1  1384 153 DIABETES AND KIDNEY DISEASE: EMPHASIS ON TREATMENT WITH SGLT-2 INHIBITORS AND GLP-1 RECEPTOR AGONISTS. KIDNEY DISEASE IS A FREQUENT MICROVASCULAR COMPLICATION OF BOTH TYPE 1 AND TYPE 2 DIABETES. HISTORIC TRIALS HAVE DEMONSTRATED THAT A TIGHT GLYCAEMIC CONTROL IS THE MOST POWERFUL APPROACH TO DECREASE THE CHANCES OF DEVELOPING DIABETIC NEPHROPATHY. HOWEVER, HAVING AN HBA1C < 7% DOES NOT COMPLETELY SUPPRESS THE RISK OF KIDNEY DISEASE. THE OBSERVED RESIDUAL RISK IS LIKELY ASCRIBABLE TO TWO PHENOMENA: 1- THE PRESENCE OF RISK FACTORS AND ALTERATIONS ADDITIVE TO AND INDEPENDENT OF GLYCAEMIA, AND 2- THE ACTIVATION OF LONG-LASTING IMBALANCES BY PERIODS OF EXPOSURE TO UNCONTROLLED GLYCEMIA, A PHENOMENON REFERRED TO AS METABOLIC MEMORY OR LEGACY EFFECT. LONG-LASTING OXIDATIVE STRESS, EPIGENETIC ALTERATIONS, CELLULAR SENESCENCE, AND THE RESULTING CHRONIC LOW-GRADE INFLAMMATION ARE ALL CANDIDATE MECHANISMS EXPLAINING THE DEVELOPMENT OF NEPHROPATHY DESPITE PROPER CONTROL OF RISK FACTORS. RECENTLY, TWO CLASSES OF DRUGS, I.E. GLUCAGON-LIKE PEPTIDE (GLP) 1 RECEPTOR AGONISTS (RA) AND SODIUM-GLUCOSE TRANSPORTER 2 INHIBITORS (SGLT-I) HAVE CHANGED THIS SCENARIO. INDEED, CARDIOVASCULAR OUTCOME AND OTHER TRIALS HAVE CLEARLY SHOWN A RENOPROTECTIVE EFFECT FOR THESE DRUGS, WELL-BEYOND THEIR GLUCOSE-LOWERING PROPERTIES. IN THIS REVIEW, WE SUMMARIZE: 1- SELECTED KEY TRIALS AND MECHANISMS UNDERLYING THE DEVELOPMENT OF DIABETIC KIDNEY DISEASE AND 2- THE RESULTS RELATIVE TO RENAL ENDPOINTS IN CLINICAL TRIALS OF GLP-1 RA AND SGLT-2I. THEN, WE BRIEFLY DISCUSS SOME OF THE HYPOTHESES POSITED TO EXPLAIN THE MARKED RENOPROTECTIVE PROPERTIES OF THESE TWO CLASSES, EVIDENCING THE STILL EXISTING GAPS IN KNOWLEDGE AND PROPOSING FUTURE DIRECTIONS TO FURTHER IMPLEMENT THE USE OF THESE POWERFUL, DISEASE-MODIFYING DRUGS.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
2   643  33 BIOME DEPLETION IN CONJUNCTION WITH EVOLUTIONARY MISMATCHES COULD PLAY A ROLE IN THE ETIOLOGY OF NEUROFIBROMATOSIS 1. NEUROFIBROMATOSIS 1 (NF1) ARISES DE NOVO IN A STRIKING 30-50% OF CASES, POINTING TOWARD AN ENVIRONMENTAL ETIOLOGY, THOUGH NONE HAS BEEN CLEARLY IDENTIFIED. THE BIOME DEPLETION THEORY POSITS THAT THE ABSENCE OF MUTUALISTIC AND COMMENSAL ORGANISMS WITHIN THE HUMAN BODY COUPLED WITH MODERN LIFESTYLE ALTERATIONS MAY HAVE PROFOUNDLY DELETERIOUS EFFECTS, INCLUSIVE OF IMMUNOLOGIC DERANGEMENT THAT IS THOUGHT TO RESULT IN ALLERGY, ATOPY, AND NUMEROUS AUTOIMMUNE DISEASES. BIOME DEPLETION HAS BEEN IMPLICATED AS A FACTOR IN THE ETIOLOGY OF BOTH MULTIPLE SCLEROSIS AND AUTISM SPECTRUM DISORDERS; BIOME RECONSTITUTION, I.E. REPLENISHMENT OF THE BIOME WITH CERTAIN KEYNOTE SPECIES, IS BEING USED IN THE TREATMENT OF THESE AND OTHER AUTOIMMUNE STATES. NEUROFIBROMATOSIS 1 HAS BEEN ASSOCIATED WITH ALLERGY, VARIOUS AUTOIMMUNE STATES, MULTIPLE SCLEROSIS, AND AUTISM. RECENT RESEARCH HAS POSITED THAT NF1, MULTIPLE SCLEROSIS AND AUTISM MAY ALL ARISE FROM DISTURBANCES IN THE NEURAL CREST DURING GESTATION. THIS PAPER HYPOTHESIZES THAT THERE IS INDIRECT EVIDENCE THAT A HIGHLY INFLAMMATORY UTERINE STATE MAY PRECIPITATE EPIGENETIC CHANGES IN VULNERABLE NF-RELATED GENES IN THE COURSE OF FETAL DEVELOPMENT. THE ETIOLOGY OF NF1 MAY LIE IN THE ABSENCE OF IMMUNOMODULATION BY COMMENSAL AND MUTUALISTIC SPECIES ONCE UBIQUITOUSLY PRESENT IN THE ENVIRONMENT, AS WELL AS THROUGH ADOPTION OF A MODERN LIFESTYLE THAT CONTRIBUTES TO CHRONIC INFLAMMATION. REPLENISHMENT OF HELMINTHS AND OTHER MISSING ORGANISMS TO THE HUMAN BIOME PRIOR TO CONCEPTION AS WELL AS ADDRESSING NUTRITIONAL STATUS, PSYCHOLOGICAL STRESS, AND ENVIRONMENTAL EXPOSURES MAY PREVENT THE DEVELOPMENT OF NF1.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
3  1992  33 EPIGENETIC AND DEVELOPMENTAL INFLUENCES ON THE RISK OF OBESITY, DIABETES, AND METABOLIC SYNDROME. METABOLIC SYNDROME IS A GROWING CAUSE OF MORBIDITY AND MORTALITY WORLDWIDE. METABOLIC SYNDROME IS CHARACTERIZED BY THE PRESENCE OF A VARIETY OF METABOLIC DISTURBANCES INCLUDING OBESITY, HYPERLIPIDEMIA, HYPERTENSION, AND ELEVATED FASTING BLOOD SUGAR. ALTHOUGH THE RISK FOR METABOLIC SYNDROME HAS LARGELY BEEN ATTRIBUTED TO ADULT LIFESTYLE FACTORS SUCH AS POOR NUTRITION, LACK OF EXERCISE, AND SMOKING, THERE IS NOW STRONG EVIDENCE SUGGESTING THAT PREDISPOSITION TO THE DEVELOPMENT OF METABOLIC SYNDROME BEGINS IN UTERO. FIRST POSITED BY HALES AND BARKER IN 1992, THE "THRIFTY PHENOTYPE" HYPOTHESIS PROPOSES THAT SUSCEPTIBILITY TO ADULT CHRONIC DISEASES CAN OCCUR IN RESPONSE TO EXPOSURES IN THE PRENATAL AND PERINATAL PERIODS. THIS HYPOTHESIS HAS BEEN CONTINUALLY SUPPORTED BY EPIDEMIOLOGIC STUDIES AND STUDIES INVOLVING ANIMAL MODELS. IN THIS REVIEW, WE DESCRIBE THE STRUCTURAL, METABOLIC AND EPIGENETIC CHANGES THAT OCCUR IN RESPONSE TO ADVERSE INTRAUTERINE ENVIRONMENTS INCLUDING PRENATAL AND POSTNATAL DIET, MATERNAL OBESITY, AND PREGNANCY COMPLICATIONS. GIVEN THE INCREASING PREVALENCE OF METABOLIC SYNDROME IN BOTH THE DEVELOPED AND DEVELOPING WORLDS, A GREATER UNDERSTANDING AND APPRECIATION FOR THE ROLE OF THE INTRAUTERINE ENVIRONMENT IN ADULT CHRONIC DISEASE ETIOLOGY IS IMPERATIVE.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
4  5312  35 PSYCHOLOGICAL FACTORS AND DNA METHYLATION OF GENES RELATED TO IMMUNE/INFLAMMATORY SYSTEM MARKERS: THE VA NORMATIVE AGING STUDY. OBJECTIVES: ALTHOUGH PSYCHOLOGICAL FACTORS HAVE BEEN ASSOCIATED WITH CHRONIC DISEASES SUCH AS CORONARY HEART DISEASE (CHD), THE UNDERLYING PATHWAYS FOR THESE ASSOCIATIONS HAVE YET TO BE ELUCIDATED. DNA METHYLATION HAS BEEN POSITED AS A MECHANISM LINKING PSYCHOLOGICAL FACTORS TO CHD RISK. IN A COHORT OF COMMUNITY-DWELLING ELDERLY MEN, WE EXPLORED THE ASSOCIATIONS BETWEEN POSITIVE AND NEGATIVE PSYCHOLOGICAL FACTORS WITH DNA METHYLATION IN PROMOTER REGIONS OF MULTIPLE GENES INVOLVED IN IMMUNE/INFLAMMATORY PROCESSES RELATED TO ATHEROSCLEROSIS. DESIGN: PROSPECTIVE COHORT STUDY. SETTING: GREATER BOSTON, MASSACHUSETTS AREA. PARTICIPANTS: SAMPLES OF 538 TO 669 MEN PARTICIPATING IN THE NORMATIVE AGING STUDY COHORT WITH PSYCHOLOGICAL MEASURES AND DNA METHYLATION MEASURES, COLLECTED ON 1-4 VISITS BETWEEN 1999 AND 2006 (MEAN AGE=72.7 YEARS AT FIRST VISIT). OUTCOME MEASURES: WE EXAMINED ANXIETY, DEPRESSION, HOSTILITY AND LIFE SATISFACTION AS PREDICTORS OF LEUCOCYTE GENE-SPECIFIC DNA METHYLATION. WE ESTIMATED REPEATED MEASURES LINEAR MIXED MODELS, CONTROLLING FOR AGE, SMOKING, EDUCATION, HISTORY OF HEART DISEASE, STROKE OR DIABETES, % LYMPHOCYTES, % MONOCYTES AND PLASMA FOLATE. RESULTS: PSYCHOLOGICAL DISTRESS MEASURED BY ANXIETY, DEPRESSION AND HOSTILITY WAS POSITIVELY ASSOCIATED, AND HAPPINESS AND LIFE SATISFACTION WERE INVERSELY ASSOCIATED WITH AVERAGE INTERCELLULAR ADHESION MOLECULE-1 (ICAM-1) AND COAGULATION FACTOR III (F3) PROMOTER METHYLATION LEVELS. THERE WAS SOME EVIDENCE THAT HOSTILITY WAS POSITIVELY ASSOCIATED WITH TOLL-LIKE RECEPTOR 2 (TLR-2) PROMOTER METHYLATION, AND THAT LIFE SATISFACTION WAS INVERSELY ASSOCIATED WITH TLR-2 AND INDUCIBLE NITRIC OXIDE SYNTHASE (INOS) PROMOTER METHYLATION. WE OBSERVED LESS CONSISTENT AND SIGNIFICANT ASSOCIATIONS BETWEEN PSYCHOLOGICAL FACTORS AND AVERAGE METHYLATION FOR PROMOTERS OF THE GENES FOR GLUCOCORTICOID RECEPTOR (NR3C1), INTERFERON-GAMMA (IFN-GAMMA) AND INTERLEUKIN 6 (IL-6). CONCLUSIONS: THESE FINDINGS SUGGEST THAT POSITIVE AND NEGATIVE PSYCHOLOGICAL FACTORS AFFECT DNA METHYLATION OF SELECTED GENES INVOLVED IN CHRONIC IMMUNE/INFLAMMATORY PROCESSES AND INFLAMMATION-RELATED ENDOTHELIAL DYSFUNCTION. SUCH EPIGENETIC CHANGES MAY REPRESENT BIOLOGICAL PATHWAYS THAT MEDIATE THE EFFECTS OF PSYCHOLOGICAL FACTORS ON CHD.	2016	

5   465  51 ARE TARGETED THERAPIES FOR DIABETIC CARDIOMYOPATHY ON THE HORIZON? DIABETES INCREASES THE RISK OF HEART FAILURE APPROXIMATELY 2.5-FOLD, INDEPENDENT OF CORONARY ARTERY DISEASE AND OTHER COMORBIDITIES. THIS PROCESS, TERMED DIABETIC CARDIOMYOPATHY, IS CHARACTERIZED BY INITIAL IMPAIRMENT OF LEFT VENTRICULAR (LV) RELAXATION FOLLOWED BY LV CONTRACTILE DYSFUNCTION. POST-MORTEM EXAMINATION REVEALS THAT HUMAN DIASTOLIC DYSFUNCTION IS CLOSELY ASSOCIATED WITH LV DAMAGE, INCLUDING CARDIOMYOCYTE HYPERTROPHY, APOPTOSIS AND FIBROSIS, WITH IMPAIRED CORONARY MICROVASCULAR PERFUSION. THE PATHOPHYSIOLOGICAL MECHANISMS UNDERPINNING THE CHARACTERISTIC FEATURES OF DIABETIC CARDIOMYOPATHY REMAIN POORLY UNDERSTOOD, ALTHOUGH MULTIPLE FACTORS INCLUDING ALTERED LIPID METABOLISM, MITOCHONDRIAL DYSFUNCTION, OXIDATIVE STRESS, ENDOPLASMIC RETICULUM (ER) STRESS, INFLAMMATION, AS WELL AS EPIGENETIC CHANGES, ARE IMPLICATED. DESPITE A RECENT RISE IN RESEARCH INTERROGATING THESE MECHANISMS AND AN INCREASED UNDERSTANDING OF THE CLINICAL IMPORTANCE OF DIABETIC CARDIOMYOPATHY, THERE REMAINS A LACK OF SPECIFIC TREATMENT STRATEGIES. HOW THE CHRONIC METABOLIC DISTURBANCES OBSERVED IN DIABETES LEAD TO STRUCTURAL AND FUNCTIONAL CHANGES REMAINS A PERTINENT QUESTION, AND IT IS HOPED THAT RECENT ADVANCES, PARTICULARLY IN THE AREA OF EPIGENETICS, AMONG OTHERS, MAY PROVIDE SOME ANSWERS. THIS REVIEW HENCE EXPLORES THE TEMPORAL ONSET OF THE PATHOLOGICAL FEATURES OF DIABETIC CARDIOMYOPATHY, AND THEIR RELATIVE CONTRIBUTION TO THE RESULTANT DISEASE PHENOTYPE, AS WELL AS BOTH CURRENT AND POTENTIAL THERAPEUTIC OPTIONS. THE EMERGENCE OF GLUCOSE-OPTIMIZING AGENTS, NAMELY GLUCAGON-LIKE PEPTIDE-1 (GLP-1) AGONISTS AND SODIUM/GLUCOSE CO-TRANSPORTER (SGLT)2 INHIBITORS THAT CONFER BENEFITS ON CARDIOVASCULAR OUTCOMES, TOGETHER WITH NOVEL EXPERIMENTAL APPROACHES, HIGHLIGHT A NEW AND EXCITING ERA IN DIABETES RESEARCH, WHICH IS LIKELY TO RESULT IN MAJOR CLINICAL IMPACT.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
6  6292  34 THE PRIMACY OF PSYCHOANALYTIC INTERVENTION IN RECOVERY FROM THE PSYCHOSES AND SCHIZOPHRENIAS. FUNCTIONAL CAPACITIES, SUCH AS ATTACHMENT AND AFFECT REGULATION, OBJECT RELATIONS CAPACITY, SYMBOLIC FUNCTION AND LANGUAGE DEVELOPMENT, NOW DOCUMENTED BY NEUROSCIENTIFIC RESEARCH AND EPIGENETICS, ARE REVIEWED. RESULTS FROM THIS RESEARCH, TOGETHER WITH OTHER FACTORS, ARE POSITED TO HAVE CONTRIBUTED TO EFFECTIVE CONTEMPORARY PSYCHOANALYTIC AND PSYCHOTHERAPEUTIC TREATMENTS FOR THE PSYCHOSES AND SCHIZOPHRENIAS. ETIOLOGICAL FACTORS INVOLVING THE SCHIZOPHRENIAS AND OTHER PSYCHOSES ARE CONSIDERED BOTH IN TERMS OF AN EPIGENETIC MODEL, AND IN TERMS OF HOW ETIOLOGY MAY, OR MAY NOT, AFFECT CLINICAL TREATMENT. THE LACANIAN 388 PROGRAM IS REVIEWED IN SOME DETAIL, AS ARE SEVERAL PSYCHOANALYTIC AND PSYCHOTHERAPEUTIC CLINICAL APPROACHES USED WITH THIS POPULATION OVER THE LAST SIX DECADES. ALL TREATMENTS FOCUS ON THE PRIMACY OF PSYCHOTHERAPEUTIC INTERVENTION, AND USE MEDICATIONS MINIMALLY, NOT AT ALL, OR ONLY AS INFORMED BY AN OVER-ARCHING PSYCHODYNAMIC MODEL OF TREATMENT. THE AUTHOR ARGUES THAT THERE IS NOW SUBSTANTIAL RESEARCH AND OUTCOME DATA SUGGESTING THAT THE PSYCHOSES AND SCHIZOPHRENIAS ARE NOT CHRONIC DETERIORATING CONDITIONS. RECOVERY IS OBSERVED IN MANY PSYCHOTIC AND SCHIZOPHRENIC PATIENTS TREATED WITH APPROACHES THAT FOCUS ON THE PRIMACY OF PSYCHOTHERAPEUTIC INTERVENTION.	2007	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
7  3595  31 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
8  3817  38 INTRAUTERINE PROGRAMMING OF THE ENDOCRINE PANCREAS. EPIDEMIOLOGICAL STUDIES HAVE REVEALED STRONG RELATIONSHIPS BETWEEN POOR FOETAL GROWTH AND SUBSEQUENT DEVELOPMENT OF THE METABOLIC SYNDROME. PERSISTING EFFECTS OF EARLY MALNUTRITION BECOME TRANSLATED INTO PATHOLOGY, THEREBY DETERMINE CHRONIC RISK FOR DEVELOPING GLUCOSE INTOLERANCE AND DIABETES. THESE EPIDEMIOLOGICAL OBSERVATIONS IDENTIFY THE PHENOMENA OF FOETAL PROGRAMMING WITHOUT EXPLAINING THE UNDERLYING MECHANISMS THAT ESTABLISH THE CAUSAL LINK. ANIMAL MODELS HAVE BEEN ESTABLISHED AND STUDIES HAVE DEMONSTRATED THAT REDUCTION IN THE AVAILABILITY OF NUTRIENTS DURING FOETAL DEVELOPMENT PROGRAMS THE ENDOCRINE PANCREAS AND INSULIN-SENSITIVE TISSUES. WHATEVER THE TYPE OF FOETAL MALNUTRITION, WHETHER THERE ARE NOT ENOUGH CALORIES OR PROTEIN IN FOOD OR AFTER PLACENTAL DEFICIENCY, MALNOURISHED PUPS ARE BORN WITH A DEFECT IN THEIR BETA-CELL POPULATION THAT WILL NEVER COMPLETELY RECOVER, AND INSULIN-SENSITIVE TISSUES WILL BE DEFINITIVELY ALTERED. DESPITE THE SIMILAR ENDPOINT, DIFFERENT CELLULAR AND PHYSIOLOGICAL MECHANISMS ARE PROPOSED. HORMONES OPERATIVE DURING FOETAL LIFE LIKE INSULIN ITSELF, INSULIN-LIKE GROWTH FACTORS AND GLUCOCORTICOIDS, AS WELL AS SPECIFIC MOLECULES LIKE TAURINE, OR ISLET VASCULARIZATION WERE IMPLICATED AS POSSIBLE FACTORS AMPLIFYING THE DEFECT. THE MOLECULAR MECHANISMS RESPONSIBLE FOR INTRAUTERINE PROGRAMMING OF THE BETA CELLS ARE STILL ELUSIVE, BUT TWO HYPOTHESES RECENTLY EMERGED: THE FIRST ONE IMPLIES PROGRAMMING OF MITOCHONDRIA AND THE SECOND, EPIGENETIC REGULATION.	2007	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
9  2511  33 EPIGENETICS AND PREECLAMPSIA: PROGRAMMING OF FUTURE OUTCOMES. PREGNANCY IS KNOWN TO INDUCE RAPID, PROGRESSIVE, AND SUBSTANTIAL CHANGES TO THE CARDIOVASCULAR SYSTEM, ULTIMATELY FACILITATING SUCCESSFUL PREGNANCY OUTCOMES. WOMEN WHO DEVELOP HYPERTENSIVE DISORDERS DURING PREGNANCY ARE CONSIDERED TO HAVE "FAILED" THE CARDIOVASCULAR STRESS TEST OF PREGNANCY AND LIKELY REPRESENT A SUBPOPULATION WITH INADEQUATE CARDIOVASCULAR ACCOMMODATION. PREECLAMPSIA IS A SERIOUS COMPLICATION WITH A MYRIAD OF MANIFESTATIONS IN BOTH MOTHER AND OFFSPRING. THIS PREGNANCY SYNDROME IS A POLYGENIC DISEASE AND HAS NOW BEEN LINKED TO A GREATER INCIDENCE OF CARDIOVASCULAR DISEASE. MOREOVER, OFFSPRINGS BORN TO PREECLAMPTIC MOTHERS EXHIBIT AN ELEVATED RISK OF CARDIOVASCULAR DISEASE, STROKE, AND MENTAL DISORDERS DURING ADULTHOOD. THIS SUGGESTS THAT PREECLAMPSIA NOT ONLY EXPOSES THE MOTHER AND THE FETUS TO COMPLICATIONS DURING PREGNANCY BUT ALSO PROGRAMS CHRONIC DISEASES DURING ADULTHOOD IN THE OFFSPRING. THE ETIOLOGY OF PREECLAMPSIA REMAINS UNKNOWN, WITH VARIOUS THEORIES BEING SUGGESTED TO EXPLAIN ITS ORIGIN. IT IS PRIMARILY THOUGHT TO BE ASSOCIATED WITH POOR PLACENTATION AND ENTAILS EXCESSIVE MATERNAL INFLAMMATION AND ENDOTHELIAL DYSFUNCTION. IT IS WELL ESTABLISHED NOW THAT THE MATERNAL IMMUNE SYSTEM AND THE PLACENTA ARE INVOLVED IN A HIGHLY CHOREOGRAPHED CROSS TALK THAT UNDERLIES ADEQUATE SPIRAL ARTERY REMODELING REQUIRED FOR UTEROPLACENTAL PERFUSION AND FREE FLOW OF NUTRIENTS TO THE FETUS. ALTHOUGH IT IS NOT CLEAR WHETHER IMMUNOLOGICAL ALTERATIONS OCCUR EARLY DURING PREGNANCY, STUDIES HAVE PROPOSED THAT DYSREGULATED SYSTEMIC AND PLACENTAL IMMUNITY CONTRIBUTE TO IMPAIRED ANGIOGENESIS AND THE ONSET OF PREECLAMPSIA. RECENTLY EMERGED STRONG EVIDENCE SUGGESTS A POTENTIAL LINK AMONG EPIGENETICS, MICRORNAS (MIRNAS), AND PREGNANCY COMPLICATIONS. THIS CHAPTER WILL FOCUS ON IMPORTANT ASPECTS OF EPIGENETICS, IMMUNOLOGICAL ASPECTS, AND CARDIOVASCULAR AND VASCULAR REMODELING OF PREECLAMPSIA.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                 
10  1376  32 DEVELOPMENTAL PROGRAMMING OF BODY COMPOSITION: UPDATE ON EVIDENCE AND MECHANISMS. PURPOSE OF REVIEW: A GROWING BODY OF EPIDEMIOLOGICAL AND EXPERIMENTAL DATA INDICATE THAT NUTRITIONAL OR ENVIRONMENTAL STRESSORS DURING EARLY DEVELOPMENT CAN INDUCE LONG-TERM ADAPTATIONS THAT INCREASE RISK OF OBESITY, DIABETES, CARDIOVASCULAR DISEASE, AND OTHER CHRONIC CONDITIONS-A PHENOMENON TERMED "DEVELOPMENTAL PROGRAMMING." A COMMON PHENOTYPE IN HUMANS AND ANIMAL MODELS IS ALTERED BODY COMPOSITION, WITH REDUCED MUSCLE AND BONE MASS, AND INCREASED FAT MASS. IN THIS REVIEW, WE SUMMARIZE THE RECENT LITERATURE LINKING PRENATAL FACTORS TO FUTURE BODY COMPOSITION AND EXPLORE CONTRIBUTING MECHANISMS. RECENT FINDINGS: MANY PRENATAL EXPOSURES, INCLUDING INTRAUTERINE GROWTH RESTRICTION, EXTREMES OF BIRTH WEIGHT, MATERNAL OBESITY, AND MATERNAL DIABETES, ARE ASSOCIATED WITH INCREASED FAT MASS, REDUCED MUSCLE MASS, AND DECREASED BONE DENSITY, WITH EFFECTS REPORTED THROUGHOUT INFANCY AND CHILDHOOD, AND PERSISTING INTO MIDDLE AGE. MECHANISMS AND MEDIATORS INCLUDE MATERNAL DIET, BREASTMILK COMPOSITION, METABOLITES, APPETITE REGULATION, GENETIC AND EPIGENETIC INFLUENCES, STEM CELL COMMITMENT AND FUNCTION, AND MITOCHONDRIAL METABOLISM. DIFFERENCES IN BODY COMPOSITION ARE A COMMON PHENOTYPE FOLLOWING DISRUPTIONS TO THE PRENATAL ENVIRONMENT, AND MAY CONTRIBUTE TO DEVELOPMENTAL PROGRAMMING OF OBESITY AND DIABETES RISK.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
11  2806  34 FETAL PROGRAMMING AND THE RISK OF NONCOMMUNICABLE DISEASE. THE "DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE" (DOHAD) HYPOTHESIS PROPOSES THAT ENVIRONMENTAL CONDITIONS DURING FETAL AND EARLY POST-NATAL DEVELOPMENT INFLUENCE LIFELONG HEALTH AND CAPACITY THROUGH PERMANENT EFFECTS ON GROWTH, STRUCTURE AND METABOLISM. THIS HAS BEEN CALLED 'PROGRAMMING'. THE HYPOTHESIS IS SUPPORTED BY EPIDEMIOLOGICAL EVIDENCE IN HUMANS LINKING NEWBORN SIZE, AND INFANT GROWTH AND NUTRITION, TO ADULT HEALTH OUTCOMES, AND BY EXPERIMENTS IN ANIMALS SHOWING THAT MATERNAL UNDER- AND OVER-NUTRITION AND OTHER INTERVENTIONS (E.G., GLUCOCORTICOID EXPOSURE) DURING PREGNANCY LEAD TO ABNORMAL METABOLISM AND BODY COMPOSITION IN THE ADULT OFFSPRING. EARLY LIFE PROGRAMMING IS NOW THOUGHT TO BE IMPORTANT IN THE ETIOLOGY OF OBESITY, TYPE 2 DIABETES, AND CARDIOVASCULAR DISEASE, OPENING UP THE POSSIBILITY THAT THESE COMMON DISEASES COULD BE PREVENTED BY ACHIEVING OPTIMAL FETAL AND INFANT DEVELOPMENT. THIS IS LIKELY TO HAVE ADDITIONAL BENEFITS FOR INFANT SURVIVAL AND HUMAN CAPITAL (E.G., IMPROVED COGNITIVE PERFORMANCE AND PHYSICAL WORK CAPACITY). FETAL NUTRITION IS INFLUENCED BY THE MOTHER'S DIET AND BODY SIZE AND COMPOSITION, BUT HARD EVIDENCE THAT THE NUTRITION OF THE HUMAN MOTHER PROGRAMMES CHRONIC DISEASE RISK IN HER OFFSPRING IS CURRENTLY LIMITED. RECENT FINDINGS FROM FOLLOW-UP OF CHILDREN BORN AFTER RANDOMISED NUTRITIONAL INTERVENTIONS IN PREGNANCY ARE MIXED, BUT SHOW SOME EVIDENCE OF BENEFICIAL EFFECTS ON VASCULAR FUNCTION, LIPID CONCENTRATIONS, GLUCOSE TOLERANCE AND INSULIN RESISTANCE. WORK IN EXPERIMENTAL ANIMALS SUGGESTS THAT EPIGENETIC PHENOMENA, WHEREBY GENE EXPRESSION IS MODIFIED BY DNA METHYLATION, AND WHICH ARE SENSITIVE TO THE NUTRITIONAL ENVIRONMENT IN EARLY LIFE, MAY BE ONE MECHANISM UNDERLYING PROGRAMMING.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
12  5197  28 PRENATAL GLUCOCORTICOIDS EXPOSURE AND FETAL ADRENAL DEVELOPMENTAL PROGRAMMING. CLINICALLY, WE APPLY SYNTHETIC GLUCOCORTICOIDS TO TREAT FETAL AND MATERNAL DISEASES, SUCH AS PREMATURE LABOR AND AUTOIMMUNE DISEASES. ALTHOUGH ITS CLINICAL EFFICACY IS POSITIVE, THE FETUS WILL BE EXPOSED TO EXOGENOUS SYNTHETIC GLUCOCORTICOIDS. PRENATAL ADVERSE ENVIRONMENTS (SUCH AS XENOBIOTICS EXPOSURE, MALNUTRITION, INFECTION, HYPOXIA AND STRESS) CAN CAUSE FETUSES OVEREXPOSURE TO EXCESSIVE ENDOGENOUS MATERNAL GLUCOCORTICOIDS. THE LEVEL OF GLUCOCORTICOIDS IS THE KEY TO FETAL TISSUE MATURATION AND POSTNATAL FATE. A LARGE NUMBER OF STUDIES HAVE FOUND THAT PRENATAL GLUCOCORTICOIDS EXPOSURE CAN LEAD TO FETAL ADRENAL DYSPLASIA AND DYSFUNCTION, CONTINUING AFTER BIRTH AND EVEN INTO ADULTHOOD. AS THE CORE ORGAN OF FETAL-ORIGINATED ADULT DISEASES, FETAL ADRENAL DYSPLASIA IS CLOSELY RELATED TO THE SUSCEPTIBILITY AND OCCURRENCE OF MULTIPLE CHRONIC DISEASES, AND THERE ARE ALSO OBVIOUS GENDER DIFFERENCES. HOWEVER, ITS INTRAUTERINE PROGRAMMING MECHANISMS HAVE NOT BEEN FULLY ELUCIDATED. THIS REVIEW SUMMARIZES RECENT ADVANCES IN PRENATAL GLUCOCORTICOIDS EXPOSURE AND FETAL ADRENAL DEVELOPMENTAL PROGRAMMING ALTERATIONS, WHICH IS OF GREAT SIGNIFICANCE FOR EXPLAINING ADRENAL DEVELOPMENTAL TOXICITY AND THE INTRAUTERINE ORIGIN OF FETAL-ORIGINATED ADULT DISEASES.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
13  3573  33 IMPACT OF MATERNAL UNDERNUTRITION ON DIABETES AND CARDIOVASCULAR DISEASE RISK IN ADULT OFFSPRING. EPIDEMIOLOGICAL, CLINICAL, AND EXPERIMENTAL OBSERVATIONS HAVE LED TO THE HYPOTHESIS THAT THE RISK OF DEVELOPING CHRONIC DISEASES IN ADULTHOOD IS INFLUENCED NOT ONLY BY GENETIC AND ADULT LIFESTYLE FACTORS, BUT ALSO BY ENVIRONMENTAL FACTORS DURING EARLY LIFE. LOW BIRTH WEIGHT, A MARKER OF INTRAUTERINE STRESS, HAS BEEN LINKED TO PREDISPOSITION TO CARDIOVASCULAR DISEASE (CVD) AND DIABETES. THE COMPELLING ANIMAL EVIDENCE AND SIGNIFICANT HUMAN DATA TO SUPPORT THIS CONCLUSION ARE REVIEWED. SPECIFICALLY, THE REVIEW DISCUSSES THE ROLE OF MATERNAL NUTRITION BEFORE AND DURING PREGNANCY, PLACENTAL INSUFFICIENCIES AND EPIGENETIC CHANGES IN THE INCREASED PREDISPOSITION TO DIABETES AND CVD IN ADULT LIFE. THE IMPACT OF LOW BIRTH WEIGHT AND CATCH-UP GROWTH AS THEY PERTAIN TO RISK OF DISEASE IN ADULT LIFE IS ALSO DISCUSSED. IN ADDITION, ADULT DISEASE RISK IN THE OVERNOURISHED FETUS IS ALSO MENTIONED. REFERENCE IS MADE TO SOME OF THE MECHANISMS OF THE INDUCTION OF DIABETES AND CVD PHENOTYPE. IT IS PROPOSED THAT FETAL NUTRITION, GROWTH AND DEVELOPMENT THROUGH EFFICIENT MATERNAL NUTRITION BEFORE AND DURING PREGNANCY COULD CONSTITUTE THE BASIS FOR NUTRITIONAL STRATEGIES FOR THE PRIMARY PREVENTION OF DIABETES AND CVD.	2009	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
14  5178  30 PREGNANCY AS A FUNDAMENTAL DETERMINANT OF CHILD HEALTH: A REVIEW. PURPOSE OF REVIEW: MATERNAL CONDITIONS AND EXPOSURES DURING PREGNANCY INCLUDING OVER- AND UNDERNUTRITION ARE ASSOCIATED WITH POOR CHILDBIRTH OUTCOMES, GROWTH, DEVELOPMENT AND CHRONIC CHILDHOOD DISEASES. WE EXAMINED CONTEMPORARY PREGNANCY-RELATED DETERMINANTS OF CHILD HEALTH. RECENT FINDINGS: WHILE MATERNAL UNDERNUTRITION REMAINS A MAJOR CONTRIBUTOR TO LOW BIRTH WEIGHT, MATERNAL OBESITY AFFECTS FOETAL GROWTH, BIRTH WEIGHT, SURVIVAL AND IS ASSOCIATED WITH CHILDHOOD OBESITY, ASTHMA AND AUTISTIC SPECTRUM DISORDERS. EMERGING EVIDENCE SUGGESTS THAT EPIGENETIC CHANGES, THE PRENATAL MICROBIOME AND MATERNAL IMMUNE ACTIVATION (MIA), A NEUROINFLAMMATORY PROCESS INDUCED BY DIET AND OTHER EXPOSURES CAUSE FOETAL PROGRAMMING RESULTING IN THESE CHRONIC CHILDHOOD DISEASES. MATERNAL DIET IS POTENTIALLY A MODIFIABLE RISK FACTOR FOR CONTROLLING LOW BIRTH WEIGHT, OBESITY AND CHRONIC DISEASE IN CHILDHOOD. FURTHER STUDIES ARE WARRANTED TO REFINE GUIDANCE ON DIETARY RESTRICTION AND PHYSICAL ACTIVITY DURING PREGNANCY AND DETERMINE HOW MIA AND PRENATAL MICROBIOTA CAN BE APPLIED TO CONTROL CHILDHOOD DISEASES ARISING FROM PROGRAMMING.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
15  4863  35 ORIGINS OF LIFETIME HEALTH AROUND THE TIME OF CONCEPTION: CAUSES AND CONSEQUENCES. PARENTAL ENVIRONMENTAL FACTORS, INCLUDING DIET, BODY COMPOSITION, METABOLISM, AND STRESS, AFFECT THE HEALTH AND CHRONIC DISEASE RISK OF PEOPLE THROUGHOUT THEIR LIVES, AS CAPTURED IN THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE CONCEPT. RESEARCH ACROSS THE EPIDEMIOLOGICAL, CLINICAL, AND BASIC SCIENCE FIELDS HAS IDENTIFIED THE PERIOD AROUND CONCEPTION AS BEING CRUCIAL FOR THE PROCESSES MEDIATING PARENTAL INFLUENCES ON THE HEALTH OF THE NEXT GENERATION. DURING THIS TIME, FROM THE MATURATION OF GAMETES THROUGH TO EARLY EMBRYONIC DEVELOPMENT, PARENTAL LIFESTYLE CAN ADVERSELY INFLUENCE LONG-TERM RISKS OF OFFSPRING CARDIOVASCULAR, METABOLIC, IMMUNE, AND NEUROLOGICAL MORBIDITIES, OFTEN TERMED DEVELOPMENTAL PROGRAMMING. WE REVIEW PERICONCEPTIONAL INDUCTION OF DISEASE RISK FROM FOUR BROAD EXPOSURES: MATERNAL OVERNUTRITION AND OBESITY; MATERNAL UNDERNUTRITION; RELATED PATERNAL FACTORS; AND THE USE OF ASSISTED REPRODUCTIVE TREATMENT. STUDIES IN BOTH HUMANS AND ANIMAL MODELS HAVE DEMONSTRATED THE UNDERLYING BIOLOGICAL MECHANISMS, INCLUDING EPIGENETIC, CELLULAR, PHYSIOLOGICAL, AND METABOLIC PROCESSES. WE ALSO PRESENT A META-ANALYSIS OF MOUSE PATERNAL AND MATERNAL PROTEIN UNDERNUTRITION THAT SUGGESTS DISTINCT PARENTAL PERICONCEPTIONAL CONTRIBUTIONS TO POSTNATAL OUTCOMES. WE PROPOSE THAT THE EVIDENCE FOR PERICONCEPTIONAL EFFECTS ON LIFETIME HEALTH IS NOW SO COMPELLING THAT IT CALLS FOR NEW GUIDANCE ON PARENTAL PREPARATION FOR PREGNANCY, BEGINNING BEFORE CONCEPTION, TO PROTECT THE HEALTH OF OFFSPRING.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
16  4973  38 PATHOPHYSIOLOGICAL EFFECTS OF CONTEMPORARY LIFESTYLE ON EVOLUTIONARY-CONSERVED SURVIVAL MECHANISMS IN POLYCYSTIC OVARY SYNDROME. POLYCYSTIC OVARY SYNDROME (PCOS) IS INCREASINGLY BEING CHARACTERIZED AS AN EVOLUTIONARY MISMATCH DISORDER THAT PRESENTS WITH A COMPLEX MIXTURE OF METABOLIC AND ENDOCRINE SYMPTOMS. THE EVOLUTIONARY MODEL PROPOSES THAT PCOS ARISES FROM A COLLECTION OF INHERITED POLYMORPHISMS THAT HAVE BEEN CONSISTENTLY DEMONSTRATED IN A VARIETY OF ETHNIC GROUPS AND RACES. IN UTERO DEVELOPMENTAL PROGRAMMING OF SUSCEPTIBLE GENOMIC VARIANTS ARE THOUGHT TO PREDISPOSE THE OFFSPRING TO DEVELOP PCOS. POSTNATAL EXPOSURE TO LIFESTYLE AND ENVIRONMENTAL RISK FACTORS RESULTS IN EPIGENETIC ACTIVATION OF DEVELOPMENTALLY PROGRAMMED GENES AND DISTURBANCE OF THE HALLMARKS OF HEALTH. THE RESULTING PATHOPHYSIOLOGICAL CHANGES REPRESENT THE CONSEQUENCES OF POOR-QUALITY DIET, SEDENTARY BEHAVIOUR, ENDOCRINE DISRUPTING CHEMICALS, STRESS, CIRCADIAN DISRUPTION, AND OTHER LIFESTYLE FACTORS. EMERGING EVIDENCE SUGGESTS THAT LIFESTYLE-INDUCED GASTROINTESTINAL DYSBIOSIS PLAYS A CENTRAL ROLE IN THE PATHOGENESIS OF PCOS. LIFESTYLE AND ENVIRONMENTAL EXPOSURES INITIATE CHANGES THAT RESULT IN DISTURBANCE OF THE GASTROINTESTINAL MICROBIOME (DYSBIOSIS), IMMUNE DYSREGULATION (CHRONIC INFLAMMATION), ALTERED METABOLISM (INSULIN RESISTANCE), ENDOCRINE AND REPRODUCTIVE IMBALANCE (HYPERANDROGENISM), AND CENTRAL NERVOUS SYSTEM DYSFUNCTION (NEUROENDOCRINE AND AUTONOMIC NERVOUS SYSTEM). PCOS CAN BE A PROGRESSIVE METABOLIC CONDITION THAT LEADS TO OBESITY, GESTATIONAL DIABETES, TYPE TWO DIABETES, METABOLIC-ASSOCIATED FATTY LIVER DISEASE, METABOLIC SYNDROME, CARDIOVASCULAR DISEASE, AND CANCER. THIS REVIEW EXPLORES THE MECHANISMS THAT UNDERPIN THE EVOLUTIONARY MISMATCH BETWEEN ANCIENT SURVIVAL PATHWAYS AND CONTEMPORARY LIFESTYLE FACTORS INVOLVED IN THE PATHOGENESIS AND PATHOPHYSIOLOGY OF PCOS.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
17  5190  35 PRENATAL CAUSES OF KIDNEY DISEASE. IT HAS RECENTLY BEEN INCREASINGLY RECOGNISED THAT DISTURBED INTRA-UTERINE DEVELOPMENT MAY IMPACT ON RENAL AND CARDIOVASCULAR RISK IN ADULT LIFE, E.G. ALBUMINURIA AND CHRONIC KIDNEY DISEASE, HYPERTENSION, TYPE 2 DIABETES OR CARDIOVASCULAR EVENTS. ACCORDING TO BARKER'S HYPOTHESIS, WHEN RESOURCES IN UTERO ARE RESTRICTED, THEIR ALLOCATION TO THE DEVELOPMENT OF THE KIDNEY AND PANCREATIC ISLETS IS RESTRICTED TO GUARANTEE APPROPRIATE DEVELOPMENT OF THE BRAIN AND HEART. THE UNDERLYING EPIGENETIC MECHANISMS INVOLVE MODIFICATION OF GENE EXPRESSION BY ALTERED DNA METHYLATION AND HISTONE ACETYLATION AS WELL AS BY ALLOCATION OF STEM CELLS. THE RESULT OF THIS TRADE-OFF BETWEEN THE BRAIN AND KIDNEY DURING ORGANOGENESIS IS A DIMINISHED NUMBER OF NEPHRONS ('NEPHRON UNDERDOSING') WHICH PREDISPOSES TO ALBUMINURIA AND RISK OF CHRONIC KIDNEY DISEASE, AS WELL AS HYPERTENSION. IN PARALLEL, CHANGED APPETITE CENTRES, INSULIN RESISTANCE AND BETA-CELL DEVELOPMENT PREDISPOSE TO OBESITY, METABOLIC SYNDROME AND TYPE 2 DIABETES AND THE RESULTING RENAL SEQUELAE. NUMEROUS FACTORS MAY TRIGGER INTRA-UTERINE RESTRICTION OF FETAL GROWTH, SUCH AS UTERINE UNDERPERFUSION, MATERNAL MALNUTRITION, HYPERGLYCAEMIA AND HYPERINSULINAEMIA OF THE MOTHER, SMOKING OR MEDICATIONS.	2009	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
18  3594  34 IMPLICATIONS OF EARLY LIFE STRESS ON FETAL METABOLIC PROGRAMMING OF SCHIZOPHRENIA: A FOCUS ON EPIPHENOMENA UNDERLYING MORBIDITY AND EARLY MORTALITY. THE FETAL ORIGIN OF ADULT DISEASE HYPOTHESIS POSTULATES THAT A STRESSFUL IN UTERO ENVIRONMENT CAN HAVE DELETERIOUS CONSEQUENCES ON FETAL PROGRAMMING, POTENTIALLY LEADING TO CHRONIC DISEASE IN LATER LIFE. FACTORS KNOWN TO IMPACT FETAL PROGRAMMING INCLUDE THE TIMING, INTENSITY, DURATION AND NATURE OF THE EXTERNAL STRESSOR DURING PREGNANCY. AS SUCH, DYNAMIC MODULATION OF FETAL PROGRAMMING IS HEAVILY INVOLVED IN SHAPING HEALTH THROUGHOUT THE LIFE COURSE, POSSIBLY BY INFLUENCING METABOLIC PARAMETERS INCLUDING INSULIN ACTION, HYPOTHALAMIC-PITUITARY-ADRENAL ACTIVITY AND IMMUNE FUNCTION. THE ABILITY OF PRENATAL INSULTS TO PROGRAM ADULT DISEASE IS LIKELY TO OCCUR AS A RESULT OF REDUCED FUNCTIONAL CAPACITY IN KEY ORGANS-A "THRIFTY" PHENOTYPE-WHERE MORE RESOURCES ARE RE-ALLOCATED TO PRESERVE CRITICAL ORGANS SUCH AS THE BRAIN. NOTABLY, IT HAS BEEN POSTULATED THAT THE MANIFESTATION OF NEUROPSYCHIATRIC DISORDERS IN INDIVIDUALS PRIORLY EXPOSED TO PRENATAL STRESS MAY ARISE FROM THE INTERACTION BETWEEN HEREDITARY FACTORS AND THE INTRAUTERINE ENVIRONMENT, WHICH TOGETHER PRECIPITATE DISEASE ONSET BY DISRUPTING THE TRAJECTORY OF NORMAL BRAIN DEVELOPMENT. IN THIS REVIEW WE DISCUSS THE EVIDENCE LINKING PRENATAL PROGRAMMING TO NEUROPSYCHIATRIC DISORDERS, MAINLY SCHIZOPHRENIA, VIA A "THRIFTY PSYCHIATRIC PHENOTYPE" CONCEPT. WE START BY OUTLINING THE CONCEPTION OF THE THRIFTY PSYCHIATRIC PHENOTYPE. NEXT, WE DISCUSS THE CONVERGENCE OF POTENTIAL MECHANISTIC PATHWAYS THROUGH WHICH PRENATAL INSULTS MAY TRIGGER EPIGENETIC CHANGES THAT CONTRIBUTE TO THE INCREASED MORBIDITY AND EARLY MORTALITY OBSERVED IN NEUROPSYCHIATRIC DISORDERS. FINALLY, WE TOUCH ON THE PUBLIC HEALTH IMPORTANCE OF FETAL PROGRAMMING FOR THESE DISORDERS. WE CONCLUDE BY PROVIDING A BRIEF OUTLOOK ON THE FUTURE OF THIS EVOLVING FIELD OF RESEARCH.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
19  2801  29 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
20  2226  36 EPIGENETIC MODIFICATIONS INDUCED BY NUTRIENTS IN EARLY LIFE PHASES: GENDER DIFFERENCES IN METABOLIC ALTERATION IN ADULTHOOD. METABOLIC CHRONIC DISEASES, ALSO NAMED NONCOMMUNICABLE DISEASES (NCDS), ARE CONSIDERED MULTIFACTORIAL PATHOLOGIES, WHICH ARE DRAMATICALLY INCREASED DURING THE LAST DECADES. NONCOMMUNICABLE DISEASES SUCH AS CARDIOVASCULAR DISEASES, OBESITY, DIABETES MELLITUS, CANCERS, AND CHRONIC RESPIRATORY DISEASES MARKEDLY INCREASE MORBIDITY, MORTALITY, AND SOCIOECONOMIC COSTS. MOREOVER, NCDS INDUCE SEVERAL AND COMPLEX CLINICAL MANIFESTATIONS THAT LEAD TO A GRADUAL DETERIORATION OF HEALTH STATUS AND QUALITY OF LIFE OF AFFECTED INDIVIDUALS. MULTIPLE FACTORS ARE INVOLVED IN THE DEVELOPMENT AND PROGRESSION OF THESE DISEASES SUCH AS SEDENTARY BEHAVIOR, SMOKING, POLLUTION, AND UNHEALTHY DIET. INDEED, NUTRITION HAS A PIVOTAL ROLE IN MAINTAINING HEALTH, AND DIETARY IMBALANCES REPRESENT MAJOR DETERMINANTS FAVORING CHRONIC DISEASES THROUGH METABOLIC HOMEOSTASIS ALTERATIONS. IN PARTICULAR, IT APPEARS THAT SPECIFIC NUTRIENTS AND ADEQUATE NUTRITION ARE IMPORTANT IN ALL PERIODS OF LIFE, BUT THEY ARE ESSENTIAL DURING SPECIFIC TIMES IN EARLY LIFE SUCH AS PRENATAL AND POSTNATAL PHASES. INDEED, EPIDEMIOLOGIC AND EXPERIMENTAL STUDIES REPORT THE DELETERIOUS EFFECTS OF AN INCORRECT NUTRITION ON HEALTH STATUS SEVERAL DECADES LATER IN LIFE. DURING THE LAST DECADE, A GROWING INTEREST ON THE POSSIBLE ROLE OF EPIGENETIC MECHANISMS AS LINK BETWEEN NUTRITIONAL IMBALANCES AND NCDS DEVELOPMENT HAS BEEN OBSERVED. FINALLY, BECAUSE OF THE PIVOTAL ROLE OF THE HORMONES IN FAT, CARBOHYDRATE, AND PROTEIN METABOLISM REGULATION THROUGHOUT LIFE, IT IS EXPECTED THAT ANY HORMONAL MODIFICATION OF THESE PROCESSES CAN IMBALANCE METABOLISM AND FAT STORAGE. THEREFORE, A PARTICULAR INTEREST TO SEVERAL CHEMICALS ABLE TO ACT AS ENDOCRINE DISRUPTORS HAS BEEN RECENTLY DEVELOPED. IN THIS REVIEW, WE WILL PROVIDE AN OVERVIEW AND DISCUSS THE EPIGENETIC ROLE OF SOME SPECIFIC NUTRIENTS AND CHEMICALS IN THE MODULATION OF PHYSIOLOGICAL AND PATHOLOGICAL MECHANISMS.	2019