44,946 FOUND SITTING AT A 30 DEGREE 5741 04:32:44,946 --> 04:32:52,988 ANGLE AND UP RIGHT I COULD 5742 04:32:52,988 --> 04:32:54,589 TRAVEL AN HOUR AND A HALF AND I 5743 04:32:54,589 --> 04:32:56,725 HAD TO FIGURE OUT HOW TO BET 5744 04:32:56,725 --> 04:32:59,094 ACROSS THE COUNTRY WITHOUT 5745 04:32:59,094 --> 04:32:59,728 CAUSING ME HARM. 5746 04:32:59,728 --> 04:33:04,833 THE NIH PROVIDED A SCHEDULE IT.. 5747 04:33:04,833 --> 04:33:06,935 AT THE TIME THE SLEEP PATTERNS 5748 04:33:06,935 --> 04:33:09,471 WERE 18 TO 22 HOURS OF SLEEP A 5749 04:33:09,471 --> 04:33:09,804 DAY. 5750 04:33:09,804 --> 04:33:11,940 THE LONGEST I STAYED WEAK WAS 5751 04:33:11,940 --> 04:33:12,774 ONE HOUR. 5752 04:33:12,774 --> 04:33:14,476 THE SCHEDULE WAS GOING REQUIRE 5753 04:33:14,476 --> 04:33:14,776 MORE. 5754 04:33:14,776 --> 04:33:17,946 I COULD STAY AWAKE AND UNRIGHT 5755 04:33:17,946 --> 04:33:20,749 FOR 15 TO 22 MINUTES AT 25 5756 04:33:20,749 --> 04:33:24,052 MINUTES I'D START TO SHAKE, FALL 5757 04:33:24,052 --> 04:33:27,255 FORWARD AND FEELING OF SHOOTING 5758 04:33:27,255 --> 04:33:31,660 PAIN A REFER TO AS ELECTRICALS 5759 04:33:31,660 --> 04:33:35,664 AND LIGHT AND SOUND WOULD BE 5760 04:33:35,664 --> 04:33:41,636 UNBEARABLE AND I'D HAVE TO LIE 5761 04:33:41,636 --> 04:33:41,903 DOWN. 5762 04:33:41,903 --> 04:33:47,876 I THOUGHT IF I CAN PARTICIPATE 5763 04:33:47,876 --> 04:33:49,744 IN THE DATA WOULD HAVE A NEW 5764 04:33:49,744 --> 04:33:50,011 DEPOSIT. 5765 04:33:50,011 --> 04:33:52,647 IT'S DIFFICULT TO DESCRIBE MY 5766 04:33:52,647 --> 04:33:54,149 EXPERIENCE WITH NIH. 5767 04:33:54,149 --> 04:33:56,451 MUCH TIME WAS SPEND TRYING TO 5768 04:33:56,451 --> 04:33:59,421 STAY AWAKE. 5769 04:33:59,421 --> 04:34:02,957 AS THE SURVEYS WERE IT MAY HAVE 5770 04:34:02,957 --> 04:34:05,660 BEEN MORE OR LESS BUT FELT 5771 04:34:05,660 --> 04:34:05,994 INTERNAL. 5772 04:34:05,994 --> 04:34:08,096 I NEVER EXPERIENCED SUCH DEVOTED 5773 04:34:08,096 --> 04:34:10,398 CARE AS I DID WITH THE STAFF AT 5774 04:34:10,398 --> 04:34:11,232 NIH. 5775 04:34:11,232 --> 04:34:14,502 STARTING WITH THE FIRST CONTACT 5776 04:34:14,502 --> 04:34:15,637 FROM DR. NATH AND BEING CHECKED 5777 04:34:15,637 --> 04:34:18,740 ON A FEW MONTHS AGO, MY TRUST IN 5778 04:34:18,740 --> 04:34:22,010 THE TEAM OF STRANGERS WAS 5779 04:34:22,010 --> 04:34:23,578 VALIDATED AN OWED THEM MY 5780 04:34:23,578 --> 04:34:24,612 DETERMINATION TO CONTINUE TO 5781 04:34:24,612 --> 04:34:25,880 LIVE WITH MY BEST EFFORT. 5782 04:34:25,880 --> 04:34:28,116 MY SWEET HUSBAND AND ONE OF MY 5783 04:34:28,116 --> 04:34:30,051 NIECES, TWO DAUGHTERS AND 5784 04:34:30,051 --> 04:34:34,689 SON-IN-LAW ALL MAKE SURE I HAVE 5785 04:34:34,689 --> 04:34:34,989 SUPPORT. 5786 04:34:34,989 --> 04:34:36,891 THEY'VE COME FROM AS FAR AS 5787 04:34:36,891 --> 04:34:37,892 UTAH, NEW YORK AND WASHINGTON, 5788 04:34:37,892 --> 04:34:39,794 D.C. TO MAKE SURE I FILL STEEL 5789 04:34:39,794 --> 04:34:43,932 CONNECTED AND MY WORK WAS VALUE. 5790 04:34:43,932 --> 04:34:50,038 THERE WAS AN OCCUPATIONAL HEALTH 5791 04:34:50,038 --> 04:34:51,873 PERSON WHO HELP ME GET BENEFITS 5792 04:34:51,873 --> 04:34:55,910 TO THE MAXIMUM AND THEN TALKED 5793 04:34:55,910 --> 04:34:59,114 ABOUT MY SORROWS AND MY LOSS OF 5794 04:34:59,114 --> 04:35:01,449 OCCUPATION AND TAKING CARE OF MY 5795 04:35:01,449 --> 04:35:02,450 FAMILY. 5796 04:35:02,450 --> 04:35:04,819 SHE KNEW WHAT QUESTIONS TO ASK 5797 04:35:04,819 --> 04:35:10,358 AND HELPED ME COME UP WITH A 5798 04:35:10,358 --> 04:35:12,093 SOLUTION AND FACE THOSE AND WHEN 5799 04:35:12,093 --> 04:35:13,795 I SAY I COOK OCCASIONALLY I MEAN 5800 04:35:13,795 --> 04:35:15,497 THREE TIMES IN ONE YEAR. 5801 04:35:15,497 --> 04:35:17,365 BUT IT HELPED AND I'M GRATEFUL I 5802 04:35:17,365 --> 04:35:19,934 WAS ABLE TO DO THOSE THREE 5803 04:35:19,934 --> 04:35:20,135 TIMES. 5804 04:35:20,135 --> 04:35:23,938 THERE WAS ANOTHER TEST THAT WAS 5805 04:35:23,938 --> 04:35:26,908 PARTICULARLY AN ELECTROMAGNETIC 5806 04:35:26,908 --> 04:35:28,576 TESTING AND SCIENTISTS CONCERNED 5807 04:35:28,576 --> 04:35:33,715 ABOUT MY COMFORT AND MY TEAM 5808 04:35:33,715 --> 04:35:36,417 SENT JOY TO BE THERE FOR THE 5809 04:35:36,417 --> 04:35:38,052 ENTIRE TIME AND ENSURE THEY DID 5810 04:35:38,052 --> 04:35:40,255 NOT CAUSE ANY HARM. 5811 04:35:40,255 --> 04:35:44,092 EVERYONE WAS SO VERY CAREFUL TO 5812 04:35:44,092 --> 04:35:44,492 LISTEN. 5813 04:35:44,492 --> 04:35:45,760 ANOTHER TIME THINGS WERE 5814 04:35:45,760 --> 04:35:46,928 PROTECTIVE WAS WHEN I WAS HAVING 5815 04:35:46,928 --> 04:35:48,229 MY SPINAL TAP. 5816 04:35:48,229 --> 04:35:51,599 THE SECOND ONE AND THEY ARE VERY 5817 04:35:51,599 --> 04:35:53,501 UNCOMFORTABLE AND HE SAID FIT 5818 04:35:53,501 --> 04:35:55,503 BECOMES TOO MUCH SAY STOP AND 5819 04:35:55,503 --> 04:35:56,171 WE'LL STOP. 5820 04:35:56,171 --> 04:35:58,439 SO I WEEKLY SAID STOP AT THE 5821 04:35:58,439 --> 04:35:59,974 POINT WHERE THEY NEEDED TWO CCs 5822 04:35:59,974 --> 04:36:05,413 MORE. 5823 04:36:05,413 --> 04:36:07,549 AND THE SCIENTISTS DID NOT HEAR 5824 04:36:07,549 --> 04:36:09,184 AND DR. WALITT WAS THERE AND 5825 04:36:09,184 --> 04:36:12,487 SAID, SHE SAID STOP. 5826 04:36:12,487 --> 04:36:14,355 AND THE WHOLE ROOM STOPPED. 5827 04:36:14,355 --> 04:36:16,958 THAT LEVEL OF PROTECTION IS 5828 04:36:16,958 --> 04:36:17,258 INVALUABLE. 5829 04:36:17,258 --> 04:36:19,194 SINCE READING THE SYNOPSIS OF 5830 04:36:19,194 --> 04:36:20,495 THE RESULTS AND ATTEMPTING TO 5831 04:36:20,495 --> 04:36:22,330 READ THE FULL STUDY I FEEL 5832 04:36:22,330 --> 04:36:22,630 RELIEF. 5833 04:36:22,630 --> 04:36:25,600 I'M GRATEFUL TO KNOW MY BODY HAS 5834 04:36:25,600 --> 04:36:27,468 ADD A SYSTEM DISRUPTION. 5835 04:36:27,468 --> 04:36:30,171 I KNOW SCIENTISTS CAN MOVE 5836 04:36:30,171 --> 04:36:31,139 FORWARD WITH ADDITIONAL 5837 04:36:31,139 --> 04:36:35,543 INFORMATION TO HELP STUDIES. 5838 04:36:35,543 --> 04:36:37,979 I ACCEPTED THE IMPACT ON MY 5839 04:36:37,979 --> 04:36:39,147 ABILITY TO FUNCTION. 5840 04:36:39,147 --> 04:36:40,949 IT TOOK NEARLY EIGHT MONTHS TO 5841 04:36:40,949 --> 04:36:42,817 RETURN TO MY LEVEL OF 5842 04:36:42,817 --> 04:36:43,418 FUNCTIONALITY PRIOR TO 5843 04:36:43,418 --> 04:36:45,820 PARTICIPATING IN THE STUDY. 5844 04:36:45,820 --> 04:36:49,757 IT'S DIFFICULT TO HAVE AN 5845 04:36:49,757 --> 04:36:50,792 ILLNESS. 5846 04:36:50,792 --> 04:36:53,194 DEVELOPING A DATA BANK IS 5847 04:36:53,194 --> 04:36:53,595 CRITICAL. 5848 04:36:53,595 --> 04:36:57,765 THE ME/CFS PATIENTS NEED ANSWER. 5849 04:36:57,765 --> 04:37:01,035 I'M GRATEFUL TO HAVE 5850 04:37:01,035 --> 04:37:01,469 PARTICIPATED. 5851 04:37:01,469 --> 04:37:06,441 I, A PATIENT WITH ME/CFS HOPE MY 5852 04:37:06,441 --> 04:37:08,776 CHILDREN'S GENERATION WILL SEE 5853 04:37:08,776 --> 04:37:10,678 BENEFIT AND BY THE CDC THE 5854 04:37:10,678 --> 04:37:13,114 MEDICAL COMMUNITY AND THE REST 5855 04:37:13,114 --> 04:37:14,515 OF THE SCIENTIFIC BODIES WORKING 5856 04:37:14,515 --> 04:37:15,116 ON THIS. 5857 04:37:15,116 --> 04:37:16,684 I HOPE MY GRANDCHILDREN'S 5858 04:37:16,684 --> 04:37:21,089 GENERATION INTERVENTIONS TO 5859 04:37:21,089 --> 04:37:24,058 MANAGE THIS DEBILITATING 5860 04:37:24,058 --> 04:37:24,325 ILLNESS. 5861 04:37:24,325 --> 04:37:26,895 AGAIN I WOULD LIKE TO THANK YOU 5862 04:37:26,895 --> 04:37:29,163 FOR THE OPPORTUNITY TO GIVE YOU 5863 04:37:29,163 --> 04:37:30,431 THE SCIENTISTS WE DEPEND ON A 5864 04:37:30,431 --> 04:37:32,600 SENSE OF MY GRATITUDE FOR YOUR 5865 04:37:32,600 --> 04:37:33,735 WILLINGNESS TO RESEARCH AND FIND 5866 04:37:33,735 --> 04:37:36,170 INFORMING TO SEEK OUT THE CAUSES 5867 04:37:36,170 --> 04:37:38,406 AND SOLUTIONS FOR ME/CFS. 5868 04:37:38,406 --> 04:37:39,874 IT IS A VERY COMPLEX AND 5869 04:37:39,874 --> 04:37:41,709 MISUNDERSTOOD AND UNDER FUNDED 5870 04:37:41,709 --> 04:37:42,343 DISEASE AND I APPRECIATE YOUR 5871 04:37:42,343 --> 04:37:42,610 SACRIFICE. 5872 04:37:42,610 --> 04:37:47,248 THANK YOU. 5873 04:37:47,248 --> 04:37:48,950 >> HELLO. 5874 04:37:48,950 --> 04:37:51,686 MY NAME IS DAVID REMER. 5875 04:37:51,686 --> 04:37:54,055 RETIRE TO ME/CFS WAYS FAMILY 5876 04:37:54,055 --> 04:37:55,957 PHYSICIAN WITH TRAINING IN 5877 04:37:55,957 --> 04:37:56,791 TROPICAL MEDICINE. 5878 04:37:56,791 --> 04:37:59,928 I WORKED IN INNER CITY TORONTO 5879 04:37:59,928 --> 04:38:02,163 AND THEN IN THE HIMALAYAN 5880 04:38:02,163 --> 04:38:05,733 COUNTRY FOR FIVE YEARS BEFORE 5881 04:38:05,733 --> 04:38:07,936 SETTLING INTO A SMALL TOWN 5882 04:38:07,936 --> 04:38:11,940 GENERAL PRACTICE IN CANADA AS 5883 04:38:11,940 --> 04:38:15,109 WELL AS MEDICINE I WITH YOU 5884 04:38:15,109 --> 04:38:18,246 INVOLVE IN NURSING HOME AND 5885 04:38:18,246 --> 04:38:21,249 TEACHING COMMUNITY GROUPS AND 5886 04:38:21,249 --> 04:38:24,919 SET ASIDE TIME FOR WIFE AND 5887 04:38:24,919 --> 04:38:26,654 THREE CHILDREN. 5888 04:38:26,654 --> 04:38:30,325 I'VE ENJOYED CHALLENGING MYSELF 5889 04:38:30,325 --> 04:38:35,930 WITH ACTIVITIES, WILDERNESS CA 5890 04:38:35,930 --> 04:38:40,268 CANOEING AND RUNNING. 5891 04:38:40,268 --> 04:38:41,869 ON A FAMILY TRIP I PICKED UP THE 5892 04:38:41,869 --> 04:38:47,375 VIRUS THAT RESULTED IN MY AND 5893 04:38:47,375 --> 04:38:49,410 STEP BY STEP I LOST THE ABILITY 5894 04:38:49,410 --> 04:38:52,947 TO DO ALL OF THESE THINGS. 5895 04:38:52,947 --> 04:38:55,984 WHEN IT WAS CLEAR I HAD THIS 5896 04:38:55,984 --> 04:38:57,085 POORLY UNDERSTAND CONDITION I 5897 04:38:57,085 --> 04:38:59,954 LOOKED FOR RESEARCH STUDIES 5898 04:38:59,954 --> 04:39:01,189 INVESTIGATING ME/CFS THAT WOULD 5899 04:39:01,189 --> 04:39:02,623 CONTRIBUTE TO BETTER INFORMATION 5900 04:39:02,623 --> 04:39:06,494 OF IT AND MAYBE EVEN OF HELP 5901 04:39:06,494 --> 04:39:07,862 PERSONALLY. 5902 04:39:07,862 --> 04:39:10,598 SO IT WAS VERY ENCOURAGING TO 5903 04:39:10,598 --> 04:39:14,268 FIND THE STUDY IN PROGRESS WITH 5904 04:39:14,268 --> 04:39:15,937 EXTENSIVE RESOURCES TRYING TO 5905 04:39:15,937 --> 04:39:19,273 FIGURE OUT WHAT WAS GOING ON. 5906 04:39:19,273 --> 04:39:21,242 I WAS IMPRESSED WITH HOW 5907 04:39:21,242 --> 04:39:23,111 THOROUGH THE INTAKE PROCESS WAS 5908 04:39:23,111 --> 04:39:24,746 AT RULING OUT OTHER POSSIBLE 5909 04:39:24,746 --> 04:39:27,215 CAUSES FOR MY SYSTEMS. 5910 04:39:27,215 --> 04:39:31,052 AND IT WAS FASCINATING BEING AT 5911 04:39:31,052 --> 04:39:33,621 THE NIH A PART OF HIGH TECH 5912 04:39:33,621 --> 04:39:38,026 TESTING SUCH AS THE METABOLIC 5913 04:39:38,026 --> 04:39:38,893 CHAMBER. 5914 04:39:38,893 --> 04:39:40,628 GENETIC SEQUENCING AND TABLE 5915 04:39:40,628 --> 04:39:44,298 TESTING AND THE MAGNETIC 5916 04:39:44,298 --> 04:39:45,266 STIMULATION. 5917 04:39:45,266 --> 04:39:46,834 POSITIONING THEIR MAGIC WAND 5918 04:39:46,834 --> 04:39:48,536 OVER THE PRECISE PLACE IN MY 5919 04:39:48,536 --> 04:39:51,039 HEAD TO STIMULATE A SINGLE 5920 04:39:51,039 --> 04:39:52,840 MUSCLE IN MY RIGHT FOREARM. 5921 04:39:52,840 --> 04:39:58,780 THROUGHOUT THE STUDY THE TEAM 5922 04:39:58,780 --> 04:40:00,581 WAS ACCOMMODATING OF MY NEED FOR 5923 04:40:00,581 --> 04:40:03,317 QUIETNESS AND REST BREAKS AND 5924 04:40:03,317 --> 04:40:04,052 OTHER ASSISTANCE. 5925 04:40:04,052 --> 04:40:11,459 OVER ALL, PARTICIPANTS WAS 5926 04:40:11,459 --> 04:40:12,427 AFFIRMING AND INTERESTING. 5927 04:40:12,427 --> 04:40:14,295 THANK YOU TO THE RESEARCH TEAM. 5928 04:40:14,295 --> 04:40:16,564 GRATEFUL TO HAVE BEEN ABLE TO 5929 04:40:16,564 --> 04:40:17,298 PARTICIPATE. 5930 04:40:17,298 --> 04:40:18,433 AT MY LOWEST IN THE YEAR 5931 04:40:18,433 --> 04:40:22,236 FOLLOWING THE STUDY, I WAS 5932 04:40:22,236 --> 04:40:24,072 APPROXIMATELY 15 OF 100 ON THE 5933 04:40:24,072 --> 04:40:26,507 DISABILITY RATING SCALE. 5934 04:40:26,507 --> 04:40:27,975 I'VE IMPROVED SIGNIFICANTLY 5935 04:40:27,975 --> 04:40:30,211 SINCE THEN BUT BY THIS TIME IN 5936 04:40:30,211 --> 04:40:31,646 THE AFTERNOON I'LL BE SLEEPING 5937 04:40:31,646 --> 04:40:32,346 AND NOT ABLE TO TAKE PART IN THE 5938 04:40:32,346 --> 04:40:37,652 DISCUSSION. 5939 04:40:37,652 --> 04:40:40,621 I HAVE A SUPPORTIVE FAMILY. 5940 04:40:40,621 --> 04:40:44,325 SO MUCH SO MY SISTER TOOK PART 5941 04:40:44,325 --> 04:40:45,493 AS A HEALTHY CONTROL AND HAS HER 5942 04:40:45,493 --> 04:40:51,132 OWN STORY. 5943 04:40:51,132 --> 04:40:53,434 >> I'M DAVE'S SISTER SUSAN. 5944 04:40:53,434 --> 04:40:58,706 I PARTICIPATED AS A HEALTHY 5945 04:40:58,706 --> 04:41:00,675 VOLUNTEER AND SAW MY BROTHER 5946 04:41:00,675 --> 04:41:02,210 SUFFERING FROM THIS STRANGE 5947 04:41:02,210 --> 04:41:02,643 ILLNESS. 5948 04:41:02,643 --> 04:41:04,679 I SIGNED UP IN HOPES OF LEARNING 5949 04:41:04,679 --> 04:41:06,214 ABOUT THE CONDITION AN HELP FIND 5950 04:41:06,214 --> 04:41:08,616 A CURE FOR MY BROTHER. 5951 04:41:08,616 --> 04:41:11,052 PARTICIPATING IN THE STUDY WAS A 5952 04:41:11,052 --> 04:41:12,687 FASCINATING EXPERIENCE AND HAD 5953 04:41:12,687 --> 04:41:14,288 ME BUSINESS AGREE DAWN TO DUSK 5954 04:41:14,288 --> 04:41:14,889 FOR A WEEK. 5955 04:41:14,889 --> 04:41:18,025 IT WAS INTIMIDATING TO BE 5956 04:41:18,025 --> 04:41:19,594 MONITORED BY SUCH BRILLIANT 5957 04:41:19,594 --> 04:41:21,963 MINDS DOING MATH EQUATIONS IN 5958 04:41:21,963 --> 04:41:23,931 THE fMRI MACHINE. 5959 04:41:23,931 --> 04:41:26,934 DURING THE MUSCLE BIOPSY I SENT 5960 04:41:26,934 --> 04:41:29,804 THIS PHOTO TO MY BROTHER WITH 5961 04:41:29,804 --> 04:41:31,372 THE CAPTION TEAM DAVE. 5962 04:41:31,372 --> 04:41:35,209 DR. WALITT WAS MONITORING FOR 5963 04:41:35,209 --> 04:41:36,477 REST RESULTS BETWEEN MY BROTHER 5964 04:41:36,477 --> 04:41:37,245 AND A. 5965 04:41:37,245 --> 04:41:38,513 PARTICIPATING WAS TRANSFORMATIVE 5966 04:41:38,513 --> 04:41:39,914 AND INSPIRED ME TO TAKE MY 5967 04:41:39,914 --> 04:41:44,318 HEALTH MORE SERIOUSLY. 5968 04:41:44,318 --> 04:41:47,922 I TOOK UP RUNNING AND TRAINED 5969 04:41:47,922 --> 04:41:51,225 FOR A HALF MARATHON AND WENT 5970 04:41:51,225 --> 04:41:51,726 BACKPACKING. 5971 04:41:51,726 --> 04:41:54,295 AFTER THE LOCKDOWN I CONTRACTED 5972 04:41:54,295 --> 04:41:57,565 A SERIOUS CASE OF COVID DESPITE 5973 04:41:57,565 --> 04:42:00,101 BEING FULLY VACCINATED. 5974 04:42:00,101 --> 04:42:04,372 I NEVER THOUGHT IT WAS HAPPEN 5975 04:42:04,372 --> 04:42:08,676 FROM ME AND I ALWAYS RECOVERED 5976 04:42:08,676 --> 04:42:10,478 BUT I BECAME PROGRESSIVELY WORSE 5977 04:42:10,478 --> 04:42:13,181 AND MY BODY WAS DYSREGULATE AND 5978 04:42:13,181 --> 04:42:14,749 SOON AFTER I WAS DIAGNOSED WITH 5979 04:42:14,749 --> 04:42:15,183 LONG COVID. 5980 04:42:15,183 --> 04:42:17,185 EIGHT THIS POINT I REACHED OUT 5981 04:42:17,185 --> 04:42:19,287 TO DR. WALITT. 5982 04:42:19,287 --> 04:42:20,254 GIVEN HOW THOROUGHLY I WAS 5983 04:42:20,254 --> 04:42:22,990 TESTED I FELT IF THEY TESTED ME 5984 04:42:22,990 --> 04:42:24,125 AGAIN IT WOULD RESULT IN 5985 04:42:24,125 --> 04:42:24,725 VALUABLE DATA. 5986 04:42:24,725 --> 04:42:29,864 I CAME BACK TO NIH AND 5987 04:42:29,864 --> 04:42:30,831 PARTICIPATED AN POST-CORONAVIRUS 5988 04:42:30,831 --> 04:42:34,936 STUDY WHICH CAN BE SEEN AS A 5989 04:42:34,936 --> 04:42:37,071 SEQUEL TO THE ME/CFS STUDY. 5990 04:42:37,071 --> 04:42:37,905 PARTICIPATING IN THE MORE RECENT 5991 04:42:37,905 --> 04:42:40,474 LONG COVID STUDY HAS BEEN SUCH A 5992 04:42:40,474 --> 04:42:42,043 BLESSING BREAKING DOWN THE 5993 04:42:42,043 --> 04:42:43,878 LONELINESS AND GAVE ME AN 5994 04:42:43,878 --> 04:42:45,313 OPPORTUNITY TO BRING GOOD FROM 5995 04:42:45,313 --> 04:42:46,013 MY OWN STORY. 5996 04:42:46,013 --> 04:42:48,282 THANK YOU FROM THE BOTTOM OF MY 5997 04:42:48,282 --> 04:42:51,452 HEART TO DOCTORS, WALITT, NATH 5998 04:42:51,452 --> 04:42:52,720 AND THE NIH STAFF FOR YOUR 5999 04:42:52,720 --> 04:42:55,022 WISDOM, COMPASSION AND SOUND 6000 04:42:55,022 --> 04:42:55,289 GUIDANCE. 6001 04:42:55,289 --> 04:43:01,095 I'M VERY AWARE MY STORE 6002 04:43:01,095 --> 04:43:02,663 SCOMBREERT OF-- MY STORY IS A PT 6003 04:43:02,663 --> 04:43:04,699 OF THE BIGGER STORY AND GLAD I 6004 04:43:04,699 --> 04:43:06,834 COULD PLAY A PART. 6005 04:43:06,834 --> 04:43:17,011 THANK YOU. 6006 04:43:28,456 --> 04:43:29,824 >> THANK YOU. 6007 04:43:29,824 --> 04:43:30,891 ARE THE INDIVIDUALS ON ZOOM? 6008 04:43:30,891 --> 04:43:41,135 ANY COMMENTS? 6009 04:43:47,675 --> 04:43:50,011 >> I WOULD START BY THANKING 6010 04:43:50,011 --> 04:43:52,513 EACH ONE. 6011 04:43:52,513 --> 04:43:55,950 NOT ONLY FOR PARTICIPATING BUT 6012 04:43:55,950 --> 04:43:57,885 SHARING THEIR STORIES AND JUST 6013 04:43:57,885 --> 04:43:59,020 MAKING THE VIDEOS IS NOT EASY 6014 04:43:59,020 --> 04:44:00,221 WHEN YOU SUFFER FROM THIS 6015 04:44:00,221 --> 04:44:06,894 DISEASE. 6016 04:44:06,894 --> 04:44:08,529 SHARING YOUR OWN ILLNESS 6017 04:44:08,529 --> 04:44:10,097 REQUIRES COVERAGE. 6018 04:44:10,097 --> 04:44:11,666 THESE PATIENTS ARE THE MOVERS 6019 04:44:11,666 --> 04:44:13,334 AND SHAKERS AND MAKE THINGS 6020 04:44:13,334 --> 04:44:15,469 HAPPEN THAT WOULDN'T HAPPEN 6021 04:44:15,469 --> 04:44:16,003 OTHERWISE FOR THAT WE'RE 6022 04:44:16,003 --> 04:44:16,370 EXTREMELY GRATE. 6023 04:44:16,370 --> 04:44:18,606 . 6024 04:44:18,606 --> 04:44:19,607 -- GRATEFUL. 6025 04:44:19,607 --> 04:44:20,941 WE HAVE OTHER PATIENTS HERE IN 6026 04:44:20,941 --> 04:44:21,909 THE AUDIENCE. 6027 04:44:21,909 --> 04:44:23,944 THAT HAVE IDENTIFIED THEMSELVES 6028 04:44:23,944 --> 04:44:24,612 PREVIOUSLY. 6029 04:44:24,612 --> 04:44:27,948 I WELCOME THEM TO COME OVER AND 6030 04:44:27,948 --> 04:44:35,256 MAYBE COMMENT IF YOU WANT. 6031 04:44:35,256 --> 04:44:36,924 TALK ABOUT YOUR EXPERIENCE AND 6032 04:44:36,924 --> 04:44:39,126 WE LEARN FROM YOU SO HERE'S A 6033 04:44:39,126 --> 04:44:40,127 GREAT OPPORTUNITY FOR YOU TO DO 6034 04:44:40,127 --> 04:44:50,237 THAT. 6035 04:44:51,238 --> 04:44:56,444 >> JOE HANSON AGAIN, PATIENT. 6036 04:44:56,444 --> 04:44:59,947 EVERYONE WORKED HARD IN THIS 6037 04:44:59,947 --> 04:45:00,414 STUDY. 6038 04:45:00,414 --> 04:45:03,517 BUT HAVING EXPERIENCED 6039 04:45:03,517 --> 04:45:05,686 POSTEXERTIONAL MALAISE OFF AND 6040 04:45:05,686 --> 04:45:09,256 ON FOR 19 1/2 YEARS, I HONESTLY 6041 04:45:09,256 --> 04:45:11,392 DO NOT CONSIDER IT TO BE A 6042 04:45:11,392 --> 04:45:11,892 SUBJECTIVE EXPERIENCE. 6043 04:45:11,892 --> 04:45:13,194 THAT WOULD BE THE LAST WAY I 6044 04:45:13,194 --> 04:45:15,963 WOULD DESCRIBE IT. 6045 04:45:15,963 --> 04:45:26,140 THANK YOU. 6046 04:45:39,153 --> 04:45:40,087 >> I'LL JUST SAY THERE'S SIMILAR 6047 04:45:40,087 --> 04:45:42,990 EXPERIENCES. 6048 04:45:42,990 --> 04:45:48,496 THANK YOU. 6049 04:45:48,496 --> 04:45:50,498 >> DO YOU HAVE ANYTHING I'D LIKE 6050 04:45:50,498 --> 04:45:51,532 TO COMMENT ON BEFORE WE WRAP UP 6051 04:45:51,532 --> 04:45:58,305 THE PANEL? 6052 04:45:58,305 --> 04:46:03,711 >> I'D LIKE TO THANK EVERYONE 6053 04:46:03,711 --> 04:46:05,279 AGAIN. 6054 04:46:05,279 --> 04:46:06,747 IT'S BEEN A TRANSFORMATIVE 6055 04:46:06,747 --> 04:46:09,950 EXPERIENCE AND GRATEFUL TO THE 6056 04:46:09,950 --> 04:46:11,952 TEAM. 6057 04:46:11,952 --> 04:46:19,493 THANK YOU. 6058 04:46:19,493 --> 04:46:25,166 >> ALSO, ABSOLUTELY GRATITUDE IS 6059 04:46:25,166 --> 04:46:27,201 MOST PREVALENT FEELING AND HOPE 6060 04:46:27,201 --> 04:46:30,871 AND EXCITEMENT IT'S JUST THE 6061 04:46:30,871 --> 04:46:34,275 BEGINNING AND WILL LEAD TO MORE 6062 04:46:34,275 --> 04:46:34,608 TO COME. 6063 04:46:34,608 --> 04:46:35,943 THANK YOU, EVERYONE. 6064 04:46:35,943 --> 04:46:46,320 >> THANK YOU EVERYONE. 6065 04:46:47,988 --> 04:46:54,361 >> NOW WE HAVE AN ESTEEMED PANEL 6066 04:46:54,361 --> 04:47:04,038 OF EXPERTS AND WELCOME THEM UP 6067 04:47:04,038 --> 04:47:05,573 FRONT AND TWO ONLINE. 6068 04:47:05,573 --> 04:47:06,607 A HYBRID PANEL. 6069 04:47:06,607 --> 04:47:12,213 WE'LL SEE HOW WE CAN MAKE THAT 6070 04:47:12,213 --> 04:47:16,417 WORK. 6071 04:47:16,417 --> 04:47:21,222 WE HAVE EXPERTS FROM A WIDE 6072 04:47:21,222 --> 04:47:23,491 VARIETY OF EXPERIENCES WITH 6073 04:47:23,491 --> 04:47:25,893 RESEARCH WITH ME/CFS AND I WANT 6074 04:47:25,893 --> 04:47:28,596 TO INTRODUCE THEM TO YOU. 6075 04:47:28,596 --> 04:47:30,898 VICKY WHITTEMORE IS THE PROGRAM 6076 04:47:30,898 --> 04:47:31,732 DIRECTOR AT NINDS. 6077 04:47:31,732 --> 04:47:35,903 SHE OVERSEES THE ME/CFS RESEARCH 6078 04:47:35,903 --> 04:47:38,405 PROGRAM AND WAS INSTRUMENTAL IN 6079 04:47:38,405 --> 04:47:39,573 PUTTING TOGETHER THE ROAD MAP 6080 04:47:39,573 --> 04:47:40,274 FOR ME/CFS. 6081 04:47:40,274 --> 04:47:45,880 THAT ENSURES THE RESEARCH WILL 6082 04:47:45,880 --> 04:47:50,918 CONTINUE AS LONG AS ANNIVERSARY 6083 04:47:50,918 --> 04:47:54,522 TO CURE THE DISEASE. 6084 04:47:54,522 --> 04:48:01,195 JOE BREEN HAS BEEN A STRONG 6085 04:48:01,195 --> 04:48:02,496 SUPPORTER OF ME/CFS RESEARCH. 6086 04:48:02,496 --> 04:48:05,466 TOGETHER THEY OVERSEE THE ENTIRE 6087 04:48:05,466 --> 04:48:07,201 PORTFOLIO ACROSS THE COUNTRY 6088 04:48:07,201 --> 04:48:09,003 FUNDED THROUGH NIH. 6089 04:48:09,003 --> 04:48:13,007 THEY HAVE A GREAT DEPTH AND 6090 04:48:13,007 --> 04:48:13,674 BREADTH OF KNOWLEDGE WITH THE 6091 04:48:13,674 --> 04:48:17,278 DISEASE. 6092 04:48:17,278 --> 04:48:27,888 NEXT I WANTED TO EINTRODUCE 6093 04:48:27,888 --> 04:48:31,225 DR. KOMAROFF AND SENIOR 6094 04:48:31,225 --> 04:48:34,628 PHYSICIAN AT THE BRIGHAM AND 6095 04:48:34,628 --> 04:48:36,764 MANY LEADERSHIP POSITIONS AND 6096 04:48:36,764 --> 04:48:39,500 WAS A PIONEER IN GETTING CLOSER 6097 04:48:39,500 --> 04:48:44,171 TO ME/CFS RESEARCH AND HAS BEEN 6098 04:48:44,171 --> 04:48:45,439 A STRONG ADVOCATE OF THIS 6099 04:48:45,439 --> 04:48:47,007 RESEARCH AND DISEASE AND 6100 04:48:47,007 --> 04:48:48,342 PATIENTS THEMSELVES AND WE'VE 6101 04:48:48,342 --> 04:48:49,276 LEARNED A TREMENDOUS AMOUNT FROM 6102 04:48:49,276 --> 04:48:50,578 THEM. 6103 04:48:50,578 --> 04:48:53,247 HE WAS ON OUR ADJUDICATION PANEL 6104 04:48:53,247 --> 04:48:56,216 AND WHEN WE FIRST STARTED THE 6105 04:48:56,216 --> 04:48:58,252 STUDY HE GAVE US EXCELLENT 6106 04:48:58,252 --> 04:49:00,688 ADVICE ON HOW TO SHAPE IT AND 6107 04:49:00,688 --> 04:49:03,991 WHAT TO DO AND THROUGHOUT THIS 6108 04:49:03,991 --> 04:49:06,260 PROCESS HE'S CONTINUED TO BE A 6109 04:49:06,260 --> 04:49:06,627 CHAMPION FOR US. 6110 04:49:06,627 --> 04:49:08,062 WE THANK HIM FOR THAT AND THANK 6111 04:49:08,062 --> 04:49:10,230 HIM FOR TAKING THE TIME TO SERVE 6112 04:49:10,230 --> 04:49:11,765 ON THIS PANEL. 6113 04:49:11,765 --> 04:49:15,603 I KNOW HE WOULD HAVE LIKED TO BE 6114 04:49:15,603 --> 04:49:22,543 HERE IN PERSON BUT HAD A LONG 6115 04:49:22,543 --> 04:49:22,977 TR 6116 04:49:22,977 --> 04:49:23,177 TRIP. 6117 04:49:23,177 --> 04:49:33,220 NEXT IS NANCY KLIMAS ON ZOOM AND 6118 04:49:33,220 --> 04:49:35,489 HAS OVER 40 YEARS ON ME/CFS AND 6119 04:49:35,489 --> 04:49:37,324 TAKE CARING OF THESE PATIENTS. 6120 04:49:37,324 --> 04:49:38,292 WE HAVE LEARNED A TREMENDOUS 6121 04:49:38,292 --> 04:49:43,464 AMOUNT FROM HER AS WELL. 6122 04:49:43,464 --> 04:49:44,999 SHE'S INSTRUMENTAL IN REFERRING 6123 04:49:44,999 --> 04:49:46,934 PATIENTS TO US AND DIRECTOR OF 6124 04:49:46,934 --> 04:49:53,307 THE INSTITUTE OF NEUROIMMUNE AT 6125 04:49:53,307 --> 04:49:55,743 NOVA SOUTHWESTERN COMMUNITY AND 6126 04:49:55,743 --> 04:49:56,510 DRUSHLTH DIRECTOR 6127 04:50:02,149 --> 04:50:03,984 CHAIR OF THE DEPARTMENT OF 6128 04:50:03,984 --> 04:50:06,620 CLINICAL IMMUNOLOGY. 6129 04:50:06,620 --> 04:50:09,790 THANK YOU FOR SERVING ON THE 6130 04:50:09,790 --> 04:50:09,990 PANEL. 6131 04:50:09,990 --> 04:50:13,360 I'D LIKE TO INTRODUCE A CLOSE 6132 04:50:13,360 --> 04:50:19,433 COLLABORATOR FRIEND AND EXPERT, 6133 04:50:19,433 --> 04:50:20,901 DR. LIPKIN. 6134 04:50:20,901 --> 04:50:26,573 THE THE JOHN SNOW PROFESSOR OF 6135 04:50:26,573 --> 04:50:27,241 EPIDEMIOLOGY AT COLUMBIA 6136 04:50:27,241 --> 04:50:29,276 UNIVERSITY AND DIRECTOR FOR THE 6137 04:50:29,276 --> 04:50:32,513 CENTER OF INFECTION AND IMMUNITY 6138 04:50:32,513 --> 04:50:35,215 AND MOST KNOW HIM AS THE VIRUS 6139 04:50:35,215 --> 04:50:35,449 HUNTER. 6140 04:50:35,449 --> 04:50:37,418 SHE'S DISCOVERED MORE VIRUSES 6141 04:50:37,418 --> 04:50:41,555 THAN ANYBODY ON THE PLANET FROM 6142 04:50:41,555 --> 04:50:45,592 WEST NILE TO SARS AND HAS BEEN 6143 04:50:45,592 --> 04:50:47,061 INVOLVED IN THE SARS COV2 6144 04:50:47,061 --> 04:50:51,965 PANDEMIC AS WELL AND HAS BEEN 6145 04:50:51,965 --> 04:50:53,167 STRONGLY COMMITTED TO STUDYING 6146 04:50:53,167 --> 04:50:54,468 ME/CFS AND DEVOTING THE REST OF 6147 04:50:54,468 --> 04:50:57,271 HIS ACADEMIC CAREER TO THIS 6148 04:50:57,271 --> 04:51:01,709 DISEASE AND HAS BEEN A STRONG 6149 04:51:01,709 --> 04:51:03,110 FOR TREATMENT TRIALS ON THE 6150 04:51:03,110 --> 04:51:03,410 DISEASE. 6151 04:51:03,410 --> 04:51:07,114 WE LEARNED TREMENDOUSLY FROM HIM 6152 04:51:07,114 --> 04:51:10,484 AND WAS TELLING ME HOW TO DO 6153 04:51:10,484 --> 04:51:13,420 ANALYSIS AND WHO TO TALK TO FOR 6154 04:51:13,420 --> 04:51:16,090 WHICH I GREATLY PATIENT. 6155 04:51:16,090 --> 04:51:17,357 THANK YOU FOR SERVING ON THE 6156 04:51:17,357 --> 04:51:17,624 PANEL. 6157 04:51:17,624 --> 04:51:27,968 I'LL TURN IT OVER TO YOU NOW TO 6158 04:51:27,968 --> 04:51:31,438 DISCUSS FINDINGS AND WHERE TO 6159 04:51:31,438 --> 04:51:41,515 GO. 6160 04:51:41,715 --> 04:51:44,318 >> THANK YOU FOR ALLOWING KNOW 6161 04:51:44,318 --> 04:51:44,618 PARTICIPATE. 6162 04:51:44,618 --> 04:51:46,920 A COMMITMENT ON THE WEST COAST 6163 04:51:46,920 --> 04:51:48,222 MADE IT IMPOSSIBLE TO BE THERE 6164 04:51:48,222 --> 04:51:48,689 TODAY. 6165 04:51:48,689 --> 04:51:54,328 I WANT TO START WITH SHORT 6166 04:51:54,328 --> 04:51:57,998 COMMENTS FOR CONTEXT. 6167 04:51:57,998 --> 04:52:04,004 40 YEARS AGO WITH INTEREST IN 6168 04:52:04,004 --> 04:52:07,241 ME/CFS RESURFACED WE DIDN'T 6169 04:52:07,241 --> 04:52:08,642 IDENTIFIED UNDERLYING 6170 04:52:08,642 --> 04:52:10,110 ABNORMALITIES THAT COULD EXPLAIN 6171 04:52:10,110 --> 04:52:13,347 THE SYMPTOMS AND THAT LED SOME 6172 04:52:13,347 --> 04:52:15,182 PEOPLE TO SAY THERE'S NOTHING 6173 04:52:15,182 --> 04:52:15,983 REALLY WRONG WITH PEOPLE WITH 6174 04:52:15,983 --> 04:52:21,221 THIS ILLNESS. 6175 04:52:21,221 --> 04:52:23,891 OVER 40 YEARS THERE'S NOW ABOUT 6176 04:52:23,891 --> 04:52:26,894 10,000 PER REVIEWED PUBLICATIONS 6177 04:52:26,894 --> 04:52:29,296 THAT INVOLVE THOUSAND OF 6178 04:52:29,296 --> 04:52:31,565 PATIENTS WITH THIS ILLNESS THAT 6179 04:52:31,565 --> 04:52:34,134 ARE REVEALED REPLICATED 6180 04:52:34,134 --> 04:52:37,571 UNDERLYING BIOLOGICAL 6181 04:52:37,571 --> 04:52:40,941 ABNORMALITIES OF THE BRAIN, 6182 04:52:40,941 --> 04:52:45,913 IMMUNE SYSTEM AND ENERGY 6183 04:52:45,913 --> 04:52:47,915 METABOLISM AND GUT MICROBIOME 6184 04:52:47,915 --> 04:52:49,583 AND CARDIO VASCULAR SYSTEM AND 6185 04:52:49,583 --> 04:52:51,218 THE STUDY PRESENTED TODAY IS THE 6186 04:52:51,218 --> 04:52:57,791 MOST INTENSIVE STUDY OF PEOPLE 6187 04:52:57,791 --> 04:53:01,595 WITH ME/CFS THAT HAS EVER BEEN 6188 04:53:01,595 --> 04:53:05,132 DONE AND MORE MEASUREMENTS OF 6189 04:53:05,132 --> 04:53:07,401 BODY SYSTEMS THAN HAS BEEN DONE 6190 04:53:07,401 --> 04:53:07,634 BEFORE. 6191 04:53:07,634 --> 04:53:18,212 IT CONFIRMED MANY PAST STUDIES 6192 04:53:18,212 --> 04:53:23,951 AND IN OF NEW ABNORMALITIES NOT 6193 04:53:23,951 --> 04:53:26,086 PREVIOUSLY RECORDED. 6194 04:53:26,086 --> 04:53:31,658 IF YOU WANTED TO BOIL DOWN WHAT 6195 04:53:31,658 --> 04:53:33,293 THE COMPLICATED STUDY WITH 6196 04:53:33,293 --> 04:53:35,295 MASSIVE AMOUNTS OF DATA HAS 6197 04:53:35,295 --> 04:53:43,670 SAID, IT SAYS ME/CFS IS A BRAIN 6198 04:53:43,670 --> 04:53:50,444 DISEASE LIKELY INDUCED BY 6199 04:53:50,444 --> 04:53:50,744 EXHAUSTION. 6200 04:53:50,744 --> 04:53:55,482 ONE NOVEL FINDING IS THIS 6201 04:53:55,482 --> 04:53:56,717 INVOLUNTARY UNDERLYING 6202 04:53:56,717 --> 04:53:59,019 ABNORMALITY IN ONE PART OF THE 6203 04:53:59,019 --> 04:54:02,756 BRAIN THAT INVOLVES DEFICIENCY 6204 04:54:02,756 --> 04:54:06,159 OF THE BRAIN CHEMICAL 6205 04:54:06,159 --> 04:54:06,827 NOREPINEPHRINE. 6206 04:54:06,827 --> 04:54:08,562 THAT ABNORMALITY IN THE IMMUNE 6207 04:54:08,562 --> 04:54:10,163 EXHAUSTION FOUND BY THE STUDY 6208 04:54:10,163 --> 04:54:11,965 HAVE BEEN IDENTIFIED BY THE 6209 04:54:11,965 --> 04:54:15,369 STUDY AT TARGETS FOR POTENTIAL 6210 04:54:15,369 --> 04:54:16,770 TREATMENTS AND WILL OPEN THE 6211 04:54:16,770 --> 04:54:19,506 DOOR TO STUDYING THE UNDERLYING 6212 04:54:19,506 --> 04:54:20,641 BIOLOGY OF THE ILLNESS. 6213 04:54:20,641 --> 04:54:26,880 I THINK THIS IS ALL REALLY GOOD 6214 04:54:26,880 --> 04:54:29,216 NEWS THAT ADDS TO THE GROWING 6215 04:54:29,216 --> 04:54:30,717 RECOGNITION THAT ME/CFS AND LONG 6216 04:54:30,717 --> 04:54:36,056 COVID-19 AND OTHER POST ACUTE 6217 04:54:36,056 --> 04:54:41,728 SYNDROMES IS A MEASURE OF THE 6218 04:54:41,728 --> 04:54:46,099 RECOGNITION AND PARADOXICALLY 6219 04:54:46,099 --> 04:54:49,002 TIME MAGAZINE ANNOUNCED THE MOST 6220 04:54:49,002 --> 04:54:50,404 INFLUENTIAL PEOPLE IN GLOBAL 6221 04:54:50,404 --> 04:54:52,372 HEALTH INCLUDING ALL DISEASES 6222 04:54:52,372 --> 04:54:53,907 AND ALL PEOPLE OVER THE WORLD AN 6223 04:54:53,907 --> 04:54:57,311 OF THOSE ONE IS A PATIENT WITH 6224 04:54:57,311 --> 04:54:57,577 ME/CFS. 6225 04:54:57,577 --> 04:55:07,587 A PATIENT ACTIVIST AND SIGNSS - 6226 04:55:07,587 --> 04:55:09,122 SCIENTISTS INCLUDING DR. NATH. 6227 04:55:09,122 --> 04:55:19,666 I THINK CONGRATULATIONS TO THEM 6228 04:55:20,867 --> 04:55:21,802 GOOD NEWS IT'S RECOGNIZED MORE 6229 04:55:21,802 --> 04:55:22,069 AND MORE. 6230 04:55:22,069 --> 04:55:23,971 LET ME THROW IT TO THE PANEL FOR 6231 04:55:23,971 --> 04:55:27,207 S ON TODAY. 6232 04:55:27,207 --> 04:55:32,179 -- OBSERVATIONS ON TODAY. 6233 04:55:32,179 --> 04:55:35,949 >> I'VE THAT'D PLEASURE OF WORK 6234 04:55:35,949 --> 04:55:44,825 WITH TONY FOUR YEARS. 6235 04:55:44,825 --> 04:55:46,093 HE'S GOOD AT SUMMING UP THE 6236 04:55:46,093 --> 04:55:47,094 STATE OF KNOWLEDGE. 6237 04:55:47,094 --> 04:55:54,368 I WANT TO ECHO HIS COMMENTS WITH 6238 04:55:54,368 --> 04:55:54,668 THE STUDY. 6239 04:55:54,668 --> 04:55:57,337 THAT NOWHERE BUT THE NIH WHERE 6240 04:55:57,337 --> 04:55:59,373 THIS COULD HAVE BEEN DONE AND 6241 04:55:59,373 --> 04:56:00,640 THE LEADERSHIP IS EXTRAORDINARY. 6242 04:56:00,640 --> 04:56:05,212 IS THIS THE LAST WORD ON ME/CFS? 6243 04:56:05,212 --> 04:56:05,612 OBVIOUSLY NOT. 6244 04:56:05,612 --> 04:56:07,781 I WANTED TO TRY TO SUMMARIZE 6245 04:56:07,781 --> 04:56:11,952 WHAT A TOOK FROM TODAY'S 6246 04:56:11,952 --> 04:56:13,887 CONVERSATION AND DISCUSS THE 6247 04:56:13,887 --> 04:56:16,256 IMPLICATIONS OF SOME FINDINGS. 6248 04:56:16,256 --> 04:56:17,924 THE IMMUNOLOGY OF ME/CFS GOES 6249 04:56:17,924 --> 04:56:28,235 BACK A LONG TIME. 6250 04:56:29,336 --> 04:56:31,805 WE FOUND EVIDENCE OF 6251 04:56:31,805 --> 04:56:34,341 ABNORMALITIES OF B CELLS IN THE 6252 04:56:34,341 --> 04:56:37,177 '90s AND CHANGE IN CELL COUNTS. 6253 04:56:37,177 --> 04:56:39,946 TODAY WE HEARD ABOUT THIS 6254 04:56:39,946 --> 04:56:44,418 MOLECULE CALLED PD1 ASSOCIATED 6255 04:56:44,418 --> 04:56:45,285 WITH IMMUNE EXHAUSTION. 6256 04:56:45,285 --> 04:56:47,954 THIS IS TARGETED IN PEOPLE WITH 6257 04:56:47,954 --> 04:56:51,291 CERTAIN TYPES OF CANCERS LIKE 6258 04:56:51,291 --> 04:56:53,160 MELANOMA WITH ANTIBODIES. 6259 04:56:53,160 --> 04:56:58,498 YOU CAN SUPPRESS ITS ACTIVITY. 6260 04:56:58,498 --> 04:57:00,367 THE IMPORTANCE OF THIS COVERS 6261 04:57:00,367 --> 04:57:01,068 SEVERAL AREAS. 6262 04:57:01,068 --> 04:57:03,603 ONE IS IF THERE'S A PERSISTENT 6263 04:57:03,603 --> 04:57:04,938 INFECTION AND NOT SAYING THERE 6264 04:57:04,938 --> 04:57:07,908 IS BUT IF THERE WERE, INCREASED 6265 04:57:07,908 --> 04:57:11,978 LEVELS OF PD1 OR ANY OF THE 6266 04:57:11,978 --> 04:57:14,581 ASSOCIATED MOLECULES WOULD 6267 04:57:14,581 --> 04:57:15,949 RESULT IN DIFFICULTIES IN 6268 04:57:15,949 --> 04:57:19,119 CLEARING INFECTIONS. 6269 04:57:19,119 --> 04:57:20,153 THAT BRINGS US AND THIS 6270 04:57:20,153 --> 04:57:23,523 PARTICULAR STUDY WAS FOCUSSED ON 6271 04:57:23,523 --> 04:57:25,525 PATIENTS WHO HAD INFECTION BUT I 6272 04:57:25,525 --> 04:57:30,197 THINK REPRESENTS THE MAJORITY O 6273 04:57:30,197 --> 04:57:31,331 OF PEOPLE WITH ME/CFS. 6274 04:57:31,331 --> 04:57:33,066 WHAT DO WE KNOW ABOUT INFECTIONS 6275 04:57:33,066 --> 04:57:33,934 WITH ME/CFS? 6276 04:57:33,934 --> 04:57:34,935 WE'VE BEEN TALKING ABOUT THAT 6277 04:57:34,935 --> 04:57:41,875 FOR A LONG TIME. 6278 04:57:41,875 --> 04:57:43,944 OUR CENTER HAS BEEN TRYING TO 6279 04:57:43,944 --> 04:57:46,746 FIND BACTERIA, VIRUSES, FUNGI 6280 04:57:46,746 --> 04:57:47,948 LINKING THEM TO ME/CFS FOR MANY 6281 04:57:47,948 --> 04:57:56,356 YEARS. 6282 04:57:56,356 --> 04:57:59,092 WE HAVE NOT FOUND SUCH EVIDENCE 6283 04:57:59,092 --> 04:57:59,993 EXCEPT FOR THE MICROBIOME WORK 6284 04:57:59,993 --> 04:58:00,560 I'LL TALK ABOUT IN THE NEXT 6285 04:58:00,560 --> 04:58:08,335 SECTION. 6286 04:58:08,335 --> 04:58:09,936 EITHER WE'RE NOT LOOKING IN THE 6287 04:58:09,936 --> 04:58:13,507 RIGHT PLACE OR AT THE RIGHT TIME 6288 04:58:13,507 --> 04:58:15,942 OR RIGHT SAMPLE OR THERE MAY 6289 04:58:15,942 --> 04:58:21,615 HAVE BEEN HIT-AND-RUN MECHANISM 6290 04:58:21,615 --> 04:58:24,551 I FAVOR SO YOU'RE NOT GOING TO 6291 04:58:24,551 --> 04:58:28,121 FIND IT USING DIRECT METHODS. 6292 04:58:28,121 --> 04:58:30,557 YOU HAVE TO LOOK FOR FOOT PRINTS 6293 04:58:30,557 --> 04:58:33,894 OF EXPOSURE AND THIS BRINGS US 6294 04:58:33,894 --> 04:58:34,528 TO ANTIBODIES. 6295 04:58:34,528 --> 04:58:39,499 THE CHALLENGE WITH ANTIBODIES IS 6296 04:58:39,499 --> 04:58:41,468 THERE IS NO HUGE TEST THAT 6297 04:58:41,468 --> 04:58:42,469 ALLOWS TO YOU SIMULTANEOUSLY 6298 04:58:42,469 --> 04:58:43,970 TEST IN A RIGOROUS WAY FOR 6299 04:58:43,970 --> 04:58:50,443 EXPOSURE. 6300 04:58:50,443 --> 04:58:52,546 THERE ARE METHODS COMING TO DO 6301 04:58:52,546 --> 04:58:53,547 THIS TO SOME EXTENT. 6302 04:58:53,547 --> 04:59:00,120 I THINK IT WILL BE IMPORTANT. 6303 04:59:00,120 --> 04:59:02,222 THE OTHER ISSUE GETS BACK TO 6304 04:59:02,222 --> 04:59:02,522 TIMING. 6305 04:59:02,522 --> 04:59:07,227 IF DO I CROSS-SECTIONAL FALSE 6306 04:59:07,227 --> 04:59:09,629 AND LOOK AT ONE POINT -- 6307 04:59:09,629 --> 04:59:11,898 ANALYSIS AND LOOK AT ONE POINT 6308 04:59:11,898 --> 04:59:14,067 IN TIME AND A YEAR LATER I MAY 6309 04:59:14,067 --> 04:59:15,969 HAVE MISSED A DISEASE THAT 6310 04:59:15,969 --> 04:59:17,571 TRIGGERED AND THAT'S IMPORTANT. 6311 04:59:17,571 --> 04:59:22,976 THE TWO APPROACHES REFERRING TO 6312 04:59:22,976 --> 04:59:24,544 WORK WE'RE DOING TOGETHER WE 6313 04:59:24,544 --> 04:59:27,948 LOOK AT INDIVIDUALS WITH AN 6314 04:59:27,948 --> 04:59:33,119 EXACERBATION IN THE SYMPTOMS AND 6315 04:59:33,119 --> 04:59:34,788 SPECIFICALLY LOOK TO SEE IF WE 6316 04:59:34,788 --> 04:59:36,923 CAN FIND EVIDENCE OF INFECTION 6317 04:59:36,923 --> 04:59:40,493 AT THAT POINT POINT AND LOOK FOR 6318 04:59:40,493 --> 04:59:42,195 EVIDENCE IN ANTIBODY PROFILES 6319 04:59:42,195 --> 04:59:43,330 THAT HAVE CHANGED. 6320 04:59:43,330 --> 04:59:47,734 THE OTHER APPROACH IS TO USE A 6321 04:59:47,734 --> 04:59:48,702 REPOSITORY AT THE DEPARTMENT OF 6322 04:59:48,702 --> 04:59:52,305 DEFENSE USED TO LOOK AT TRIGGERS 6323 04:59:52,305 --> 04:59:54,140 FOR MULTIPLE SCLEROSIS AND YOU 6324 04:59:54,140 --> 04:59:58,678 CAN LOOK FOR PEOPLE WHO 6325 04:59:58,678 --> 04:59:59,946 SUBSEQUENTLY DEVELOPED ME/CFS OR 6326 04:59:59,946 --> 05:00:02,082 RELATED SYNDROME AND ASK WHETHER 6327 05:00:02,082 --> 05:00:03,550 OR NOT THE YEAR PRIOR BECAUSE 6328 05:00:03,550 --> 05:00:07,921 THE SAMPLES WERE COLLECTED 6329 05:00:07,921 --> 05:00:08,555 ANNUALLY WHETHER THERE'S AN 6330 05:00:08,555 --> 05:00:19,065 EXPOSURE THAT MIGHT BE LINKED. 6331 05:00:21,101 --> 05:00:25,272 AND WHAT SOME PEOPLE ALLUDED TO 6332 05:00:25,272 --> 05:00:27,974 IS THE INNATE IMMUNE SYSTEM. 6333 05:00:27,974 --> 05:00:33,713 IT'S PRIMITIVE. 6334 05:00:33,713 --> 05:00:35,949 YOU CAN FIND IT IN FRUIT FLIES 6335 05:00:35,949 --> 05:00:38,918 AND WORMS AND ELIMINATING 6336 05:00:38,918 --> 05:00:45,058 VIRUSES AND BACTERIA FUNGI AND 6337 05:00:45,058 --> 05:00:47,327 IF NOT CONTROLLED YOU CAN FIND 6338 05:00:47,327 --> 05:00:49,129 OF THE EXPRESSION OF VARIOUS 6339 05:00:49,129 --> 05:00:51,031 MOLECULES THAT GIVE RISE TO 6340 05:00:51,031 --> 05:00:52,265 SICKNESS BEHAVIORS, FOR EXAMPLE. 6341 05:00:52,265 --> 05:00:58,004 THEY CAN HAVE INDIRECT AND 6342 05:00:58,004 --> 05:00:59,072 DIRECT EFFECTS ON MITOCHONDRIA 6343 05:00:59,072 --> 05:01:09,482 AND IMPACT THE FUNCTION. 6344 05:01:17,957 --> 05:01:19,993 BUTYRATE MODULATES IMMUNE 6345 05:01:19,993 --> 05:01:23,963 RESPONSES AND MAINTAINS THE 6346 05:01:23,963 --> 05:01:27,133 INTEGRITY OF THE CLONIC 6347 05:01:27,133 --> 05:01:28,268 EPITHELIUM AND KEEPS WHAT'S 6348 05:01:28,268 --> 05:01:30,737 SUPPOSED TO BE OUTSIDE OF THE 6349 05:01:30,737 --> 05:01:33,273 BODY AND PREVENTS IT FROM GOING 6350 05:01:33,273 --> 05:01:33,673 INSIDE. 6351 05:01:33,673 --> 05:01:37,777 THE IMPLICATIONS ARE IF WE CAN 6352 05:01:37,777 --> 05:01:39,946 FIND WAYS TO DAMPEN THE IMMUNE 6353 05:01:39,946 --> 05:01:47,187 RESPONSES PARTICULARLY INNATE 6354 05:01:47,187 --> 05:01:49,222 IMMUNE RESPONSES IT HAS TO BE 6355 05:01:49,222 --> 05:01:50,657 DOWN SAFELY AND RIGOROUSLY BUT 6356 05:01:50,657 --> 05:01:54,160 WHERE THE TIME HAS COME. 6357 05:01:54,160 --> 05:01:57,497 SIMILARLY WITH BUTYRATE AND THE 6358 05:01:57,497 --> 05:01:59,332 THERE ARE WAYS BY USING 6359 05:01:59,332 --> 05:02:00,934 PREBIOTICS SPECIFIC FOODS THAT 6360 05:02:00,934 --> 05:02:03,002 ENCOURAGE THE GROWTH OF SPECIFIC 6361 05:02:03,002 --> 05:02:06,306 BACTERIA AND PROBIOTICS THAT 6362 05:02:06,306 --> 05:02:08,108 CHANGE THE COMPOSITION OF THE 6363 05:02:08,108 --> 05:02:08,375 GUT. 6364 05:02:08,375 --> 05:02:11,778 THESE ARE THINGS WE CAN BE 6365 05:02:11,778 --> 05:02:13,213 PURSUING AND I THINK AGAIN THE 6366 05:02:13,213 --> 05:02:15,248 TIME HAS COME TO START THINK 6367 05:02:15,248 --> 05:02:21,588 ABOUT HOW TO DO THIS. 6368 05:02:21,588 --> 05:02:26,259 AS I THINK ABOUT THE DISEASE TO 6369 05:02:26,259 --> 05:02:36,636 THE METABOLIC FACTORS. 6370 05:02:36,936 --> 05:02:39,105 THERE'S A VARIETY OF SMALL 6371 05:02:39,105 --> 05:02:41,808 MOLECULES RELEASED TO MEASURE 6372 05:02:41,808 --> 05:02:42,075 PROFILE. 6373 05:02:42,075 --> 05:02:45,345 THE IF YEAR INTERESTED IN 6374 05:02:45,345 --> 05:02:47,947 SOMETHING HAPPENING IN SIDE OF 6375 05:02:47,947 --> 05:02:50,283 THE CELL THAT FACTOR MAY BE 6376 05:02:50,283 --> 05:02:54,754 DILUTED BY THE TIME IT GETS OUT 6377 05:02:54,754 --> 05:02:58,024 INTO A FLUID LIKE PLASMA TO 6378 05:02:58,024 --> 05:02:58,291 MEASURE. 6379 05:02:58,291 --> 05:03:00,560 NONETHELESS, DESPITE THE LACK OF 6380 05:03:00,560 --> 05:03:03,430 SENSITIVITY, WE AND OTHERS ARE 6381 05:03:03,430 --> 05:03:05,865 FINDING SIGNALS THAT WILL BE 6382 05:03:05,865 --> 05:03:07,567 VERY IMPORTANT. 6383 05:03:07,567 --> 05:03:11,104 NOW, WHAT WE DIDN'T TALK A LOT 6384 05:03:11,104 --> 05:03:13,640 ABOUT TODAY WERE SEX SPECIFIC 6385 05:03:13,640 --> 05:03:14,974 DIFFERENCES AND I THINK THIS IS 6386 05:03:14,974 --> 05:03:17,110 AN OVERSIGHT. 6387 05:03:17,110 --> 05:03:19,946 PROBABLY BECAUSE THERE WEREN'T 6388 05:03:19,946 --> 05:03:22,048 ENOUGH SUBJECTS. 6389 05:03:22,048 --> 05:03:26,619 IN OUR EXPERIENCE MORE WOMEN ARE 6390 05:03:26,619 --> 05:03:32,292 AFFECTED THAN MEN AND WOMEN HAVE 6391 05:03:32,292 --> 05:03:35,562 DIFFERENT METABOLIC 6392 05:03:35,562 --> 05:03:36,996 ABNORMALITIES AND WE FOUND 6393 05:03:36,996 --> 05:03:39,232 RESULTS IN THE ELABORATION OF 6394 05:03:39,232 --> 05:03:45,538 THE ENERGY MOLECULES AND ATP YOU 6395 05:03:45,538 --> 05:03:51,511 HEARD ABOUT THERE'S THERE'S ALSO 6396 05:03:51,511 --> 05:03:55,782 LIPID PROBLEMS ASSOCIATED WITH 6397 05:03:55,782 --> 05:03:56,115 INFLAMMATION. 6398 05:03:56,115 --> 05:03:59,719 SOME MAY REMEMBER THE MOVIE 6399 05:03:59,719 --> 05:04:02,021 CALLED SUPER SIZE ME? 6400 05:04:02,021 --> 05:04:03,590 DOES ANYBODY REMEMBER THAT? 6401 05:04:03,590 --> 05:04:07,694 HE GOES ON THIS DIET TO 6402 05:04:07,694 --> 05:04:14,334 McDONALDS AND EVERY TIME THEY 6403 05:04:14,334 --> 05:04:18,104 SAY SUPER SIZE ME AND EATS IT 6404 05:04:18,104 --> 05:04:23,643 AND GETS THE IT INFLAMMATORY 6405 05:04:23,643 --> 05:04:30,149 DISEASE ASSOCIATED. 6406 05:04:30,149 --> 05:04:31,951 I'M TRYING TO SAY LIPIDS AREN'T 6407 05:04:31,951 --> 05:04:42,362 NECESSARY GOOD FOR YOU. 6408 05:05:31,811 --> 05:05:37,317 >> THEY'VE FOUND ABNORMALITIES 6409 05:05:37,317 --> 05:05:39,485 AND THE FINDINGS ON 6410 05:05:39,485 --> 05:05:41,020 CATECHOLAMINE WERE INTERESTING. 6411 05:05:41,020 --> 05:05:44,457 I'M WONDERING WHETHER EVERYTHING 6412 05:05:44,457 --> 05:05:47,460 WAS WITH DECREASE IN SYNTHESIS 6413 05:05:47,460 --> 05:05:48,661 AND WHETHER THERE'S PROBLEMS IN 6414 05:05:48,661 --> 05:05:51,965 REUP TAKE AND I DON'T FLOW IF 6415 05:05:51,965 --> 05:06:02,375 GOLDSTEIN IS STILL HERE. 6416 05:06:03,276 --> 05:06:10,216 AND THERE'S THINGS LIKE REUP 6417 05:06:10,216 --> 05:06:20,493 TAKE INHIBITERS. 6418 05:06:24,731 --> 05:06:26,499 WE DON'T HAVE ENOUGH RESOURCES 6419 05:06:26,499 --> 05:06:29,636 WHAT WE NEED TO DO AND IF I 6420 05:06:29,636 --> 05:06:31,070 LEARNED ANYTHING AT 40 YEARS OF 6421 05:06:31,070 --> 05:06:31,704 DOING THIS WORK WE NEED BETTER 6422 05:06:31,704 --> 05:06:41,047 ADVOCATES. 6423 05:06:41,047 --> 05:06:44,150 THE SQUEAKY WHEEL GETS TE 6424 05:06:44,150 --> 05:06:45,018 GREASE. 6425 05:06:45,018 --> 05:06:45,418 OVER. 6426 05:06:45,418 --> 05:06:47,320 >> CAN I ASK VICKY WHITMORE TO 6427 05:06:47,320 --> 05:06:52,825 COMMENT ON TODAY'S PRESENTATION. 6428 05:06:52,825 --> 05:06:55,962 SURE, THANK YOU TONY AND IAN. 6429 05:06:55,962 --> 05:07:06,205 NICE SUMMARY. 6430 05:07:28,594 --> 05:07:33,900 I ASKED ABOUT AUTONOMIC DISEASE 6431 05:07:33,900 --> 05:07:39,806 AND I LEARNED A LOT AND THE 6432 05:07:39,806 --> 05:07:42,775 WINDOW IN THE RESEARCH HAS AND 6433 05:07:42,775 --> 05:07:45,578 WHEN DR. KOROSHETZ AGREED TO 6434 05:07:45,578 --> 05:07:47,447 TAKE OVER COORDINATING THE TRANS 6435 05:07:47,447 --> 05:07:50,616 NIH ME/CFS WORKING GROUP AND 6436 05:07:50,616 --> 05:07:52,385 MOVED THAT TO NINDS AND JOE AND 6437 05:07:52,385 --> 05:07:54,087 I HAVE BEEN WORKING CLOSELY WITH 6438 05:07:54,087 --> 05:07:58,958 DR. KOROSHETZ SINCE THEN. 6439 05:07:58,958 --> 05:08:02,228 LOOKING AT THE DATA AND RESEARCH 6440 05:08:02,228 --> 05:08:07,900 BEING DONE THERE WAS AND WHERE 6441 05:08:07,900 --> 05:08:09,936 WE ARE TODAY, WE'RE CONSIDERING 6442 05:08:09,936 --> 05:08:15,742 THE LENGTH OF ILLNESS THE ITSELF 6443 05:08:15,742 --> 05:08:18,578 OF THE INDIVIDUAL AND CONSIDER 6444 05:08:18,578 --> 05:08:20,279 ABOUT WHAT IS POTENTIALLY THE 6445 05:08:20,279 --> 05:08:21,714 TRIGGER OF THE DISEASE AND 6446 05:08:21,714 --> 05:08:23,282 FACTORS IF YOU LOOK AT THE OLDER 6447 05:08:23,282 --> 05:08:24,851 LITERATURE EVERYONE WAS PUT INTO 6448 05:08:24,851 --> 05:08:26,419 ONE BUCKET WHETHER YOU'D BEEN 6449 05:08:26,419 --> 05:08:31,524 ILL FOR THREE YEARS OR 30 YEARS. 6450 05:08:31,524 --> 05:08:33,926 WE'RE FINDING FROM THE RESULTS 6451 05:08:33,926 --> 05:08:35,027 OF THE COLLABORATIVE CENTERS 6452 05:08:35,027 --> 05:08:36,295 THERE'S A SIGNIFICANT DIFFERENCE 6453 05:08:36,295 --> 05:08:38,631 BETWEEN THE INDIVIDUALS WHO HAVE 6454 05:08:38,631 --> 05:08:41,367 BEEN ILL FOR A FEW YEARS VERSUS 6455 05:08:41,367 --> 05:08:47,173 ILL FOR 10 MORE YEARS. 6456 05:08:47,173 --> 05:08:48,274 THOSE WILL ARE CRITICALLY 6457 05:08:48,274 --> 05:08:50,309 IMPORTANT AS WE THINK ABOUT THE 6458 05:08:50,309 --> 05:08:51,711 DISEASE AND THINK ABOUT 6459 05:08:51,711 --> 05:08:56,182 PERFORMING RIGOROUS RESEARCH ON 6460 05:08:56,182 --> 05:08:58,284 THE DISEASE. 6461 05:08:58,284 --> 05:09:00,653 YOU HEARD THE RESEARCH ROAD MAP 6462 05:09:00,653 --> 05:09:02,655 WE'VE WORKED ON FOR A YEAR AND A 6463 05:09:02,655 --> 05:09:05,691 HALF. 6464 05:09:05,691 --> 05:09:08,628 TUNE IN ON THE AFTERNOON OF MAY 6465 05:09:08,628 --> 05:09:10,663 15 WHEN THE REPORT WILL BE 6466 05:09:10,663 --> 05:09:12,198 PRESENTED TO THE NINDS ADVISORY 6467 05:09:12,198 --> 05:09:16,302 COUNCIL AND IT'S JUST THE 6468 05:09:16,302 --> 05:09:17,737 BEGINNING OF CONTINUING TO MOVE 6469 05:09:17,737 --> 05:09:19,272 FORWARD AND STIMULATE RESEARCH. 6470 05:09:19,272 --> 05:09:26,979 I'M NOT GOING STEAL THE THUNDER 6471 05:09:26,979 --> 05:09:30,817 OF THE PRESENTATION BUT WE WENT 6472 05:09:30,817 --> 05:09:31,951 INTO DEVELOPING THE REPORT WITH 6473 05:09:31,951 --> 05:09:34,487 THE PREMISE ASKING ALL THE 6474 05:09:34,487 --> 05:09:37,824 SPEAKERS WHO PARTICIPATED IN THE 6475 05:09:37,824 --> 05:09:40,092 WEBINARS WHAT DO WE KNOW AND 6476 05:09:40,092 --> 05:09:43,963 DON'T WE KNOW AND NEED TO KNOW 6477 05:09:43,963 --> 05:09:47,333 TO NOVE CLINICAL TRIALS. 6478 05:09:47,333 --> 05:09:50,036 PUT THE FOCUS ON THE SCIENTIFIC 6479 05:09:50,036 --> 05:09:51,938 EVIDENCE TO AS RAPIDLY AS 6480 05:09:51,938 --> 05:09:53,973 POSSIBLE GET CLINICAL TRIALS 6481 05:09:53,973 --> 05:09:54,874 GOING FOR INDIVIDUALS WITH 6482 05:09:54,874 --> 05:09:55,942 ME/CFS WHO HAVE BEEN WAITING FOR 6483 05:09:55,942 --> 05:10:03,916 SO LONG. 6484 05:10:03,916 --> 05:10:05,918 CLEARLY THEY NEED TO BE SAFELY, 6485 05:10:05,918 --> 05:10:07,186 RIGOROUSLY AND THOUGHTFULLY. 6486 05:10:07,186 --> 05:10:08,554 THAT'S THE FUTURE DIRECTION OF 6487 05:10:08,554 --> 05:10:10,923 WHERE THE RESEARCH ROAD MAP WILL 6488 05:10:10,923 --> 05:10:13,926 HELPFULLY TAKE US TO ACCELERATE 6489 05:10:13,926 --> 05:10:16,162 THE RESEARCH INTO NEW TREATMENTS 6490 05:10:16,162 --> 05:10:21,767 FOR INDIVIDUALS WITH ME/CFS. 6491 05:10:21,767 --> 05:10:32,178 SO I THINK ALL THE DATA 6492 05:10:36,015 --> 05:10:38,684 REPLICATES SOME DATA AND I THINK 6493 05:10:38,684 --> 05:10:40,786 OPENS AVENUES FOR EXTENSIVE 6494 05:10:40,786 --> 05:10:41,487 RESEARCH. 6495 05:10:41,487 --> 05:10:43,356 WHEN YOU SEE THE RESEARCH REPORT 6496 05:10:43,356 --> 05:10:47,727 YOU'LL SEE WE HAD SIGNIFICANT 6497 05:10:47,727 --> 05:10:49,295 DIFFICULTY NARROWING DOWN THE 6498 05:10:49,295 --> 05:10:50,463 RESEARCH PRIORITIES. 6499 05:10:50,463 --> 05:10:52,164 THERE ARE PROBABLY MORE THAN 100 6500 05:10:52,164 --> 05:10:54,166 RESEARCH PRIORITIES IN THE 6501 05:10:54,166 --> 05:10:56,669 RESEARCH ROAD MAP BECAUSE THAT 6502 05:10:56,669 --> 05:10:58,004 JUST INDICATES HOW MUCH IS YET 6503 05:10:58,004 --> 05:11:01,240 TO BE KNOWN AND HOW MUCH IS YET 6504 05:11:01,240 --> 05:11:03,576 TO BE DONE TO MOVE TOWARDS 6505 05:11:03,576 --> 05:11:06,646 TREATMENTS BUT THE RESEARCH DONE 6506 05:11:06,646 --> 05:11:14,687 AT NIH HAS BEEN SIGNIFICANT AND 6507 05:11:14,687 --> 05:11:18,491 HELPED IN WAYS THAT COULDN'T 6508 05:11:18,491 --> 05:11:19,358 HAVE BEEN DONE ANYWHERE OTHER 6509 05:11:19,358 --> 05:11:24,263 THAN HERE AT THE CLUB CLINICAL 6510 05:11:24,263 --> 05:11:25,031 CENTER. 6511 05:11:25,031 --> 05:11:26,699 THANK YOU. 6512 05:11:26,699 --> 05:11:31,938 >> JOE BREEN, ANY THOUGHTS? 6513 05:11:31,938 --> 05:11:33,673 >> A FEW THOUGHTS. 6514 05:11:33,673 --> 05:11:39,612 NIAID HAS HAD A LONG STANDING IN 6515 05:11:39,612 --> 05:11:44,016 ME/CFS BECAUSE OF THIS 6516 05:11:44,016 --> 05:11:46,485 CONNECTION WITH POSTINFECTION 6517 05:11:46,485 --> 05:11:49,488 AND THE CONNECTION IS THERE THE 6518 05:11:49,488 --> 05:11:51,824 EPIDEMIOLOGIC DATA IS CLEAR TA 6519 05:11:51,824 --> 05:11:55,528 LOOKS LIKE A VIRUS BUT HAVEN'T 6520 05:11:55,528 --> 05:11:57,396 BEEN ABLE TO ISOLATE WHATEVER IT 6521 05:11:57,396 --> 05:11:57,563 IS. 6522 05:11:57,563 --> 05:12:00,866 I HAVE A FEW THOUGHTS FROM 6523 05:12:00,866 --> 05:12:01,100 TODAY. 6524 05:12:01,100 --> 05:12:07,606 I GUESS WE JUST HEARD FROM SOME 6525 05:12:07,606 --> 05:12:11,944 PATIEN 6526 05:12:11,944 --> 05:12:14,347 PATIENTS AND I WAS STRUCK BY 6527 05:12:14,347 --> 05:12:19,518 THEIR CONTRIBUTIONS TO THE STUDY 6528 05:12:19,518 --> 05:12:22,588 BUT THE IDEA THE HOPE THAT 6529 05:12:22,588 --> 05:12:23,923 GRANDKIDS WOULD BENEFIT STRUCK 6530 05:12:23,923 --> 05:12:24,256 ME. 6531 05:12:24,256 --> 05:12:26,759 I HOPE WE DON'T HAVE TO WAIT 6532 05:12:26,759 --> 05:12:31,731 THAT LONG. 6533 05:12:31,731 --> 05:12:34,133 THAT HIT ME HARD AND WANTED TO 6534 05:12:34,133 --> 05:12:35,701 NOTE THAT. 6535 05:12:35,701 --> 05:12:38,771 THAT SHOWED A LOT OF GRACE FRANK 6536 05:12:38,771 --> 05:12:41,974 FLIP -- FRANKLY. 6537 05:12:41,974 --> 05:12:46,379 WE STARTED THIS EFFORT 10, 15 6538 05:12:46,379 --> 05:12:51,951 YEARS AGO WHEN WE 6539 05:12:51,951 --> 05:12:53,486 REOESHREOESHRGANIZED 6540 05:12:53,486 --> 05:12:58,591 THE DISEASE AND I WAS IN 6541 05:12:58,591 --> 05:13:00,459 POST-LYME DISEASE AND I'M STRUCK 6542 05:13:00,459 --> 05:13:03,996 BY OTHER O SIMILARITIES AND 6543 05:13:03,996 --> 05:13:07,867 POSTINFECTIOUS SEQUELAE AND LONG 6544 05:13:07,867 --> 05:13:18,411 COVID NOW I EXPECT SOME OF THE 6545 05:13:19,812 --> 05:13:22,048 BENEFITS WILL TRANSLATE AND THE 6546 05:13:22,048 --> 05:13:23,949 STRUCTURE IN HOW TO STUDY IT 6547 05:13:23,949 --> 05:13:26,452 WITH OUTCOMES THAT ARE PATIENT 6548 05:13:26,452 --> 05:13:27,953 DERIVED AND STANDARDIZED ACROSS 6549 05:13:27,953 --> 05:13:33,426 DIFFERENT MECHANISMS AND 6550 05:13:33,426 --> 05:13:36,362 INTERVENT 6551 05:13:36,362 --> 05:13:41,400 INTERVENTIONS I DON'T KNOW 6552 05:13:41,400 --> 05:13:43,369 ME/CFS IDENTIFIED BEFORE COVID 6553 05:13:43,369 --> 05:13:45,237 IS SAME AS LONG COVID. 6554 05:13:45,237 --> 05:13:47,673 PERHAPS WHEN WE HAVE THE RESULTS 6555 05:13:47,673 --> 05:13:52,511 OF THE MORE IN DEPTH PHENOTYPING 6556 05:13:52,511 --> 05:13:55,948 WE'LL HAVE THAT BUT WE DON'T 6557 05:13:55,948 --> 05:14:00,152 HAVE THAT YET. 6558 05:14:00,152 --> 05:14:02,721 I'M HOPEFUL BECAUSE I SAW NEW 6559 05:14:02,721 --> 05:14:04,523 AVENUES OF RESEARCH AND 6560 05:14:04,523 --> 05:14:06,058 UNDERSTANDING THAT SHOULD 6561 05:14:06,058 --> 05:14:08,194 HOPEFULLY LEAD TO DIFFERENT 6562 05:14:08,194 --> 05:14:10,096 INTERVENTIONS I WOULD HAVE 6563 05:14:10,096 --> 05:14:13,532 GUESSED FROM AN EXHAUSTED T CELL 6564 05:14:13,532 --> 05:14:17,403 PHENOTYPE FOR EXAMPLE OR PD1 6565 05:14:17,403 --> 05:14:18,537 PATHWAY UTILIZING SOME 6566 05:14:18,537 --> 05:14:20,973 NEUROLOGY. 6567 05:14:20,973 --> 05:14:22,808 WE SAW INCLUDE FROM THE DECEMBER 6568 05:14:22,808 --> 05:14:28,481 ABOUT BRAIN IMAGING AND fMRI IN 6569 05:14:28,481 --> 05:14:30,783 THE NATURE PAPER. 6570 05:14:30,783 --> 05:14:32,585 THOSE ARE ALL AREAS THAT CAN BE 6571 05:14:32,585 --> 05:14:37,823 THOUGHT ABOUT BY A NUMBER OF 6572 05:14:37,823 --> 05:14:40,693 GROUPS AND EXPLORED. 6573 05:14:40,693 --> 05:14:43,529 I'M ENTHUSIASTIC BUT TEMPERED 6574 05:14:43,529 --> 05:14:45,097 FROM THE TALK OF THE PATIENT 6575 05:14:45,097 --> 05:14:47,133 THAT TODAY THEY FEEL TERRIBLE 6576 05:14:47,133 --> 05:14:48,367 AND THESE THINGS THEY TAKE TIME 6577 05:14:48,367 --> 05:14:50,402 TO DEVELOP. 6578 05:14:50,402 --> 05:14:54,240 I LOOK FORWARD TO THE CHALLENGE 6579 05:14:54,240 --> 05:14:55,074 BUT HEALTHY RESPECT OF THE 6580 05:14:55,074 --> 05:14:55,941 SUFFERING OCCURRING AT THE SAME 6581 05:14:55,941 --> 05:14:59,678 TIME. 6582 05:14:59,678 --> 05:15:04,717 >> THANK YOU, JOE. 6583 05:15:04,717 --> 05:15:11,557 FINALLY PROFESSOR KLIMAS. 6584 05:15:11,557 --> 05:15:13,659 TELL US YOUR THOUGHTS 6585 05:15:13,659 --> 05:15:15,461 >> WE FIRST TALKED ABOUT THIS IN 6586 05:15:15,461 --> 05:15:18,964 THE EARLY '90s. 6587 05:15:18,964 --> 05:15:20,266 >> I THINK LATE '80s. 6588 05:15:20,266 --> 05:15:29,208 >> I REMEMBER THAT. 6589 05:15:29,208 --> 05:15:30,409 SOME THINGS DISCOVERED IN THE 6590 05:15:30,409 --> 05:15:33,145 EFFORT WERE IN THE EARLY PAPERS. 6591 05:15:33,145 --> 05:15:34,980 THE CHRONIC IMMUNE ACTIVATION 6592 05:15:34,980 --> 05:15:36,148 AND THE INFLAMMATORY MARKERS AND 6593 05:15:36,148 --> 05:15:46,258 SO ON. 6594 05:15:57,403 --> 05:16:03,142 THE STUDY SHOWED IMMUNE 6595 05:16:03,142 --> 05:16:07,146 EXHAUSTION AND WAYS OF MEASURING 6596 05:16:07,146 --> 05:16:10,783 THAT. 6597 05:16:10,783 --> 05:16:12,851 THERE'S AN IMPORTANT CLINICAL 6598 05:16:12,851 --> 05:16:18,257 OBSERVATION WE ACT ON IN OUR 6599 05:16:18,257 --> 05:16:25,064 CARE AND OTHERS HAVE REMARKED. 6600 05:16:25,064 --> 05:16:30,769 IT'S IMPORTANT TO KNOW NOT JUST 6601 05:16:30,769 --> 05:16:33,639 IF THE CELLS ARE BROKEN 6602 05:16:33,639 --> 05:16:35,941 ENERGETICALLY SPEAKING BUT WHEN 6603 05:16:35,941 --> 05:16:39,044 DID THEY GET THAT WAY? 6604 05:16:39,044 --> 05:16:43,949 THESE ARE IMPORTANT AND CUTTING 6605 05:16:43,949 --> 05:16:47,519 EDGE QUESTIONS. 6606 05:16:47,519 --> 05:16:51,523 WHAT'S SPECIAL ABOUT THE STUDY 6607 05:16:51,523 --> 05:16:54,827 AND THE ELEPHANT AND BLINDFOLDED 6608 05:16:54,827 --> 05:16:58,264 WISE PEOPLE SAYING IT'S A 6609 05:16:58,264 --> 05:17:00,899 BIOLOGIC DISEASE, NO IT'S 6610 05:17:00,899 --> 05:17:03,168 MICROBIOME AND OTHERS AND HAVE 6611 05:17:03,168 --> 05:17:05,838 YOU THE WHOLE ELEPHANT IN THE 6612 05:17:05,838 --> 05:17:06,038 STUDY. 6613 05:17:06,038 --> 05:17:10,609 THE DEPTH OF THE WORK DONE IN 6614 05:17:10,609 --> 05:17:11,944 EVERY ASPECT EVERY WAY YOU CAN 6615 05:17:11,944 --> 05:17:21,153 PIER -- PEER THROUGH THE ONE -- 6616 05:17:21,153 --> 05:17:23,789 WINDOW AND LOOKED AT THE ILLNESS 6617 05:17:23,789 --> 05:17:26,959 AND DEMONSTRATED WHAT THE VIEW 6618 05:17:26,959 --> 05:17:27,259 WAS. 6619 05:17:27,259 --> 05:17:32,464 THE REAL STRENGTH THAT WILL COME 6620 05:17:32,464 --> 05:17:35,534 FROM THIS IS TAKING THE DATA AND 6621 05:17:35,534 --> 05:17:38,470 MODELLING IT TO MECHANISMS OF 6622 05:17:38,470 --> 05:17:43,509 ILLNESS AND TARGETS FOR 6623 05:17:43,509 --> 05:17:45,010 THERAPEUTIC INTERVENTION. 6624 05:17:45,010 --> 05:17:46,478 WHAT BRIAN TALKED ABOUT DATA 6625 05:17:46,478 --> 05:17:53,686 SHARING AND OPEN ACCESS TO DATA 6626 05:17:53,686 --> 05:17:59,425 HOW AMAZING WE CAN DO IT IN A 6627 05:17:59,425 --> 05:18:01,226 WAY THAT CAN POTENTIALLY TEACH 6628 05:18:01,226 --> 05:18:02,094 US NEW THINGS. 6629 05:18:02,094 --> 05:18:04,930 OUR GROUP HAS BEEN DOING DYNAMIC 6630 05:18:04,930 --> 05:18:07,199 MODELLING AND COMING UP WITH 6631 05:18:07,199 --> 05:18:08,667 MODELS AND INTERVENTIONS A 6632 05:18:08,667 --> 05:18:10,202 NUMBER OF YEARS NOW AND LOOKED 6633 05:18:10,202 --> 05:18:15,941 AT IT THROUGH THE IMMUNE WINDOW 6634 05:18:15,941 --> 05:18:19,845 AND THROUGH NEUROPEPTIDES AND 6635 05:18:19,845 --> 05:18:20,579 CELLULAR FUNCTION. 6636 05:18:20,579 --> 05:18:24,550 NOT WHAT'S THE BRAIN DOING? 6637 05:18:24,550 --> 05:18:26,151 YET IT'S THE MOST IMPORTANT. 6638 05:18:26,151 --> 05:18:30,222 HOW COOL WE'LL BE ABLE TO TAKE 6639 05:18:30,222 --> 05:18:33,158 THE NEUROPHYSIOL DATA AND DROP 6640 05:18:33,158 --> 05:18:35,961 IT IN THE MODELLING SYSTEMS AND 6641 05:18:35,961 --> 05:18:38,530 THE MOST GRANULAR DATA SET AND 6642 05:18:38,530 --> 05:18:43,902 MOST DATA TO PULL IN THE MODEL. 6643 05:18:43,902 --> 05:18:46,705 ONE THING THAT'S EXCITING IS 6644 05:18:46,705 --> 05:18:47,873 THEY'RE NEVER COWED BY TOO MUCH 6645 05:18:47,873 --> 05:18:48,340 DATA. 6646 05:18:48,340 --> 05:18:51,176 MORE IS BETTER. 6647 05:18:51,176 --> 05:19:01,387 I LOVE THAT. 6648 05:19:02,020 --> 05:19:04,089 I THINK THAT'S EXCITING. 6649 05:19:04,089 --> 05:19:06,925 AND COMPARING ANY ME/CFS TO 6650 05:19:06,925 --> 05:19:10,396 OTHER ILLNESSES WITH ACUTE BRAIN 6651 05:19:10,396 --> 05:19:12,698 TRIGGERS LIKE LONG COVID OR IN 6652 05:19:12,698 --> 05:19:15,401 THE CASE OF THE STUDY THE V.A. 6653 05:19:15,401 --> 05:19:19,738 IS IS PROCEEDINGS TO DO IN 6654 05:19:19,738 --> 05:19:22,040 PARTNERSHIP WITH DR. NATH IN 6655 05:19:22,040 --> 05:19:28,280 GULF WAR ILLNESS A NEUROTOXIC 6656 05:19:28,280 --> 05:19:33,085 INJURY IN 1991 WITH 1 IN 3 6657 05:19:33,085 --> 05:19:35,220 VETERANS DEPLOYED STILL 6658 05:19:35,220 --> 05:19:38,490 SUFFERING FROM NEUROTOXIN AND IT 6659 05:19:38,490 --> 05:19:40,926 PRESENTS IDENTICALLY TO ME/CFS 6660 05:19:40,926 --> 05:19:43,929 AND I ASKED HOW THINGS GOT 6661 05:19:43,929 --> 05:19:49,034 STARTED AND BIO LOGICALLY THERE 6662 05:19:49,034 --> 05:19:50,135 ARE DIFFERENCES AND 6663 05:19:50,135 --> 05:19:50,469 SIMILARITIES. 6664 05:19:50,469 --> 05:19:54,106 THE DIFFERENCES MATTER. 6665 05:19:54,106 --> 05:19:56,175 THAT MIGHT INFLUENCE TREATMENT. 6666 05:19:56,175 --> 05:19:58,410 WHAT'S THE COMMONALITY BETWEEN 6667 05:19:58,410 --> 05:20:01,513 THE ILLNESSES THAT HAS A 6668 05:20:01,513 --> 05:20:03,081 CLINICIAN LIKE ME SCRATCHING MY 6669 05:20:03,081 --> 05:20:05,951 HEAD AND I DIDN'T KNOW THE 6670 05:20:05,951 --> 05:20:08,787 HISTORY AND COULDN'T TELL LONG 6671 05:20:08,787 --> 05:20:10,656 COVID FROM ME/CFS OR ANOTHER 6672 05:20:10,656 --> 05:20:14,760 MOLD EXPOSURE INJURY OR TOXIC 6673 05:20:14,760 --> 05:20:15,027 INJURIES. 6674 05:20:15,027 --> 05:20:17,729 THEY PRESENT IN SIMILAR WAYS. 6675 05:20:17,729 --> 05:20:22,301 WHAT WE LEARNED CALLING A.I. AND 6676 05:20:22,301 --> 05:20:26,171 COMPUTATION MODELLING FOR A LONG 6677 05:20:26,171 --> 05:20:31,977 TIME WILL GIVE INSIGHTS THAT ARE 6678 05:20:31,977 --> 05:20:40,085 TRANSLATABLE TO INTERVENTION. 6679 05:20:40,085 --> 05:20:43,956 WE KHAVE BEEN TAKING CARE OF 6680 05:20:43,956 --> 05:20:46,658 THESE PATIENTS A LONG TIME AND 6681 05:20:46,658 --> 05:20:49,228 WANTING TO MOVE THE NEEDLE AND 6682 05:20:49,228 --> 05:20:51,930 GET FOCUSSED THERAPIES WITH 6683 05:20:51,930 --> 05:20:53,131 SYMPTOM MANAGEMENT AND YOU NEED 6684 05:20:53,131 --> 05:20:53,765 THIS KIND OF SCIENCE TO PUSH 6685 05:20:53,765 --> 05:21:00,706 THAT THROUGH. 6686 05:21:00,706 --> 05:21:02,674 IF I WOULD UNDER SCORE WHAT 6687 05:21:02,674 --> 05:21:03,208 HAPPENS NEXT? 6688 05:21:03,208 --> 05:21:04,576 LET'S GET CLINICAL TRIALS. 6689 05:21:04,576 --> 05:21:08,380 LET'S TAKE THIS TYPE OF DATA AND 6690 05:21:08,380 --> 05:21:11,683 DO THE NEXT LEVEL OF STUDIES AND 6691 05:21:11,683 --> 05:21:14,186 TAKE THE THINGS VALIDATED BY THE 6692 05:21:14,186 --> 05:21:19,791 STUDY AND ACT ON THAT 6693 05:21:19,791 --> 05:21:26,164 INFORMATION. 6694 05:21:26,164 --> 05:21:27,933 WE WOULDN'T HAVE REASONABLE 6695 05:21:27,933 --> 05:21:29,434 HYPOTHESES THAT INVOLVE A 6696 05:21:29,434 --> 05:21:30,402 CLINICAL TRIAL TO TEST TO GET 6697 05:21:30,402 --> 05:21:39,211 PEOPLE BACK TOWARDS HEALTH. 6698 05:21:39,211 --> 05:21:39,545 GREAT STUDY. 6699 05:21:39,545 --> 05:21:42,414 AND YOU CAN DO END OF ONE 6700 05:21:42,414 --> 05:21:43,081 MODELLING AND THAT. 6701 05:21:43,081 --> 05:21:45,751 YOU CAN GET TO A SINGLE 6702 05:21:45,751 --> 05:21:48,086 INDIVIDUAL AND MODEL THE DISEASE 6703 05:21:48,086 --> 05:21:51,490 THANE ONE PERSON. 6704 05:21:51,490 --> 05:21:52,457 THAT'S VERY COOL. 6705 05:21:52,457 --> 05:21:55,327 IF YOU CAN DO THE MODELLING WITH 6706 05:21:55,327 --> 05:21:58,063 THE GROUP ANALYSIS AND BREAK THE 6707 05:21:58,063 --> 05:21:59,898 MEN AND WOMEN A PART AND TAKE 6708 05:21:59,898 --> 05:22:02,568 ONE AT A TIME AND MODEL EACH 6709 05:22:02,568 --> 05:22:05,971 PERSON'S UNDER PINNINGS OF 6710 05:22:05,971 --> 05:22:07,973 ILLNESS AND FIND WHERE THEY 6711 05:22:07,973 --> 05:22:11,543 OVERLAP. 6712 05:22:11,543 --> 05:22:12,678 THAT'S ANOTHER SCIENTIFIC 6713 05:22:12,678 --> 05:22:15,080 APPROACH OUR GROUP IS ENGAGING 6714 05:22:15,080 --> 05:22:17,649 IN AND THIS HIGHLY GRANULAR DATA 6715 05:22:17,649 --> 05:22:21,787 SET WILL ALLOW THAT. 6716 05:22:21,787 --> 05:22:22,888 >> THANK YOU. 6717 05:22:22,888 --> 05:22:25,324 SPEAKING OF NEXT STEPS, THAT'S 6718 05:22:25,324 --> 05:22:30,696 THE NEXT PANEL IN THIS MEETING. 6719 05:22:30,696 --> 05:22:35,434 >> TONY, WE'VE TALKED ABOUT 6720 05:22:35,434 --> 05:22:35,968 EARLY VERSUS LATE DISEASE. 6721 05:22:35,968 --> 05:22:40,839 THIS IS IMPORTANT. 6722 05:22:40,839 --> 05:22:44,343 WHEN YOU LOOK AT CYTOKINES THEY 6723 05:22:44,343 --> 05:22:46,878 TEND TO BE UP AND PEOPLE BURN 6724 05:22:46,878 --> 05:22:49,648 OUT AND THE LEVELS DROP AS 6725 05:22:49,648 --> 05:22:51,350 YOU'RE ASSESSING DIFFERENT 6726 05:22:51,350 --> 05:22:52,084 POPULATIONS. 6727 05:22:52,084 --> 05:22:54,052 YOU HAVE TO MAKE SURE WHAT 6728 05:22:54,052 --> 05:22:57,689 YOU'RE COMPARING PEOPLE RECENT 6729 05:22:57,689 --> 05:22:59,758 ONSET VERSUS 10 YEARS LATER. 6730 05:22:59,758 --> 05:23:03,261 IF YOU MIX THOSE TWO POPULATIONS 6731 05:23:03,261 --> 05:23:07,933 YOU MAY MISS SIGNAL. 6732 05:23:07,933 --> 05:23:09,267 THE OTHER THING ABOUT THE 6733 05:23:09,267 --> 05:23:10,202 THERAPEUTIC RESPONSE THE TIME 6734 05:23:10,202 --> 05:23:14,640 COURSE IS NOT GOING TO BE SHORT. 6735 05:23:14,640 --> 05:23:16,675 AS WE DEVELOP CLINICAL TRIALS 6736 05:23:16,675 --> 05:23:18,510 IT'S IMPORTANT TO MAKE SURE 6737 05:23:18,510 --> 05:23:23,615 WHATEVER THE INTERVENTION IS 6738 05:23:23,615 --> 05:23:24,916 CONTINUES FOR MONTHS BECAUSE IT 6739 05:23:24,916 --> 05:23:26,051 TOOK MONTHS TO GENERATE THE 6740 05:23:26,051 --> 05:23:29,454 PROBLEM AND WON'T BE SIMPLE 6741 05:23:29,454 --> 05:23:29,755 THINGS. 6742 05:23:29,755 --> 05:23:31,289 EVEN THOSE CLINICAL TRIALS WE 6743 05:23:31,289 --> 05:23:36,461 THINK IT'S UNLIKELY IT'S GOING 6744 05:23:36,461 --> 05:23:37,963 PAN OUT AND RESULT IN 6745 05:23:37,963 --> 05:23:42,134 IDENTIFICATION OF PANNEE SEE YA 6746 05:23:42,134 --> 05:23:44,202 AND -- PANACEA AND IT'S 6747 05:23:44,202 --> 05:23:47,939 IMPORTANT TO TEST THE THINGS 6748 05:23:47,939 --> 05:23:50,842 EVEN THEY YIELD SOME NEGATIVE 6749 05:23:50,842 --> 05:23:52,377 RESULT WILL RESULT DOWN STREAM 6750 05:23:52,377 --> 05:23:53,945 IN PEOPLE SHIFT FROM THINGS 6751 05:23:53,945 --> 05:23:57,182 INAPPROPRIATE AND ALLOW TO US 6752 05:23:57,182 --> 05:23:58,483 FOCUS ON THINGS THAT MIGHT BE 6753 05:23:58,483 --> 05:23:59,951 CONSTRUCTIVE. 6754 05:23:59,951 --> 05:24:02,320 THANKS. 6755 05:24:02,320 --> 05:24:04,690 >> THANKS TO ALL THE PANELISTS 6756 05:24:04,690 --> 05:24:07,025 AND TURN IT BACK TO DR. NATH FOR 6757 05:24:07,025 --> 05:24:17,536 SUMMARY AND FUTURE DIRECTION. 6758 05:24:18,603 --> 05:24:19,805 >> THANK YOU VERY MUCH. 6759 05:24:19,805 --> 05:24:23,075 THANKS FOR YOUR SUPPORT OF OUR 6760 05:24:23,075 --> 05:24:27,245 STUDIES AND ADVICE NOW AND 6761 05:24:27,245 --> 05:24:31,083 THROUGHOUT THE STUDY. 6762 05:24:31,083 --> 05:24:38,390 A COUPLE SLIDES HERE. 6763 05:24:38,390 --> 05:24:42,828 IN SUMMARY ME/CFS MAY HAVE 6764 05:24:42,828 --> 05:24:47,432 UNDERLYING TREATABLE DISEASES 6765 05:24:47,432 --> 05:24:50,202 AND SOME PATIENTS THEN WERE 6766 05:24:50,202 --> 05:24:52,504 STUDIED AND FOUND THERE WERE 6767 05:24:52,504 --> 05:24:55,941 OTHER DISEASES UNDERLYING AND 6768 05:24:55,941 --> 05:24:56,908 WERE MISSED. 6769 05:24:56,908 --> 05:24:59,511 I THINK IT'S IMPORTANT AS A 6770 05:24:59,511 --> 05:25:04,583 PHYSICIAN WHEN YOU SEE THEM THEY 6771 05:25:04,583 --> 05:25:07,486 BE CLOSELY FOLLOWED. 6772 05:25:07,486 --> 05:25:10,989 IT'S IMPOSSIBLE TO DO A MILLION 6773 05:25:10,989 --> 05:25:13,458 DOLLAR WORKUP BUT IF YOU FOLLOW 6774 05:25:13,458 --> 05:25:15,260 ALONG YOU'LL DISCOVER AN 6775 05:25:15,260 --> 05:25:21,099 UNDERLYING DISEASE. 6776 05:25:21,099 --> 05:25:28,106 WE LEARNED SOME RECOVER. 6777 05:25:28,106 --> 05:25:30,375 THAT IS FASCINATING TO IDENTIFY 6778 05:25:30,375 --> 05:25:33,278 WHAT THAT HAPPENS CAN TEACH US 6779 05:25:33,278 --> 05:25:38,049 ABOUT THE DISEASE AND HOW TO 6780 05:25:38,049 --> 05:25:48,293 DESIGN TRIALS. 6781 05:25:49,427 --> 05:25:51,263 THE THIRD IS MULTIPLE BIOLOGICAL 6782 05:25:51,263 --> 05:25:52,531 SYSTEMS ARE INVOLVED. 6783 05:25:52,531 --> 05:25:55,934 WE'RE FOCUSSED ON THE BRAIN AND 6784 05:25:55,934 --> 05:25:59,371 WHAT YOU'RE SEEING THROUGH THE 6785 05:25:59,371 --> 05:26:00,772 WORK DONE THE ANNIVERSARY SYSTEM 6786 05:26:00,772 --> 05:26:04,442 PLAYS AN IMPORTANT CRITICAL ROLE 6787 05:26:04,442 --> 05:26:07,045 AND WE NEED TO PAY MORE 6788 05:26:07,045 --> 05:26:09,181 ATTENTION TO OTHER SYSTEMS AND 6789 05:26:09,181 --> 05:26:11,216 STUDY THEM EXTENSIVELY. 6790 05:26:11,216 --> 05:26:15,287 THEN THERE ARE MULTIPLE TARGETS 6791 05:26:15,287 --> 05:26:19,257 FOR INTERVENTION. 6792 05:26:19,257 --> 05:26:22,394 THAT'S AN IMPORTANT OUTCOME OF 6793 05:26:22,394 --> 05:26:27,933 THE STUDY AND THERE ARE KEY SEX 6794 05:26:27,933 --> 05:26:30,535 DIFFERENCES IN THE PATH YO 6795 05:26:30,535 --> 05:26:32,370 PHYSIOLOGY AND NEED TO PAY 6796 05:26:32,370 --> 05:26:35,941 ATTENTION TO WHO WE'RE TREATING 6797 05:26:35,941 --> 05:26:37,909 AND SELECT THE RIGHT POPULATION. 6798 05:26:37,909 --> 05:26:43,715 ONE SIZE MAY NOT FIT ALL. 6799 05:26:43,715 --> 05:26:47,853 WHAT ABOUT THERAPEUTICS? 6800 05:26:47,853 --> 05:26:51,323 GOING BACK TO THAT FIGURE IN 6801 05:26:51,323 --> 05:26:53,725 MANY WAYS I WANT TO NOW SHOW YOU 6802 05:26:53,725 --> 05:26:56,528 WHEN YOU THINK ABOUT 6803 05:26:56,528 --> 05:26:57,662 THERAPEUTICS YOU CAN DIVIDE THEM 6804 05:26:57,662 --> 05:26:59,664 INTO TWO PARTS. 6805 05:26:59,664 --> 05:27:03,368 THE FIRST IS IS IT POSSIBLE YOU 6806 05:27:03,368 --> 05:27:08,773 ATTACK THE EARLY STAGES THE 6807 05:27:08,773 --> 05:27:13,478 IMMUNE SYSTEM ITSELF COULD YOU 6808 05:27:13,478 --> 05:27:18,717 REVERSE THE DISEASE OR HALT IT? 6809 05:27:18,717 --> 05:27:21,319 MAYBE YOU CAN INTERVENE AND 6810 05:27:21,319 --> 05:27:23,221 CAUSE SYSTEMATIC TREATMENT AND 6811 05:27:23,221 --> 05:27:23,922 INTERVENE AND HELP THE PATIENT 6812 05:27:23,922 --> 05:27:29,227 IN MANY WAYS. 6813 05:27:29,227 --> 05:27:31,930 THE QUESTION IS IF YOU WERE TO 6814 05:27:31,930 --> 05:27:34,499 BE ABLE TO ACT HERE CAN YOU 6815 05:27:34,499 --> 05:27:35,901 PREVENT EVERYTHING DOWN STREAM? 6816 05:27:35,901 --> 05:27:39,304 I DON'T KNOW THAT IS POSSIBLE OR 6817 05:27:39,304 --> 05:27:40,338 NOT. 6818 05:27:40,338 --> 05:27:43,942 IF IT'S REACTIONRY IT MAY BE 6819 05:27:43,942 --> 05:27:47,045 POSSIBLE TO CATCH IT EARLY ON 6820 05:27:47,045 --> 05:27:54,119 ABLE TO MAKE AN INTERVENTION 6821 05:27:54,119 --> 05:27:55,553 PREVENT THIS DOWN STREAM AND 6822 05:27:55,553 --> 05:27:59,557 THIS COULD BE SELF-PERPETUATING. 6823 05:27:59,557 --> 05:28:06,197 THAT HAPPENS WITH PAIN SYNDROME. 6824 05:28:06,197 --> 05:28:08,133 YOU COULD TREAT THE UNDERLYING 6825 05:28:08,133 --> 05:28:09,067 CAUSE OF THE PAIN RESEARCH. 6826 05:28:09,067 --> 05:28:11,937 IF THAT'S THE CASE YOU NEED 6827 05:28:11,937 --> 05:28:18,743 BOTH. 6828 05:28:18,743 --> 05:28:21,346 AT THE SAME TIME YOU ARE GOING 6829 05:28:21,346 --> 05:28:23,949 TO NEED THIS. 6830 05:28:23,949 --> 05:28:24,783 YOU'LL NEED COMBINATION 6831 05:28:24,783 --> 05:28:34,960 THERAPIES. 6832 05:28:35,393 --> 05:28:39,764 I'LL TALK ABOUT THE EARLY PART. 6833 05:28:39,764 --> 05:28:43,935 IF THERE'S AN IMMUNE PHENOMENON 6834 05:28:43,935 --> 05:28:46,304 WHAT CHOICES DO WE HAVE? 6835 05:28:46,304 --> 05:28:49,708 WE SHOULD STUDY ME/CFS BUT CAN 6836 05:28:49,708 --> 05:28:53,144 ALSO STUDY LONG COVID PATIENTS. 6837 05:28:53,144 --> 05:28:56,815 THE PROBLEM THEY HAVE VACCINES 6838 05:28:56,815 --> 05:28:57,349 AND COVID. 6839 05:28:57,349 --> 05:29:02,454 IT BECOMES DIFFICULT TO SORT OUT 6840 05:29:02,454 --> 05:29:05,223 WHAT IS DOING WHAT. 6841 05:29:05,223 --> 05:29:09,361 THERE'S AN OPPORTUNITY TO DO 6842 05:29:09,361 --> 05:29:17,035 CLINICAL TRIAL CAN HELP IN 6843 05:29:17,035 --> 05:29:17,602 STUD 6844 05:29:17,602 --> 05:29:17,836 STUDIES. 6845 05:29:17,836 --> 05:29:21,139 WHAT WE NEED TO DO IS LOOK AND 6846 05:29:21,139 --> 05:29:23,942 SEE WHAT CATEGORY THE PATIENTS 6847 05:29:23,942 --> 05:29:24,843 FALL INTO. 6848 05:29:24,843 --> 05:29:27,946 ONE THING I'M KEEN TO STUDY IS 6849 05:29:27,946 --> 05:29:32,550 THE POPULATION WITH IMMUNE 6850 05:29:32,550 --> 05:29:35,920 EXHAUSTION AND CHECK INHIBITORS 6851 05:29:35,920 --> 05:29:39,824 TO MAKE A DIFFERENCE IN THE 6852 05:29:39,824 --> 05:29:40,058 DISEASE? 6853 05:29:40,058 --> 05:29:43,862 SOME HAVE D CELL ACTIVATION AND 6854 05:29:43,862 --> 05:29:44,562 AUTO ANTIBODIES. 6855 05:29:44,562 --> 05:29:47,432 WE EXCLUDED THOSE BUT AS THE AN 6856 05:29:47,432 --> 05:29:50,702 OPPORTUNITY THERE TO BE ABLE TO 6857 05:29:50,702 --> 05:29:53,571 INTERVENE INDIVIDUALS WITH B 6858 05:29:53,571 --> 05:29:55,273 CELL ACTIVATION AND THERAPEUTIC 6859 05:29:55,273 --> 05:29:59,878 AGENTS AVAILABLE AND SAME WITH T 6860 05:29:59,878 --> 05:30:06,684 CELL ACTIVATION AND THE INNATE 6861 05:30:06,684 --> 05:30:09,387 IMMUNE ACTIVATION AND NON 6862 05:30:09,387 --> 05:30:20,532 SPECIFIC IMMUNE MODULA MODULATOE 6863 05:30:35,046 --> 05:30:37,782 PATIENTS HAVE PROFOUND SIDE 6864 05:30:37,782 --> 05:30:39,050 EFFECT PROFILES. 6865 05:30:39,050 --> 05:30:43,955 I URGE WE DO THEM IN THE CONTEXT 6866 05:30:43,955 --> 05:30:54,299 OF CLINICAL TRIALS. 6867 05:31:12,317 --> 05:31:15,420 THERE'S NALL TREXON AND ABILIFY 6868 05:31:15,420 --> 05:31:16,521 AND VARIOUS SUPPLEMENTS. 6869 05:31:16,521 --> 05:31:21,426 WE NEED TO LOOK AT THESE AND TRY 6870 05:31:21,426 --> 05:31:24,062 TO SEE WHAT MAKES THE BEST SENSE 6871 05:31:24,062 --> 05:31:24,529 WHATTED TO TRY. 6872 05:31:24,529 --> 05:31:25,196 -- WHAT TO TRY. 6873 05:31:25,196 --> 05:31:31,169 IF YOU WERE TO STUDY ONE 6874 05:31:31,169 --> 05:31:36,040 COMPOUND AFTER ANOTHER IT WOULD 6875 05:31:36,040 --> 05:31:40,145 TAKE A CENTURY TO GO THROUGH THE 6876 05:31:40,145 --> 05:31:42,413 LAST AND LIFE SPANS ARE SHORT 6877 05:31:42,413 --> 05:31:44,549 AND MINE IS SHORTER THAN MOST 6878 05:31:44,549 --> 05:31:44,716 YOU. 6879 05:31:44,716 --> 05:31:48,586 WE NEED OTHER INNOVATIVE WAYS OF 6880 05:31:48,586 --> 05:31:51,055 DOING TRIALS. 6881 05:31:51,055 --> 05:31:57,328 ONE IS DOING PLATFORM STUDY. 6882 05:31:57,328 --> 05:32:03,468 YOU CAN STUDY MULTIPLE DRUGS 6883 05:32:03,468 --> 05:32:14,012 COMPARED TO A SINGLE PLACEBO ARM 6884 05:32:18,082 --> 05:32:21,252 AND COMPARE AND CONTRAST. 6885 05:32:21,252 --> 05:32:24,822 THAT'S IMPOSSIBLE AT A SINGLE 6886 05:32:24,822 --> 05:32:29,894 SITE AND THAT'S ONE WAY TO GET 6887 05:32:29,894 --> 05:32:31,629 TO HELP OUR ANSWER. 6888 05:32:31,629 --> 05:32:33,198 ANOTHER WAY IS CROSSOVER 6889 05:32:33,198 --> 05:32:33,598 STUDIES. 6890 05:32:33,598 --> 05:32:36,601 PATIENTS ARE PUT ON A SINGLE 6891 05:32:36,601 --> 05:32:36,801 DRUG. 6892 05:32:36,801 --> 05:32:39,404 MULTIPLE DRUGS ARMS. 6893 05:32:39,404 --> 05:32:40,705 THEY HAVE AN OPPORTUNITY AFTER 6894 05:32:40,705 --> 05:32:44,142 THEY FINISH ONE ARM TO MOVE ON 6895 05:32:44,142 --> 05:32:46,010 TO THE NEXT. 6896 05:32:46,010 --> 05:32:54,219 EVERY PERSON WHO WAS IN PLACEBO 6897 05:32:54,219 --> 05:32:55,653 HAS CROSSOVER DESIGNS. 6898 05:32:55,653 --> 05:32:58,623 OTHER FUTURE DIRECTIONS WE NEED 6899 05:32:58,623 --> 05:33:00,758 TO PURSUE AND THAT IS CONTINUE 6900 05:33:00,758 --> 05:33:02,460 THE ANALYSIS AND PUBLICATION OF 6901 05:33:02,460 --> 05:33:06,598 DATA AND SAMPLES COLLECTED AND 6902 05:33:06,598 --> 05:33:08,766 DATA TO OUTLINE THE FUTURE 6903 05:33:08,766 --> 05:33:10,702 DIRECTIONS AND RE-ANALYSIS OF 6904 05:33:10,702 --> 05:33:12,670 DATA BY OTHER RESEARCHERS AND 6905 05:33:12,670 --> 05:33:16,274 VALIDATION OF FINDINGS AND OTHER 6906 05:33:16,274 --> 05:33:16,507 COHORTS. 6907 05:33:16,507 --> 05:33:19,544 AND DISCUSS PLANS FOR CLINICAL 6908 05:33:19,544 --> 05:33:21,512 TRIALS AND CONTINUE TO STUDY THE 6909 05:33:21,512 --> 05:33:23,948 CONTEXT OF CLINICAL TRIALS. 6910 05:33:23,948 --> 05:33:29,187 THAT'S IMPORTANT. 6911 05:33:29,187 --> 05:33:31,756 YOU CAN NEVER DO ENOUGH 6912 05:33:31,756 --> 05:33:32,323 PATHOPHYSIOLOGY AND THERE'S 6913 05:33:32,323 --> 05:33:39,464 ALWAYS ANOTHER QUESTION. 6914 05:33:39,464 --> 05:33:41,199 IF YOU KEEP WAITING YOU'LL NEVER 6915 05:33:41,199 --> 05:33:43,568 GET TO THE CONTEXT OF CLINICAL 6916 05:33:43,568 --> 05:33:43,801 TRIALS. 6917 05:33:43,801 --> 05:33:48,106 YOU CAN CONTINUE TO STUDY 6918 05:33:48,106 --> 05:33:48,706 PATHOPHYSIOLOGY. 6919 05:33:48,706 --> 05:33:51,242 WHAT I WOULD ADVOCATE WITH WE 6920 05:33:51,242 --> 05:33:53,378 HOLD HANDS TOGETHER AND MOVE 6921 05:33:53,378 --> 05:33:54,345 FORWARD WITH THE PATIENT 6922 05:33:54,345 --> 05:33:55,546 COMMUNITY AND RESEARCHERS AND 6923 05:33:55,546 --> 05:33:57,415 THERE'S LIGHT AT THE END OF THE 6924 05:33:57,415 --> 05:33:59,917 TUNNEL AND I'M HOPEFUL WE'LL 6925 05:33:59,917 --> 05:34:02,220 FIND CURES FOR THIS DISEASE. 6926 05:34:02,220 --> 05:34:05,890 I'LL END HERE AND IF DR. SCHOR 6927 05:34:05,890 --> 05:34:10,561 IS THERE ONLINE I'LL ASK OR THE 6928 05:34:10,561 --> 05:34:11,729 GIVE CLOSING REMARKS. 6929 05:34:11,729 --> 05:34:16,301 SHE'S THE DEPUTY DIRECTOR OF THE 6930 05:34:16,301 --> 05:34:17,835 INTRAMURAL PROGRAM AT THE 6931 05:34:17,835 --> 05:34:19,537 NATIONAL INSTITUTES OF HEALTH 6932 05:34:19,537 --> 05:34:21,873 AND USED TO BE THE CHAIR IN 6933 05:34:21,873 --> 05:34:23,808 PITTSBURGH AND THEN DIRECTOR OF 6934 05:34:23,808 --> 05:34:25,710 PEDIATRICS AT UNIVERSITY OF 6935 05:34:25,710 --> 05:34:30,348 RODCHESTER AND CAME TO NIH AS TE 6936 05:34:30,348 --> 05:34:31,949 DEPUTY DIRECTOR OF NINDS. 6937 05:34:31,949 --> 05:34:35,953 THIS STUDY STARTED AND HAS BEEN 6938 05:34:35,953 --> 05:34:41,159 STRONGLY SUPPORTIVE OF OUR 6939 05:34:41,159 --> 05:34:41,592 EFFORTS. 6940 05:34:41,592 --> 05:34:45,129 SHE WAS NOT ONLY THE DEPUTY 6941 05:34:45,129 --> 05:34:46,297 DIRECTOR BUT ACTING SCIENTIFIC 6942 05:34:46,297 --> 05:34:46,597 DIRECTOR. 6943 05:34:46,597 --> 05:34:52,704 SHE PLAYED A CRITICAL ROLE IN 6944 05:34:52,704 --> 05:34:54,405 THE INTRAMURAL PROGRAM AT EVERY 6945 05:34:54,405 --> 05:34:56,407 LEVEL AND I'LL GIVE THE PODIUM 6946 05:34:56,407 --> 05:34:58,076 TO HER FOR CLOSING REMARKS. 6947 05:34:58,076 --> 05:34:59,977 SHE'S CURRENTLY IN RODCHESTER 6948 05:34:59,977 --> 05:35:02,780 AND HAS A BUSY SCHEDULE BUT MADE 6949 05:35:02,780 --> 05:35:03,915 SURE SHE'D BE AVAILABLE FOR 6950 05:35:03,915 --> 05:35:14,025 THIS. 6951 05:35:15,226 --> 05:35:17,128 >> THANK YOU FOR THOSE WHO MADE 6952 05:35:17,128 --> 05:35:19,831 IT POSSIBLE FOR KNOW PARTICIPATE 6953 05:35:19,831 --> 05:35:21,399 VIRTUALLY AND WATCH THE 6954 05:35:21,399 --> 05:35:22,834 CONFERENCE ON VIDEOCAST. 6955 05:35:22,834 --> 05:35:27,772 PRIVILEGE TO BE WITH YOU IN 6956 05:35:27,772 --> 05:35:33,211 WHATEVER FASHION. 6957 05:35:33,211 --> 05:35:37,315 I WANT TO UNDER SCORE THE 6958 05:35:37,315 --> 05:35:39,250 COMPLEXITIES YOU HEARD WITH 6959 05:35:39,250 --> 05:35:42,620 REGARD TO THIS DISORDER, 6960 05:35:42,620 --> 05:35:47,692 DISEASE, SYNDROME ALL THESE 6961 05:35:47,692 --> 05:35:49,193 COMPLEXITIES ARE WHAT MAKE IT SO 6962 05:35:49,193 --> 05:35:51,829 THAT THIS IS A TEAM APPROACH 6963 05:35:51,829 --> 05:35:56,234 KIND OF DISORDER. 6964 05:35:56,234 --> 05:36:01,506 THIS NOT A DISEASE WE'LL SOLVE 6965 05:36:01,506 --> 05:36:05,510 OR CURE OR PREVENT WITH ISOLATED 6966 05:36:05,510 --> 05:36:11,349 SCIENTIST IN A LABORATORY OR 6967 05:36:11,349 --> 05:36:11,582 CLINIC. 6968 05:36:11,582 --> 05:36:15,953 YOU HEARD THIS DISORDER INVOLVES 6969 05:36:15,953 --> 05:36:18,589 THE IMMUNE SYSTEM AND 6970 05:36:18,589 --> 05:36:20,591 INFLAMMATION AT EVERY LEVEL THAT 6971 05:36:20,591 --> 05:36:23,961 CAN INVOLVE THE MICROBIOME AND 6972 05:36:23,961 --> 05:36:27,565 CHANGES THAT OCCUR THERE. 6973 05:36:27,565 --> 05:36:33,938 IT CAN INVOLVE THE AUTONOMIC 6974 05:36:33,938 --> 05:36:39,210 NERVOUS SYSTEM AND INJURY TO 6975 05:36:39,210 --> 05:36:39,777 THAT SYSTEM. 6976 05:36:39,777 --> 05:36:43,981 BECAUSE OF THAT IT TAKES MANY 6977 05:36:43,981 --> 05:36:45,983 PEOPLE APPROACHING IT FROM MANY 6978 05:36:45,983 --> 05:36:47,018 ADVANTAGE POINTS. 6979 05:36:47,018 --> 05:36:49,720 IT'S ALSO NOT A DISEASE THAT'S 6980 05:36:49,720 --> 05:36:51,122 GOING TO BE INVOLVED BY 6981 05:36:51,122 --> 05:36:53,724 SCIENTISTS AND PHYSICIANS ALONE. 6982 05:36:53,724 --> 05:36:59,831 THE PARTNERSHIP WITH COLLEAGUES 6983 05:36:59,831 --> 05:37:04,001 WHO ARE PATIENTS AND ADVOCATES 6984 05:37:04,001 --> 05:37:14,545 IN THIS COMMUNITY UNIVERSITY AND 6985 05:37:15,413 --> 05:37:19,050 GOVERNMENT AND ARE IMPORTANT. 6986 05:37:19,050 --> 05:37:21,152 I'M GRATEFUL TO ALL WHO HAVE 6987 05:37:21,152 --> 05:37:23,688 COME TOGETHER TODAY IN THE 6988 05:37:23,688 --> 05:37:25,022 CONTEXT AND PARTICIPATED IN 6989 05:37:25,022 --> 05:37:27,825 THESE STUDIES YOU HEARD ABOUT 6990 05:37:27,825 --> 05:37:31,529 TODAY AND WHAT WE DO IN THE 6991 05:37:31,529 --> 05:37:31,762 FUTURE. 6992 05:37:31,762 --> 05:37:35,099 WITHOUT ALL OF YOU, WITHOUT THE 6993 05:37:35,099 --> 05:37:36,934 TEAM AND WITHOUT PARTNERSHIP 6994 05:37:36,934 --> 05:37:39,203 THERE IS NO WAY WE WILL SOLVE 6995 05:37:39,203 --> 05:37:41,105 THE KINDS OF DISORDERS THAT ARE 6996 05:37:41,105 --> 05:37:43,908 LEFT FOR US TO SOLVE. 6997 05:37:43,908 --> 05:37:49,947 AND SO IT IS IN THIS SPIRIT OF 6998 05:37:49,947 --> 05:37:55,953 GRATITUDE AND SPIRIT OF HOPE AND 6999 05:37:55,953 --> 05:37:58,055 PARTNERSHIP AND COLLEAGUESHIP I 7000 05:37:58,055 --> 05:38:01,392 THANK YOU FOR BEING A PART OF 7001 05:38:01,392 --> 05:38:03,094 THIS IMPORTANT CONFERENCE TODAY 7002 05:38:03,094 --> 05:38:06,230 FOR AND PARTNERING WITH EACH 7003 05:38:06,230 --> 05:38:11,969 OTHER, FOR EDUCATING ME AND FOR 7004 05:38:11,969 --> 05:38:15,973 ALLOWING SCIENTISTS LIKE BRIAN 7005 05:38:15,973 --> 05:38:23,381 AND CLINICIANS TOE TO COME 7006 05:38:23,381 --> 05:38:27,451 TOGETHER AND REALLY BRING MANY 7007 05:38:27,451 --> 05:38:30,388 PERSPECTIVES TOGETHER IN THE 7008 05:38:30,388 --> 05:38:32,857 PURSUIT OF TREATMENT, CURE AND 7009 05:38:32,857 --> 05:38:36,394 PREVENTION FOR ME/CFS. 7010 05:38:36,394 --> 05:38:37,962 THANKS TO ALL OF YOU FOR MAKE 7011 05:38:37,962 --> 05:38:48,272 THIS HAPPEN TODAY. 7012 05:38:50,007 --> 05:38:54,078 >> THANK YOU. 7013 05:38:54,078 --> 05:38:54,712 THE MEETING IS ADJOURNED. 7014 05:38:54,712 --> 05:38:55,913