1  5216 129 PRETERM BIRTH: LONG TERM CARDIOVASCULAR AND RENAL CONSEQUENCES. BACKGROUND: CARDIOVASCULAR AND CHRONIC KIDNEY DISEASES ARE A PART OF NONCOMMUNICABLE CHRONIC DISEASES, THE LEADING CAUSES OF PREMATURE DEATH WORLDWIDE. THEY ARE RECOGNIZED AS HAVING EARLY ORIGINS THROUGH ALTERED DEVELOPMENTAL PROGRAMMING, DUE TO ADVERSE ENVIRONMENTAL CONDITIONS DURING DEVELOPMENT. PRETERM BIRTH IS SUCH AN ADVERSE FACTOR. RATES OF PRETERM BIRTH INCREASED IN THE LAST DECADES, HOWEVER, WITH THE IMPROVEMENT IN PERINATAL AND NEONATAL CARE, A GROWING NUMBER OF PRETERM BORN SUBJECTS HAS NOW ENTERED ADULTHOOD. CLINICAL AND EXPERIMENTAL EVIDENCE SUGGESTS THAT PRETERM BIRTH IS ASSOCIATED WITH IMPAIRED OR ARRESTED STRUCTURAL OR FUNCTIONAL DEVELOPMENT OF KEY ORGANS/SYSTEMS MAKING PRETERM INFANTS VULNERABLE TO CARDIOVASCULAR AND CHRONIC RENAL DISEASES AT ADULTHOOD. THIS REVIEW ANALYZES THE EVIDENCE OF SUCH CARDIOVASCULAR AND RENAL CHANGES, THE ROLE OF PERINATAL AND NEONATAL FACTORS SUCH AS ANTENATAL STEROIDS AND POTENTIAL PATHOGENIC MECHANISMS, INCLUDING DEVELOPMENTAL PROGRAMMING AND EPIGENETIC ALTERATIONS. CONCLUSION: PRETERM BORN SUBJECTS ARE EXPOSED TO A SIGNIFICANTLY INCREASED RISK FOR ALTERED CARDIOVASCULAR AND RENAL FUNCTIONS AT YOUNG ADULTHOOD. ADEQUATE, SPECIFIC FOLLOW-UP MEASURES REMAIN TO BE DETERMINED. WHILE ANTENATAL STEROIDS HAVE CONSIDERABLY IMPROVED PRETERM BIRTH OUTCOMES, REPEATED THERAPY SHOULD BE CONSIDERED WITH CAUTION, AS ANTENATAL STEROIDS INDUCE LONG-TERM CARDIOVASCULAR AND METABOLIC ALTERATIONS IN ANIMALS' MODELS AND THEIR INVOLVEMENT IN THE ACCELERATED CELLULAR SENESCENCE OBSERVED IN HUMAN STUDIES CANNOT BE EXCLUDED.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
2  5962  45 TELOMERES, OXIDATIVE STRESS, AND TIMING FOR SPONTANEOUS TERM AND PRETERM LABOR. TELOMERES ARE NUCLEOPROTEIN COMPLEXES LOCATED AT THE DISTAL ENDS OF CHROMOSOMES. IN ADULTS, PROGRESSIVE TELOMERE SHORTENING OCCURS THROUGHOUT THE LIFETIME AND IS THOUGHT TO CONTRIBUTE TO PROGRESSIVE AGING, PHYSIOLOGICAL SENESCENCE, MULTIORGAN DYSFUNCTION, AND ULTIMATELY, DEATH. AS DISCUSSED IN THIS REVIEW, MULTIPLE LINES OF EVIDENCE PROVIDE SUPPORT FOR THE BIOLOGICAL PLAUSIBILITY THAT A TELOMERE-BASED CLOCK MECHANISM ALSO DETERMINES THE LENGTH OF GESTATION, LEADING TO THE ONSET OF LABOR (PARTURITION). AFTER TELOMERE EXPANSION AT THE BEGINNING OF PREGNANCY, THE TELOMERE LENGTHS IN THE GESTATIONAL TISSUES (IE, THE PLACENTA AND FETAL MEMBRANES) PROGRESSIVELY SHORTEN THROUGHOUT THE REMAINDER OF PREGNANCY. THE RATE OF TELOMERE SHORTENING CAN BE ACCELERATED BY CONDITIONS THAT AFFECT THE MOTHER AND RESULT IN OXIDATIVE STRESS. PRETERM BIRTHS IN THE UNITED STATES ARE ASSOCIATED WITH MULTIPLE RISK FACTORS THAT ARE LINKED WITH INCREASED OXIDATIVE STRESS. ANTIOXIDANT VITAMINS (IE, VITAMINS E AND C) MITIGATE THE EFFECTS OF OXIDATIVE STRESS AND DELAY OR PREVENT TELOMERE SHORTENING. CLINICAL TRIALS WITH VITAMINS E AND C AND WITH MULTIVITAMINS STARTED DURING THE PERICONCEPTION PERIOD HAVE BEEN ASSOCIATED WITH REDUCED RATES OF PRETERM BIRTHS. IN THE UNITED STATES, AFRICAN-AMERICAN WOMEN HAVE A 2-3-FOLD HIGHER RATE OF PRETERM BIRTH. AFRICAN-AMERICAN WOMEN HAVE MULTIPLE RISK FACTORS FOR PREMATURE BIRTH, ALL OF WHICH ARE DISTINCT AND POTENTIALLY ADDITIVE WITH REGARD TO EPIGENETIC TELOMERE SHORTENING. THE "WEATHERING EFFECT" IS THE HYPOTHESIS TO EXPLAIN THE INCREASED RATES OF CHRONIC ILLNESS, DISABILITIES, AND EARLY DEATH OBSERVED IN AFRICAN-AMERICANS. WITH REGARD TO PREGNANCY, ACCELERATED WEATHERING WITH THE ASSOCIATED TELOMERE SHORTENING IN THE GESTATIONAL TISSUES WOULD NOT ONLY EXPLAIN THE PRETERM BIRTH DISPARITY BUT COULD ALSO EXPLAIN WHY HIGHLY EDUCATED, AFFLUENT AFRICAN-AMERICAN WOMEN CONTINUE TO HAVE AN INCREASED RATE OF PRETERM BIRTH. THESE STUDIES SUGGEST THAT THE RACIAL DISPARITIES IN PRETERM BIRTH ARE POTENTIALLY MEDIATED BY TELOMERE SHORTENING PRODUCED BY LIFETIME OR EVEN GENERATIONAL EXPOSURE TO THE EFFECTS OF SYSTEMIC RACISM AND SOCIOECONOMIC MARGINALIZATION. IN CONCLUSION, THIS REVIEW PRESENTS MULTIPLE LINES OF EVIDENCE SUPPORTING A NOVEL HYPOTHESIS REGARDING THE BIOLOGICAL CLOCK MECHANISM THAT DETERMINES THE LENGTH OF PREGNANCY, AND IT OPENS THE POSSIBILITY OF NEW APPROACHES TO PREVENT OR REDUCE THE RATE OF SPONTANEOUS PRETERM BIRTH.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
3  2605  33 EPIGENETICS-A POTENTIAL MEDIATOR BETWEEN AIR POLLUTION AND PRETERM BIRTH. PRETERM BIRTH IS A MAJOR CAUSE OF INFANT MORBIDITY AND MORTALITY AND A POTENTIAL RISK FACTOR FOR ADULT CHRONIC DISEASE. WITH OVER 15 MILLION INFANTS BORN PRETERM WORLDWIDE EACH YEAR, PRETERM BIRTH POSES A GLOBAL HEALTH CONCERN. THERE IS A POSSIBLE ASSOCIATION BETWEEN AIR POLLUTION AND PRETERM BIRTH, THOUGH STUDIES HAVE BEEN INCONSISTENT, LIKELY DUE TO VARIATION IN STUDY DESIGN. HOW AIR POLLUTION INDUCES HEALTH EFFECTS IS UNCERTAIN; HOWEVER, STUDIES HAVE REPEATEDLY DEMONSTRATED THE EFFECTS OF AIR POLLUTION ON EPIGENETIC MODIFICATIONS. MORE RECENT EVIDENCE SUGGESTS THAT EPIGENETICS MAY, IN TURN, BE LINKED TO PRETERM BIRTH. DISCOVERY OF ENVIRONMENTALLY MODIFIABLE EPIGENETIC PROCESSES CONNECTED TO PRETERM BIRTH MAY HELP TO IDENTIFY WOMEN AT RISK OF PRETERM BIRTH, AND ULTIMATELY LEAD TO DEVELOPMENT OF NEW PRETERM BIRTH PREVENTION MEASURES.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
4  4062  40 MATERNAL AND CHILD HEALTH SERVICES AND AN INTEGRATED, LIFE-CYCLE APPROACH TO THE PREVENTION OF NON-COMMUNICABLE DISEASES. DESCRIBED AS THE 'INVISIBLE EPIDEMIC', NON-COMMUNICABLE DISEASES (NCDS) ARE THE WORLD'S LEADING CAUSE OF DEATH. MOST ARE CAUSED BY PREVENTABLE FACTORS, INCLUDING POOR DIET, TOBACCO USE, HARMFUL USE OF ALCOHOL AND PHYSICAL INACTIVITY. DIABETES, CANCER AND CARDIOVASCULAR AND CHRONIC LUNG DISEASES WERE RESPONSIBLE FOR 38 MILLION (68%) OF GLOBAL DEATHS IN 2012. SINCE 1990, PROPORTIONATE NCD MORTALITY HAS INCREASED SUBSTANTIALLY AS POPULATIONS HAVE AGED AND COMMUNICABLE DISEASES DECLINE. THE MAJORITY OF NCD DEATHS, ESPECIALLY PREMATURE NCD DEATHS (<70 YEARS, 82%), OCCUR IN LOW-INCOME AND MIDDLE-INCOME COUNTRIES, AND AMONG POOR COMMUNITIES WITHIN THEM. ADDRESSING NCDS IS RECOGNISED AS CENTRAL TO THE POST-2015 AGENDA; ACCORDINGLY, NCDS HAVE A SPECIFIC OBJECTIVE AND TARGET IN THE SUSTAINABLE DEVELOPMENT GOALS. WHILE DEATHS FROM NCDS OCCUR MAINLY IN ADULTHOOD, MANY HAVE THEIR ORIGINS IN EARLY LIFE, INCLUDING THROUGH EPIGENETIC MECHANISMS OPERATING BEFORE CONCEPTION. GOOD NUTRITION BEFORE CONCEPTION AND INTERVENTIONS AIMED AT PREVENTING NCDS DURING THE FIRST 1000 DAYS (FROM CONCEPTION TO AGE 2 YEARS), CHILDHOOD AND ADOLESCENCE MAY BE MORE COST-EFFECTIVE THAN MANAGING ESTABLISHED NCDS IN LATER LIFE WITH COSTLY TESTS AND DRUGS. FOLLOWING A LIFE-COURSE APPROACH, MATERNAL AND CHILD HEALTH INTERVENTIONS, BEFORE DELIVERY AND DURING CHILDHOOD AND ADOLESCENCE, CAN PREVENT NCDS AND SHOULD INFLUENCE GLOBAL HEALTH AND SOCIOECONOMIC DEVELOPMENT. THIS PAPER DESCRIBES HOW SUCH AN APPROACH MAY BE PURSUED, INCLUDING THROUGH THE ENGAGEMENT OF NON-HEALTH SECTORS. IT ALSO EMPHASISES EVALUATING AND DOCUMENTING RELATED INITIATIVES TO UNDERWRITE SYSTEMATIC AND EVIDENCE-BASED CROSS-SECTORAL ENGAGEMENT ON NCD PREVENTION IN THE FUTURE.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
5  6066  47 THE DEVELOPMENTAL ORIGINS OF HEALTH AND CHRONIC KIDNEY DISEASE: CURRENT STATUS AND PRACTICES IN JAPAN. THE CONCEPT OF THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) VIEWS UNFAVORABLE PERINATAL CIRCUMSTANCES AS CONTRIBUTING TO THE DEVELOPMENT OF DISEASES IN LATER LIFE. IT IS WELL KNOWN THAT SUCH UNFAVORABLE CIRCUMSTANCES PLAY AN IMPORTANT ROLE AS A RISK FACTOR FOR CHRONIC KIDNEY DISEASE (CKD) IN INFANTS BORN WITH PREMATURITY. LOW BIRTHWEIGHT (LBW) IS BELIEVED TO BE A POTENTIAL CONTRIBUTOR TO CKD IN ADULTHOOD. PRETERM AND/OR LBW INFANTS ARE BORN WITH INCOMPLETE NEPHROGENESIS. AS A RESULT, THE NUMBER OF NEPHRONS IS LOW. THE POOR INTRAUTERINE ENVIRONMENT ALSO CAUSES EPIGENETIC CHANGES THAT ADVERSELY AFFECT POSTNATAL RENAL FUNCTION. AFTER BIRTH, HYPERFILTRATION OF INDIVIDUAL NEPHRONS DUE TO LOW NEPHRON NUMBERS CAUSES PROTEINURIA AND SECONDARY GLOMERULOSCLEROSIS. FURTHERMORE, THE RISK OF CKD INCREASES AS RENAL DAMAGE TAKES A SECOND HIT FROM EXPOSURE TO NEPHROTOXIC SUBSTANCES AND ACQUIRED INSULTS SUCH AS ACUTE KIDNEY INJURY AFTER BIRTH AMONG INFANTS IN NEONATAL INTENSIVE CARE. MEANWHILE, UNFORTUNATELY, RECENT STUDIES HAVE SHOWN THAT THE NUMBER OF NEPHRONS IN HEALTHY JAPANESE INDIVIDUALS IS APPROXIMATELY TWO-THIRDS LOWER THAN THAT IN PREVIOUS REPORTS. THIS MEANS THAT JAPANESE PREMATURE INFANTS ARE CLEARLY AT A HIGH RISK OF DEVELOPING CKD IN LATER LIFE. RECENTLY, SEVERAL DOHAD-RELATED CKD STUDIES FROM JAPANESE RESEARCHERS HAVE BEEN REPORTED. HERE, WE SUMMARIZE THE RELEVANCE OF CKD IN CONJUNCTION WITH DOHAD AND REVIEW RECENT STUDIES THAT HAVE EXAMINED THE IMPACT OF THE UPWARD LBW TREND IN JAPAN ON RENAL HEALTH.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
6  4797  38 NUTRITIONAL INTERVENTIONS TO IMPROVE BRAIN OUTCOMES IN PRETERM INFANTS. THE LAST 20 YEARS HAVE SEEN DRAMATIC IMPROVEMENTS IN SURVIVAL FOR PRETERM INFANTS IN BOTH HIGH- AND LOW-INCOME SETTINGS. SURVIVAL RATES OF OVER 50% IN INFANTS BORN 16 WEEKS EARLY (24 WEEKS' GESTATION) ARE NOW COMMONPLACE IN WELL-RESOURCED NEONATAL INTENSIVE CARE UNITS. HOWEVER, ENSURING ADEQUATE NUTRIENT INTAKES ESPECIALLY IN THE FIRST FEW DAYS AND WEEKS IS CHALLENGING, AND MANY INFANTS SHOW POOR GROWTH AND NUTRITIONAL STATUS. GOOD NUTRITIONAL MANAGEMENT SHOULD BE SEEN AS THE CORNERSTONE OF GOOD NEONATAL CARE AND IS KEY TO IMPROVING A RANGE OF IMPORTANT OUTCOMES INCLUDING REDUCED RATES OF RETINOPATHY OF PREMATURITY, CHRONIC LUNG DISEASE, NECROTIZING ENTEROCOLITIS (NEC), AND SEPSIS. EQUALLY IMPORTANTLY, IS THAT GOOD NUTRITIONAL STATUS IS ESSENTIAL TO OPTIMIZE BRAIN GROWTH AND DIFFERENTIATION. THERE ARE MULTIPLE POTENTIAL MECHANISMS THAT LINK NUTRITION TO BRAIN OUTCOMES IN PRETERM INFANTS INCLUDING NEEDS FOR TISSUE ACCRETION, ENERGY SUPPLY, SIGNALING ROLES, FUNCTIONAL COMPONENTS IN HUMAN MILK, EPIGENETIC REGULATION, PREVENTION OF NEC AND DISEASE, AND IMPACTS ON THE GUT BRAIN AXES. THIS ARTICLE WILL REVIEW DATA IN SUPPORT OF DIFFERENT MECHANISTIC LINKS FOR THE IMPACT OF NUTRITION ON BRAIN OUTCOMES IN PRETERM INFANTS.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
7  5185  40 PREMATURE PHYSIOLOGIC AGING AS A PARADIGM FOR UNDERSTANDING INCREASED RISK OF ADVERSE HEALTH ACROSS THE LIFESPAN OF SURVIVORS OF CHILDHOOD CANCER. THE IMPROVEMENT IN SURVIVAL OF CHILDHOOD CANCER OBSERVED ACROSS THE PAST 50 YEARS HAS RESULTED IN A GROWING ACKNOWLEDGMENT THAT SIMPLY EXTENDING THE LIFESPAN OF SURVIVORS IS NOT ENOUGH. IT IS INCUMBENT ON BOTH THE CANCER RESEARCH AND THE CLINICAL CARE COMMUNITIES TO ALSO IMPROVE THE HEALTH SPAN OF SURVIVORS. IT IS WELL ESTABLISHED THAT AGING ADULT SURVIVORS OF CHILDHOOD CANCER ARE AT INCREASED RISK OF CHRONIC HEALTH CONDITIONS, RELATIVE TO THE GENERAL POPULATION. HOWEVER, AS THE FIRST GENERATION OF SURVIVORS AGE INTO THEIR 50S AND 60S, IT HAS BECOME INCREASINGLY EVIDENT THAT THIS POPULATION IS ALSO AT RISK OF EARLY ONSET OF PHYSIOLOGIC AGING. GERIATRIC MEASURES HAVE UNCOVERED EVIDENCE OF REDUCED STRENGTH AND SPEED AND INCREASED FATIGUE, ALL COMPONENTS OF FRAILTY, AMONG SURVIVORS WITH A MEDIAN AGE OF 33 YEARS, WHICH IS SIMILAR TO ADULTS OLDER THAN 65 YEARS OF AGE IN THE GENERAL POPULATION. FURTHERMORE, FRAILTY IN SURVIVORS INDEPENDENTLY INCREASED THE RISK OF MORBIDITY AND MORTALITY. ALTHOUGH THERE HAS BEEN A PAUCITY OF RESEARCH INVESTIGATING THE UNDERLYING BIOLOGIC MECHANISMS FOR ADVANCED PHYSIOLOGIC AGE IN SURVIVORS, RESULTS FROM GERIATRIC POPULATIONS SUGGEST FIVE BIOLOGICALLY PLAUSIBLE MECHANISMS THAT MAY BE POTENTIATED BY EXPOSURE TO CANCER THERAPIES: INCREASED CELLULAR SENESCENCE, REDUCED TELOMERE LENGTH, EPIGENETIC MODIFICATIONS, SOMATIC MUTATIONS, AND MITOCHONDRIAL DNA INFIDELITY. THERE IS NOW A CRITICAL NEED FOR RESEARCH TO ELUCIDATE THE BIOLOGIC MECHANISMS OF PREMATURE AGING IN SURVIVORS OF CHILDHOOD CANCER. THIS RESEARCH COULD PAVE THE WAY FOR NEW FRONTIERS IN THE PREVENTION OF THESE LIFE-CHANGING OUTCOMES.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
8  5179  47 PREGNANCY: AN UNDERUTILIZED WINDOW OF OPPORTUNITY TO IMPROVE LONG-TERM MATERNAL AND INFANT HEALTH-AN APPEAL FOR CONTINUOUS FAMILY CARE AND INTERDISCIPLINARY COMMUNICATION. PHYSIOLOGIC ADAPTATIONS DURING PREGNANCY UNMASK A WOMAN'S PREDISPOSITION TO DISEASES. COMPLICATIONS ARE INCREASINGLY PREDICTED BY FIRST-TRIMESTER ALGORITHMS, AMPLIFY A PRE-EXISTING MATERNAL PHENOTYPE AND ACCELERATE RISKS FOR CHRONIC DISEASES IN THE OFFSPRING UP TO ADULTHOOD (BARKER HYPOTHESIS). RECENT EVIDENCE SUGGESTS THAT VICE VERSA, PREGNANCY DISEASES ALSO INDICATE MATERNAL AND EVEN GRANDPARENT'S RISKS FOR CHRONIC DISEASES (REVERSE BARKER HYPOTHESIS). PUB-MED AND EMBASE WERE REVIEWED FOR MESH TERMS "FETAL PROGRAMMING" AND "PREGNANCY COMPLICATIONS COMBINED WITH MATERNAL DISEASE" UNTIL JANUARY 2017. STUDIES LINKING PREGNANCY COMPLICATIONS TO FUTURE CARDIOVASCULAR, METABOLIC, AND THROMBOTIC RISKS FOR MOTHER AND OFFSPRING WERE REVIEWED. WOMEN WITH A HISTORY OF MISCARRIAGE, FETAL GROWTH RESTRICTION, PREECLAMPSIA, PRETERM DELIVERY, OBESITY, EXCESSIVE GESTATIONAL WEIGHT GAIN, GESTATIONAL DIABETES, SUBFERTILITY, AND THROMBOPHILIA MORE FREQUENTLY DEMONSTRATE WITH ECHOCARDIOGRAPHIC ABNORMALITIES, HIGHER FASTING INSULIN, DEVIATING LIPIDS OR CLOTTING FACTORS AND SHOW DEFECTIVE ENDOTHELIAL FUNCTION. THROMBOPHILIA HINTS TO THROMBOTIC RISKS IN LATER LIFE. PREGNANCY ABNORMALITIES CORRELATE WITH FUTURE CARDIOVASCULAR AND METABOLIC COMPLICATIONS AND EARLIER MORTALITY. CONVERSELY, WOMEN WITH A NORMAL PREGNANCY HAVE LOWER RATES OF SUBSEQUENT DISEASES THAN THE GENERAL FEMALE POPULATION CREATING THE TERM: "PREGNANCY AS A WINDOW FOR FUTURE HEALTH." ALTHOUGH THE PLACENTA WORKS AS A GATEKEEPER, MANY PREGNANCY COMPLICATIONS MAY LEAD TO SICKNESS AND EARLIER DEATH IN LATER LIFE WHEN THE CHILD BECOMES AN ADULT. THE EPIGENETIC MECHANISMS AND THE MISMATCH BETWEEN PRE- AND POSTNATAL LIFE HAVE CREATED THE TERM "FETAL ORIGIN OF ADULT DISEASE." UP TO NOW, THE IMPACT OF CARDIOVASCULAR, METABOLIC, OR THROMBOTIC RISK PROFILES HAS BEEN INVESTIGATED SEPARATELY FOR MOTHER AND CHILD. IN THIS MANUSCRIPT, WE STRIVE TO ILLUSTRATE THE CONSEQUENCES FOR BOTH, FETUS AND MOTHER WITHIN A COHESIVE PERSPECTIVE AND THUS TRY TO DEMONSTRATE THE COMPLEX INTERRELATIONSHIP OF GENETICS AND EPIGENETICS FOR LONG-TERM HEALTH OF SOCIETIES AND FUTURE GENERATIONS. MATERNAL-FETAL MEDICINE SPECIALISTS SHOULD HAVE A KEY ROLE IN THE PREVENTION OF NON-COMMUNICABLE DISEASES BY IMPLEMENTING A FRAMEWORK FOR PATIENT CONSULTATION AND INTERDISCIPLINARY NETWORKS. HEALTH-CARE PROVIDERS AND POLICY MAKERS SHOULD INCREASINGLY INVEST IN A STRATIFIED PRIMARY PREVENTION AND FOLLOW-UP TO REDUCE THE INCREASING NUMBER OF MANIFEST CARDIOVASCULAR AND METABOLIC DISEASES AND TO PREVENT WASTE OF HEALTH-CARE RESOURCES.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
9  4078  48 MATERNAL INFLAMMATION, GROWTH RETARDATION, AND PRETERM BIRTH: INSIGHTS INTO ADULT CARDIOVASCULAR DISEASE. THE "FETAL ORIGIN OF ADULT DISEASE HYPOTHESIS" ORIGINALLY DESCRIBED BY BARKER ET AL. IDENTIFIED THE RELATIONSHIP BETWEEN IMPAIRED IN UTERO GROWTH AND ADULT CARDIOVASCULAR DISEASE RISK AND DEATH. SINCE THEN, NUMEROUS CLINICAL AND EXPERIMENTAL STUDIES HAVE CONFIRMED THAT EARLY DEVELOPMENTAL INFLUENCES CAN LEAD TO CARDIOVASCULAR, PULMONARY, METABOLIC, AND PSYCHOLOGICAL DISEASES DURING ADULTHOOD WITH AND WITHOUT ALTERATIONS IN BIRTH WEIGHT. THIS SO CALLED "FETAL PROGRAMMING" INCLUDES DEVELOPMENTAL DISRUPTION, IMMEDIATE ADAPTATION, OR PREDICTIVE ADAPTATION AND CAN LEAD TO EPIGENETIC CHANGES AFFECTING A SPECIFIC ORGAN OR OVERALL HEALTH. THE INTRAUTERINE ENVIRONMENT IS DRAMATICALLY IMPACTED BY THE OVERALL MATERNAL HEALTH. BOTH PREMATURE BIRTH OR LOW BIRTH WEIGHT CAN RESULT FROM A VARIETY OF MATERNAL CONDITIONS INCLUDING UNDERNUTRITION OR DYSNUTRITION, METABOLIC DISEASES, CHRONIC MATERNAL STRESSES INDUCED BY INFECTIONS AND INFLAMMATION, AS WELL AS HYPERCHOLESTEROLEMIA AND SMOKING. NUMEROUS ANIMAL STUDIES HAVE SUPPORTED THE IMPORTANCE OF BOTH MATERNAL HEALTH AND MATERNAL ENVIRONMENT ON THE LONG TERM OUTCOMES OF THE OFFSPRING. WITH INCREASING RATES OF OBESITY AND DIABETES AND SURVIVAL OF PRETERM INFANTS BORN AT EARLY GESTATIONAL AGES, THE NEED TO ELUCIDATE MECHANISMS RESPONSIBLE FOR PROGRAMMING OF ADULT CARDIOVASCULAR DISEASE IS ESSENTIAL FOR THE TREATMENT OF UPCOMING GENERATIONS.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
10  5439  49 RENAL CONSEQUENCES OF PRETERM BIRTH. BACKGROUND: THE DEVELOPMENTAL ORIGIN OF HEALTH AND DISEASE CONCEPT IDENTIFIES THE BRAIN, CARDIOVASCULAR, LIVER, AND KIDNEY SYSTEMS AS TARGETS OF FETAL ADVERSE PROGRAMMING WITH ADULT CONSEQUENCES. AS THE LIMITS OF VIABILITY IN PREMATURE INFANTS HAVE BEEN PUSHED TO LOWER GESTATIONAL AGES, THE LONG-TERM IMPACT OF PREMATURITY ON KIDNEYS STILL REMAINS A SIGNIFICANT BURDEN DURING HOSPITAL STAY AND BEYOND. OBJECTIVES: THE PURPOSE OF THIS STUDY IS TO SUMMARIZE AVAILABLE EVIDENCE, MECHANISMS, AND SHORT- AND LONG-TERM RENAL CONSEQUENCES OF PREMATURITY AND IDENTIFY NEPHROPROTECTIVE STRATEGIES AND AREAS OF UNCERTAINTY. RESULTS: KIDNEY SIZE AND NEPHRON NUMBER ARE KNOWN TO BE REDUCED IN SURVIVING PREMATURE INFANTS DUE TO DISRUPTION OF ORGANOGENESIS AT A CRUCIAL DEVELOPMENTAL TIME POINT. INFLAMMATION, HYPEROXIA, AND ANTIANGIOGENIC FACTORS PLAY A ROLE IN EPIGENETIC CONDITIONING WITH POTENTIAL LIFE-LONG CONSEQUENCES. ADDITIONAL KIDNEY INJURY FROM HYPOPERFUSION AND NEPHROTOXICITY RESULTS IN STRUCTURAL AND FUNCTIONAL CHANGES OVER TIME WHICH ARE OFTEN UNNOTICED. NEPHROPATHY OF PREMATURITY AND ACUTE KIDNEY INJURY CONFOUND GLOMERULAR AND TUBULAR MATURATION OF PRETERM KIDNEYS. KIDNEY PROTECTIVE STRATEGIES MAY AMELIORATE GROWTH FAILURE AND SUBOPTIMAL NEURODEVELOPMENTAL OUTCOMES IN THE SHORT TERM. IN LATER LIFE, SUBCLINICAL CHRONIC RENAL DISEASE MAY PROGRESS, EVEN IN ASYMPTOMATIC SURVIVORS. CONCLUSION: AWARENESS OF RENAL IMPLICATIONS OF THERAPEUTIC INTERVENTIONS AND RENAL CONSERVATION EFFORTS MAY LEAD TO A VARIETY OF SHORT AND LONG-TERM BENEFITS. ADEQUATE MONITORING AND SUPPLEMENTATION OF MICROELEMENT LOSSES, GATHERING IMPROVED DATA ON RENAL HANDLING, AND EXPLORATION OF NEW AVENUES SUCH AS RELIABLE MARKERS OF INJURY AND NEW THERAPEUTIC STRATEGIES IN CONTEMPORARY POPULATIONS, AS WELL AS LONG-TERM FOLLOW-UP OF RENAL FUNCTION, IS WARRANTED.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
11  2801  36 FEMALE OBESITY: SHORT- AND LONG-TERM CONSEQUENCES ON THE OFFSPRING. THE WORLDWIDE PREVALENCE OF OBESITY HAS RISEN OVER THE PAST FEW DECADES AND WOMEN ARE CURRENTLY MORE LIKELY THAN EVER TO ENTER PREGNANCY OBESE. PRE-PREGNANCY OBESITY AND EXCESSIVE GESTATIONAL WEIGHT GAIN INCREASE MISCARRIAGE RATES AND OBSTETRIC AND NEONATAL COMPLICATIONS, WHICH RESULT IN A LOWER HEALTHY LIVE BIRTH RATE. IN ADDITION TO ITS NEGATIVE CONSEQUENCES FOR THE MOTHER, OBESITY HAS BEEN SHOWN TO BE AN IMPORTANT RISK FACTOR FOR CHRONIC ILLNESSES, SUCH AS CARDIOVASCULAR DISEASE, METABOLIC SYNDROME AND TYPE 2 DIABETES IN THE ADOLESCENCE AND ADULTHOOD OF THE OFFSPRING. MOREOVER, MATERNAL OBESITY CAUSES PSYCHOLOGICAL PROBLEMS, PHYSICAL DISABILITIES AND HIGHER HEALTHCARE COSTS. FETAL PROGRAMMING OF METABOLIC FUNCTION INDUCED BY OBESITY, THROUGH PHYSIOLOGICAL AND/OR EPIGENETIC MECHANISMS, MAY HAVE AN INTERGENERATIONAL EFFECT AND COULD, THUS, PERPETUATE OBESITY IN THE NEXT GENERATION. IN ORDER TO BREAK THIS VICIOUS CIRCLE AND AVOID SERIOUS SHORT- AND LONG-TERM NEGATIVE OUTCOMES FOR BOTH MOTHERS AND FETUSES, THE PREVENTION AND ADEQUATE MANAGEMENT OF OBESITY AND GESTATIONAL WEIGHT GAIN ARE ESSENTIAL.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
12  3595  39 IMPLICATIONS OF MATERNAL CONDITIONS AND PREGNANCY COURSE ON OFFSPRING'S MEDICAL PROBLEMS IN ADULT LIFE. IN THE LAST DECADE, NUMEROUS EPIDEMIOLOGICAL, CLINICAL AND EXPERIMENTAL DATA SHOW THAT PERICONCEPTIONAL, PERINATAL AND POSTNATAL ENVIRONMENT DETERMINES THE OFFSPRING'S RISK FOR LATER-LIFE CHRONIC DISEASE. FOR THIS PHENOMENON, THE TERM "FETAL" OR "PERINATAL PROGRAMMING" IS USED. IN EXPOSED OFFSPRING ALREADY IN CHILDHOOD AND EARLY ADULTHOOD, METABOLIC AND CARDIOVASCULAR CHANGES CAN BE OBSERVED, LEADING TO OBESITY, DIABETES AND HYPERTENSION. NOWADAYS, THE MODE OF CONCEPTION (E.G., IN VITRO FERTILIZATION), MATERNAL METABOLIC CONDITIONS (E.G., UNDERNUTRITION, OVERNUTRITION, DIABETES) AND COMPLICATIONS DURING PREGNANCY (E.G., PREECLAMPSIA, INTRAUTERINE GROWTH RESTRICTION) ARE SUSPECTED TO BE NEGATIVE PREDICTORS FOR OFFSPRING'S LONG-TERM HEALTH. MECHANISMS RESPONSIBLE FOR THESE EFFECTS STILL REMAIN MAINLY UNCLEAR, BUT INCLUDE EPIGENETIC, TRANSCRIPTIONAL, ENDOPLASMIC RETICULUM STRESS, AND REACTIVE OXYGEN SPECIES. THIS REVIEW PRESENTS A PIECE OF THE PUZZLE WITH REGARDS TO PERICONCEPTIONAL AND EARLY PERINATAL CONDITIONS DETERMINING LATER-LIFE RISK FOR CHRONIC ADULT DISEASE.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
13  6625  37 UNDERSTANDING RACIAL DISPARITIES OF PRETERM BIRTH THROUGH THE PLACENTA. THE RACIAL DISPARITY ASSOCIATED WITH PRETERM BIRTH IS A PUBLIC HEALTH CONCERN IN THE UNITED STATES. THE PLACENTA IS THE PRINCIPAL METABOLIC, RESPIRATORY, AND ENDOCRINE ORGAN OF THE FETUS AND A KEY ROUTE BY WHICH ENVIRONMENTAL EXPOSURES ARE TRANSMITTED FROM MOTHER TO OFFSPRING. AVAILABLE AT EVERY DELIVERY, IT MAY SERVE AS A MARKER OF DIFFERENCES IN PRENATAL EXPOSURES THAT MANIFEST DIFFERENTLY BY RACE. RECENTLY, WE DESCRIBED DIFFERENCES IN PLACENTAL PATHOLOGY BETWEEN AFRICAN-AMERICAN AND WHITE PRETERM BIRTHS: THE PREVALENCE OF CHRONIC INFLAMMATION WAS HIGHER AMONG AFRICAN-AMERICAN WOMEN'S PLACENTAS COMPARED WITH THOSE OF WHITE WOMEN. SIMILARLY, RACIAL DIFFERENCES HAVE BEEN SHOWN IN PLACENTAL MALPERFUSION AND PLACENTAL WEIGHT. SOCIAL DETERMINANTS SUCH AS POVERTY AND STRESS FROM DISCRIMINATION HAVE BEEN IMPLICATED IN RACIAL DISPARITIES IN PRETERM BIRTH. TO DATE, HOWEVER, THE UNDERLYING BIOLOGICAL MECHANISMS, WHETHER THROUGH INFLAMMATORY, OXIDATIVE STRESS, OR OTHER PATHWAYS INVOLVING EPIGENETIC PROGRAMMING, REMAIN LARGELY UNKNOWN. THE PLACENTA, COMPLEMENTED BY MATERNAL AND UMBILICAL CORD BLOOD BIOMARKERS, MAY PROVIDE IMPORTANT INFORMATION ON THE PERINATAL ENVIRONMENT THAT EXPLAINS THE ORIGINS OF RACIAL DISPARITIES IN PRETERM BIRTH RATES AND SUBSEQUENT HEALTH OUTCOMES. THIS ARTICLE REVIEWS EXISTING LITERATURE AND CURRENT RESEARCH GAPS. OPPORTUNITIES ARE DISCUSSED FOR FUTURE PLACENTAL RESEARCH THAT MAY REVEAL NOVEL MECHANISMS LEADING TO THE DEVELOPMENT OF NEW APPROACHES IN THE PREVENTION AND MANAGEMENT OF PRETERM BIRTH AND ITS OUTCOMES.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
14   805  36 CHALLENGES AND PERSPECTIVES OF THE DOUBLE BURDEN OF MALNUTRITION IN LATIN AMERICA. NUTRITION IS A KEY FACTOR IN THE DEVELOPMENT OF NON-COMMUNICABLE CHRONIC DISEASES (NCCDS), ESPECIALLY CARDIOVASCULAR DISEASES (CVD) AND THEIR RISK FACTORS. THE "DOUBLE BURDEN OF MALNUTRITION" (DBM) IS THE COEXISTENCE OF UNDERNUTRITION AND OVERNUTRITION IN THE SAME POPULATION ACROSS THE LIFE-COURSE. IN LATIN AMERICA, THE TRANSITION FROM A PREDOMINANTLY UNDERWEIGHT TO AN OVERWEIGHT AND OBESE POPULATION HAS INCREASED MORE RAPIDLY THAN IN OTHER REGIONS IN THE WORLD. UNDERNUTRITION AND THE MICRONUTRIENT DEFICIENCIES PARTICULARLY IRON, ZINC, AND VITAMINS A AND D, PRESENT HIGH HETEROGENEITY IN LATIN AMERICAN COUNTRIES, AND ARE CURRENTLY CONSIDERED IMPORTANT PUBLIC HEALTH PROBLEMS. IN THIS REGION, NCCDS ACCOUNT FOR 50% OF THE DISABILITY-ADJUSTED LIFE-YEARS, LED BY CVD. THE MOST PREVALENT CARDIOVASCULAR RISK FACTORS ARE OVERWEIGHT, OBESITY, HYPERTENSION, DYSLIPIDEMIA AND TYPE 2 DIABETES MELLITUS. BECAUSE OF THE COST OF TREATMENT AND THE POTENTIAL YEARS OF LIFE LOST DUE TO PREMATURE DEATH, CVD IS KNOWN TO AFFECT THE POOREST SEGMENTS OF THE POPULATION, AFFECTING COMMUNITIES, AND GOVERNMENTS. MORE THAN 80% OF CVD DEATHS OCCUR IN LOW- AND MIDDLE-INCOME COUNTRIES. THE PERSISTENCE OF DAMAGE IN SOME CELLS DUE TO UNDERNUTRITION MAY EXPLAIN CERTAIN FINDINGS REGARDING THE INCREASE IN NCCD. THESE ASPECTS TOGETHER WITH EPIGENETIC CHANGES HAVE HIGHLIGHTED THE IMPORTANCE OF A LIFELONG APPROACH TO NUTRITIONAL POLICY DEVELOPMENT. REDUCING DBM REQUIRES MAJOR SOCIETAL INTERVENTIONS IN PUBLIC HEALTH AND NUTRITION TO ACHIEVE HOLISTIC CHANGE THAT CAN BE SUSTAINED OVER THE LONG TERM AND SPREAD THROUGHOUT THE GLOBAL FOOD SYSTEM. THE IMPLEMENTATION OF EFFECTIVE STATE POLICIES OF DOUBLE IMPACT ACTIONS SHOULD INFLUENCE BOTH SIDES OF THE BURDEN AND BE CONSIDERED AN URGENT PRIORITY, CONSIDERING COUNTRY-SPECIFIC INEQUALITIES AND SOCIO-DEMOGRAPHIC DIFFERENCES IN THE LATIN AMERICAN REGION, USING DIVERSE AND MULTIDISCIPLINARY STRATEGIES.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
15  3786  41 INTERGENERATIONAL INFLUENCES ON CHILD GROWTH AND UNDERNUTRITION. INTERGENERATIONAL EFFECTS ON LINEAR GROWTH ARE WELL DOCUMENTED. SEVERAL GENERATIONS ARE NECESSARY IN ANIMAL MODELS TO 'WASH OUT' EFFECTS OF UNDERNUTRITION, CONSISTENT WITH THE UNFOLDING OF THE SECULAR TREND IN HEIGHT IN EUROPE AND NORTH AMERICA. BIRTHWEIGHT IS CORRELATED ACROSS GENERATIONS AND SHORT MATERNAL STATURE, WHICH REFLECTS INTRAUTERINE AND INFANT GROWTH FAILURE, IS ASSOCIATED WITH LOW BIRTHWEIGHT, CHILD STUNTING, DELIVERY COMPLICATIONS AND INCREASED CHILD MORTALITY, EVEN AFTER ADJUSTING FOR SOCIO-ECONOMIC STATUS. A NUTRITION INTERVENTION IN GUATEMALA REDUCED CHILDHOOD STUNTING; IT ALSO IMPROVED GROWTH OF THE NEXT GENERATION, BUT ONLY IN THE OFFSPRING OF GIRLS. POSSIBLE MECHANISMS EXPLAINING INTERGENERATIONAL EFFECTS ON LINEAR GROWTH ARE NOT MUTUALLY EXCLUSIVE AND INCLUDE, AMONG OTHERS, SHARED GENETIC CHARACTERISTICS, EPIGENETIC EFFECTS, PROGRAMMING OF METABOLIC CHANGES, AND THE MECHANICS OF A REDUCED SPACE FOR THE FETUS TO GROW. THERE ARE ALSO SOCIO-CULTURAL FACTORS AT PLAY THAT ARE IMPORTANT SUCH AS THE INTERGENERATIONAL TRANSMISSION OF POVERTY AND THE FEAR OF BIRTHING A LARGE BABY, WHICH LEADS TO 'EATING DOWN' DURING PREGNANCY. IT IS NOT CLEAR WHETHER THERE IS AN UPPER LIMIT FOR IMPACT ON INTRAUTERINE AND INFANT LINEAR GROWTH THAT PROGRAMMES IN DEVELOPING COUNTRIES COULD ACHIEVE THAT IS SET BY EARLY CHILDHOOD MALNUTRITION IN THE MOTHER. SUBSTANTIAL IMPROVEMENTS IN LINEAR GROWTH CAN BE ACHIEVED THROUGH ADOPTION AND MIGRATION, AND IN A FEW SELECTED COUNTRIES, FOLLOWING RAPID ECONOMIC AND SOCIAL DEVELOPMENT. IT WOULD SEEM, DESPITE CLEAR DOCUMENTATION OF INTERGENERATIONAL EFFECTS, THAT NEARLY NORMAL LENGTHS CAN BE ACHIEVED IN CHILDREN BORN TO MOTHERS WHO WERE MALNOURISHED IN CHILDHOOD WHEN PROFOUND IMPROVEMENTS IN HEALTH, NUTRITION AND THE ENVIRONMENT TAKE PLACE BEFORE CONCEPTION. TO ACHIEVE SIMILAR LEVELS OF IMPACT THROUGH PUBLIC HEALTH PROGRAMMES ALONE IN POOR COUNTRIES IS HIGHLY UNLIKELY. THE REALITY IN POOR COUNTRIES LIMITS THE SCOPE, QUALITY AND COVERAGE OF PROGRAMMES THAT CAN BE IMPLEMENTED AND MODEST IMPACT SHOULD BE EXPECTED INSTEAD. THE LANCET SERIES ON MATERNAL AND CHILD UNDERNUTRITION ESTIMATED THAT IMPLEMENTATION TO SCALE OF PROVEN INTERVENTIONS IN HIGH BURDEN COUNTRIES WOULD REDUCE STUNTING BY ONE-THIRD; THIS IS PERHAPS A REALISTIC UPPER BOUND FOR IMPACT FOR HIGH QUALITY PROGRAMMES, UNLESS ACCOMPANIED BY SWEEPING IMPROVEMENTS IN SOCIAL SERVICES AND MARKED REDUCTIONS IN POVERTY. FINALLY, BECAUSE SO MUCH CAN BE ACHIEVED IN A SINGLE GENERATION, INTERGENERATIONAL INFLUENCES ARE UNLIKELY TO BE AN IMPORTANT EXPLANATION FOR LACK OF PROGRAMME IMPACT AIMED AT THE WINDOW OF THE FIRST 1000 DAYS. FAILURE TO PREVENT LINEAR GROWTH FAILURE IN DEVELOPING COUNTRIES HAS SERIOUS CONSEQUENCES FOR SHORT- AND LONG-TERM HEALTH AS WELL AS FOR THE FORMATION OF HUMAN CAPITAL. THE NUTRITION TRANSITION HAS CREATED A DOUBLE BURDEN BY ADDING OBESITY AND RELATED CHRONIC DISEASES TO THE PUBLIC HEALTH AGENDA OF COUNTRIES STILL STRUGGLING WITH THE 'OLD' PROBLEMS OF MATERNAL AND CHILD UNDERNUTRITION. THE CHALLENGE AHEAD IS TO INCREASE EFFORTS TO PREVENT LINEAR GROWTH FAILURE WHILE KEEPING CHILD OVERWEIGHT AT BAY.	2012	

16  6030  41 THE BURGEONING CARDIOVASCULAR DISEASE EPIDEMIC IN INDIANS - PERSPECTIVES ON CONTEXTUAL FACTORS AND POTENTIAL SOLUTIONS. CARDIOVASCULAR DISEASES (CVD) ARE THE LEADING CAUSE OF DEATH AND DISABILITY IN INDIA. THE CVD EPIDEMIC IN INDIANS IS CHARACTERIZED BY A HIGHER RELATIVE RISK BURDEN, AN EARLIER AGE OF ONSET, HIGHER CASE FATALITY AND HIGHER PREMATURE DEATHS. FOR DECADES, RESEARCHERS HAVE BEEN TRYING TO UNDERSTAND THE REASON FOR THIS INCREASED BURDEN AND PROPENSITY OF CVD AMONG INDIANS. IT CAN PARTLY BE EXPLAINED BY POPULATION-LEVEL CHANGES AND THE REMAINING BY INCREASED INHERENT BIOLOGICAL RISK. WHILE INCREASED BIOLOGICAL RISK CAN BE ATTRIBUTED TO PHENOTYPIC CHANGES CAUSED BY EARLY LIFE INFLUENCES, SIX MAJOR TRANSITIONS CAN BE CONSIDERED LARGELY RESPONSIBLE FOR THE POPULATION-LEVEL CHANGES IN INDIA-EPIDEMIOLOGICAL, DEMOGRAPHIC, NUTRITIONAL, ENVIRONMENTAL, SOCIAL-CULTURAL AND ECONOMIC. ALTHOUGH CONVENTIONAL RISK FACTORS EXPLAIN SUBSTANTIAL POPULATION ATTRIBUTABLE RISK, THE THRESHOLDS AT WHICH THESE RISK FACTORS OPERATE ARE DIFFERENT AMONG INDIANS COMPARED WITH OTHER POPULATIONS. THEREFORE, ALTERNATE EXPLANATIONS FOR THESE ECOLOGICAL DIFFERENCES HAVE BEEN SOUGHT AND MULTIPLE HYPOTHESES HAVE BEEN PROPOSED OVER THE YEARS. PRENATAL FACTORS THAT INCLUDE MATERNAL AND PATERNAL INFLUENCES ON THE OFFSPRING, AND POSTNATAL FACTORS, RANGING FROM BIRTH THROUGH CHILDHOOD, ADOLESCENCE AND YOUNG ADULTHOOD, AS WELL AS INTER-GENERATIONAL INFLUENCES HAVE BEEN EXPLORED USING THE LIFE COURSE APPROACH TO CHRONIC DISEASE. IN ADDITION TO THIS, RECENT RESEARCH HAS ILLUSTRATED THE IMPORTANCE OF THE ROLE OF INHERENT BIOLOGICAL DIFFERENCES IN LIPID METABOLISM, GLUCOSE METABOLISM, INFLAMMATORY STATES, GENETIC PREDISPOSITIONS AND EPIGENETIC INFLUENCES FOR THE INCREASED RISK. A MULTIFACETED AND HOLISTIC APPROACH TO CVD PREVENTION THAT TAKES INTO CONSIDERATION POPULATION-LEVEL AS WELL AS BIOLOGICAL RISK FACTORS WOULD BE NEEDED TO CONTROL THE BURGEONING CVD EPIDEMIC AMONG INDIANS.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
17  4202  28 METABOLIC SYNDROME IN CHILDREN BORN SMALL-FOR-GESTATIONAL AGE. BEING BORN SMALL-FOR-GESTATIONAL AGE AND A RAPID INCREASE IN WEIGHT DURING EARLY CHILDHOOD AND INFANCY HAS BEEN STRONGLY LINKED WITH CHRONIC DISEASES, INCLUDING METABOLIC SYNDROME, WHICH HAS BEEN RELATED TO INTRAUTERINE LIFE ENVIRONMENT AND LINKED TO EPIGENETIC FETAL PROGRAMMING. METABOLIC SYNDROME INCLUDES WAIST CIRCUMFERENCE >/= 90(TH) PERCENTILE FOR AGE, SEX AND RACE, HIGHER LEVELS OF BLOOD PRESSURE, TRIGLYCERIDES AND FASTING GLUCOSE, AND LOW LEVELS OF HDL-CHOLESTEROL. INSULIN RESISTANCE MAY BE PRESENT AS EARLY AS 1 YEAR OF AGE, AND OBESITY AND/OR TYPE 2 DIABETES ARE MORE PREVALENT IN THOSE BORN SGA THAN THOSE BORN AGA. THE PROGRAMMING OF ADAPTIVE RESPONSES IN CHILDREN BORN SGA INCLUDES AN ASSOCIATION WITH INCREASED BLOOD PRESSURE, CHANGES IN ENDOTHELIAL FUNCTION, ARTERIAL PROPERTIES AND CORONARY DISEASE. EARLY INTERVENTIONS SHOULD BE DIRECTED TO APPROPRIATE MATERNAL NUTRITION, BEFORE AND DURING PREGNANCY, PROMOTION OF BREAST FEEDING, AND PREVENTION OF RAPID WEIGHT GAIN DURING INFANCY, AND TO PROMOTE A HEALTHY LIFESTYLE.	2011	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
18  1776  36 ECONOMIC HARDSHIP AND BIOLOGICAL WEATHERING: THE EPIGENETICS OF AGING IN A U.S. SAMPLE OF BLACK WOMEN. BACKGROUND: PAST RESEARCH HAS LINKED LOW SOCIO-ECONOMIC STATUS (SES) TO INFLAMMATION, METABOLIC DYSREGULATION, AND VARIOUS CHRONIC AND AGE-RELATED DISEASES SUCH AS TYPE 2 DIABETES, CORONARY HEART DISEASE, STROKE, AND DEMENTIA. THESE STUDIES SUGGEST THAT THE CHALLENGES AND ADVERSITIES ASSOCIATED WITH LOW SES MAY RESULT IN PREMATURE AGING AND INCREASED RISK OF MORBIDITY AND MORTALITY. OBJECTIVE: BUILDING UPON THIS RESEARCH, THE PRESENT STUDY INVESTIGATES VARIOUS AVENUES WHEREBY LOW INCOME MIGHT ACCELERATE BIOLOGICAL AGING. METHODS: STRUCTURAL EQUATION MODELING AND LONGITUDINAL DATA FROM A SAMPLE OF 100 BLACK, MIDDLE-AGED WOMEN RESIDING IN THE UNITED STATES WAS USED TO INVESTIGATE THE EFFECT OF INCOME ON A RECENTLY DEVELOPED EPIGENETIC MEASURE OF BIOLOGICAL AGING. THIS MEASURE CAN BE USED AS A "BIOLOGICAL CLOCK" TO ASSESS, AT ANY POINT DURING ADULTHOOD, THE EXTENT TO WHICH AN INDIVIDUAL IS EXPERIENCING ACCELERATED OR DECELERATED BIOLOGICAL AGING. RESULTS: LOW INCOME DISPLAYED A ROBUST ASSOCIATION WITH ACCELERATED AGING THAT WAS UNAFFECTED AFTER CONTROLLING FOR OTHER SES-RELATED FACTORS SUCH AS EDUCATION, MARITAL STATUS, AND CHILDHOOD ADVERSITY. FURTHER, OUR ANALYSES INDICATED THAT THE ASSOCIATION BETWEEN INCOME AND BIOLOGICAL AGING WAS NOT EXPLAINED BY HEALTH-RELATED BEHAVIORS SUCH AS DIET, EXERCISE, SMOKING, ALCOHOL CONSUMPTION, OR HAVING HEALTH INSURANCE. RATHER, IN LARGE MEASURE, IT WAS FINANCIAL PRESSURE (DIFFICULTY PAYING BILLS, BUYING NECESSITIES, OR MEETING DAILY EXPENSES) THAT ACCOUNTED FOR THE ASSOCIATION BETWEEN LOW INCOME AND ACCELERATED AGING. CONCLUSIONS: THESE FINDINGS SUPPORT THE VIEW THAT CHRONIC FINANCIAL PRESSURES ASSOCIATED WITH LOW INCOME EXERT A WEATHERING EFFECT THAT RESULTS IN PREMATURE AGING.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
19  2805  44 FETAL MALNUTRITION AND LONG-TERM OUTCOMES. EPIDEMIOLOGICAL STUDIES HAVE SHOWN THAT LOWER BIRTHWEIGHT IS ASSOCIATED WITH A WIDE RANGE OF ADVERSE OUTCOMES IN LATER LIFE, INCLUDING POORER 'HUMAN CAPITAL' (SHORTER STATURE, LOWER COGNITIVE PERFORMANCE), INCREASED RISK FACTORS FOR LATER DISEASE (HIGHER BLOOD PRESSURE AND REDUCED GLUCOSE TOLERANCE, AND LUNG, KIDNEY AND IMMUNE FUNCTION), CLINICAL DISEASE (DIABETES, CORONARY HEART DISEASE, CHRONIC LUNG AND KIDNEY DISEASE), AND INCREASED ALL-CAUSE AND CARDIOVASCULAR MORTALITY. HIGHER BIRTHWEIGHT IS ASSOCIATED WITH AN INCREASED RISK OF CANCER AND (IF CAUSED BY GESTATIONAL DIABETES) OBESITY AND DIABETES. THE 'DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE' HYPOTHESIS PROPOSES THAT FETAL NUTRITION HAS PERMANENT EFFECTS ON GROWTH, STRUCTURE AND METABOLISM ('PROGRAMMING'). THIS IS SUPPORTED BY STUDIES IN ANIMALS SHOWING THAT MATERNAL UNDER- AND OVERNUTRITION DURING PREGNANCY CAN PRODUCE SIMILAR ABNORMALITIES IN THE ADULT OFFSPRING. COMMON CHRONIC DISEASES COULD POTENTIALLY BE PREVENTED BY ACHIEVING OPTIMAL FETAL NUTRITION, AND THIS COULD HAVE ADDITIONAL BENEFITS FOR SURVIVAL AND HUMAN CAPITAL. RECENT FOLLOW-UP OF CHILDREN BORN AFTER RANDOMIZED NUTRITIONAL INTERVENTIONS IN PREGNANCY PROVIDES WEAK EVIDENCE OF BENEFICIAL EFFECTS ON GROWTH, VASCULAR FUNCTION, LIPID CONCENTRATIONS, GLUCOSE TOLERANCE AND INSULIN RESISTANCE. ANIMAL STUDIES INDICATE THAT EPIGENETIC PHENOMENA MAY BE AN IMPORTANT MECHANISM UNDERLYING PROGRAMMING, AND THAT NUTRITIONAL INTERVENTIONS MAY NEED TO START PRECONCEPTIONALLY.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
20   303  35 AIR POLLUTION STRESS AND THE AGING PHENOTYPE: THE TELOMERE CONNECTION. AGING IS A COMPLEX PHYSIOLOGICAL PHENOMENON. THE QUESTION WHY SOME SUBJECTS GROW OLD WHILE REMAINING FREE FROM DISEASE WHEREAS OTHERS PREMATURELY DIE REMAINS LARGELY UNANSWERED. WE FOCUS HERE ON THE ROLE OF AIR POLLUTION IN BIOLOGICAL AGING. HALLMARKS OF AGING CAN BE GROUPED INTO THREE MAIN CATEGORIES: GENOMIC INSTABILITY, TELOMERE ATTRITION, AND EPIGENETIC ALTERATIONS LEADING TO ALTERED MITOCHONDRIAL FUNCTION AND CELLULAR SENESCENCE. AT BIRTH, THE INITIAL TELOMERE LENGTH OF A PERSON IS LARGELY DETERMINED BY ENVIRONMENTAL FACTORS. TELOMERE LENGTH SHORTENS WITH EACH CELL DIVISION AND EXPOSURE TO AIR POLLUTION AS WELL AS LOW RESIDENTIAL GREENS SPACE EXPOSURE IS ASSOCIATED WITH SHORTER TELOMERE LENGTH. RECENT STUDIES SHOW THAT THE ESTIMATED EFFECTS OF PARTICULATE AIR POLLUTION EXPOSURE ON THE TELOMERE MITOCHONDRIAL AXIS OF AGING MAY PLAY AN IMPORTANT ROLE IN CHRONIC HEALTH EFFECTS OF AIR POLLUTION. THE EXPOSOME ENCOMPASSES ALL EXPOSURES OVER AN ENTIRE LIFE. AS TELOMERES CAN BE CONSIDERED AS THE CELLULAR MEMORIES OF EXPOSURE TO OXIDATIVE STRESS AND INFLAMMATION, TELOMERE MAINTENANCE MAY BE A PROXY FOR ASSESSING THE "EXPOSOME". IF TELOMERES ARE CAUSALLY RELATED TO THE AGING PHENOTYPE AND ENVIRONMENTAL AIR POLLUTION IS AN IMPORTANT DETERMINANT OF TELOMERE LENGTH, THIS MIGHT PROVIDE NEW AVENUES FOR FUTURE PREVENTIVE STRATEGIES.	2016