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>> HELLO, EVERYONE.

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I WOULD LIKE TO WELCOME YOU TO

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OUR SEMINAR TODAY, WHICH IS THE

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OBESITY, NUTRITION AND PHYSICAL

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ACTIVITY SEMINAR.

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MY NAME IS CHARLOTTE PRATT.

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I AM A DEPUTY BRANCH CHIEF IN

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THE DIVISION OF CARDIOVASCULAR

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SCIENCES AT THE NATIONAL HEART,

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LUNG AND BLOOD INSTITUTE.

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I WILL BE MODERATING THIS

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SESSION, WHICH IS HOSTED BY THE

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INSTITUTE'S OBESITY WORKING

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GROUP.

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PAST PRESENTATIONS HAVE

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HIGHLIGHTED A VARIETY OF TOPICS

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THAT HAVE BEEN ARCHIVED ON THIS

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VIDEOCAST AND AVAILABLE TO THE

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PUBLIC.

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THESE INCLUDE NEW DIRECTIONS IN

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COMMUNITY-BASED INTERVENTIONS TO

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IMPROVE FOOD ACCESS AND REDUCE

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OBESITY.

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CARDIOVASCULAR DISEASE RISK, AND

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INTERMITTENT FASTING AND THE

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CIRCADIAN CLOCK, DOES WHEN YOU

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EAT AFFECT YOUR HEALTH?

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TODAY WE ARE SO FORTUNATE TO

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HAVE DR. CASEY REBHOLZ PRESENT

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ON DIETARY BIOMARKERS AND

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CARDIOPROTECTIVE MECHANISMS OF

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THE DASH DIET.

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BEFORE I START, I WANT TO REVIEW

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A FEW HOUSEKEEPING ITEMS.

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THROUGHOUT THE PRESENTATION AND

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DURING THE QUESTIONS AND ANSWER

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DISCUSSIONS, PLEASE SEND YOUR

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QUESTIONS TO THE EMAIL LISTED

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BELOW ON SCREEN AT

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ONPA@MAIL.NIH.GOV.

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OR YOU MAY CLICK THE "LIVE

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FEEDBACK" AT THE BOTTOM OF THE

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VIDEOCAST SCREEN TO SUBMIT YOUR

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QUESTION.

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NOW LET ME INTRODUCE OUR

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SPEAKER.

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DR. CASEY REBHOLZ IS AN

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ASSOCIATE PROFESSOR IN THE

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DEPARTMENT OF EPIDEMIOLOGY AT

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THE JOHNS HOPKINS BLOOMBERG

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SCHOOL OF PUBLIC HEALTH.

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SHE'S ALSO A FACULTY MEMBER AT

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THE WELCH CENTER FOR PREVENTION,

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EPIDEMIOLOGY AND CLINICAL

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RESEARCH AND HAS A JOINT

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APPOINTMENT IN THE DIVISION OF

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NEPHROLOGY IN THE DEPARTMENT OF

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MEDICINE AT JOHNS HOPKINS SCHOOL

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OF MEDICINE.

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HER RESEARCH FOCUSES ON

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BIOMARKERS OF DIETARY INTAKE AND

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CHRONIC DISEASE RISK.

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DR. REBHOLZ IS CURRENTLY FROM

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THE NHLBI AND IS CONDUCTING

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RESEARCH USING ONE OF OUR MANY

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COHORT STUDIES, THE

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ATHEROSCLEROSIS RISK IN

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COMMUNITIES, OR AS WE TYPICALLY

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KNOW IT, ARIC.

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HER RESEARCH FOCUSES ON

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METABOLOMICS AND PROTEOMICS TO

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IDENTIFY NEW AND OBJECTIVE

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BIOMARKERS OF DIETARY INTAKE AND

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DISEASE RISK.

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PLEASE WELCOME DR. REB HOLDS. R.

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>> THANK YOU SO MUCH, DR. PRATT,

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FOR THE INTRODUCTION, AND THANK

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YOU TO NHLBI FOR THE OPPORTUNITY

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TO PRESENT TODAY.

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SO HERE'S AN OUTLINE OF THE

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TALK.

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I'LL FIRST TALK ABOUT THE DASH

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DIET AND HEALTH OUTCOMES

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ASSOCIATED WITH THE DASH DIET,

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AND THEN A LITTLE BIT ABOUT

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DIETARY ASSESSMENT, AND THEN

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INTO MY RESEARCH ON THE

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METABOLOMICS OF THE DASH DIET IN

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THE DASH TRIAL, IN THE DASH

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SODIUM TRIAL, IN THE ARIC STUDY

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AND IN THE CRIC STUDY AND THEN

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FOLLOWING THAT, TALK ABOUT SOME

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PROTEOMICS RESEARCH IN THE DASH

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DIET IN THE ARIC STUDY AND THE

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DASH SODIUM TRIALS, AND THEN

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I'LL CONCLUDE.

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SO WHAT IS THE DASH DIET?

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IT'S A DIETARY PATTERN THAT'S

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RICH IN FRUITS, VEGETABLES AND

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LOW FAT DAIRY.

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IT'S MODERATE IN A WIDE RANGE OF

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PROTEIN SOURCES, AND LOW IN

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SUGAR SWEETENED BEVERAGES,

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SWEETS AND RED MEAT.

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IT'S BEEN SHOWN IN CLINICAL

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TRIALS TO REDUCE BLOOD PRESSURE

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AND IN SUBSEQUENT EP DEEM YO

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LICK STUDIES TO REDUCE THE RISK

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OF HYPERTENSION, DIABETES,

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STROKE, CARDIOVASCULAR DISEASE

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AND MORTALITY.

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AND IT'S BEEN WIDELY RECOMMENDED

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AS HEALTHY DIETARY PATTERNS FOR

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THE GENERATION POPULATION IN THE

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U.S. DIETARY GUIDELINES FOR

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AMERICANS AS WELL AS FOR THE

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PREVENTION OF CARDIOVASCULAR

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DISEASE BY THE AMERICAN HEART

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ASSOCIATION.

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AND HERE'S A FIGURE FROM A

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RECENT SCIENTIFIC STATEMENT FROM

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THE AMERICAN HEART ASSOCIATION

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EVALUATING POPULAR DIETS.

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AND THEY FOUND THAT THE

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DASH-STYLE DIET WAS MOST ALIGNED

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WITH THE LATEST DIETARY GUIDANCE

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FROM THE AMERICAN HEART

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ASSOCIATION.

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SO WITH RESPECT TO HEALTH

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OUTCOMES, HERE ARE THE FINDINGS

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FROM THE ORIGINAL CLINICAL

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TRIALS ON THE LEFT, THE DASH

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TRIAL, AND ON THE RIGHT, THE

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DASH SODIUM TRIAL.

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SO YOU CAN SEE THAT AFTER THE

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INITIAL TWO-WEEK PERIOD, THERE'S

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A SUBSTANTIAL DROP IN BO BOTH

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SYSTOLIC AND DIASTOLIC BLOOD

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PRESSURE WHICH WAS SUSTAINED

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OVER 8-WEEK PERIOD AND THIS

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REDUCTION WAS MARKEDLY GREATER

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FOR THE COMBINATION DIET

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FOLLOWED BY THE FRUITS AND

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VEGETABLES DIET COMPARED TO THE

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CONTROL DIET.

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SUBSEQUENT TO THE ORIGINAL

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TRIAL, THE COMBINATION DIET HAS

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BEEN REFERRED TO AS THE DASH

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DIET.

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ON THE RIGHT-HAND SIDE IN THE

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DASH SODIUM TRIAL, WE HAVE

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SIMILAR GRAPHS.

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PARTICIPANTS WERE RANDOMIZED TO

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THE DASH AND CONTROL DIET IN A

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PARALLEL ARM DESIGN AND

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SUBSEQUENTLY TO THREE SODIUM

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LEVELS, HIGH, INTERMEDIATE AND

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LOW, AND  -- IN A CROSSOVER

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DESIGN.

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THOSE WHO EXPERIENCED THE

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GREATEST REDUCTION IN BOTH

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SYSTOLIC AND DIASTOLIC BLOOD

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PRESSURE WERE FOLLOWING THE DASH

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DIET DURING THE LOW SODIUM

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INTERVENTION.

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THEN BASED ON THE DESIGN OF THE

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DASH DIET, SUBSEQUENT SCORES

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HAVE BEEN CREATED TO ASSESS

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ADHERENCE TO THE DASH DIET IN

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FREE LIVING POPULATIONS.

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ON THE LEFT IS A PRIMARILY FOOD

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AND NUTRIENT FOCUSED SCORING

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SYSTEM, AND ON THE RIGHT IS

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PRIMARILY A NUTRIENT-FOCUSED

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SYSTEM WITH MACRO AND MICRO.

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SO ON THE LEFT, WE SEE THAT

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HIGHER INTAKE OF SODIUM, RED AND

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PROCESSED MEAT AND SUGAR

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SWEETENED BEVERAGES RECEIVED

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LOWER SCORES, AND HIGHER INTAKE

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OF FRUITS, VEGETABLES, NUTS AND

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LEGUMES, WHOLE GRAINS AND LOW

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FAT DAIRY RECEIVE HIGHER SCORES.

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ON THE RIGHT, WE SEE THAT LOWER

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INTAKE OF SATURATED FAT, TOTAL

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FAT, CHOLESTEROL AND SODIUM

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RECEIVE HIGHER SCORES, AND

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HIGHER INTAKE OF PROTEIN, FIBER,

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MAGNESIUM, CALCIUM AND POTASSIUM

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RECEIVED HIGHER SCORES ON THESE

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TWO SCORING SYSTEMS.

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SO HERE I'LL INTRODUCE THE ARIC

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STUDY, WHICH I'LL MENTION AT

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MANY POINTS THROUGHOUT THIS

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PRESENTATION, WHICH DR. PRATT

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ALREADY TALKED ABOUT.

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BUT IT'S PRIMARILY AN NHLBI

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COHORT, CERTAINLY AT ITS

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INCEPTION IT HAS SUBSEQUENTLY

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RECEIVED FUNDING FROM

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DIFFERENT -- OTHER INSTITUTES.

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IT WAS ESTABLISHED IN 1987 TO

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1989, WAS THE VISIT 1, AT WHICH

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POINT 15,792 MIDDLE AGED,

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PREDOMINANTLY BUT NOT

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EXCLUSIVELY WHITE AND BLACK MEN

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00:08:04,116 --> 00:08:05,918
AND WOMEN FROM FOUR U.S.

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COMMUNITIES INDICATED WITH THE

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00:08:06,986 --> 00:08:09,522
RED STARS HERE ON THE MAP WERE

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ENROLLED IN THE STUDY.

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SUBSEQUENTLY THERE HAVE BEEN

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MANY FOLLOW-UP VISITS THROUGHOUT

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TIME.

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THE FOOD FREQUENCY QUESTIONNAIRE

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WAS ADMINISTERED AT BOTH VISIT Y

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INTAKE.

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AND I'LL MENTION SOME KIDNEY

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FUNCTION SO I'VE NOTED HERE THAT

219
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GFR IS A MEASURE OF KIDNEY

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FUNCTION, WAS ESTIMATED AT MOST

221
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OF THE FOLLOW-UP STUDY VISITS.

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AND WE DEFINE INCIDENT CHRONIC

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KIDNEY DISEASE AS A REDUCTION OF

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GFR BELOW 60 AND AT LEAST A 25%

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DECLINE RELATIVE TO BASELINE, AS

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WELL AS ANY CKD RELATED

227
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HOSPITALIZATION DEATHS OR ANY

228
00:08:52,698 --> 00:08:54,500
INSTANCES OF END STAGE RENAL

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DISEASE IDENTIFIED WITH THE

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00:08:56,435 --> 00:08:58,004
REGISTRY WHICH CAPTURES DIALYSIS

231
00:08:58,070 --> 00:09:00,740
AND TRANSPLANT.

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SO WE FOUND THAT WITH TERTILE

233
00:09:12,018 --> 00:09:12,985
3 -- LOWER LEVELS OF ADHERENCE

234
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WERE ASSOCIATED WITH HIGHER RISK

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OF INCIDENT CHRONIC KIDNEY

236
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DISEASE AND THIS ASSOCIATION

237
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PERSISTED AFTER ADJUSTMENT FOR

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MULTIPLE SOCIODEMOGRAPHIC,

239
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HEALTH BEHAVIOR, KIDNEY

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FUNCTION, BODY MASS, CLINICAL

241
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CHARACTERISTICS AS WELL AS

242
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HYPERTENSION LOWERING

243
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MEDICATION.

244
00:09:36,575 --> 00:09:38,244
AND THIS ASSOCIATION WAS

245
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CONSISTENT WITH BOTH OF THE

246
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SCORES THAT I PRESENTED, THE

247
00:09:42,348 --> 00:09:47,486
FOOD-FOCUSED ONE AND THE KNEW

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NUTRIENT FOCUSED ONE.

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00:09:50,556 --> 00:09:52,892
THIS WORK LED BY A FORMER PH.D.

250
00:09:52,959 --> 00:09:54,427
STUDENT OF MINE, WE LOOKED AT

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DASH DIET ADHERENCE AND

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CARDIOVASCULAR DISEASE,

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MORTALITY AND ALL CAUSE

254
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MORTALITY.

255
00:09:59,899 --> 00:10:01,867
WITH THE LOWEST QUINTILE AS THE

256
00:10:01,934 --> 00:10:04,070
REFERENCE GROUP, NOW WE SEE THAT

257
00:10:04,136 --> 00:10:05,137
HIGHER ADHERENCE IS ASSOCIATED

258
00:10:05,204 --> 00:10:07,239
WITH A REDUCED RISK OF

259
00:10:07,306 --> 00:10:09,075
CARDIOVASCULAR DISEASE MORTALITY

260
00:10:09,141 --> 00:10:10,509
AND ALL CAUSE MORTALITY IN THE

261
00:10:10,576 --> 00:10:14,347
OVERALL POPULATION.

262
00:10:14,413 --> 00:10:17,283
AND SUGGESTION OF REDUCED RISK

263
00:10:17,350 --> 00:10:18,284
OF CARDIOVASCULAR DISEASE AS

264
00:10:18,351 --> 00:10:19,352
WELL.

265
00:10:19,418 --> 00:10:21,020
AND THEN IN A DIFFERENT COHORT,

266
00:10:21,087 --> 00:10:23,189
THIS IS THE CRIC STUDY OR

267
00:10:23,255 --> 00:10:25,725
CHRONIC RENAL INSUFFICIENCY

268
00:10:25,791 --> 00:10:27,526
COHORT STUDY FUNDED BY THE NIDDK

269
00:10:27,593 --> 00:10:30,296
OF PEOPLE LIVING WITH KIDNEY

270
00:10:30,363 --> 00:10:32,064
DISEASE, WIDE RANGE OF BASELINE

271
00:10:32,131 --> 00:10:35,668
GFRs FROM 20 TO 70, IN THAT

272
00:10:35,735 --> 00:10:37,970
POPULATION, AND WE FOUND THAT

273
00:10:38,037 --> 00:10:40,039
HIGHER ADHERENCE TO THE DASH

274
00:10:40,106 --> 00:10:42,775
DIET RELATIVE TO TERTILE

275
00:10:42,842 --> 00:10:44,643
1 REPRESENTING THE LOWERED

276
00:10:44,710 --> 00:10:46,312
ADHERENCE WAS ASSOCIATED WITH A

277
00:10:46,379 --> 00:10:48,147
SIGNIFICANTLY REDUCED RISK OF

278
00:10:48,214 --> 00:10:49,715
BOTH PROGRESSION OF CHRONIC

279
00:10:49,782 --> 00:10:51,083
KIDNEY DISEASE AS WELL AS

280
00:10:51,150 --> 00:10:55,121
ALL-CAUSE MORTALITY.

281
00:10:55,187 --> 00:10:57,757
SO NOW A FEW THOUGHTS ON DIETARY

282
00:10:57,823 --> 00:10:58,357
ASSESSMENT.

283
00:10:58,424 --> 00:11:00,726
SO MEASURING DIET IS

284
00:11:00,793 --> 00:11:01,427
CHALLENGING, AND IT'S IMPORTANT

285
00:11:01,494 --> 00:11:02,895
THAT WE HAVE ACCURATE MEASURES

286
00:11:02,962 --> 00:11:04,663
OF DIET FOR RESEARCH PURPOSES,

287
00:11:04,730 --> 00:11:06,499
BOTH IN CLINICAL TRIALS AND

288
00:11:06,565 --> 00:11:07,933
EPIDEMIOLOGIC STUDIES.

289
00:11:08,000 --> 00:11:09,802
TYPICALLY WE USE SELF-REPORTED

290
00:11:09,869 --> 00:11:12,104
DIETARY INTAKE, USING A FOOD

291
00:11:12,171 --> 00:11:13,406
FREQUENCY QUESTIONNAIRE OR

292
00:11:13,472 --> 00:11:15,474
24-HOUR DIETARY RECALL OR A FOOD

293
00:11:15,541 --> 00:11:16,042
DIARY.

294
00:11:16,108 --> 00:11:19,111
HOWEVER, THESE TOOLS ARE

295
00:11:19,178 --> 00:11:21,280
SUBJECTIVE, AS WELL AS THE FOOD

296
00:11:21,347 --> 00:11:22,715
COMPOSITION DATABASES THAT LINK

297
00:11:22,782 --> 00:11:26,852
THE REPORTED INTAKE TO THE

298
00:11:26,919 --> 00:11:28,721
NUTRIENTS WITHIN THOSE FOODS TO

299
00:11:28,788 --> 00:11:30,890
ESTIMATE NUTRIENTS FOR A GIVEN

300
00:11:30,956 --> 00:11:34,393
INDIVIDUAL, THEY ALSO HAVE THEIR

301
00:11:34,460 --> 00:11:35,594
LIMITATIONS IN THAT THEY'RE

302
00:11:35,661 --> 00:11:36,796
INCOMPLETE AND MAY BE

303
00:11:36,862 --> 00:11:39,231
INACCURATE.

304
00:11:39,298 --> 00:11:42,601
AND SO HEREIN LIES THE

305
00:11:42,668 --> 00:11:45,771
ADVANTAGES OF DIET BIOMARKERS IN

306
00:11:45,838 --> 00:11:48,174
THAT THEY'RE OBJECTIVE AND LESS

307
00:11:48,240 --> 00:11:50,709
INFLUENCED BY BIAS AND ERROR,

308
00:11:50,776 --> 00:11:52,011
SPECIFICALLY RECALL BIAS AND

309
00:11:52,078 --> 00:11:53,646
SOCIAL DESIRABILITY BIAS.

310
00:11:53,712 --> 00:11:58,350
BIOMARKERS ARE MORE PRECISE AND

311
00:11:58,417 --> 00:11:59,885
LESS -- RANDOM ERRORS ARE LESS

312
00:11:59,952 --> 00:12:00,686
OF A CONCERN.

313
00:12:00,753 --> 00:12:01,754
HOWEVER, WITH DIETARY

314
00:12:01,821 --> 00:12:02,621
BIOMARKERS, THE ONES THAT WE

315
00:12:02,688 --> 00:12:05,891
HAVE TODAY THAT ARE CURRENTLY

316
00:12:05,958 --> 00:12:09,061
USED REPRESENT PRIMARILY SINGLE

317
00:12:09,128 --> 00:12:09,628
NUTRIENTS.

318
00:12:09,695 --> 00:12:11,063
FOR EXAMPLE.

319
00:12:11,130 --> 00:12:13,232
24-HOUR URINE EXCRETION OF

320
00:12:13,299 --> 00:12:14,333
SODIUM TO ESTIMATE DIETARY

321
00:12:14,400 --> 00:12:17,403
INTAKE OF SODIUM, POTASSIUM TO

322
00:12:17,470 --> 00:12:18,704
ESTIMATE DIETARY INTAKE OF

323
00:12:18,771 --> 00:12:22,108
POTASSIUM, AND UREA NITROGEN TO

324
00:12:22,174 --> 00:12:25,277
ESTIMATE PROTEIN INTAKE.

325
00:12:25,344 --> 00:12:29,215
HOWEVER, THE 24-HOUR URINE

326
00:12:29,281 --> 00:12:32,485
COLLECTION IS BURDENSOME FOR

327
00:12:32,551 --> 00:12:34,120
PARTICIPANTS, AND SO WHAT I'VE

328
00:12:34,186 --> 00:12:40,459
DONE IS USED OMICS TECHNIQUES TO

329
00:12:40,526 --> 00:12:41,460
DISCOVER NEW BIOMARKERS OF

330
00:12:41,527 --> 00:12:43,195
DIETARY IB TAKE.

331
00:12:43,262 --> 00:12:43,762
INTAKE.

332
00:12:43,829 --> 00:12:45,264
THIS IS AN OVERVIEW OF

333
00:12:45,331 --> 00:12:46,165
HIGH-THROUGHPUT TECHNOLOGIES

334
00:12:46,232 --> 00:12:49,768
THAT ARE AVAILABLE TODAY IN

335
00:12:49,835 --> 00:12:51,504
BIOLOGICAL RESEARCH RANGING FROM

336
00:12:51,570 --> 00:12:55,007
THE MOST BROAD GENOMICS WHICH

337
00:12:55,074 --> 00:12:57,309
MEASURES BIOLOGICAL POTENTIAL,

338
00:12:57,376 --> 00:12:58,944
TRANSCRIPTOMICS WHICH

339
00:12:59,011 --> 00:13:00,346
MEASURES -- AND THEN PROTEINS,

340
00:13:00,412 --> 00:13:01,580
WHICH ARE ESSENTIAL FOR

341
00:13:01,647 --> 00:13:03,215
BIOLOGICAL FUNCTION, AND THEN

342
00:13:03,282 --> 00:13:06,719
FINALLY METABOLOMICS, WHICH ARE

343
00:13:06,785 --> 00:13:08,821
ASSESSING ONE'S PHYSIOLOGIC

344
00:13:08,888 --> 00:13:10,756
STATE, AND I'LL FOCUS TODAY ON

345
00:13:10,823 --> 00:13:14,360
PROTEOMICS AND METABOLOMICS.

346
00:13:14,426 --> 00:13:15,928
SO METABOLOMICS, SPECIFICALLY

347
00:13:15,995 --> 00:13:18,197
GLOBAL OR UNTARGETED

348
00:13:18,264 --> 00:13:19,899
METABOLOMICS PROFILING PROVIDES

349
00:13:19,965 --> 00:13:22,601
AN UNBIASED AND COMPREHENSIVE

350
00:13:22,668 --> 00:13:24,003
CHARACTERIZATION OF A COMPLEX

351
00:13:24,069 --> 00:13:29,008
BIOSIS TEM.

352
00:13:29,074 --> 00:13:29,808
BIOSYSTEM.

353
00:13:29,875 --> 00:13:30,776
FURTHERMORE, ANOTHER ADVANTAGE

354
00:13:30,843 --> 00:13:32,645
OF METABOLOMICS IS THE ABILITY

355
00:13:32,711 --> 00:13:34,046
TO DETECT MANY SMALL COMPOUNDS,

356
00:13:34,113 --> 00:13:35,781
AND THIS NUMBER IS INCREASING

357
00:13:35,848 --> 00:13:39,952
EVERY DAY.

358
00:13:40,019 --> 00:13:42,588
INTEGRATING THE METABALOME WITH

359
00:13:42,655 --> 00:13:45,858
DIETARY DATA ALLOWS US TO LEARN

360
00:13:45,925 --> 00:13:47,760
ABOUT FOOD INTAKE, AS WELL AS

361
00:13:47,826 --> 00:13:50,596
FOOD METABOLISM.

362
00:13:50,663 --> 00:13:53,098
AND IT COULD HELP US IDENTIFY

363
00:13:53,165 --> 00:13:55,401
NOVEL BIOMARKERS FOR NUTRITION

364
00:13:55,467 --> 00:13:56,035
RESEARCH, AS WELL AS

365
00:13:56,101 --> 00:13:59,638
INTERVENTION TARGETS.

366
00:13:59,705 --> 00:14:02,808
SO THIS PICTURE SHOWS YOU

367
00:14:02,875 --> 00:14:04,343
INFLUENCES OF THE OVERALL

368
00:14:04,410 --> 00:14:05,477
METABALOME, SO THERE ARE

369
00:14:05,544 --> 00:14:09,315
COMPOUNDS THAT ARE IN THE BODY

370
00:14:09,381 --> 00:14:11,951
ENDOGENOUSLY THAT ARE USED FOR

371
00:14:12,017 --> 00:14:14,086
CELLULAR METABOLISM, AND THEN

372
00:14:14,153 --> 00:14:17,523
THE FOOD METABALOME REPRESENTS A

373
00:14:17,590 --> 00:14:21,260
WIDE RANGE OF FACTORS INCLUDING

374
00:14:21,327 --> 00:14:22,394
INDIVIDUAL FOODS, OVERALL

375
00:14:22,461 --> 00:14:24,697
DIETARY PATTERNS, FOOD ADDITIVES

376
00:14:24,763 --> 00:14:27,499
AND CONTAMINANTS, DIETARY

377
00:14:27,566 --> 00:14:30,502
SUPPLEMENTS, AND IN THE

378
00:14:30,569 --> 00:14:31,604
METABALOME, WE'RE MEASURING

379
00:14:31,670 --> 00:14:33,339
COMPOUNDS THAT ARE DERIVED FROM

380
00:14:33,405 --> 00:14:35,307
THAT FOOD AFTER DIGESTION AND

381
00:14:35,374 --> 00:14:38,477
METABOLISM.

382
00:14:38,544 --> 00:14:41,647
THE METABALOME ALSO REPRESENTS

383
00:14:41,714 --> 00:14:45,150
EXPOSURES TO DRUGS AND BROADER

384
00:14:45,217 --> 00:14:48,420
ENVIRONMENTAL EXPOSURES SUCH AS

385
00:14:48,487 --> 00:14:49,388
POLLUTANTS.

386
00:14:49,455 --> 00:14:51,056
SO NOW ON TO METABOLOMICS OF THE

387
00:14:51,123 --> 00:14:52,391
DASH DIET.

388
00:14:52,458 --> 00:14:54,326
SO THIS, WE'LL BE STARTING WITH

389
00:14:54,393 --> 00:14:55,227
THE DASH TRIAL, THE ORIGINAL

390
00:14:55,294 --> 00:14:57,296
TRIAL.

391
00:14:57,363 --> 00:14:58,731
HERE'S AN OVERVIEW OF THE DASH

392
00:14:58,797 --> 00:15:00,132
TRIAL.

393
00:15:00,199 --> 00:15:01,000
PARTICIPANTS FOLLOWED THE

394
00:15:01,066 --> 00:15:02,635
CONTROL DIET FOR A THREE-WEEK

395
00:15:02,701 --> 00:15:03,836
PERIOD AND THEN WERE RANDOMIZED

396
00:15:03,902 --> 00:15:05,504
IN A PARALLEL ARM DESIGNED TO

397
00:15:05,571 --> 00:15:07,039
EITHER THE CONTROL DIET, FRUITS

398
00:15:07,106 --> 00:15:08,907
AND VEGETABLES DIET AND WHAT WAS

399
00:15:08,974 --> 00:15:10,976
ORIGINALLY REFERRED TO AS THE

400
00:15:11,043 --> 00:15:11,944
COMBINATION DIET BUT WE NOW CALL

401
00:15:12,011 --> 00:15:15,781
THE DASH DIET FOR 8 WEEKS.

402
00:15:15,848 --> 00:15:18,183
AND I OBTAINED THE SERUM

403
00:15:18,250 --> 00:15:20,719
SPECIMENS FROM THE NHLBI'S

404
00:15:20,786 --> 00:15:23,789
BIOLINCC REPOSITORY, A FABULOUS

405
00:15:23,856 --> 00:15:24,523
RESOURCE.

406
00:15:24,590 --> 00:15:27,826
THERE ARE 459 PARTICIPANTS

407
00:15:27,893 --> 00:15:28,961
AVAILABLE WHO PARTICIPATED IN

408
00:15:29,028 --> 00:15:32,064
THE ORIGINAL TRIAL AND A

409
00:15:32,131 --> 00:15:33,265
SLIGHTLY SMALLER SUBSET WERE

410
00:15:33,332 --> 00:15:35,134
AVAILABLE IN THE REPOSITORY FOR

411
00:15:35,200 --> 00:15:36,902
THIS ANALYSIS.

412
00:15:36,969 --> 00:15:38,070
THE METABOLOMICS PROFILING FOR

413
00:15:38,137 --> 00:15:40,839
THIS STUDY WAS CONDUCTED BY

414
00:15:40,906 --> 00:15:41,473
METABOL.

415
00:15:41,540 --> 00:15:44,109
OH N, USING THEIR HD4 UNTARGETED

416
00:15:44,176 --> 00:15:45,878
PLATFORM SO THIS USES FOUR

417
00:15:45,944 --> 00:15:48,480
METHODS TO REVERSE PHASE ULTRA

418
00:15:48,547 --> 00:15:51,116
PERFORMANCE LIQUID CHROME MA

419
00:15:51,183 --> 00:15:52,318
TOGRAPHY TANDEM MASS

420
00:15:52,384 --> 00:15:55,254
SPECTROMETRY WITH FOSTIVE ION

421
00:15:55,321 --> 00:15:57,122
ELECTROSPRAY EYE ONIZATION,

422
00:15:57,189 --> 00:15:59,191
REVERSE PHASE ULTRA PERFORMANCE

423
00:15:59,258 --> 00:16:00,192
LIQUID CHROMATOGRAPHY WITH

424
00:16:00,259 --> 00:16:03,929
NEGATIVE ION MODE ELECTROSPRAY

425
00:16:03,996 --> 00:16:06,098
EYE ONIZATION HYDROPHILIC

426
00:16:06,165 --> 00:16:08,000
INTERACTION YOU PRA PERFORMANCE

427
00:16:08,067 --> 00:16:10,035
LICK YOU WID CHROMATOGRAPHY WITH

428
00:16:10,102 --> 00:16:12,004
NEGATIVE ION MODE ELECTROSPRAY

429
00:16:12,071 --> 00:16:12,438
EYE ONIZATION.

430
00:16:12,504 --> 00:16:17,910
AND I PULLED 20 VIALS THAT WERE

431
00:16:17,976 --> 00:16:23,649
MASKED TO THE LABORATORY, AND

432
00:16:23,716 --> 00:16:29,722
WERE DUPLICATES OF THE ORIGINAL

433
00:16:29,788 --> 00:16:31,156
VIALS, AND THE PERFORMANCE BY

434
00:16:31,223 --> 00:16:34,426
THE LAB WAS EXCELLENT WITH A

435
00:16:34,493 --> 00:16:38,831
MEDIAN CORRELATION OF .91, AND

436
00:16:38,897 --> 00:16:40,132
72 METABOLITES HAVING A

437
00:16:40,199 --> 00:16:42,101
CORRELATION ABOVE .8 WITHIN

438
00:16:42,167 --> 00:16:43,168
THOSE 20.

439
00:16:43,235 --> 00:16:46,705
A TOTAL OF 1238 METABOLITES WERE

440
00:16:46,772 --> 00:16:48,340
DETECTED, AND FOR THIS, I

441
00:16:48,407 --> 00:16:51,510
PRIMARILY FOCUSED ON THE KNOWN

442
00:16:51,577 --> 00:16:52,611
METABOLITES EXCLUDING THE

443
00:16:52,678 --> 00:16:54,880
UNKNOWNS, AND THOSE WERE 818

444
00:16:54,947 --> 00:16:57,316
METABOLITES.

445
00:16:57,383 --> 00:16:59,051
SO HERE ARE THE OVERALL RESULTS

446
00:16:59,118 --> 00:17:02,755
FROM THIS STUDY.

447
00:17:02,821 --> 00:17:04,390
97 SERUM KNOWN METABOLITES WERE

448
00:17:04,456 --> 00:17:05,491
SIGNIFICANTLY DIFFERENT BETWEEN

449
00:17:05,557 --> 00:17:07,159
THE DASH DIET AND THE CONTROL

450
00:17:07,226 --> 00:17:07,459
DIET.

451
00:17:07,526 --> 00:17:09,862
HERE WE HAVE A MODIFIED

452
00:17:09,928 --> 00:17:12,264
MANHATTAN PLOT DISPLAYING THE

453
00:17:12,331 --> 00:17:14,900
SIGNIFICANCE PLOTTED ALONG THE Y

454
00:17:14,967 --> 00:17:17,202
AXIS AND CAT DWRIS OF THE

455
00:17:17,269 --> 00:17:19,071
INDIVIDUAL METABOLITES ALONG THE

456
00:17:19,138 --> 00:17:21,907
X AXIS.

457
00:17:21,974 --> 00:17:24,209
AND THE HORIZONTAL LINE

458
00:17:24,276 --> 00:17:27,279
REPRESENTS THE THRESHOLD FOR

459
00:17:27,346 --> 00:17:27,846
STATISTICAL SIGNIFICANCE

460
00:17:27,913 --> 00:17:29,248
ACCOUNTING FOR THE NUMBER OF

461
00:17:29,314 --> 00:17:31,216
STATISTICAL COMPARISONS

462
00:17:31,283 --> 00:17:33,218
CONDUCTED, THAT IS THE NUMBER OF

463
00:17:33,285 --> 00:17:35,487
METABOLITES THAT WERE ANALYZED.

464
00:17:35,554 --> 00:17:39,625
AND SO WE SEE A LARGE NUMBER OF

465
00:17:39,691 --> 00:17:41,326
LIPIDS THAT WERE DIFFERENT AS

466
00:17:41,393 --> 00:17:45,397
WELL AS AMINO ACIDS, XENOBIOTICS

467
00:17:45,464 --> 00:17:46,965
WHICH INCLUDES FOOD AND

468
00:17:47,032 --> 00:17:47,833
PLANT-DERIVED COMPOUNDS,

469
00:17:47,900 --> 00:17:50,135
COFACTORS AND VITAMINS, A

470
00:17:50,202 --> 00:17:51,870
CARBOHYDRATE AND A NUCLEOTIDE.

471
00:17:51,937 --> 00:17:54,940
HERE ARE THE RESULTS FROM THE

472
00:17:55,007 --> 00:17:56,909
PARTIALLY SQUARED DISKRIM NAT

473
00:17:56,975 --> 00:17:59,878
ANALYSIS, AND WE SEE VERY CLEAR

474
00:17:59,945 --> 00:18:00,946
SEPARATION IN THE PLOTS FOR THE

475
00:18:01,013 --> 00:18:05,350
DASH AND THE CONTROL DIET, WITH

476
00:18:05,417 --> 00:18:06,518
THE FIRST TWO COMPONENTS

477
00:18:06,585 --> 00:18:07,753
EXPLAINING A LARGE PROPORTION OF

478
00:18:07,820 --> 00:18:09,488
THE VARIABILITY, 29.4 FOR

479
00:18:09,555 --> 00:18:12,424
COMPONENT 1 AND 12.6 FOR

480
00:18:12,491 --> 00:18:12,758
COMPONENT 2.

481
00:18:12,825 --> 00:18:16,061
AND FROM THIS ANALYSIS, WE WERE

482
00:18:16,128 --> 00:18:19,665
ABLE TO IDENTIFY VARIABLE

483
00:18:19,731 --> 00:18:22,167
IMPORTANCE AND PROJECTION

484
00:18:22,234 --> 00:18:25,471
SCORES, WHICH CHARACTERIZES THE

485
00:18:25,537 --> 00:18:27,439
MOST INFLUENTIAL METABOLITES FOR

486
00:18:27,506 --> 00:18:29,608
DISCRIMINATING BETWEEN THE TWO

487
00:18:29,675 --> 00:18:31,276
DIETS IN THIS STUDY, AND WE

488
00:18:31,343 --> 00:18:32,678
FOUND SIX METABOLITES IDENTIFIED

489
00:18:32,744 --> 00:18:36,415
HERE THAT WERE HIGHER ON THE

490
00:18:36,482 --> 00:18:37,282
DASH DIET COMAIRED TO THE

491
00:18:37,349 --> 00:18:40,219
CONTROL DIET AND THEN FOR

492
00:18:40,285 --> 00:18:40,886
METABOLITES HIGHER ON THE

493
00:18:40,953 --> 00:18:45,791
CONTROL DIET THAN THE DASH DIET.

494
00:18:45,858 --> 00:18:47,226
IN A RANDOMLY SELECTED

495
00:18:47,292 --> 00:18:49,761
TWO-THIRDS SAMPLE, THESE

496
00:18:49,828 --> 00:18:52,364
METABOLITES WERE VERY IMPORTANT

497
00:18:52,431 --> 00:18:54,766
IN PREDICTING THE DASH VERSUS

498
00:18:54,833 --> 00:18:57,069
THE CONTROL DIET, AND SIMILARLY

499
00:18:57,135 --> 00:18:59,371
FOR THE REMAINING ONE-THIRD

500
00:18:59,438 --> 00:19:03,842
SAMPLE.

501
00:19:03,909 --> 00:19:10,182
AND SO THESE TOP 10 METABOLITES

502
00:19:10,249 --> 00:19:11,183
VERY MUCH REPRESENT THE KEY

503
00:19:11,250 --> 00:19:20,359
FACTORS OF THE DASH DIET, SO

504
00:19:20,425 --> 00:19:23,095
CHIRO-INOSITOL, STRUCTURALLY

505
00:19:23,161 --> 00:19:25,297
RELATED TO FRUITS, BEANS,

506
00:19:25,364 --> 00:19:29,768
GRAINS, NUTS AND SEEDS, AND N

507
00:19:29,835 --> 00:19:33,171
METHYL PROLINE, CITRUS FRUIT AND

508
00:19:33,238 --> 00:19:34,573
JUICE.

509
00:19:34,640 --> 00:19:37,409
TRYPTOPHAN BETAINE, LEN TILS AND

510
00:19:37,476 --> 00:19:41,813
LEGUMES.

511
00:19:41,880 --> 00:19:42,781
GLUCOPYRANOSIDE, CAREER YELLS

512
00:19:42,848 --> 00:19:45,250
AND CEREAL PRODUCTS AS WELL AS

513
00:19:45,317 --> 00:19:51,657
TOTAL FRUIT INTAKE, B

514
00:19:51,723 --> 00:19:56,895
CRYPTOXANTHIN, AND THE LAST FOUR

515
00:19:56,962 --> 00:20:02,367
WERE -- THEOBROMINE,

516
00:20:02,434 --> 00:20:06,939
7 METHYLXANTHINE,

517
00:20:07,005 --> 00:20:08,507
3 METHYLXANTHINE, 7 METHYL

518
00:20:08,574 --> 00:20:12,010
LURATE, CAFFE KA WHICH REPRESENT

519
00:20:12,077 --> 00:20:12,844
CHOCOLATE HAVE BEEN ASSOCIATED

520
00:20:12,911 --> 00:20:14,413
WITH LOWER DIET QAWLTD RELATED

521
00:20:14,479 --> 00:20:15,514
TO COFFEE AND DESSERTS.

522
00:20:15,581 --> 00:20:16,915
I'M GOING TO TRANSITION INTO THE

523
00:20:16,982 --> 00:20:19,651
SECOND STUDY WITH IS URINE

524
00:20:19,718 --> 00:20:23,255
METABOLOMICS OF THE DASH TRIAL

525
00:20:23,322 --> 00:20:24,656
AND THE SECOND DASH SODIUM

526
00:20:24,723 --> 00:20:24,856
TRIAL.

527
00:20:24,923 --> 00:20:26,091
HERE'S THE OVERALL DESIGN IN

528
00:20:26,158 --> 00:20:27,292
WHICH PARTICIPANTS FOLLOWED A

529
00:20:27,359 --> 00:20:28,627
CONTROL DIET AND THEN WERE

530
00:20:28,694 --> 00:20:30,162
RANDOMIZED TO EITHER THE DASH OR

531
00:20:30,228 --> 00:20:34,199
THE CONTROL DIET AND THEN IN A

532
00:20:34,266 --> 00:20:37,202
CROSSOVER DESIGN RECEIVED ONE OF

533
00:20:37,269 --> 00:20:40,105
THREE DIFFERENT SODIUM

534
00:20:40,172 --> 00:20:40,739
INTERVENTIONS.

535
00:20:40,806 --> 00:20:42,507
FOR THIS ANALYSIS, I WAS

536
00:20:42,574 --> 00:20:46,678
PARTICULARLY INTERESTED IN THE

537
00:20:46,745 --> 00:20:47,946
DASH DIET COMPARED TO THE

538
00:20:48,013 --> 00:20:49,414
CONTROL DIET.

539
00:20:49,481 --> 00:20:52,250
BUT WE SELECTED DIFFERENT SODIUM

540
00:20:52,317 --> 00:20:53,251
INTERVENTIONS, SO THE FIRST

541
00:20:53,318 --> 00:20:56,855
COMPARISON IS THE DASH HIGH

542
00:20:56,922 --> 00:20:58,490
SODIUM, VERSUS THE CONTROL HIGH

543
00:20:58,557 --> 00:20:58,824
SODIUM.

544
00:20:58,890 --> 00:21:00,892
SO THE ONLY DIFFERENCE HERE IS

545
00:21:00,959 --> 00:21:02,995
THE DASH DIET, AND THEN THE DASH

546
00:21:03,061 --> 00:21:04,396
LOW SODIUM VERSUS THE CONTROL

547
00:21:04,463 --> 00:21:07,699
HIGH SODIUM TO SEE A MAXIMAL

548
00:21:07,766 --> 00:21:10,969
CONTRAST BETWEEN THE DASH DIET,

549
00:21:11,036 --> 00:21:13,372
WHICH IS CURRENTLY RECOMMENDED

550
00:21:13,438 --> 00:21:16,008
AS THE LOW SODIUM DIET VERSUS A

551
00:21:16,074 --> 00:21:16,975
TYPICAL AMERICAN DIET WHICH IS

552
00:21:17,042 --> 00:21:18,944
HIGHER IN SODIUM.

553
00:21:19,011 --> 00:21:21,013
AND WE USED URINE THAT'S

554
00:21:21,079 --> 00:21:23,315
COLLECTED AT THE END OF EACH

555
00:21:23,382 --> 00:21:25,517
INTERVENTION PERIOD AND OF THE

556
00:21:25,584 --> 00:21:28,787
1425 METABOLITES IDENTIFIED

557
00:21:28,854 --> 00:21:30,322
FOCUSED ON THE KNOWN METABOLITES

558
00:21:30,389 --> 00:21:34,026
WHICH WERE 938.

559
00:21:34,092 --> 00:21:35,961
AND HERE IN THIS PLOT ON THE

560
00:21:36,028 --> 00:21:40,198
RIGHT-HAND SIDE, WE SEE THE

561
00:21:40,265 --> 00:21:42,367
DISTRIBUTION OF THE KNOWN

562
00:21:42,434 --> 00:21:45,804
METABOLITES THAT WERE DETEACTED

563
00:21:45,871 --> 00:21:49,374
IDETECTEDIN THE PLATFORM BY PAT.

564
00:21:49,441 --> 00:21:51,109
THEN FOR DASH HIGH SODIUM, THESE

565
00:21:51,176 --> 00:21:52,744
ARE THE METABOLITES THAT WERE

566
00:21:52,811 --> 00:21:54,179
SIGNIFICANTLY DIFFERENT FROM THE

567
00:21:54,246 --> 00:21:56,114
CONTROL DIET, AND SIMILARLY FOR

568
00:21:56,181 --> 00:21:57,783
THE DASH LOW SODIUM, THESE ARE

569
00:21:57,849 --> 00:21:59,317
THE METABOLITES THAT WERE

570
00:21:59,384 --> 00:21:59,951
SIGNIFICANTLY DIFFERENT BETWEEN

571
00:22:00,018 --> 00:22:01,687
THE DASH LOW SODIUM DIET AND THE

572
00:22:01,753 --> 00:22:07,059
CONTROL DIET.

573
00:22:07,125 --> 00:22:08,393
SO THE DISTRIBUTION OF THE

574
00:22:08,460 --> 00:22:12,764
CATEGORIES WAS SIMILAR ACROSS

575
00:22:12,831 --> 00:22:14,366
THE COMPARISONS AND THE MOST

576
00:22:14,433 --> 00:22:18,670
COMMON METABOLITE CATEGORY WAS

577
00:22:18,737 --> 00:22:20,906
XENOBIOTICS, SO THESE FOOD

578
00:22:20,972 --> 00:22:21,406
DERIVED COMPOUNDS.

579
00:22:21,473 --> 00:22:24,576
AND HERE'S THE VOLCANO PLOT,

580
00:22:24,643 --> 00:22:27,746
SHOWING THE SIGNIFICANT

581
00:22:27,813 --> 00:22:30,916
METABOLITES THAT WERE DIFFERENT,

582
00:22:30,982 --> 00:22:33,318
SO THE SIGNIFICANCE IS

583
00:22:33,385 --> 00:22:35,620
IDENTIFIED AS THOUGHTS THAT

584
00:22:35,687 --> 00:22:37,289
APPEAR -- DOTS THAT APPEAR ABOVE

585
00:22:37,355 --> 00:22:40,859
THE RED DASHED LINE FOR THE DASH

586
00:22:40,926 --> 00:22:43,061
HIGH SODIUM DIET ON PANEL A ON

587
00:22:43,128 --> 00:22:45,697
THE LEFT AND FOR THE DASH LOW

588
00:22:45,764 --> 00:22:46,765
SODIUM DIET IN PANEL B ON THE

589
00:22:46,832 --> 00:22:47,099
RIGHT.

590
00:22:47,165 --> 00:22:49,634
SO WE SEE -- AND THEN COLORS

591
00:22:49,701 --> 00:22:50,702
REPRESENTING EACH OF THE

592
00:22:50,769 --> 00:22:53,672
PATHWAYS.

593
00:22:53,739 --> 00:22:58,276
SO WE SEE LOTS OF XENOBIOTICS

594
00:22:58,343 --> 00:22:59,578
HERE ON BOTH SIDES WITH

595
00:22:59,644 --> 00:23:01,446
POSITIVELY AND NEGATIVELY

596
00:23:01,513 --> 00:23:05,250
ASSOCIATED WITH DASH DIET.

597
00:23:05,317 --> 00:23:07,319
AND HERE ARE THE SCORES PLOTS

598
00:23:07,385 --> 00:23:09,121
FROM THE PARTIALLY SQUARED

599
00:23:09,187 --> 00:23:11,156
DISKRIM NAT ANALYSIS AGAIN SHOWS

600
00:23:11,223 --> 00:23:12,424
VERY CLEAR DIFFERENTIATION

601
00:23:12,491 --> 00:23:13,992
BETWEEN THE DASH DIET AND THE

602
00:23:14,059 --> 00:23:14,993
CONTROL DIET FOR BOTH

603
00:23:15,060 --> 00:23:18,396
COMPARISONS.

604
00:23:18,463 --> 00:23:21,333
AND BASED ON THE VARIABLE

605
00:23:21,399 --> 00:23:22,701
IMPORTANCE AND PROJECTION SCORES

606
00:23:22,768 --> 00:23:24,069
WE'RE LISTING THE TOP 10

607
00:23:24,136 --> 00:23:25,070
METABOLITES IN THE DASH SODIUM

608
00:23:25,137 --> 00:23:27,239
STUDY FOR THE DASH HIGH SODIUM

609
00:23:27,305 --> 00:23:29,875
CONTRAST AND THE DASH LOW SODIUM

610
00:23:29,941 --> 00:23:31,409
CONTRAST, AND THE RESULTS HERE

611
00:23:31,476 --> 00:23:33,111
ARE VERY SIMILAR ACROSS THE TWO

612
00:23:33,178 --> 00:23:35,981
CONTRASTS.

613
00:23:36,047 --> 00:23:38,083
WITH THREE OF THE METABOLITES

614
00:23:38,150 --> 00:23:41,920
AND METHYL PROLINE -- BEING ALSO

615
00:23:41,987 --> 00:23:43,522
AMONG THE TOP 10 IN THE DASH

616
00:23:43,588 --> 00:23:44,289
TRIAL, WHICH I'VE PRESENTED

617
00:23:44,356 --> 00:23:46,258
BEFORE.

618
00:23:46,324 --> 00:23:48,593
AND HERE THE TOP 10 MOST

619
00:23:48,660 --> 00:23:53,165
IMPORTANT METABOLITES WERE

620
00:23:53,231 --> 00:23:54,900
EXCEEDINGLY INFLUENTIAL IN

621
00:23:54,966 --> 00:23:56,001
PREDICTING THE INTERVENTION OF

622
00:23:56,067 --> 00:23:57,335
THE DASH DIET.

623
00:23:57,402 --> 00:24:00,071
IN BOTH TESTING AND VALIDATION

624
00:24:00,138 --> 00:24:01,673
SAMPLES.

625
00:24:01,740 --> 00:24:03,975
SO IN SUMMARY, IN THIS FEEDING

626
00:24:04,042 --> 00:24:05,844
TRIAL OF ADULTS WITH HIGHER THAN

627
00:24:05,911 --> 00:24:06,745
OPTIMAL BLOOD PRESSURE, WE

628
00:24:06,812 --> 00:24:07,813
IDENTIFIED MANY METABOLITES

629
00:24:07,879 --> 00:24:09,247
ASSOCIATED WITH THE DASH DIET

630
00:24:09,314 --> 00:24:11,550
AFTER ADJUSTING FOR PARTICIPANT

631
00:24:11,616 --> 00:24:12,317
CHARACTERISTICS AND ACCOUNTING

632
00:24:12,384 --> 00:24:15,487
FOR MULTIPLE COMPARISONS.

633
00:24:15,554 --> 00:24:16,354
AND SEVERAL OF THESE

634
00:24:16,421 --> 00:24:17,222
ASSOCIATIONS WERE REPLICATED

635
00:24:17,289 --> 00:24:18,557
COMPARED TO THE RESULTS I SHOWED

636
00:24:18,623 --> 00:24:22,928
BEFORE IN THE DASH TRIAL.

637
00:24:22,994 --> 00:24:24,462
THESE THREE METABOLITES AND

638
00:24:24,529 --> 00:24:28,166
METHYL PROLINE, TRYPTOPHAN -- IN

639
00:24:28,233 --> 00:24:31,436
THE TOP 10, AND THEN SIX TOTAL

640
00:24:31,503 --> 00:24:33,972
METABOLITES, THREE ADDITIONAL

641
00:24:34,039 --> 00:24:36,474
METABOLITES, WERE REPLICATED IN

642
00:24:36,541 --> 00:24:41,847
THE TOP 15 FOR DASH SODIUM.

643
00:24:41,913 --> 00:24:45,350
WITH THE EXCEPTION OF

644
00:24:45,417 --> 00:24:49,588
GLUCOPYRANOSIDE AND B CRYPTO SAN

645
00:24:49,654 --> 00:24:51,022
THIN, THEY WERE ENTIRELY

646
00:24:51,089 --> 00:24:51,990
REPLICATED IN DASH SODIUM.

647
00:24:52,057 --> 00:24:54,659
OF THE 97 METABOLITES THAT WERE

648
00:24:54,726 --> 00:24:59,331
SIGNIFICANTLY DIFFERENT IN DASH,

649
00:24:59,397 --> 00:25:01,199
17 AND 18 IN DASH HIGH SODIUM

650
00:25:01,266 --> 00:25:03,268
AND DASH LOW SODIUM WERE ALSO

651
00:25:03,335 --> 00:25:04,903
SIGNIFICANT AND SIMILAR IN

652
00:25:04,970 --> 00:25:07,005
MAGNITUDE AS WELL AS IN

653
00:25:07,072 --> 00:25:09,074
DIRECTION.

654
00:25:09,140 --> 00:25:10,575
SO WITH THE FIRST STUDY BEING

655
00:25:10,642 --> 00:25:11,576
CONDUCTED IN SERUM METABOLITES

656
00:25:11,643 --> 00:25:14,546
AND THE SECOND IN URINE, THIS

657
00:25:14,613 --> 00:25:18,383
PROVIDES SOME SUPPORT THAT THESE

658
00:25:18,450 --> 00:25:20,252
MATRICES ARE POTENTIALLY

659
00:25:20,318 --> 00:25:22,187
INTERCHANGEABLE FOR

660
00:25:22,254 --> 00:25:23,822
CHARACTERIZING THE NUTRITION

661
00:25:23,889 --> 00:25:24,289
METABALOME.

662
00:25:24,356 --> 00:25:28,326
NOW BACK TO THE ARIC STUDY.

663
00:25:28,393 --> 00:25:32,697
MOVING FROM A FEEDING TRIAL,

664
00:25:32,764 --> 00:25:34,332
VERY WELL CONTROLLED ENVIRONMENT

665
00:25:34,399 --> 00:25:37,269
TO A FREE LIVING POPULATION.

666
00:25:37,335 --> 00:25:39,905
AGAIN, WE SEE THAT AT BASELINE,

667
00:25:39,971 --> 00:25:43,308
VISIT 1, WE HAVE A NUMBER OF

668
00:25:43,375 --> 00:25:45,710
PARTICIPANTS WHO COMPLETED THE

669
00:25:45,777 --> 00:25:46,611
FOOD FREQUENCY QUESTIONNAIRE.

670
00:25:46,678 --> 00:25:49,547
AND IN TERMS OF WHO WAS SELECTED

671
00:25:49,614 --> 00:25:50,749
FOR METABOLOMICS PROFILING,

672
00:25:50,815 --> 00:25:52,417
THERE WERE TWO SEPARATE, THE

673
00:25:52,484 --> 00:25:53,818
FIRST ONE CONSISTED OF A RANDOM

674
00:25:53,885 --> 00:25:56,321
SAMPLE OF ARIC PARTICIPANTS, AND

675
00:25:56,388 --> 00:25:57,856
THE SECOND SUBGROUP CONSISTED OF

676
00:25:57,923 --> 00:26:00,158
PARTICIPANTS WITH SEQUENCING

677
00:26:00,225 --> 00:26:01,693
DATA.

678
00:26:01,760 --> 00:26:03,795
AND THE OVERLAP IN TERMS OF THE

679
00:26:03,862 --> 00:26:06,698
TWO METABOLOMICS PROFILING IN

680
00:26:06,765 --> 00:26:09,334
THE TWO SUBGROUPS WAS A TOTAL OF

681
00:26:09,401 --> 00:26:11,303
374 METABOLITES.

682
00:26:11,369 --> 00:26:15,473
SO THIS ANALYSIS USES SUBGROUP P

683
00:26:15,540 --> 00:26:18,610
2 FOR REPLICATION OF AGAIN THE

684
00:26:18,677 --> 00:26:21,379
37 OVERLAPPING METABOLITES, AND

685
00:26:21,446 --> 00:26:24,883
WE USE MULTIVARIABLE LINEAR

686
00:26:24,950 --> 00:26:26,618
REGRESSION TO EXAMINE

687
00:26:26,685 --> 00:26:27,485
ASSOCIATIONS BETWEEN DIETARY

688
00:26:27,552 --> 00:26:29,554
PATTERNS AND INDIVIDUAL SERUM

689
00:26:29,621 --> 00:26:31,856
METABOLITES ADJUSTING FOR

690
00:26:31,923 --> 00:26:32,524
PARTICIPANT CHARACTERISTICS AND

691
00:26:32,590 --> 00:26:33,825
WE ADJUSTED FOR MULTIPLE

692
00:26:33,892 --> 00:26:36,027
COMPARISONS USING THE BON

693
00:26:36,094 --> 00:26:38,530
FERRONI METHOD AND THEN META

694
00:26:38,596 --> 00:26:39,731
ANALYZED SIGNIFICANT METABOLITES

695
00:26:39,798 --> 00:26:41,833
ACROSS THE TWO SUBGROUPS USING

696
00:26:41,900 --> 00:26:43,034
FIXED EFFECTS MODELS AND THEN

697
00:26:43,101 --> 00:26:45,337
TESTED FOR PREDICTION WITH THE

698
00:26:45,403 --> 00:26:46,738
ADDITION OF SIGNIFICANT

699
00:26:46,805 --> 00:26:47,605
METABOLITES BEYOND PARTICIPANT

700
00:26:47,672 --> 00:26:47,973
CHARACTERISTICS.

701
00:26:48,039 --> 00:26:50,909
SO HERE WE SEE THAT 14

702
00:26:50,976 --> 00:26:52,677
METABOLITES WERE SIGNIFICANTLY

703
00:26:52,744 --> 00:26:53,912
ASSOCIATED WITH THE DASH DIET IN

704
00:26:53,979 --> 00:26:56,614
THE ARIC STUDY IN SUBGROUP 1 AS

705
00:26:56,681 --> 00:26:59,451
WELL AS SUBGROUP 2 AND THEY'RE

706
00:26:59,517 --> 00:27:03,588
LISTED HERE:  AMINO ACIDS,

707
00:27:03,655 --> 00:27:04,923
CARBOHYDRATES, COFACTORS AND

708
00:27:04,990 --> 00:27:08,059
VITAMINS, LIPIDS, AND A COUPLE

709
00:27:08,126 --> 00:27:08,393
XENOBIOTICS.

710
00:27:08,460 --> 00:27:09,627
FIVE OF THESE WERE ALSO

711
00:27:09,694 --> 00:27:13,331
SIGNIFICANT IN THE DASH TRIAL,

712
00:27:13,398 --> 00:27:21,539
SO N METHYL PRO NEEN, N ACETYL

713
00:27:21,606 --> 00:27:26,578
ORNITHINE -- ADDITIONAL

714
00:27:26,644 --> 00:27:27,645
METABOLITES WERE ALSO

715
00:27:27,712 --> 00:27:30,081
SIGNIFICANT IN THE DASH SODIUM

716
00:27:30,148 --> 00:27:31,916
TRIAL.

717
00:27:31,983 --> 00:27:38,490
SO N METHYL -- IF YOU'LL

718
00:27:38,556 --> 00:27:40,225
REMEMBER FROM THE DESIGN SLIDE,

719
00:27:40,291 --> 00:27:41,993
THERE WERE MORE METABOLITES

720
00:27:42,060 --> 00:27:44,195
IDENTIFIED IN SUBGROUP 2, SO

721
00:27:44,262 --> 00:27:45,930
THERE WERE ADDITIONAL 20

722
00:27:45,997 --> 00:27:46,598
METABOLITES THAT WERE ASSOCIATED

723
00:27:46,664 --> 00:27:49,000
WITH THE DASH DIET, ONLY IN THIS

724
00:27:49,067 --> 00:27:51,169
SUBGROUP.

725
00:27:51,236 --> 00:27:54,105
AND MANY OF THOSE WERE

726
00:27:54,172 --> 00:27:55,540
XENOBIOTICS AS WELL AS AMINO

727
00:27:55,607 --> 00:27:57,942
ACIDS, CARBOHYDRATES, COFACTORS

728
00:27:58,009 --> 00:28:00,445
AND VITAMINS AND LIPIDS.

729
00:28:00,512 --> 00:28:02,647
SO OVERALL -- SO THIS ANALYSIS

730
00:28:02,714 --> 00:28:04,949
WAS STUDYING THE OVERALL DASH

731
00:28:05,016 --> 00:28:06,684
DIET, BUT THEN WITHIN THE ARIC

732
00:28:06,751 --> 00:28:09,654
STUDY, WE HAVE THE BENEFIT OF

733
00:28:09,721 --> 00:28:11,089
HAVING MORE DETAILED DIETARY

734
00:28:11,156 --> 00:28:13,792
INFORMATION, SO WE LOOKED AT

735
00:28:13,858 --> 00:28:14,793
FOOD GROUPS THAT CONTRIBUTE TO

736
00:28:14,859 --> 00:28:18,196
THE DASH DIET SCORE, AND WE

737
00:28:18,263 --> 00:28:19,597
INVESTIGATED OF THOSE

738
00:28:19,664 --> 00:28:20,465
METABOLITES THAT ARE

739
00:28:20,532 --> 00:28:21,066
SIGNIFICANTLY ASSOCIATED WITH

740
00:28:21,132 --> 00:28:24,536
THE DASH DIET, WHICH FOOD

741
00:28:24,602 --> 00:28:26,071
COMPONENTS OF THE OVERALL DASH

742
00:28:26,137 --> 00:28:28,907
DIET SCORE ARE THEY ASSOCIATED

743
00:28:28,973 --> 00:28:32,510
WITH?

744
00:28:32,577 --> 00:28:41,386
SO YOU SEE N METHYLPROLINE ALSO

745
00:28:41,453 --> 00:28:44,556
ASSOCIATED WITH FRUITS.

746
00:28:44,622 --> 00:28:47,625
AND YOU CAN GO DOWN THE LIST.

747
00:28:47,692 --> 00:28:52,330
BUT IT ALIGNS WELL WITH THE --

748
00:28:52,397 --> 00:28:53,398
THE METABOLITES ASSOCIATED WITH

749
00:28:53,465 --> 00:28:55,266
THE DASH DIET ALIGN WELL WITH

750
00:28:55,333 --> 00:28:57,469
THE KEY COMPONENTS OF THE DASH

751
00:28:57,535 --> 00:28:59,003
DIET SCORE AND IT HELPS US

752
00:28:59,070 --> 00:29:02,040
INTERPRET THESE FINDINGS.

753
00:29:02,107 --> 00:29:04,042
IN TERMS OF WHICH SPECIFIC FOOD

754
00:29:04,109 --> 00:29:06,211
GROUPS THEY REPRESENT.

755
00:29:06,277 --> 00:29:07,645
AND THEN WE SEE THAT THE

756
00:29:07,712 --> 00:29:13,218
ADDITION OF THE METABOLITES

757
00:29:13,284 --> 00:29:14,986
SIGNIFICANTLY IMPROVE PREDICTION

758
00:29:15,053 --> 00:29:16,588
OF HIGH ADHERENCE TO THE DASH

759
00:29:16,654 --> 00:29:18,022
DIET BEYOND THE PARTICIPANT

760
00:29:18,089 --> 00:29:19,891
CHARACTERISTICS IN BOTH SUBGROUP

761
00:29:19,958 --> 00:29:20,658
1 AND SUBGROUP 2.

762
00:29:20,725 --> 00:29:22,660
SO IN SUMMARY, WE IDENTIFIED 14

763
00:29:22,727 --> 00:29:23,695
METABOLITES ASSOCIATED WITH DASH

764
00:29:23,761 --> 00:29:25,130
DIET IN TWO DIFFERENT SUBGROUPS

765
00:29:25,196 --> 00:29:27,532
WITHIN THE ARIC STUDY, AND

766
00:29:27,599 --> 00:29:28,967
ANOTHER 20 METABOLITES THAT

767
00:29:29,033 --> 00:29:30,268
SERVE AS CANDIDATE BIOMARKERS

768
00:29:30,335 --> 00:29:31,769
THAT WERE ONLY AVAILABLE IN THAT

769
00:29:31,836 --> 00:29:34,539
SECOND SUBGROUP.

770
00:29:34,606 --> 00:29:38,076
AND THEN OF THESE FINDINGS,

771
00:29:38,143 --> 00:29:39,677
THERE WAS REPLICATION ACROSS

772
00:29:39,744 --> 00:29:41,312
BOTH THE TWO SUBSAMPLES WITHIN

773
00:29:41,379 --> 00:29:43,081
THE ARIC STUDY AS WELL AS THE

774
00:29:43,148 --> 00:29:44,816
DASH TRIAL AND THE DASH SODIUM

775
00:29:44,883 --> 00:29:49,387
TRIAL, SO N METHYL PROLINE, 3

776
00:29:49,454 --> 00:29:52,257
3-4 HYDROXYPHENYL ACETATE, N

777
00:29:52,323 --> 00:29:54,859
ACETYL LORN THEEN, PEER

778
00:29:54,926 --> 00:29:59,030
DOCKSITE, GAMMA -- THESE

779
00:29:59,097 --> 00:29:59,931
METABOLITES WERE ASSOCIATED WITH

780
00:29:59,998 --> 00:30:02,200
FOODS INCLUDING FRUIT,

781
00:30:02,267 --> 00:30:03,067
VEGETABLES, WHOLE GRAINS, NUTS

782
00:30:03,134 --> 00:30:06,704
AND LEGUMES, DAIRY, RED MEAT,

783
00:30:06,771 --> 00:30:08,439
SUGAR SWEETENED BERCHLS AND

784
00:30:08,506 --> 00:30:10,074
SODIUM, SO ALL THE KEY

785
00:30:10,141 --> 00:30:10,375
COMPONENTS.

786
00:30:10,441 --> 00:30:12,377
AND THEN THESE METABOLITES

787
00:30:12,443 --> 00:30:13,912
SIGNIFICANTLY IMPROVED ADHERENCE

788
00:30:13,978 --> 00:30:14,913
TO THE DASH DIET.

789
00:30:14,979 --> 00:30:16,414
SO NOW COMING BACK AGAIN TO THE

790
00:30:16,481 --> 00:30:20,451
CRIC STUDY, THIS COHORT STUDY OF

791
00:30:20,518 --> 00:30:21,786
PARTICIPANTS LIVING WITH KIDNEY

792
00:30:21,853 --> 00:30:22,220
DISEASE.

793
00:30:22,287 --> 00:30:26,558
SO AS BASELINE, WHICH WAS IN

794
00:30:26,624 --> 00:30:30,862
2003 TO 2008, 3,930 PARTICIPANTS

795
00:30:30,929 --> 00:30:34,766
WERE ENROLLED, WIDE RANGE OF

796
00:30:34,832 --> 00:30:35,400
AGES, 21 TO 74 AND A WIDE RANGE

797
00:30:35,466 --> 00:30:38,303
OF KIDNEY FUNCTIONS, 20 TO 70.

798
00:30:38,369 --> 00:30:41,906
ONLY A SUBSET OF THESE HAD A

799
00:30:41,973 --> 00:30:43,541
DIET HISTORY QUESTIONNAIRE THAT

800
00:30:43,608 --> 00:30:48,046
WAS ADMINISTERED AND

801
00:30:48,112 --> 00:30:50,548
METABOLOMICS DATA THAT WAS

802
00:30:50,615 --> 00:30:51,549
AVAILABLE CONDUCTED IN PLASMA.

803
00:30:51,616 --> 00:30:53,952
IN THIS STUDY, THE METABALOME

804
00:30:54,018 --> 00:30:55,053
PROFILING WAS CONDUCTED AT THE

805
00:30:55,119 --> 00:30:57,655
BROAD INSTITUTE IN BOSTON, AND

806
00:30:57,722 --> 00:31:00,725
YOU CAN SEE THAT THE PLATFORM IS

807
00:31:00,792 --> 00:31:03,695
QUITE DIFFERENT FROM THE DATA

808
00:31:03,761 --> 00:31:06,531
WHICH WAS GENERATED FROM THE

809
00:31:06,598 --> 00:31:07,198
BROAD INSTITUTE.

810
00:31:07,265 --> 00:31:08,499
WE TRY TO CLASSIFY THE

811
00:31:08,566 --> 00:31:09,934
METABOLITES IN A SIMILAR FASHION

812
00:31:10,001 --> 00:31:13,438
AS IN THE PREVIOUS ANALYSIS.

813
00:31:13,504 --> 00:31:16,808
AND WE SEE THAT THIS PLATFORM

814
00:31:16,874 --> 00:31:19,310
SPECIFICALLY HAS A LARGE

815
00:31:19,377 --> 00:31:21,512
REPRESENTATION OF LIPIDS AND

816
00:31:21,579 --> 00:31:24,282
LIPID SUBCLASSES.

817
00:31:24,349 --> 00:31:28,186
SO IN TERMS OF THE ANALYSIS, WE

818
00:31:28,253 --> 00:31:29,287
RAN MULTIVARIABLE LINEAR

819
00:31:29,354 --> 00:31:31,155
REGRESSION MODELS TO EXAMINE

820
00:31:31,222 --> 00:31:33,891
ASSOCIATIONS BETWEEN DASH DIET

821
00:31:33,958 --> 00:31:35,560
SCORES AND INDIVIDUAL PLASMA

822
00:31:35,627 --> 00:31:37,395
METABOLITES, ADJUSTING FOR

823
00:31:37,462 --> 00:31:38,029
SOCIODEM GRARVEG

824
00:31:38,096 --> 00:31:38,796
CHARACTERISTICS, HEALTH

825
00:31:38,863 --> 00:31:41,532
BEHAVIORS AND CLINICAL FACTORS

826
00:31:41,599 --> 00:31:43,301
ADJUSTING FOR MULTIPLE FACTORS

827
00:31:43,368 --> 00:31:47,872
USING THE BONFERRONI METHODS.

828
00:31:47,939 --> 00:31:49,741
THEN WE ALSO USED PRINCIPAL

829
00:31:49,807 --> 00:31:51,542
COMPONENTS ANALYSIS TO LOOK AT

830
00:31:51,609 --> 00:31:53,678
OF THE METABOLITES WHICH WERE

831
00:31:53,745 --> 00:31:54,279
SIGNIFICANTLY ASSOCIATED WITH

832
00:31:54,345 --> 00:31:58,283
THE DASH DIET, HOW WERE THESE

833
00:31:58,349 --> 00:31:59,250
FORM IN PRINCIPLE COMPONENTS,

834
00:31:59,317 --> 00:32:03,187
HOW DO THEY FALL TOGETHER IN

835
00:32:03,254 --> 00:32:04,055
PRINCIPAL COMPONENTS AND WHICH

836
00:32:04,122 --> 00:32:05,290
FOOD COMPONENTS ARE THEY RELATED

837
00:32:05,356 --> 00:32:06,357
TO OF THE COMPONENTS REPRESENTED

838
00:32:06,424 --> 00:32:09,427
WITHIN THE DASH DIET?

839
00:32:09,494 --> 00:32:11,496
AND WE RETAINED FIVE COMPONENTS

840
00:32:11,562 --> 00:32:14,565
FOR THE DASH DIET WHICH TOGETHER

841
00:32:14,632 --> 00:32:21,005
EXPLAINED 64% OF THE VARIANTS.

842
00:32:21,072 --> 00:32:21,939
VARIANCE.

843
00:32:22,006 --> 00:32:22,573
HERE IN THE GRAPH ON THE

844
00:32:22,640 --> 00:32:24,208
RIGHT-HAND SIDE, WE CAN SEE A

845
00:32:24,275 --> 00:32:25,610
SIMILAR PICTURE AS WHAT WE SAW

846
00:32:25,677 --> 00:32:27,478
BEFORE, BUT AGAIN, MANY MORE

847
00:32:27,545 --> 00:32:30,114
SUBCLASSES OF LIPIDS IN THE

848
00:32:30,181 --> 00:32:31,749
IDENTIFIED METABOLITES BY THE

849
00:32:31,816 --> 00:32:33,117
PLATFORM, AND THEN ON THE

850
00:32:33,184 --> 00:32:35,119
LEFT-HAND SIDE, THOSE THAT WERE

851
00:32:35,186 --> 00:32:35,853
SIGNIFICANTLY ASSOCIATED WITH

852
00:32:35,920 --> 00:32:37,422
THE DASH DIET.

853
00:32:37,488 --> 00:32:40,058
AND THERE WERE A TOTAL OF

854
00:32:40,124 --> 00:32:42,126
77 THAT WERE ASSOCIATED WITH THE

855
00:32:42,193 --> 00:32:44,095
DASH DIET, AND THE MAJOR

856
00:32:44,162 --> 00:32:50,668
CATEGORIES HERE ARE

857
00:32:50,735 --> 00:32:51,536
TRIACYLGLYCEROLS IN THE BRIGHT

858
00:32:51,602 --> 00:32:53,971
GREEN COLOR AND THEN PCs,

859
00:32:54,038 --> 00:32:56,107
PEs AND PSs, SO THAT IS IN

860
00:32:56,174 --> 00:32:58,609
THE ROYAL BLUE, WHICH WERE 13%

861
00:32:58,676 --> 00:33:05,750
OF THE SAMPLE AND THEN THE

862
00:33:05,817 --> 00:33:06,951
TRIACYLGLYCEROLS WERE AT 39% OF

863
00:33:07,018 --> 00:33:08,119
THE SIGNIFICANT METABOLITES

864
00:33:08,186 --> 00:33:09,587
ASSOCIATED WITH THE DASH DIET.

865
00:33:09,654 --> 00:33:13,191
AND HERE IS A VOLCANO PLOT OF

866
00:33:13,257 --> 00:33:15,727
THE BETA COEFFICIENTS FOR THE

867
00:33:15,793 --> 00:33:16,461
ASSOCIATION OF THE INDIVIDUAL

868
00:33:16,527 --> 00:33:17,995
METABOLITES WITH THE DASH DIET

869
00:33:18,062 --> 00:33:20,198
ALONG THE X AXIS AND THE

870
00:33:20,264 --> 00:33:22,166
NEGATIVE LOG TIME KEY VALUES

871
00:33:22,233 --> 00:33:23,368
PLOTTED ALONG THE Y AXIS WITH

872
00:33:23,434 --> 00:33:25,536
THE VERTICAL RED DASHED LINE

873
00:33:25,603 --> 00:33:27,071
REPRESENTING THE NULL VALUE OF

874
00:33:27,138 --> 00:33:29,173
ZERO, AND THE HORIZONTAL RED

875
00:33:29,240 --> 00:33:33,010
DASHED LINE REPRESENTING THE

876
00:33:33,077 --> 00:33:34,645
BONFERRONI ADJUSTED THRESHOLD

877
00:33:34,712 --> 00:33:35,513
FOR STATISTICAL SIGNIFICANCE.

878
00:33:35,580 --> 00:33:38,349
SO TO THE LEFT -- UPPER

879
00:33:38,416 --> 00:33:39,650
LEFT-HAND SIDE, WE SEE

880
00:33:39,717 --> 00:33:42,086
METABOLITES THAT WERE INVERSELY

881
00:33:42,153 --> 00:33:44,789
ASSOCIATED WITH THE DASH DIET,

882
00:33:44,856 --> 00:33:51,396
AND MANY OF THESE ARE GREEN SO

883
00:33:51,462 --> 00:34:01,205
TRY ACLGLIGLYCEROLS AND

884
00:34:01,272 --> 00:34:03,074
DIACYLGLYCEROLS IN THE BLUE.

885
00:34:03,141 --> 00:34:04,375
AND THEN THOSE THAT WERE

886
00:34:04,442 --> 00:34:05,476
POSITIVELY ASSOCIATED WE SEE

887
00:34:05,543 --> 00:34:07,111
SOME AMINO ACIDS IN RED AND

888
00:34:07,178 --> 00:34:08,880
CHOLESTEROL ESTERS IN YELLOW.

889
00:34:08,946 --> 00:34:11,048
WE ALSO LOOKED AT -- GIVEN THE

890
00:34:11,115 --> 00:34:12,150
PREDOMINENCE OF LIPIDS IN THIS

891
00:34:12,216 --> 00:34:14,786
PLATFORM, WE DECIDED TO LOOK AT

892
00:34:14,852 --> 00:34:18,589
ASSOCIATIONS WITH ACYL CHAIN

893
00:34:18,656 --> 00:34:19,490
LENGTH AS WELL AS DOUBLE BONDS,

894
00:34:19,557 --> 00:34:20,892
AND WE FOUND THAT AS YOU GO

895
00:34:20,958 --> 00:34:23,127
ALONG THIS X AXIS ON THE

896
00:34:23,194 --> 00:34:27,131
LEFT-HAND SIDE PANEL, YOU HAVE

897
00:34:27,198 --> 00:34:33,271
LONGER CHAIN LENGTH, AND MORE

898
00:34:33,337 --> 00:34:36,007
STRONGLY NEGATIVE BETA

899
00:34:36,073 --> 00:34:37,842
COEFFICIENTS, WHICH IS

900
00:34:37,909 --> 00:34:39,477
INTERPRETED AS LIPIDS WITH

901
00:34:39,544 --> 00:34:41,245
LONGER CHAIN LENGTH WERE

902
00:34:41,312 --> 00:34:42,113
INVERSELY ASSOCIATED WITH THE

903
00:34:42,180 --> 00:34:42,713
DASH DIET.

904
00:34:42,780 --> 00:34:46,417
AND THEN YOU SEE SOME POSITIVE

905
00:34:46,484 --> 00:34:49,387
ASSOCIATIONS FOR SOME OF THESE

906
00:34:49,454 --> 00:34:51,122
VERY LONG CHAINS, SO WE

907
00:34:51,189 --> 00:34:56,127
INTERPRETED THIS AS LONGER TRY

908
00:34:56,194 --> 00:34:56,994
ASELLGLYCEROLS WERE POSITIVELY

909
00:34:57,061 --> 00:34:58,996
ASSOCIATED WITH THE DASH DIET.

910
00:34:59,063 --> 00:35:00,298
THEN IF HE WITH LOOK AT THE

911
00:35:00,364 --> 00:35:01,065
PANEL ON THE RIGHT-HAND SIDE OF

912
00:35:01,132 --> 00:35:03,801
DOUBLE BONDS, WE SEE IN GREEN

913
00:35:03,868 --> 00:35:09,006
THE TRY ACYLGLYCEROLS THAT HAD

914
00:35:09,073 --> 00:35:10,575
SEVEN OR MORE DOUBLE BONDS WERE

915
00:35:10,641 --> 00:35:11,242
POSITIVELY ASSOCIATED WITH THE

916
00:35:11,309 --> 00:35:12,643
DASH DIET.

917
00:35:12,710 --> 00:35:15,713
THESE ARE THE RESULTS OF THE

918
00:35:15,780 --> 00:35:20,651
PRINCIPAL COMPONENTS ANALYSIS.

919
00:35:20,718 --> 00:35:23,488
SO WE'RE PRESENTING THE RESULTS

920
00:35:23,554 --> 00:35:24,155
FROM FOUR PRINCIPAL COMPONENTS,

921
00:35:24,222 --> 00:35:27,225
SO THE FIRST PRINCIPAL COMPONENT

922
00:35:27,291 --> 00:35:31,929
WAS LOW IN DAGs AND TAGs

923
00:35:31,996 --> 00:35:34,665
WITH A FEW DOUBLE BONDS.

924
00:35:34,732 --> 00:35:35,967
THIS WAS POSITIVELY ASSOCIATED

925
00:35:36,033 --> 00:35:37,835
WITH TOTAL VEGETABLES AND NUTS

926
00:35:37,902 --> 00:35:40,338
AND LEGUMES.

927
00:35:40,404 --> 00:35:42,974
THE SECOND PRINCIPAL COMPONENT

928
00:35:43,040 --> 00:35:46,043
WAS LOW AND THIS WAS POSITIVELY

929
00:35:46,110 --> 00:35:47,912
ASSOCIATED WITH RED AND

930
00:35:47,979 --> 00:35:49,413
PROCESSED MEAT, INDICATING LOWER

931
00:35:49,480 --> 00:35:50,948
INTAKE JUST BECAUSE OF HOW THE

932
00:35:51,015 --> 00:35:52,383
SCORING SYSTEM WORKS AND THEN

933
00:35:52,450 --> 00:35:54,118
THE THIRD PRINCIPAL COMPONENT

934
00:35:54,185 --> 00:35:55,219
CONSISTED -- WAS LOW IN

935
00:35:55,286 --> 00:35:57,188
COFACTORS AND VITAMINS, AND THIS

936
00:35:57,255 --> 00:36:00,925
WAS INVERSELY ASSOCIATED WITH

937
00:36:00,992 --> 00:36:03,528
SUGAR SWEETENED BEVERAGES,

938
00:36:03,594 --> 00:36:10,101
REPRESENTING HIGHER INTAKE.

939
00:36:10,167 --> 00:36:12,970
SUGAR SWEETENED BEVERAGES AND

940
00:36:13,037 --> 00:36:17,108
THE PRINCIPAL COMPONENT 4 WAS

941
00:36:17,174 --> 00:36:18,142
LOW -- THAT WAS INVERSELY

942
00:36:18,209 --> 00:36:19,176
ASSOCIATED WITH TOTAL

943
00:36:19,243 --> 00:36:22,246
VEGETABLES.

944
00:36:22,313 --> 00:36:24,782
SO IN SUMMARY WE FOUND IN THE

945
00:36:24,849 --> 00:36:27,552
CRIC STUDY, 77 METABOLITES

946
00:36:27,618 --> 00:36:28,753
ASSOCIATED WITH THE DASH DIET

947
00:36:28,819 --> 00:36:30,254
AND LIPIDS WITH LONGER CHAIN

948
00:36:30,321 --> 00:36:31,355
LENGTH AND MORE DOUBLE BONDS SO

949
00:36:31,422 --> 00:36:33,891
THE MORE UNSATURATED THEY WERE,

950
00:36:33,958 --> 00:36:34,959
THE MORE POSITIVELY ASSOCIATED

951
00:36:35,026 --> 00:36:37,695
WITH THE DASH DIET.

952
00:36:37,762 --> 00:36:40,898
SATURATED FATS, TAGs AND

953
00:36:40,965 --> 00:36:42,099
DAGs WERE INVERSELY ASSOCIATED

954
00:36:42,166 --> 00:36:43,868
WITH HEALTHY FOODS, VEGETABLES

955
00:36:43,935 --> 00:36:45,836
BE NUTS AND LEGUMES, AND

956
00:36:45,903 --> 00:36:48,773
UNSATURATED TAGs, THOSE WITH 7 E

957
00:36:48,839 --> 00:36:49,774
POSITIVELY ASSOCIATED WITH

958
00:36:49,840 --> 00:36:54,645
VEGETABLE INTAKE.

959
00:36:54,712 --> 00:36:56,280
SO COME BACK TO THE SUMMARY SIDE

960
00:36:56,347 --> 00:36:58,249
OF HIGH-THROUGHPUT TECHNOLOGIES

961
00:36:58,316 --> 00:36:59,884
WE'VE TALKED A LOT ABOUT THE

962
00:36:59,951 --> 00:37:01,085
METABOLOMICS OF THE DASH DIET

963
00:37:01,152 --> 00:37:03,120
AND I'M GOING TO TRANSITION NOW

964
00:37:03,187 --> 00:37:04,589
INTO THE PROTEOMICS OF THE DASH

965
00:37:04,655 --> 00:37:06,357
DIE E SO STARTING WITH

966
00:37:06,424 --> 00:37:07,491
PROTEOMICS OF THE DASH DIET IN

967
00:37:07,558 --> 00:37:09,627
THE ARIC STUDY.

968
00:37:09,694 --> 00:37:12,363
THIS WORK WAS LED BY A CURRENT

969
00:37:12,430 --> 00:37:15,967
PH.D. STUDENT OF MINE, SHUTONG

970
00:37:16,033 --> 00:37:18,903
DU, AND IT WAS CONDUCTED IN THE

971
00:37:18,970 --> 00:37:26,577
ARIC STUDY USING A SOMALOGIC

972
00:37:26,644 --> 00:37:29,747
ASSAY THAT USES CHEMICALLY

973
00:37:29,814 --> 00:37:34,118
MODIFIED NUCLEOTIDES, APTAMERS,

974
00:37:34,185 --> 00:37:38,589
AS PROTEIN BINDING REAGENTS.

975
00:37:38,656 --> 00:37:41,125
WE HAVE FOUR THOWN 955 PROTEINS

976
00:37:41,192 --> 00:37:44,295
AVAILABLE FOR ANALYSIS.

977
00:37:44,362 --> 00:37:46,497
AGAIN IN THESE MASS DUPLICATES,

978
00:37:46,564 --> 00:37:50,534
THE CV WAS VERY LOW, AND THE

979
00:37:50,601 --> 00:37:51,736
CORRELATION OR RELIABILITY

980
00:37:51,802 --> 00:37:57,441
COEFFICIENT WAS HIGH.

981
00:37:57,508 --> 00:38:02,046
WHICH MEANS THE ASSAY WORKED

982
00:38:02,113 --> 00:38:03,247
WELL, HIGH PERFORMING ASSAY,

983
00:38:03,314 --> 00:38:04,248
HIGH QUALITY ASSAY.

984
00:38:04,315 --> 00:38:06,017
AND HERE AGAIN IS THE VOLCANO

985
00:38:06,083 --> 00:38:07,952
PLOT WITH THE BETA COEFFICIENT

986
00:38:08,019 --> 00:38:09,153
FOR THE ASSOCIATION OF PROTEINS

987
00:38:09,220 --> 00:38:11,989
WITH THE DASH DIET ALONG THE X

988
00:38:12,056 --> 00:38:17,261
AXIS AND THEN LOG 10P VALUES

989
00:38:17,328 --> 00:38:17,895
REPRESENTING STATISTICAL CYST

990
00:38:17,962 --> 00:38:19,897
CANS ALONG THE Y ACCESS.

991
00:38:19,964 --> 00:38:21,966
WE SEE A TOTAL OF 254 PROTEINS

992
00:38:22,033 --> 00:38:22,967
THAT WERE SIGNIFICANTLY

993
00:38:23,034 --> 00:38:26,771
ASSOCIATED WITH THE DASH DIET AT

994
00:38:26,837 --> 00:38:31,275
THE BONFERRONI THRESHOLD, P

995
00:38:31,342 --> 00:38:33,377
VALUES BELOW 1 TIMES 10 TO THE

996
00:38:33,444 --> 00:38:35,780
NEGATIVE 5TH AND THESE MODELS

997
00:38:35,846 --> 00:38:38,382
WERE ADJUSTED FOR A NUMBER OF

998
00:38:38,449 --> 00:38:39,917
SOCIODEMOGRAPHIC, SOCIOECONOMIC

999
00:38:39,984 --> 00:38:41,452
HEALTH BEHAVIORS, BODY MASS

1000
00:38:41,519 --> 00:38:41,886
INDEX AND CLINICAL

1001
00:38:41,952 --> 00:38:48,025
CHARACTERISTICS.

1002
00:38:48,092 --> 00:38:49,660
SO WE SEE EIGHT OF THESE

1003
00:38:49,727 --> 00:38:50,861
METABOLITES THAT IMPROVED THE

1004
00:38:50,928 --> 00:38:51,996
PREDICTION OF HIGH ADHERENCE TO

1005
00:38:52,063 --> 00:38:59,303
THE DASH DIET BEYOND PARTICIPANT

1006
00:38:59,370 --> 00:38:59,670
CHARACTERISTICS.

1007
00:38:59,737 --> 00:39:02,573
AND IN PATHWAY ANALYSIS, THE

1008
00:39:02,640 --> 00:39:05,309
COMPLEMENT AND COAGULATION

1009
00:39:05,376 --> 00:39:06,410
CASCADE AND CELL ADHESION

1010
00:39:06,477 --> 00:39:09,380
MOLECULES WERE OVERREPRESENTED.

1011
00:39:09,447 --> 00:39:10,915
SO WHAT DO ALL THESE FINDINGS

1012
00:39:10,981 --> 00:39:12,883
MEAN?

1013
00:39:12,950 --> 00:39:15,086
WELL, I'LL HIGHLIGHT A FEW KEY

1014
00:39:15,152 --> 00:39:16,620
PROTEINS WE FOUND.

1015
00:39:16,687 --> 00:39:18,255
SO ONE IS EPIDERMAL GROWTH

1016
00:39:18,322 --> 00:39:19,557
FACTOR RECEPTOR, SO THIS IS

1017
00:39:19,623 --> 00:39:21,459
INVOLVED IN INFLAMMATION

1018
00:39:21,525 --> 00:39:23,928
ASSOCIATED WITH ANGIOGENESIS,

1019
00:39:23,994 --> 00:39:28,632
ATHEROSCLEROSIS AND DIABETES.

1020
00:39:28,699 --> 00:39:30,735
INSULIN-LIKE GROWTH FACTOR

1021
00:39:30,801 --> 00:39:31,469
BINDING PROTEIN IS ASSOCIATED

1022
00:39:31,535 --> 00:39:37,341
WITH LOW LEVELS OF -- IMPAIRED

1023
00:39:37,408 --> 00:39:38,943
GLUE COST TOLERANCE,

1024
00:39:39,009 --> 00:39:40,444
CARDIOVASCULAR DISEASE AND

1025
00:39:40,511 --> 00:39:41,779
HYPERTENSION, HIGHER LEVELS

1026
00:39:41,846 --> 00:39:45,616
PROMOTE NITRIC ACID PRODUCTION.

1027
00:39:45,683 --> 00:39:47,284
CONTACTIN-1 IS A CELL ADHESION

1028
00:39:47,351 --> 00:39:48,919
PROTEIN AND HAS BEEN INVERSELY

1029
00:39:48,986 --> 00:39:51,088
ASSOCIATED WITH MYOCARDIAL

1030
00:39:51,155 --> 00:39:52,123
INFARCTION, HEART FAILURE AND

1031
00:39:52,189 --> 00:39:52,857
DEATH.

1032
00:39:52,923 --> 00:39:55,259
NEURONAL GROWTH FACTOR 1 WAS

1033
00:39:55,326 --> 00:39:57,561
ASSOCIATED IN OTHER STUDIES WITH

1034
00:39:57,628 --> 00:40:02,700
BODY WEIGHT REGULATION, VIA THE

1035
00:40:02,767 --> 00:40:04,034
HYPOTHALAMUS, WHICH CONTROLS

1036
00:40:04,101 --> 00:40:06,637
FOOD CONSUMPTION, ESPECIALLY

1037
00:40:06,704 --> 00:40:09,940
FOODS THAT ARE HIGHER IN CARBS

1038
00:40:10,007 --> 00:40:13,010
AND FIBER AND LOWER IN FAT.

1039
00:40:13,077 --> 00:40:15,646
AND ALSO LOW LEVELS OF THIS

1040
00:40:15,713 --> 00:40:16,947
PROTEIN WERE ASSOCIATED WITH

1041
00:40:17,014 --> 00:40:22,887
ABNORMAL FAT DISTRIBUTION.

1042
00:40:22,953 --> 00:40:24,021
NEUROEXOPHILIN-1 HAS BEEN SHOWN

1043
00:40:24,088 --> 00:40:29,460
TO REGULATE MANY CARDIOVASCULAR

1044
00:40:29,527 --> 00:40:30,895
PARAMETERS, INCLUDING BLOOD

1045
00:40:30,961 --> 00:40:35,366
PRESSURE, LDL CHOLESTEROL, HDL

1046
00:40:35,432 --> 00:40:38,769
CHOLESTEROL AND ASSOCIATED WITH

1047
00:40:38,836 --> 00:40:40,404
DIABETES.

1048
00:40:40,471 --> 00:40:43,240
ENDO NUCLEOSIDE TRIPHOSPHATE

1049
00:40:43,307 --> 00:40:45,209
INVOLVED IN BODY WEIGHT REG EU

1050
00:40:45,276 --> 00:40:46,844
LAITION, ENERGY METABOLISM AND

1051
00:40:46,911 --> 00:40:48,612
INSULIN SENSITIVITY.

1052
00:40:48,679 --> 00:40:53,217
NEUROPEPTIDE W IS A WELL-KNOWN

1053
00:40:53,284 --> 00:40:55,085
HORMONE INVOLVED IN REGULATING

1054
00:40:55,152 --> 00:40:58,255
FOOD CONSUMPTION AND ENERGY

1055
00:40:58,322 --> 00:40:58,923
HOMEOSTASIS IN PERIODS OF

1056
00:40:58,989 --> 00:40:59,223
STRESS.

1057
00:40:59,290 --> 00:41:00,324
SO SOME REALLY INTERESTING

1058
00:41:00,391 --> 00:41:01,425
FINDINGS THAT ALIGN WELL WITH

1059
00:41:01,492 --> 00:41:03,727
THE BASIC SCIENCE RESEARCH AND

1060
00:41:03,794 --> 00:41:04,829
SOME EPIDEMIOLOGIC RESEARCH

1061
00:41:04,895 --> 00:41:06,497
LOOKING AT CLINICAL OUTCOMES

1062
00:41:06,564 --> 00:41:12,269
ASSOCIATED WITH THESE PROTEINS.

1063
00:41:12,336 --> 00:41:13,571
SO THE PATHWAYS THAT WE

1064
00:41:13,637 --> 00:41:15,339
IDENTIFIED THAT WERE

1065
00:41:15,406 --> 00:41:16,340
OVERREPRESENTED AMONG THE

1066
00:41:16,407 --> 00:41:19,844
SIGNIFICANT PROTEINS WERE THE

1067
00:41:19,910 --> 00:41:20,611
COMPLEMENT AND COAGULATION

1068
00:41:20,678 --> 00:41:22,680
PROCESSES THAT ARE INVOLVED IN

1069
00:41:22,746 --> 00:41:24,682
INNATE IMMUNITY, TISSUE INJURY

1070
00:41:24,748 --> 00:41:26,317
AND INFLAMMATORY RESPONSE, AND

1071
00:41:26,383 --> 00:41:31,956
THEN CELL ADHESION MOLECULES

1072
00:41:32,022 --> 00:41:36,193
INVOLVED IN HEMOYOE STASIS,

1073
00:41:36,260 --> 00:41:37,928
IMMUNE RESPONSE, INFLAMMATION

1074
00:41:37,995 --> 00:41:38,362
AND ATHEROSCLEROSIS.

1075
00:41:38,429 --> 00:41:39,463
SO THE LAST PROJECT I'LL MENTION

1076
00:41:39,530 --> 00:41:40,798
TODAY IS ON THE PROTEOMICS OF

1077
00:41:40,865 --> 00:41:43,634
THE DASH DIET IN THE TWO FEEDING

1078
00:41:43,701 --> 00:41:45,269
TRIALS, THE ORIGINAL DASH TRIAL

1079
00:41:45,336 --> 00:41:49,874
AND THEN THE FOLLOWING DASH

1080
00:41:49,940 --> 00:41:52,276
SODIUM TRIAL.

1081
00:41:52,343 --> 00:41:54,044
SO HERE WE COLLECTED SERUM

1082
00:41:54,111 --> 00:41:55,579
SPECIMENS AND THESE WERE

1083
00:41:55,646 --> 00:41:58,082
OBTAINED AGAIN FROM THE NHLBI

1084
00:41:58,148 --> 00:42:00,517
BIOLINCC REPOSITORY.

1085
00:42:00,584 --> 00:42:02,152
FROM THE END OF THE DASH DIET

1086
00:42:02,219 --> 00:42:03,454
WITHIN THE DASH TRIAL AND THE

1087
00:42:03,520 --> 00:42:07,858
DASH SODIUM TRIALS.

1088
00:42:07,925 --> 00:42:09,593
THIS VERSION OF THE SOMALOGIC

1089
00:42:09,660 --> 00:42:13,764
PLATFORM IDENTIFIED 7,241

1090
00:42:13,831 --> 00:42:16,834
PROTEINS, AND THEN PROTEINS THAT

1091
00:42:16,901 --> 00:42:18,469
WERE STATISTICALLY SIGNIFICANT

1092
00:42:18,535 --> 00:42:19,536
IN THE META-ANALYSIS ACROSS THE

1093
00:42:19,603 --> 00:42:21,238
TWO FEEDING TRIALS, SO DASH AND

1094
00:42:21,305 --> 00:42:23,841
DASH SODIUM, WERE THEN EVALUATED

1095
00:42:23,908 --> 00:42:27,912
IN THE ARIC STUDY.

1096
00:42:27,978 --> 00:42:30,214
SO HERE'S THE VOLCANO PLOT, AND

1097
00:42:30,281 --> 00:42:33,717
YOU'VE SEEN THIS DISPLAYED

1098
00:42:33,784 --> 00:42:34,685
BEFORE.

1099
00:42:34,752 --> 00:42:36,687
WE FOUND 71 PROTEINS THAT WERE

1100
00:42:36,754 --> 00:42:38,322
DIFFERENT BETWEEN THE DASH AND

1101
00:42:38,389 --> 00:42:41,258
CONTROL DIET, FROM THE

1102
00:42:41,325 --> 00:42:42,026
META-ANALYSIS ACROSS THE TWO

1103
00:42:42,092 --> 00:42:45,095
TRIALS.

1104
00:42:45,162 --> 00:42:46,463
AND THESE MODELS WERE ADJUSTED

1105
00:42:46,530 --> 00:42:48,599
FOR AGE, SEX, RACE, ETHNICITY,

1106
00:42:48,666 --> 00:42:54,204
AND BODY MASS INDEX, AND WE USED

1107
00:42:54,271 --> 00:42:57,608
AN FDR CUT POINT OF .05 TO

1108
00:42:57,675 --> 00:42:59,276
ASSESS STATISTICAL SIGNIFICANCE

1109
00:42:59,343 --> 00:43:00,444
FOR THIS PROJECT.

1110
00:43:00,511 --> 00:43:05,482
AND THEN OF THE 71, 50 WERE

1111
00:43:05,549 --> 00:43:06,817
AVAILABLE AND DETECTED IN THE

1112
00:43:06,884 --> 00:43:08,118
ARIC STUDY.

1113
00:43:08,185 --> 00:43:12,923
OF THOSE 50, 19 WERE ALSO

1114
00:43:12,990 --> 00:43:13,557
SIGNIFICANTLY ASSOCIATED WITH

1115
00:43:13,624 --> 00:43:16,460
THE DASH DIET IN THE ARIC STUDY,

1116
00:43:16,527 --> 00:43:18,429
AND WE CALL THOSE VALIDATED.

1117
00:43:18,495 --> 00:43:19,296
SO ON THE LEFT-HAND SIDE, YOU

1118
00:43:19,363 --> 00:43:22,833
SEE THESE 19 METABOLITES AND THE

1119
00:43:22,900 --> 00:43:27,404
BETA COEFFICIENTS -- SORRY, NOT

1120
00:43:27,471 --> 00:43:28,572
METABOLITES, PROTEINS, FOR

1121
00:43:28,639 --> 00:43:29,373
ASSOCIATION OF THESE PROTEINS

1122
00:43:29,440 --> 00:43:31,909
WITH THE DASH DIET IN THE

1123
00:43:31,976 --> 00:43:34,011
META-ANALYSIS OF THE DASH TRIAL,

1124
00:43:34,078 --> 00:43:36,080
IN THE DASH SODIUM TRIAL.

1125
00:43:36,146 --> 00:43:36,847
IN THE RIGHT-HAND SIDE PANEL,

1126
00:43:36,914 --> 00:43:37,948
YOU SEE RESULTS FROM THE ARIC

1127
00:43:38,015 --> 00:43:39,683
STUDY.

1128
00:43:39,750 --> 00:43:41,652
SO THESE METABOLITES WERE NOT

1129
00:43:41,719 --> 00:43:44,321
ONLY STATISTICALLY SIGNIFICANT

1130
00:43:44,388 --> 00:43:46,590
IN ALL THREE TRIALS, ALL THREE

1131
00:43:46,657 --> 00:43:50,294
STUDY POPULATIONS, BUT ALSO WERE

1132
00:43:50,361 --> 00:43:52,096
VERY CONSISTENT IN TERMS OF

1133
00:43:52,162 --> 00:43:57,101
THEIR DIRECTION OF ASSOCIATION.

1134
00:43:57,167 --> 00:44:01,705
SO WE FOUND 19 PRO T PROTEINS TT

1135
00:44:01,772 --> 00:44:04,174
COLLECTIVELY IMPROVED THE

1136
00:44:04,241 --> 00:44:05,009
PREDICTION OF THE DASH DIET IN

1137
00:44:05,075 --> 00:44:07,077
THE FEEDING STUDIES, AND THE

1138
00:44:07,144 --> 00:44:10,347
DASH DIET SCORE ASSOCIATED WITH

1139
00:44:10,414 --> 00:44:11,915
ADHERENCE TO THE DASH DIET AND

1140
00:44:11,982 --> 00:44:13,650
THE ARIC STUDY BEYOND

1141
00:44:13,717 --> 00:44:14,852
PARTICIPANT CHARACTERISTICS.

1142
00:44:14,918 --> 00:44:19,690
SO TO INTERPRET SOME OF THESE

1143
00:44:19,757 --> 00:44:23,227
PROTEIN NAMES, RBP4 IS A CARRIER

1144
00:44:23,293 --> 00:44:24,962
PROTEIN FOR VITAMIN A, AND IT'S

1145
00:44:25,029 --> 00:44:27,164
DERIVED FROM FRUITS AND

1146
00:44:27,231 --> 00:44:29,133
VEGETABLES.

1147
00:44:29,199 --> 00:44:35,272
FOLR2 BINDS TO FOLATE AND

1148
00:44:35,339 --> 00:44:36,807
DELIVERS 5 METHYL

1149
00:44:36,874 --> 00:44:40,778
TETRAHYDROFOLATE TO THE CELL.

1150
00:44:40,844 --> 00:44:43,480
AFM IS A VITAMIN E BINDING

1151
00:44:43,547 --> 00:44:44,715
PROTEIN, POSITIVELY ASSOCIATED

1152
00:44:44,782 --> 00:44:49,520
WITH ADIPOSITY, METABOLIC

1153
00:44:49,586 --> 00:44:50,521
SYNDROME, FATTY LIVER AND

1154
00:44:50,587 --> 00:44:50,921
DIABETES.

1155
00:44:50,988 --> 00:44:53,524
I MEMBERS OF THE JURIED EGFR,

1156
00:44:53,590 --> 00:44:55,592
INVOLVED IN CELL ADHESION FOR

1157
00:44:55,659 --> 00:44:56,727
STABILITY OF PLAQUES AND

1158
00:44:56,794 --> 00:44:58,462
INVERSELY ASSOCIATED WITH

1159
00:44:58,529 --> 00:44:58,962
CARDIOVASCULAR DISEASE.

1160
00:44:59,029 --> 00:44:59,997
THERE WERE SEVERAL PROTEINS THAT

1161
00:45:00,064 --> 00:45:03,500
HAVE A ROLE IN THE INFLAMMATORY

1162
00:45:03,567 --> 00:45:04,501
PROCESS.

1163
00:45:04,568 --> 00:45:06,670
AND THEN SEVERAL PROTEINS THAT

1164
00:45:06,737 --> 00:45:08,972
ARE INVOLVED IN KOL JENS

1165
00:45:09,039 --> 00:45:10,507
DEPOSITION, AND LOWERING

1166
00:45:10,574 --> 00:45:12,476
ARTERIAL STIFFNESS.

1167
00:45:12,543 --> 00:45:16,080
AND THEN CD163, WHICH IS A

1168
00:45:16,146 --> 00:45:18,449
TRANSMEMBRANE SCAVENGER RECEPTOR

1169
00:45:18,515 --> 00:45:20,584
PROTEIN IN MACROPHAGES AND

1170
00:45:20,651 --> 00:45:21,585
MONOCYTES INVOLVED IN

1171
00:45:21,652 --> 00:45:22,453
INFLAMMATION AND IS ASSOCIATED

1172
00:45:22,519 --> 00:45:26,757
WITH BOTH DIABETES AND OBESITY.

1173
00:45:26,824 --> 00:45:31,428
IN OTHER RESEARCH.

1174
00:45:31,495 --> 00:45:36,233
SO I'LL MOVE INTO THE CONCLUSION

1175
00:45:36,300 --> 00:45:40,104
NOW, SO IN SUMMARY, FROM THIS

1176
00:45:40,170 --> 00:45:41,738
LAST PROJECT, WE IDENTIFIED 19

1177
00:45:41,805 --> 00:45:43,140
PROTEINS THAT WERE ROBUSTLY

1178
00:45:43,207 --> 00:45:46,877
ASSOCIATED WITH THE DASH DIET IN

1179
00:45:46,944 --> 00:45:47,311
THREE STUDIES.

1180
00:45:47,377 --> 00:45:49,079
IN THE DASH TRIAL, DASH SODIUM

1181
00:45:49,146 --> 00:45:51,482
TRIAL AND ARIC STUDY.

1182
00:45:51,548 --> 00:45:54,751
THESE PROTEINS REFLECTED DIETARY

1183
00:45:54,818 --> 00:45:55,853
INTAKE, AS WELL AS LOWER

1184
00:45:55,919 --> 00:45:58,722
INFLAMMATION AND COLLAGEN

1185
00:45:58,789 --> 00:45:59,323
DEPOSITION.

1186
00:45:59,389 --> 00:46:00,924
OTHER PATHWAYS AS WELL, BUT THIS

1187
00:46:00,991 --> 00:46:04,628
IS KIND OF -- THERE WAS MANY

1188
00:46:04,695 --> 00:46:08,232
PROTEINS INVOLVED IN THESE

1189
00:46:08,298 --> 00:46:11,735
SPECIFIC PATHWAYS.

1190
00:46:11,802 --> 00:46:14,605
AND SO OUR FINDINGS SUGGEST

1191
00:46:14,671 --> 00:46:17,074
POTENTIAL PATHWAYS THAT ARE

1192
00:46:17,141 --> 00:46:18,976
IMPACTED BY CONSUMING THE DASH

1193
00:46:19,042 --> 00:46:21,411
DIET.

1194
00:46:21,478 --> 00:46:25,115
SO OVERALL FROM TODAY'S TALK,

1195
00:46:25,182 --> 00:46:27,417
THE DASH DIET IS A KNOWN HEALTHY

1196
00:46:27,484 --> 00:46:30,487
DIETARY PATTERN THAT HAS BEEN

1197
00:46:30,554 --> 00:46:32,823
SHOWN TO REPEATEDLY REDUCE BLOOD

1198
00:46:32,890 --> 00:46:35,559
PRESSURE LEVELS, AS WELL AS

1199
00:46:35,626 --> 00:46:39,930
REDUCE THE RISK OF INCIDENT

1200
00:46:39,997 --> 00:46:42,666
CHRONIC KIDNEY DISEASE,

1201
00:46:42,733 --> 00:46:43,967
CARDIOVASCULAR DISEASE MORTALITY

1202
00:46:44,034 --> 00:46:44,868
AND ALL-CAUSE MORTALITY IN

1203
00:46:44,935 --> 00:46:46,270
HEALTHY INDIVIDUALS, AS WELL AS

1204
00:46:46,336 --> 00:46:51,341
KIDNEY DISEASE PROGRESSION I AND

1205
00:46:51,408 --> 00:46:52,476
MORTALITY IN KIDNEY PATIENTS, SO

1206
00:46:52,543 --> 00:46:53,944
THESE ARE THE RESULTS FROM THE

1207
00:46:54,011 --> 00:46:55,946
ARIC STUDY AND FROM THE CRIC

1208
00:46:56,013 --> 00:46:59,783
STUDY.

1209
00:46:59,850 --> 00:47:01,852
FOLLOWING THE FINDINGS FROM THE

1210
00:47:01,919 --> 00:47:05,355
ORIGINAL CLINICAL TRIALS.

1211
00:47:05,422 --> 00:47:06,823
NUTRITIONAL METABOLOMICS IS A

1212
00:47:06,890 --> 00:47:12,496
USEFUL APPROACH FOR DISCOVERY OF

1213
00:47:12,563 --> 00:47:15,098
DIETARY BIOMARKERS.

1214
00:47:15,165 --> 00:47:16,466
AND METABOLOMICS MARKERS OF THE

1215
00:47:16,533 --> 00:47:19,736
DASH DIET FROM FEEDING TRIALS,

1216
00:47:19,803 --> 00:47:21,371
AS WELL AS COHORT STUDIES, COULD

1217
00:47:21,438 --> 00:47:25,876
BE USED IN FUTURE STUDIES.

1218
00:47:25,943 --> 00:47:27,511
I ALSO TALKED ABOUT PROTEOMICS,

1219
00:47:27,578 --> 00:47:31,348
SO I THINK PROTEOMICS OFFERS

1220
00:47:31,415 --> 00:47:33,650
COMPLEMENTARY INFORMATION BEYOND

1221
00:47:33,717 --> 00:47:36,720
METABOLOMICS THAT POINTS TO KEY

1222
00:47:36,787 --> 00:47:40,324
PATHWAYS THAT UNDERLINE -- THAT

1223
00:47:40,390 --> 00:47:42,226
UNDERLIE THE DIET-DISEASE

1224
00:47:42,292 --> 00:47:43,527
RELATIONSHIP AND PATHWAYS THAT

1225
00:47:43,594 --> 00:47:48,131
ARE RELEVANT FOR FOOD DIGESTION,

1226
00:47:48,198 --> 00:47:49,566
ABSORPTION AND METABOLISM.

1227
00:47:49,633 --> 00:47:51,201
I DIDN'T LINK THE PROTEOMICS TO

1228
00:47:51,268 --> 00:47:52,169
DISEASE OUTCOMES TODAY, BUT

1229
00:47:52,236 --> 00:47:53,937
THOSE FINDINGS ARE COMING, AND I

1230
00:47:54,004 --> 00:47:58,775
THINK WE CAN INFER THIS BASED ON

1231
00:47:58,842 --> 00:48:00,944
WHAT WE KNOW ABOUT THE PROTEINS

1232
00:48:01,011 --> 00:48:04,681
FROM OTHER RESEARCH.

1233
00:48:04,748 --> 00:48:06,883
SO WHAT'S NEXT?

1234
00:48:06,950 --> 00:48:10,821
THIS IS REALLY A DISCOVERY-BASED

1235
00:48:10,887 --> 00:48:12,589
APPROACH TO IDENTIFYING NEW

1236
00:48:12,656 --> 00:48:14,658
MARKERS OF DIETARY INTAKE, SO

1237
00:48:14,725 --> 00:48:15,626
THERE'S A LOT MORE THAT NEEDS TO

1238
00:48:15,692 --> 00:48:18,028
BE DONE.

1239
00:48:18,095 --> 00:48:19,263
SO SOME OF THE FUTURE RESEARCH

1240
00:48:19,329 --> 00:48:24,735
THAT I HAVE PLANNED IS TO LOOK

1241
00:48:24,801 --> 00:48:26,703
AT THESE DASH DIET RELATED

1242
00:48:26,770 --> 00:48:28,272
METABOLITES AND PROTEINS AND

1243
00:48:28,338 --> 00:48:31,308
LINK THEM TO CLINICAL

1244
00:48:31,375 --> 00:48:33,477
PARAMETERS, SO MY FIRST INTEREST

1245
00:48:33,543 --> 00:48:35,245
IS BLOOD PRESSURE AND

1246
00:48:35,312 --> 00:48:36,280
HYPERTENSION, BUT ALSO OTHER

1247
00:48:36,346 --> 00:48:39,016
OUTCOMES.

1248
00:48:39,082 --> 00:48:41,852
SECOND, TO FOLLOW UP ON THESE

1249
00:48:41,918 --> 00:48:44,154
CANDIDATE MARKERS, I AM

1250
00:48:44,221 --> 00:48:47,557
DEVELOPING QUANTITATIVE ASSAYS,

1251
00:48:47,624 --> 00:48:49,092
AND THEN WE'LL BE TESTING THEM

1252
00:48:49,159 --> 00:48:51,528
USING SPECIMENS.

1253
00:48:51,595 --> 00:48:54,364
AND THEN THE DASH DIET CLEARLY

1254
00:48:54,431 --> 00:48:59,169
IS VERY IMPORTANT, IS WIDELY

1255
00:48:59,236 --> 00:49:02,639
PROMOTED, AND IS RELEVANT

1256
00:49:02,706 --> 00:49:04,641
SPECIFICALLY FOR THE U.S.

1257
00:49:04,708 --> 00:49:05,108
POPULATION.

1258
00:49:05,175 --> 00:49:06,543
BUT THERE'S OTHER DIETARY

1259
00:49:06,610 --> 00:49:09,513
PATTERNS OF INTEREST, AND

1260
00:49:09,579 --> 00:49:10,681
THERE'S OTHER DIETARY FACTORS OF

1261
00:49:10,747 --> 00:49:11,181
INTEREST.

1262
00:49:11,248 --> 00:49:15,519
SO THERE'S MORE WORK TO DO TO

1263
00:49:15,585 --> 00:49:17,387
BUILD THIS EVIDENCE ON

1264
00:49:17,454 --> 00:49:21,792
BIOMARKERS OF DIET.

1265
00:49:21,858 --> 00:49:24,528
I'D LIKE TO MAKE A FEW

1266
00:49:24,594 --> 00:49:26,263
ACKNOWLEDGMENTS, PRIMARILY

1267
00:49:26,330 --> 00:49:28,699
FUNDING, FROM THE NHLBI.

1268
00:49:28,765 --> 00:49:31,101
SO I HAVE THE BENEFIT OF HAVING

1269
00:49:31,168 --> 00:49:35,205
BEEN FUNDED BY THE NHLBI A FEW

1270
00:49:35,272 --> 00:49:41,611
TIMES IN THIS INITIAL R21 WAS TO

1271
00:49:41,678 --> 00:49:43,013
ENCOURAGE USE OF THE BIOLINCC

1272
00:49:43,080 --> 00:49:44,147
REPOSITORY, WHICH I MENTIONED A

1273
00:49:44,214 --> 00:49:47,084
COUPLE TIMES TODAY, AND THEN

1274
00:49:47,150 --> 00:49:50,020
THIS R56 HIGH IMPACT ONE-YEAR

1275
00:49:50,087 --> 00:49:53,457
AWARD FOLLOWED BY MY FIRST R01,

1276
00:49:53,523 --> 00:49:55,225
SO I'M VERY GRATEFUL FOR

1277
00:49:55,292 --> 00:49:56,093
FUNDING.

1278
00:49:56,159 --> 00:49:57,394
I ALSO WOULD LIKE TO ACKNOWLEDGE

1279
00:49:57,461 --> 00:50:00,197
ALL THE PARTICIPANTS WHO WERE

1280
00:50:00,263 --> 00:50:03,133
INVOLVED IN THESE STUDIES, AND

1281
00:50:03,200 --> 00:50:04,234
THE MANY PEOPLE WHO CONTRIBUTED

1282
00:50:04,301 --> 00:50:06,570
TO THIS RESEARCH AT MANY STAGES.

1283
00:50:06,636 --> 00:50:08,105
I DON'T HAVE THEM ALL LISTED

1284
00:50:08,171 --> 00:50:10,273
BECAUSE I RISK LEAVING SOMEONE

1285
00:50:10,340 --> 00:50:15,245
OFF, BUT THERE ARE MANY PEOPLE.

1286
00:50:15,312 --> 00:50:16,646
SO THAT'S ALL I HAVE FOR TODAY.

1287
00:50:16,713 --> 00:50:18,949
I WELCOME ANY QUESTIONS THAT

1288
00:50:19,015 --> 00:50:21,818
YOU HAVE.

1289
00:50:21,885 --> 00:50:24,688
>> THANK YOU SO MUCH,

1290
00:50:24,755 --> 00:50:25,322
DR. REBHOLZ.

1291
00:50:25,389 --> 00:50:27,858
THIS WAS FANTASTIC!

1292
00:50:27,924 --> 00:50:30,160
YOUR PRESENTATION REALLY CALLED

1293
00:50:30,227 --> 00:50:32,028
ATTENTION TO THE NEED FOR

1294
00:50:32,095 --> 00:50:35,332
OBJECTIVE MEASURES OF DIETARY

1295
00:50:35,399 --> 00:50:37,934
INTAKE, AND YOU REALLY TOUCHED

1296
00:50:38,001 --> 00:50:42,572
BASE ON SEVERAL COMPONENTS, THE

1297
00:50:42,639 --> 00:50:45,208
DASH DIET, AS WELL AS THE ARIC

1298
00:50:45,275 --> 00:50:48,245
STUDY AND THE CHRONIC KID NIGH

1299
00:50:48,311 --> 00:50:53,216
DISEASE KIDNEYDISEASE STUDY, SOO

1300
00:50:53,283 --> 00:50:53,784
MUCH.

1301
00:50:53,850 --> 00:50:56,353
JUST A REMINDER, PLEASE PUT YOUR

1302
00:50:56,420 --> 00:50:58,822
QUESTIONS IN THE CHAT BOX OR

1303
00:50:58,889 --> 00:51:07,764
SEND TO THE ONPA LINK ON YOUR

1304
00:51:07,831 --> 00:51:10,667
SCREEN, IT'S THE

1305
00:51:10,734 --> 00:51:12,502
ONPA@MAIL.NIH.GOV.

1306
00:51:12,569 --> 00:51:15,906
AND WE WILL BE COLLECTING

1307
00:51:15,972 --> 00:51:22,679
QUESTIONS SO THAT DR. REBHOLZ

1308
00:51:22,746 --> 00:51:23,980
CAN PROVIDE ANSWERS TO THOSE

1309
00:51:24,047 --> 00:51:24,347
QUESTIONS.

1310
00:51:24,414 --> 00:51:25,982
SO TO START US OFF, I HAVE ONE

1311
00:51:26,049 --> 00:51:26,516
QUESTION.

1312
00:51:26,583 --> 00:51:29,920
I NOTICED STRONG VARIABILITY IN

1313
00:51:29,986 --> 00:51:35,091
THE PLOTS THAT YOU PROVIDED, AND

1314
00:51:35,158 --> 00:51:40,697
I WAS WONDERING WHETHER YOU HAVE

1315
00:51:40,764 --> 00:51:42,966
SOME DIRECTIONS IN TERMS OF

1316
00:51:43,033 --> 00:51:45,635
PERHAPS MAYBE WE NEED TO LOOK AT

1317
00:51:45,702 --> 00:51:48,839
PRECISION NUTRITION BECAUSE OF

1318
00:51:48,905 --> 00:51:53,610
THIS KIND OF VARIABILITY IN THE

1319
00:51:53,677 --> 00:51:55,812
PLOTS, EVEN WITH THE

1320
00:51:55,879 --> 00:51:56,146
METABOLITES.

1321
00:51:56,213 --> 00:51:59,783
SO I WONDERED IF YOU HAVE ANY

1322
00:51:59,850 --> 00:52:02,319
RESPONSE TO THAT.

1323
00:52:02,385 --> 00:52:06,556
>> YEAH, I THINK, YOU KNOW,

1324
00:52:06,623 --> 00:52:08,592
OVERALL, WE WERE ABLE TO FIND

1325
00:52:08,658 --> 00:52:11,528
VERY CONSISTENT ASSOCIATIONS

1326
00:52:11,595 --> 00:52:13,563
ACROSS THE FEEDING TRIALS, AS

1327
00:52:13,630 --> 00:52:17,033
WELL AS TRANSLATING TO COHORT

1328
00:52:17,100 --> 00:52:18,535
STUDIES, WHICH IS A VERY

1329
00:52:18,602 --> 00:52:20,070
DIFFERENT DESIGN, VERY DIFFERENT

1330
00:52:20,136 --> 00:52:21,938
SETTING, PEOPLE WEREN'T

1331
00:52:22,005 --> 00:52:23,306
RECOMMENDED TO FOLLOW THE DASH

1332
00:52:23,373 --> 00:52:26,243
DIET, SO THAT'S MY TAKE-HOME,

1333
00:52:26,309 --> 00:52:28,545
THAT THE RESULTS ARE QUITE

1334
00:52:28,612 --> 00:52:30,547
CONSISTENT.

1335
00:52:30,614 --> 00:52:33,617
ACROSS THE STUDIES.

1336
00:52:33,683 --> 00:52:38,421
AND I THINK IT'S USEFUL, AGAIN,

1337
00:52:38,488 --> 00:52:41,491
TO FIND BIOMARKERS THAT, ON

1338
00:52:41,558 --> 00:52:45,228
AVERAGE, ASSESS -- ARE USED FOR

1339
00:52:45,295 --> 00:52:46,563
INDICATING ADHERENCE TO THE DASH

1340
00:52:46,630 --> 00:52:48,298
DIET AND OTHER DIETARY FACTORS.

1341
00:52:48,365 --> 00:52:49,766
BUT YOUR POINT IS A GOOD ONE,

1342
00:52:49,833 --> 00:52:54,671
YOU KNOW, IT IMPORTANT TO

1343
00:52:54,738 --> 00:52:56,306
UNDERSTAND, YOU KNOW, ARE THESE

1344
00:52:56,373 --> 00:53:00,410
UNIVERSAL OR DO THEY DIFFER FOR

1345
00:53:00,477 --> 00:53:02,612
CERTAIN SUBGROUPS OF THE

1346
00:53:02,679 --> 00:53:03,246
POPULATION.

1347
00:53:03,313 --> 00:53:08,051
AND WE HAVE STARTED DOING THAT,

1348
00:53:08,118 --> 00:53:09,853
LOOKING AT SIMILAR -- IF THE

1349
00:53:09,920 --> 00:53:14,124
ASSOCIATIONS ARE SIMILAR BY --

1350
00:53:14,190 --> 00:53:20,230
BETWEEN MEN AND WOMEN, BETWEEN

1351
00:53:20,297 --> 00:53:22,032
RACIAL/ETHNIC GROUPS AS WELL,

1352
00:53:22,098 --> 00:53:23,567
AND LARGELY -- I DIDN'T PRESENT

1353
00:53:23,633 --> 00:53:24,768
THIS, BUT LARGELY THE RESULTS

1354
00:53:24,834 --> 00:53:26,603
ARE VERY CONSISTENT.

1355
00:53:26,670 --> 00:53:28,705
BUT THAT ISN'T TO SAY, YOU KNOW,

1356
00:53:28,772 --> 00:53:29,940
THERE IS VARIABILITY AND IT

1357
00:53:30,006 --> 00:53:33,643
NEEDS TO BE UNDERSTOOD, AND SO I

1358
00:53:33,710 --> 00:53:37,948
THINK THAT IS A VERY IMPORTANT

1359
00:53:38,014 --> 00:53:43,286
NEXT STEP AND APPROACH TO TRYING

1360
00:53:43,353 --> 00:53:44,621
TO FIND SOME MEANING BEHIND

1361
00:53:44,688 --> 00:53:46,256
THESE DATA.

1362
00:53:46,323 --> 00:53:48,692
>> THANK YOU SO MUCH.

1363
00:53:48,758 --> 00:53:51,661
SEVERAL QUESTIONS HAVE COME UP.

1364
00:53:51,728 --> 00:53:54,164
THERE'S A QUESTION SOMEONE SENT

1365
00:53:54,230 --> 00:53:59,836
WANTS TO KNOW, YOU MENTIONED

1366
00:53:59,903 --> 00:54:01,304
THEOBROMINE WAS IDENTIFIED IN

1367
00:54:01,371 --> 00:54:03,607
THE CLINICAL TRIAL, AND THIS

1368
00:54:03,673 --> 00:54:04,574
METABOLITE IS ALSO ASSOCIATED

1369
00:54:04,641 --> 00:54:10,313
WITH CHOCOLATE AND LOWER DIE DIY

1370
00:54:10,380 --> 00:54:10,547
QUALITY.

1371
00:54:10,614 --> 00:54:12,282
SO DO YOU KNOW IF THIS

1372
00:54:12,349 --> 00:54:14,217
METABOLITE HAS ASSOCIATION WITH

1373
00:54:14,284 --> 00:54:15,986
CARDIOMETABOLIC HEALTH?

1374
00:54:16,052 --> 00:54:17,988
>> YEAH, THAT'S A GREAT

1375
00:54:18,054 --> 00:54:18,755
QUESTION.

1376
00:54:18,822 --> 00:54:20,390
SO FOR TODAY, I WAS MOSTLY

1377
00:54:20,457 --> 00:54:22,192
FOCUSING ON, YOU KNOW, WORK

1378
00:54:22,258 --> 00:54:24,928
TRYING TO UNDERSTAND BIOMARKERS

1379
00:54:24,995 --> 00:54:26,363
OF DIET WHICH I THINK IS AN

1380
00:54:26,429 --> 00:54:28,264
IMPORTANT GOAL IN AND OF ITSELF,

1381
00:54:28,331 --> 00:54:36,673
BUT OF COURSE, YOU KNOW, A MAJOR

1382
00:54:36,740 --> 00:54:38,975
BENEFIT OF THESE TECHNIQUES,

1383
00:54:39,042 --> 00:54:39,943
METABOLOMICS AND PROTEOMICS, IS

1384
00:54:40,010 --> 00:54:41,177
THAT THEY CAN HELP POINT US IN

1385
00:54:41,244 --> 00:54:44,347
THE RIGHT DIRECTION IN TERMS OF

1386
00:54:44,414 --> 00:54:46,116
UNDERSTANDING WHICH METABOLITES

1387
00:54:46,182 --> 00:54:47,350
AND PROTEINS ARE ASSOCIATED WITH

1388
00:54:47,417 --> 00:54:50,654
CLINICAL OUTCOMES.

1389
00:54:50,720 --> 00:54:51,721
SO -- AND WE'VE STARTED TO DO

1390
00:54:51,788 --> 00:54:55,492
THAT WORK AND THEO BROMINE, I

1391
00:54:55,558 --> 00:55:02,732
BELIEVE WE'VE REPORTED TO BE

1392
00:55:02,799 --> 00:55:05,035
ADVERSELY ASSOCIATED WITH

1393
00:55:05,101 --> 00:55:07,537
CARDIOVASCULAR DISEASE, BUT I'LL

1394
00:55:07,604 --> 00:55:08,672
HAVE TO CHECK THE RESEARCH AND

1395
00:55:08,738 --> 00:55:12,709
GET BACK TO YOU ON THAT.

1396
00:55:12,776 --> 00:55:14,744
>> THANK YOU FOR THAT.

1397
00:55:14,811 --> 00:55:16,980
THERE'S ALSO A QUESTION THAT I

1398
00:55:17,047 --> 00:55:18,181
THINK YOU'VE ALREADY ANSWERED,

1399
00:55:18,248 --> 00:55:20,283
SOMEONE WAS ASKING ABOUT RACE

1400
00:55:20,350 --> 00:55:30,994
AND ETHNICITY BECAUSE OF BLP BLD

1401
00:55:37,200 --> 00:55:42,205
PRESSURE BEING HIGH.

1402
00:55:42,272 --> 00:55:48,178
YO.

1403
00:55:48,244 --> 00:55:49,446
>> I DIDN'T PRESENT THAT TODAY

1404
00:55:49,512 --> 00:55:51,114
BUT WE DO ANALYZE THE UNKNOWNS.

1405
00:55:51,181 --> 00:55:55,518
WE FOCUS ON THE NOANS BECAUSE

1406
00:55:55,585 --> 00:55:57,153
IT'S EASIER TO INTERPRET THEM,

1407
00:55:57,220 --> 00:55:58,588
THERE IS SOME INFORMATION IN THE

1408
00:55:58,655 --> 00:56:00,156
LITERATURE THAT CAN HELP US

1409
00:56:00,223 --> 00:56:05,161
UNDERSTAND THOSE FINDINGS, AND

1410
00:56:05,228 --> 00:56:06,563
ALSO IT'S HELPFUL TO LIMIT THE

1411
00:56:06,629 --> 00:56:07,797
NUMBER OF COMPARISONS IN TERMS

1412
00:56:07,864 --> 00:56:10,567
OF YOUR TYPE I ERROR, LIMITING

1413
00:56:10,633 --> 00:56:11,334
YOUR TYPE I ERROR.

1414
00:56:11,401 --> 00:56:15,405
WITBUT WE ALSO DO THE ANALYSIS F

1415
00:56:15,472 --> 00:56:17,273
UNKNOWNS AND IT'S PART OF THIS

1416
00:56:17,340 --> 00:56:20,977
PROCESS OF MOVING THE FIELD

1417
00:56:21,044 --> 00:56:23,780
FORWARD AND COMMUNICATE THOSE

1418
00:56:23,847 --> 00:56:25,615
RESULTS WITH THE LABORATORY THAT

1419
00:56:25,682 --> 00:56:26,816
GENERATED THE FINDINGS AND WE'RE

1420
00:56:26,883 --> 00:56:29,352
HAVING DISCUSSIONS ABOUT, YOU

1421
00:56:29,419 --> 00:56:33,456
KNOW, WHAT ARE HIGH PRIORITY

1422
00:56:33,523 --> 00:56:35,859
METABOLITES TO FURTHER

1423
00:56:35,925 --> 00:56:39,996
CHARACTERIZE.

1424
00:56:40,063 --> 00:56:42,532
THEY'LL USUALLY BE IN THE

1425
00:56:42,599 --> 00:56:42,832
SUPPLEMENT.

1426
00:56:42,899 --> 00:56:43,767
>> THANKS FOR THAT.

1427
00:56:43,833 --> 00:56:45,935
SOMEONE WANTS TO KNOW WHETHER

1428
00:56:46,002 --> 00:56:49,038
YOU HAVE DONE WORK ON

1429
00:56:49,105 --> 00:56:50,440
METABOLOMICS AND PROTEOMICS AS

1430
00:56:50,507 --> 00:56:54,110
IT RELATES TO THE MEDITERRANEAN

1431
00:56:54,177 --> 00:56:54,544
DIET.

1432
00:56:54,611 --> 00:56:56,746
THERE ARE SOME SIMILARITIES

1433
00:56:56,813 --> 00:57:00,984
BETWEEN THE TWO DIETARY

1434
00:57:01,050 --> 00:57:01,951
PATTERNS, SO --

1435
00:57:02,018 --> 00:57:04,554
>> YEAH, YEAH, SO IN THESE

1436
00:57:04,621 --> 00:57:05,955
ANALYSES THAT I SHOWED IN THE

1437
00:57:06,022 --> 00:57:09,793
ARIC STUDY, ATHEROSCLEROSIS IN

1438
00:57:09,859 --> 00:57:12,195
COMMUNITIES AND THE CRIC,

1439
00:57:12,262 --> 00:57:13,429
CHRONIC RENAL INSUFFICIENCY

1440
00:57:13,496 --> 00:57:15,732
COHORT STUDY, WE LOOKED AT OTHER

1441
00:57:15,799 --> 00:57:17,500
DIETARY PATTERNS THAT FOCUSED

1442
00:57:17,567 --> 00:57:18,868
TODAY ON THE DASH BUT WE ALSO

1443
00:57:18,935 --> 00:57:20,270
LOOKED AT THE MEDITERRANEAN DIET

1444
00:57:20,336 --> 00:57:21,805
SCORE AND REPORTED THOSE

1445
00:57:21,871 --> 00:57:22,071
FINDINGS.

1446
00:57:22,138 --> 00:57:24,574
SO SOME OF THEM OVERLAP WITH THE

1447
00:57:24,641 --> 00:57:25,675
DASH BECAUSE THEY'RE SIMILAR

1448
00:57:25,742 --> 00:57:27,110
DIETS AND SOME OF THEM ARE

1449
00:57:27,177 --> 00:57:28,678
UNIQUE, YOU KNOW, MANY OF THE

1450
00:57:28,745 --> 00:57:32,515
FISH METABOLITES COME OUT AS

1451
00:57:32,582 --> 00:57:35,351
REPRESENTATIVE OF MEDITERRANEAN

1452
00:57:35,418 --> 00:57:39,622
DIET, WHICH TRACKS.

1453
00:57:39,689 --> 00:57:42,292
THE PREDIMED INVESTIGATORS HAVE

1454
00:57:42,358 --> 00:57:43,827
ALSO DONE SOME METABOLOMICS

1455
00:57:43,893 --> 00:57:45,028
RESEARCH AND HAVE PUBLISHED

1456
00:57:45,094 --> 00:57:45,895
THOSE FINDINGS.

1457
00:57:45,962 --> 00:57:48,164
SO THOSE ARE GREAT, AND I THINK

1458
00:57:48,231 --> 00:57:50,567
IF THERE'S OTHER, YOU KNOW, WELL

1459
00:57:50,633 --> 00:57:53,670
CONTROLLED FEEDING TRIALS OF THE

1460
00:57:53,736 --> 00:57:54,971
MEDITERRANEAN DIET, IT WOULD BE

1461
00:57:55,038 --> 00:57:58,274
REALLY NICE TO EXPLORE MARKERS

1462
00:57:58,341 --> 00:57:59,809
OF THE MEDITERRANEAN DIET WITHIN

1463
00:57:59,876 --> 00:58:01,177
THAT SETTING.

1464
00:58:01,244 --> 00:58:03,213
>> VERY NICE.

1465
00:58:03,279 --> 00:58:04,414
SOMEONE WANTS TO KNOW WHETHER

1466
00:58:04,480 --> 00:58:07,283
THIS IS BEING USED IN CLINICAL

1467
00:58:07,350 --> 00:58:07,750
PRACTICE.

1468
00:58:07,817 --> 00:58:11,254
I THINK WE HAVE A LONG WAY TO

1469
00:58:11,321 --> 00:58:14,657
GO, BUT THE METABOLOMICS AND

1470
00:58:14,724 --> 00:58:15,859
PROTEOMICS BEFORE WE CAN START

1471
00:58:15,925 --> 00:58:17,327
USING THEM IN CLINICAL PRACTICE,

1472
00:58:17,393 --> 00:58:18,528
BUT I WONDER IF YOU CAN COMMENT

1473
00:58:18,595 --> 00:58:21,531
ON THAT.

1474
00:58:21,598 --> 00:58:22,899
>> I THINK SOME PEOPLE WOULD

1475
00:58:22,966 --> 00:58:25,235
LIKE TO DO METABOLOMICS AND

1476
00:58:25,301 --> 00:58:27,737
PROTEOMICS ON EVERYBODY,

1477
00:58:27,804 --> 00:58:29,272
INCLUDING IN CLINICAL PRACTICE

1478
00:58:29,339 --> 00:58:32,609
AND THERE'S A MODEL FOR DOING

1479
00:58:32,675 --> 00:58:34,777
THAT.

1480
00:58:34,844 --> 00:58:38,314
I AM OF THE VIEWPOINT THAT WE

1481
00:58:38,381 --> 00:58:42,785
NEED TO DEVELOP QUANTITATIVE

1482
00:58:42,852 --> 00:58:46,222
ASSAYS THAT MEASURE ABSOLUTE

1483
00:58:46,289 --> 00:58:51,461
INTAKE OR ABSOLUTE LEVELS IN THE

1484
00:58:51,527 --> 00:58:53,997
BODY, AND NARROW IT DOWN FROM

1485
00:58:54,063 --> 00:58:56,900
THOUSANDS OR HUNDREDS TO NOT A

1486
00:58:56,966 --> 00:58:58,534
SINGLE METABOLITE THAT

1487
00:58:58,601 --> 00:59:00,169
REPRESENTS A DIETARY PATTERN BUT

1488
00:59:00,236 --> 00:59:04,374
A SMALLER SUBSET OF METABOLITES.

1489
00:59:04,440 --> 00:59:09,379
SO I DON'T ENVISION MAYBE

1490
00:59:09,445 --> 00:59:10,480
REPEATING UNTARGETED

1491
00:59:10,546 --> 00:59:13,483
METABOLOMICS AND PROTEOMICS IN

1492
00:59:13,549 --> 00:59:14,684
EVERYONE WHO WALKS INTO THE

1493
00:59:14,751 --> 00:59:16,686
OFFICE, BUT EVENTUALLY, I THINK,

1494
00:59:16,753 --> 00:59:18,888
YOU KNOW, THAT'S THE IDEA, THAT

1495
00:59:18,955 --> 00:59:19,889
THESE BIOMARKERS COULD BE USED

1496
00:59:19,956 --> 00:59:22,191
IN CLINICAL SETTINGS.

1497
00:59:22,258 --> 00:59:23,159
>> VERY GOOD.

1498
00:59:23,226 --> 00:59:23,927
THANK YOU SO MUCH.

1499
00:59:23,993 --> 00:59:26,596
I THINK WE HAVE -- WE ARE AT THE

1500
00:59:26,663 --> 00:59:28,131
END OF OUR SESSION, AND I WANT

1501
00:59:28,197 --> 00:59:32,168
TO THANK EVERYONE FOR COMING,

1502
00:59:32,235 --> 00:59:35,838
AND I THINK WE HAVE A SLIDE TO

1503
00:59:35,905 --> 00:59:39,876
SHOW FOR THE NEXT UPCOMING

1504
00:59:39,943 --> 00:59:44,380
MEETING SOMETIME IN MAY OF THIS

1505
00:59:44,447 --> 00:59:46,983
YEAR.

1506
00:59:47,050 --> 00:59:48,518
YES.

1507
00:59:48,584 --> 00:59:51,321
SO THANK YOU AGAIN FOR JOINING

1508
00:59:51,387 --> 00:59:51,754
US.

1509
00:59:51,821 --> 00:59:54,157
PLEASE STAY TUNED FOR OUR NEXT

1510
00:59:54,223 --> 00:59:58,695
ONPA SEMINAR, WHICH IS TITLED

1511
00:59:58,761 --> 01:00:01,331
CARDIOVASCULAR HEALTH IN THE

1512
01:00:01,397 --> 01:00:03,399
PERIPARTUM PERIOD, DRIVERS &

1513
01:00:03,466 --> 01:00:04,600
DETERMINANTS, COMING UP MAY 29TH

1514
01:00:04,667 --> 01:00:06,002
OF THIS YEAR AT 1:00 P.M., AND

1515
01:00:06,069 --> 01:00:07,270
IT WILL ALSO BE AVAILABLE FOR

1516
01:00:07,337 --> 01:00:10,773
THE PUBLIC ON THE NIH WEBSITE.

1517
01:00:10,840 --> 01:00:12,141
OR THE NIH VIDEOCAST.

1518
01:00:12,208 --> 01:00:13,142
SO THANK YOU ALL VERY MUCH.

1519
01:00:13,209 --> 01:00:17,046
THANK YOU, DR. CASEY REBHOLZ,

1520
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PARTICULARLY FOR PRESENTING

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THIS, AND  HAVE A GOOD AFTERNOO,

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EVERYONE.

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>> THANK YOU SO MUCH, DR. PRATT.