1 1377 105 DEVELOPMENTAL PROGRAMMING: STATE-OF-THE-SCIENCE AND FUTURE DIRECTIONS-SUMMARY FROM A PENNINGTON BIOMEDICAL SYMPOSIUM. OBJECTIVE: ON DECEMBER 8-9, 2014, THE PENNINGTON BIOMEDICAL RESEARCH CENTER CONVENED A SCIENTIFIC SYMPOSIUM TO REVIEW THE STATE-OF-THE-SCIENCE AND FUTURE DIRECTIONS FOR THE STUDY OF DEVELOPMENTAL PROGRAMMING OF OBESITY AND CHRONIC DISEASE. THE OBJECTIVES OF THE SYMPOSIUM WERE TO DISCUSS: (I) PAST AND CURRENT SCIENTIFIC ADVANCES IN ANIMAL MODELS, POPULATION-BASED COHORT STUDIES, AND HUMAN CLINICAL TRIALS, (II) THE STATE-OF-THE-SCIENCE OF EPIGENETIC-BASED RESEARCH, AND (III) CONSIDERATIONS FOR FUTURE STUDIES. RESULTS: THIS SYMPOSIUM PROVIDED A COMPREHENSIVE ASSESSMENT OF THE STATE OF THE SCIENTIFIC FIELD AND IDENTIFIED RESEARCH GAPS AND OPPORTUNITIES FOR FUTURE RESEARCH IN ORDER TO UNDERSTAND THE MECHANISMS CONTRIBUTING TO THE DEVELOPMENTAL PROGRAMMING OF HEALTH AND DISEASE. CONCLUSIONS: IDENTIFYING THE MECHANISMS WHICH CAUSE OR CONTRIBUTE TO DEVELOPMENTAL PROGRAMMING OF FUTURE GENERATIONS WILL BE INVALUABLE TO THE SCIENTIFIC AND MEDICAL COMMUNITY. THE ABILITY TO INTERVENE DURING CRITICAL PERIODS OF PRENATAL AND EARLY POSTNATAL LIFE TO PROMOTE LIFELONG HEALTH IS THE ULTIMATE GOAL. CONSIDERATIONS FOR FUTURE RESEARCH INCLUDING THE USE OF ANIMAL MODELS, THE STUDY DESIGN IN HUMAN COHORTS WITH CONSIDERATIONS ABOUT THE TIMING OF THE INTRAUTERINE EXPOSURE, AND THE RESULTING TISSUE-SPECIFIC EPIGENETIC SIGNATURE WERE EXTENSIVELY DISCUSSED AND ARE PRESENTED IN THIS MEETING SUMMARY. 2016 2 421 33 ANIMAL MODELS IN EPIGENETIC RESEARCH: INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE CONSIDERATIONS ACROSS THE LIFESPAN. THE RAPID EXPANSION AND EVOLUTION OF EPIGENETICS AS A CORE SCIENTIFIC DISCIPLINE HAVE RAISED NEW QUESTIONS ABOUT HOW ENDOGENOUS AND ENVIRONMENTAL FACTORS CAN INFORM THE MECHANISMS THROUGH WHICH BIOLOGICAL FORM AND FUNCTION ARE REGULATED. EXISTING AND PROPOSED ANIMAL MODELS USED FOR EPIGENETIC RESEARCH HAVE TARGETED A MYRIAD OF HEALTH AND DISEASE ENDPOINTS THAT MAY BE ACUTE, CHRONIC, AND TRANSGENERATIONAL IN NATURE. INITIATING EVENTS AND OUTCOMES MAY EXTEND ACROSS THE ENTIRE LIFESPAN TO ELICIT UNANTICIPATED PHENOTYPES THAT ARE OF PARTICULAR CONCERN TO INSTITUTIONAL ANIMAL CARE AND USE COMMITTEES (IACUCS). THE DYNAMICS AND PLASTICITY OF EPIGENETIC MECHANISMS PRODUCE EFFECTS AND CONSEQUENCES THAT ARE MANIFEST DIFFERENTIALLY WITHIN DISCREET SPATIAL AND TEMPORAL CONTEXTS, INCLUDING PRENATAL DEVELOPMENT, STEM CELLS, ASSISTED REPRODUCTIVE TECHNOLOGIES, PRODUCTION OF SEXUAL DIMORPHISMS, SENESCENCE, AND OTHERS. MANY DIETARY AND NUTRITIONAL INTERVENTIONS HAVE ALSO BEEN SHOWN TO HAVE A SIGNIFICANT IMPACT ON BIOLOGICAL FUNCTIONS AND DISEASE SUSCEPTIBILITIES THROUGH ALTERED EPIGENETIC PROGRAMMING. THE ENVIRONMENTAL, CHEMICAL, TOXIC, THERAPEUTIC, AND PSYCHOSOCIAL STRESSORS USED IN ANIMAL STUDIES TO ELICIT EPIGENETIC CHANGES CAN BECOME EXTREME AND SHOULD RAISE IACUC CONCERNS FOR THE WELL-BEING AND PROPER CARE OF ALL RESEARCH ANIMALS INVOLVED. EPIGENETICS RESEARCH IS RAPIDLY BECOMING AN INTEGRAL PART OF THE SEARCH FOR MECHANISMS IN EVERY MAJOR AREA OF BIOMEDICAL AND BEHAVIORAL RESEARCH AND WILL FOSTER THE CONTINUED DEVELOPMENT OF NEW ANIMAL MODELS. FROM THE IACUC PERSPECTIVE, CARE MUST BE TAKEN TO ACKNOWLEDGE THE PARTICULAR NEEDS AND CONCERNS CREATED BY SUPERIMPOSITION OF EPIGENETIC MECHANISMS OVER DIVERSE FIELDS OF INVESTIGATION TO ENSURE THE PROPER CARE AND USE OF ANIMALS WITHOUT IMPEDING SCIENTIFIC PROGRESS. 2012 3 1248 38 CURRENT EVIDENCE FOR BIOLOGICAL BIOMARKERS AND MECHANISMS UNDERLYING ACUTE TO CHRONIC PAIN TRANSITION ACROSS THE PEDIATRIC AGE SPECTRUM. CHRONIC PAIN IS HIGHLY PREVALENT IN THE PEDIATRIC POPULATION. MANY FACTORS ARE INVOLVED IN THE TRANSITION FROM ACUTE TO CHRONIC PAIN. CURRENTLY, THERE ARE CONCEPTUAL MODELS PROPOSED, BUT THEY LACK A MECHANISTICALLY SOUND INTEGRATED THEORY CONSIDERING THE STAGES OF CHILD DEVELOPMENT. OBJECTIVE BIOMARKERS ARE CRITICALLY NEEDED FOR THE DIAGNOSIS, RISK STRATIFICATION, AND PROGNOSIS OF THE PATHOLOGICAL STAGES OF PAIN CHRONIFICATION. IN THIS ARTICLE, WE SUMMARIZE THE CURRENT EVIDENCE ON MECHANISMS AND BIOMARKERS OF ACUTE TO CHRONIC PAIN TRANSITIONS IN INFANTS AND CHILDREN THROUGH THE DEVELOPMENTAL LENS. THE GOAL IS TO IDENTIFY GAPS AND OUTLINE FUTURE DIRECTIONS FOR BASIC AND CLINICAL RESEARCH TOWARD A DEVELOPMENTALLY INFORMED THEORY OF PAIN CHRONIFICATION IN THE PEDIATRIC POPULATION. AT THE OUTSET, THE IMPORTANCE OF OBJECTIVE BIOMARKERS FOR CHRONIFICATION OF PAIN IN CHILDREN IS OUTLINED, FOLLOWED BY A SUMMARY OF THE CURRENT EVIDENCE ON THE MECHANISMS OF ACUTE TO CHRONIC PAIN TRANSITION IN ADULTS, IN ORDER TO CONTRAST WITH THE DEVELOPMENTAL MECHANISMS OF PAIN CHRONIFICATION IN THE PEDIATRIC POPULATION. EVIDENCE IS PRESENTED TO SHOW THAT CHRONIC PAIN MAY HAVE ITS ORIGIN FROM INSULTS EARLY IN LIFE, WHICH PRIME THE CHILD FOR THE DEVELOPMENT OF CHRONIC PAIN IN LATER LIFE. FURTHERMORE, AVAILABLE GENETIC, EPIGENETIC, PSYCHOPHYSICAL, ELECTROPHYSIOLOGICAL, NEUROIMAGING, NEUROIMMUNE, AND SEX MECHANISMS ARE DESCRIBED IN INFANTS AND OLDER CHILDREN. IN CONCLUSION, FUTURE DIRECTIONS ARE DISCUSSED WITH A FOCUS ON RESEARCH GAPS, TRANSLATIONAL AND CLINICAL IMPLICATIONS. UTILIZATION OF DEVELOPMENTAL MECHANISMS FRAMEWORK TO INFORM CLINICAL DECISION-MAKING AND STRATEGIES FOR PREVENTION AND MANAGEMENT OF ACUTE TO CHRONIC PAIN TRANSITIONS IN CHILDREN, IS HIGHLIGHTED. 2023 4 5650 25 SEX DIFFERENCES IN THE DEVELOPMENT OF PHYSICAL AGGRESSION: AN INTERGENERATIONAL PERSPECTIVE AND IMPLICATIONS FOR PREVENTIVE INTERVENTIONS. THIS ARTICLE REVIEWS THE STATE OF KNOWLEDGE ON THE DEVELOPMENT OF CHRONIC PHYSICAL AGGRESSION (CPA), WITH THE AIM OF IDENTIFYING THE MOST EFFECTIVE PREVENTION STRATEGIES. WE SPECIFICALLY FOCUS ON THE EARLY DEVELOPMENT OF PHYSICAL AGGRESSION, ON SEX DIFFERENCES IN THE USE OF PHYSICAL AGGRESSION, AND ON THE TRANSMISSION OF BEHAVIOR PROBLEMS FROM ONE GENERATION TO THE OTHER. THE BODY OF RESEARCH ON THE DEVELOPMENT OF CPA FROM THE PAST THREE DECADES THAT WE REVIEW SHOWS INCREASING EVIDENCE THAT ITS PREVENTION REQUIRES A LONG-TERM BIOPSYCHOSOCIAL DEVELOPMENTAL APPROACH WHICH ALSO MUST INCLUDE AN INTERGENERATIONAL PERSPECTIVE. RECENT GENETIC AND EPIGENETIC RESEARCH HAS INDICATED THAT THERE ARE BOTH IMPORTANT GENETIC AND ENVIRONMENTAL EFFECTS ON GENE EXPRESSION WHICH START AT CONCEPTION. WE CONCLUDE THAT ONE OF THE MOST EFFECTIVE STRATEGIES TO BREAK THE INTERGENERATIONAL TRANSMISSION OF CPA INVOLVES GIVING LONG-TERM SUPPORT TO PREGNANT WOMEN WITH A HISTORY OF BEHAVIOR PROBLEMS, THEIR SPOUSE, AND THEIR OFFSPRING. 2019 5 1865 37 EMERGING CONCEPTS ON THE ROLE OF EPIGENETICS IN THE RELATIONSHIPS BETWEEN NUTRITION AND HEALTH. UNDERSTANDING THE PHYSIOLOGICAL AND METABOLIC UNDERPINNINGS THAT CONFER INDIVIDUAL DIFFERENCES IN RESPONSES TO DIET AND DIET-RELATED CHRONIC DISEASE IS ESSENTIAL TO ADVANCE THE FIELD OF NUTRITION. THIS INCLUDES ELUCIDATING THE DIFFERENCES IN GENE EXPRESSION THAT ARE MEDIATED THROUGH PROGRAMMING OF THE GENOME THROUGH EPIGENETIC CHROMATIN MODIFICATIONS. EPIGENETIC LANDSCAPES ARE INFLUENCED BY AGE, GENETICS, TOXINS AND OTHER ENVIRONMENTAL FACTORS, INCLUDING DIETARY EXPOSURES AND NUTRITIONAL STATUS. EPIGENETIC MODIFICATIONS INFLUENCE TRANSCRIPTION AND GENOME STABILITY ARE ESTABLISHED DURING DEVELOPMENT WITH LIFE-LONG CONSEQUENCES. THEY CAN BE INHERITED FROM ONE GENERATION TO THE NEXT. THE COVALENT MODIFICATIONS OF CHROMATIN, WHICH INCLUDE METHYLATION AND ACETYLATION, ON DNA NUCLEOTIDE BASES, HISTONE PROTEINS AND RNA ARE DERIVED FROM INTERMEDIATES OF ONE-CARBON METABOLISM AND CENTRAL METABOLISM. THEY INFLUENCE KEY PHYSIOLOGICAL PROCESSES THROUGHOUT LIFE, AND TOGETHER WITH INHERITED DNA PRIMARY SEQUENCE, CONTRIBUTE TO RESPONSIVENESS TO ENVIRONMENTAL STRESSES, DIET AND RISK FOR AGE-RELATED CHRONIC DISEASE. REVEALING DIET-EPIGENETIC RELATIONSHIPS HAS THE POTENTIAL TO TRANSFORM NUTRITION SCIENCE BY INCREASING OUR FUNDAMENTAL UNDERSTANDING OF: (I) THE ROLE OF NUTRIENTS IN BIOLOGICAL SYSTEMS, (II) THE RESILIENCE OF LIVING ORGANISMS IN RESPONDING TO ENVIRONMENTAL PERTURBATIONS, AND (III) THE DEVELOPMENT OF DIETARY PATTERNS THAT PROGRAMME PHYSIOLOGY FOR LIFE-LONG HEALTH. EPIGENETICS MAY ALSO ENABLE THE CLASSIFICATION OF INDIVIDUALS WITH CHRONIC DISEASE FOR SPECIFIC DIETARY MANAGEMENT AND/OR FOR EFFICACIOUS DIET-PHARMACEUTICAL COMBINATION THERAPIES. THESE NEW EMERGING CONCEPTS AT THE INTERFACE OF NUTRITION AND EPIGENETICS WERE DISCUSSED, AND FUTURE RESEARCH NEEDS IDENTIFIED BY LEADING EXPERTS AT THE 26TH MARABOU SYMPOSIUM ENTITLED 'NUTRITION, EPIGENETICS, GENETICS: IMPACT ON HEALTH AND DISEASE'. FOR A COMPILATION OF THE GENERAL DISCUSSION AT THE MARABOU SYMPOSIUM, CLICK HERE HTTP://WWW.MARABOUSYMPOSIUM.ORG/. 2018 6 2521 25 EPIGENETICS AND THE INTERNATIONAL CLASSIFICATION OF FUNCTIONING, DISABILITY AND HEALTH MODEL: BRIDGING NATURE, NURTURE, AND PATIENT-CENTERED POPULATION HEALTH. EPIGENETIC PROCESSES ENABLE ENVIRONMENTAL INPUTS SUCH AS DIET, EXERCISE, AND HEALTH BEHAVIORS TO REVERSIBLY TAG DNA WITH CHEMICAL "MARKS" THAT INCREASE OR DECREASE THE EXPRESSION OF AN INDIVIDUAL'S GENETIC TEMPLATE. OVER TIME, EPIGENETIC ADAPTATIONS ENABLE THE EFFECTS OF HEALTHY OR UNHEALTHY STRESSES TO BECOME STABLY EXPRESSED IN THE TISSUE OF AN ORGANISM, WITH IMPORTANT CONSEQUENCES FOR HEALTH AND DISEASE. NEW RESEARCH INDICATES THAT SEEMINGLY NON-BIOLOGICAL FACTORS SUCH AS SOCIAL STRESS, POVERTY, AND CHILDHOOD HARDSHIP INITIATE EPIGENETIC ADAPTATIONS IN GENE PATHWAYS THAT GOVERN INFLAMMATION AND IMMUNITY, TWO OF THE GREATEST CONTRIBUTORS TO CHRONIC DISEASES SUCH AS DIABETES AND OBESITY. EPIGENETIC PROCESSES THEREFORE PROVIDE A BIOLOGICAL BRIDGE BETWEEN THE GENOME-AN INDIVIDUAL'S GENETIC INHERITANCE-AND THE SOCIAL DETERMINANTS OF HEALTH-THE CONDITIONS IN WHICH THEY ARE BORN, GROW, LIVE, WORK, AND AGE. THIS PERSPECTIVE PAPER ARGUES THAT PHYSICAL THERAPY CLINICIANS, RESEARCHERS, AND EDUCATORS CAN USE THE THEORETICAL FRAMEWORK PROVIDED BY THE INTERNATIONAL CLASSIFICATION OF FUNCTIONING, DISABILITY, AND HEALTH (ICF MODEL) TO HARMONIZE NEW DISCOVERIES FROM BOTH PUBLIC HEALTH RESEARCH AND MEDICALLY FOCUSED GENOMIC RESEARCH. THE ICF MODEL LIKEWISE CAPTURES THE ESSENTIAL ROLE PLAYED BY PHYSICAL ACTIVITY AND EXERCISE, WHICH INITIATE POWERFUL AND WIDESPREAD EPIGENETIC ADAPTATIONS THAT PROMOTE HEALTH AND FUNCTIONING. IN THIS PROPOSED FRAMEWORK, EPIGENETIC PROCESSES TRANSDUCE THE EFFECTS OF THE SOCIAL DETERMINANTS OF HEALTH AND BEHAVIORS SUCH AS EXERCISE INTO STABLE BIOLOGICAL ADAPTATIONS THAT AFFECT AN INDIVIDUAL'S DAILY ACTIVITIES AND THEIR PARTICIPATION IN SOCIAL ROLES. BY HARMONIZING "NATURE" AND "NURTURE," PHYSICAL THERAPISTS CAN APPROACH PATIENT CARE WITH A MORE INTEGRATED PERSPECTIVE, CAPITALIZING ON NOVEL DISCOVERIES IN PRECISION MEDICINE, REHABILITATION SCIENCE, AND IN POPULATION-LEVEL RESEARCH. AS THE EXPERTS IN PHYSICAL ACTIVITY AND EXERCISE, PHYSICAL THERAPISTS ARE IDEALLY POSITIONED TO DRIVE PROGRESS IN THE NEW ERA OF PATIENT-CENTERED POPULATION HEALTH CARE. 2022 7 6823 26 [GENERAL CONCEPTS OF EPIGENETICS: PROJECTIONS IN PAEDIATRICS]. CURRENT EVIDENCE SUPPORTS THE NOTION THAT ALTERATIONS IN INTRAUTERINE GROWTH AND DURING THE FIRST YEARS OF LIFE HAVE A SUBSTANTIAL EFFECT ON THE RISK FOR THE DEVELOPMENT OF CHRONIC DISEASE, WHICH IN SOME CASES IS EVEN HIGHER THAN THOSE DUE TO GENETIC FACTORS. THE PERSISTENCE AND REPRODUCIBILITY OF THE PHENOTYPES ASSOCIATED WITH ALTERED EARLY DEVELOPMENT SUGGEST THE PARTICIPATION OF MECHANISMS THAT WOULD RECORD ENVIRONMENTAL CUES, GENERATING A CELLULAR REPROGRAMMING (I.E., EPIGENETIC MECHANISMS). THIS REVIEW IS AN INTRODUCTION TO A SERIES OF FIVE ARTICLES FOCUSED ON THE PARTICIPATION OF EPIGENETIC MECHANISMS IN THE DEVELOPMENT OF HIGHLY PREVALENT CHRONIC DISEASES (I.E., CARDIOVASCULAR, METABOLIC, ASTHMA/ALLERGIES AND CANCER) AND THEIR ORIGINS IN THE FOETAL AND NEONATAL PERIOD. THIS SERIES OF ARTICLES AIMS TO SHOW THE STATE OF THE ART IN THIS RESEARCH AREA AND PRESENT THE UPCOMING CLUES AND CHALLENGES, IN WHICH PAEDIATRICIANS HAVE A PROMINENT ROLE, DEVELOPING STRATEGIES FOR THE PREVENTION, EARLY DETECTION AND FOLLOW-UP. 2016 8 1766 38 EARLY-LIFE EXPERIENCES AND THE DEVELOPMENT OF ADULT DISEASES WITH A FOCUS ON MENTAL ILLNESS: THE HUMAN BIRTH THEORY. IN MAMMALS, EARLY ADVERSE EXPERIENCES, INCLUDING MOTHER-PUP INTERACTIONS, SHAPE THE RESPONSE OF AN INDIVIDUAL TO CHRONIC STRESS OR TO STRESS-RELATED DISEASES DURING ADULT LIFE. THIS HAS LED TO THE ELABORATION OF THE THEORY OF THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE, IN PARTICULAR ADULT DISEASES SUCH AS CARDIOVASCULAR AND METABOLIC DISORDERS. IN ADDITION, IN HUMANS, AS STATED BY MASSIMO FAGIOLI'S HUMAN BIRTH THEORY, BIRTH IS HEALTHY AND EQUAL FOR ALL INDIVIDUALS, SO THAT MENTAL ILLNESS DEVELOP EXCLUSIVELY IN THE POSTNATAL PERIOD BECAUSE OF THE QUALITY OF THE RELATIONSHIP IN THE FIRST YEAR OF LIFE. THUS, THIS REVIEW FOCUSES ON THE IMPORTANCE OF PROGRAMMING DURING THE EARLY DEVELOPMENTAL PERIOD ON THE MANIFESTATION OF ADULT DISEASES IN BOTH ANIMAL MODELS AND HUMANS. CONSIDERING THE OBVIOUS DIFFERENCES BETWEEN ANIMALS AND HUMANS WE CANNOT SYSTEMATICALLY MOVE FROM ANIMAL MODELS TO HUMANS. CONSEQUENTLY, IN THE FIRST PART OF THIS REVIEW, WE WILL DISCUSS HOW ANIMAL MODELS CAN BE USED TO DISSECT THE INFLUENCE OF ADVERSE EVENTS OCCURRING DURING THE PRENATAL AND POSTNATAL PERIODS ON THE DEVELOPMENTAL TRAJECTORIES OF THE OFFSPRING, AND IN THE SECOND PART, WE WILL DISCUSS THE ROLE OF POSTNATAL CRITICAL PERIODS ON THE DEVELOPMENT OF MENTAL DISEASES IN HUMANS. EPIGENETIC MECHANISMS THAT CAUSE REVERSIBLE MODIFICATIONS IN GENE EXPRESSION, DRIVING THE DEVELOPMENT OF A PATHOLOGICAL PHENOTYPE IN RESPONSE TO A NEGATIVE EARLY POSTNATAL ENVIRONMENT, MAY LIE AT THE CORE OF THIS PROGRAMMING, THEREBY PROVIDING POTENTIAL NEW THERAPEUTIC TARGETS. THE CONCEPT OF THE HUMAN BIRTH THEORY LEADS TO A COMPREHENSION OF THE MENTAL ILLNESS AS A PATHOLOGY OF THE HUMAN RELATIONSHIP IMMEDIATELY AFTER BIRTH AND DURING THE FIRST YEAR OF LIFE. 2017 9 1453 21 DISCOVERING HOW ENVIRONMENTAL EXPOSURES ALTER GENES COULD LEAD TO NEW TREATMENTS FOR CHRONIC ILLNESSES. EMERGING RESEARCH DEMONSTRATES THAT DIET, POLLUTION, AND OTHER ENVIRONMENTAL TRIGGERS CAN ALTER BOTH THE FUNCTION AND EXPRESSION OF HUMAN GENES AND LEAD TO A HEIGHTENED DISEASE RISK. THESE ENVIRONMENT-GENE INTERACTIONS CAN CAUSE SO-CALLED EPIGENETIC CHANGES IN GENE EXPRESSION-PATTERNS OF WHICH GENES ARE SWITCHED "ON" OR "OFF"-THAT MAY ACCOUNT FOR THE RISING MORTALITY FROM CHRONIC DISEASES IN INDUSTRIALIZED NATIONS. IN THIS PAPER, WE CALL FOR A NEW TRANSDISCIPLINARY APPROACH TO PUBLIC HEALTH THAT WOULD EXAMINE HOW ENVIRONMENTAL EXPOSURES, BOTH PHYSICAL AND SOCIAL, INFLUENCE GENE EXPRESSION AND A PERSON'S SUSCEPTIBILITY TO CHRONIC DISEASE. THIS INITIATIVE COULD LEAD TO NEW WAYS TO PREVENT AND TREAT SUCH ILLNESSES. 2011 10 2492 23 EPIGENETICS AND CHILDHOOD ASTHMA: CURRENT EVIDENCE AND FUTURE RESEARCH DIRECTIONS. ASTHMA IS THE MOST COMMON CHRONIC DISEASE OF CHILDHOOD, AFFECTING ONE IN EIGHT CHILDREN IN THE USA AND WORLDWIDE. IT IS A COMPLEX DISEASE, INFLUENCED BY BOTH ENVIRONMENTAL EXPOSURES AND GENETIC FACTORS. ALTHOUGH EPIGENETIC MODIFICATIONS (DNA METHYLATION, HISTONE MODIFICATION AND MIRNA) CAN AFFECT TRANSCRIPTIONAL ACTIVITY IN MULTIPLE GENETIC PATHWAYS RELEVANT FOR ASTHMA DEVELOPMENT, VERY LIMITED WORK HAS BEEN CARRIED OUT SO FAR TO EXAMINE THE ROLE OF EPIGENETIC VARIATIONS ON ASTHMA DEVELOPMENT AND MANAGEMENT. THIS REVIEW PROVIDES A BRIEF OVERVIEW OF EPIGENETIC MODIFICATIONS, SUMMARIZES RECENT FINDINGS, AND DISCUSSES SOME OF THE MAJOR METHODOLOGICAL CONCERNS THAT ARE RELEVANT FOR ASTHMA EPIGENETICS. 2012 11 2136 32 EPIGENETIC INFLUENCES IN THE OBESITY/COLORECTAL CANCER AXIS: A NOVEL THERAGNOSTIC AVENUE. THE WORLD HEALTH ORGANIZATION (WHO) CONSIDERS THAT OBESITY HAS REACHED PROPORTIONS OF PANDEMIC. EXPERTS ALSO INSIST ON THE IMPORTANCE OF CONSIDERING OBESITY AS A CHRONIC DISEASE AND ONE OF THE MAIN CONTRIBUTORS TO THE WORLDWIDE BURDEN OF OTHER NONTRANSMISSIBLE CHRONIC DISEASES, WHICH HAVE A GREAT IMPACT ON HEALTH, LIFESTYLE, AND ECONOMIC COST. ONE OF THE MOST CURRENT CHALLENGES OF BIOMEDICAL SCIENCE FACES IS TO UNDERSTAND THE ORIGIN OF THE CHRONIC NONTRANSMISSIBLE DISEASES, SUCH AS OBESITY AND CANCER. THERE IS A LARGE EVIDENCE, BOTH IN EPIDEMIOLOGICAL STUDIES IN HUMANS AND IN ANIMAL MODELS, OF THE ASSOCIATION BETWEEN OBESITY AND AN INCREASED RISK OF CANCER INCIDENCE. IN THE LAST YEARS, THE INITIAL DISCOVERY OF EPIGENETIC MECHANISMS REPRESENTS THE MOST RELEVANT FINDING TO EXPLAIN HOW THE GENOME INTERACTS WITH ENVIRONMENTAL FACTORS AND THE RIPPLE EFFECTS ON DISEASE PATHOGENESES. SINCE THEN, ALL EPIGENETIC PROCESS HAS BEEN INVESTIGATED BY THE SCIENTIFIC COMMUNITIES FOR NEARLY TWO DECADES TO DETERMINE WHICH COMPONENTS ARE INVOLVED IN THIS PROCESS. DNA/RNA METHYLATION AND MIRNA ARE CLASSIFIED AS TWO OF THE MOST IMPORTANT REPRESENTATIVE CLASSES OF SUCH EPIGENETIC MECHANISMS AND DYSREGULATED ACTIVITY OF SUCH MECHANISM CAN CERTAINLY CONTRIBUTE TO DISEASE PATHOGENESIS AND/OR PROGRESSION ESPECIALLY IN TUMORS. THIS REVIEW ARTICLE SERVES TO HIGHLIGHT THE IMPACT OF DNA/RNA METHYLATION AND MIRNA-BASED EPIGENETIC MECHANISM ACTIVITIES IN THE INTERPLAY BETWEEN OBESITY AND THE DEVELOPMENT AND CLINICAL SIGNIFICANCE OF COLORECTAL CANCER. 2019 12 6459 15 TIME TO CHANGE FROM A SIMPLE LINEAR MODEL TO A COMPLEX SYSTEMS MODEL. A SIMPLE LINEAR MODEL TO TEST THE HYPOTHESIS BASED ON ONE-ON-ONE RELATIONSHIP HAS BEEN USED TO FIND THE CAUSATIVE FACTORS OF DISEASES. HOWEVER, WE NOW KNOW THAT NOT JUST ONE, BUT MANY FACTORS FROM DIFFERENT SYSTEMS SUCH AS CHEMICAL EXPOSURE, GENES, EPIGENETIC CHANGES, AND PROTEINS ARE INVOLVED IN THE PATHOGENESIS OF CHRONIC DISEASES SUCH AS DIABETES MELLITUS. SO, WITH AVAILABILITY OF MODERN TECHNOLOGIES TO UNDERSTAND THE INTRICATE NATURE OF RELATIONS AMONG COMPLEX SYSTEMS, WE NEED TO MOVE FORWARD TO THE FUTURE BY TAKING COMPLEX SYSTEMS MODEL. 2016 13 2517 25 EPIGENETICS AND THE BURDEN OF NONCOMMUNICABLE DISEASE: A PAUCITY OF RESEARCH IN AFRICA. EPIDEMIOLOGICAL EVIDENCE SUGGESTS THAT AN ADVERSE IN UTERO ENVIRONMENT IS ASSOCIATED WITH AN INCREASED RISK FOR DEVELOPING ADULT ONSET DISEASES. THE MOLECULAR MECHANISMS FOR SUSCEPTIBILITY TO CHRONIC NONCOMMUNICABLE DISEASES ARE NOT FULLY UNDERSTOOD, ALTHOUGH RECENT RESEARCH HAS PROPOSED THAT EPIGENETIC MODIFICATIONS PLAY AN IMPORTANT ROLE IN FETAL PROGRAMMING. GENETIC AND ENVIRONMENTAL FACTORS CONTRIBUTE TO INTERINDIVIDUAL AND SPATIOTEMPORAL TISSUE-SPECIFIC METHYLATION PATTERNS. ALTHOUGH THE DIVERSE ENVIRONMENTS AND HIGH GENETIC DIVERSITY OF AFRICAN POPULATIONS PROVIDE UNPARALLELED POTENTIAL TO INVESTIGATE THE EFFECTS OF ENVIRONMENTAL CHANGE ON THE EPIGENETIC PROFILE IN HUMANS, ONLY A SMALL PERCENTAGE OF GENOMIC AND EPIGENETIC STUDIES HAVE FOCUSED ON POPULATIONS FROM THIS CONTINENT. THIS EMPHASIZES THE NEED TO BUILD CAPACITY IN AFRICA FOR RESEARCH THAT LEADS TO AN UNDERSTANDING OF THE ASSOCIATION BETWEEN GENETIC, EPIGENETIC AND ENVIRONMENTAL RISK FACTORS FOR NONCOMMUNICABLE DISEASES ON THE CONTINENT. 2015 14 1409 26 DIETARY INTERVENTIONS AND NUTRITIONAL FACTORS IN THE PREVENTION OF PEDIATRIC ASTHMA. ASTHMA IS THE MOST FREQUENT CHRONIC DISEASE IN CHILDREN, AND ITS PATHOGENESIS INVOLVES GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS. THE RAPID RISE IN THE PREVALENCE OF ASTHMA REGISTERED OVER THE LAST FEW DECADES HAS STRESSED THE NEED TO IDENTIFY THE ENVIRONMENTAL AND MODIFIABLE FACTORS ASSOCIATED WITH THE DEVELOPMENT OF THE DISEASE. IN PARTICULAR, THERE IS INCREASING INTEREST IN THE ROLE OF MODIFIABLE NUTRITIONAL FACTORS SPECIFIC TO BOTH THE PRENATAL AND POST-NATAL EARLY LIFE AS, DURING THIS TIME, THE IMMUNE SYSTEM IS PARTICULARLY VULNERABLE TO EXOGENOUS INTERFERENCES. SEVERAL DIETARY FACTORS, INCLUDING MATERNAL DIET DURING PREGNANCY, THE DURATION OF BREASTFEEDING, THE USE OF SPECIAL MILK FORMULAS, THE TIMING OF THE INTRODUCTION OF COMPLEMENTARY FOODS, AND PRENATAL AND EARLY LIFE SUPPLEMENTATION WITH VITAMINS AND PROBIOTICS/PREBIOTICS, HAVE BEEN ADDRESSED AS POTENTIAL TARGETS FOR THE PREVENTION OF ASTHMA. IN THIS REVIEW, WE OUTLINE RECENT FINDINGS ON THE POTENTIAL ROLE OF PRENATAL AND PERINATAL DIETARY AND NUTRITIONAL INTERVENTIONS FOR THE PRIMARY PREVENTION OF PEDIATRIC ASTHMA. MOREOVER, WE ADDRESSED UNMET NEEDS AND AREAS FOR FUTURE RESEARCH IN THE PREVENTION OF CHILDHOOD-ONSET ASTHMA. 2020 15 4802 32 OBESITY AND LIFESPAN HEALTH--IMPORTANCE OF THE FETAL ENVIRONMENT. A MARKED INCREASE IN THE FREQUENCY OF OBESITY AT THE POPULATION LEVEL HAS RESULTED IN AN INCREASING NUMBER OF OBESE WOMEN ENTERING PREGNANCY. THE INCREASING REALIZATION OF THE IMPORTANCE OF THE FETAL ENVIRONMENT IN RELATION TO CHRONIC DISEASE ACROSS THE LIFESPAN HAS FOCUSED ATTENTION ON THE ROLE OF MATERNAL OBESITY IN FETAL DEVELOPMENT. PREVIOUS STUDIES HAVE DEMONSTRATED THAT OBESITY DURING ADOLESCENCE AND ADULTHOOD CAN BE TRACED BACK TO FETAL AND EARLY CHILDHOOD EXPOSURES. THIS REVIEW FOCUSES ON FACTORS THAT CONTRIBUTE TO EARLY DEVELOPMENTAL EVENTS, SUCH AS EPIGENETIC MODIFICATIONS, THE POTENTIAL FOR AN INCREASE IN INFLAMMATORY BURDEN, EARLY DEVELOPMENTAL PROGRAMMING CHANGES SUCH AS THE VARIABLE DEVELOPMENT OF WHITE VERSUS BROWN ADIPOSE TISSUE, AND ALTERATIONS IN ORGAN ONTOGENY. WE HYPOTHESIZE THAT THESE MECHANISMS PROMOTE AN UNFAVORABLE FETAL ENVIRONMENT AND CAN HAVE A LONG-STANDING IMPACT, WITH EARLY MANIFESTATIONS OF CHRONIC DISEASE THAT CAN RESULT IN AN INCREASED DEMAND FOR FUTURE HEALTH CARE. IN ORDER TO IDENTIFY APPROPRIATE PREVENTIVE MEASURES, ATTENTION NEEDS TO BE PLACED BOTH ON REDUCING MATERNAL OBESITY AS WELL AS UNDERSTANDING THE MOLECULAR, CELLULAR, AND EPIGENETIC MECHANISMS THAT MAY BE RESPONSIBLE FOR THE PRENATAL ONSET OF CHRONIC DISEASE. 2014 16 5457 32 RESEARCH AND THE PROMOTION OF CHILD HEALTH: A POSITION PAPER OF THE EUROPEAN SOCIETY FOR PEDIATRIC GASTROENTEROLOGY, HEPATOLOGY, AND NUTRITION. CHILDREN COMPRISE ONE-FIFTH OF EUROPE'S POPULATION. PROMOTING CHILD HEALTH AND DEVELOPMENT IS OF KEY IMPORTANCE FOR SOCIETY AND ITS FUTURE. THIS POSITION PAPER HIGHLIGHTS OPPORTUNITIES OF INVESTING IN GASTROINTESTINAL, LIVER, AND NUTRITIONAL RESEARCH TO PROMOTE CHILD HEALTH AND DELINEATES PRIORITIES FOR RESEARCH. INVESTING IN CHILD HEALTH PLAYS A KEY ROLE IN THE PROMOTION OF POPULATION HEALTH, WELL-BEING, AND DISEASE PREVENTION LIFELONG, WITH LARGE HEALTH ECONOMIC BENEFITS. MAJOR OPPORTUNITIES FOR IMPROVING KNOWLEDGE AND TRANSLATIONAL APPLICATION ARISE FROM RECENT SCIENTIFIC AND TECHNOLOGICAL DEVELOPMENTS, FOR EXAMPLE, THE LONG-TERM IMPACT OF EARLY ENVIRONMENTAL CUES INTERACTING WITH GENES. PERSONALISED APPROACHES TO THERAPY AND PREVENTION SHOULD BE ENHANCED. DECIPHERING THE MICROBIOME AND ITS EFFECTS ON FUNCTIONS CAN HELP IN PROMOTING LONG-TERM HEALTH. EPIGENETIC RESEARCH CAN HELP TO UNDERSTAND HOW EARLY ENVIRONMENTAL FACTORS INFLUENCE LATER GASTROINTESTINAL AND HEPATIC HEALTH AND DISEASE. A LINKED NUTRITION AND PHYSICAL ACTIVITY STRATEGY CAN PROMOTE HEALTH AND PREVENT NUTRITIONAL DEFICIENCIES, INACTIVITY, AND CHRONIC NONCOMMUNICABLE DISEASES, SUCH AS DIABETES, TO ENSURE OPTIMAL HEALTH AND COGNITION. SPECIAL ATTENTION SHOULD BE DEVOTED TO POPULATIONS WITH LOW SOCIOECONOMIC STATUS, MIGRANT BACKGROUND, AND ETHNIC MINORITIES, AND TO CRITICAL LIFE PERIODS, INCLUDING PREGNANCY, LACTATION, INFANCY, AND CHILDHOOD. IMPROVED UNDERSTANDING OF OPTIMAL NUTRITION AND ON MAINTAINING GUT AND LIVER HOMEOSTASIS THROUGHOUT CHILDHOOD WILL HELP PREVENT CHRONIC DISEASES IN LATER LIFE. 2014 17 6858 24 [NUTRIGENOMICS, OBESITY AND PUBLIC HEALTH]. FUNCTIONAL GENOMICS WILL CHANGE KNOWLEDGE AND PRACTICE IN CLINICAL NUTRITION IN THE FORTHCOMING YEARS. THE POSSIBILITY OF PERFORMING AN INDIVIDUAL'S GENETIC PROFILE (GENETIC VARIATIONS AND EPIGENETIC MODIFICATIONS) AS WELL AS THE ABILITY OF ITS INTEGRATION IN A COMPLEX NETWORK OF METABOLIC INTERACTIONS REPRESENTS A HUGE CHALLENGE IN HUMAN NUTRITION. THE INFLUENCE OF NUTRIGENOMICS IN TERMS OF PREVENTION AND TREATMENT OF CHRONIC DISEASES, SUCH AS OBESITY, TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE IN A POPULATION LEVEL REMAINS UNDETERMINED FOR THE MOMENT. THE OPPORTUNITY OF NUTRITIONAL INTERVENTION IN CRITICAL STAGES OF DEVELOPMENT AND THE CHANCE OF CHANGING GENETIC SUSCEPTIBILITY TO DISEASES THROUGH DIET IN A PUBLIC HEALTH BASIS SHOULD LEAD THE FUTURE OF NUTRIGENOMICS BEYOND THE MERE DESIGN OF "PERSONALIZED" FUNCTIONAL FOOD OR DIETS. 2007 18 2049 24 EPIGENETIC CODE AND POTENTIAL EPIGENETIC-BASED THERAPIES AGAINST CHRONIC DISEASES IN DEVELOPMENTAL ORIGINS. ACCUMULATED FINDINGS HAVE DEMONSTRATED THAT THE EPIGENETIC CODE PROVIDES A POTENTIAL LINK BETWEEN PRENATAL STRESS AND CHANGES IN GENE EXPRESSION THAT COULD BE INVOLVED IN THE DEVELOPMENTAL PROGRAMMING OF VARIOUS CHRONIC DISEASES IN LATER LIFE. MEANWHILE, BASED ON THE FACT THAT EPIGENETIC MODIFICATIONS ARE REVERSIBLE AND CAN BE MANIPULATED, THIS PROVIDES A UNIQUE CHANCE TO DEVELOP MULTIPLE NOVEL EPIGENETIC-BASED THERAPEUTIC STRATEGIES AGAINST MANY CHRONIC DISEASES IN EARLY DEVELOPMENTAL PERIODS. THIS ARTICLE WILL GIVE A SHORT REVIEW OF RECENT FINDINGS OF PRENATAL INSULT-INDUCED EPIGENETIC CHANGES IN DEVELOPMENTAL ORIGINS OF SEVERAL CHRONIC DISEASES, AND WILL ATTEMPT TO PROVIDE AN OVERVIEW OF THE CURRENT EPIGENETIC-BASED STRATEGIES APPLIED IN THE EARLY PREVENTION, DIAGNOSIS AND POSSIBLE THERAPIES FOR HUMAN CHRONIC DISEASES. 2014 19 4591 24 NARRATIVE REVIEW OF THE COMPLEX INTERACTION BETWEEN PAIN AND TRAUMA IN CHILDREN: A FOCUS ON BIOLOGICAL MEMORY, PRECLINICAL DATA, AND EPIGENETIC PROCESSES. THE INCIDENCE AND COLLECTIVE IMPACT OF EARLY ADVERSE EXPERIENCES, TRAUMA, AND PAIN CONTINUE TO INCREASE. THIS UNDERSCORES THE URGENT NEED FOR TRANSLATIONAL EFFORTS BETWEEN CLINICAL AND PRECLINICAL RESEARCH TO BETTER UNDERSTAND THE UNDERLYING MECHANISMS AND DEVELOP EFFECTIVE THERAPEUTIC APPROACHES. AS OUR UNDERSTANDING OF THESE ISSUES IMPROVES FROM STUDIES IN CHILDREN AND ADOLESCENTS, WE CAN CREATE MORE PRECISE PRECLINICAL MODELS AND ULTIMATELY TRANSLATE OUR FINDINGS BACK TO CLINICAL PRACTICE. A MULTIDISCIPLINARY APPROACH IS ESSENTIAL FOR ADDRESSING THE COMPLEX AND WIDE-RANGING EFFECTS OF THESE EXPERIENCES ON INDIVIDUALS AND SOCIETY. THIS NARRATIVE REVIEW AIMS TO (1) DEFINE PAIN AND TRAUMA EXPERIENCES IN CHILDHOOD AND ADOLESCENTS, (2) DISCUSS THE RELATIONSHIP BETWEEN PAIN AND TRAUMA, (3) CONSIDER THE ROLE OF BIOLOGICAL MEMORY, (4) DECIPHER THE RELATIONSHIP BETWEEN PAIN AND TRAUMA USING PRECLINICAL DATA, AND (5) EXAMINE THE ROLE OF THE ENVIRONMENT BY INTRODUCING THE IMPORTANCE OF EPIGENETIC PROCESSES. THE ULTIMATE SCOPE IS TO BETTER UNDERSTAND THE WIDE-RANGING EFFECTS OF TRAUMA, ABUSE, AND CHRONIC PAIN ON CHILDREN AND ADOLESCENTS, HOW THEY OCCUR, AND HOW TO PREVENT OR MITIGATE THEIR EFFECTS AND DEVELOP EFFECTIVE TREATMENT STRATEGIES THAT ADDRESS BOTH THE UNDERLYING CAUSES AND THE ASSOCIATED PHYSIOLOGICAL AND PSYCHOLOGICAL EFFECTS. 2023 20 2651 30 EPIGENOMICS AND TRANSCRIPTOMICS IN THE PREDICTION AND DIAGNOSIS OF CHILDHOOD ASTHMA: ARE WE THERE YET? ASTHMA IS THE MOST COMMON NON-COMMUNICABLE CHRONIC DISEASE OF CHILDHOOD. DESPITE ITS HIGH PREVALENCE, TO DATE WE LACK METHODS THAT ARE BOTH EFFICIENT AND ACCURATE IN DIAGNOSING ASTHMA. MOST TRADITIONAL APPROACHES HAVE BEEN BASED ON GARNERING CLINICAL EVIDENCE, SUCH AS RISK FACTORS AND EXPOSURES. GIVEN THE HIGH HERITABILITY OF ASTHMA, MORE RECENT APPROACHES HAVE LOOKED AT GENETIC POLYMORPHISMS AS POTENTIAL "RISK FACTORS." HOWEVER, GENETIC VARIANTS EXPLAIN ONLY A SMALL PROPORTION OF ASTHMA RISK, AND HAVE BEEN LESS THAN OPTIMAL AT PREDICTING RISK FOR INDIVIDUAL SUBJECTS. EPIGENOMIC STUDIES OFFER SIGNIFICANT ADVANTAGES OVER PREVIOUS APPROACHES. EPIGENETIC REGULATION IS HIGHLY TISSUE-SPECIFIC, AND CAN INDUCE BOTH SHORT- AND LONG-TERM CHANGES IN GENE EXPRESSION. SUCH CHANGES CAN START IN UTERO, CAN VARY THROUGHOUT THE LIFE SPAN, AND IN SOME INSTANCES CAN BE PASSED ON FROM ONE GENERATION TO ANOTHER. MOST IMPORTANTLY, THE EPIGENOME CAN BE MODIFIED BY ENVIRONMENTAL FACTORS AND EXPOSURES, AND THUS EPIGENETIC AND TRANSCRIPTOMIC PROFILING MAY YIELD THE MOST ACCURATE RISK ESTIMATES FOR A GIVEN PATIENT BY INCORPORATING ENVIRONMENTAL (AND TREATMENT) EFFECTS THROUGHOUT THE LIFESPAN. HERE WE WILL REVIEW THE MOST RECENT ADVANCES IN THE USE OF EPIGENETIC AND TRANSCRIPTOMIC ANALYSIS FOR THE EARLY DIAGNOSIS OF ASTHMA AND ATOPY, AS WELL AS CHALLENGES AND FUTURE DIRECTIONS IN THE FIELD AS IT MOVES FORWARD. WE WILL PARTICULARLY FOCUS ON DNA METHYLATION, THE MOST STUDIED MECHANISM OF EPIGENETIC REGULATION. 2019