1 6867 115 [PARENTAL AGEING AND ASSISTED REPRODUCTION TECHNOLOGIES: ANALYSIS OF RISK OF CHRONIC DISEASES IN THE PROGENY]. CONCEPTION OF A CHILD AT ADVANCED PARENTAL AGE (> 35 YEARS) HAS BEEN STEADILY INCREASING IN RECENT DECADES, ESPECIALLY IN DEVELOPED COUNTRIES. SOCIO-ECONOMIC FACTORS, EFFECTIVE CONTRACEPTIVES, AND THE AVAILABILITY OF ASSISTED REPRODUCTION TECHNOLOGIES (ART) HAVE A DIRECT IMPACT ON POSTPONING THE DECISION TO HAVE A BABY. ART ENABLES REPRODUCTIVE SUCCESS FOR PEOPLE DIAGNOSED AS INFERTILE OR WITH REDUCED POSSIBILITIES OF BECOMING PREGNANT DUE TO CONCOMITANT PATHOLOGIES. EPIDEMIOLOGICAL STUDIES INDICATE THAT BOTH ADVANCED PARENTAL AGE AND ART ARE ASSOCIATED WITH PATHOLOGIES OF PREGNANCY, SUCH AS GESTATIONAL DIABETES, RISK OF PRE-ECLAMPSIA, MISCARRIAGE, PLACENTAL ABRUPTION, PRETERM LABOR, STILLBIRTH, NEURODEVELOPMENTAL DISORDERS AND CHRONIC DISEASE OF THE OFFSPRING. IN OUR WORK, WE WILL FOCUS ON THE AVAILABLE INFORMATION ON METABOLIC CHANGES THAT INCREASE THE RISK OF DEVELOPING CARDIOVASCULAR DISEASES IN THE OFFSPRING OF PARENTS AT AN ADVANCED AGE AND CONCEIVED THROUGH ART. FINALLY, WE WILL ADDRESS THE SOURCES OF THE OBSERVED DISTURBANCES AT THE GAMETE AND EMBRYO LEVEL, RELATED TO OXYGEN STRESS, EPIGENETIC MODIFICATIONS AND DNA DAMAGE, CONSIDERING POSSIBLE RESCUE ACTIONS. 2022 2 167 31 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 3 6914 28 [VITAMIN D DEFICIENCY IN PREGNANCY AND ITS IMPACT ON THE FETUS, THE NEWBORN AND IN CHILDHOOD]. OBJECTIVE: VITAMIN D DEFICIENCY (VDD) IN PREGNANT WOMEN AND THEIR CHILDREN IS AN IMPORTANT HEALTH PROBLEM WITH SEVERE CONSEQUENCES FOR THE HEALTH OF BOTH. THUS, THE OBJECTIVES OF THIS REVIEW WERE TO REASSESS THE MAGNITUDE AND CONSEQUENCES OF VDD DURING PREGNANCY, LACTATION AND INFANCY, ASSOCIATED RISK FACTORS, PREVENTION METHODS, AND TO EXPLORE EPIGENETIC MECHANISMS IN EARLY FETAL LIFE CAPABLE OF EXPLAINING MANY OF THE NON-SKELETAL BENEFITS OF VITAMIN D (VID). DATA SOURCE: ORIGINAL AND REVIEW ARTICLES, AND CONSENSUS DOCUMENTS WITH ELEVATED LEVEL OF EVIDENCE FOR VDD-RELATED CLINICAL DECISIONS ON THE HEALTH OF PREGNANT WOMEN AND THEIR CHILDREN, AS WELL AS ARTICLES ON THE INFLUENCE OF VID ON EPIGENETIC MECHANISMS OF FETAL PROGRAMMING OF CHRONIC DISEASES IN ADULTHOOD WERE SELECTED AMONG ARTICLES PUBLISHED ON PUBMED OVER THE LAST 20 YEARS, USING THE SEARCH TERM VITD STATUS, IN COMBINATION WITH PREGNANCY, OFFSPRING HEALTH, CHILD OUTCOMES, AND PROGRAMMING. DATA SYNTHESIS: THE FOLLOWING ITEMS WERE ANALYZED: VID PHYSIOLOGY AND METABOLISM, RISK FACTORS FOR VDD AND IMPLICATIONS IN PREGNANCY, LACTATION AND INFANCY, CONCENTRATION CUTOFF TO DEFINE VDD, THE VARIABILITY OF METHODS FOR VDD DETECTION, RECOMMENDATIONS ON VID REPLACEMENT IN PREGNANT WOMEN, THE NEWBORN AND THE CHILD, AND THE EPIGENETIC INFLUENCE OF VID. CONCLUSIONS: VDD IS A COMMON CONDITION AMONG HIGH-RISK PREGNANT WOMEN AND THEIR CHILDREN. THE ROUTINE MONITORING OF SERUM 25(OH)D3 LEVELS IN ANTENATAL PERIOD IS MANDATORY. EARLY PREVENTIVE MEASURES SHOULD BE TAKEN AT THE SLIGHTEST SUSPICION OF VDD IN PREGNANT WOMEN, TO REDUCE MORBIDITY DURING PREGNANCY AND LACTATION, AS WELL AS ITS SUBSEQUENT IMPACT ON THE FETUS, THE NEWBORN AND THE CHILD. 2015 4 5091 30 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 5 608 29 BEYOND HOMEOSTASIS: UNDERSTANDING THE IMPACT OF PSYCHOSOCIAL FACTORS ON APPETITE USING NONHUMAN PRIMATE MODELS. ANIMAL MODELS HAVE PROVEN TO BE EXCEPTIONALLY INFORMATIVE IN DEFINING NEUROPEPTIDE REGULATION OF APPETITE AND ENERGY HOMEOSTASIS (GAO AND HORVATH 2007, BERTHOUD 2012, WILLIAMS AND ELMQUIST 2012). MORE RECENT STUDIES USING A RANGE OF ANIMAL MODELS AND MOLECULAR TOOLS ARE ELUCIDATING HOW EPIGENETIC CHANGES RESULTING FROM SPECIFIC PRENATAL AND POSTNATAL DIETARY ENVIRONMENTS OR EXPERIENCES AFFECT METABOLIC PROCESSES AND APPETITE REGULATION (LEVIN 2008, ZAMBRANO AND NATHANIELSZ 2013, BURDGE AND LILLYCROP 2014). TAKEN TOGETHER, THESE APPROACHES ARE HELPING TO DEFINE POSSIBLE TREATMENT INTERVENTIONS FOR EATING DISORDERS IN PEOPLE (CASPER, SULLIVAN, AND TECOTT 2008, FOLTIN 2012, VAN GESTEL ET AL. 2014, LUTTER, CROGHAN, AND CUI 2016). THE CHOICE OF ANIMAL USED IS BEST DICTATED BY THE QUESTION BEING ADDRESSED. BECAUSE OF SIMILARITIES IN PHYSIOLOGY AND NEUROBIOLOGY, STUDIES OF CAPTIVE NONHUMAN PRIMATES HAVE BEGUN TO CONTRIBUTE SIGNIFICANTLY TO OUR UNDERSTANDING OF APPETITE REGULATION (SEE WILSON ET AL. 2014 FOR A REVIEW). IMPORTANTLY, THE USE OF NONHUMAN PRIMATE MODELS PROVIDES THE UNIQUE OPPORTUNITY TO EXTEND ANALYSES BEYOND A FOCUS ON THE HOMEOSTATIC REGULATION OF APPETITE. THIS IS PARTICULARLY RELEVANT GIVEN THE WELL-ESTABLISHED NOTION THAT A NUMBER OF PSYCHOSOCIAL FACTORS INFLUENCE FOOD INTAKE IN PEOPLE (BRUCE AND RICCIARDELLI 2015), INCLUDING CHRONIC STRESSOR EXPOSURE (TSENKOVA, BOYLAN, AND RYFF 2013), EVEN IN CHILDREN (NGUYEN-RODRIGUEZ, UNGER, AND SPRUIJT-METZ 2009). WHILE THE IMPORTANCE OF PSYCHOSOCIAL FACTORS CAN BE MODELED IN NONPRIMATE ANIMALS (TAMASHIRO, HEGEMAN, AND SAKAI 2006), SOCIALLY HOUSED NONHUMAN PRIMATES SHARE MANY CHARACTERISTICS IN ADDITION TO PHYSIOLOGY AND NEUROBIOLOGY, WITH HUMANS INCREASING THE TRANSLATIONAL VALUE OF THESE PRE-CLINICAL STUDIES. 2017 6 4281 37 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 7 6173 43 THE HEALTH OUTCOMES OF HUMAN OFFSPRING CONCEIVED BY ASSISTED REPRODUCTIVE TECHNOLOGIES (ART). CONCERNS HAVE BEEN RAISED ABOUT THE HEALTH AND DEVELOPMENT OF CHILDREN CONCEIVED BY ASSISTED REPRODUCTIVE TECHNOLOGIES (ART) SINCE 1978. CONTROVERSIALLY, ART HAS BEEN LINKED WITH ADVERSE OBSTETRIC AND PERINATAL OUTCOMES, AN INCREASED RISK OF BIRTH DEFECTS, CANCERS, AND GROWTH AND DEVELOPMENT DISORDERS. EMERGING EVIDENCE SUGGESTS THAT ART TREATMENT MAY ALSO PREDISPOSE INDIVIDUALS TO AN INCREASED RISK OF CHRONIC AGEING RELATED DISEASES SUCH AS OBESITY, TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE. THIS REVIEW WILL SUMMARIZE THE AVAILABLE EVIDENCE ON THE SHORT-TERM AND LONG-TERM HEALTH OUTCOMES OF ART SINGLETONS, AS MULTIPLE PREGNANCIES AFTER MULTIPLE EMBRYOS TRANSFER, ARE ASSOCIATED WITH LOW BIRTH WEIGHT AND PRETERM DELIVERY, WHICH CAN SEPARATELY INCREASE RISK OF ADVERSE POSTNATAL OUTCOMES, AND IMPACT LONG-TERM HEALTH. WE WILL ALSO EXAMINE THE POTENTIAL FACTORS THAT MAY CONTRIBUTE TO THESE HEALTH RISKS, AND DISCUSS UNDERLYING MECHANISMS, INCLUDING EPIGENETIC CHANGES THAT MAY OCCUR DURING THE PREIMPLANTATION PERIOD AND REPROGRAM DEVELOPMENT IN UTERO, AND ADULT HEALTH, LATER IN LIFE. LASTLY, THIS REVIEW WILL CONSIDER THE FUTURE DIRECTIONS WITH THE VIEW TO OPTIMIZE THE LONG-TERM HEALTH OF ART CHILDREN. 2017 8 5763 20 SOME COMMENTS ON MASOCHISM AND THE DELUSION OF OMNIPOTENCE FROM A DEVELOPMENTAL PERSPECTIVE. THIS PAPER EXPLORES THE RELATION OF THE DELUSION OF OMNIPOTENCE TO MASOCHISM AND SUGGESTS THAT THIS FANTASY CONSTITUTES A MAJOR COMPONENT OF THE RESISTANCE SO PROMINENT IN WORK WITH MASOCHISTIC PATIENTS. THE CONNECTIONS AMONG MASOCHISM, OMNIPOTENCE, NEGATIVE THERAPEUTIC REACTION, AND CLINGING TO PAIN ARE DISCUSSED. THE CLASSICAL VIEW HAS BEEN THAT THE FAILURE OF INFANTILE OMNIPOTENCE FORCES THE CHILD TO TURN TO REALITY. OUR EXPERIENCE WITH MASOCHISTIC PATIENTS SUGGESTS THAT IT IS THE REAL FAILURE TO ACHIEVE COMPETENT INTERACTIONS WITH OTHERS THAT FORCES THE CHILD TO TURN TO OMNIPOTENT SOLUTIONS. THE DISTINCTION IS MADE BETWEEN FANTASIES THAT ENHANCE THE REAL CAPACITIES OF THE SELF AND THOSE AIMED AT DENYING AND TRANSFORMING THE PAIN AND INADEQUACY OF THE MOTHER-CHILD RELATIONSHIP. THE EPIGENETIC TRANSFORMATIONS OF OMNIPOTENT FANTASIES THROUGH ALL LEVELS OF DEVELOPMENT ARE DESCRIBED. THE PATIENT'S NEED TO PROTECT THE OMNIPOTENT FANTASY IS DISCUSSED IN RELATION TO RESISTANCE AT EACH PHASE OF ANALYSIS. 1991 9 2986 36 GENETIC ENGINEERING TO ENHANCE CROP-BASED PHYTONUTRIENTS (NUTRACEUTICALS) TO ALLEVIATE DIET-RELATED DISEASES. NUTRITION STUDIES HAVE PROVIDED UNAMBIGUOUS EVIDENCE THAT A NUMBER OF HUMAN HEALTH MALADIES INCLUDING CHRONIC CORONARY ARTERY, HYPERTENSION, DIABETES, OSTEOPOROSIS, CANCER AND AGE- AND LIFESTYLE-RELATED DISEASES ARE ASSOCIATED WITH THE DIET. SEVERAL FAVORABLE AND A FEW DELETERIOUS NATURAL DIETARY INGREDIENTS HAVE BEEN IDENTIFIED THAT PREDISPOSE HUMAN POPULATIONS TO VARIOUS GENETIC AND EPIGENETIC BASED DISORDERS. MEDIA DISSEMINATION OF THIS INFORMATION HAS GREATLY RAISED PUBLIC AWARENESS OF THE BENEFICIAL EFFECTS DUE TO INCREASED CONSUMPTION OF FRUIT, VEGETABLES AND WHOLE GRAIN CEREALS-FOODS RICH IN PHYTONUTRIENTS, PROTEIN AND FIBER. HOWEVER, THE PRESENCE OF INTRINSICALLY LOW LEVELS OF THE BENEFICIAL PHYTONUTRIENTS IN THE AVAILABLE GENOTYPES OF CROP PLANTS IS NOT ALWAYS AT PAR WITH THE RECOMMENDED DAILY ALLOWANCE (RDA) FOR DIFFERENT PHYTONUTRIENTS (NUTRACEUTICALS). MOLECULAR ENGINEERING OF CROP PLANTS HAS OFFERED A NUMBER OF TOOLS TO MARKEDLY ENHANCE INTRACELLULAR CONCENTRATIONS OF SOME OF THE BENEFICIAL NUTRIENTS, LEVELS THAT, IN SOME CASES, ARE CLOSER TO THE RDA THRESHOLD. THIS REVIEW BRINGS TOGETHER LITERATURE ON VARIOUS STRATEGIES UTILIZED FOR BIOENGINEERING BOTH MAJOR AND MINOR CROPS TO INCREASE THE LEVELS OF DESIRABLE PHYTONUTRIENTS WHILE ALSO DECREASING THE CONCENTRATIONS OF DELETERIOUS METABOLITES. SOME OF THESE INCLUDE INCREASES IN: PROTEIN LEVEL IN POTATO; LYSINE IN CORN AND RICE; METHIONINE IN ALFALFA; CAROTENOIDS (BETA-CAROTENE, PHYTOENE, LYCOPENE, ZEAXANTHIN AND LUTEIN) IN RICE, POTATO, CANOLA, TOMATO; CHOLINE IN TOMATO; FOLATES IN RICE, CORN, TOMATO AND LETTUCE; VITAMIN C IN CORN AND LETTUCE; POLYPHENOLICS SUCH AS FLAVONOL, ISOFLAVONE, RESVERATROL, CHLOROGENIC ACID AND OTHER FLAVONOIDS IN TOMATO; ANTHOCYANIN LEVELS IN TOMATO AND POTATO; ALPHA-TOCOPHEROL IN SOYBEAN, OIL SEED, LETTUCE AND POTATO; IRON AND ZINC IN TRANSGENIC RICE. ALSO, MOLECULAR ENGINEERING HAS SUCCEEDED IN CONSIDERABLY REDUCING THE LEVELS OF THE OFFENDING PROTEIN GLUTELIN IN RICE, OFFERING PROOF OF CONCEPT AND A NEW BEGINNING FOR THE DEVELOPMENT OF SUPER-LOW GLUTELIN CEREALS FOR CELIAC DISEASE PATIENTS. 2010 10 6490 24 TRACING SLOW PHENOPTOSIS TO THE PRENATAL STAGE IN SOCIAL VERTEBRATES. VLADIMIR SKULACHEV'S COINING OF THE TERM "PHENOPTOSIS" 25 YEARS AGO (SKULACHEV, V. P., BIOCHEMISTRY (MOSCOW), 62, 1997) HIGHLIGHTED THE THEORETICAL POSSIBILITY THAT AGING IS A PROGRAMMED PROCESS TO SPEED THE EXIT OF INDIVIDUALS POSING SOME DANGER TO THEIR SOCIAL GROUP. WHILE RAPID "ACUTE PHENOPTOSIS" MIGHT OCCUR AT ANY AGE (E.G., TO PREVENT SPREAD OF DEADLY INFECTIONS), "SLOW PHENOPTOSIS" IS GENERALLY CONSIDERED TO OCCUR LATER IN LIFE IN THE FORM OF CHRONIC AGE-RELATED DISORDERS. HOWEVER, RECENT RESEARCH INDICATES THAT RISKS FOR SUCH CHRONIC DISORDERS CAN BE GREATLY RAISED BY EARLY LIFE ADVERSITY, ESPECIALLY DURING THE PRENATAL STAGE. MUCH OF THIS RESEARCH USES INDICATORS OF BIOLOGICAL AGING, THE SPEEDING OR SLOWING OF NATURAL PHYSIOLOGICAL DETERIORATION IN RESPONSE TO ENVIRONMENTAL INPUTS, LEADING TO DIVERGENCE FROM CHRONOLOGICAL AGE. STUDIES USING BIOLOGICAL AGING INDICATORS COMMONLY FIND IT IS ACCELERATED NOT ONLY IN OLDER INDIVIDUALS WITH CHRONIC DISORDERS, BUT ALSO IN VERY YOUNG INDIVIDUALS WITH HEALTH PROBLEMS. THIS REVIEW WILL EXPLAIN HOW ACCELERATED BIOLOGICAL AGING EQUATES TO SLOW PHENOPTOSIS. ITS OCCURRENCE EVEN IN THE PRENATAL STAGE IS THEORETICALLY SUPPORTED BY W. D. HAMILTON'S PROPOSAL THAT OFFSPRINGS DETECTING THEY HAVE DANGEROUS MUTATIONS SHOULD THEN AUTOMATICALLY SPEED THEIR DEMISE, IN ORDER TO IMPROVE THEIR INCLUSIVE FITNESS BY GIVING THEIR PARENTS THE CHANCE TO PRODUCE OTHER FITTER SIBLINGS. 2022 11 6744 31 WHO CARES ABOUT OLIGOZOOSPERMIA WHEN WE HAVE ICSI. THE VALUE OF ASSESSING SUBFERTILE MALES WITH OLIGOZOOSPERMIA IS CONTROVERSIAL DUE TO PREVAILING NOTIONS THAT THERAPIES ARE LIMITED AND ICSI MAY PROVIDE THE COUPLE WITH A BABY WITHOUT THE NEED TO EXPLAIN THE NATURE OR CAUSE OF UNDERLYING MALE INFERTILITY. THIS ARTICLE HIGHLIGHTS THAT INDISCRIMINATELY OFFERING ICSI TO OLIGOZOOSPERMIC MEN IS NOT FREE OF POTENTIAL ADVERSE EFFECTS AND DOES NOT GRANT SUBFERTILE MEN THE BEST FERTILITY PATHWAY. RECENT DATA SUPPORT ASSOCIATIONS BETWEEN OLIGOZOOSPERMIA AND POOR MALE REPRODUCTIVE HEALTH, DNA AND EPIGENETIC DAMAGE IN SPERMATOZOA, AND POSSIBLE ADVERSE HEALTH CONSEQUENCES TO OFFSPRING. MANY CONDITIONS AFFECTING THE TESTICLES ARE CAPABLE OF CAUSING OLIGOZOOSPERMIA (VARICOCELE, GENITAL INFECTIONS, CONGENITAL AND GENETIC DEFECTS TESTICULAR TORSION/TRAUMA, CHRONIC DISEASES, INADEQUATE LIFESTYLE, OCCUPATIONAL/ENVIRONMENTAL EXPOSURE TO TOXICANTS, DRUGS, CANCER AND RELATED TREATMENTS, ACUTE FEBRILE ILLNESS, ENDOCRINE DISORDERS, AND IATROGENIC DAMAGE TO THE GENITOURINARY SYSTEM). IF OLIGOZOOSPERMIA IS DETECTED, THERAPEUTIC INTERVENTIONS CAN IMPROVE SPERM QUANTITY/QUALITY AND THE OVERALL MALE HEALTH, ULTIMATELY RESULTING IN BETTER PREGNANCY OUTCOMES EVEN WHEN ICSI IS USED. FERTILITY CLINICS ARE URGED TO ENGAGE MALE INFERTILITY SPECIALISTS IN DIAGNOSING AND TREATING OLIGOZOOSPERMIA AS A MATTER OF BEST CLINICAL PRACTICE. A WELL-CONDUCTED MALE INFERTILITY EVALUATION REPRESENTS A UNIQUE OPPORTUNITY TO IDENTIFY RELEVANT MEDICAL AND INFERTILITY CONDITIONS, MANY OF WHICH MAY BE TREATED OR ALLEVIATED. THE ANDROLOGICAL ASSESSMENT MAY ALSO HELP GUIDE THE OPTIMAL APPLICATION OF ICSI. THE FINAL GOALS ARE TO POSITIVELY IMPACT THE OVERALL PATIENT HEALTH, THE COUPLE'S PREGNANCY PROSPECTS, AND THE OFFSPRING'S WELL-BEING. 2022 12 5814 16 STRESS AND FELINE HEALTH. IN THE HEALTH SCIENCES, STRESS OFTEN IS DEFINED IN TERMS OF STRESSORS; EVENTS THAT ARE PERCEIVED AS THREATS TO ONE'S PERCEPTION OF CONTROL. FROM THIS PERSPECTIVE, A STRESSOR IS ANYTHING THAT ACTIVATES THE CENTRAL THREAT RESPONSE SYSTEM (CTRS). RECENT RESEARCH SHOWS THAT THE CTRS CAN BE SENSITIZED TO ENVIRONMENTAL EVENTS THROUGH EPIGENETIC MODULATION OF GENE EXPRESSION. WHEN CTRS ACTIVATION IS CHRONIC, HEALTH AND WELFARE MAY BE HARMED. ENVIRONMENTAL MODIFICATION CAN MITIGATE THE HARMFUL EFFECTS OF CHRONIC CTRS ACTIVATION BY REDUCING THE INDIVIDUAL'S PERCEPTION OF THREAT AND INCREASING ITS PERCEPTION OF CONTROL, WHICH IMPROVES HEALTH AND WELFARE. 2020 13 5809 25 STRAWBERRY AND HUMAN HEALTH: EFFECTS BEYOND ANTIOXIDANT ACTIVITY. THE USEFULNESS OF A DIET RICH IN VEGETABLES AND FRUITS ON HUMAN HEALTH HAS BEEN WIDELY RECOGNIZED: A HIGH INTAKE OF ANTIOXIDANT AND BIOACTIVE COMPOUNDS MAY IN FACT PLAY A CRUCIAL ROLE IN THE PREVENTION OF SEVERAL DISEASES, SUCH AS CANCER, CARDIOVASCULAR, NEURODEGENERATIVE, AND OTHER CHRONIC PATHOLOGIES. THE STRAWBERRY (FRAGARIA X ANANASSA DUCH.) POSSESSES A REMARKABLE NUTRITIONAL COMPOSITION IN TERMS OF MICRONUTRIENTS, SUCH AS MINERALS, VITAMIN C, AND FOLATES, AND NON-NUTRIENT ELEMENTS, SUCH AS PHENOLIC COMPOUNDS, THAT ARE ESSENTIAL FOR HUMAN HEALTH. ALTHOUGH STRAWBERRY PHENOLICS ARE KNOWN MAINLY FOR THEIR ANTI-INFLAMMATORY AND ANTIOXIDANT ACTIONS, RECENT STUDIES HAVE DEMONSTRATED THAT THEIR BIOLOGICAL ACTIVITIES ALSO SPREAD TO OTHER PATHWAYS INVOLVED IN CELLULAR METABOLISM AND CELLULAR SURVIVAL. THIS PAPER HAS THE MAIN OBJECTIVE OF REVIEWING CURRENT INFORMATION ABOUT THE POTENTIAL MECHANISMS INVOLVED IN THE EFFECTS ELICITED BY STRAWBERRY POLYPHENOLS ON HUMAN HEALTH, DEVOTING SPECIAL ATTENTION TO THE LATEST FINDINGS. 2014 14 4046 39 MADE IN THE WOMB: MATERNAL PROGRAMMING OF OFFSPRING CARDIOVASCULAR FUNCTION BY AN OBESOGENIC WOMB. OBESITY INCIDENCE HAS BEEN INCREASING AT AN ALARMING RATE, ESPECIALLY IN WOMEN OF REPRODUCTIVE AGE. IT IS ESTIMATED THAT 50% OF PREGNANCIES OCCUR IN OVERWEIGHT OR OBESE WOMEN. IT HAS BEEN DESCRIBED THAT MATERNAL OBESITY (MO) PREDISPOSES THE OFFSPRING TO AN INCREASED RISK OF DEVELOPING MANY CHRONIC DISEASES IN AN EARLY STAGE OF LIFE, INCLUDING OBESITY, TYPE 2 DIABETES, AND CARDIOVASCULAR DISEASE (CVD). CVD IS THE MAIN CAUSE OF DEATH WORLDWIDE AMONG MEN AND WOMEN, AND IT IS MANIFESTED IN A SEX-DIVERGENT WAY. MATERNAL NUTRITION AND MO DURING GESTATION COULD PROMPT CVD DEVELOPMENT IN THE OFFSPRING THROUGH ADAPTATIONS OF THE OFFSPRING'S CARDIOVASCULAR SYSTEM IN THE WOMB, INCLUDING CARDIAC EPIGENETIC AND PERSISTENT METABOLIC PROGRAMMING OF SIGNALING PATHWAYS AND MODULATION OF MITOCHONDRIAL METABOLIC FUNCTION. CURRENTLY, DESPITE DIET SUPPLEMENTATION, EFFECTIVE THERAPEUTICAL SOLUTIONS TO PREVENT THE DELETERIOUS CARDIAC OFFSPRING FUNCTION PROGRAMMING BY AN OBESOGENIC WOMB ARE LACKING. IN THIS REVIEW, WE DISCUSS THE MECHANISMS BY WHICH AN OBESOGENIC INTRAUTERINE ENVIRONMENT COULD PROGRAM THE OFFSPRING'S CARDIOVASCULAR METABOLISM IN A SEX-DIVERGENT WAY, WITH A SPECIAL FOCUS ON CARDIAC MITOCHONDRIAL FUNCTION, AND DEBATE POSSIBLE STRATEGIES TO IMPLEMENT DURING MO PREGNANCY THAT COULD AMELIORATE, REVERT, OR EVEN PREVENT DELETERIOUS EFFECTS OF MO ON THE OFFSPRING'S CARDIOVASCULAR SYSTEM. THE IMPACT OF MATERNAL PHYSICAL EXERCISE DURING AN OBESOGENIC PREGNANCY, NUTRITIONAL INTERVENTIONS, AND SUPPLEMENTATION ON OFFSPRING'S CARDIAC METABOLISM ARE DISCUSSED, HIGHLIGHTING CHANGES THAT MAY BE FAVORABLE TO MO OFFSPRING'S CARDIOVASCULAR HEALTH, WHICH MIGHT RESULT IN THE ATTENUATION OR EVEN PREVENTION OF THE DEVELOPMENT OF CVD IN MO OFFSPRING. THE OBJECTIVES OF THIS MANUSCRIPT ARE TO COMPREHENSIVELY EXAMINE THE VARIOUS ASPECTS OF MO DURING PREGNANCY AND EXPLORE THE UNDERLYING MECHANISMS THAT CONTRIBUTE TO AN INCREASED CVD RISK IN THE OFFSPRING. WE REVIEW THE CURRENT LITERATURE ON MO AND ITS IMPACT ON THE OFFSPRING'S CARDIOMETABOLIC HEALTH. FURTHERMORE, WE DISCUSS THE POTENTIAL LONG-TERM CONSEQUENCES FOR THE OFFSPRING. UNDERSTANDING THE MULTIFACETED EFFECTS OF MO ON THE OFFSPRING'S HEALTH IS CRUCIAL FOR HEALTHCARE PROVIDERS, RESEARCHERS, AND POLICYMAKERS TO DEVELOP EFFECTIVE STRATEGIES FOR PREVENTION AND INTERVENTION TO IMPROVE CARE. 2023 15 3166 28 GROCERY DELIVERY TO SUPPORT HEALTHY WEIGHT GAIN AMONG PREGNANT YOUNG WOMEN WITH LOW INCOME: PROTOCOL FOR A RANDOMIZED CONTROLLED TRIAL. BACKGROUND: EXCESSIVE WEIGHT GAIN DURING PREGNANCY IS ASSOCIATED WITH COMPLICATIONS FOR BOTH THE MOTHER AND HER INFANT INCLUDING GESTATIONAL DIABETES, HYPERTENSIVE DISORDERS, OPERATIVE DELIVERY, AND LONG-TERM OBESITY. A HEALTHY DIET DURING PREGNANCY PROMOTES HEALTHY GESTATIONAL WEIGHT GAIN AND DETERMINES FETAL EPIGENETIC PROGRAMMING IN INFANTS THAT IMPACTS RISK FOR FUTURE CHRONIC DISEASE. OBJECTIVE: THIS PROJECT WILL EXAMINE THE IMPACT OF GROCERY DELIVERY DURING PREGNANCY ON THE WEIGHT, DIET, AND HEALTH OUTCOMES OF YOUNG PREGNANT WOMEN AND THEIR INFANTS. METHODS: A THREE-ARM RANDOMIZED CONTROLLED TRIAL DESIGN WILL BE PERFORMED. A TOTAL OF 855 YOUNG PREGNANT WOMEN, AGED 14-24 YEARS, FROM ACROSS THE STATE OF MICHIGAN WILL BE ENROLLED AND RANDOMIZED EQUALLY INTO THE THREE STUDY ARMS. PARTICIPANTS IN ARM ONE (CONTROL) WILL RECEIVE USUAL CARE FROM THE SPECIAL SUPPLEMENTAL NUTRITION PROGRAM FOR WOMEN, INFANTS, AND CHILDREN (WIC); ARM TWO WILL RECEIVE WIC PLUS BIWEEKLY GROCERY DELIVERY; AND ARM THREE WILL RECEIVE WIC PLUS BIWEEKLY GROCERY AND UNSWEETENED BEVERAGE DELIVERY. WEIGHT WILL BE ASSESSED WEEKLY DURING PREGNANCY, AND TOTAL PREGNANCY WEIGHT GAIN WILL BE CATEGORIZED AS ABOVE, BELOW, OR WITHIN GUIDELINES. ADDITIONALLY, DIETARY INTAKE WILL BE ASSESSED AT THREE TIME POINTS (BASELINE, SECOND TRIMESTER, AND THIRD TRIMESTER), AND PREGNANCY OUTCOMES WILL BE EXTRACTED FROM MEDICAL RECORDS. THE APPROPRIATENESS OF PREGNANCY WEIGHT GAIN, DIET QUALITY, AND OCCURRENCE OF POOR OUTCOMES WILL BE COMPARED BETWEEN GROUPS USING STANDARD PRACTICES FOR MULTINOMIAL REGRESSION AND CONFOUNDER ADJUSTMENT. RESULTS: THIS STUDY WAS FUNDED IN APRIL 2021, DATA COLLECTION STARTED IN DECEMBER 2021, AND DATA COLLECTION IS EXPECTED TO BE CONCLUDED IN 2026. CONCLUSIONS: THIS STUDY WILL TEST WHETHER GROCERY DELIVERY OF HEALTHY FOODS IMPROVES WEIGHT, DIET, AND PREGNANCY OUTCOMES OF YOUNG MOMS WITH LOW INCOME. THE FINDINGS WILL INFORM POLICIES AND PRACTICES THAT PROMOTE A HEALTHY DIET DURING PREGNANCY, WHICH HAS MULTIGENERATIONAL IMPACTS ON HEALTH. TRIAL REGISTRATION: CLINICALTRIALS.GOV NCT05000645; HTTPS://CLINICALTRIALS.GOV/CT2/SHOW/NCT05000645. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/40568. 2022 16 4809 34 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 17 4886 29 OVERWEIGHT AND OBESITY BEFORE, DURING AND AFTER PREGNANCY: PART 1: PATHOPHYSIOLOGY, MOLECULAR BIOLOGY AND EPIGENETIC CONSEQUENCES. OVERWEIGHT AND OBESITY BEFORE CONCEPTION AS WELL AS EXCESSIVE WEIGHT GAIN DURING PREGNANCY ARE ASSOCIATED WITH ENDOCRINOLOGICAL CHANGES OF MOTHER AND FETUS. INSULIN RESISTANCE PHYSIOLOGICALLY INCREASES DURING PREGNANCY, ADDITIONAL OBESITY FURTHER INCREASES INSULIN RESISTANCE. IN COMBINATION WITH REDUCED INSULIN SECRETION THIS LEADS TO GESTATIONAL DIABETES WHICH MAY DEVELOP INTO TYPE-2-DIABETES. THE ADIPOSE TISSUE PRODUCES TNF-ALPHA, INTERLEUKINS AND LEPTIN AND UPREGULATES THESE ADIPOKINES. INSULIN RESISTANCE AND OBESITY INDUCE INFLAMMATORY PROCESSES AND VASCULAR DYSFUNCTION, WHICH EXPLAINS THE INCREASED RATE OF PREGNANCY-RELATED HYPERTENSION AND PRE-ECLAMPSIA IN OBESE PREGNANT WOMEN. BETWEEN 14 AND 28 GESTATIONAL WEEKS, THE FETAL ADIPOSE TISSUE IS GENERATED AND THE NUMBER OF FAT LOBULES IS DETERMINED. THEREAFTER, AN INCREASE IN ADIPOSE TISSUE IS ARRANGED BY AN ENLARGEMENT OF THE LOBULES (HYPERTROPHY), OR EVEN AN INCREASE IN THE NUMBER OF FAT CELLS (HYPERPLASIA). HUMAN AND ANIMAL STUDIES HAVE SHOWN THAT MATERNAL OBESITY "PROGRAMMES" THE OFFSPRING FOR FURTHER OBESITY AND CHRONIC DISEASE. PREGNANT WOMEN, MIDWIVES, PHYSICIANS AND HEALTH CARE POLITICIANS SHOULD BE BETTER INFORMED ABOUT PREVENTION, PATHOPHYSIOLOGICAL MECHANISMS, AND THE BURDEN FOR SOCIETY CAUSED BY OBESITY BEFORE, DURING AND AFTER PREGNANCY. 2014 18 3578 31 IMPACT OF PARENTAL OVER- AND UNDERWEIGHT ON THE HEALTH OF OFFSPRING. PARENTAL EXCESS WEIGHT AND ESPECIALLY PREGESTATIONAL MATERNAL OBESITY AND EXCESSIVE WEIGHT GAIN DURING PREGNANCY HAVE BEEN RELATED TO AN INCREASED RISK OF METABOLIC (OBESITY, TYPE 2 DIABETES, CARDIOVASCULAR DISEASE, METABOLIC SYNDROME) AND NONMETABOLIC (CANCER, OSTEOPOROSIS, ASTHMA, NEUROLOGIC ALTERATIONS) DISEASES IN THE OFFSPRING, PROBABLY MEDIATED BY EPIGENETIC MECHANISMS OF FETAL PROGRAMMING. MATERNAL UNDERWEIGHT IS LESS COMMON IN DEVELOPED SOCIETIES, BUT THE DISCREPANCY BETWEEN A POOR NUTRITIONAL ENVIRONMENT IN UTERO AND A NORMAL OR EXCESSIVE POSTNATAL FOOD SUPPLY WITH RAPID GROWTH CATCH-UP APPEARS TO BE THE MAIN CANDIDATE MECHANISM OF THE DEVELOPMENT OF CHRONIC DISEASES DURING THE OFFSPRING'S ADULTHOOD. THE ROLE OF THE POSTNATAL ENVIRONMENT IN BOTH SCENARIOS (PARENTAL OVERWEIGHT OR UNDERWEIGHT) ALSO SEEMS TO INFLUENCE THE OFFSPRING'S HEALTH. LIFESTYLE INTERVENTIONS BEFORE AND DURING PREGNANCY IN BOTH PARENTS, BUT ESPECIALLY IN THE MOTHER, AS WELL AS IN CHILDREN AFTER BIRTH, ARE ADVISABLE TO COUNTERACT THE MANY UNDESIRABLE CHRONIC CONDITIONS DESCRIBED. 2019 19 4995 36 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 20 3903 22 LEP, LDLR AND APOA4 GENE POLYMORPHISMS AND THEIR RELATIONSHIP WITH THE RISK OF OVERWEIGHT, OBESITY AND CHRONIC DISEASES IN ADULTS OF THE STATE OF SUCRE, VENEZUELA. INTRODUCTION: OVERWEIGHT, OBESITY AND SOME CHRONIC DISEASES HAVE BECOME MORE PREVALENT RECENTLY. IT IS WELL KNOWN THAT THEIR CAUSES MAY BE GENETIC, EPIGENETIC, ENVIRONMENTAL, OR A MIXTURE OF THESE. OBJECTIVE: TO ANALYZE THE RELATIONSHIP BETWEEN NINE SINGLE NUCLEOTIDE POLYMORPHISMS OF GENES LEP (RS2167270), LDLR (RS885765, RS688, RS5925, RS55903358, RS5742911) AND APOA4 (RS5095, RS675, RS5110) WITH OBESITY-RELATED PHENOTYPES AND OTHER COMORBIDITIES. MATERIAL AND METHODS: WE RECRUITED 144 ADULTS (76 MALES AND 68 FEMALES, WITH AVERAGE AGES OF 29.93+/-8.29 AND 32.49+/-11.15 YEARS, RESPECTIVELY) IN THE STATE OF SUCRE, VENEZUELA. CLINICAL AND ANTHROPOMETRIC PARAMETERS WERE OBTAINED. GENOTYPE-RISK ASSOCIATIONS WERE STUDIED. WE THEN COMPARED THE AVERAGES REGISTERED FOR ANTHROPOMETRIC AND BIOCHEMICAL VARIABLES PREVIOUSLY ADJUSTED FOR BIOLOGICAL AND ENVIRONMENTAL FACTORS. RESULTS: ACCORDING TO THE BODY MASS INDEX, 38.9% OF THE INDIVIDUALS IN THE SAMPLE WERE OVERWEIGHT (25/=30 KG/M2). GENOTYPE AND ALLELE FREQUENCIES DID NOT DIFFER STATISTICALLY FOR GROUPS WITH NORMAL AND HIGH BODY MASS INDEX (OVERWEIGHT PLUS OBESITY). THE ASSOCIATION BETWEEN LDLR RS5742911 ANCESTRAL GENOTYPE A/A AND HIGH RISK CONDITION RELATED TO HDL-CHOLESTEROL WAS THE ONLY ONE FOUND TO BE SIGNIFICANT (OR=2.944, 95% CI: 1.446-5.996; P=0.003). THE DIFFERENCE IN ADJUSTED MEAN HDL-CHOLESTEROL FOR LDLR RS5742911 GENOTYPES WAS STATISTICALLY SIGNIFICANT (P=0.005) (A/A: 41.50+/-14.81 MG/DL; A/G: 45.00+/-12.07 MG/DL; G/G: 47.17+/-9.43 MG/DL). CONCLUSIONS: FOR MOST OF THE GENETIC VARIANTS STUDIED, THERE WAS AN ASSOCIATION WITH THE PRESENCE OF OVERWEIGHT AND OBESITY AMONG ANCESTRAL GENOTYPE CARRIERS, ALTHOUGH THIS WAS NOT STATISTICALLY SIGNIFICANT. THE RS5742911 POLYMORPHISM MAY BE USEFUL AS AN INDICATOR OF A RISK OF CHRONIC DISEASES. 2016