1 5000 148 PERINATAL PROGRAMMING PREVENTION MEASURES. OVER THE PAST 10 YEARS, THERE HAS BEEN OUTSTANDING SCIENTIFIC PROGRESS RELATED TO PERINATAL PROGRAMMING AND ITS EPIGENETIC EFFECTS IN HEALTH, AND WE CAN ANTICIPATE THIS TREND WILL CONTINUE IN THE NEAR FUTURE. WE NEED TO MAKE USE AND APPLY THESE ACHIEVEMENTS TO HUMAN NEURODEVELOPMENT VIA PREVENTION INTERVENTIONS. BASED ON THE CONCEPT OF THE INTERACTION BETWEEN GENOME AND AMBIOME, THIS CHAPTER PROPOSES LOW-COST EASY-IMPLEMENTATION PREVENTIVE STRATEGIES FOR MATERNAL AND INFANT HEALTH INSTITUTIONS.BREASTFEEDING AND HUMAN MILK ADMINISTRATION ARE THE FIRST PREVENTIVE MEASURES, AS HAS BEEN REVIEWED IN THE POLICY STATEMENT OF THE AMERICAN ACADEMY OF PEDIATRICS. ANOTHER STRATEGY IS THE SAFE AND FAMILY-CENTERED MATERNITY HOSPITALS INITIATIVE THAT PROMOTES AND EMPOWERS THE INCLUSION OF THE FAMILIES AND THE RESPECT FOR THEIR RIGHTS, ESPECIALLY DURING PREGNANCY AND BIRTH. (THIS CHANGE OF PARADIGM WAS APPROVED AND IS RECOMMENDED BY BOTH UNITED NATIONS CHILDREN'S FUND, UNICEF, AND PAN AMERICAN HEALTH ORGANIZATION, PAHO.) THEN, THERE IS ALSO AN IMPORTANT EMPHASIS GIVEN TO THE SACRED HOUR-WHICH HIGHLIGHTS THE IMPACT OF BONDING, ATTACHMENT, AND BREASTFEEDING DURING THE FIRST HOUR OF LIFE-THE PAIN PREVENTION AND TREATMENT IN NEWBORNS, THE CONTROL OF THE "NEW MORBIDITY" REPRESENTED BY LATE PRETERM INFANTS, AND FINALLY, THE IMPORTANCE OF AVOIDING INTRAUTERINE AND EXTRAUTERINE GROWTH RESTRICTION. (HOWEVER, THERE ARE NOT YET CLEAR RECOMMENDATIONS ABOUT NUTRITIONAL INTERVENTIONS IN ORDER TO DIMINISH THE POTENTIAL METABOLIC SYNDROME CONSEQUENCE IN THE ADULT.). 2015 2 1749 30 EARLY LIFE INTERVENTIONS CAN SHAPE AGING. IT IS WELL DOCUMENTED THAT THE ENVIRONMENT OF THE DEVELOPING FETUS, INCLUDING AVAILABILITY OF NUTRIENTS AND PRESENCE OF TOXINS, CAN HAVE MAJOR IMPACT ON ADULT PHENOTYPE, AGE-RELATED TRAITS AND RISK OF CHRONIC DISEASE. THERE IS ALSO ACCUMULATING EVIDENCE THAT POSTNATAL ENVIRONMENT CAN IMPACT ADULT CHARACTERISTICS RELATED TO EVOLUTIONARY FITNESS, HEALTH, AND AGING. TO DETERMINE WHETHER EARLY LIFE HORMONAL INTERVENTIONS CAN ALTER TRAJECTORY OF AGING, WE HAVE EXAMINED THE EFFECTS OF EARLY LIFE GROWTH HORMONE (GH) REPLACEMENT THERAPY IN PROP1(DF) (AMES DWARF) MICE WHICH ARE GH DEFICIENT AND REMARKABLY LONG LIVED. TWICE-DAILY GH INJECTIONS BETWEEN THE AGES OF TWO AND EIGHT WEEKS COMPLETELY NORMALIZED ("RESCUED") A NUMBER OF ADULT METABOLIC CHARACTERISTICS BELIEVED TO CONTRIBUTE TO EXTENDED LONGEVITY OF THESE MUTANTS. IMPORTANTLY, LONGEVITY OF AMES DWARF MICE WAS REDUCED BY EARLY LIFE GH TREATMENT. THIS WAS ASSOCIATED WITH HISTONE H3 MODIFICATIONS. WE CONCLUDE THAT THE TRAJECTORY OF MAMMALIAN AGING CAN BE MODIFIED BY EARLY LIFE INTERVENTIONS. MECHANISTIC LINKS AMONG INTERVENTIONS DURING POSTNATAL DEVELOPMENT, ADULT METABOLIC CHARACTERISTICS, AGING, AND LONGEVITY, APPARENTLY INVOLVE EPIGENETIC PHENOMENA. 2022 3 4995 35 PERINATAL ENVIRONMENT AND ITS INFLUENCES ON METABOLIC PROGRAMMING OF OFFSPRING. THE INTRAUTERINE ENVIRONMENT SUPPORTS THE DEVELOPMENT AND HEALTH OF OFFSPRING. PERTURBATIONS TO THIS ENVIRONMENT CAN HAVE DETRIMENTAL EFFECTS ON THE FETUS THAT HAVE PERSISTENT PATHOLOGICAL CONSEQUENCES THROUGH ADOLESCENCE AND ADULTHOOD. THE DEVELOPMENTAL ORIGINS OF THE HEALTH AND DISEASE CONCEPT, ALSO KNOWN AS THE "BARKER HYPOTHESIS", HAS BEEN PUT FORTH TO DESCRIBE THE INCREASED INCIDENCE OF CHRONIC DISEASE SUCH AS CARDIOVASCULAR DISEASE AND DIABETES IN HUMANS AND ANIMALS EXPOSED TO A LESS THAN IDEAL INTRAUTERINE ENVIRONMENT. MATERNAL INFECTION, POOR OR EXCESS NUTRITION, AND STRESSFUL EVENTS CAN NEGATIVELY INFLUENCE THE DEVELOPMENT OF DIFFERENT CELL TYPES, TISSUES AND ORGAN SYSTEMS ULTIMATELY PREDISPOSING THE ORGANISM TO PATHOLOGICAL CONDITIONS. ALTHOUGH THERE ARE A VARIETY OF CONDITIONS ASSOCIATED TO EXPOSURE TO ALTERED INTRAUTERINE ENVIRONMENTS, THE FOCUS OF THIS REVIEW WILL BE ON THE CONSEQUENCES OF STRESS AND HIGH FAT DIET DURING THE PRE- AND PERINATAL PERIODS AND ASSOCIATED OUTCOMES RELATED TO OBESITY AND OTHER METABOLIC CONDITIONS. WE FURTHER DISCUSS POSSIBLE NEUROENDOCRINE AND EPIGENETIC MECHANISMS RESPONSIBLE FOR THE METABOLIC PROGRAMMING OF OFFSPRING. THE PAPER REPRESENTS AN INVITED REVIEW BY A SYMPOSIUM, AWARD WINNER OR KEYNOTE SPEAKER AT THE SOCIETY FOR THE STUDY OF INGESTIVE BEHAVIOR [SSIB] ANNUAL MEETING IN PORTLAND, JULY 2009. 2010 4 5091 28 PLACENTAL DISEASES ASSOCIATED WITH ASSISTED REPRODUCTIVE TECHNOLOGY. THE PLACENTA DEVELOPS FROM THE OUTER TROPHOBLASTIC LAYER FOLLOWING THE DIFFERENTIATION OF THE FERTILIZED OVUM AND IS THEREFORE MORE SUSCEPTIBLE TO EPIGENETIC REGULATORY CHANGES CAUSED BY ENVIRONMENTAL INTERVENTIONS AND INFLUENCES DURING ASSISTED REPRODUCTIVE TECHNOLOGY. FURTHERMORE, THE PLACENTA REGULATES THE DEVELOPMENT OF THE FETAL HEART, BRAIN, KIDNEYS, BONES, AND OTHER TISSUES AND ORGANS [1]. PLACENTAL DYSPLASIA LEADS TO POOR PERINATAL OUTCOMES AS WELL AS LONG-TERM HEALTH RISKS LATER IN LIFE, INCLUDING NEURODEVELOPMENTAL DISORDERS, TUMORS, AND ADULT METABOLIC SYNDROME [2,3]. IN VIEW OF THE DECISIVE ROLE OF THE PLACENTA DURING INTRAUTERINE FETAL DEVELOPMENT, GRAHAM J. BURTON, AN EXPERT IN PLACENTOLOGY FROM THE UNIVERSITY OF CAMBRIDGE, FORMALLY PROPOSED THE THEORY OF "PLACENTA-DERIVED CHRONIC DISEASES" IN 2018 BASED ON EMBRYONIC-DERIVED DISEASES [4]. IN THIS REVIEW, WE SUMMARIZED THE CHANGES IN PLACENTAL MORPHOLOGY AND STRUCTURE, GROWTH DYNAMICS, IMPRINTED AND NON-IMPRINTED GENES, AND OTHER ASPECTS ATTRIBUTABLE TO ASSISTED REPRODUCTION TECHNOLOGY. OUR REVIEW PROVIDES A THEORETICAL BASIS FOR FURTHER RESEARCH ON PLACENTAL CHANGES CAUSED BY ASSISTED REPRODUCTIVE TECHNOLOGY THAT ARE MOST STRONGLY ASSOCIATED WITH AN INCREASED RISK OF NEONATAL LONG-TERM DISEASES. 2021 5 4809 37 OBESITY PREVENTION. ONCE CONSIDERED A PROBLEM ONLY IN HIGH-INCOME COUNTRIES (HICS), OBESITY HAS BECOME A MAJOR CONTRIBUTOR TO THE GLOBAL DISEASE BURDEN (FINUCANE AND OTHERS 2011; MISRA AND KHURANA 2008). EXCESS ADIPOSITY, PARTICULARLY AROUND THE VISCERAL ABDOMINAL REGION, IS AN IMPORTANT RISK FACTOR FOR MORBIDITY AND MORTALITY FROM TYPE 2 DIABETES, CARDIOVASCULAR DISEASES, AND SOME CANCERS (DANAEI AND OTHERS 2009; WHITLOCK AND OTHERS 2009; WHO 2009). ALTHOUGH SOME STUDIES HAVE SUGGESTED LOWER MORTALITY AMONG OVERWEIGHT OR OBESE PERSONS THAN AMONG HEALTHY-WEIGHT PERSONS (CARNETHON AND OTHERS 2012), THIS OUTCOME HAS NOT BEEN OBSERVED IN STUDIES THAT PROPERLY ACCOUNT FOR THE CONFOUNDING EFFECTS OF SMOKING, PREEXISTING CHRONIC CONDITIONS, AND OTHER BIASES (GLOBAL BMI MORTALITY COLLABORATION 2016; TOBIAS, PAN, AND HU 2014). THE COSTS OF OBESITY AND COMORBID CONDITIONS ARE STAGGERING AS MEASURED BY BOTH HEALTH CARE EXPENDITURES AND QUALITY OF LIFE, UNDERSCORING THE IMPORTANCE OF IMPLEMENTING OBESITY PREVENTION STRATEGIES AND TREATMENT STRATEGIES ON A GLOBAL SCALE. THE CHANGES NEEDED TO REVERSE GLOBAL TRENDS IN OBESITY WILL LIKELY REQUIRE NUMEROUS INTERVENTIONS AND POLICY RECOMMENDATIONS THAT TARGET DIET, LIFESTYLE, ACCESS TO CARE, AND ENVIRONMENTAL RISK FACTORS. IN THIS CHAPTER, WE SUMMARIZE THE GLOBAL BURDEN OF OBESITY AND THE IMPACT OF A SPECTRUM OF OBESITY RISK FACTORS, RANGING FROM SOCIOPOLITICAL AND ECONOMIC FORCES THAT ARE LARGELY BEYOND AN INDIVIDUAL'S CONTROL TO MODIFIABLE LIFESTYLE FACTORS, AND DISCUSS GENETIC AND EPIGENETIC RISKS. WE ALSO REVIEW THE EFFECTIVENESS OF POPULATION-BASED INTERVENTIONS AND POLICIES FOR PREVENTING OBESITY, SOME INDIVIDUAL-LEVEL TREATMENT OPTIONS ACROSS VARIOUS PLATFORMS, AND THE COST-EFFECTIVENESS OF SELECT INTERVENTIONS. 2017 6 6853 37 [NEUROBIOLOGY OF EARLY LIFE TRAUMATIC STRESS AND TRAUMA: PROLONGED NEUROENDOCRINE DYSREGULATION AS A NEURODEVELOPMENTAL RISK FACTOR]. EARLY LIFE STRESSORS DISPLAY A HIGH UNIVERSAL PREVALENCE AND CONSTITUTE A MAJOR PUBLIC HEALTH PROBLEM WITH TWO THIRDS OF YOUTH BEING EXPOSED TO POTENTIALLY TRAUMATIC EXPERIENCES BY THE AGE OF 17. TRAUMATIC STRESS EXPOSURE DURING CRITICAL PERIODS OF DEVELOPMENT MAY HAVE ESSENTIAL AND LONG-LASTING EFFECTS ON THE PHYSICAL AND MENTAL HEALTH OF INDIVIDUALS AND REPRESENTS A DEVELOPMENTAL RISK FACTOR MEDIATING RISK FOR DISEASE. EARLY-LIFE STRESS (ELS) AND CHILDHOOD TRAUMA (CT) CAN BOTH HAVE AN IMPACT ON SENSITIVE NEURONAL BRAIN NETWORKS INVOLVED IN STRESS REACTIONS, AND COULD EXERT A PROGRAMMING EFFECT ON GLUCOCORTICOID SIGNALING LEADING TO CHRONIC HYPER- OR HYPO-ACTIVATION OF THE STRESS SYSTEM. IN ADDITION, ALTERATIONS IN EMOTIONAL AND AUTONOMIC REACTIVITY, CIRCADIAN RHYTHM DISRUPTION, FUNCTIONAL AND STRUCTURAL CHANGES IN THE BRAIN, AS WELL AS IMMUNE AND METABOLIC DYSREGULATION HAVE BEEN LATELY IDENTIFIED AS IMPORTANT RISK FACTORS FOR A CHRONICALLY IMPAIRED HOMEOSTATIC BALANCE AFTER ELS/CT. FURTHERMORE, HUMAN GENETIC BACKGROUND AND EPIGENETIC MODIFICATIONS THROUGH STRESS-RELATED GENE EXPRESSION COULD INTERACT WITH THESE ALTERATIONS AND EXPLAIN INTER-INDIVIDUAL VARIATION IN VULNERABILITY OR RESILIENCE TO STRESS. THIS NARRATIVE REVIEW PRESENTS RELEVANT EVIDENCE FROM MAINLY HUMAN RESEARCH ON THE MOST ACKNOWLEDGED NEUROBIOLOGICAL ALLOSTATIC PATHWAYS EXERTING ENDURING ADVERSE EFFECTS OF ELS/CT EVEN DECADES LATER. FUTURE STUDIES SHOULD PROSPECTIVELY INVESTIGATE POTENTIAL CONFOUNDERS, THEIR TEMPORAL SEQUENCE AND COMBINED EFFECTS AT THE BIOLOGICAL LEVEL, WHILE CONSIDERING THE POTENTIALLY DELAYED TIME-FRAME FOR THE EXPRESSION OF THEIR EFFECTS. FINALLY, SCREENING STRATEGIES FOR ELS/CT AND TRAUMA NEED TO BE IMPROVED. INFORMATION ABOUT ELS/CT HISTORY AND THE NUMBER OF ADVERSE EXPERIENCES COULD HELP TO BETTER IDENTIFY THE INDIVIDUAL RISK FOR DISEASE DEVELOPMENT, PREDICT INDIVIDUAL TREATMENT RESPONSE AND DESIGN PREVENTION STRATEGIES TO REDUCE THE NEGATIVE EFFECTS OF ELS/CT. 2023 7 1927 27 ENVIRONMENTAL EPIGENOMICS AND DISEASE SUSCEPTIBILITY. KEYSTONE SYMPOSIA ON MOLECULAR AND CELLULAR BIOLOGY. THE GROVE PARK HOTEL & SPA, ASHVILLE, NC, USA, 27 MARCH-1 APRIL 2011. THE MAIN OBJECTIVE OF THIS CONFERENCE WAS TO PROVIDE SOLID EVIDENCE THAT ENVIRONMENTAL EXPOSURES DURING EARLY DEVELOPMENT CAN AFFECT FAITHFUL REPRODUCTION OF INDIVIDUAL PARENTAL EPIGENOMES WITHOUT CHANGING DNA SEQUENCE IN THE OFFSPRING. NO DOUBT, THIS IMPORTANT GOAL HAS BEEN SUCCESSFULLY ACHIEVED OWING TO THE HIGH QUALITY OF PRESENTED EPIDEMIOLOGICAL AND EXPERIMENTAL STUDIES AND ENGAGING DISCUSSIONS OF MANY YET TO BE PUBLISHED RESULTS. COMPELLING DATA SUGGESTED A STRONG CAUSAL LINK BETWEEN PRENATAL VULNERABILITY OF FUTURE PARENTAL EPIGENOMES TO DAMAGING ENVIRONMENTAL FACTORS AGGRAVATED BY ABNORMAL SOCIO-CULTURAL CONDITIONS (INCLUDING, FOR INSTANCE, MALNUTRITION AND CHRONIC STRESS) AND THE ALARMING RISK OF DEVELOPING HERITABLE COMPLEX MEDICAL CONDITIONS LATER IN LIFE, SUCH AS ASTHMA, AUTISM, CANCER, CARDIOVASCULAR DISEASE, DIABETES, OBESITY, SCHIZOPHRENIA AND A WHOLE RANGE OF RARE NEUROMUSCULAR PATHOLOGIES. IT WAS CONCLUDED THAT MODERN EPIGENETIC RESEARCH PROMISES TO MARKEDLY IMPROVE OUR ABILITY TO DIAGNOSE, PREVENT AND TREAT THESE AND OTHER PATHOLOGICAL CONDITIONS OF HUMANS. HOWEVER, THE COMPLEX HERITABILITY PATTERN OF 'EPIGENETIC SYNDROMES' ALSO INTRODUCES UNIQUE LEGAL AND ETHICAL ISSUES THAT WERE DISCUSSED AT THE END OF THIS OUTSTANDING MEETING. 2011 8 14 38 3RD COLLEGE OF PAEDIATRICS AND CHILD HEALTH LECTURE--THE PAST, THE PRESENT AND THE SHAPE OF THINGS TO COME.. THE GROWTH TRENDS OF SINGAPORE CHILDREN SPANNING 5 DECADES ARE REVIEWED, BASED ON 8 ANTHROPOMETRIC STUDIES FROM 1957 TILL 2002. THE HEIGHTS OF PRE-SCHOOL CHILDREN AND SCHOOL AGE CHILDREN APPEAR TO HAVE OPTIMISED ACCORDING TO THEIR GENETIC POTENTIAL, BUT THE WEIGHTS AND BODY MASS INDICES OF CHILDREN STILL APPEAR TO BE INCREASING FROM 6 TO 18 YEARS FOR BOTH SEXES, PROBABLY AS A CONSEQUENCE OF INCREASING AFFLUENCE. THIS TREND IS REFLECTED IN THE INCREASING OBESITY PREVALENCE IN SCHOOL CHILDREN OVER THE PAST 30 YEARS, AND THE CONCOMITANT INCREASED MORBIDITY ASSOCIATED WITH THE METABOLIC SYNDROME, NECESSITATES FURTHER RESEARCH INTO THE CAUSES OF OBESITY. BARKER'S HYPOTHESIS FIRST SUGGESTED THAT CHANGES IN THE INTRA-UTERINE ENVIRONMENT CAN CAUSE FETAL ADAPTATIONS WHICH PERSIST INTO ADULTHOOD, AND ARE RESPONSIBLE FOR MANY CHRONIC DISEASES OF ADULT LIFE. MORE RECENTLY, INTENSE RESEARCH IN THE FIELD OF EPIGENETICS SUGGESTS THAT THE ENVIRONMENT CAN ALSO INFLUENCE THE PHENOTYPE THROUGH GENE EXPRESSION, THROUGH MODIFICATION OF DNA METHYLATION AND HISTONES WHICH, IN TURN, INFLUENCES GENE EXPRESSION. THE CHALLENGE FOR THE FUTURE IS TO DETERMINE IF THERE ARE CLEAR EPIGENETIC CHANGES, WHICH ARE RESPONSIBLE FOR THE INCREASED PREVALENCE OF CHILDHOOD AND ADOLESCENT OBESITY, AND WHETHER THESE CHANGES ARE TRANSMITTED THROUGH GENERATIONS. UNRAVELLING THESE EPIGENETIC MECHANISMS MAY BE THE KEY TO THE PREVENTION OF OBESITY AND THE METABOLIC SYNDROME. 2008 9 6422 29 THE THIN-FAT PHENOTYPE AND GLOBAL METABOLIC DISEASE RISK. PURPOSE OF REVIEW: THERE HAS BEEN A GREAT DEAL OF INTEREST IN THE THIN-FAT PHENOTYPE EVIDENT IN ASIAN INDIANS AND ITS RISK ASSOCIATIONS IN THE EPIDEMIC OF NONCOMMUNICABLE CHRONIC DISEASE ASSOCIATED WITH IT. THE CAUSE OF THIS PHENOTYPE IS PROBABLY RELATED TO LIFESTYLE AND ENVIRONMENT; HOWEVER, GENOTYPIC AND EPIGENETIC MODIFICATIONS IN UTERO ALSO HAVE BEEN CONSIDERED. RECENT FINDINGS: THE THIN-FAT PHENOTYPE OCCURS WHEN FAT IS ADDED TO AN ALREADY THIN FRAME. THIS MAY OCCUR WITH RURAL-URBAN MIGRATION, WHEN POSITIVE ENERGY BALANCE OCCURS IN A MIGRATING POPULATION WHO WERE PREDOMINANTLY THIN AND PHYSICALLY ACTIVE TO BEGIN WITH. THE ROLE OF THE PRE-EXISTING SKELETAL MUSCLE MASS AND ITS INTERACTION WITH NEWLY DEPOSITED FAT MUST BE CONSIDERED. THE THIN-FAT PHENOTYPE MAY BE PROGRAMMED DURING FETAL GROWTH, BUT THE EVIDENCE FOR THIS PHENOMENON IS STILL NOT COMPLETELY CLEAR. FINALLY, ALTHOUGH THERE IS INCREASED CHRONIC DISEASE MORBIDITY AT LOWER BMI AND YOUNGER AGE IN SOUTH ASIAN POPULATIONS, BMI-RELATED MORTALITY DOES NOT APPEAR TO FOLLOW THIS TREND. SUMMARY: AT PRESENT, THE WEIGHT OF EVIDENCE APPEARS TO LINK THE THIN-FAT PHENOTYPE TO AN ENVIRONMENTAL AND LIFESTYLE PHENOMENON OCCURRING IN PREVIOUSLY THIN PEOPLE. THIS IS PARTICULARLY RELEVANT IN INDIA, GIVEN THE PACE OF TRANSITION OVER THE LAST TWO DECADES. 2011 10 4808 31 OBESITY MANAGEMENT: AT THE FOREFRONT AGAINST DISEASE STIGMA AND THERAPEUTIC INERTIA. OBESITY IS A COMPLEX CHRONIC RELAPSING DISEASE, RESULTING FROM THE INTERACTION BETWEEN MULTIPLE ENVIRONMENTAL, GENETIC AND EPIGENETIC CAUSES, AND SUPPORTED BY CHANGES IN THE NEUROENDOCRINE MECHANISMS REGULATING ENERGY BALANCE AND BODY WEIGHT. ADIPOSE TISSUE DYSFUNCTION CONTRIBUTES TO OBESITY-RELATED COMPLICATIONS. HOWEVER, THE PREVALENT NARRATIVE ABOUT THE CAUSES AND MECHANISMS OF OBESITY REMAINS A MUCH MORE SIMPLISTIC ONE, BASED ON THE FALSE ASSUMPTION THAT INDIVIDUALS CAN FULLY CONTROL THEIR BODY WEIGHT THROUGH APPROPRIATE BEHAVIOURAL CHOICES. ACCORDING TO THIS NARRATIVE, OBESITY IS SIMPLY REVERSIBLE "PERSUADING" THE PATIENT TO FOLLOW HEALTHIER AND MORE VIRTUOUS INDIVIDUAL BEHAVIOURS (MORAL JUDGEMENT). THIS PERSISTENT NARRATIVE FORMS THE DEEP ROOT OF THE STIGMATISATION OF PEOPLE WITH OBESITY AT THE INDIVIDUAL LEVEL AND CREATES A CLEAR DISCREPANCY ON HOW OBESITY PREVENTION AND CURE ARE DESIGNED IN COMPARISON WITH THE CASE OF OTHER NON-COMMUNICABLE CHRONIC DISEASES (CLINICAL STIGMA). THE PROMOTION OF SYSTEMIC PREVENTIVE MEASURES AGAINST OBESITY IS NOT SUPPORTED AT A POLITICAL AND SOCIAL LEVEL BY THE PERSISTENCE OF A NARRATIVE OF OBESITY AS THE SIMPLE CONSEQUENCE OF INDIVIDUAL FAILURES AND LACK OF WILLPOWER. THE SIMPLISTIC NARRATIVE OF OBESITY AS A SELF-IMPOSED CONDITION WITH AN EASY WAY-OUT ("EAT LESS AND MOVE MORE") CREATES A CLEAR DISCREPANCY ON HOW OBESITY IS MANAGED BY HEALTH CARE SYSTEMS IN COMPARISON WITH OTHER NCDS. THE OVER-ESTIMATION OF THE EFFICACY OF THERAPEUTIC INTERVENTION SOLELY BASED ON PATIENTS EDUCATION AND LIFESTYLE MODIFICATION IS RESPONSIBLE OF THERAPEUTIC INERTIA IN HEALTH CARE PROFESSIONALS AND IN CLINICAL GUIDELINES, LIMITING OR DELAYING THE ADOPTION OF MORE EFFECTIVE THERAPEUTIC STRATEGIES, LIKE ANTI-OBESITY MEDICATIONS AND BARIATRIC SURGERY. IN CONCLUSION, THE PERSISTENCE OF A NARRATIVE DESCRIBING OBESITY AS A SELF-INDUCED EASILY REVERSIBLE CONDITION HAS PROFOUND CONSEQUENCES ON HOW OBESITY PREVENTION AND MANAGEMENT ARE BUILD, INCLUDING THE DESIGN AND IMPLEMENTATION OF OBESITY MANAGEMENT GUIDELINES AND A TENDENCY TO THERAPEUTIC INERTIA.LEVEL OF EVIDENCE: NO LEVEL OF EVIDENCE. 2022 11 1386 32 DIABETES: AN UPDATE ON THE PANDEMIC AND POTENTIAL SOLUTIONS. DIABETES MELLITUS IS A CHRONIC METABOLIC DISEASE WITH DEADLY, DISABLING, AND COSTLY CONSEQUENCES FOR INDIVIDUALS, FAMILIES, COMMUNITIES, AND COUNTRIES. ALTHOUGH THEY ARE PHENOTYPICALLY DISTINCT, DIABETES SUBTYPES (TYPE 1, TYPE 2, GESTATIONAL, AND OTHER FORMS) ARE ALL DEFINED BY ELEVATED BLOOD GLUCOSE LEVELS. APPROXIMATELY 95 PERCENT OF DIABETES CASES WORLDWIDE ARE TYPE 2 DIABETES (PREVIOUSLY KNOWN AS ADULT-ONSET OR NON-INSULIN-DEPENDENT DIABETES), WHICH IS THE FOCUS OF THIS CHAPTER. TYPE 1 DIABETES (PREVIOUSLY KNOWN AS INSULIN-DEPENDENT DIABETES) MOST COMMONLY BEGINS IN CHILDHOOD AND ADOLESCENCE. GESTATIONAL DIABETES REFERS TO ELEVATED BLOOD GLUCOSE LEVELS DURING PREGNANCY AMONG WOMEN WITHOUT PREVIOUS DIABETES AND IS ASSOCIATED WITH FETAL, BIRTHING, AND EARLY CHILDHOOD COMPLICATIONS AS WELL AS HIGHER RISK OF THE MOTHER DEVELOPING POSTGESTATION DIABETES. THE GROWTH OF DIABETES AND ITS IMPACTS HAVE ACCELERATED WORLDWIDE SINCE THE END OF THE TWENTIETH CENTURY (NCD-RISC 2016), LIKELY CORRELATED WITH EXPANSION OF DIABETES RISK FACTORS, ESPECIALLY POPULATION AGING AND OBESITY. DIABETES IS A MULTIFACTORIAL CONDITION. BECAUSE GENETIC, EPIGENETIC, LIFESTYLE, ECONOMIC, AND PSYCHOSOCIAL FACTORS ALL CONTRIBUTE TO THE DEVELOPMENT OF DIABETES (MCCARTHY 2010; STUMVOLL, GOLDSTEIN, AND VAN HAEFTEN 2005), PREVENTING AND MANAGING THE CONDITION REQUIRE ACTION AT POLICY, PROGRAM, CLINICAL PRACTICE, AND INDIVIDUAL LEVELS (HILL AND OTHERS 2013). RELIABLE AND MEANINGFUL ESTIMATES OF BURDENS, RISK FACTORS, AND EFFECTIVENESS AND COST-EFFECTIVENESS OF INTERVENTIONS AS WELL AS EVALUATIONS OF EXISTING POLICIES, ARE LIMITED; DATA ARE ESPECIALLY SCARCE IN LOW- AND MIDDLE-INCOME COUNTRIES (LMICS). THIS CHAPTER FOCUSES ON WHAT CAN AND SHOULD BE DONE TO ADDRESS DIABETES. WE PRESENT THE AVAILABLE DATA REGARDING GLOBAL BURDENS AND TRENDS IN DIABETES; REVIEW AVAILABLE EVIDENCE AND ASSESS THE EFFECTIVENESS AND COST-EFFECTIVENESS OF INTERVENTIONS TO PREVENT, DETECT, AND CONTROL DIABETES; AND REPORT SUMMARY EXPERT OPINIONS REGARDING THE PRIORITY AND FEASIBILITY OF IMPLEMENTING THESE INTERVENTIONS. ASSIMILATING EVIDENCE FROM COUNTRIES AT DIFFERENT INCOME LEVELS, WE PROVIDE GLOBAL PERSPECTIVES ON THE DIABETES PANDEMIC, RECOMMEND PRIORITY INTERVENTIONS, AND IDENTIFY REMAINING DATA GAPS. 2017 12 421 35 ANIMAL MODELS IN EPIGENETIC RESEARCH: INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE CONSIDERATIONS ACROSS THE LIFESPAN. THE RAPID EXPANSION AND EVOLUTION OF EPIGENETICS AS A CORE SCIENTIFIC DISCIPLINE HAVE RAISED NEW QUESTIONS ABOUT HOW ENDOGENOUS AND ENVIRONMENTAL FACTORS CAN INFORM THE MECHANISMS THROUGH WHICH BIOLOGICAL FORM AND FUNCTION ARE REGULATED. EXISTING AND PROPOSED ANIMAL MODELS USED FOR EPIGENETIC RESEARCH HAVE TARGETED A MYRIAD OF HEALTH AND DISEASE ENDPOINTS THAT MAY BE ACUTE, CHRONIC, AND TRANSGENERATIONAL IN NATURE. INITIATING EVENTS AND OUTCOMES MAY EXTEND ACROSS THE ENTIRE LIFESPAN TO ELICIT UNANTICIPATED PHENOTYPES THAT ARE OF PARTICULAR CONCERN TO INSTITUTIONAL ANIMAL CARE AND USE COMMITTEES (IACUCS). THE DYNAMICS AND PLASTICITY OF EPIGENETIC MECHANISMS PRODUCE EFFECTS AND CONSEQUENCES THAT ARE MANIFEST DIFFERENTIALLY WITHIN DISCREET SPATIAL AND TEMPORAL CONTEXTS, INCLUDING PRENATAL DEVELOPMENT, STEM CELLS, ASSISTED REPRODUCTIVE TECHNOLOGIES, PRODUCTION OF SEXUAL DIMORPHISMS, SENESCENCE, AND OTHERS. MANY DIETARY AND NUTRITIONAL INTERVENTIONS HAVE ALSO BEEN SHOWN TO HAVE A SIGNIFICANT IMPACT ON BIOLOGICAL FUNCTIONS AND DISEASE SUSCEPTIBILITIES THROUGH ALTERED EPIGENETIC PROGRAMMING. THE ENVIRONMENTAL, CHEMICAL, TOXIC, THERAPEUTIC, AND PSYCHOSOCIAL STRESSORS USED IN ANIMAL STUDIES TO ELICIT EPIGENETIC CHANGES CAN BECOME EXTREME AND SHOULD RAISE IACUC CONCERNS FOR THE WELL-BEING AND PROPER CARE OF ALL RESEARCH ANIMALS INVOLVED. EPIGENETICS RESEARCH IS RAPIDLY BECOMING AN INTEGRAL PART OF THE SEARCH FOR MECHANISMS IN EVERY MAJOR AREA OF BIOMEDICAL AND BEHAVIORAL RESEARCH AND WILL FOSTER THE CONTINUED DEVELOPMENT OF NEW ANIMAL MODELS. FROM THE IACUC PERSPECTIVE, CARE MUST BE TAKEN TO ACKNOWLEDGE THE PARTICULAR NEEDS AND CONCERNS CREATED BY SUPERIMPOSITION OF EPIGENETIC MECHANISMS OVER DIVERSE FIELDS OF INVESTIGATION TO ENSURE THE PROPER CARE AND USE OF ANIMALS WITHOUT IMPEDING SCIENTIFIC PROGRESS. 2012 13 1375 31 DEVELOPMENTAL PROGRAMMING OF ADULT HAEMATOPOIESIS SYSTEM. THE BARKER HYPOTHESIS OF 'FOETAL ORIGIN OF ADULT DISEASES' HAS LED TO EMPHASIZE THE CONCEPT OF 'DEVELOPMENTAL PROGRAMMING', BASED ON THE CRUCIAL ROLE OF EPIGENETIC FACTORS. ACCORDINGLY, IT HAS BEEN DEMONSTRATED THAT PARENTAL ADVERSITY (BEFORE CONCEPTION AND DURING PREGNANCY) AND FOETAL FACTORS (I.E., HYPOXIA, MALNUTRITION AND PLACENTAL INSUFFICIENCY) PERMANENTLY MODIFY THE PHYSIOLOGICAL SYSTEMS OF THE PROGENY, PREDISPOSING THEM TO PREMATURE AGEING AND CHRONIC DISEASE DURING ADULTHOOD. THUS, AN ALTERED FUNCTIONALITY OF THE ENDOCRINE, IMMUNE, NERVOUS AND CARDIOVASCULAR SYSTEMS IS OBSERVED IN THE PROGENY. HOWEVER, IT REMAINS TO BE UNDERSTOOD WHETHER THE HAEMATOPOIETIC SYSTEM ITSELF ALSO REPRESENTS A PORTRAIT OF FOETAL PROGRAMMING. HERE, WE PROVIDE EVIDENCE, REPORTING AND DISCUSSING RELATED THEORIES, AND RESULTS OF STUDIES DESCRIBED IN THE LITERATURE. IN ADDITION, WE HAVE OUTLINED OUR OPINIONS AND SUGGEST HOW IT IS POSSIBLE TO INTERVENE TO CORRECT FOETAL MAL-PROGRAMMING. SOME PRO-HEALTH INTERVENTIONS AND RECOMMENDATIONS ARE PROPOSED, WITH THE HOPE OF GUARANTEE THE HEALTH OF FUTURE GENERATIONS AND TRYING TO COMBAT THE CONTINUOUS INCREASE IN AGE-RELATED DISEASES IN HUMAN POPULATIONS. 2019 14 167 20 ABNORMAL PLACENTATION ASSOCIATED WITH INFERTILITY AS A MARKER OF OVERALL HEALTH. INFERTILITY AND THE FERTILITY TREATMENTS UTILIZED ARE ASSOCIATED WITH ABNORMAL PLACENTATION LEADING TO ADVERSE PREGNANCY OUTCOMES RELATED TO PLACENTATION, INCLUDING PRETERM BIRTH, LOW BIRTH WEIGHT, PLACENTA ACCRETE AND PLACENTA PREVIA. THIS MAY BE DUE TO THE UNDERLYING GENETICS PREDISPOSING TO INFERTILITY OR THE EPIGENETIC CHANGES ASSOCIATED WITH THE FERTILITY TREATMENTS UTILIZED, AS SPECIFIC DISEASE STATES LEADING TO INFERTILITY ARE AT INCREASED RISK OF ADVERSE OUTCOMES, INCLUDING PLACENTAL ABRUPTION, FETAL LOSS, GDM, AND OUTCOMES RELATED TO PLACENTATION, AS WELL AS THE TREATMENTS UTILIZED INCLUDING IN VITRO FERTILIZATION (IVF) AND NIFT (NON-IVF FERTILITY TREATMENT). PLACENTATION DEFECTS, LEADING TO ADVERSE MATERNAL AND FETAL OUTCOMES, WHICH ARE MORE PRONOUNCED IN THE INFERTILE POPULATION, OCCUR DUE TO CHANGES IN TROPHOBLAST INVASION, VASCULAR DEFECTS, CHANGES IN THE ENVIRONMENTAL MILIEU, CHRONIC INFLAMMATION AND OXIDATIVE STRESS. THESE SIMILAR PROCESSES ARE RECOGNIZED AS MAJOR CONTRIBUTORS TO LIFELONG RISK OF CARDIOVASCULAR AND METABOLIC DISEASE FOR BOTH THE MOTHER AND HER OFFSPRING. THUS, ABNORMAL PLACENTATION, FOUND TO BE MORE PREVALENT IN THE INFERTILE POPULATION, MAY BE THE KEY TO BETTER UNDERSTAND HOW INFERTILITY AFFECTS OVERALL AND LONG TERM HEALTH. 2017 15 705 22 BUILDING RISK-ON-A-CHIP MODELS TO IMPROVE BREAST CANCER RISK ASSESSMENT AND PREVENTION. PREVENTIVE ACTIONS FOR CHRONIC DISEASES HOLD THE PROMISE OF IMPROVING LIVES AND REDUCING HEALTHCARE COSTS. FOR SEVERAL DISEASES, INCLUDING BREAST CANCER, MULTIPLE RISK AND PROTECTIVE FACTORS HAVE BEEN IDENTIFIED BY EPIDEMIOLOGISTS. THE IMPACT OF MOST OF THESE FACTORS HAS YET TO BE FULLY UNDERSTOOD AT THE ORGANISM, TISSUE, CELLULAR AND MOLECULAR LEVELS. IMPORTANTLY, COMBINATIONS OF EXTERNAL AND INTERNAL RISK AND PROTECTIVE FACTORS INVOLVE COOPERATIVITY THUS, SYNERGIZING OR ANTAGONIZING DISEASE ONSET. MODELS ARE NEEDED TO MECHANISTICALLY DECIPHER CANCER RISKS UNDER DEFINED CELLULAR AND MICROENVIRONMENTAL CONDITIONS. HERE, WE BRIEFLY REVIEW BREAST CANCER RISK MODELS BASED ON 3D CELL CULTURE AND PROPOSE TO IMPROVE RISK MODELING WITH LAB-ON-A-CHIP APPROACHES. WE SUGGEST EPITHELIAL TISSUE POLARITY, DNA REPAIR AND EPIGENETIC PROFILES AS ENDPOINTS IN RISK ASSESSMENT MODELS AND DISCUSS THE DEVELOPMENT OF 'RISKS-ON-CHIPS' INTEGRATING BIOSENSORS OF THESE ENDPOINTS AND OF GENERAL TISSUE HOMEOSTASIS. RISKS-ON-CHIPS WILL HELP IDENTIFY BIOMARKERS OF RISK, SERVE AS SCREENING PLATFORMS FOR CANCER PREVENTIVE AGENTS, AND PROVIDE A BETTER UNDERSTANDING OF RISK MECHANISMS, HENCE RESULTING IN NOVEL DEVELOPMENTS IN DISEASE PREVENTION. 2013 16 4999 31 PERINATAL PROGRAMMING OF CIRCADIAN CLOCK-STRESS CROSSTALK. AN INTACT COMMUNICATION BETWEEN CIRCADIAN CLOCKS AND THE STRESS SYSTEM IS IMPORTANT FOR MAINTAINING PHYSIOLOGICAL HOMEOSTASIS UNDER RESTING CONDITIONS AND IN RESPONSE TO EXTERNAL STIMULI. THERE IS ACCUMULATING EVIDENCE FOR A RECIPROCAL INTERACTION BETWEEN BOTH-FROM THE SYSTEMIC TO THE MOLECULAR LEVEL. DISRUPTION OF THIS INTERACTION BY EXTERNAL FACTORS SUCH AS SHIFTWORK, JETLAG, OR CHRONIC STRESS INCREASES THE RISK OF DEVELOPING METABOLIC, IMMUNE, OR MOOD DISORDERS. FROM EXPERIMENTS IN RODENTS, WE KNOW THAT BOTH SYSTEMS MATURATE DURING THE PERINATAL PERIOD. DURING THAT TIME, EXOGENOUS FACTORS SUCH AS STRESS OR ALTERATIONS IN THE EXTERNAL PHOTOPERIOD MAY CRITICALLY AFFECT-OR PROGRAM-PHYSIOLOGICAL FUNCTIONS LATER IN LIFE. THIS DEVELOPMENTAL PROGRAMMING PROCESS HAS BEEN ATTRIBUTED TO MATERNAL STRESS SIGNALS REACHING THE EMBRYO, WHICH LASTINGLY CHANGE GENE EXPRESSION THROUGH THE INDUCTION OF EPIGENETIC MECHANISMS. DESPITE THE WELL-KNOWN FUNCTION OF THE ADULT CIRCADIAN SYSTEM IN TEMPORAL COORDINATION OF PHYSIOLOGY AND BEHAVIOR, THE ROLE OF MATERNAL AND EMBRYONIC CIRCADIAN CLOCKS DURING PREGNANCY AND POSTNATAL DEVELOPMENT IS STILL POORLY DEFINED. A BETTER UNDERSTANDING OF THE CIRCADIAN-STRESS CROSSTALK AT DIFFERENT PERIODS OF DEVELOPMENT MAY HELP TO IMPROVE STRESS RESISTANCE AND DEVISE PREVENTIVE AND THERAPEUTIC STRATEGIES AGAINST CHRONIC STRESS-ASSOCIATED DISORDERS. 2018 17 1766 34 EARLY-LIFE EXPERIENCES AND THE DEVELOPMENT OF ADULT DISEASES WITH A FOCUS ON MENTAL ILLNESS: THE HUMAN BIRTH THEORY. IN MAMMALS, EARLY ADVERSE EXPERIENCES, INCLUDING MOTHER-PUP INTERACTIONS, SHAPE THE RESPONSE OF AN INDIVIDUAL TO CHRONIC STRESS OR TO STRESS-RELATED DISEASES DURING ADULT LIFE. THIS HAS LED TO THE ELABORATION OF THE THEORY OF THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE, IN PARTICULAR ADULT DISEASES SUCH AS CARDIOVASCULAR AND METABOLIC DISORDERS. IN ADDITION, IN HUMANS, AS STATED BY MASSIMO FAGIOLI'S HUMAN BIRTH THEORY, BIRTH IS HEALTHY AND EQUAL FOR ALL INDIVIDUALS, SO THAT MENTAL ILLNESS DEVELOP EXCLUSIVELY IN THE POSTNATAL PERIOD BECAUSE OF THE QUALITY OF THE RELATIONSHIP IN THE FIRST YEAR OF LIFE. THUS, THIS REVIEW FOCUSES ON THE IMPORTANCE OF PROGRAMMING DURING THE EARLY DEVELOPMENTAL PERIOD ON THE MANIFESTATION OF ADULT DISEASES IN BOTH ANIMAL MODELS AND HUMANS. CONSIDERING THE OBVIOUS DIFFERENCES BETWEEN ANIMALS AND HUMANS WE CANNOT SYSTEMATICALLY MOVE FROM ANIMAL MODELS TO HUMANS. CONSEQUENTLY, IN THE FIRST PART OF THIS REVIEW, WE WILL DISCUSS HOW ANIMAL MODELS CAN BE USED TO DISSECT THE INFLUENCE OF ADVERSE EVENTS OCCURRING DURING THE PRENATAL AND POSTNATAL PERIODS ON THE DEVELOPMENTAL TRAJECTORIES OF THE OFFSPRING, AND IN THE SECOND PART, WE WILL DISCUSS THE ROLE OF POSTNATAL CRITICAL PERIODS ON THE DEVELOPMENT OF MENTAL DISEASES IN HUMANS. EPIGENETIC MECHANISMS THAT CAUSE REVERSIBLE MODIFICATIONS IN GENE EXPRESSION, DRIVING THE DEVELOPMENT OF A PATHOLOGICAL PHENOTYPE IN RESPONSE TO A NEGATIVE EARLY POSTNATAL ENVIRONMENT, MAY LIE AT THE CORE OF THIS PROGRAMMING, THEREBY PROVIDING POTENTIAL NEW THERAPEUTIC TARGETS. THE CONCEPT OF THE HUMAN BIRTH THEORY LEADS TO A COMPREHENSION OF THE MENTAL ILLNESS AS A PATHOLOGY OF THE HUMAN RELATIONSHIP IMMEDIATELY AFTER BIRTH AND DURING THE FIRST YEAR OF LIFE. 2017 18 650 20 BISPHENOL A AND HUMAN CHRONIC DISEASES: CURRENT EVIDENCES, POSSIBLE MECHANISMS, AND FUTURE PERSPECTIVES. BISPHENOL-A (BPA) IS ONE OF THE HIGHEST VOLUME CHEMICALS PRODUCED WORLDWIDE, WITH OVER 6BILLION POUNDS PRODUCED AND OVER 100T RELEASED INTO THE ATMOSPHERE EACH YEAR. RECENT EXTENSIVE LITERATURE HAS RAISED CONCERNS ABOUT ITS POSSIBLE IMPLICATION IN THE ETIOLOGY OF SOME HUMAN CHRONIC DISEASES SUCH AS DIABETES, OBESITY, REPRODUCTIVE DISORDERS, CARDIOVASCULAR DISEASES, BIRTH DEFECTS, CHRONIC RESPIRATORY AND KIDNEY DISEASES AND BREAST CANCER. IN THIS REVIEW, WE PRESENT THE HIGHLIGHTED EVIDENCES ON THE RELATIONSHIP BETWEEN BPA EXPOSURE AND HUMAN CHRONIC DISEASES AND WE DISCUSS ITS EVENTUAL MECHANISMS OF ACTION, ESPECIALLY GENETIC, EPIGENETIC AND ENDOCRINE DISRUPTION MECHANISMS WITH THE POSSIBLE INVOLVEMENT OF OXIDATIVE STRESS, MITOCHONDRIAL DYSFUNCTION AND CELL SIGNALING. 2014 19 4281 40 MICRONUTRIENTS IN PREGNANCY IN LOW- AND MIDDLE-INCOME COUNTRIES. PREGNANCY IS ONE OF THE MORE IMPORTANT PERIODS IN LIFE WHEN INCREASED MICRONUTRIENTS, AND MACRONUTRIENTS ARE MOST NEEDED BY THE BODY; BOTH FOR THE HEALTH AND WELL-BEING OF THE MOTHER AND FOR THE GROWING FOETUS AND NEWBORN CHILD. THIS BRIEF REVIEW AIMS TO IDENTIFY THE MICRONUTRIENTS (VITAMINS AND MINERALS) LIKELY TO BE DEFICIENT IN WOMEN OF REPRODUCTIVE AGE IN LOW- AND MIDDLE-INCOME COUNTRIES (LMIC), ESPECIALLY DURING PREGNANCY, AND THE IMPACT OF SUCH DEFICIENCIES. A GLOBAL PREVALENCE OF SOME TWO BILLION PEOPLE AT RISK OF MICRONUTRIENT DEFICIENCIES, AND MULTIPLE MICRONUTRIENT DEFICIENCIES OF MANY PREGNANT WOMEN IN LMIC UNDERLINE THE URGENCY TO ESTABLISHING THE OPTIMAL RECOMMENDATIONS, INCLUDING FOR DELIVERY. IT HAS LONG BEEN RECOGNIZED THAT ADEQUATE IRON IS IMPORTANT FOR BEST REPRODUCTIVE OUTCOMES, INCLUDING GESTATIONAL COGNITIVE DEVELOPMENT. SIMILARLY, IODINE AND CALCIUM HAVE BEEN RECOGNIZED FOR THEIR ROLES IN DEVELOPMENT OF THE FOETUS/NEONATE. LESS CLEAR EFFECTS OF DEFICIENCIES OF ZINC, COPPER, MAGNESIUM AND SELENIUM HAVE BEEN REPORTED. FOLATE SUFFICIENCY PERICONCEPTIONALLY IS RECOGNIZED BOTH BY THE PRACTICE OF PROVIDING FOLIC ACID IN ANTENATAL IRON/FOLIC ACID SUPPLEMENTATION AND BY INCREASING NUMBERS OF COUNTRIES FORTIFYING FLOURS WITH FOLIC ACID. OTHER VITAMINS LIKELY TO BE IMPORTANT INCLUDE VITAMINS B12, D AND A WITH THE WATER-SOLUBLE VITAMINS GENERALLY LESS LIKELY TO BE A PROBLEM. EPIGENETIC INFLUENCES AND THE LIKELY INFLUENCE OF MICRONUTRIENT DEFICIENCIES ON FOETAL ORIGINS OF ADULT CHRONIC DISEASES ARE CURRENTLY BEING CLARIFIED. MICRONUTRIENTS MAY HAVE OTHER MORE SUBTLE, UNRECOGNIZED EFFECTS. THE NECESSITY FOR IMPROVED DIETS AND HEALTH AND SANITATION ARE CONSISTENTLY RECOMMENDED, ALTHOUGH THESE ARE NOT ALWAYS AVAILABLE TO MANY OF THE WORLD'S PREGNANT WOMEN. CONSEQUENTLY, SUPPLEMENTATION PROGRAMMES, FORTIFICATION OF STAPLES AND CONDIMENTS, AND NUTRITION AND HEALTH SUPPORT NEED TO BE SCALED-UP, SUPPORTED BY SOCIAL AND CULTURAL MEASURES. BECAUSE OF THE LIFE-LONG INFLUENCES ON REPRODUCTIVE OUTCOMES, INCLUDING INTER-GENERATIONAL ONES, BOTH CLINICAL AND PUBLIC HEALTH MEASURES NEED TO ENSURE ADEQUATE MICRONUTRIENT INTAKES DURING PREGNANCY, BUT ALSO DURING ADOLESCENCE, THE FIRST FEW YEARS OF LIFE, AND DURING LACTATION. MANY ANTENATAL PROGRAMMES ARE NOT CURRENTLY ACHIEVING THIS. WE AIM TO ADDRESS THE NEED FOR MICRONUTRIENTS DURING PREGNANCY, THE IMPORTANCE OF MICRONUTRIENT DEFICIENCIES DURING GESTATION AND BEFORE, AND PROPOSE THE SCALING-UP OF CLINICAL AND PUBLIC HEALTH APPROACHES THAT ACHIEVE HEALTHIER PREGNANCIES AND IMPROVED PREGNANCY OUTCOMES. 2015 20 6730 20 WALK MORE, EAT LESS, DON'T STRESS. UNHEALTHY DIET, OBESITY, LACK OF PHYSICAL ACTIVITY, AND PSYCHOLOGIC STRESS ARE ASSOCIATED WITH INCREASED INFLAMMATION, OXIDATIVE STRESS, INSULIN RESISTANCE, AND DNA METHYLATION, WHICH ARE THE MAIN MECHANISMS OF CHRONIC DISEASES SUCH AS CANCER, HYPERTENSION, DIABETES, CARDIOVASCULAR DISEASE, AND ALZHEIMER'S DISEASE. IT HAS RECENTLY BEEN FOUND THAT HEALTHY DIET AND PHYSICAL ACTIVITY CAN REDUCE INFLAMMATORY MARKERS AND IMPROVE INSULIN SENSITIVITY RESULTING IN BETTER SURVIVORSHIP OUTCOMES IN PATIENTS WITH PROSTATE CANCER. AN "ANTI-INFLAMMATORY" LIFESTYLE, INCLUDING PHYSICAL ACTIVITY, HEALTHY BODY WEIGHT, HEALTHY DIET, AND STRESS REDUCTION, HAS BEEN ASSOCIATED WITH DECREASED CANCER RISK AND PROGRESSION. EPIGENETIC CHANGES DUE TO DNA METHYLATION AND ALTERED GENE EXPRESSION ASSOCIATED WITH UNHEALTHY LIFESTYLE CAN BE MODULATED BY HEALTHY BEHAVIORS. NATIONAL CENTER FOR COMPLEMENTARY AND INTEGRATIVE HEALTH (NCCIH) FOCUSES ON HEALTHY LIFESTYLE, AND IT SUPPORTS RESEARCH ON PSYCHOLOGIC AND PHYSICAL APPROACHES INCLUDING DIETARY SUPPLEMENTS AND PLANT-BASED PRODUCTS, AS WELL AS MIND AND BODY APPROACHES, SUCH AS YOGA, MASSAGE, MEDITATION, MINDFULNESS-BASED STRESS REDUCTION, AND ACUPUNCTURE. SEE RELATED ARTICLE BY LANGLAIS ET AL., P. 1760. 2022