1 00:00:11,440 --> 00:00:13,640 Welcome to the Clinical Center Grand Rounds, 2 00:00:13,640 --> 00:00:17,440 a weekly series of educational lectures for physicians and 3 00:00:17,440 --> 00:00:20,080 health care professionals broadcast from the Clinical 4 00:00:20,080 --> 00:00:23,040 Center at the National Institutes of Health in 5 00:00:23,040 --> 00:00:24,840 Bethesda, MD. 6 00:00:24,840 --> 00:00:28,400 The NIH Clinical Center is the world's largest hospital totally 7 00:00:28,400 --> 00:00:32,080 dedicated to investigational research and leads the global 8 00:00:32,080 --> 00:00:35,040 effort in training today's investigators and discovering 9 00:00:35,040 --> 00:00:37,200 tomorrow's cures. 10 00:00:37,200 --> 00:00:47,200 Learn more by visiting us online at http://clinicalcenter.nih.gov 11 00:00:47,200 --> 00:00:50,520 SPEAKER TODAY IS DR. IAN MILES, 12 00:00:50,520 --> 00:00:53,600 COMMANDER US PUBLIC HEALTH 13 00:00:53,600 --> 00:00:54,080 CENTER AND TENURE-TRACK 14 00:00:54,080 --> 00:00:55,840 INVESTIGATOR IN CLINICAL COLOR 15 00:00:55,840 --> 00:01:04,280 AND CHIEF OF THE EPITHELIAL 16 00:01:04,280 --> 00:01:04,760 THERAPEUTIC UNIT AT THE 17 00:01:04,760 --> 00:01:05,360 NATIONAL INST. OF ALLERGY AND 18 00:01:05,360 --> 00:01:05,960 INFECTIOUS DISEASES DR. MILES 19 00:01:05,960 --> 00:01:06,720 RECEIVED HIS BACHELORS DEGREE 20 00:01:06,720 --> 00:01:07,320 IN BIOLOGY FROM COLORADO STATE 21 00:01:07,320 --> 00:01:07,960 UNIVERSITY, AND THEN EARNED HIS 22 00:01:07,960 --> 00:01:09,320 MEDICAL DEGREE FROM THE 23 00:01:09,320 --> 00:01:10,360 UNIVERSITY OF COLORADO. AND 24 00:01:10,360 --> 00:01:17,320 LATER AN MPA FROM GEORGE 25 00:01:17,320 --> 00:01:17,960 WASHINGTON UNIVERSITY FOLLOWING 26 00:01:17,960 --> 00:01:18,560 MEDICAL SCHOOL HE COMPLETED HIS 27 00:01:18,560 --> 00:01:19,200 INTERNAL MEDICINE RESIDENCY AT 28 00:01:19,200 --> 00:01:20,400 THE OHIO STATE UNIVERSITY AND 29 00:01:20,400 --> 00:01:21,000 AFTERWARDS FELLOWSHIP TRAINING 30 00:01:21,000 --> 00:01:21,600 IN ALLERGY AND CLINICAL 31 00:01:21,600 --> 00:01:32,120 IMMUNOLOGY AT THE NIH. FOLLOW 32 00:01:39,680 --> 00:01:40,240 HIS FELLOWSHIP HE REMAINED AS A 33 00:01:40,240 --> 00:01:40,880 POSTDOCTORAL FELLOW AND BECAME 34 00:01:40,880 --> 00:01:42,440 A CLINICAL INVESTIGATOR IN 2016 35 00:01:42,440 --> 00:01:43,040 AT THE TRANSITION PROGRAM IN 36 00:01:43,040 --> 00:01:44,400 CLINICAL RESEARCH AND BECAME 37 00:01:44,400 --> 00:01:44,920 HAD BEEN LABORATORY AND 38 00:01:44,920 --> 00:01:45,400 CLINICAL IMMUNOLOGY AND 39 00:01:45,400 --> 00:01:50,960 MICROBIOLOGY. 40 00:01:50,960 --> 00:01:51,440 DR. MILES RESEARCH GROUP 41 00:01:51,440 --> 00:01:52,080 FOCUSES ON HOW HUMAN HEALTH IS 42 00:01:52,080 --> 00:01:52,720 AFFECTED BY MICROORGANISMS THAT 43 00:01:52,720 --> 00:01:58,720 LIVE IN OUR SKIN. HER EMPHASIS 44 00:01:58,720 --> 00:02:07,160 IS ON ATOPIC -- AND 45 00:02:07,160 --> 00:02:17,720 INFLAMMATORY DISEASE OF THE THE 46 00:02:24,320 --> 00:02:24,840 FOCUS OF HIS GROUP FOCUSES ON 47 00:02:24,840 --> 00:02:27,240 THE ROLE OF MICROBIOLOGY TISSUE 48 00:02:27,240 --> 00:02:33,440 REPAIR. AND HE IS FOCUSED ON -- 49 00:02:33,440 --> 00:02:34,040 AND RECEIVED 12 PATENTS FOR 50 00:02:34,040 --> 00:02:34,640 HIS WORK PAST AND CURRENT AND 51 00:02:34,640 --> 00:02:35,160 HE IS A HIGHLY REGARDED 52 00:02:35,160 --> 00:02:36,600 EDUCATOR FOUNDING THE FAES 53 00:02:36,600 --> 00:02:47,000 PRECLINICAL ACADEMY FOR 54 00:02:56,960 --> 00:02:57,520 PREMEDICAL STUDENT AND HAS BEEN 55 00:02:57,520 --> 00:02:58,080 A MENTOR AND RESEARCHER FOR 56 00:02:58,080 --> 00:02:58,640 OVER TRAINEES FROM CLINICAL 57 00:02:58,640 --> 00:02:59,240 STUDENTS TO POST DOCS AND DR. 58 00:02:59,240 --> 00:02:59,880 MILES HAS BEEN THE RECIPIENT OF 59 00:02:59,880 --> 00:03:00,520 NUMEROUS RECOGNITIONS INCLUDING 60 00:03:00,520 --> 00:03:01,200 AN AGE MEDICAL HONOR AWARDS FOR 61 00:03:01,200 --> 00:03:07,200 HIS RESEARCH. HIS FOCUS IS BEEN 62 00:03:07,200 --> 00:03:07,680 ON STRUCTURAL RACISM IN 63 00:03:07,680 --> 00:03:08,320 PROMOTING RACIAL REPRESENTATION 64 00:03:08,320 --> 00:03:08,920 AND INCLUSION AND IN ADDITION 65 00:03:08,920 --> 00:03:10,320 TO HIS IMPECCABLE CAREER AS AN 66 00:03:10,320 --> 00:03:12,120 INVESTIGATOR AND EDUCATOR, DR. 67 00:03:12,120 --> 00:03:12,760 MOUTH AS A COMMISSIONED OFFICER 68 00:03:12,760 --> 00:03:13,400 IN THE US PUBLIC HEALTH SERVICE 69 00:03:13,400 --> 00:03:19,480 AND SUPPORTED NUMEROUS PHS 70 00:03:19,480 --> 00:03:20,120 MISSIONS FROM THE EBOLA VACCINE 71 00:03:20,120 --> 00:03:21,440 TRIAL FROM THE CONGRESSIONAL 72 00:03:21,440 --> 00:03:22,000 TERMS OF THE US CAPITAL HAS 73 00:03:22,000 --> 00:03:22,520 RECEIVED NUMEROUS SERVICE 74 00:03:22,520 --> 00:03:32,920 AWARDS FOR EMERGENCY 75 00:03:33,640 --> 00:03:34,200 PREPAREDNESS, COVID PANDEMIC 76 00:03:34,200 --> 00:03:34,800 AND GLOBAL RESPONSE TO EBOLA 77 00:03:34,800 --> 00:03:35,240 AND TO INDIVIDUAL PHS 78 00:03:35,240 --> 00:03:37,760 COMMENDATION MEDALS. PLEASE 79 00:03:37,760 --> 00:03:39,640 WELCOME OUR SPEAKER FOR HIS 80 00:03:39,640 --> 00:03:40,520 PRESENTATION ATOPIC 81 00:03:40,520 --> 00:03:41,400 DERMATITIS. 82 00:03:41,400 --> 00:03:42,000 THANK YOU FOR KIND INTRODUCTION 83 00:03:42,000 --> 00:03:44,960 AND FOR EVERYBODY ON OUR 84 00:03:44,960 --> 00:03:49,960 GROUP THANK YOU FOR LOGGING IN, 85 00:03:49,960 --> 00:03:50,560 AND WE'RE GOING TO TALK ABOUT 86 00:03:50,560 --> 00:03:51,200 THE ROLE OF THE ENVIRONMENT IN 87 00:03:51,200 --> 00:03:55,600 ATOPIC DERMATITIS. 88 00:03:55,600 --> 00:03:56,200 NO FINANCIAL DISCLOSURES WILL 89 00:03:56,200 --> 00:03:56,800 TALK ABOUT CLINICAL TRIALS FROM 90 00:03:56,800 --> 00:04:07,360 SOME OF OUR TOPICAL PROBIOTICS 91 00:04:13,120 --> 00:04:13,680 BUT THAT IS NOT YET BEEN VETTED 92 00:04:13,680 --> 00:04:14,280 BY THE FDA. YOU WILL LEARN A 93 00:04:14,280 --> 00:04:14,880 LOT OF WONDERFUL THINGS ABOUT 94 00:04:14,880 --> 00:04:15,520 MICROBIOME MOST OF THE AUDIENCE 95 00:04:15,520 --> 00:04:21,960 IS AWARE, AND INTERMITTENT AND 96 00:04:21,960 --> 00:04:22,560 OFTEN UNPREDICTABLE THIS IS AND 97 00:04:22,560 --> 00:04:25,000 THAT IS WHERE THE TITLE OF THE 98 00:04:25,000 --> 00:04:27,720 TALK COMES FROM AND A HAT PUT 99 00:04:27,720 --> 00:04:28,240 OUT BY THE NATIONAL EXAM 100 00:04:28,240 --> 00:04:28,800 ASSOCIATION TO ATTEMPT TO 101 00:04:28,800 --> 00:04:29,400 COMMUNICATE THAT PATIENTS CAN 102 00:04:29,400 --> 00:04:30,000 BE DOING ANYTHING RIGHT, TAKING 103 00:04:30,000 --> 00:04:33,320 THEIR MEDICINES, AVOIDING THE 104 00:04:33,320 --> 00:04:33,920 THINGS THEY NEED TO AVOID AND 105 00:04:33,920 --> 00:04:34,520 STILL HAVE A FLAREUP IN WHAT 106 00:04:34,520 --> 00:04:35,160 THEY PERCEIVED TO BE APPLICABLE 107 00:04:35,160 --> 00:04:37,840 AND JOKINGLY INSINUATING THAT 108 00:04:37,840 --> 00:04:38,480 SOMETHING AS EASY AS AIR MIGHT 109 00:04:38,480 --> 00:04:46,520 GENERATE THEIR IT FLARES. 110 00:04:46,520 --> 00:04:47,120 IT IS A RASH, PRIMARILY, THE 111 00:04:47,120 --> 00:04:47,720 PROBLEM IS EACH WHICH CAN LEAD 112 00:04:47,720 --> 00:04:55,960 TO DISTURBANCE OF SLEEP AND 113 00:04:55,960 --> 00:04:56,560 PSYCHOLOGICAL PROBLEMS AND IT 114 00:04:56,560 --> 00:05:00,840 IS SPREADING SINCE 1970 IT HAS 115 00:05:00,840 --> 00:05:05,520 INCREASED 3-6 FOLD FOR THE 116 00:05:05,520 --> 00:05:06,120 PREVIOUS INDUSTRY NUMBERS IN 117 00:05:06,120 --> 00:05:09,120 THE PATHOLOGICAL FEATURES ARE 118 00:05:09,120 --> 00:05:09,720 IT CANNOT KEEP THEIR WATER IN 119 00:05:09,720 --> 00:05:10,320 THE SKIN SO SKIN WILL DRY OUT 120 00:05:10,320 --> 00:05:12,640 AND THEY CANNOT KEEP THE WORLD 121 00:05:12,640 --> 00:05:13,280 OUT WHICH LEADS TO PENETRATION 122 00:05:13,280 --> 00:05:13,880 THROUGH THE SKIN AND ALLERGIC 123 00:05:13,880 --> 00:05:17,040 INFLAMMATION AND WE THINK IT 124 00:05:17,040 --> 00:05:17,600 PREDISPOSES PEOPLE TO THOSE 125 00:05:17,600 --> 00:05:20,680 OTHER ALLERGIC DISEASES THAT 126 00:05:20,680 --> 00:05:21,240 OR JUST MENTION AND WILL GET 127 00:05:21,240 --> 00:05:21,720 TO THE IMBALANCE OF THE 128 00:05:21,720 --> 00:05:25,400 MICROBES OF THE SKIN. AND SO I 129 00:05:25,400 --> 00:05:26,040 WILL COME BACK AT THE VERY END 130 00:05:26,040 --> 00:05:27,840 AS TO WHY I AM A LITTLE HARSH 131 00:05:27,840 --> 00:05:28,880 ON THE PRECEDING GENETICS AND 132 00:05:28,880 --> 00:05:36,000 ATOPIC DERM. 133 00:05:36,000 --> 00:05:36,600 AS THE FIELD BEGAN AND THEY 134 00:05:36,600 --> 00:05:37,120 STARTED TO RESEARCH AS AN 135 00:05:37,120 --> 00:05:37,640 EARNEST THE 18TH-CENTURY 136 00:05:37,640 --> 00:05:39,040 MATHEMATICS AND TWIN STUDIES 137 00:05:39,040 --> 00:05:39,560 SAID IT WAS GOING TO BE 138 00:05:39,560 --> 00:05:40,160 SOMEWHERE IN THE BALLPARK OF 139 00:05:40,160 --> 00:05:43,360 85% GENETIC. 140 00:05:43,360 --> 00:05:43,920 AND THERE WERE SOME SUPPORT 141 00:05:43,920 --> 00:05:47,160 FOR THAT, FOR FIRST OFF 142 00:05:47,160 --> 00:05:51,080 PARENTAL ALLERGY WAS VERY 143 00:05:51,080 --> 00:05:51,600 PROTECTIVE. KIND OF THIS 144 00:05:51,600 --> 00:05:52,160 NEEDLESSLY DEFINED ALLERGY 145 00:05:52,160 --> 00:06:00,960 SOMEWHAT RUNS IN FAMILIES, AND 146 00:06:00,960 --> 00:06:01,560 THAT WAS TRUE AND THERE WERE 147 00:06:01,560 --> 00:06:02,200 DEFINITIVE MENDELIAN DISORDERS 148 00:06:02,200 --> 00:06:05,800 THAT INCLUDED EXEMIS PHENOTYPE 149 00:06:05,800 --> 00:06:06,320 AND THEY WOULD COME TO A 150 00:06:06,320 --> 00:06:08,400 SPECIALIST AT THE WORLD-FAMOUS 151 00:06:08,400 --> 00:06:09,000 ALEXANDER FREEMAN BECAUSE THEY 152 00:06:09,000 --> 00:06:09,480 HAVE A SERIOUS IMMUNE 153 00:06:09,480 --> 00:06:10,120 DEFICIENCY THAT WENT ALONG WITH 154 00:06:10,120 --> 00:06:14,280 HER ECZEMA. THERE ARE SOME 155 00:06:14,280 --> 00:06:14,920 MINOR GENIC FAMILIES THAT HAVE 156 00:06:14,920 --> 00:06:21,480 COME TO DR. JON LYONS' GROUP 157 00:06:21,480 --> 00:06:22,120 WERE THEY DESCRIBED OBVIOUSLY A 158 00:06:22,120 --> 00:06:22,720 MINOGENIC DISORDER BUT THESE 159 00:06:22,720 --> 00:06:24,960 ARE RARE AND THEY HAVE A 160 00:06:24,960 --> 00:06:25,480 PREDICTABLE INHERITANCE 161 00:06:25,480 --> 00:06:25,960 PATTERN, BUT DEFINITELY 162 00:06:25,960 --> 00:06:26,520 SUGGESTION THE POTENTIAL 163 00:06:26,520 --> 00:06:27,240 GENETIC PATHWAYS THAT WILL BE 164 00:06:27,240 --> 00:06:37,400 INVOLVED. 165 00:06:38,680 --> 00:06:39,280 THE FIRST POPULATION ATTEMPTED 166 00:06:39,280 --> 00:06:39,920 THIS HIT ON THE GENE PELLEGRIN 167 00:06:39,920 --> 00:06:40,520 WHICH IS A PROTEIN EXPRESSION 168 00:06:40,520 --> 00:06:46,760 ON THE SKIN. AND THE OTHER 169 00:06:46,760 --> 00:06:47,400 ONES ARE THE DON'T APPLY ACROSS 170 00:06:47,400 --> 00:06:47,920 MULTIPLE POPULATIONS EVEN 171 00:06:47,920 --> 00:06:48,520 WITHIN LET'S SAY SOUTHERN VS. 172 00:06:48,520 --> 00:06:53,360 CENTRAL NORWEGIANS; WE DON'T 173 00:06:53,360 --> 00:06:53,920 HAVE A FUNCTIONAL MODEL TO 174 00:06:53,920 --> 00:06:54,480 VALIDATE THEM IN TODAY THEY 175 00:06:54,480 --> 00:06:56,880 ACCOUNT FOR MAYBE 5% OF THE 176 00:06:56,880 --> 00:06:57,560 OVERALL DISEASE BURDEN AND THAT 177 00:06:57,560 --> 00:07:00,760 IS BEING GENEROUS. 178 00:07:00,760 --> 00:07:01,280 DESPITE THAT WHEN YOU GO 179 00:07:01,280 --> 00:07:01,840 THROUGH PUB MED YOU CAN SEE 180 00:07:01,840 --> 00:07:02,440 WHOLE LOT MORE ATTENTION PAID 181 00:07:02,440 --> 00:07:05,560 TO TERMS LIKE ATOPIC DERMATITIS 182 00:07:05,560 --> 00:07:09,040 VS. GENETIC AND VS. THE 183 00:07:09,040 --> 00:07:09,640 ENVIRONMENT. LIKE I SAID THE 184 00:07:09,640 --> 00:07:10,120 DISEASE IS INCREASED 185 00:07:10,120 --> 00:07:13,960 SUBSTANTIALLY IN THE UNITED 186 00:07:13,960 --> 00:07:14,520 STATES. THERE IS DATA FROM 187 00:07:14,520 --> 00:07:15,120 FINLAND AND THE UK THAT SHOWS 188 00:07:15,120 --> 00:07:25,640 THE SAME THING THAT) 1970 YOU 189 00:07:29,640 --> 00:07:30,160 SEE THIS INCREASE IN YOU HAVE 190 00:07:30,160 --> 00:07:33,920 GONE FROM 1% OR LESS. 191 00:07:33,920 --> 00:07:37,040 IF YOU COME ACROSS A LAKE AND 192 00:07:37,040 --> 00:07:41,160 THERE'S ONLY ONE DEAD FISH 193 00:07:41,160 --> 00:07:41,800 FLOATING IN THE WATER IT MAKES 194 00:07:41,800 --> 00:07:42,360 SENSE TO TEASE APART TO SEE 195 00:07:42,360 --> 00:07:45,400 WHAT HAPPENED TO THAT PHASE BUT 196 00:07:45,400 --> 00:07:48,560 IF YOU COME ACROSS 20 FOR SURE 197 00:07:48,560 --> 00:07:49,120 MORE DEBT IN THE WATER YOU 198 00:07:49,120 --> 00:07:49,680 DON'T WANT TO GET INTO THAT 199 00:07:49,680 --> 00:07:50,280 WATER. YOU WANT TO KNOW WHAT 200 00:07:50,280 --> 00:07:51,480 POLLUTANT IS THERE. AND IF 201 00:07:51,480 --> 00:07:52,040 THERE'S ANYTHING THAT WENT 202 00:07:52,040 --> 00:07:58,200 WRONG WITH THE KIDS, IT WENT ON 203 00:07:58,200 --> 00:07:58,800 AROUND 1970 AND FOR BETTER OR 204 00:07:58,800 --> 00:07:59,440 WORSE THE ENVIRONMENT IMPRINTS 205 00:07:59,440 --> 00:08:03,560 ONTO YOUR MICROBIOMES. 206 00:08:03,560 --> 00:08:04,120 YOU CAN USE THIS TO TEASE IT 207 00:08:04,120 --> 00:08:04,720 OUT AND THIS IS DATA OUT OF 208 00:08:04,720 --> 00:08:05,320 STANFORD WEATHER TOOK STOOL 209 00:08:05,320 --> 00:08:07,800 SAMPLES FROM ALL OVER THE GLOBE 210 00:08:07,800 --> 00:08:08,440 AND TRY TO GET A GLOBAL PICTURE 211 00:08:08,440 --> 00:08:12,680 OF THE GOT MICROBIOME IN THE 212 00:08:12,680 --> 00:08:13,240 SUBJECTS AND THE FIRST MOST 213 00:08:13,240 --> 00:08:13,840 IMPORTANT COMPONENT TO SERVE 214 00:08:13,840 --> 00:08:14,200 PEOPLE OUT WAS 215 00:08:14,200 --> 00:08:18,200 INDUSTRIALIZATION. 216 00:08:18,200 --> 00:08:28,560 THIS -- YOU CAN SEE THIS 217 00:08:40,080 --> 00:08:42,440 PROGRESSION IN INFANTS ALL THE 218 00:08:42,440 --> 00:08:43,040 WAY TO AGE 5 AND YOU CAN SEE 219 00:08:43,040 --> 00:08:50,280 THE GLOBALLY STANDARDIZED. AND 220 00:08:50,280 --> 00:08:51,360 YOU CAN SEE THIS EARLY IN LIFE 221 00:08:51,360 --> 00:08:52,360 YOU CAN GENERALIZE YOUR 222 00:08:52,360 --> 00:09:02,880 ENVIRONMENT AND SO WHAT IS THIS 223 00:09:04,680 --> 00:09:05,200 MICROBIOME? WHEN YOU TRY TO 224 00:09:05,200 --> 00:09:05,800 ENGAGE WITH THE PATIENT ABOUT 225 00:09:05,800 --> 00:09:06,360 THE MICROBIOME, YOU CAN SIT 226 00:09:06,360 --> 00:09:07,000 THERE AND SAY THERE'S ALL KINDS 227 00:09:07,000 --> 00:09:10,680 OF DIFFERENT ORGANISMS, AND 228 00:09:10,680 --> 00:09:11,240 GET BROAD STROKES INTO THE 229 00:09:11,240 --> 00:09:11,840 TYPES OF ANIMALS ALL THE WAY 230 00:09:11,840 --> 00:09:12,360 DOWN TO WHAT REFER TO AS 231 00:09:12,360 --> 00:09:12,960 ISOLATE LEVEL ANALYSIS WHERE 232 00:09:12,960 --> 00:09:17,280 YOU CAN HAVE LOWLY THE WORM AND 233 00:09:17,280 --> 00:09:22,560 HUCKLE THE CAT RIGHT HERE AND 234 00:09:22,560 --> 00:09:23,160 ALSO EXPAND TO THE CONVERSATION 235 00:09:23,160 --> 00:09:28,000 ABOUT JOBS. THE MICROBIOMES 236 00:09:28,000 --> 00:09:28,640 ROLE IS NEVER OF HYDRATION BUT 237 00:09:28,640 --> 00:09:31,640 IN BROAD STROKES IF YOU REALLY, 238 00:09:31,640 --> 00:09:38,400 REALLY NEED A TOW TRUCK DRIVER 239 00:09:38,400 --> 00:09:39,040 YOU CANNOT JUST GRAB A ANY PIG 240 00:09:39,040 --> 00:09:42,000 OFF THE STREET. 241 00:09:42,000 --> 00:09:42,600 IN THE GOT A LOT OF THE MAJOR 242 00:09:42,600 --> 00:09:43,120 ROLES HAVE BEEN PARTIALLY 243 00:09:43,120 --> 00:09:46,120 WORKED OUT. YOU GOT MICROBIOME 244 00:09:46,120 --> 00:09:52,480 WILL DIGEST FIBER, THE FIBER 245 00:09:52,480 --> 00:09:53,080 THAT HUMANS CANNOT DIGEST AND 246 00:09:53,080 --> 00:09:53,560 THEY WILL TURN IT INTO 247 00:09:53,560 --> 00:09:54,200 SHORT-CHAIN FATTY ACIDS ARE THE 248 00:09:54,200 --> 00:09:57,000 MOST RELEVANT OF WHICH TENDS TO 249 00:09:57,000 --> 00:10:00,600 BE OF BUTYRATE, WHEN IT IS 250 00:10:00,600 --> 00:10:01,200 SHOWN TO THE DENDRITIC CELLS 251 00:10:01,200 --> 00:10:06,080 THAT HELP TO PRIME THE SYSTEM 252 00:10:06,080 --> 00:10:08,600 AND MAKES MARKERS TO MAKE 253 00:10:08,600 --> 00:10:09,200 REGULATORY T CELLS, THE CELLS 254 00:10:09,200 --> 00:10:09,760 THAT KEEP THE IMMUNE SYSTEM 255 00:10:09,760 --> 00:10:14,880 FROM OVERREACTING. 256 00:10:14,880 --> 00:10:15,440 IF THOSE SHORT CHAIN FATTY 257 00:10:15,440 --> 00:10:15,960 ACIDS ARE NOT PRESENT IN 258 00:10:15,960 --> 00:10:16,560 PARTICULARLY IF THE FIBER IS 259 00:10:16,560 --> 00:10:19,320 NOT PRESENT, THE SAME ORGANISMS 260 00:10:19,320 --> 00:10:19,960 INSTEAD OF CHEWING UP THE FIBER 261 00:10:19,960 --> 00:10:20,560 WILL HAVE NO OTHER CHOICE BUT 262 00:10:20,560 --> 00:10:22,200 TO EAT THE MUCUS LAYER LINING 263 00:10:22,200 --> 00:10:23,680 YOU GOT IN RIGHT NOW THIS IS 264 00:10:23,680 --> 00:10:24,320 ONE OF THE POTENTIAL THEORIES 265 00:10:24,320 --> 00:10:29,360 BEHIND THE RISE OF INFLAMMATORY 266 00:10:29,360 --> 00:10:33,520 BOWEL DISEASE. THE EROSION OF 267 00:10:33,520 --> 00:10:34,160 THE MUCUS BY OTHERWISE HELPING 268 00:10:34,160 --> 00:10:34,800 ORGANISMS THAT CANNOT BE GIVEN 269 00:10:34,800 --> 00:10:35,360 ANYTHING ELSE THAT THEY CAN 270 00:10:35,360 --> 00:10:36,400 SURVIVE ON, AN ASIDE INSTEAD TO 271 00:10:36,400 --> 00:10:40,560 EAT YOUR STOMACH LINING. 272 00:10:40,560 --> 00:10:41,120 SO OTHER BIG-TICKET ITEMS IN 273 00:10:41,120 --> 00:10:50,000 THE UPPER GOT. FIBER. YOU GET 274 00:10:50,000 --> 00:10:50,600 A LOSS OF THE REGULAR IS ALSO 275 00:10:50,600 --> 00:10:51,120 THE DESTRUCTION OF THOSE 276 00:10:51,120 --> 00:10:51,680 ORGANISMS AND ANOTHER BIG 277 00:10:51,680 --> 00:10:52,200 TICKET OR THE INCREASE OF 278 00:10:52,200 --> 00:10:52,720 SATURATED FATS PARTICULAR 279 00:10:52,720 --> 00:10:58,400 PROCESSED ONCE. NATURALLY 280 00:10:58,400 --> 00:10:59,000 OCCURRING SATURATED FATS LIKE 281 00:10:59,000 --> 00:10:59,600 YOU MIGHT GETTING PEANUTS AND 282 00:10:59,600 --> 00:11:00,160 OTHER SOURCES TEND TO HAVE 283 00:11:00,160 --> 00:11:00,960 MULTIPLE DIFFERENT TYPES OF 284 00:11:00,960 --> 00:11:04,400 MOLECULAR SATURATED FATS 285 00:11:04,400 --> 00:11:05,000 WHEREAS REFINED FOODS ARE ONLY 286 00:11:05,000 --> 00:11:05,640 PALMITIC ACID AND STEARIC ACID 287 00:11:05,640 --> 00:11:09,680 AND ACTIVATE TL-4S. 288 00:11:09,680 --> 00:11:10,280 REFINED SUGARS OF THE NEXT BIG 289 00:11:10,280 --> 00:11:19,760 ONE AND INCREASED-- ANALYSIS 290 00:11:19,760 --> 00:11:20,280 ANOTHER PRO-INFLAMMATORY 291 00:11:20,280 --> 00:11:20,920 MARKERS IN THE ADDICTION CENTER 292 00:11:20,920 --> 00:11:21,440 HERE AT NIH SHOWS THEIR 293 00:11:21,440 --> 00:11:31,200 PARTIALLY NEGATIVE AND CAUSING 294 00:11:31,200 --> 00:11:31,760 YOU TO OVERRATE THE OTHER 295 00:11:31,760 --> 00:11:32,360 ANTI-INFLAMMATORY PRODUCT AND 296 00:11:32,360 --> 00:11:32,960 LASTLY ANTIMICROBIALS, TAKING A 297 00:11:32,960 --> 00:11:33,560 TABLET OF ANTIBIOTICS GETS A 298 00:11:33,560 --> 00:11:36,960 LOT OF ATTENTION BECAUSE THEY 299 00:11:36,960 --> 00:11:39,680 COULD PREVENT FOOD SPOILAGE BUT 300 00:11:39,680 --> 00:11:40,960 COULD HAVE THE SIDE EFFECT OF 301 00:11:40,960 --> 00:11:42,400 KILLING OFF THE MICROBIOME. THE 302 00:11:42,400 --> 00:11:46,200 GOOD GUTS. 303 00:11:46,200 --> 00:11:56,640 WHAT IS THE GUT? WE WENT TO 304 00:11:57,680 --> 00:11:58,160 THE LITERATURE AND SUBJECT 305 00:11:58,160 --> 00:11:58,760 COLLATED INTO FOUR DIFFERENT 306 00:11:58,760 --> 00:11:59,320 CATEGORIES. WE HAVE ALREADY 307 00:11:59,320 --> 00:12:01,320 TALKED ABOUT PROCESSED FOODS 308 00:12:01,320 --> 00:12:01,920 AND ANTIBIOTICS BUT LIVING IN 309 00:12:01,920 --> 00:12:02,520 AN INDUSTRIAL AREA SEEMS TO 310 00:12:02,520 --> 00:12:03,120 MATTER AND LIKE I SAID THERE IS 311 00:12:03,120 --> 00:12:04,160 THIS NEBULOUS VERSION OF FAMILY 312 00:12:04,160 --> 00:12:04,760 HISTORY OF HAVING AN OLDER 313 00:12:04,760 --> 00:12:05,360 SIBLING IS PROTECTED AND THERE 314 00:12:05,360 --> 00:12:05,920 IS SOME VARIANCE IN THE 315 00:12:05,920 --> 00:12:09,760 LITERATURE. THE SHORT VERSION 316 00:12:09,760 --> 00:12:10,360 IS THE MORE OLDER SIBLINGS YOU 317 00:12:10,360 --> 00:12:11,800 HAVE THE LESS LIKELY YOUR RISK 318 00:12:11,800 --> 00:12:15,920 OF ATOPIC DERM GOING TO BE IN 319 00:12:15,920 --> 00:12:16,520 GOING TO DAYCARE IS PROTECTED 320 00:12:16,520 --> 00:12:17,120 AND LIVING ON A FARM IS ALSO 321 00:12:17,120 --> 00:12:18,040 PROTECTED. 322 00:12:18,040 --> 00:12:20,400 SOME THINGS INSIDE THE HOUSE. 323 00:12:20,400 --> 00:12:22,640 MOVING TO THE UNITED STATES OR 324 00:12:22,640 --> 00:12:26,360 EUROPE FROM A NONINDUSTRIALIZED 325 00:12:26,360 --> 00:12:27,000 COUNTRY, BEFORE THE TWO YEAR'S 326 00:12:27,000 --> 00:12:31,960 MARK WILL INCREASE YOUR RISK. 327 00:12:31,960 --> 00:12:32,440 THERE IS AN ADDITIONAL 328 00:12:32,440 --> 00:12:33,040 CALCULATING DISK OF LIVING IN 329 00:12:33,040 --> 00:12:33,560 IN THE UNITED STATES IN 330 00:12:33,560 --> 00:12:42,920 URBANIZED ENVIRONMENTS. AGAIN 331 00:12:42,920 --> 00:12:43,440 SPEAKING TO SOME KIND OF 332 00:12:43,440 --> 00:12:44,080 CRITICAL WINDOW BECAUSE IF YOU 333 00:12:44,080 --> 00:12:44,680 MOVE AFTER YOUR SIX YEARS OF 334 00:12:44,680 --> 00:12:45,280 AGE YOU CAN MOVE WHEREVER YOU 335 00:12:45,280 --> 00:12:45,920 WANT AND YOUR RISK LIST IS NOT 336 00:12:45,920 --> 00:12:56,080 CHANGED. 337 00:12:59,080 --> 00:12:59,680 NORMALLY IN THE POPULATION 338 00:12:59,680 --> 00:13:00,280 DENSITY IN THE UNITED STATES IT 339 00:13:00,280 --> 00:13:00,880 IS A DE FACTO CONVERSATION 340 00:13:00,880 --> 00:13:01,480 ABOUT AUTOMOBILE EXHAUST AND 341 00:13:01,480 --> 00:13:02,080 INDEED THERE IS DATA OUTSIDE OF 342 00:13:02,080 --> 00:13:02,720 KOREA THAT BEING PREGNANT NEAR 343 00:13:02,720 --> 00:13:03,360 HIGHWAY SUBSTANTIALLY INCREASES 344 00:13:03,360 --> 00:13:03,920 THE RISK OF YOUR CHILD WILL 345 00:13:03,920 --> 00:13:11,240 HAVE ECZEMA. 346 00:13:11,240 --> 00:13:11,760 THE INDIVIDUAL COMPONENTS 347 00:13:11,760 --> 00:13:12,400 WOULD TYPICALLY LOOK AT OUT OF 348 00:13:12,400 --> 00:13:13,000 THE BACK OF THE IN AUTO WILL 349 00:13:13,000 --> 00:13:13,640 EXHAUST EACH ARE ASSOCIATED IN 350 00:13:13,640 --> 00:13:20,800 INTERESTINGLY HAVE GONE DOWN 351 00:13:20,800 --> 00:13:21,400 SUBSTANTIALLY SINCE THE 1980S 352 00:13:21,400 --> 00:13:22,000 AND DURING THAT SAME TIME THE 353 00:13:22,000 --> 00:13:24,000 ECZEMA RISES AND THEY NOT HAVE 354 00:13:24,000 --> 00:13:24,600 BEEN DROPPING EQUALLY FOREVER 355 00:13:24,600 --> 00:13:25,240 AND EVER SO I CANNOT EXONERATE 356 00:13:25,240 --> 00:13:25,840 THEM BUT THEY DO NOT LINE UP 357 00:13:25,840 --> 00:13:26,360 FOR EPIDEMIOLOGY. 358 00:13:26,360 --> 00:13:26,960 WILDFIRES WAS JUST PUT ON THE 359 00:13:26,960 --> 00:13:33,720 LIST BY DR. MARIA WADE (SOUNDS 360 00:13:33,720 --> 00:13:34,280 LIKE), OUT OF SAN FRANCISCO 361 00:13:34,280 --> 00:13:34,880 AFTER THE MAJOR CALIFORNIA 362 00:13:34,880 --> 00:13:37,200 WILDFIRES NOT JUST AS A 363 00:13:37,200 --> 00:13:41,160 SUBSEQUENT DEVELOPMENT OF 364 00:13:41,160 --> 00:13:41,760 EPIDERMAL DEVELOPMENT BUT THE 365 00:13:41,760 --> 00:13:42,320 IMMEDIATE FLARES OF THOSE 366 00:13:42,320 --> 00:13:42,880 EXPOSURES AND THE LAST ONE 367 00:13:42,880 --> 00:13:45,040 WOULD BE THINGS THAT ARE 368 00:13:45,040 --> 00:13:48,080 BROADLY REFERRED TO AS 369 00:13:48,080 --> 00:13:48,600 REMODELING BEHAVIORS WITH 370 00:13:48,600 --> 00:13:49,240 THINGS THAT YOU DIRECTLY BRING 371 00:13:49,240 --> 00:13:49,760 IN THE HOME, LIKE NYLON, 372 00:13:49,760 --> 00:13:53,640 SPANDEX AND POLYESTER, THE 373 00:13:53,640 --> 00:13:56,760 FABRICS THAT PATIENTS WITH 374 00:13:56,760 --> 00:13:59,680 ATOPIC DERMIS GRAVITATE TO AN 375 00:13:59,680 --> 00:14:00,320 TOBACCO SMOKE MAKES EVERYTHING 376 00:14:00,320 --> 00:14:02,880 WORSE THE NEW FLOORING, 377 00:14:02,880 --> 00:14:08,560 FURNITURE AND WALLPAPERING BUT 378 00:14:08,560 --> 00:14:09,160 AGAIN, BEFORE TO IT MEDICINE 379 00:14:09,160 --> 00:14:09,800 AFTER FOR IT DOES NOT MATTER SO 380 00:14:09,800 --> 00:14:10,400 THERE'S A CRITICAL EXPOSURE 381 00:14:10,400 --> 00:14:20,560 WINDOW. 382 00:14:23,000 --> 00:14:23,560 SO WHAT ARE THE ORGANISMS ON 383 00:14:23,560 --> 00:14:25,160 THE SKIN THAT THESE FACTORS MY 384 00:14:25,160 --> 00:14:25,800 BEEN INFLUENCING? THESE ARE THE 385 00:14:25,800 --> 00:14:27,720 THINGS THAT ARE KNOWN TO WORSEN 386 00:14:27,720 --> 00:14:35,400 ATOPIC DERM. THE BIGGEST 387 00:14:35,400 --> 00:14:36,040 PROBLEMS I SHOWED YOU IS HAVING 388 00:14:36,040 --> 00:14:39,600 OLDER SIBLINGS IS PROTECTED, 389 00:14:39,600 --> 00:14:40,080 AND GOING TO DAYCARE IS 390 00:14:40,080 --> 00:14:40,600 PROTECTED AND STAFF IS 391 00:14:40,600 --> 00:14:41,120 INCREDIBLY CONTAGIOUS AND 392 00:14:41,120 --> 00:14:46,480 ECZEMA IS NOT. MANY OF THE 393 00:14:46,480 --> 00:14:47,000 PATIENTS AND PARENTS HAVE 394 00:14:47,000 --> 00:14:47,600 DEFIED WITH SCHOOL NURSES AND 395 00:14:47,600 --> 00:14:53,760 PARENTS WE SHOULD KNOW BETTER 396 00:14:53,760 --> 00:14:54,280 THAT THE SKIN RASH IS NOT 397 00:14:54,280 --> 00:14:54,920 CONTAGIOUS TO REMOVE THE STIGMA 398 00:14:54,920 --> 00:15:03,080 SO STAFF SHOULD ALSO CANNOT 399 00:15:03,080 --> 00:15:03,640 CREATE THE UNDERLYING FLAIR 400 00:15:03,640 --> 00:15:04,320 BECAUSE WHATEVER THE UNDERLYING 401 00:15:04,320 --> 00:15:08,440 DISORDER IS IF STAFF COULD COME 402 00:15:08,440 --> 00:15:10,600 AND HIGHLIGHT THAT PATHWAY, 403 00:15:10,600 --> 00:15:15,080 SOMETHING ELSE IS TO UNDERLINE 404 00:15:15,080 --> 00:15:15,680 THE CONDITION THAT THIS TAKE 405 00:15:15,680 --> 00:15:16,280 ADVANTAGE OF SO MANY OTHER 406 00:15:16,280 --> 00:15:16,880 GROUPS ARE LOOKING TOWARD SOME 407 00:15:16,880 --> 00:15:27,440 OF THE OTHER ORGANISMS LIKE -- 408 00:15:33,640 --> 00:15:34,160 GROUP PUBLISHED THE ROLE OF 409 00:15:34,160 --> 00:15:34,680 STAFF EPIDERMIS TO ASSIST 410 00:15:34,680 --> 00:15:35,240 HUMANS TO MAKE LIPIDS LIKE 411 00:15:35,240 --> 00:15:36,200 SERAMIDS. YOU CAN GO TO THE 412 00:15:36,200 --> 00:15:36,680 GROCERY STORE 413 00:15:36,680 --> 00:15:37,200 AND BY THEN BECAUSE OF THE 414 00:15:37,200 --> 00:15:37,840 POTENTIAL EFFECTS FOR THE SKIN 415 00:15:37,840 --> 00:15:38,440 AND PRESUMABLY VITAMIN D AS 416 00:15:38,440 --> 00:15:40,720 WELL AS VICTORY WE LIKE TO WORK 417 00:15:40,720 --> 00:15:42,640 ON, ROSIMONAS MICOSA 418 00:15:42,640 --> 00:15:48,240 (PHONETIC). AND THE OTHER 419 00:15:48,240 --> 00:15:57,520 COAGULATES NEGATIVE STAFF CAN 420 00:15:57,520 --> 00:15:58,160 GENERATE STEROIDS AND WE WILL 421 00:15:58,160 --> 00:15:58,720 REMEMBER THAT VITAMIN D AND 422 00:15:58,720 --> 00:15:59,320 STEROIDS ARE BOTH CHOLESTEROL 423 00:15:59,320 --> 00:15:59,880 DERIVATIVES, LIPID CENTRIC 424 00:15:59,880 --> 00:16:03,800 PATHWAY. 425 00:16:03,800 --> 00:16:04,400 AFTER THE PATHWAY OF THE HUMAN 426 00:16:04,400 --> 00:16:05,000 MICROBIOME PROJECT HEAR FROM 427 00:16:05,000 --> 00:16:13,040 -- -- I HAVE COLORED IN AND 428 00:16:13,040 --> 00:16:13,600 THEY LOOK AT THE DIFFERENT 429 00:16:13,600 --> 00:16:14,080 LOCATIONS OF WHERE THE 430 00:16:14,080 --> 00:16:14,640 DIFFERENT ORGANISMS ARE AND 431 00:16:14,640 --> 00:16:15,120 UNCOVERING WHERE THE 432 00:16:15,120 --> 00:16:16,760 GRAM-NEGATIVE BACTERIA ARE. 433 00:16:16,760 --> 00:16:17,400 AND YOU CONTRASTED TO WHERE YOU 434 00:16:17,400 --> 00:16:18,040 TEND TO SEE THE MANIFESTATIONS 435 00:16:18,040 --> 00:16:25,120 OF ATOPIC DERM, NOT A PERFECT 436 00:16:25,120 --> 00:16:26,120 OVERLAP BUT WE THOUGHT IT WAS 437 00:16:26,120 --> 00:16:26,680 INTRIGUING BECAUSE WHEN YOU 438 00:16:26,680 --> 00:16:27,320 LOOK AT PATIENTS WHO ARE UNDER 439 00:16:27,320 --> 00:16:34,000 EXCELLENT CONTROL, THE SKIN IS 440 00:16:34,000 --> 00:16:34,640 LOOKING GOOD AND FEELING GOOD, 441 00:16:34,640 --> 00:16:35,120 THEY STILL HAVE THIS 442 00:16:35,120 --> 00:16:40,000 PHOSPHOLIPID BASELINE DEFECT. 443 00:16:40,000 --> 00:16:40,560 SINGLE LIPID PATHWAYS STILL 444 00:16:40,560 --> 00:16:41,200 ABNORMAL EVEN WHEN THE SYMPTOMS 445 00:16:41,200 --> 00:16:46,320 ARE NOT THERE. 446 00:16:46,320 --> 00:16:46,880 WHEN YOU PULL THEMSELVES OUT 447 00:16:46,880 --> 00:16:47,440 OF HEALTHY VOLUNTEERS, THEY 448 00:16:47,440 --> 00:16:50,440 DON'T HAVE AN INTRINSIC, CELL 449 00:16:50,440 --> 00:16:51,040 INTRINSIC DIFFERENT BUT THE 450 00:16:51,040 --> 00:16:51,680 GRAM-NEGATIVE BACTERIA ARE MADE 451 00:16:51,680 --> 00:16:54,600 FROM PHOSPHOLIPIDS. THEY DON'T 452 00:16:54,600 --> 00:16:55,200 DO NOTHING BUT PRODUCE IS TO 453 00:16:55,200 --> 00:16:55,760 LINE THEIR OUTER SHELLS SO 454 00:16:55,760 --> 00:16:59,200 MAYBE ATOPIC DERM IS A DEFECT 455 00:16:59,200 --> 00:17:00,320 IN THE GRAM-NEGATIVE 456 00:17:00,320 --> 00:17:00,920 COMMENSALS, AND THAT MIGHT BE 457 00:17:00,920 --> 00:17:03,720 THE UPSTREAM PROBLEM. 458 00:17:03,720 --> 00:17:04,160 WE GOT A LITTLE BIT OF 459 00:17:04,160 --> 00:17:06,360 VALIDATION FROM THIS RECENTLY. 460 00:17:06,360 --> 00:17:06,960 ONLY THREE PROOF SO I DON'T 461 00:17:06,960 --> 00:17:09,760 HAVE ACCESS TO ALL THE DATA, 462 00:17:09,760 --> 00:17:10,320 BUT THIS GROUP BASED OUT OF 463 00:17:10,320 --> 00:17:20,480 KOREA AND DENVER, TOOK TAPE 464 00:17:20,480 --> 00:17:21,040 STRIPS, THE SAMPLE THE SKIN 465 00:17:21,040 --> 00:17:21,640 GENTLY TO SEE WHO DEVELOPED 466 00:17:21,640 --> 00:17:26,520 ECZEMA AT TWO YEARS OF AGE. 467 00:17:26,520 --> 00:17:27,080 WHEN THEY PULLED ALL THE 468 00:17:27,080 --> 00:17:27,680 DIFFERENT FACTORS TOGETHER LIKE 469 00:17:27,680 --> 00:17:28,120 FAMILY HISTORY AND 470 00:17:28,120 --> 00:17:28,680 PRO-INFLAMMATORY ALLERGIC 471 00:17:28,680 --> 00:17:35,560 MOLECULES LIKE TSLP-- YOU LOOK 472 00:17:35,560 --> 00:17:36,200 AT ALL THE DIFFERENT POTENTIAL 473 00:17:36,200 --> 00:17:37,200 METABOLITES AND YOU CAN EXPLAIN 474 00:17:37,200 --> 00:17:40,560 IT INDEED IT WAS CERAMIDES AND 475 00:17:40,560 --> 00:17:41,200 SINGLE LIPIDS THAT PRODUCE THE 476 00:17:41,200 --> 00:17:41,800 GREATEST POTENTIAL SCREENING 477 00:17:41,800 --> 00:17:42,400 TOOL TO SAY ABNORMALITIES AT 478 00:17:42,400 --> 00:17:44,960 TWO MONTHS AND THE CERAMIDES 479 00:17:44,960 --> 00:17:47,640 SINGLE LIPID PATHWAY, IT IS 480 00:17:47,640 --> 00:17:49,120 EVIDENCE OF THE STRONGEST 481 00:17:49,120 --> 00:17:52,280 PREDICTOR. 482 00:17:52,280 --> 00:17:52,880 THESE AUTHORS STILL THINK THAT 483 00:17:52,880 --> 00:17:57,080 THESE LIPIDS MAY BE 484 00:17:57,080 --> 00:17:57,600 HOST-DERIVED, THAT IS A 485 00:17:57,600 --> 00:17:58,160 POSSIBILITY BUT LIKE I SAID 486 00:17:58,160 --> 00:17:58,800 THERE IS NO CELLULAR INTRINSIC 487 00:17:58,800 --> 00:17:59,960 DEFECT. THEN WE HAVE A PROJECT 488 00:17:59,960 --> 00:18:04,360 WITH DR.-- -- TENURE-TRACK HERE 489 00:18:04,360 --> 00:18:05,080 WHERE SHE HAS ACCESS TO A 490 00:18:05,080 --> 00:18:08,160 COHORT. THEY DID A SKIN SWAP AT 491 00:18:08,160 --> 00:18:10,840 ONE WEEK OF AGE, THE FIRST WEEK 492 00:18:10,840 --> 00:18:11,480 OF LIFE AND THEY LOOKED ALL THE 493 00:18:11,480 --> 00:18:13,080 WAY OUT TO THREE YEARS TO SORT 494 00:18:13,080 --> 00:18:18,160 WHETHER OR NOT SOMEBODY HAS 495 00:18:18,160 --> 00:18:18,760 ECZEMA OR OTHERWISE AND VERY 496 00:18:18,760 --> 00:18:19,360 BRIEFLY THE ONLY SPECIES THAT 497 00:18:19,360 --> 00:18:21,560 WAS DIFFERENT IS THE 498 00:18:21,560 --> 00:18:29,200 GRAM-NEGATIVE PROVATELLA 499 00:18:29,200 --> 00:18:29,840 (PHONETIC) WHICH CAME FROM THE 500 00:18:29,840 --> 00:18:30,400 MOTHER MOST LIKELY AND MOST 501 00:18:30,400 --> 00:18:31,040 CORRELATED WITH THE AREAS THAT 502 00:18:31,040 --> 00:18:34,200 HAVE DISEASE. WHEN WE LOOK AT 503 00:18:34,200 --> 00:18:35,600 ALL THE DIFFERENT KIND OF 504 00:18:35,600 --> 00:18:36,240 METABOLIC PATHWAYS, THERE IS NO 505 00:18:36,240 --> 00:18:39,240 WAY ANYBODY CAN READ THIS. THE 506 00:18:39,240 --> 00:18:40,280 ONE THAT IS MOST INDICATIVE OF 507 00:18:40,280 --> 00:18:43,280 CONFIRMED ECZEMA IS THAT SAME 508 00:18:43,280 --> 00:18:45,160 OF GLYCOLSPHINGLE LIPID 509 00:18:45,160 --> 00:18:50,760 PATHWAY. SPEAKING TO POTENTIAL 510 00:18:50,760 --> 00:18:51,360 COMMENSAL DEFECTS AND LIPIDS 511 00:18:51,360 --> 00:18:51,920 THAT MAY DISPOSE ONE TO THE 512 00:18:51,920 --> 00:18:53,800 DISEASE. 513 00:18:53,800 --> 00:18:54,360 WITH THAT WE CAN SPLIT THESE 514 00:18:54,360 --> 00:18:55,200 INTO TWO MAJOR CONVERSATIONS. 515 00:18:55,200 --> 00:18:59,680 THE FIRST IS COULD WE USE THE 516 00:18:59,680 --> 00:19:01,000 MICROBIOME IS A KIND OF THE 517 00:19:01,000 --> 00:19:05,040 CANARY IN THE COAL MINE? IF ANY 518 00:19:05,040 --> 00:19:05,680 OF THE EXPOSURES KILLED OFF THE 519 00:19:05,680 --> 00:19:06,240 LIPID PRODUCING BACTERIA OR 520 00:19:06,240 --> 00:19:08,480 PREVENTED THEM FROM MAKING THE 521 00:19:08,480 --> 00:19:09,040 LIPIDS, THAT WILL BE HIGHLY 522 00:19:09,040 --> 00:19:09,640 CONCERNING AND OBVIOUSLY THE 523 00:19:09,640 --> 00:19:11,320 SECOND ONE WOULD BE, CAN WE USE 524 00:19:11,320 --> 00:19:18,400 JUST A PROBIOTIC? 525 00:19:18,400 --> 00:19:19,000 WE WILL START WITH THE SECOND 526 00:19:19,000 --> 00:19:19,560 ONE AND I WILL SHOW YOU THE 527 00:19:19,560 --> 00:19:21,360 TRAJECTORY OF HOW WE GOT TO THE 528 00:19:21,360 --> 00:19:22,560 CLINICAL TRIAL. THE FIRST THING 529 00:19:22,560 --> 00:19:23,160 IS TO FIGURE OUT HOW TO GROW 530 00:19:23,160 --> 00:19:27,240 GRAND NEGATIVES OFF THE SKIN. 531 00:19:27,240 --> 00:19:27,800 WE FOUND ONE THAT WAS VERY 532 00:19:27,800 --> 00:19:28,960 FREQUENT IN HEALTHY VOLUNTEERS. 533 00:19:28,960 --> 00:19:39,040 -- -- WE PUT IT INTO DIFFERENT 534 00:19:39,040 --> 00:19:39,640 MODELS AND IT SHOWED THAT IT 535 00:19:39,640 --> 00:19:40,160 IMPROVED OUTCOMES OF CELL 536 00:19:40,160 --> 00:19:40,760 CULTURE AND MOUSE MODELS AND 537 00:19:40,760 --> 00:19:44,640 KILLED OFF STAFF TO SOME DEGREE 538 00:19:44,640 --> 00:19:45,240 IN VISUALLY YOU CAN SEE THAT 539 00:19:45,240 --> 00:19:47,360 EVEN THOSE OF GENETICALLY 540 00:19:47,360 --> 00:19:48,000 SIMILAR, THE MORPHOLOGY OF THE 541 00:19:48,000 --> 00:19:48,600 HEALTH ASSOCIATED BACTERIA IS 542 00:19:48,600 --> 00:19:49,160 STARKLY DIFFERENT FROM THAT 543 00:19:49,160 --> 00:19:50,680 WITH THE PATIENTS WITH ECZEMA. 544 00:19:50,680 --> 00:19:51,320 THE SAME ORGANISM BUT THEY ARE 545 00:19:51,320 --> 00:19:55,160 BEHAVING VERY DIFFERENTLY. 546 00:19:55,160 --> 00:19:58,160 WE WANTED TO PLAN FOR THE 547 00:19:58,160 --> 00:20:00,760 PROBIOTIC. CAN YOU USE A 548 00:20:00,760 --> 00:20:01,360 BACTERIAL EXTRACT? IT TURNED 549 00:20:01,360 --> 00:20:05,440 OUT THAT WHEN YOU GAVE MICE 550 00:20:05,440 --> 00:20:06,000 INDUCED DERMATITIS AND GAVE 551 00:20:06,000 --> 00:20:13,040 THEM LIVING BACTERIA, YOU COULD 552 00:20:13,040 --> 00:20:13,640 KILL THE BACTERIA OFF AND WE 553 00:20:13,640 --> 00:20:14,160 COULD DO THIS IN MULTIPLE 554 00:20:14,160 --> 00:20:15,080 DIFFERENT WAYS AND YOU JUST 555 00:20:15,080 --> 00:20:15,680 COULDN'T SO YOU NEED A LIVING 556 00:20:15,680 --> 00:20:16,280 ORGANISM TO PULL THIS OFF AND 557 00:20:16,280 --> 00:20:18,800 ONE OF THE THINGS THAT THE FDA 558 00:20:18,800 --> 00:20:21,160 DOES NOT REQUIRE BUT WE FELT 559 00:20:21,160 --> 00:20:22,120 STRONGLY ABOUT, IS THERE IS A 560 00:20:22,120 --> 00:20:22,680 PROPENSITY IN PROBIOTICS 561 00:20:22,680 --> 00:20:23,320 THINKING AND I HAD THIS THOUGHT 562 00:20:23,320 --> 00:20:24,720 AT ONE TIME TOO. IT IS A 563 00:20:24,720 --> 00:20:28,840 NATURAL BACTERIA NATURAL 564 00:20:28,840 --> 00:20:29,400 EXPOSURE. NOTHING TO WORRY 565 00:20:29,400 --> 00:20:33,000 ABOUT BUT BY DESIGN, YOU ARE 566 00:20:33,000 --> 00:20:34,680 HYPER CONCENTRATING A NATURAL 567 00:20:34,680 --> 00:20:38,440 EXPOSURE TO AN UNNATURAL EXTENT. 568 00:20:38,440 --> 00:20:39,040 AND SO WHAT YOU ARE LOOKING AT 569 00:20:39,040 --> 00:20:39,680 HERE IS THE AMOUNT OF BACTERIA 570 00:20:39,680 --> 00:20:40,720 WE CAN PULL OUT OF A MOUSE 571 00:20:40,720 --> 00:20:41,360 AFTER WE INJECTED IT WITH VERY 572 00:20:41,360 --> 00:20:42,880 LARGE AMOUNTS OF THESE 573 00:20:42,880 --> 00:20:45,240 DIFFERENT ORGANISMS AND YOU CAN 574 00:20:45,240 --> 00:20:52,600 SEE ROSIEMONA (PHONETIC) IS 575 00:20:52,600 --> 00:20:53,120 INCAPABLE OF CREATING A 576 00:20:53,120 --> 00:20:53,720 SYSTEMIC INFECTION IN THE MICE 577 00:20:53,720 --> 00:20:56,000 AND IN ANY OTHER ORGAN TISSUES 578 00:20:56,000 --> 00:20:56,600 AND THAT IS NOT TRUE FOR THE 579 00:20:56,600 --> 00:20:59,720 OTHER COMMENSALS LIKE NEGATIVE 580 00:20:59,720 --> 00:21:00,280 STAFF THAT I SHOWED YOU AND 581 00:21:00,280 --> 00:21:00,760 EVEN SOME OF THE OTHER 582 00:21:00,760 --> 00:21:01,400 COMMENSALS SKIN ORGANISMS THAT 583 00:21:01,400 --> 00:21:05,280 WE GOT. SO THIS FELT SAFE AND 584 00:21:05,280 --> 00:21:05,840 THEN WE PUT THEM INTO ADULT 585 00:21:05,840 --> 00:21:08,440 TRIALS IN AN OPEN LABEL FORMAT, 586 00:21:08,440 --> 00:21:09,000 WITH SOME PRETTY IMPRESSIVE 587 00:21:09,000 --> 00:21:10,640 RESULTS TO START. 588 00:21:10,640 --> 00:21:13,520 AND SO THAT LED US TO THE 589 00:21:13,520 --> 00:21:15,240 CLINICAL TRIAL FOR CHILDREN. 590 00:21:15,240 --> 00:21:20,760 THIS IS STILL THE OPEN LABEL 591 00:21:20,760 --> 00:21:25,520 PHASE, TWO DIFFERENT DOZING 592 00:21:25,520 --> 00:21:26,040 REGIMENTS.-- THIS IS AN 593 00:21:26,040 --> 00:21:26,640 MEASUREMENT OF HOW SEVERE THE 594 00:21:26,640 --> 00:21:27,280 RUSSIAN PEOPLE GOT ABOUT 75% 595 00:21:27,280 --> 00:21:29,720 BETTER WITH TWICE-WEEKLY, THREE 596 00:21:29,720 --> 00:21:30,320 TIMES WEEKLY EXPOSURE OVER THE 597 00:21:30,320 --> 00:21:33,720 COURSE OF FOUR MONTHS. AND THE 598 00:21:33,720 --> 00:21:34,280 IMPORTANT THING WAS THAT WE 599 00:21:34,280 --> 00:21:34,960 TOLD PEOPLE TO STOP USING THE 600 00:21:34,960 --> 00:21:42,600 TREATMENT, AND COME BACK 4-8 A 601 00:21:42,600 --> 00:21:43,200 MONTH LATER BECAUSE WHEN YOU 602 00:21:43,200 --> 00:21:43,800 ENGAGE WITH THE PATIENT THEY 603 00:21:43,800 --> 00:21:44,440 DON'T WANT JUST ANOTHER TOPICAL 604 00:21:44,440 --> 00:21:45,120 THEY HAVE TO APPLY FOR THE REST 605 00:21:45,120 --> 00:21:47,480 OF THE LIFE. THEY WANT 606 00:21:47,480 --> 00:21:48,040 SOMETHING THAT IS DISEASE 607 00:21:48,040 --> 00:21:48,600 MODIFYING AND LIBERATE THEM 608 00:21:48,600 --> 00:21:49,200 FROM THE BURDEN OF CONSTANTLY 609 00:21:49,200 --> 00:21:52,480 NEEDING TO WORRY ABOUT THEIR 610 00:21:52,480 --> 00:21:53,080 DISEASE SO WE DID SEE THAT 611 00:21:53,080 --> 00:21:53,680 WHATEVER IMPROVEMENT THEY HAD 612 00:21:53,680 --> 00:21:54,280 WHEN THEY LEFT IT WAS PRESERVED 613 00:21:54,280 --> 00:21:58,480 OVER TIME OUT TO 36 WEEKS, AND 614 00:21:58,480 --> 00:21:58,960 WE NO LONGER OFFICIALLY 615 00:21:58,960 --> 00:22:07,600 TRACKED. 616 00:22:07,600 --> 00:22:08,160 WE LOOK BY PCR AND IT SHOWS 617 00:22:08,160 --> 00:22:08,800 THAT OUR SPECIFIC BACTERIA ARE 618 00:22:08,800 --> 00:22:09,360 PRESENT ON THE SKIN AT THE 619 00:22:09,360 --> 00:22:09,960 TIME. NOBODY HAD THE EXACT 620 00:22:09,960 --> 00:22:10,840 THREE ISOLATES WHEN THEY WALKED 621 00:22:10,840 --> 00:22:11,440 IN BUT THEY ALL HAD AT LEAST 622 00:22:11,440 --> 00:22:13,080 ONE OF THEM AT THE END OF THE 623 00:22:13,080 --> 00:22:18,120 TREATMENT. AND NOW HERE IT IS 624 00:22:18,120 --> 00:22:18,640 LICENSED OUT TO A PRIVATE 625 00:22:18,640 --> 00:22:19,240 COMPANY THAT RAN THE PLACEBO 626 00:22:19,240 --> 00:22:23,840 CONTROL TRIAL. THEY DID THINGS 627 00:22:23,840 --> 00:22:27,520 WITH THE COMMERCIAL DEVELOPMENT 628 00:22:27,520 --> 00:22:28,080 MINDSET. AND THEY SET THEIR 629 00:22:28,080 --> 00:22:33,280 ENDPOINT WHERE YOU WOULD, WHAT 630 00:22:33,280 --> 00:22:33,880 YOU TYPICALLY WOULD FOR DRUG 631 00:22:33,880 --> 00:22:34,480 DEVELOPMENT WHICH IS ACTIVE 632 00:22:34,480 --> 00:22:37,800 TREATMENT. SADLY, THAT WAS THE 633 00:22:37,800 --> 00:22:38,440 ONE THAT WAS NOT STATISTICALLY 634 00:22:38,440 --> 00:22:38,960 SIGNIFICANT SO FROM THAT 635 00:22:38,960 --> 00:22:47,920 STANDPOINT A COMMERCIAL FAILURE. 636 00:22:47,920 --> 00:22:48,480 YOU CAN SEE THAT THE SECOND 637 00:22:48,480 --> 00:22:49,120 THE TREATMENTS WERE STOPPED THE 638 00:22:49,120 --> 00:22:49,680 PLACEBOS HAD INSIGNIFICANT 639 00:22:49,680 --> 00:22:50,320 INCREASE IN SEVERITY AND EXTENT 640 00:22:50,320 --> 00:22:53,240 OF THE RASH. WE ONLY LOOK FOR 641 00:22:53,240 --> 00:22:53,840 FOUR WEEKS BUT ALL IMPROVEMENTS 642 00:22:53,840 --> 00:22:56,200 WERE PRESERVED OVER THAT TIME. 643 00:22:56,200 --> 00:22:56,800 OBVIOUSLY WE NEED TO DO THIS 644 00:22:56,800 --> 00:23:07,320 TRIAL OVER AGAIN, AND WE PLAN 645 00:23:08,160 --> 00:23:08,720 TO DO SO IN THE LONGER WASHOUT 646 00:23:08,720 --> 00:23:09,320 PERIOD WITH MODIFICATIONS OF 647 00:23:09,320 --> 00:23:09,920 THE PLACEBO GROUP THAT CAUSED 648 00:23:09,920 --> 00:23:10,560 UP TO OVER PERFORM BUT AGAIN AT 649 00:23:10,560 --> 00:23:11,200 LEAST INTRIGUING THAT THERE WAS 650 00:23:11,200 --> 00:23:11,840 SOME RESIDUAL BENEFIT THE LAST 651 00:23:11,840 --> 00:23:12,840 LONGER THAN THE PLACEBO. 652 00:23:12,840 --> 00:23:13,440 SO NOW WE CAN ASK ABOUT USING 653 00:23:13,440 --> 00:23:16,640 THEM IN THE COAL MINES 654 00:23:16,640 --> 00:23:17,240 ESPECIALLY SINCE THE BACTERIA 655 00:23:17,240 --> 00:23:17,760 SEEM TO HAVE SOME KIND OF 656 00:23:17,760 --> 00:23:18,400 EFFICACY. WHAT HAPPENS IF WE 657 00:23:18,400 --> 00:23:18,960 BLOCK IT? TO DO THAT JORDAN 658 00:23:18,960 --> 00:23:22,960 SELDEN IS THE MED STUDENT IN 659 00:23:22,960 --> 00:23:23,600 THE LAB AND FIRST WE TOOK THE 660 00:23:23,600 --> 00:23:26,640 CLINICAL DATABASES THAT ALL 661 00:23:26,640 --> 00:23:32,520 BILLING CODES, SO ANYTIME 662 00:23:32,520 --> 00:23:33,160 SOMEBODY WENT TO A PROVIDER AND 663 00:23:33,160 --> 00:23:36,280 WAS SEEN FOR ATOPIC DERMATITIS, 664 00:23:36,280 --> 00:23:36,920 THEY GO INTO DATABASE AND THEY 665 00:23:36,920 --> 00:23:37,520 CAN TELL US PER CAPITA WHERE 666 00:23:37,520 --> 00:23:43,200 ARE THE ECZEMA HOTSPOTS. WE 667 00:23:43,200 --> 00:23:43,800 CONTRASTED WITH THE PUBLISHED 668 00:23:43,800 --> 00:23:45,240 EPA DATA AND WHAT ARE THE MOST 669 00:23:45,240 --> 00:23:45,880 POLLUTANTS MOST ASSOCIATED WITH 670 00:23:45,880 --> 00:23:46,720 HOTSPOT? 671 00:23:46,720 --> 00:23:49,760 HEY, IS GOING TO BE MESSY AND 672 00:23:49,760 --> 00:23:50,360 I DON'T THINK WE ARE GOING TO 673 00:23:50,360 --> 00:23:56,360 HAVE A -- MOMENT, OBVIOUSLY 674 00:23:56,360 --> 00:23:56,880 SPEAKING TO THE FEMINIST 675 00:23:56,880 --> 00:23:57,520 ACTIVIST AND AUTHOR AND I WILL 676 00:23:57,520 --> 00:23:59,120 SHOW YOU ONE OF THESE GRAPHS. 677 00:23:59,120 --> 00:23:59,720 JORDAN DID MULTIPLE DIFFERENT 678 00:23:59,720 --> 00:24:02,800 MATHEMATICAL MODELS. THEY ARE 679 00:24:02,800 --> 00:24:05,480 VERY SIMILAR AND THIS IS 680 00:24:05,480 --> 00:24:06,080 PREDICTING WHAT POLLUTANTS ARE 681 00:24:06,080 --> 00:24:07,240 MOST ASSOCIATED WITH VISITS TO 682 00:24:07,240 --> 00:24:10,560 THE PEDIATRICIAN FOR ATOPIC 683 00:24:10,560 --> 00:24:11,080 DERM, UNDER THOUGHT THE 684 00:24:11,080 --> 00:24:11,640 CHILDREN OF THE SELECTED TO 685 00:24:11,640 --> 00:24:13,080 MOVE AWAY FROM THAT EARLY 686 00:24:13,080 --> 00:24:13,720 CHILDHOOD WINDOW AS ADULTS AND 687 00:24:13,720 --> 00:24:24,080 SO THIS THING CALLED 688 00:24:25,000 --> 00:24:27,120 DISOCYANATES JUMPED OFF, FOR 689 00:24:27,120 --> 00:24:27,680 ANYONE WHO HAS TWO OF THESE 690 00:24:27,680 --> 00:24:30,000 MOLECULES TWO OF THESE 691 00:24:30,000 --> 00:24:37,280 DISOCYANATE SITE CHANGES AND 692 00:24:37,280 --> 00:24:37,880 DISOCYANATE WORT/BALTHAT WAS 693 00:24:37,880 --> 00:24:44,120 ALREADY A CONNECTION WITH 694 00:24:44,120 --> 00:24:47,360 ALLERGIC DISEASE TO BEGIN WITH 695 00:24:47,360 --> 00:24:49,560 AND DISOCYANATE WAS NUMBER ONE 696 00:24:49,560 --> 00:24:55,880 FOR -- AND TWO FOUR PEDIATRIC 697 00:24:55,880 --> 00:24:56,240 ASTHMA. 698 00:24:56,240 --> 00:24:56,840 IT WOULD BE WISER TO OPEN UP A 699 00:24:56,840 --> 00:25:01,280 FACTORY THAT PRODUCES 700 00:25:01,280 --> 00:25:01,920 DISOCYANATES 30 MILES AWAY THEN 701 00:25:01,920 --> 00:25:02,520 TO ADD A PEDIATRIC ALLERGIST 702 00:25:02,520 --> 00:25:05,320 YOUR HOSPITAL. THESE WERE NOT 703 00:25:05,320 --> 00:25:05,840 ASSOCIATED JUST WITH ANY 704 00:25:05,840 --> 00:25:09,320 DISEASE. WE WILL LOOK AT 705 00:25:09,320 --> 00:25:09,920 THINGS LIKE PSORIASIS IT WAS 706 00:25:09,920 --> 00:25:13,200 NOWHERE ON THE LIST. IT WAS NOT 707 00:25:13,200 --> 00:25:13,760 JUST SOME NONSPECIFIC SKIN 708 00:25:13,760 --> 00:25:17,680 IRRITANT THAT SCHIZOPHRENIA AND 709 00:25:17,680 --> 00:25:18,280 MENTAL HEALTH DISORDERS IT DOES 710 00:25:18,280 --> 00:25:18,880 NOT APPEAR ON THAT ALSO THE 711 00:25:18,880 --> 00:25:20,720 ASSOCIATIONS WAS LIMITED TO 712 00:25:20,720 --> 00:25:21,320 ATOPIC DISEASES ESPECIALLY IN 713 00:25:21,320 --> 00:25:24,800 CHILDREN. 714 00:25:24,800 --> 00:25:25,360 SO WE ASKED, WE WOULD I BE 715 00:25:25,360 --> 00:25:34,000 EXPOSED TO DISOCYANATES? SO I 716 00:25:34,000 --> 00:25:34,600 WILL CONTRAST THAT TO THE LIST 717 00:25:34,600 --> 00:25:36,960 OF EXPOSURES AND THEY WERE 718 00:25:36,960 --> 00:25:37,800 INVENTED IN 1940; THEY WERE 719 00:25:37,800 --> 00:25:38,440 MANUFACTURED IN EARNEST IN THE 720 00:25:38,440 --> 00:25:39,040 UNITED STATES STARTING RIGHT 721 00:25:39,040 --> 00:25:39,640 AROUND 1970. THE TWO MOST 722 00:25:39,640 --> 00:25:43,400 PREVALENT ONES ARE TDI, THE 723 00:25:43,400 --> 00:25:45,200 VOLATILE VERSION AND MDI WHICH 724 00:25:45,200 --> 00:25:50,000 IS THE SECOND MOST COMMON ONE. 725 00:25:50,000 --> 00:25:50,600 AGAIN AN ASSOCIATION FOR WHEN 726 00:25:50,600 --> 00:25:51,200 THINGS STARTED TO SHOW UP ON 727 00:25:51,200 --> 00:25:54,800 THE MARKET. 728 00:25:54,800 --> 00:25:55,320 LIVING NEAR A HIGHWAY YOU 729 00:25:55,320 --> 00:25:56,960 WOULD BE EXPOSED TO AUTOMOBILE 730 00:25:56,960 --> 00:25:57,560 EXHAUST, BUT ONLY IF IT GOES 731 00:25:57,560 --> 00:25:58,760 THROUGH A CATALYTIC CONVERTER. 732 00:25:58,760 --> 00:26:00,240 GATLINBURG NORMALLY DOES NOT 733 00:26:00,240 --> 00:26:09,000 CREATE DISOCYANATES, BUT THE 734 00:26:09,000 --> 00:26:09,600 CATALYTIC CONVERTER IS THE 735 00:26:09,600 --> 00:26:10,200 REASON THAT ALL OF THOSE OTHER 736 00:26:10,200 --> 00:26:10,800 THINGS I MENTIONED HAVE BEEN 737 00:26:10,800 --> 00:26:12,840 GOING DOWN, AND IT IS VERY 738 00:26:12,840 --> 00:26:13,440 ESSENTIAL TO PROTECT US FROM 739 00:26:13,440 --> 00:26:18,040 THOSE THINGS IT DOES PRODUCE 740 00:26:18,040 --> 00:26:18,640 DISOCYANATES IN THE CATALYTIC 741 00:26:18,640 --> 00:26:19,640 CONVERTER. THERE IS ONLY ONE 742 00:26:19,640 --> 00:26:28,680 MAJOR NATURAL SOURCE OF 743 00:26:28,680 --> 00:26:29,240 DISOCYANATES, THAT WILL BE 744 00:26:29,240 --> 00:26:29,800 WILDFIRES IN THE CORRELATE 745 00:26:29,800 --> 00:26:32,880 NICELY WITH THE CO2 PRODUCTION 746 00:26:32,880 --> 00:26:34,080 BUT IT IS PRESENT IN WILDFIRES 747 00:26:34,080 --> 00:26:34,680 DEPENDING ON THE PLANT AND IF 748 00:26:34,680 --> 00:26:35,240 YOU ARE TRYING TO FILL YOUR 749 00:26:35,240 --> 00:26:38,600 HOME WITH DISOCYANATES ON 750 00:26:38,600 --> 00:26:39,200 PURPOSE YOU SHOULD TRY TO GET 751 00:26:39,200 --> 00:26:43,240 NYLONS AND POLYESTER, AND START 752 00:26:43,240 --> 00:26:48,040 SMOKING AND GO GET NEW 753 00:26:48,040 --> 00:26:48,800 FLOORING, NON-LATEX FOAM AND 754 00:26:48,800 --> 00:26:56,640 WALLPAPER GLUE. SO 755 00:26:56,640 --> 00:26:57,240 DISOCYANATES PRODUCE EFFECTS 756 00:26:57,240 --> 00:26:57,880 LIKE CIGARETTE SMOKE SO A VERY 757 00:26:57,880 --> 00:26:58,520 CONCERNING EPIDEMIOLOGICAL LINK 758 00:26:58,520 --> 00:27:07,720 OF ALL OF THESE DEBACLES. 759 00:27:07,720 --> 00:27:08,160 WHAT WILL WE DO TO THE 760 00:27:08,160 --> 00:27:11,480 BACTERIA IF WE EXPOSED IT? SO 761 00:27:11,480 --> 00:27:12,120 BASED ON THE ONES WE PULL FROM 762 00:27:12,120 --> 00:27:14,080 PATIENTS WITH ATOPIC DERM AND 763 00:27:14,080 --> 00:27:20,480 EXPOSE IT IN A CANISTER WITH 764 00:27:20,480 --> 00:27:21,120 TDI IT WOULD KILL THEM OFF AND 765 00:27:21,120 --> 00:27:21,720 THE DISEASE WILL ALSO DIE OFF 766 00:27:21,720 --> 00:27:25,160 BUT LESS SEVERE, THEY ARE A 767 00:27:25,160 --> 00:27:25,760 LITTLE BIT BETTER ADAPTED AND 768 00:27:25,760 --> 00:27:26,200 IF YOU LOOK AT THE 769 00:27:26,200 --> 00:27:26,800 GRAM-POSITIVE ORGANISMS THEY 770 00:27:26,800 --> 00:27:27,400 HELP ASSOCIATED STAFF DIE OFF 771 00:27:27,400 --> 00:27:33,520 TO SOME EXTENT WITH DISOCYANATE 772 00:27:33,520 --> 00:27:34,120 EXPOSURE BUT STAFF IS WELL 773 00:27:34,120 --> 00:27:34,720 ADAPTED TO METABOLIZE IT THAT 774 00:27:34,720 --> 00:27:37,640 WAY AND PROTECT ITSELF. 775 00:27:37,640 --> 00:27:38,040 WE PUBLISH ALL THE 776 00:27:38,040 --> 00:27:38,600 NITTY-GRITTY DETAILS IN THE 777 00:27:38,600 --> 00:27:39,240 PAPER IF YOU WANT TO SEE IT. I 778 00:27:39,240 --> 00:27:39,880 WILL GIVE YOU THE UPSHOT WHICH 779 00:27:39,880 --> 00:27:47,440 IS FOR ROSIEMONAS, IT IS 780 00:27:47,440 --> 00:27:48,040 CREATING THESE LIPIDS OUT OF 781 00:27:48,040 --> 00:27:49,640 THE AIR. THERE IS AN OBLIGATE 782 00:27:49,640 --> 00:27:56,280 NITROGEN FIXER AND IT WILL ALSO 783 00:27:56,280 --> 00:27:56,960 FIX THE CO2 AND PUT BOTH OF 784 00:27:56,960 --> 00:27:57,560 THEM INTO THE -- GROUPS WHICH 785 00:27:57,560 --> 00:28:00,080 HAVE THESE TABS, WHICH 786 00:28:00,080 --> 00:28:00,680 OCCUPATIONAL ASTHMA RESEARCH 787 00:28:00,680 --> 00:28:02,920 HAS SHOWN NICELY, THE 788 00:28:02,920 --> 00:28:10,240 DISOCYANATE TAG TO THOSE -- 789 00:28:10,240 --> 00:28:10,840 TAGS, THAT IS WHAT IS CAUSING 790 00:28:10,840 --> 00:28:11,440 THE LIPID DISRUPTION AND YOU 791 00:28:11,440 --> 00:28:12,160 CAN WHAT IS HAPPENING IN THE 792 00:28:12,160 --> 00:28:12,760 BACTERIA AS WE INCREASE THE 793 00:28:12,760 --> 00:28:19,840 EXPOSURE TO DISOCYANATE, THE 794 00:28:19,840 --> 00:28:21,000 REDLINE IS A TOTAL AMOUNT OF 795 00:28:21,000 --> 00:28:26,920 THE BACTERIA. AND EVEN AT THOSE 796 00:28:26,920 --> 00:28:27,560 THAT ALLOW THE BACTERIA TO GROW 797 00:28:27,560 --> 00:28:28,160 BETTER IT CAN METABOLIZE AND 798 00:28:28,160 --> 00:28:28,760 GROW BETTER ON IT BUT WHEN IT 799 00:28:28,760 --> 00:28:30,480 DOES IT HAS TO CHANGE HIS 800 00:28:30,480 --> 00:28:31,920 PHYSIOLOGY. BECAUSE IT IS 801 00:28:31,920 --> 00:28:32,560 PROVIDED AN ALTERNATE NITROGEN 802 00:28:32,560 --> 00:28:36,960 SOURCE SO WE EXPOSE THE 803 00:28:36,960 --> 00:28:37,520 DISOCYANATE TO SEE IF IT IS 804 00:28:37,520 --> 00:28:38,120 ENHANCING ITS GROWTH AND YOU 805 00:28:38,120 --> 00:28:38,720 TAKE AWAY NITROGEN HE GOES 806 00:28:38,720 --> 00:28:42,720 AWAY. SO NITROGEN IS A FIXER 807 00:28:42,720 --> 00:28:52,080 AND TDI PARTIALLY PROTECTS THE 808 00:28:52,080 --> 00:28:52,600 TOY GIVES IT AN ALTERNATE 809 00:28:52,600 --> 00:28:53,200 NITROGEN SOURCE FROM THE AIR, 810 00:28:53,200 --> 00:28:53,680 EXCHANGING IT FOR THE 811 00:28:53,680 --> 00:28:59,360 PRODUCTION OF DISOCYANATES. WE 812 00:28:59,360 --> 00:28:59,960 ALSO LEARNED THIS EXACT TRICK 813 00:28:59,960 --> 00:29:00,440 TO PROTECT ITSELF FROM 814 00:29:00,440 --> 00:29:03,520 ANTIMICROBIAL PEPTIDES AND 815 00:29:03,520 --> 00:29:08,440 OTHER -- IN ITS ENVIRONMENTAL 816 00:29:08,440 --> 00:29:13,680 EXPOSURE TO DISOCYANATES, YOU 817 00:29:13,680 --> 00:29:14,320 CAN PRE-TREATED THEM WITH EXTRA 818 00:29:14,320 --> 00:29:14,920 LYSINE YOU CAN GET PROTECTION 819 00:29:14,920 --> 00:29:18,560 AND THAT IS THE TRADE-OFF IT IS 820 00:29:18,560 --> 00:29:19,160 MAKING AN IS SUB DOING THE JOB 821 00:29:19,160 --> 00:29:19,800 THAT YOU NEEDED TO DO AND START 822 00:29:19,800 --> 00:29:20,440 PROTECTING ITSELF. COMES AT OUR 823 00:29:20,440 --> 00:29:21,760 EXPENSE. 824 00:29:21,760 --> 00:29:22,360 YOU CAN SEE THIS IN THE MOUSE 825 00:29:22,360 --> 00:29:23,640 MODELS DIRECTLY. THIS IS A 826 00:29:23,640 --> 00:29:24,240 MODEL OF INFLAMMATION IN THE 827 00:29:24,240 --> 00:29:30,360 MOUSE EARS. THE BIGGER THE BAR 828 00:29:30,360 --> 00:29:30,920 THE MORE INFORMATION IN THE 829 00:29:30,920 --> 00:29:41,480 WORSE THE OUTCOME FOR THE MOUSE. 830 00:29:43,640 --> 00:29:44,040 IF YOU TREATED WITH 831 00:29:44,040 --> 00:29:45,080 ROSIEMONIAS YOU SEE THE 832 00:29:45,080 --> 00:29:47,920 REDUCTION. IF YOU EXPOSE IT TO 833 00:29:47,920 --> 00:29:49,360 TDI, YOU REMOVE THE THERAPEUTIC 834 00:29:49,360 --> 00:29:51,200 EFFECT. YOU CAN SEE THE 835 00:29:51,200 --> 00:29:54,760 DISOCYANATE SIDE CHAIN, SAME 836 00:29:54,760 --> 00:29:56,960 DEAL AND YOU CAN BLOG WITH THE 837 00:29:56,960 --> 00:29:58,800 TREATMENT OF ROSIMONAS BUT IF 838 00:29:58,800 --> 00:30:02,000 YOU COULD PREDISPOSE IT WITH 839 00:30:02,000 --> 00:30:09,440 DISOCYANATE (INDISCERNIBLE). 840 00:30:09,440 --> 00:30:10,000 YOU CAN ATTEMPT A CLINICAL 841 00:30:10,000 --> 00:30:13,080 TRIAL AS WELL SO THIS IS 842 00:30:13,080 --> 00:30:16,480 ENTIRELY POSTDOC. THERE IS NO 843 00:30:16,480 --> 00:30:17,080 WAY THE COMPANY COULD HAVE 844 00:30:17,080 --> 00:30:17,680 KNOWN THIS BUT WHEN THEY RAN 845 00:30:17,680 --> 00:30:18,280 THIS TRIAL IT WAS 15 DIFFERENT 846 00:30:18,280 --> 00:30:18,920 STUDY SITES IN 15 DIFFERENT ZIP 847 00:30:18,920 --> 00:30:23,080 CODES. NOW WE CAN GO BACK 848 00:30:23,080 --> 00:30:23,720 AND SAY CAN WE STRATIFY BY HOW 849 00:30:23,720 --> 00:30:24,320 WELL YOU DID IT IN A CLINICAL 850 00:30:24,320 --> 00:30:24,920 TRIAL BASED ON WHAT THE INDIAN 851 00:30:24,920 --> 00:30:28,040 LEVEL OF DISOCYANATES WERE IN 852 00:30:28,040 --> 00:30:29,960 YOUR REGION? 853 00:30:29,960 --> 00:30:30,520 INDEED WE CAN AND YOU CAN SEE 854 00:30:30,520 --> 00:30:31,120 THAT IF YOU LIVE HERE IN THE 855 00:30:31,120 --> 00:30:34,640 ABOVE AVERAGE TDI REGIONS YOU 856 00:30:34,640 --> 00:30:43,520 GET A GREATER REDUCTION IN YOUR 857 00:30:43,520 --> 00:30:44,080 DISEASE AND IF YOU LIVED IN 858 00:30:44,080 --> 00:30:44,640 BELOW AVERAGE REGIONS. YOU 859 00:30:44,640 --> 00:30:45,240 NOTED THAT IN BOTH OF THE 860 00:30:45,240 --> 00:30:50,280 TREATMENT HOLES, AND WE 861 00:30:50,280 --> 00:30:50,880 INTERPRETED THIS TO MEAN THAT 862 00:30:50,880 --> 00:30:51,480 IF YOU ARE IN AN AREA WHERE 863 00:30:51,480 --> 00:30:55,440 YOUR NATURAL BACTERIA BEING 864 00:30:55,440 --> 00:30:56,040 DETOXIFIED, REPLENISHING THEM 865 00:30:56,040 --> 00:30:56,680 IS MORE BENEFICIAL THAN IF YOU 866 00:30:56,680 --> 00:30:57,280 WERE TO LIVE IN AN OTHERWISE 867 00:30:57,280 --> 00:30:59,080 CLEAN ENVIRONMENT, WITH THIS 868 00:30:59,080 --> 00:30:59,720 PARTICULAR MECHANISM MAY NOT BE 869 00:30:59,720 --> 00:31:00,760 THE SOURCE OF YOUR PROBLEM AND 870 00:31:00,760 --> 00:31:01,320 YOU MIGHT GET BENEFIT FROM 871 00:31:01,320 --> 00:31:07,160 SOMETHING ELSE. 872 00:31:07,160 --> 00:31:07,560 AGAIN WILL HAVE TO 873 00:31:07,560 --> 00:31:08,000 INTENTIONALLY DO THIS 874 00:31:08,000 --> 00:31:08,640 PROSPECTIVELY ANNEXED TRIAL BY 875 00:31:08,640 --> 00:31:10,960 PICKING SELECTED STUDIES SIDES. 876 00:31:10,960 --> 00:31:12,920 THAT IS INTRIGUING. 877 00:31:12,920 --> 00:31:18,880 MAKING SURE WE ARE NOT JUST 878 00:31:18,880 --> 00:31:19,480 ROSIEMONAS-CENTRIC, WE LOOKED 879 00:31:19,480 --> 00:31:21,760 AT THE OTHER ORGANISMS THAT 880 00:31:21,760 --> 00:31:25,400 INDUCE-- -- AND YOU CAN SEE 881 00:31:25,400 --> 00:31:26,000 THIS REDUCTION IF YOU EXPOSE 882 00:31:26,000 --> 00:31:30,840 THE STAFF TO THE TDI BEFOREHAND 883 00:31:30,840 --> 00:31:31,320 AND THIS IS JUST A BIG 884 00:31:31,320 --> 00:31:34,440 COMPLICATED PLOT OF ALL THE 885 00:31:34,440 --> 00:31:35,040 METABOLIC PROCESSES THAT WERE 886 00:31:35,040 --> 00:31:35,600 AFFECTED IN STAFF WHEN YOU 887 00:31:35,600 --> 00:31:46,040 EXPOSE IT. IT WAS ENTIRELY IN 888 00:31:46,040 --> 00:31:49,640 THAT GLYCOSINGLIPID PATHWAY. 889 00:31:49,640 --> 00:31:50,240 IT IS THE SAME THING AS USING 890 00:31:50,240 --> 00:31:51,480 MOUSE MODELS FOR YOU GET THIS 891 00:31:51,480 --> 00:31:55,960 INCREASE IN SWELLING TREAT IT 892 00:31:55,960 --> 00:31:56,840 WITH-- AND IT GOES AWAY BUT NOT 893 00:31:56,840 --> 00:32:07,160 IF EXPOSE STAFF --. 894 00:32:07,640 --> 00:32:08,200 AND SO I DON'T HAVE DATA ON 895 00:32:08,200 --> 00:32:11,280 THIS BUT I THINK IT IS 896 00:32:11,280 --> 00:32:11,880 INTRIGUING. MY HYPOTHESIS IS 897 00:32:11,880 --> 00:32:12,400 THAT MAYBE THE PROTECTIVE 898 00:32:12,400 --> 00:32:13,040 SIBLING EFFECT WHICH ORIGINALLY 899 00:32:13,040 --> 00:32:14,480 WAS THOUGHT TO BE, MAYBE THE 900 00:32:14,480 --> 00:32:15,320 OLDER KIDS ARE BRINGING THE 901 00:32:15,320 --> 00:32:20,960 SNIFFLES HOME, BUT THAT DID NOT 902 00:32:20,960 --> 00:32:21,560 END UP BEING TRUE. GENERALLY 903 00:32:21,560 --> 00:32:23,240 PROTECTED INFECTIONS AGAINST 904 00:32:23,240 --> 00:32:23,800 ALLERGY AND TAPEWORMS AND 905 00:32:23,800 --> 00:32:25,120 PARASITES AND RUNNY NOSES, THE 906 00:32:25,120 --> 00:32:28,480 FIRST KID GETS A FANCY, NEW 907 00:32:28,480 --> 00:32:29,080 RENOVATED NURSERY IN THE FOURTH 908 00:32:29,080 --> 00:32:29,840 GET JUST GET WHATEVER THE FIRST 909 00:32:29,840 --> 00:32:35,520 THREE HAVE NOT DESTROYED. AND 910 00:32:35,520 --> 00:32:36,160 YOU ACTUALLY GO TO THE HARDWARE 911 00:32:36,160 --> 00:32:36,760 STORE AND BOUGHT THESE THINGS 912 00:32:36,760 --> 00:32:39,240 OFF THE SHELF. POLYURETHANE 913 00:32:39,240 --> 00:32:40,640 BASED GLUE PARTIALLY INCREASES 914 00:32:40,640 --> 00:32:46,480 THE GROWTH OF THE HV STRANGE 915 00:32:46,480 --> 00:32:47,120 BUT NOT TO A SIGNIFICANT DEGREE 916 00:32:47,120 --> 00:32:48,720 BUT YOU NOTICE THAT THE DISEASE 917 00:32:48,720 --> 00:32:49,200 ASSOCIATED ISOLATES ARE 918 00:32:49,200 --> 00:32:52,320 EXCEPTIONAL AT METABOLIZING THE 919 00:32:52,320 --> 00:32:52,920 FUMES FOR POLYURETHANE GLUE. 920 00:32:52,920 --> 00:32:54,440 THAT IS AGAIN INTRIGUING. 921 00:32:54,440 --> 00:32:55,920 922 00:32:55,920 --> 00:32:59,120 THAT IS TEACHING US AGAIN 923 00:32:59,120 --> 00:32:59,720 USING THE CANARY IN THE COAL 924 00:32:59,720 --> 00:33:01,120 MINE, DOES NOT MEAN THAT THE 925 00:33:01,120 --> 00:33:02,080 ONLY THING THAT IS AFFECTED IS 926 00:33:02,080 --> 00:33:07,600 THE MICROBIOME; IT COULD BE 927 00:33:07,600 --> 00:33:08,240 DOING OTHER THINGS IN THE HOST 928 00:33:08,240 --> 00:33:08,800 AND AGAIN LOOKING BACK AT 929 00:33:08,800 --> 00:33:09,400 OCCUPATIONAL ASTHMA THEY MADE 930 00:33:09,400 --> 00:33:10,040 IT CONNECTION WITH A PARTICULAR 931 00:33:10,040 --> 00:33:13,880 RECEPTOR CALLED TRIPP A-1. WE 932 00:33:13,880 --> 00:33:24,400 ALL KIND OF NOTICE, TRIPP-V1 IS 933 00:33:24,400 --> 00:33:24,960 THE REASON WHY CHILI POWDER 934 00:33:24,960 --> 00:33:25,600 TASTES HOT. AND SO EVEN THOUGH 935 00:33:25,600 --> 00:33:26,160 IT IS ONLY SUPPOSED TO BE A 936 00:33:26,160 --> 00:33:26,680 THERMAL RECEPTOR. 937 00:33:26,680 --> 00:33:31,720 IF YOU PUT TDI DIRECTLY ON MOC 938 00:33:31,720 --> 00:33:32,240 WHICH IS ALREADY A 939 00:33:32,240 --> 00:33:32,760 WELL-ESTABLISHED MODEL OF 940 00:33:32,760 --> 00:33:38,080 ATOPIC DERM, WHEN YOU HAVE THAT 941 00:33:38,080 --> 00:33:39,280 DISOCYANATES TURNS OUT THAT 942 00:33:39,280 --> 00:33:45,960 PEOPLE INTENTIONALLY USES TO 943 00:33:45,960 --> 00:33:46,480 INDUCE ECZEMA IN MICE AND 944 00:33:46,480 --> 00:33:47,080 PRECLINICAL TRIALS AND USING 945 00:33:47,080 --> 00:33:49,320 VARIOUS DRUGS TO IMPROVE THE 946 00:33:49,320 --> 00:33:49,840 OUTCOMES TO JUSTIFY HUMAN 947 00:33:49,840 --> 00:33:50,480 TRIALS OF THE FDA. WHEN YOU PUT 948 00:33:50,480 --> 00:33:51,120 TDI HERE ON THE MOUSE, YOU GET 949 00:33:51,120 --> 00:33:51,720 THIS BIG SWELLING BUT LESS SO 950 00:33:51,720 --> 00:33:54,480 IF YOU DO NOT HAVE TRIPP-A1 951 00:33:54,480 --> 00:33:58,120 RECEPTOR. 952 00:33:58,120 --> 00:33:58,640 YOU CAN ACTUALLY SEE THIS 953 00:33:58,640 --> 00:34:03,360 HAPPEN IN NERVE CELLS. WE TOOK 954 00:34:03,360 --> 00:34:06,280 NERVE CELLS THROUGH TDI INTO 955 00:34:06,280 --> 00:34:07,880 THE BROTH HAVING PRE-BLOCKED IT 956 00:34:07,880 --> 00:34:18,440 WITH TRIPP-A1 BLOCK YOU CAN SEE 957 00:34:21,440 --> 00:34:21,960 THE DIFFERENCE AND WHEN THESE 958 00:34:21,960 --> 00:34:22,560 CELLS ARE ACTIVATED IN THIS 959 00:34:22,560 --> 00:34:23,160 PARTICULAR RECEPTOR THEY WILL 960 00:34:23,160 --> 00:34:23,760 SEND A SIGNAL TO THE BRAIN FOR 961 00:34:23,760 --> 00:34:24,360 AGE AND THE BRAIN WILL SEND A 962 00:34:24,360 --> 00:34:25,000 SIGNAL BACK FOR INFORMATION AND 963 00:34:25,000 --> 00:34:25,480 RASH SO AGAIN ANOTHER 964 00:34:25,480 --> 00:34:35,040 CONNECTION. BLOCKING TRIPP-A1 965 00:34:35,040 --> 00:34:35,640 IN OUR MODEL DID NOT PROVIDE A 966 00:34:35,640 --> 00:34:36,240 BENEFIT TO THE MICE BUT THERE 967 00:34:36,240 --> 00:34:36,840 WAS A SYNERGISTIC EFFECT TO 968 00:34:36,840 --> 00:34:37,440 THOSE WE WE REDO THE CLINICAL 969 00:34:37,440 --> 00:34:41,880 TRIAL WE WILL ADD A TRIPP-A1 970 00:34:41,880 --> 00:34:42,480 LUCKY TO GET A BETTER EFFICACY 971 00:34:42,480 --> 00:34:43,720 AND IMPROVEMENT IN PATIENTS. 972 00:34:43,720 --> 00:34:48,600 OTHER THINGS THAT CONNECT 973 00:34:48,600 --> 00:34:49,200 TRIPP-A1 TO THE ALLERGIC PATH 974 00:34:49,200 --> 00:34:55,360 WAS MENTIONED AT THE BEGINNING, 975 00:34:55,360 --> 00:34:55,960 TSLP IS AGAIN AN INFLAMMATORY 976 00:34:55,960 --> 00:34:59,400 MARKER THAT INDUCES AGE AND IS 977 00:34:59,400 --> 00:34:59,960 UPSTREAM FROM A LOT OF THE 978 00:34:59,960 --> 00:35:00,600 LOGIC SIGNALING AND IF YOU PUT 979 00:35:00,600 --> 00:35:03,320 IT ON THE EAR OF THE MOUSE, THE 980 00:35:03,320 --> 00:35:03,840 MOUSE WILL SIT THERE AND 981 00:35:03,840 --> 00:35:04,440 SCRATCH AND PEOPLE CAN COUNT 982 00:35:04,440 --> 00:35:08,560 HOW OFTEN IT IS DOING SO AND 983 00:35:08,560 --> 00:35:09,120 HOW ITCHY IT IS. IT INDUCES 984 00:35:09,120 --> 00:35:19,680 ITCHING IN THE MOUSE. IT ISN'T 985 00:35:25,440 --> 00:35:25,960 INVOLVED IN THE PARTICULAR 986 00:35:25,960 --> 00:35:26,560 ITCH, THERE HAS NOT BEEN A LOT 987 00:35:26,560 --> 00:35:27,160 OF THAT ASSESSMENT, THERE'S A 988 00:35:27,160 --> 00:35:27,760 SMALL NUMBER OF PATIENTS THAT 989 00:35:27,760 --> 00:35:28,360 SUGGEST THERE IS INCREASED 990 00:35:28,360 --> 00:35:28,960 EXPRESSION IN PATIENTS WITH 991 00:35:28,960 --> 00:35:29,560 ATOPIC DERM, AND HERE IS THE 992 00:35:29,560 --> 00:35:36,600 STAINING FOR AISLE 13, IN 993 00:35:36,600 --> 00:35:38,400 DISTRICT OF ACTIVATION OF 994 00:35:38,400 --> 00:35:42,320 TRIPP-A1. ACTIVATING BOTH TSLP 995 00:35:42,320 --> 00:35:52,560 AND AISLE 13. 996 00:35:57,080 --> 00:35:57,640 IN SUMMARY FOR THIS PART, WE 997 00:35:57,640 --> 00:35:58,200 SAID THAT THE DISOCYANATES 998 00:35:58,200 --> 00:35:58,840 ASSOCIATED WITH AD AND AT TIMES 999 00:35:58,840 --> 00:35:59,560 FACE AND EPIDEMIOLOGY, 1000 00:35:59,560 --> 00:36:04,360 INDUCING A DETAIL PHENOTYPE AND 1001 00:36:04,360 --> 00:36:09,320 INDUCES COMMENSALS-- AND 1002 00:36:09,320 --> 00:36:09,920 THEY'RE A DIRECT ACTIVATOR OF 1003 00:36:09,920 --> 00:36:13,320 THE THERMAL INTERSECT OR 1004 00:36:13,320 --> 00:36:14,640 TRIPP-A1 AND INTENTIONALLY 1005 00:36:14,640 --> 00:36:19,800 INDUCE ATOPIC DERM IN MICE. 1006 00:36:19,800 --> 00:36:21,280 THERE IS SOME MECHANISTIC 1007 00:36:21,280 --> 00:36:21,920 OVERLAP POTENTIALLY. WHAT HAS 1008 00:36:21,920 --> 00:36:26,800 BEEN EST. AS THE WAY IN WHICH 1009 00:36:26,800 --> 00:36:35,160 TDA ACTIVATES TRIPP-A1 IS BY 1010 00:36:35,160 --> 00:36:39,240 BINDING TO EFFECTIVE RESIDUES. 1011 00:36:39,240 --> 00:36:48,600 THE CORE ESSENTIALS SITE, 1012 00:36:48,600 --> 00:36:49,240 ESSENTIAL AMINO ACIDS NECESSARY 1013 00:36:49,240 --> 00:36:49,840 FOR BINDING NITROGEN OF THE AIR 1014 00:36:49,840 --> 00:36:54,480 BY THIS ENZYME, WHETHER TDI 1015 00:36:54,480 --> 00:36:55,080 AFFIXES DIRECTLY SOMETHING WE 1016 00:36:55,080 --> 00:36:55,560 HAVE TO WORK ON AND HOW 1017 00:36:55,560 --> 00:36:56,160 BACTERIA AFFIXES NITROGEN IN 1018 00:36:56,160 --> 00:36:57,680 THE FIRST PLACE BUT I AM 1019 00:36:57,680 --> 00:36:58,320 INTRIGUED THAT BOTH MY CHAIR IS 1020 00:36:58,320 --> 00:37:01,360 VERY SIMILAR BIOCHEMISTRY. AND 1021 00:37:01,360 --> 00:37:02,680 WHAT THAT SAYS TO US THAT THESE 1022 00:37:02,680 --> 00:37:03,280 CAN BE SCREEN TOOLS FOR MAYBE 1023 00:37:03,280 --> 00:37:03,920 OTHER CHEMICALS THAT MIGHT HAVE 1024 00:37:03,920 --> 00:37:14,400 THE SAME EFFECT. DYOSOSIENATE 1025 00:37:19,200 --> 00:37:25,200 JUMPS OUT. 1026 00:37:25,200 --> 00:37:35,640 YOU CAN SEE THERE'S BIG PULL 1027 00:37:36,720 --> 00:37:39,360 HERE IN THE UPPER CORNER HERE. 1028 00:37:39,360 --> 00:37:39,960 THERE'S DEFINITELY ECZEMA BUT 1029 00:37:39,960 --> 00:37:43,200 HE WILL LIMIT OUR ANALYSIS TO 1030 00:37:43,200 --> 00:37:44,520 THAT AND SAY ALL RIGHT WHAT ARE 1031 00:37:44,520 --> 00:37:45,160 THE MAJOR COMPONENTS, THE MAJOR 1032 00:37:45,160 --> 00:37:45,760 POLLUTANTS IN THE AREAS THAT 1033 00:37:45,760 --> 00:37:51,480 DON'T HAVE DYOSOSIENATE 1034 00:37:51,480 --> 00:37:52,120 FACTORIES? ANTIMONY JUMPS OUT. 1035 00:37:52,120 --> 00:37:56,680 ANTIMONY IS AN ELEMENT. IT HAS 1036 00:37:56,680 --> 00:37:57,280 BEEN AROUND FOREVER AND THERE 1037 00:37:57,280 --> 00:37:57,840 IS NO REASON TO THINK THAT 1038 00:37:57,840 --> 00:38:01,040 WOULD INCREASE 1960. BUT WE DID 1039 00:38:01,040 --> 00:38:01,640 EXPERIMENT WITH THAT AND JUST 1040 00:38:01,640 --> 00:38:02,280 LIKE NITROGEN DEPRIVATION AS I 1041 00:38:02,280 --> 00:38:05,480 TOLD YOU BEFORE, ANTIMONY CAN 1042 00:38:05,480 --> 00:38:10,520 SUPPRESS CERAMIDES FROM YOUR 1043 00:38:10,520 --> 00:38:11,040 COMMENSAL ORGANISMS AND 1044 00:38:11,040 --> 00:38:11,680 ACTIVATE THOSE CELLS IT BUT NOT 1045 00:38:11,680 --> 00:38:15,160 IF YOU PRE-BLOCK TRIPP-A1. THIS 1046 00:38:15,160 --> 00:38:15,640 CAN DO BOTH AND IT IS 1047 00:38:15,640 --> 00:38:16,280 ASSOCIATED WITH THE DISEASE AS 1048 00:38:16,280 --> 00:38:16,960 WELL. 1049 00:38:16,960 --> 00:38:19,960 WHERE YOU WOULD COME ACROSS 1050 00:38:19,960 --> 00:38:23,200 ANTIMONY IN AN UNNATURAL 1051 00:38:23,200 --> 00:38:23,800 FASHION WOULD BE MOSTLY BRAKE 1052 00:38:23,800 --> 00:38:24,440 PAD DUST, SHOWING A CORRELATION 1053 00:38:24,440 --> 00:38:29,280 WITH THE ROAD. DUST STORMS, 1054 00:38:29,280 --> 00:38:31,880 BLOWING THE DIRT THROUGH THE 1055 00:38:31,880 --> 00:38:32,520 AIR, AND IT IS VERY FREQUENTLY 1056 00:38:32,520 --> 00:38:36,360 USED IN SMELTING. IT IS ALSO 1057 00:38:36,360 --> 00:38:42,920 PART OF BOTTLED WATER AND TV 1058 00:38:42,920 --> 00:38:43,520 DINNERS WHICH DON'T ASSOCIATE 1059 00:38:43,520 --> 00:38:44,080 WITH ECZEMA BUT I PUT THEM 1060 00:38:44,080 --> 00:38:44,720 THERE SO WE COULD COLLECTIVELY 1061 00:38:44,720 --> 00:38:45,280 FEEL MORE SUBCULTURES ABOUT 1062 00:38:45,280 --> 00:38:46,880 LIVING IN AN INDUSTRIALIZED 1063 00:38:46,880 --> 00:38:47,520 ENVIRONMENT. SO THE CONNECTION 1064 00:38:47,520 --> 00:38:48,080 WITH ECZEMA AND SOME OF THE 1065 00:38:48,080 --> 00:38:52,760 WORK FOR ANTIMONY AS WELL. 1066 00:38:52,760 --> 00:38:53,320 YOU PUT IT ALL BACK TOGETHER 1067 00:38:53,320 --> 00:38:53,840 AND YOU PUT THE BLOBS FOR 1068 00:38:53,840 --> 00:38:54,440 ANTIMONY ON TOP YOU CAN SEE A 1069 00:38:54,440 --> 00:38:56,440 BETTER OVERLAP BUT THERE ARE 1070 00:38:56,440 --> 00:38:57,000 STILL SOME GAPS AND OTHER 1071 00:38:57,000 --> 00:38:57,560 IMPROVEMENTS THAT MIGHT BE 1072 00:38:57,560 --> 00:39:00,040 IMPORTANT. WHAT WE REALLY NEED 1073 00:39:00,040 --> 00:39:00,640 TO DO IS TO STOP LOOKING AT THE 1074 00:39:00,640 --> 00:39:03,040 RICH INFORMATION AND START 1075 00:39:03,040 --> 00:39:03,600 MEASURING THIS DIRECTIVE 1076 00:39:03,600 --> 00:39:04,200 BECAUSE MORE THAN ANYTHING WE 1077 00:39:04,200 --> 00:39:08,960 WOULD LIKE TO HAVE SOMETHING 1078 00:39:08,960 --> 00:39:18,840 THAT COULD TRACE ISOCYANADES 1079 00:39:18,840 --> 00:39:19,480 OVER TIME AND SPACE AND ALL THE 1080 00:39:19,480 --> 00:39:20,080 CURRENT DETECTION SYSTEMS ARE 1081 00:39:20,080 --> 00:39:22,760 FAR LESS THAN THE SKIN BACTERIA 1082 00:39:22,760 --> 00:39:23,320 ARE. THE BACTERIA IS STILL 1083 00:39:23,320 --> 00:39:23,960 BEING CALCIFIED SO IT TELLS US 1084 00:39:23,960 --> 00:39:34,480 WE NEED FAR SUPERIOR DETECTION 1085 00:39:41,960 --> 00:39:42,480 METHODS THAN WHAT WE HAVE 1086 00:39:42,480 --> 00:39:43,080 NOW AND WITH THAT WE CAN PUT 1087 00:39:43,080 --> 00:39:43,680 THAT THROUGH THREE DIFFERENT 1088 00:39:43,680 --> 00:39:44,280 PATHWAYS, THE FIRST WILL BE 1089 00:39:44,280 --> 00:39:44,800 TEAMING UP WITH LIKE THE 1090 00:39:44,800 --> 00:39:45,400 NATIONAL EXAM ASSOCIATION AND 1091 00:39:45,400 --> 00:39:45,960 ECZEMA TRACKER, GROUPS THAT 1092 00:39:45,960 --> 00:39:46,560 HAVE PATIENTS WHERE THEY PUT 1093 00:39:46,560 --> 00:39:47,200 THEIR INFORMATION, THERE FLARES 1094 00:39:47,200 --> 00:39:47,800 AND INCREASING DRUG NEEDS AND 1095 00:39:47,800 --> 00:39:48,320 DO THOSE SPIKES IN THE 1096 00:39:48,320 --> 00:39:50,480 COMMUNITY CORRELATE WITH ANY 1097 00:39:50,480 --> 00:39:53,280 SPIKE OF PARTICULAR POLLUTANTS 1098 00:39:53,280 --> 00:39:53,840 THAT HAPPENED MAYBE IN THE 1099 00:39:53,840 --> 00:39:57,920 PRECEDING DAYS? 1100 00:39:57,920 --> 00:39:58,480 THE THINGS THAT PATIENTS ARE 1101 00:39:58,480 --> 00:39:58,920 PROCEEDING AS BEING 1102 00:39:58,920 --> 00:39:59,560 UNPREDICTABLE MAY VERY WELL BE 1103 00:39:59,560 --> 00:40:01,000 PREDICTABLE, IF YOU HAD THAT 1104 00:40:01,000 --> 00:40:04,160 INFORMATION. 1105 00:40:04,160 --> 00:40:04,760 WE WOULD LIKE TO VET SPECIFIC 1106 00:40:04,760 --> 00:40:09,880 FILTRATION SYSTEMS. WE DON'T 1107 00:40:09,880 --> 00:40:10,520 HAVE ANY PHOTOS RIGHT NOW THAT 1108 00:40:10,520 --> 00:40:11,040 ARE RATED TO PULL THIS UP 1109 00:40:11,040 --> 00:40:11,560 BECAUSE WE DO NOT HAVE 1110 00:40:11,560 --> 00:40:15,280 DETECTION SYSTEMS. BUT THAT 1111 00:40:15,280 --> 00:40:15,880 WILL BE SOMETHING FOR SOME OF 1112 00:40:15,880 --> 00:40:16,480 THESE EXPOSURES THAT WILL BE 1113 00:40:16,480 --> 00:40:18,680 ABSOLUTELY UNAVOIDABLE, LIKE 1114 00:40:18,680 --> 00:40:19,280 WILDFIRES AND SO FORTH AND 1115 00:40:19,280 --> 00:40:19,880 VENTILATION SYSTEMS MIGHT BE 1116 00:40:19,880 --> 00:40:24,880 HELPFUL. AND THE LAST ONE 1117 00:40:24,880 --> 00:40:25,520 WOULD BE THINGS THAT EVERY TIME 1118 00:40:25,520 --> 00:40:26,120 PRESENTED TO A PATIENT GROUP 1119 00:40:26,120 --> 00:40:27,480 THE NEXT IMMEDIATE QUESTION IS, 1120 00:40:27,480 --> 00:40:35,480 THIS FEELS OVERWHELMING. WHAT 1121 00:40:35,480 --> 00:40:36,120 ELSE AM I SUPPOSED TO AVOID? 1122 00:40:36,120 --> 00:40:36,640 YOU GO BACK AND START TO 1123 00:40:36,640 --> 00:40:37,240 MEASURE SPECIFIC PRODUCT AND 1124 00:40:37,240 --> 00:40:37,800 SPECIFIC BRANDS TO SEE WHAT 1125 00:40:37,800 --> 00:40:42,200 THOSE EXPOSURES ARE. 1126 00:40:42,200 --> 00:40:42,800 YOU WE CAN GET A HINT OF THAT 1127 00:40:42,800 --> 00:40:43,680 AND WE PUT OUT A SURVEY. AT 1128 00:40:43,680 --> 00:40:45,440 THIS POINT WE HAVE ABOUT 500 1129 00:40:45,440 --> 00:40:54,280 RESPONSES, YES/NO. SO THESE ARE 1130 00:40:54,280 --> 00:40:54,880 SORTED BETWEEN ECZEMA OR NOT 1131 00:40:54,880 --> 00:40:55,440 RANKED BY HOW SEVERE IT WAS 1132 00:40:55,440 --> 00:40:57,080 BASED ON BODY SERVICE AND ITS 1133 00:40:57,080 --> 00:40:57,680 COMPONENT AND OBVIOUSLY WITH 1134 00:40:57,680 --> 00:40:59,760 ANY SURVEY, YOU HAVE RECALL 1135 00:40:59,760 --> 00:41:00,400 MYOSIN WE COMPLETELY UNDERSTAND 1136 00:41:00,400 --> 00:41:02,600 THAT BUT YOU WILL NOTICE THAT 1137 00:41:02,600 --> 00:41:03,200 NONE OF THE ABOVE ARE MOSTLY 1138 00:41:03,200 --> 00:41:03,800 OVER HERE AND YOU CAN SEE THE 1139 00:41:03,800 --> 00:41:07,760 STRONG ASSOCIATION WITH THE 1140 00:41:07,760 --> 00:41:08,400 OTHER ALLERGY DISEASES AND FOR 1141 00:41:08,400 --> 00:41:14,560 THE MOST PART THE EXPOSURES, 1142 00:41:14,560 --> 00:41:15,120 ASKING ALL OF THIS AT ONCE 1143 00:41:15,120 --> 00:41:15,640 CORRELATES STRONGLY WITH 1144 00:41:15,640 --> 00:41:16,320 DISEASE AND RECORDED THOSE WITH 1145 00:41:16,320 --> 00:41:17,040 REGRESSION MODELS AND WE SAY 1146 00:41:17,040 --> 00:41:20,960 ALL OF THOSE ARE ASSOCIATED 1147 00:41:20,960 --> 00:41:23,600 WITH THE DISEASE. WHICH WOULD 1148 00:41:23,600 --> 00:41:24,240 SEEM TO BE THE MOST IMPORTANT? 1149 00:41:24,240 --> 00:41:24,960 WHAT WOULD YOU PRIORITIZE IN 1150 00:41:24,960 --> 00:41:25,840 AVOIDING? 1151 00:41:25,840 --> 00:41:26,440 LOOKS LIKE EARLY LIFE EXPOSURE 1152 00:41:26,440 --> 00:41:30,520 TO POLYESTER, EITHER SHEET OR 1153 00:41:30,520 --> 00:41:31,040 CLOTHING WILL BE THE MOST 1154 00:41:31,040 --> 00:41:31,520 PREDICTIVE IN TERMS OF 1155 00:41:31,520 --> 00:41:34,920 SUBSEQUENT RISKS AND STATED 1156 00:41:34,920 --> 00:41:35,520 RISKS, WHETHER WALLPAPER AND 1157 00:41:35,520 --> 00:41:37,840 CARPET. IT IS NOT THE CARPET 1158 00:41:37,840 --> 00:41:41,200 ITSELF. IT IS THE PADDING 1159 00:41:41,200 --> 00:41:41,880 UNDERNEATH. THE CARPET PADS ARE 1160 00:41:41,880 --> 00:41:50,840 MADE OUT OF ISOSOSIENATE, WHICH 1161 00:41:50,840 --> 00:41:51,440 IS UNFORTUNATE BECAUSE WE TELL 1162 00:41:51,440 --> 00:41:52,080 PATIENTS WITH ASTHMA TO REMOVE 1163 00:41:52,080 --> 00:41:53,480 CARPET FROM THE HOME TO AVOID 1164 00:41:53,480 --> 00:41:54,120 THE DUST TRAPPED IN THE CARPET 1165 00:41:54,120 --> 00:41:55,480 BECAUSE IT DOES IMPROVE THE 1166 00:41:55,480 --> 00:42:01,920 OUTCOMES. 1167 00:42:01,920 --> 00:42:02,520 AND SO NOW WE COME BACK WHERE 1168 00:42:02,520 --> 00:42:07,360 WE STARTED AT THE END. ALL OF 1169 00:42:07,360 --> 00:42:07,920 THIS KIND OF ENVIRONMENTAL 1170 00:42:07,920 --> 00:42:09,240 INFORMATION AND WHY START OFF 1171 00:42:09,240 --> 00:42:12,960 BY BEING DEROGATORY AGAINST 1172 00:42:12,960 --> 00:42:17,600 GENETICS? PARTICULARLY AT AN 1173 00:42:17,600 --> 00:42:18,160 INSTITUTION WHICH IS PRETTY 1174 00:42:18,160 --> 00:42:19,560 GENETICS FOCUS. THE FIRST IS 1175 00:42:19,560 --> 00:42:20,000 THAT HE CAN BE VERY 1176 00:42:20,000 --> 00:42:20,600 STIGMATIZING PARTICULARLY TO 1177 00:42:20,600 --> 00:42:21,240 PATIENTS AND FOR THOSE WHO HAVE 1178 00:42:21,240 --> 00:42:27,720 A GENUINE, MONOGENIC MOLECULAR 1179 00:42:27,720 --> 00:42:29,320 DIAGNOSIS, THAT CAN BE VERY 1180 00:42:29,320 --> 00:42:29,920 LIBERATING. MY NAME IS A NAME 1181 00:42:29,920 --> 00:42:32,960 AND NOW WE CAN ADDRESS IT. WHEN 1182 00:42:32,960 --> 00:42:34,800 THERE IS A MORE NEBULOUS THING 1183 00:42:34,800 --> 00:42:35,360 WHERE THE GENES PLAY A ROLE 1184 00:42:35,360 --> 00:42:37,360 SOMETIMES LITERATURE IN THE 1185 00:42:37,360 --> 00:42:37,880 FIELD SAYS THAT CAN BE 1186 00:42:37,880 --> 00:42:41,160 STIGMATIZING TO THE PATIENTS 1187 00:42:41,160 --> 00:42:41,760 PARTICULARLY BETWEEN SIBLINGS 1188 00:42:41,760 --> 00:42:42,360 WHEN ONE HAS A DISEASE AND THE 1189 00:42:42,360 --> 00:42:47,600 OTHER DOES NOT. 1190 00:42:47,600 --> 00:42:48,200 IT CAN BE STIGMATIZING TO THE 1191 00:42:48,200 --> 00:42:48,800 PARENTS WHO EXPRESSED GUILT 1192 00:42:48,800 --> 00:42:49,440 ABOUT HAVING PASSED ON WHATEVER 1193 00:42:49,440 --> 00:42:50,040 PRESUME HEREDITY THEY BELIEVE 1194 00:42:50,040 --> 00:42:51,760 IS THERE, AND CREATE STRIFE 1195 00:42:51,760 --> 00:42:52,400 BETWEEN COUPLES ON ONE SIDE OF 1196 00:42:52,400 --> 00:42:53,720 THE FAMILY HAS FAMILY HISTORY 1197 00:42:53,720 --> 00:42:57,840 OF ALLERGIES AND ONE DOES NOT, 1198 00:42:57,840 --> 00:42:58,440 THUS BEING PERCEIVED THAT OUR 1199 00:42:58,440 --> 00:42:59,040 CHILD IS SUFFERING BECAUSE OF 1200 00:42:59,040 --> 00:43:02,120 YOUR SIDE OF THE FAMILY. 1201 00:43:02,120 --> 00:43:02,520 AND IT CAN ALSO BE 1202 00:43:02,520 --> 00:43:06,160 STIGMATIZING FOR ENTIRE 1203 00:43:06,160 --> 00:43:06,680 POPULATIONS IS THAT GET 1204 00:43:06,680 --> 00:43:07,240 EXPANDED I WILL SHOW YOU A 1205 00:43:07,240 --> 00:43:07,880 QUOTE FROM THE AMERICAN ACADEMY 1206 00:43:07,880 --> 00:43:08,880 OF DERMATOLOGY GUIDELINES ON 1207 00:43:08,880 --> 00:43:14,400 ATOPIC DERM. BEING A BLACK RACE 1208 00:43:14,400 --> 00:43:15,000 APPEARS TO INCREASE THE RISK 1209 00:43:15,000 --> 00:43:15,560 BUT SOCIOECONOMIC STATUS IS 1210 00:43:15,560 --> 00:43:18,560 UNCLEAR. 1211 00:43:18,560 --> 00:43:19,120 I KNOW SOME OF THE AUTHORS 1212 00:43:19,120 --> 00:43:20,200 WROTE THIS AND I HAVE NO DOUBT 1213 00:43:20,200 --> 00:43:20,800 THAT HE DID NOT INTEND FOR IT 1214 00:43:20,800 --> 00:43:26,720 TO COME OFF THIS WAY. BUT WHEN 1215 00:43:26,720 --> 00:43:27,320 YOU SAY IN THIS WAY, WHEN YOU 1216 00:43:27,320 --> 00:43:27,920 SAY BEING BLACK IS A PROBLEM 1217 00:43:27,920 --> 00:43:31,080 BUT BEING POOR CANNOT EXPLAIN 1218 00:43:31,080 --> 00:43:31,680 IT, YOU ARE INSINUATING THAT 1219 00:43:31,680 --> 00:43:32,320 THERE IS SOMETHING INNATE ABOUT 1220 00:43:32,320 --> 00:43:32,880 THE BLACKNESS THAT IS THE 1221 00:43:32,880 --> 00:43:37,480 PROBLEM. 1222 00:43:37,480 --> 00:43:38,080 AT LEAST FOR ECZEMA IT IS A 1223 00:43:38,080 --> 00:43:38,680 SKIN DISEASE OR PERHAPS YOU ARE 1224 00:43:38,680 --> 00:43:39,320 PREPARED TO INVOKE PIGMENTATION. 1225 00:43:39,320 --> 00:43:39,880 THE PROBLEM WITH THAT OF 1226 00:43:39,880 --> 00:43:44,600 COURSE IS AFRICA, WHERE IN 1227 00:43:44,600 --> 00:43:48,880 THEIR DATA IS CLEAR THAT IF 1228 00:43:48,880 --> 00:43:49,480 YOU'RE IN A NONINDUSTRIALIZED 1229 00:43:49,480 --> 00:43:50,040 PART OF AFRICA THE RATES OF 1230 00:43:50,040 --> 00:43:54,360 ECZEMA CAN BE BELOW 1%. THE 1231 00:43:54,360 --> 00:43:55,000 ONLY PART OF AFRICA WITH RATES 1232 00:43:55,000 --> 00:43:55,600 OF ECZEMA THAT APPROACH OR CAN 1233 00:43:55,600 --> 00:43:58,920 CONTEND WITH UNITED STATES, ARE 1234 00:43:58,920 --> 00:43:59,480 THERE HIGHLY INDUSTRIALIZED 1235 00:43:59,480 --> 00:44:00,960 CENTERS LIKE SENEGAL AND 1236 00:44:00,960 --> 00:44:01,720 NIGERIA. 1237 00:44:01,720 --> 00:44:02,200 THERE ARE DISEASES OF 1238 00:44:02,200 --> 00:44:05,280 PIGMENTATION. THERE ARE 1239 00:44:05,280 --> 00:44:05,760 DISEASES LINKED WITH 1240 00:44:05,760 --> 00:44:09,200 PIGMENTATION NO MATTER WHERE 1241 00:44:09,200 --> 00:44:09,840 YOU GO. SO FOR EXAMPLE KELOIDS 1242 00:44:09,840 --> 00:44:14,920 ARE LINKED WITH PIGMENTATION 1243 00:44:14,920 --> 00:44:15,520 BUT EVEN IN SOUTH AMERICA OR 1244 00:44:15,520 --> 00:44:16,160 PARTS OF INDIA WHERE PEOPLE CAN 1245 00:44:16,160 --> 00:44:16,720 BE JUST AS PIGMENTED AS IT 1246 00:44:16,720 --> 00:44:20,000 MIGHT BE IN AFRICA. 1247 00:44:20,000 --> 00:44:20,600 SO AS IT RELATES TO THE UNITED 1248 00:44:20,600 --> 00:44:23,400 STATES CLEARLY IN THIS CONTEXT, 1249 00:44:23,400 --> 00:44:23,960 BLACKNESS IS A MARKER FOR 1250 00:44:23,960 --> 00:44:24,480 UNEVEN DISSOLUTION OF THE 1251 00:44:24,480 --> 00:44:27,760 ENVIRONMENTAL INJUSTICES. 1252 00:44:27,760 --> 00:44:28,320 THAT REALLY I THINK WOULD BE 1253 00:44:28,320 --> 00:44:28,960 MORE OBVIOUS IF THIS PAPER HAD 1254 00:44:28,960 --> 00:44:32,520 BEEN WRITTEN ABOUT EDUCATIONAL 1255 00:44:32,520 --> 00:44:33,120 ATTAINMENT AND MENTAL HEALTH 1256 00:44:33,120 --> 00:44:33,720 AND THAT IS AN INAPPROPRIATE 1257 00:44:33,720 --> 00:44:37,120 WAY OF SAYING IT. I THINK IT 1258 00:44:37,120 --> 00:44:37,720 FOCUSES A PROBLEM ON THE FISH 1259 00:44:37,720 --> 00:44:41,200 INSTEAD OF THE SURROUNDINGS. 1260 00:44:41,200 --> 00:44:41,800 THE SECOND PART IS THAT IT CAN 1261 00:44:41,800 --> 00:44:45,360 BE VERY DISEMPOWERING BECAUSE 1262 00:44:45,360 --> 00:44:45,960 YOU MIGHT MISS WHAT YOU THINK 1263 00:44:45,960 --> 00:44:53,120 CAN BE PREDISPOSITION. IF YOU 1264 00:44:53,120 --> 00:44:53,680 TRULY BELIEVE THAT GENE IS 1265 00:44:53,680 --> 00:44:54,280 CAUSING ALL THE PROBLEMS, BUT 1266 00:44:54,280 --> 00:44:57,240 IF YOU DON'T, SOME 1267 00:44:57,240 --> 00:44:57,840 ENVIRONMENTAL FACTOR MUST BE 1268 00:44:57,840 --> 00:44:58,520 ACTING ON THIS THAT PREDISPOSES 1269 00:44:58,520 --> 00:45:02,960 THE DISEASE AND IF YOU DO NOT 1270 00:45:02,960 --> 00:45:03,520 ENCOUNTER THE ENVIRONMENTAL 1271 00:45:03,520 --> 00:45:04,080 FACTOR THE ENVIRONMENT YOU 1272 00:45:04,080 --> 00:45:04,720 MIGHT MISS WHAT YOU THINK AND 1273 00:45:04,720 --> 00:45:05,800 BE A PREDISPOSITION. THAT WAS 1274 00:45:05,800 --> 00:45:06,320 WRITTEN EXTENSIVELY AND 1275 00:45:06,320 --> 00:45:08,960 PROBABLY THE FIRST GENUINE 1276 00:45:08,960 --> 00:45:10,320 ANTIRACIST OF THE GENETIC ERA, 1277 00:45:10,320 --> 00:45:13,080 RICHARD WANT (PHONETIC) WHO 1278 00:45:13,080 --> 00:45:18,360 WROTE AN ENTIRE BOOK ABOUT 1279 00:45:18,360 --> 00:45:18,880 GENES AND MENTAL HEALTH 1280 00:45:18,880 --> 00:45:19,400 DISORDERS BUT HE PUT THE 1281 00:45:19,400 --> 00:45:24,720 FOLLOWING THOUGHT EXPERIMENT. 1282 00:45:24,720 --> 00:45:28,160 IF YOU HAVE PLANS THAT HAD 1283 00:45:28,160 --> 00:45:28,800 NORMAL NUTRIENTS IN GOOD LIGHT 1284 00:45:28,800 --> 00:45:29,400 AND WATER VS. ONES THAT HAVE 1285 00:45:29,400 --> 00:45:30,000 DEFICIENT NUTRIENTS, IN BOTH 1286 00:45:30,000 --> 00:45:30,640 CASES BECAUSE THE ENVIRONMENTS 1287 00:45:30,640 --> 00:45:33,760 ARE THE SAME, HEIGHT WOULD BE 1288 00:45:33,760 --> 00:45:34,280 COMPLETELY DETERMINED BY 1289 00:45:34,280 --> 00:45:35,280 GENETICS ARE SO THE 1290 00:45:35,280 --> 00:45:35,920 HERITABILITY IN BOTH CASES WILL 1291 00:45:35,920 --> 00:45:36,400 BE 100% BUT THE GROUP 1292 00:45:36,400 --> 00:45:39,240 DIFFERENCES WOULD STILL BE 1293 00:45:39,240 --> 00:45:39,840 ENVIRONMENTAL AND THE POINT 1294 00:45:39,840 --> 00:45:41,680 HERE BEING, IF YOU DON'T 1295 00:45:41,680 --> 00:45:43,920 ACKNOWLEDGE THAT YOU CAN MISS 1296 00:45:43,920 --> 00:45:45,040 SOMETHING BECAUSE YOU CAN'T 1297 00:45:45,040 --> 00:45:50,880 FIGURE OUT IF YOU'RE FINDING A 1298 00:45:50,880 --> 00:45:51,480 DROUGHT RESISTANT GENE IF YOU 1299 00:45:51,480 --> 00:45:52,080 ARE NOT AWARE THAT YOUR PLANS 1300 00:45:52,080 --> 00:45:55,360 ARE EXPERIENCING DROUGHT 1301 00:45:55,360 --> 00:45:55,960 I WOULD TAKE IT A STEP FURTHER 1302 00:45:55,960 --> 00:46:00,280 TO SAY THIS IS GREAT IN PLANTS 1303 00:46:00,280 --> 00:46:00,920 AND POTENTIAL ANIMALS BUT THERE 1304 00:46:00,920 --> 00:46:01,480 IS NO SUCH THING AS UNIFORM 1305 00:46:01,480 --> 00:46:02,440 NUTRIENT EXPOSURE, OR UNIFORM 1306 00:46:02,440 --> 00:46:05,240 LIGHT OR WATER FOR HUMAN BEINGS. 1307 00:46:05,240 --> 00:46:05,800 THESE THINGS ARE EXTREMELY 1308 00:46:05,800 --> 00:46:08,960 VARIABLE AND WE SAW THIS EVEN 1309 00:46:08,960 --> 00:46:15,120 WITH FAMILIES WITH WATER CRISIS 1310 00:46:15,120 --> 00:46:18,400 WHETHER FLUCTUATION AND LED 1311 00:46:18,400 --> 00:46:19,000 LEVELS, ONE KID MIGHT TAKE A 1312 00:46:19,000 --> 00:46:19,560 SHOWER WHEN LED LEVELS WERE 1313 00:46:19,560 --> 00:46:30,080 INCREDIBLY HIGH AND TWO HOURS 1314 00:46:35,840 --> 00:46:36,360 LATER THERE SOMETHING IN THE 1315 00:46:36,360 --> 00:46:36,960 SAME EXACT SHOWER, THE LEAD 1316 00:46:36,960 --> 00:46:44,480 LEVELS WILL BE MUCH LOWER. 1317 00:46:44,480 --> 00:46:45,040 BY NOT FACTORING THESE THINGS 1318 00:46:45,040 --> 00:46:45,680 LATER YOU CANNOT EVEN BEGIN TO 1319 00:46:45,680 --> 00:46:46,280 TELL WHERE THE GENE SIGNAL IS 1320 00:46:46,280 --> 00:46:51,520 REAL. IF I WANTED TO BECOME A 1321 00:46:51,520 --> 00:46:54,480 BOND VILLAIN AND OPEN THESE 1322 00:46:54,480 --> 00:46:55,040 FACTORS AND RANDOMLY SPEW 1323 00:46:55,040 --> 00:46:55,640 PEANUTS IN THE AIR YOU WOULD 1324 00:46:55,640 --> 00:46:57,360 EXPECT THAT WE START INDUCING 1325 00:46:57,360 --> 00:46:57,920 THE DISEASE AND SUBSEQUENT 1326 00:46:57,920 --> 00:46:59,720 AREAS 1327 00:46:59,720 --> 00:47:00,280 IF I PUT WHAT IN LOS ANGELES 1328 00:47:00,280 --> 00:47:01,880 AND ATLANTA YOU WOULD EXPECT 1329 00:47:01,880 --> 00:47:02,480 FAMILY HISTORY BECAUSE PEOPLE 1330 00:47:02,480 --> 00:47:02,960 WHO LIVE CLOSER TO THE 1331 00:47:02,960 --> 00:47:03,600 FACTORIES WOULD BE MOST LIKELY 1332 00:47:03,600 --> 00:47:07,360 TO HAVE THE DISEASE. YOU EXPECT 1333 00:47:07,360 --> 00:47:08,000 GENETIC HITS ON YOUR ASSAY, AND 1334 00:47:08,000 --> 00:47:08,960 SOME OF THEM WILL BE REAL IN 1335 00:47:08,960 --> 00:47:11,960 TERMS OF YOUR ABILITY TO HANDLE 1336 00:47:11,960 --> 00:47:12,560 THE PEANUT PROTEIN IN THE AIR 1337 00:47:12,560 --> 00:47:16,080 AND SOME OF IT WOULD BE 1338 00:47:16,080 --> 00:47:16,680 CONFOUNDERS, JUST A MARKER OF 1339 00:47:16,680 --> 00:47:17,280 FAMILY HERITAGE AND IF YOU DO 1340 00:47:17,280 --> 00:47:20,800 NOT KNOW THE INCITING EVENT, 1341 00:47:20,800 --> 00:47:21,400 YOU WILL BE ABLE TO TELL THE 1342 00:47:21,400 --> 00:47:21,920 SUPPORT, YOU WOULD EXPECT 1343 00:47:21,920 --> 00:47:29,840 RACIAL DISPARITIES. 1344 00:47:29,840 --> 00:47:30,320 BUT IF THEY IN PARISH OR 1345 00:47:30,320 --> 00:47:30,960 MINORITY COMMUNITIES ARE LIVING 1346 00:47:30,960 --> 00:47:41,440 NEAR THE FACTORY ARE MAKING 1347 00:47:43,680 --> 00:47:44,240 PRODUCTS THAT ARE GOING TO RICH 1348 00:47:44,240 --> 00:47:44,760 PEOPLE'S HOMES YOU EXPECT 1349 00:47:44,760 --> 00:47:45,360 SOCIAL ECONOMIC STATUS TO BE 1350 00:47:45,360 --> 00:47:47,000 UNCLEAR. 1351 00:47:47,000 --> 00:47:52,520 YOU WOULD EXPECT INCREASE IN 1352 00:47:52,520 --> 00:47:53,160 INCIDENCE AND IDIOPATHIC FLARES 1353 00:47:53,160 --> 00:47:53,720 WITH PATIENTS RANDOMLY COME 1354 00:47:53,720 --> 00:47:54,240 INTO CONTACT WITH THESE 1355 00:47:54,240 --> 00:47:56,640 CHEMICALS ADULT KNOW IT. WHEN 1356 00:47:56,640 --> 00:47:57,240 WE FACTOR ALL OF THESE THINGS 1357 00:47:57,240 --> 00:47:57,840 LIKE WIND DIRECTION AND SO 1358 00:47:57,840 --> 00:47:59,400 FORTH JUST BY THE RELEASE, WE 1359 00:47:59,400 --> 00:47:59,920 CAN GET A MAP THAT LOOKS 1360 00:47:59,920 --> 00:48:00,560 SOMETHING LIKE THIS IN TERMS OF 1361 00:48:00,560 --> 00:48:03,480 THE OVERALL RISK OF ECZEMA IN A 1362 00:48:03,480 --> 00:48:07,440 PARTICULAR AREA, AND CERTAINLY 1363 00:48:07,440 --> 00:48:08,040 YOU CAN SEE SOME ORIGINALITY 1364 00:48:08,040 --> 00:48:08,920 BUT YOU CAN ALSO APPRECIATE 1365 00:48:08,920 --> 00:48:10,920 THAT IT IS STILL VERY 1366 00:48:10,920 --> 00:48:11,520 HETEROGENEOUS. AND WE HAVE A 1367 00:48:11,520 --> 00:48:12,120 LAYER ON TOP OF THIS AND THE 1368 00:48:12,120 --> 00:48:13,840 COMPLEXITY OF WILDFIRE 1369 00:48:13,840 --> 00:48:14,480 EXPOSURE, AND THE POTENTIAL FOR 1370 00:48:14,480 --> 00:48:15,080 ADDITIONAL DATABASES ON WATER 1371 00:48:15,080 --> 00:48:21,240 AND SO FORTH. SO THERE REALLY 1372 00:48:21,240 --> 00:48:21,840 ISN'T-- EVEN THE GROUNDWATER 1373 00:48:21,840 --> 00:48:22,400 ANALYSIS WHERE EVERYBODY'S 1374 00:48:22,400 --> 00:48:24,600 DOING THE SAME LAKE-- DOES NOT 1375 00:48:24,600 --> 00:48:25,200 FIT BECAUSE THE REAL WORLD IS 1376 00:48:25,200 --> 00:48:25,760 FAR MORE HOMOGENOUS THAN A 1377 00:48:25,760 --> 00:48:26,760 SINGLE LAKE. 1378 00:48:26,760 --> 00:48:35,040 AND THERE IS A DEEPER QUESTION. 1379 00:48:35,040 --> 00:48:35,640 WHICH IS THE BEST SOLUTION 1380 00:48:35,640 --> 00:48:36,240 FOR PROBLEMS LIKE THIS WHERE 1381 00:48:36,240 --> 00:48:36,760 YOU KNOW YOU ARE SPEWING 1382 00:48:36,760 --> 00:48:37,400 SOMETHING INTO THE ENVIRONMENT 1383 00:48:37,400 --> 00:48:38,040 AND CREATING PROBLEMS TO GIVE 1384 00:48:38,040 --> 00:48:38,640 EVERYBODY INCREASINGLY FANCY 1385 00:48:38,640 --> 00:48:40,520 BIOLOGIC AND IMMUNE REGULATORS 1386 00:48:40,520 --> 00:48:48,200 MAYBE SOME RESCUE MEDS. I'M 1387 00:48:48,200 --> 00:48:48,840 GLAD THAT ECZEMA HAS ENTERED A 1388 00:48:48,840 --> 00:48:49,800 FIELD IN AN ERA WHERE PATIENTS 1389 00:48:49,800 --> 00:48:50,400 HAVE GENUINE OPTIONS BEYOND 1390 00:48:50,400 --> 00:48:51,040 TOPICAL STEROIDS AND I CAUTION 1391 00:48:51,040 --> 00:48:51,720 THAT MAYBE THAT IS NOT THE ONLY 1392 00:48:51,720 --> 00:48:52,760 ROUTE. MAY BE ENVIRONMENTAL 1393 00:48:52,760 --> 00:48:56,200 MITIGATION CAN HELP AS WELL. 1394 00:48:56,200 --> 00:48:56,760 AND SO IS MY FINAL SLIDE I'M 1395 00:48:56,760 --> 00:49:07,280 GOING TO GET A JUMP ON THE Q&A. 1396 00:49:08,480 --> 00:49:09,000 WHEN I PRESENT THIS THE FIRST 1397 00:49:09,000 --> 00:49:09,600 QUESTION EVERYBODY EVER ASKS 1398 00:49:09,600 --> 00:49:18,680 IS, USING IT CAN BE ONE THING? 1399 00:49:18,680 --> 00:49:19,320 THERE ARE 350,000 NEW CHEMICALS 1400 00:49:19,320 --> 00:49:21,320 ADDED TO THE GLOBAL MARKET 1401 00:49:21,320 --> 00:49:23,960 SINCE 1960. ONLY 235,000 HAVE A 1402 00:49:23,960 --> 00:49:24,440 KNOWN NAME AND CHEMICAL 1403 00:49:24,440 --> 00:49:25,040 STRUCTURE. A LOT OF THEM ARE 1404 00:49:25,040 --> 00:49:30,440 ORGANICS. BUT I WOULD CAUTION 1405 00:49:30,440 --> 00:49:31,080 THAT THE ROAD CAN BE UNNATURAL 1406 00:49:31,080 --> 00:49:31,720 AND THE DEGREE OF EXPOSURE CAN 1407 00:49:31,720 --> 00:49:34,800 BE A NATURAL. YOU'RE LOOKING AT 1408 00:49:34,800 --> 00:49:35,800 SOMETHING CLOSE TO ALMOST OVER 1409 00:49:35,800 --> 00:49:43,680 75,000 NEW MOLECULES THAT 1410 00:49:43,680 --> 00:49:44,280 NEITHER OUR HUMAN CELLS OR OUR 1411 00:49:44,280 --> 00:49:44,800 BACTERIAL OR MICROBIAL 1412 00:49:44,800 --> 00:49:45,400 COUNTERPARTS HAVE EVER HAD TO 1413 00:49:45,400 --> 00:49:47,760 DEAL WITH THROUGHOUT EVOLUTION 1414 00:49:47,760 --> 00:49:48,400 SO THERE'S A LOT OF THINGS OUT 1415 00:49:48,400 --> 00:49:49,000 THERE THAT MIGHT BE CAUSING A 1416 00:49:49,000 --> 00:49:49,640 PROBLEM FOR A DISEASE THAT HAS 1417 00:49:49,640 --> 00:49:51,360 BEEN AROUND SINCE ANTIQUITY. 1418 00:49:51,360 --> 00:49:51,960 THE WORD ECZEMA COMES FROM THE 1419 00:49:51,960 --> 00:49:56,720 ANCIENT GREEKS. AND SO PEOPLE 1420 00:49:56,720 --> 00:49:57,280 WHO HAVE THIS DISEASE FOR A 1421 00:49:57,280 --> 00:49:58,600 LONG TIME HAVE VERY SIMILAR 1422 00:49:58,600 --> 00:49:59,200 SYMPTOMS. SO HOW DO YOU THINK 1423 00:49:59,200 --> 00:50:06,000 THAT THESE CAN BE CONNECTED? 1424 00:50:06,000 --> 00:50:06,640 THIS ONLY IF YOU THINK THAT IN 1425 00:50:06,640 --> 00:50:07,240 THEORY COULD HAVE CREATED THE 1426 00:50:07,240 --> 00:50:13,480 DISEASE AND SAY ARISTOTLE, THEY 1427 00:50:13,480 --> 00:50:14,080 COULD STILL BE CREATING THE 1428 00:50:14,080 --> 00:50:14,680 DECEASED TODAY AND DESPITE THE 1429 00:50:14,680 --> 00:50:15,320 BADMOUTHING I DID OF GENETICS, 1430 00:50:15,320 --> 00:50:21,320 GENETICS IS NUMBER ONE ON THAT 1431 00:50:21,320 --> 00:50:21,920 LIST. IT WILL BE MORE RARE 1432 00:50:21,920 --> 00:50:22,520 BACK THEN BECAUSE YOU WOULD NOT 1433 00:50:22,520 --> 00:50:23,120 HAVE PEOPLE LIKE DR. FREEMAN 1434 00:50:23,120 --> 00:50:25,120 AROUND KEEP YOU FROM DYING FROM 1435 00:50:25,120 --> 00:50:25,760 SUBSEQUENT IMMUNODEFICIENCY TO 1436 00:50:25,760 --> 00:50:28,760 GO ALONG. 1437 00:50:28,760 --> 00:50:29,360 BUT ALSO WILDFIRES AND DUST 1438 00:50:29,360 --> 00:50:29,880 STORMS WOULD VERY MUCH BE 1439 00:50:29,880 --> 00:50:30,480 SOMETHING PRESENT BACK THEN. 1440 00:50:30,480 --> 00:50:33,480 THIS PRESENTS A SPECTRUM OF 1441 00:50:33,480 --> 00:50:34,040 THEORY. ON THE ONE END OVER 1442 00:50:34,040 --> 00:50:36,160 HERE IN THE MODERNITY SIDE, 1443 00:50:36,160 --> 00:50:36,800 MAYBE IT IS NUMEROUS DIFFERENT 1444 00:50:36,800 --> 00:50:39,920 CHEMICALS THAT ARE KIND OF 1445 00:50:39,920 --> 00:50:40,560 UNRELATED IN TIME AND SPACE IN 1446 00:50:40,560 --> 00:50:41,160 EACH ONE COULD INDUCE ECZEMA 1447 00:50:41,160 --> 00:50:44,520 THROUGH ITS OWN UNIQUE PATHWAY 1448 00:50:44,520 --> 00:50:45,120 OR BEARING PATHWAYS AND TO BE 1449 00:50:45,120 --> 00:50:50,000 HONEST THIS IS KIND OF WHERE I 1450 00:50:50,000 --> 00:50:50,560 WAS WHEN I WAS MAKING THAT 1451 00:50:50,560 --> 00:50:51,160 COMMENT ABOUT NOT THINKING WE 1452 00:50:51,160 --> 00:50:53,920 WOULD HAVE AN AARON BROCKOVICH 1453 00:50:53,920 --> 00:50:54,560 MOMENT. DOES LOTS OF THINGS YOU 1454 00:50:54,560 --> 00:50:55,160 CAN CREATE ECZEMA AND LOTS OF 1455 00:50:55,160 --> 00:50:56,520 DIFFERENT WAYS AND ON THE OTHER 1456 00:50:56,520 --> 00:50:57,080 SIDE IT WOULD BE TO SAY, 1457 00:50:57,080 --> 00:50:57,600 CHEMICALS THAT ARE SHARED 1458 00:50:57,600 --> 00:51:00,360 ACROSS HUMAN EXPOSURE AND TIME 1459 00:51:00,360 --> 00:51:00,960 AND SPACE HAVE A VERY SIMILAR 1460 00:51:00,960 --> 00:51:05,720 CHEMISTRY. THEY HAVE BEEN 1461 00:51:05,720 --> 00:51:06,360 INDUCING THAT CHEMISTRY AND THE 1462 00:51:06,360 --> 00:51:06,920 SAME PATHOLOGY IN HUMANOID 1463 00:51:06,920 --> 00:51:09,400 AWARE OR WHEN YOU LIVED AND IT 1464 00:51:09,400 --> 00:51:13,240 IS ONLY THE INTENSITY AND 1465 00:51:13,240 --> 00:51:13,840 FREQUENCY OF THOSE EXPOSURES 1466 00:51:13,840 --> 00:51:14,440 THAT THEY HAVE GONE UP THAT 1467 00:51:14,440 --> 00:51:17,040 EXPLAIN THE INTENSITY AND 1468 00:51:17,040 --> 00:51:17,640 FREQUENCY OF THE INCREASE IN 1469 00:51:17,640 --> 00:51:21,400 ALLERGIC DISEASES. 1470 00:51:21,400 --> 00:51:21,960 THERE IS ONLY A SPECTRUM IN 1471 00:51:21,960 --> 00:51:22,600 BETWEEN AND I DON'T KNOW WHERE 1472 00:51:22,600 --> 00:51:29,760 WE ARE. THE TRUTH WILL BE 1473 00:51:29,760 --> 00:51:30,320 SOMEWHERE IN BETWEEN BUT I 1474 00:51:30,320 --> 00:51:30,960 DON'T THINK THAT IT IS AS SILLY 1475 00:51:30,960 --> 00:51:31,560 AS I INITIALLY THOUGHT IN MY 1476 00:51:31,560 --> 00:51:32,120 OWN MIND THAT IT COULD BE 1477 00:51:32,120 --> 00:51:32,640 REALLY JUST ONE THING. IF 1478 00:51:32,640 --> 00:51:33,280 NOTHING ELSE IT IS A LEAST ONE 1479 00:51:33,280 --> 00:51:36,560 MECHANISM, LIKE ISOSOSIENATE 1480 00:51:36,560 --> 00:51:37,160 AND ANTIMONY COMMENTS ARE VERY 1481 00:51:37,160 --> 00:51:41,520 DIFFERENT AND THERE IS AN 1482 00:51:41,520 --> 00:51:42,120 EROSION OF THE BARRIER LIPIDS 1483 00:51:42,120 --> 00:51:44,960 WHILE SIMULTANEOUSLY ACTIVATING 1484 00:51:44,960 --> 00:51:55,480 YOUR THERMAL AGENT RECEPTORS 1485 00:52:00,640 --> 00:52:01,160 AND ITCH AND THOSE TWO THINGS 1486 00:52:01,160 --> 00:52:01,800 TOGETHER I BELIEVE WE GENUINELY 1487 00:52:01,800 --> 00:52:05,240 DRIVE ATOPIC DERM. 1488 00:52:05,240 --> 00:52:05,840 THIS IS A FANTASTIC GROUP AND 1489 00:52:05,840 --> 00:52:06,560 I'M OPEN FOR YOUR QUESTIONS. 1490 00:52:06,560 --> 00:52:11,120 >> DR. MILES. THANK YOU VERY 1491 00:52:11,120 --> 00:52:11,760 MUCH FOR SHARING YOUR INSPIRING 1492 00:52:11,760 --> 00:52:16,320 WORK. AND THE INSIGHT THAT YOU 1493 00:52:16,320 --> 00:52:16,840 ARE OFFERING INTO HOW OUR 1494 00:52:16,840 --> 00:52:19,800 ENVIRONMENT IS INFLUENCING THE 1495 00:52:19,800 --> 00:52:24,240 ATOPIC DERMITITIS. I AM 1496 00:52:24,240 --> 00:52:25,040 OVERWHELMED AND I'M HESITANT TO 1497 00:52:25,040 --> 00:52:28,120 LEAVE MY OFFICE. BASED ON WHAT 1498 00:52:28,120 --> 00:52:28,680 YOU JUST SHARED AM NOT SURE 1499 00:52:28,680 --> 00:52:32,880 THIS IS A SAFE PLACE EITHER. 1500 00:52:32,880 --> 00:52:35,440 I DO WANT TO MAKE ONE COMMENT. 1501 00:52:35,440 --> 00:52:36,040 WHEN I READ ABOUT THE RACIAL 1502 00:52:36,040 --> 00:52:36,600 DISPARITY DISEASE MY FIRST 1503 00:52:36,600 --> 00:52:42,560 RESPONSE NOWADAYS IS, ARE WE 1504 00:52:42,560 --> 00:52:44,960 LOOKING AT DATA DEEP ENOUGH AND 1505 00:52:44,960 --> 00:52:54,160 WHETHER RACE IS ONLY ONE OF 1506 00:52:54,160 --> 00:52:57,040 VARIOUS FACTORS. WE DO HAVE A 1507 00:52:57,040 --> 00:53:00,360 QUESTIONS COMING IN. 1508 00:53:00,360 --> 00:53:00,920 FIRST OF WHAT IS KNOWN ABOUT 1509 00:53:00,920 --> 00:53:03,280 THE AGE OF ONSET ABOUT ATOPIC 1510 00:53:03,280 --> 00:53:12,000 DERM? PRIMARILY A PEDIATRIC 1511 00:53:12,000 --> 00:53:12,600 ONSET OR CAN IT MANIFESTATION 1512 00:53:12,600 --> 00:53:18,960 BE IN A DULL HOLD. 1513 00:53:18,960 --> 00:53:23,160 >> ADULT ONSET IS RARE. MOST 1514 00:53:23,160 --> 00:53:23,760 KIDS WILL MANIFEST BEFORE THE 1515 00:53:23,760 --> 00:53:24,400 AGE OF FOUR AND EVEN MORE SO 1516 00:53:24,400 --> 00:53:29,000 UNDER TWO. AGE OF ONSET IS 1517 00:53:29,000 --> 00:53:29,600 DEFINITELY IN THE NEWBORN TO 1518 00:53:29,600 --> 00:53:35,480 FOUR YEAR WINDOW. AND 1519 00:53:35,480 --> 00:53:36,080 SUBSEQUENT TO THAT YOU SEE A 1520 00:53:36,080 --> 00:53:36,680 RESOLUTION OF THE ITCH AND RASH 1521 00:53:36,680 --> 00:53:37,320 COMPONENTS OVER TIME SO BY THE 1522 00:53:37,320 --> 00:53:45,920 TIME KIDS ARE ABOUT 12 OR 13 OR 1523 00:53:45,920 --> 00:53:49,080 BEFORE THAT YOU COULD EXPECT TO 1524 00:53:49,080 --> 00:53:49,720 SEE THE SLOWER GRADATION. MANY 1525 00:53:49,720 --> 00:53:50,200 OF THE KIDS WILL HAVE A 1526 00:53:50,200 --> 00:53:50,800 SPONTANEOUS RESOLUTION OF THE 1527 00:53:50,800 --> 00:53:53,480 EACH AND RASH, UNFORTUNATELY 1528 00:53:53,480 --> 00:53:56,560 THEY WOULD BE LEFT WITH 1529 00:53:56,560 --> 00:53:57,120 ALLERGIC RHINITIS AND FOOD 1530 00:53:57,120 --> 00:53:57,760 ALLERGIES AND MAYBE PEAK AGAIN 1531 00:53:57,760 --> 00:53:58,320 AS WE GET MORE TOWARDS THE 1532 00:53:58,320 --> 00:54:00,360 ELDERLY AGE. DEFINITELY 1533 00:54:00,360 --> 00:54:00,920 OVERWHELMINGLY A PEDIATRIC 1534 00:54:00,920 --> 00:54:11,080 DISEASE. 1535 00:54:13,400 --> 00:54:13,920 >> SO THESE INDIVIDUALS ARE 1536 00:54:13,920 --> 00:54:14,560 PREDISPOSED AT THE BEGINNING IN 1537 00:54:14,560 --> 00:54:15,200 EARLY CHILDHOOD. I GUESS THERE 1538 00:54:15,200 --> 00:54:15,800 IS ACCORDING TO THE QUESTION. 1539 00:54:15,800 --> 00:54:16,400 IN ADDITION TO CORRELATION TO 1540 00:54:16,400 --> 00:54:17,280 ENVIRONMENTAL EXPOSURE, 1541 00:54:17,280 --> 00:54:22,400 ISOSOSIENATES AND ATOPIC DERM, 1542 00:54:22,400 --> 00:54:22,840 HAS YOUR GROUP LOOK 1543 00:54:22,840 --> 00:54:23,520 SPECIFICALLY AT OCCUPATION HAVE 1544 00:54:23,520 --> 00:54:25,600 A HIGHER EXPOSURE TO 1545 00:54:25,600 --> 00:54:32,880 ISOSOSIENATES? 1546 00:54:32,880 --> 00:54:33,480 >> YES THE OCCUPATION THAT WILL 1547 00:54:33,480 --> 00:54:36,600 BE THE MOST EXPOSURE OTHER 1548 00:54:36,600 --> 00:54:37,080 CREWS TO DO SPRAY FOAM 1549 00:54:37,080 --> 00:54:38,520 INSULATION. TO THE CREDIT OF 1550 00:54:38,520 --> 00:54:39,080 THE CHEMICAL COMPANIES THAT 1551 00:54:39,080 --> 00:54:41,520 MAKE THIS THING, THEY KNOW THAT 1552 00:54:41,520 --> 00:54:45,040 AND THEY ARE VERY STRICT ABOUT 1553 00:54:45,040 --> 00:54:46,760 HAVING FULL BODY HEAD SUITS AND 1554 00:54:46,760 --> 00:54:48,040 RESPIRATORS THAT LOG INTO THE 1555 00:54:48,040 --> 00:54:48,800 MASK, TO KEEP THE EXPOSURES 1556 00:54:48,800 --> 00:54:55,360 LOW. THEY WILL HAVE CONTACT 1557 00:54:55,360 --> 00:54:55,960 DERM SOMETIMES AND THERE IS 1558 00:54:55,960 --> 00:54:56,560 CERTAINLY AN ASTHMATIC RISK BUT 1559 00:54:56,560 --> 00:54:57,160 THEY DON'T NECESSARILY GET 1560 00:54:57,160 --> 00:54:59,760 ATOPIC DERM. AGAIN THESE ARE 1561 00:54:59,760 --> 00:55:04,160 PEOPLE WHO ARE OLDER. THE THING 1562 00:55:04,160 --> 00:55:04,800 I DON'T YET UNDERSTAND IS THAT 1563 00:55:04,800 --> 00:55:10,120 RESOLUTION WITH AGE. EVEN 1564 00:55:10,120 --> 00:55:10,720 THOUGH WE GET WAY MORE ECZEMA 1565 00:55:10,720 --> 00:55:12,960 IN THE WORLD THAN WE HAVE EVER 1566 00:55:12,960 --> 00:55:17,440 HAD BEFORE, YOU STILL SEE THAT 1567 00:55:17,440 --> 00:55:18,040 PATTERN THAT MOST OF IT WILL 1568 00:55:18,040 --> 00:55:21,400 SELF RESOLVE BY THE TIME PEOPLE 1569 00:55:21,400 --> 00:55:21,960 HIT ADULTHOOD SO THERE DOES 1570 00:55:21,960 --> 00:55:24,720 NEED TO BE SOMETHING INTRINSIC 1571 00:55:24,720 --> 00:55:25,320 ABOUT AGING THAT REMOVES THAT 1572 00:55:25,320 --> 00:55:26,000 RISK FOR USE OF BY THE TIME YOU 1573 00:55:26,000 --> 00:55:26,600 ARE OLD ENOUGH TO GO WORK IN 1574 00:55:26,600 --> 00:55:29,600 THE SPRAY FOAM PLANT YOU ARE 1575 00:55:29,600 --> 00:55:30,200 NOT AT RISK ANYMORE HOWEVER I 1576 00:55:30,200 --> 00:55:30,800 WILL NOTE THAT YOUR PULMONARY 1577 00:55:30,800 --> 00:55:38,520 RISK DOES NOT GO AWAY. THE 1578 00:55:38,520 --> 00:55:39,160 ASTHMA RISK IS THERE THIS WHICH 1579 00:55:39,160 --> 00:55:39,720 IS WHY THEY ARE EXCEEDINGLY 1580 00:55:39,720 --> 00:55:40,360 STRICT ABOUT HAVING THE PROPER 1581 00:55:40,360 --> 00:55:44,840 RESPIRATORS. 1582 00:55:44,840 --> 00:55:45,440 >> ANOTHER QUESTION HOW MY LACK 1583 00:55:45,440 --> 00:55:46,040 OF ACCESS TO HEALTHCARE IN 1584 00:55:46,040 --> 00:55:46,640 RURAL AREAS HAS AFFECTED YOUR 1585 00:55:46,640 --> 00:55:47,880 ANALYSIS OF THE ISOSOSIENATE 1586 00:55:47,880 --> 00:55:53,520 AND ATOPIC DERM? OUR RURAL 1587 00:55:53,520 --> 00:55:59,200 FOLKS NOT GETTING DIAGNOSED? 1588 00:55:59,200 --> 00:56:03,120 >> THE DENOMINATOR IS VISITS TO 1589 00:56:03,120 --> 00:56:03,720 THE PROVIDER SO THE DATABASE 1590 00:56:03,720 --> 00:56:06,080 DOES HAVE MEDICARE AND MEDICAID 1591 00:56:06,080 --> 00:56:06,680 INVOLVED. SO YOU HAVE SOME OF 1592 00:56:06,680 --> 00:56:08,600 THAT BUT YES, IF YOU ARE NOT 1593 00:56:08,600 --> 00:56:13,880 BEING SEEN BY ANY PROVIDER AT 1594 00:56:13,880 --> 00:56:14,480 ALL, YOU WILL NOT SHOW UP IN 1595 00:56:14,480 --> 00:56:15,040 THIS DATABASE. THAT WILL BE 1596 00:56:15,040 --> 00:56:18,720 TRUE BOTH FOR THE RURAL 1597 00:56:18,720 --> 00:56:19,320 COMMUNITIES, WE HAVE TO DRIVE 1598 00:56:19,320 --> 00:56:20,680 VERY FAR TO FIND A PROVIDER OR 1599 00:56:20,680 --> 00:56:21,280 URBAN COMMUNITIES WHERE YOU 1600 00:56:21,280 --> 00:56:21,840 CANNOT AFFORD TO GO TO YOUR 1601 00:56:21,840 --> 00:56:26,360 PROVIDER. THIS IS WHAT WE ARE 1602 00:56:26,360 --> 00:56:30,600 DOING KIND OF VISITS TO THE 1603 00:56:30,600 --> 00:56:31,240 DOCTOR, AND REALLY WHAT WE NEED 1604 00:56:31,240 --> 00:56:31,880 TO DO IS DIRECT MEASUREMENT OF 1605 00:56:31,880 --> 00:56:32,400 THE POLLUTANTS VS. ACTIVE 1606 00:56:32,400 --> 00:56:38,000 SURVEYS OF THE PATIENTS. DO YOU 1607 00:56:38,000 --> 00:56:38,640 HAVE DISEASE AND HOW BAD IS IT 1608 00:56:38,640 --> 00:56:44,200 TODAY? SO YES COMPLETE LACK OF 1609 00:56:44,200 --> 00:56:44,720 ACCESS WILL INFLUENCE OUR 1610 00:56:44,720 --> 00:56:45,240 RESULTS BUT IT SHOULD BE 1611 00:56:45,240 --> 00:56:45,800 SOMEWHAT DISTRIBUTED ACROSS 1612 00:56:45,800 --> 00:56:46,400 COUNTRY BECAUSE THIS DATABASE 1613 00:56:46,400 --> 00:56:47,200 WAS FOR THE ENTIRE POPULATION. 1614 00:56:47,200 --> 00:56:51,440 >> ANOTHER QUESTION. WHAT IS 1615 00:56:51,440 --> 00:56:52,040 KNOWN ABOUT THE CONFUSION OF 1616 00:56:52,040 --> 00:56:52,640 INDOOR COOKING FIRES? INCLUDING 1617 00:56:52,640 --> 00:56:57,480 NATURAL GAS TO ATOPIC DERM? 1618 00:56:57,480 --> 00:56:58,040 >> I HAVE NOT SEEN THAT ONE 1619 00:56:58,040 --> 00:57:03,720 BEING LINKED. WE HAVE LOOKED AT 1620 00:57:03,720 --> 00:57:05,160 THAT IN THE LINK IS OBVIOUSLY 1621 00:57:05,160 --> 00:57:06,160 WITH ASTHMA, AND CONVERSATIONS 1622 00:57:06,160 --> 00:57:06,760 ABOUT POTENTIALLY WHAT TO DO 1623 00:57:06,760 --> 00:57:08,120 ABOUT GAS STOVES. BUT I DID 1624 00:57:08,120 --> 00:57:16,200 NOT SEE ANY LINK TO ATOPIC DERM 1625 00:57:16,200 --> 00:57:16,800 ROUTINELY REPORTED AND THERE 1626 00:57:16,800 --> 00:57:17,400 IS NO REASON TO SUSPECT THESE 1627 00:57:17,400 --> 00:57:18,080 PARTICULAR CHEMICALS WOULD COME 1628 00:57:18,080 --> 00:57:28,000 OUT OF A NATURAL GAS FIRE. YOU 1629 00:57:28,000 --> 00:57:28,560 REALLY WOULD HAVE TO HAVE A 1630 00:57:28,560 --> 00:57:29,160 CATALYTIC CONVERSION; SHOULD 1631 00:57:29,160 --> 00:57:29,800 NOT EVEN START WITH NATURAL GAS 1632 00:57:29,800 --> 00:57:32,440 AS A LIQUID. 1633 00:57:32,440 --> 00:57:33,920 >> THE NEXT QUESTION IS TWO 1634 00:57:33,920 --> 00:57:38,520 PARTS. WHAT DID YOU DISCOVER 1635 00:57:38,520 --> 00:57:39,320 ABOUT (INDISCERNIBLE) CREAM OR 1636 00:57:39,320 --> 00:57:44,400 OINTMENT? 1637 00:57:44,400 --> 00:57:44,920 >> THE OPTIMAL DEPENDS ON 1638 00:57:44,920 --> 00:57:45,480 WHETHER YOU ARE TALKING THE 1639 00:57:45,480 --> 00:57:48,320 CLINICAL TRIAL OR PATIENT 1640 00:57:48,320 --> 00:57:48,960 TREATMENT. FOR A CLINICAL TRIAL 1641 00:57:48,960 --> 00:57:49,480 THE PLACEBO WILL BE WATER 1642 00:57:49,480 --> 00:57:50,080 BECAUSE OF FREEZE-DRIED WHICH 1643 00:57:50,080 --> 00:57:52,200 IS SUGAR RECONSTITUTED IN WATER 1644 00:57:52,200 --> 00:57:52,800 SO THE PLACEBO WILL BE SURE 1645 00:57:52,800 --> 00:57:54,040 WATER. THIS WOULD BE SUGAR 1646 00:57:54,040 --> 00:57:56,440 WATER WITH -- AND TRIPP-A1 1647 00:57:56,440 --> 00:58:01,720 BLOCKER. THAT IS THE BEST TO 1648 00:58:01,720 --> 00:58:02,360 DISCERN SO YOU DON'T HAVE MUCH 1649 00:58:02,360 --> 00:58:04,680 OF A VEHICLE TYPE. 1650 00:58:04,680 --> 00:58:05,200 PART OF THE PROBLEM IN THE 1651 00:58:05,200 --> 00:58:05,840 CLINICAL TRIAL IS THAT THEY HAD 1652 00:58:05,840 --> 00:58:13,400 EVERYBODY USE TOPICAL CERAMIDE- 1653 00:58:13,400 --> 00:58:14,000 CONTAINING LOTION SO NOW YOU 1654 00:58:14,000 --> 00:58:14,560 MAKE A SITUATION WHERE THE 1655 00:58:14,560 --> 00:58:15,960 VEHICLE MAKES CERAMIDE AND THE 1656 00:58:15,960 --> 00:58:16,600 VICTORY MAKES MORE AND THIS IS 1657 00:58:16,600 --> 00:58:18,160 WHY THE PLACEBO MAKES MORE AND 1658 00:58:18,160 --> 00:58:25,440 WHEN YOU ADD THE ROSIEMONAS ONE 1659 00:58:25,440 --> 00:58:26,000 OF THE CERAMIDE CONTAINING 1660 00:58:26,000 --> 00:58:29,800 LOTIONS THAT WOULD BE THE 1661 00:58:29,800 --> 00:58:30,440 OPTIMAL OUTPUT SO IF THIS WERE 1662 00:58:30,440 --> 00:58:31,000 TO BE USED OVER THE COUNTER 1663 00:58:31,000 --> 00:58:32,840 SOME OF THE FORM OUT IN THE 1664 00:58:32,840 --> 00:58:33,440 COMMUNITY YOU WOULD TAKE THE 1665 00:58:33,440 --> 00:58:37,680 FROZEN ROSIEMONAS AND MIX IT 1666 00:58:37,680 --> 00:58:39,280 WITH LOTION AND USE THAT AND 1667 00:58:39,280 --> 00:58:40,360 THAT WILL BE YOUR BIGGEST 1668 00:58:40,360 --> 00:58:40,960 IMPROVEMENT. FOR THE CLINICAL 1669 00:58:40,960 --> 00:58:41,560 TRIAL WOULD HAVE TO KEEP THE 1670 00:58:41,560 --> 00:58:42,160 VEHICLE AFFECT OUT AS MUCH AS 1671 00:58:42,160 --> 00:58:42,800 WE CAN. 1672 00:58:42,800 --> 00:58:44,120 >> THE SECOND PART OF THAT 1673 00:58:44,120 --> 00:58:50,560 QUESTION. DOES ROSIEMONS NEED 1674 00:58:50,560 --> 00:58:52,560 TO BE PRODUCED AT GMP QUALITY? 1675 00:58:52,560 --> 00:58:53,160 AND IF SO WHAT CHALLENGES DID 1676 00:58:53,160 --> 00:58:53,640 YOU ENCOUNTER IN YOUR 1677 00:58:53,640 --> 00:58:56,200 PRODUCTION PROCESS? 1678 00:58:56,200 --> 00:58:56,800 >> WE DID NOT HAVE ANY PROBLEM 1679 00:58:56,800 --> 00:58:57,320 AND THERE IS A SEPARATE 1680 00:58:57,320 --> 00:59:02,040 CATEGORY CALLED TOPICAL GMP, 1681 00:59:02,040 --> 00:59:02,640 LITTLE BIT EASIER TO DO BUT THE 1682 00:59:02,640 --> 00:59:07,280 SUBSEQUENT TRIAL ALL WILL BE 1683 00:59:07,280 --> 00:59:07,880 GMP. BECAUSE WE ARE STARTING 1684 00:59:07,880 --> 00:59:08,480 WITH A PURIFIED ISOLATE, WE DID 1685 00:59:08,480 --> 00:59:09,000 THINK THAT MIXING THREE 1686 00:59:09,000 --> 00:59:10,520 ISOLATES TOGETHER OBVIOUSLY YOU 1687 00:59:10,520 --> 00:59:14,480 TRY TO BALANCE THEM OUT. 1688 00:59:14,480 --> 00:59:15,080 SUBSEQUENT STUDIES SHOWS THAT 1689 00:59:15,080 --> 00:59:15,680 ONLY ONE OF THOSE ISOLATES IS 1690 00:59:15,680 --> 00:59:22,920 SUPERIOR IN MULTIPLE OTHER 1691 00:59:22,920 --> 00:59:24,960 MODELS WE ONLY MOVE ONE 1692 00:59:24,960 --> 00:59:25,560 PURIFIED ISOLATE TO REMOVE A 1693 00:59:25,560 --> 00:59:26,160 LOT OF THE CHALLENGES TO THE 1694 00:59:26,160 --> 00:59:30,360 GMP STATUS. 1695 00:59:30,360 --> 00:59:30,960 >> THANK YOU VERY MUCH AND THAT 1696 00:59:30,960 --> 00:59:31,600 BRINGS US TO THE QUESTION, AND 1697 00:59:31,600 --> 00:59:32,200 IT TAKES US TO THE TOP OF THE 1698 00:59:32,200 --> 00:59:36,960 HOUR. DR. MILES, THANK YOU FOR 1699 00:59:36,960 --> 00:59:37,600 SHARING YOUR WORK INTO THE NIH 1700 00:59:37,600 --> 00:59:38,080 COMMUNITY. HAVE A GREAT 1701 00:59:38,080 --> 00:59:38,520 AFTERNOON. 1702 00:59:38,520 --> 00:00:00,000 THANK YOU.