1 6744 156 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
2 5000  29 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
3 6698  33 VARICOCOELE AND OXIDATIVE STRESS: NEW PERSPECTIVES FROM ANIMAL AND HUMAN STUDIES. BACKGROUND: VARICOCOELE (VCL), ONE OF THE MAIN CAUSES OF MALE SUBFERTILITY, NEGATIVELY AFFECTS TESTICULAR FUNCTION. DUE TO LIMITED ACCESS TO HUMAN TESTICULAR TISSUE, ANIMAL MODEL STUDIES HAVE BEEN USED TO EVALUATE MOLECULAR AND, RECENTLY, EPIGENETIC CHANGES ATTRIBUTED TO PATHOPHYSIOLOGY INDUCED BY VCL. OBJECTIVES: THIS REVIEW AIMS TO PROVIDE AN UPDATE ON THE LATEST FINDINGS REGARDING THE LINK BETWEEN VCL-INDUCED BIOCHEMICAL STRESS AND MOLECULAR CHANGES IN GERM CELLS AND SPERMATOZOA. ENDOCRINE AND ANTIOXIDANT STATUS, TESTICULAR CHAPERONE-SPECIFIC HEMOSTASIS FAILURE, ALTERED TESTICULAR ION BALANCE, METABOLIC DISORDERS, AND ALTERED CARBON CYCLING DURING SPERMATOGENESIS ARE AMONG THE MANY FEATURES THAT WILL BE PRESENTED. DISCUSSION: LITERATURE REVIEW COUPLED WITH OUR OWN FINDINGS SUGGESTS THAT IONIC IMBALANCE, HYPOXIA, HYPERTHERMIA, AND ALTERED BLOOD FLOW COULD LEAD TO SEVERE CHRONIC OXIDATIVE AND NITROSATIVE STRESS IN PATIENTS WITH VCL LEADING TO DEFECTIVE SPERMATOGENESIS AND IMPAIRMENT OF THE INTEGRITY OF ALL SPERM CELL COMPONENTS AND COMPARTMENTS DOWN TO THE EPIGENETIC INFORMATION THEY CARRY. CONCLUSION: SINCE OXIDATIVE STRESS IS AN IMPORTANT FEATURE OF THE REPRODUCTIVE PATHOLOGY OF VCL, THERAPEUTIC STRATEGIES SUCH AS THE ADMINISTRATION OF APPROPRIATE ANTIOXIDANTS COULD BE UNDERTAKEN AS A COMPLEMENTARY NON-INVASIVE TREATMENT LINE.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
4 4019  32 LOW-DOSE OR LOW-DOSE-RATE IONIZING RADIATION-INDUCED BIOEFFECTS IN ANIMAL MODELS. ANIMAL EXPERIMENTAL STUDIES INDICATE THAT ACUTE OR CHRONIC LOW-DOSE IONIZING RADIATION (LDIR) (</=100 MSV) OR LOW-DOSE-RATE IONIZING RADIATION (LDRIR) (<6 MSV/H) EXPOSURES MAY BE HARMFUL. IT INDUCES GENETIC AND EPIGENETIC CHANGES AND IS ASSOCIATED WITH A RANGE OF PHYSIOLOGICAL DISTURBANCES THAT INCLUDES ALTERED IMMUNE SYSTEM, ABNORMAL BRAIN DEVELOPMENT WITH RESULTANT COGNITIVE IMPAIRMENT, CATARACTOGENESIS, ABNORMAL EMBRYONIC DEVELOPMENT, CIRCULATORY DISEASES, WEIGHT GAIN, PREMATURE MENOPAUSE IN FEMALE ANIMALS, TUMORIGENESIS AND SHORTENED LIFESPAN. PATERNAL OR PRENATAL LDIR/LDRIR EXPOSURE IS ASSOCIATED WITH REDUCED FERTILITY AND NUMBER OF LIVE FETUSES, AND TRANSGENERATIONAL GENOMIC ABERRATIONS. ON THE OTHER HAND, IN SOME EXPERIMENTAL STUDIES, LDIR/LDRIR EXPOSURE HAS ALSO BEEN REPORTED TO BRING ABOUT BENEFICIAL EFFECTS SUCH AS REDUCTION IN TUMORIGENESIS, PROLONGED LIFESPAN AND ENHANCED FERTILITY. THE DIFFERENCES IN REPORTED EFFECTS OF LDIR/LDRIR EXPOSURE ARE DEPENDENT ON ANIMAL GENETIC BACKGROUND (SUSCEPTIBILITY), AGE (PRENATAL OR POSTNATAL DAYS), SEX, NATURE OF RADIATION EXPOSURE (I.E. ACUTE, FRACTIONATED OR CHRONIC RADIATION EXPOSURE), TYPE OF RADIATION, COMBINATION OF RADIATION WITH OTHER TOXIC AGENTS (SUCH AS SMOKING, PESTICIDES OR OTHER CHEMICAL TOXINS) OR ANIMAL EXPERIMENTAL DESIGNS. IN THIS REVIEW PAPER, WE AIMED TO UPDATE RADIATION RESEARCHERS AND RADIOLOGISTS ON THE CURRENT PROGRESS ACHIEVED IN UNDERSTANDING THE LDIR/LDRIR-INDUCED BIONEGATIVE AND BIOPOSITIVE EFFECTS REPORTED IN THE VARIOUS ANIMAL MODELS. THE ROLES PLAYED BY A VARIETY OF MOLECULES THAT ARE IMPLICATED IN LDIR/LDRIR-INDUCED HEALTH EFFECTS WILL BE ELABORATED. THE REVIEW WILL HELP IN FUTURE INVESTIGATIONS OF LDIR/LDRIR-INDUCED HEALTH EFFECTS BY PROVIDING CLUES FOR DESIGNING IMPROVED ANIMAL RESEARCH MODELS IN ORDER TO CLARIFY THE CURRENT CONTROVERSIAL/CONTRADICTORY FINDINGS FROM EXISTING STUDIES.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
5 1749  27 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
6 1927  28 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
7 4808  30 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	
                                                                                                                                                                                                                                         
8  167  32 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
9 5091  24 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
10 4809  28 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
11 3899  31 LATE NEUROLOGICAL CONSEQUENCES OF ZIKA VIRUS INFECTION: RISK FACTORS AND PHARMACEUTICAL APPROACHES. ZIKA VIRUS (ZIKV) INFECTION WAS HISTORICALLY CONSIDERED A DISEASE WITH MILD SYMPTOMS AND NO MAJOR CONSEQUENCES TO HUMAN HEALTH. HOWEVER, SEVERAL LONG-TERM, LATE ONSET, AND CHRONIC NEUROLOGICAL COMPLICATIONS, BOTH IN CONGENITALLY-EXPOSED BABIES AND IN ADULT PATIENTS, HAVE BEEN REPORTED AFTER ZIKV INFECTION, ESPECIALLY AFTER THE 2015 EPIDEMICS IN THE AMERICAN CONTINENT. THE DEVELOPMENT OR SEVERITY OF THESE CONDITIONS CANNOT BE FULLY PREDICTED, BUT IT IS POSSIBLE THAT GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS MAY CONTRIBUTE TO DETERMINE ZIKV INFECTION OUTCOMES. THIS REINFORCES THE IMPORTANCE THAT INDIVIDUALS EXPOSED TO ZIKV ARE SUBMITTED TO LONG-TERM CLINICAL SURVEILLANCE AND HIGHLIGHTS THE URGENT NEED FOR THE DEVELOPMENT OF THERAPEUTIC APPROACHES TO REDUCE OR ELIMINATE THE NEUROLOGICAL BURDEN OF INFECTION. HERE, WE REVIEW THE EPIDEMIOLOGY OF ZIKV-ASSOCIATED NEUROLOGICAL COMPLICATIONS AND THE ROLE OF FACTORS THAT MAY INFLUENCE DISEASE OUTCOME. MOREOVER, WE DISCUSS EXPERIMENTAL AND CLINICAL EVIDENCE OF DRUGS THAT HAVE SHOWN PROMISING RESULTS IN VITRO OR IN VITRO AGAINST VIRAL REPLICATION AND AND/OR ZIKV-INDUCED NEUROTOXICITY.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
12  650  25 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
13 6911  21 [TWO GERMAN BIRTH COHORTS: GINIPLUS AND LISAPLUS]. NUMEROUS CHRONIC DISEASES IN CHILDHOOD AND ADULTHOOD HAVE THEIR ORIGINS IN PERINATAL LIFE AND ARE POTENTIALLY INFLUENCED BY TRANS-GENERATIONAL EPIGENETIC PROCESSES. THEREFORE, PROSPECTIVE BIRTH COHORTS CAN SUBSTANTIALLY CONTRIBUTE TO OUR KNOWLEDGE ABOUT THE ETIOLOGY OF DISEASES INCLUDING MODIFIABLE RISK FACTORS. THE TWO POPULATION-BASED GERMAN BIRTH COHORTS GINIPLUS AND LISAPLUS AIM TO DESCRIBE THE NATURAL COURSE OF CHRONIC DISEASES AND INTERMEDIATE PHENOTYPES IN CHILDHOOD AND ITS DETERMINANTS, AND TO IDENTIFY POTENTIAL GENETIC EFFECT MODIFICATIONS. IN THE MID-1990S, 5,991 (GINIPLUS) AND 3,097 (LISAPLUS) HEALTHY, TERM NEWBORNS WERE RECRUITED FOR LONG-TERM FOLLOW-UP IN FOUR REGIONS OF GERMANY. THE FOLLOW-UP RATE FOR THE FIRST 10 YEARS WAS ABOUT 55%. WE ANALYZED THE GROWTH AND DEVELOPMENT OF OVERWEIGHT, INFECTIONS AND ALLERGIC DISEASES, MENTAL AND ORAL HEALTH, METABOLIC AND INFLAMMATORY PARAMETERS AND THE ROLE OF POTENTIAL RISK FACTORS INCLUDING GENETICS. THE RESULTS OF THESE TWO BIRTH COHORTS SUBSTANTIALLY CONTRIBUTE TO THE CURRENT KNOWLEDGE ABOUT THE NATURAL COURSE OF THESE HEALTH PARAMETERS. THESE DATA WERE INCLUDED IN MANY INTERNATIONAL PROJECTS AND CONSORTIA FOR PURPOSES OF INTERNATIONAL COMPARISONS OF PREVALENCE AND CONSISTENCY OF FINDINGS, AND TO INCREASE THE POWER OF THE ANALYSES.	2012	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
14 2799  33 FEED COMPOSITION DIFFERENCES RESULTING FROM ORGANIC AND CONVENTIONAL FARMING PRACTICES AFFECT PHYSIOLOGICAL PARAMETERS IN WISTAR RATS-RESULTS FROM A FACTORIAL, TWO-GENERATION DIETARY INTERVENTION TRIAL. RECENT HUMAN COHORT STUDIES REPORTED POSITIVE ASSOCIATIONS BETWEEN ORGANIC FOOD CONSUMPTION AND A LOWER INCIDENCE OF OBESITY, CANCER, AND SEVERAL OTHER DISEASES. HOWEVER, THERE ARE VERY FEW ANIMAL AND HUMAN DIETARY INTERVENTION STUDIES THAT PROVIDE SUPPORTING EVIDENCE OR A MECHANISTIC UNDERSTANDING OF THESE ASSOCIATIONS. HERE WE REPORT RESULTS FROM A TWO-GENERATION, DIETARY INTERVENTION STUDY WITH MALE WISTAR RATS TO IDENTIFY THE EFFECTS OF FEEDS MADE FROM ORGANIC AND CONVENTIONAL CROPS ON GROWTH, HORMONAL, AND IMMUNE SYSTEM PARAMETERS THAT ARE KNOWN TO AFFECT THE RISK OF A NUMBER OF CHRONIC, NON-COMMUNICABLE DISEASES IN ANIMALS AND HUMANS. A 2 X 2 FACTORIAL DESIGN WAS USED TO SEPARATE THE EFFECTS OF CONTRASTING CROP PROTECTION METHODS (USE OR NON-USE OF SYNTHETIC CHEMICAL PESTICIDES) AND FERTILIZERS (MINERAL NITROGEN, PHOSPHORUS AND POTASSIUM (NPK) FERTILIZERS VS. MANURE USE) APPLIED IN CONVENTIONAL AND ORGANIC CROP PRODUCTION. CONVENTIONAL, PESTICIDE-BASED CROP PROTECTION RESULTED IN SIGNIFICANTLY LOWER FIBER, POLYPHENOL, FLAVONOID, AND LUTEIN, BUT HIGHER LIPID, ALDICARB, AND DIQUAT CONCENTRATIONS IN ANIMAL FEEDS. CONVENTIONAL, MINERAL NPK-BASED FERTILIZATION RESULTED IN SIGNIFICANTLY LOWER POLYPHENOL, BUT HIGHER CADMIUM AND PROTEIN CONCENTRATIONS IN FEEDS. FEED COMPOSITION DIFFERENCES RESULTING FROM THE USE OF PESTICIDES AND/OR MINERAL NPK-FERTILIZER HAD A SIGNIFICANT EFFECT ON FEED INTAKE, WEIGHT GAIN, PLASMA HORMONE, AND IMMUNOGLOBULIN CONCENTRATIONS, AND LYMPHOCYTE PROLIFERATION IN BOTH GENERATIONS OF RATS AND IN THE SECOND GENERATION ALSO ON THE BODY WEIGHT AT WEANING. RESULTS SUGGEST THAT RELATIVELY SMALL CHANGES IN DIETARY INTAKES OF (A) PROTEIN, LIPIDS, AND FIBER, (B) TOXIC AND/OR ENDOCRINE-DISRUPTING PESTICIDES AND METALS, AND (C) POLYPHENOLS AND OTHER ANTIOXIDANTS (RESULTING FROM PESTICIDE AND/OR MINERAL NPK-FERTILIZER USE) HAD COMPLEX AND OFTEN INTERACTIVE EFFECTS ON ENDOCRINE, IMMUNE SYSTEMS AND GROWTH PARAMETERS IN RATS. HOWEVER, THE PHYSIOLOGICAL RESPONSES TO CONTRASTING FEED COMPOSITION/INTAKE PROFILES DIFFERED SUBSTANTIALLY BETWEEN THE FIRST AND SECOND GENERATIONS OF RATS. THIS MAY INDICATE EPIGENETIC PROGRAMMING AND/OR THE GENERATION OF "ADAPTIVE" PHENOTYPES AND SHOULD BE INVESTIGATED FURTHER.	2021	

15 6853  35 [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	
                                                                                                                                                                                                                                                                                                                                            
16 6730  27 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
17 5213  30 PRESYMPTOMATIC RISK ASSESSMENT FOR CHRONIC NON-COMMUNICABLE DISEASES. THE PREVALENCE OF COMMON CHRONIC NON-COMMUNICABLE DISEASES (CNCDS) FAR OVERSHADOWS THE PREVALENCE OF BOTH MONOGENIC AND INFECTIOUS DISEASES COMBINED. ALL CNCDS, ALSO CALLED COMPLEX GENETIC DISEASES, HAVE A HERITABLE GENETIC COMPONENT THAT CAN BE USED FOR PRE-SYMPTOMATIC RISK ASSESSMENT. COMMON SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) THAT TAG RISK HAPLOTYPES ACROSS THE GENOME CURRENTLY ACCOUNT FOR A NON-TRIVIAL PORTION OF THE GERM-LINE GENETIC RISK AND WE WILL LIKELY CONTINUE TO IDENTIFY THE REMAINING MISSING HERITABILITY IN THE FORM OF RARE VARIANTS, COPY NUMBER VARIANTS AND EPIGENETIC MODIFICATIONS. HERE, WE DESCRIBE A NOVEL MEASURE FOR CALCULATING THE LIFETIME RISK OF A DISEASE, CALLED THE GENETIC COMPOSITE INDEX (GCI), AND DEMONSTRATE ITS PREDICTIVE VALUE AS A CLINICAL CLASSIFIER. THE GCI ONLY CONSIDERS SUMMARY STATISTICS OF THE EFFECTS OF GENETIC VARIATION AND HENCE DOES NOT REQUIRE THE RESULTS OF LARGE-SCALE STUDIES SIMULTANEOUSLY ASSESSING MULTIPLE RISK FACTORS. COMBINING GCI SCORES WITH ENVIRONMENTAL RISK INFORMATION PROVIDES AN ADDITIONAL TOOL FOR CLINICAL DECISION-MAKING. THE GCI CAN BE POPULATED WITH HERITABLE RISK INFORMATION OF ANY TYPE, AND THUS REPRESENTS A FRAMEWORK FOR CNCD PRE-SYMPTOMATIC RISK ASSESSMENT THAT CAN BE POPULATED AS ADDITIONAL RISK INFORMATION IS IDENTIFIED THROUGH NEXT-GENERATION TECHNOLOGIES.	2010	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
18 6422  25 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
19 4995  32 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 4399  33 MODULATION OF GENOMIC AND POSTGENOMIC ALTERATIONS IN NONCANCER DISEASES AND CRITICAL PERIODS OF LIFE. GENOMIC AND POSTGENOMIC CHANGES ARE EXTENSIVELY INVESTIGATED IN CANCER RESEARCH. SIMILAR ALTERATIONS, AFFECTING GENOME, TRANSCRIPTOME, MIRNOME AND/OR PROTEOME END-POINTS, HAVE BEEN DETECTED IN A VARIETY OF OTHER CHRONIC DEGENERATIVE DISEASES, SUCH AS ATHEROSCLEROSIS, DEGENERATIVE HEART DISEASES, CHRONIC OBSTRUCTIVE PULMONARY DISEASES, NEUROLOGICAL DISORDERS, EYE DISEASES, DIABETES, METABOLIC SYNDROME, SKIN AGEING AND ALOPECIA. NO GENERALIZATION CAN BE MADE DUE TO THE MYRIAD OF DIVERSE CLINICAL ENTITIES CLASSIFIED AS CHRONIC DEGENERATIVE DISEASES. MOREOVER, THE DETECTION OF MOLECULAR CHANGES DOES NOT AUTOMATICALLY IMPLY THEIR CAUSAL ROLE. NEVERTHELESS, COMMON MECHANISMS, SUCH AS DNA DAMAGE, EPIGENETIC ALTERATIONS, OXIDATIVE STRESS, AND CHRONIC INFLAMMATION, IN ADDITION TO GENETIC PREDISPOSITION, ARE OFTEN INVOLVED IN NONCANCER DISEASES. WE DEBATE HERE IN MORE DETAIL THE SUBJECTS OF CARDIOVASCULAR DISEASES AND OF SKIN DISEASES. MOREOVER, WE DISCUSS OUR EXPERIMENTAL STUDIES SUGGESTING THAT GENOMIC AND POSTGENOMIC CHANGES DO ALSO OCCUR DURING CRITICAL PERIODS OF LIFE, INCLUDING THE PRENATAL LIFE, THE PERINATAL PERIOD, AND AGEING. IN ADDITION, WE COMMENT ON THE FINDING THAT STEM-DERIVED CELLS ARE MORE SUSCEPTIBLE TO MOLECULAR DAMAGE THAN MORE DIFFERENTIATED CELLS. ALL THESE DATA ARE VIEWED IN THE PERSPECTIVE OF PREVENTIVE MEDICINE. IN FACT, THERE IS EVIDENCE THAT THE GENOMIC AND POSTGENOMIC ALTERATIONS OCCURRING NOT ONLY IN SEVERAL PATHOLOGICAL CONDITIONS BUT ALSO IN PARAPHYSIOLOGICAL SITUATIONS THAT AFFECT CRITICAL PERIODS OF LIFE CAN BE MODULATED BY MEANS OF DIETARY AND PHARMACOLOGICAL AGENTS. THE DISCOVERY THAT CHEMOPREVENTIVE AGENTS ARE ALSO ABLE TO ATTENUATE NUCLEOTIDE DAMAGE IN STEM-DERIVED CELLS WARRANTS FURTHER STUDIES IN VIEW OF POSSIBLE CLINICAL APPLICATIONS.	2009