1 1147 152 CONDYLE MODELING STABILITY, CRANIOFACIAL ASYMMETRY AND ACTN3 GENOTYPES: CONTRIBUTION TO TMD PREVALENCE IN A COHORT OF DENTOFACIAL DEFORMITIES. CRANIOFACIAL ASYMMETRY, MANDIBULAR CONDYLAR MODELING AND TEMPOROMANDIBULAR JOINT DISORDERS ARE COMMON COMORBIDITIES OF SKELETALLY DISPROPORTIONATE MALOCCLUSIONS, BUT ETIOLOGY OF OCCURRENCE TOGETHER IS POORLY UNDERSTOOD. WE COMPARED ASYMMETRY, CONDYLE MODELING STABILITY AND TEMPOROMANDIBULAR HEALTH IN A COHORT OF 128 PATIENTS HAVING ORTHODONTICS AND ORTHOGNATHIC SURGERY TO CORRECT DENTOFACIAL DEFORMITY MALOCCLUSIONS. WE ALSO COMPARED ACTN3 AND ENPP1 GENOTYPES FOR ASSOCIATION TO CLINICAL CONDITIONS. PRE-SURGICAL POSTERIOR-ANTERIOR CEPHALOMETRIC AND PANOMETRIC RADIOGRAPHIC ANALYSES; JAW PAIN AND FUNCTION QUESTIONNAIRE AND CLINICAL EXAMINATION OF TMD; AND SNP-GENOTYPE ANALYSIS FROM SALIVA SAMPLES WERE COMPARED TO ASSESS INTERRELATIONSHIPS. ALMOST HALF HAD ASYMMETRIES IN NEED OF SURGICAL CORRECTION, WHICH COULD BE SUBDIVIDED INTO FOUR DISTINCT MORPHOLOGICAL PATTERNS. ASYMMETRIC CONDYLE MODELING BETWEEN SIDES WAS SIGNIFICANTLY GREATER IN CRANIOFACIAL ASYMMETRY, BUT MOST COMMONLY HAD AN UNANTICIPATED PATTERN. OFTEN, LONGER OR LARGER CONDYLES OCCURRED ON THE SHORTER MANDIBULAR RAMUS SIDE. SUBJECTS WITH LONGER RAMUS BUT DIMENSIONALLY SMALLER CONDYLES WERE MORE LIKELY TO HAVE SELF-REPORTED TMD SYMPTOMS (P = 0.023) AND SIGNIFICANTLY GREATER CLINICAL DIAGNOSIS OF TMD (P = 0 .000001), WITH MASTICATORY MYALGIA MOST PROMINENT. GENOTYPING FOUND TWO SIGNIFICANT GENOTYPE ASSOCIATIONS FOR ACTN3 RS1671064 (Q523R MISSENSE) P = 0.02; RS678397 (INTRONIC SNP) P = 0.04 AND ONE SIGNIFICANT ALLELE ASSOCIATION RS1815739 (R577X NONSENSE) P = 0.00. SKELETAL ASYMMETRY, UNUSUAL CONDYLE MODELING AND TMD ARE COMMON AND INTERRELATED COMPONENTS OF MANY DENTOFACIAL DEFORMITIES. IMBALANCED MUSCULOSKELETAL FUNCTIONAL ADAPTATIONS AND GENETIC OR EPIGENETIC INFLUENCES CONTRIBUTE TO THE ETIOLOGY, AND REQUIRE FURTHER INVESTIGATION. 2020 2 6792 21 [DOHAD AND EPIGENETIC INFORMATION: SOCIETAL CHALLENGES]. THE CONCEPT OF THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) ALTERS OUR UNDERSTANDING OF WHAT CONSTITUTES "HEALTH" OR "DISEASE" INTENDED AS CHRONIC, NON-COMMUNICABLE DISEASES, WHICH DEVELOP OVER THE LIFE COURSE IN HIGH INCOME AND EMERGING COUNTRIES. IT IMPLIES A CHANGE IN PARADIGM FORMING A BASIS FOR PREVENTION POLICIES ACROSS THE GLOBE. IT ALSO IMPACTS PSYCHOLOGICAL, SOCIAL, ECONOMIC, ETHICAL AND LEGAL SCIENCES. IN LINE WITH THE UNANTICIPATED UNDERPINNING EPIGENETIC MECHANISMS ARE ALSO THE SOCIAL ISSUES (INCLUDING PUBLIC POLICIES) THAT COULD BE PRODUCED BY THE KNOWLEDGE RELATED TO DOHAD THAT OPENS A WIDE FIELD OF INQUIRY. THE INFORMATION UNVEILED BY EPIGENETICS COUPLED WITH INFORMATION ON LIFESTYLE INCLUDING DURING THE DEVELOPMENT PHASE, IS OF UNFORESEEN NATURE, RAISING ISSUES OF DIFFERENT NATURE. THEREFORE IT REQUIRES SPECIFIC ATTENTION AND RESEARCH, AND A SPECIFIC SUPPORT BY A PLURIDISCIPLINARY REFLECTION SINCE THE VERY BEGINNING OF ITS PRODUCTION, TO ANTICIPATE THE QUESTIONS THAT MIGHT BE RAISED IN THE FUTURE. 2016 3 421 25 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 4 5176 26 PREFACE TO COAST 2016 INNOVATORS' WORKSHOP ON PERSONALIZED AND PRECISION ORTHODONTIC THERAPY. OBJECTIVE: A SECOND FOCUSED WORKSHOP EXPLORED HOW TO TRANSFER NOVEL FINDINGS INTO CLINICAL ORTHODONTIC PRACTICE. SETTING AND SAMPLE POPULATION: PARTICIPANTS MET IN WEST PALM BEACH (FLORIDA, USA), ON 9-11 SEPTEMBER 2016 FOR THE CONSORTIUM FOR ORTHODONTIC ADVANCES IN SCIENCE AND TECHNOLOGY 2016 INNOVATORS' WORKSHOP (COAST). APPROXIMATELY 65 REGISTERED ATTENDEES CONSIDERED AND DISCUSSED INFORMATION FROM 27 TO 34 SPEAKERS, 8 TO 15 POSTER PRESENTERS AND FOUR LUNCH-HOUR FOCUS GROUP LEADERS. MATERIAL AND METHODS: THE INNOVATORS' WORKSHOPS WERE ORGANIZED ACCORDING TO FIVE THEMED SESSIONS. THE AIMS OF THE DISCUSSION SESSIONS WERE TO IDENTIFY THE FOLLOWING: I) THE STRENGTH AND IMPACT OF THE EVIDENCED-BASED DISCOVERIES, II) REQUIRED STEPS TO ENABLE FURTHER DEVELOPMENT AND III) REQUIRED STEPS TO TRANSLATE THESE NEW DISCOVERIES INTO ORTHODONTIC PRACTICE. RESULTS: THE ROLE OF GENE-ENVIRONMENT INTERACTIONS THAT UNDERLIE COMPLEX CRANIOFACIAL TRAITS WAS THE FOCUS OF SEVERAL SESSIONS. IT WAS AGREED THAT DIVERSE APPROACHES ARE CALLED FOR, SUCH AS (I) LARGE-SCALE COLLABORATIVE EFFORTS FOR FUTURE GENETIC STUDIES OF COMPLEX TRAITS; (II) DEEP GENOME SEQUENCING TO ADDRESS THE ISSUES OF ISOLATED MUTATIONS; (III) QUANTIFYING EPIGENETIC-ENVIRONMENTAL VARIABLES IN DIVERSE AREAS MYOFASCIAL PAIN, ALVEOLAR REMODELLING AND MANDIBULAR GROWTH. COMMON NEEDS IDENTIFIED FROM THE THEMED SESSIONS WERE MULTISCALE/MULTISPECIES MODELLING AND EXPERIMENTATION USING CONTROLLED AND QUANTIFIED MECHANICS AND TRANSLATION OF THE FINDINGS IN BONE BIOLOGY BETWEEN SPECIES. PANEL DISCUSSIONS LED TO THE CONSENSUS THAT A CONSORTIUM APPROACH TO ESTABLISH STANDARDS FOR INTRA-ORAL SCANNING AND 3D IMAGING SHOULD BE INITIATED. CONCLUSIONS: CURRENT AND EMERGING TECHNOLOGIES STILL REQUIRE SUPPORTED RESEARCH TO TRANSLATE NEW FINDINGS FROM THE LABORATORY TO ORTHODONTIC PRACTICE. 2017 5 3400 32 HOW CAN PRECISION MEDICINE BE APPLIED TO TEMPOROMANDIBULAR DISORDERS AND ITS COMORBIDITIES? THE EIGHTH SCIENTIFIC MEETING OF THE TMJ ASSOCIATION, LTD. WAS HELD IN BETHESDA, MARYLAND, SEPTEMBER 11-13, 2016. AS IN THE PAST, THE MEETING WAS COSPONSORED BY COMPONENTS OF THE NATIONAL INSTITUTES OF HEALTH WITH SPEAKERS INVITED TO REVIEW THE STATE OF TEMPOROMANDIBULAR DISORDER SCIENCE AND PROPOSE RECOMMENDATIONS TO FURTHER PROGRESS. THE THEME OF PRECISION MEDICINE, WHICH AIMS TO TAILOR DISEASE TREATMENT AND PREVENTION TO MATCH THE CHARACTERISTICS OF AN INDIVIDUAL PATIENT (GENETIC, EPIGENETIC, ENVIRONMENTAL, LIFESTYLE) UNDERSCORED THE CURRENT CONSENSUS THAT TEMPOROMANDIBULAR DISORDERS ARE NO LONGER VIEWED AS LOCAL CONDITIONS OF JAW PAIN AND DYSFUNCTION. RATHER, THEY REPRESENT A COMPLEX FAMILY OF BIOPSYCHOSOCIAL DISORDERS THAT CAN PROGRESS TO CHRONIC PAIN, MOST OFTEN ACCOMPANIED BY ONE OR MORE OTHER CHRONIC PAIN CONDITIONS. TEMPOROMANDIBULAR DISORDERS AND THESE COMORBIDITIES, CALLED CHRONIC OVERLAPPING PAIN CONDITIONS, PREDOMINANTLY OR EXCLUSIVELY AFFECT WOMEN IN THEIR CHILDBEARING YEARS AND REFLECT CENTRAL NERVOUS SYSTEM SENSITIZATION. PRESENTERS AT THE MEETING INCLUDED LEADERS IN TEMPOROMANDIBULAR DISORDER AND PAIN RESEARCH, TEMPOROMANDIBULAR DISORDER PATIENTS AND ADVOCATES, AND EXPERTS IN OTHER FIELDS OR IN THE USE OF TECHNOLOGIES THAT COULD FACILITATE THE DEVELOPMENT OF PRECISION MEDICINE APPROACHES IN TEMPOROMANDIBULAR DISORDERS. 2017 6 7 24 'BIOLOGIZING' PSYCHOPATHY: ETHICAL, LEGAL, AND RESEARCH IMPLICATIONS AT THE INTERFACE OF EPIGENETICS AND CHRONIC ANTISOCIAL CONDUCT. EPIGENETICS, A FIELD THAT LINKS GENETICS AND ENVIRONMENTAL INFLUENCES ON THE EXPRESSION OF PHENOTYPIC TRAITS, OFFERS TO INCREASE OUR UNDERSTANDING OF THE DEVELOPMENT AND TRAJECTORY OF DISEASE AND PSYCHOLOGICAL DISORDERS BEYOND THAT THOUGHT OF TRADITIONAL GENETIC RESEARCH AND BEHAVIOURAL MEASURES. BY EXTENSION, THIS NEW PERSPECTIVE HAS IMPLICATIONS FOR RISK AND RISK MANAGEMENT OF ANTISOCIAL BEHAVIOUR WHERE THERE IS A BIOLOGICAL COMPONENT, SUCH AS PSYCHOPATHY. PSYCHOPATHY IS A PERSONALITY DISORDER ASSOCIATED WITH REPEAT DISPLAYS OF ANTISOCIAL BEHAVIOUR, AND IS ASSOCIATED WITH THE DISPROPORTIONATE IMPOSITION OF HARM ON COMMUNITIES. DESPITE ADVANCES IN OUR KNOWLEDGE OF PSYCHOPATHIC INDIVIDUALS, THE CONSTRUCT REMAINS COMPLEX AND IS HAMPERED BY A LACK OF INTEGRATION ACROSS A RANGE OF FUNDAMENTAL DOMAINS. THE CLINICAL AND FORENSIC RESEARCH ON PSYCHOPATHY IS BROUGHT INTO CONVERSATION WITH THE EMERGING FIELD OF EPIGENETICS TO HIGHLIGHT CRITICAL ISSUES OF (1) CLINICAL DEFINITION AND DIAGNOSIS, (2) ASSESSMENT, (3) AETIOLOGY OF PSYCHOPATHIC PHENOTYPES, AND (4) TREATMENT AND REHABILITATION APPROACHES. BROADER ETHICAL AND LEGAL QUESTIONS OF THE ROLE OF EPIGENETIC MECHANISMS IN THE MANAGEMENT OF PSYCHOPATHY BEYOND THE CRIMINAL JUSTICE ARENA ARE ALSO OUTLINED. 2015 7 6894 22 [SOCIAL INEQUALITY AND MENTAL HEALTH]. SOCIAL INEQUALITY REFERS TO THE INEQUITABLE DISTRIBUTION OF SOCIAL PROSPERITY INCLUDING THE RESOURCE OF HEALTH. THE RELATIONSHIP BETWEEN SOCIAL INEQUALITY AND MENTAL HEALTH CAN BE ESTABLISHED BY MEANS OF INDICATORS OF SOCIAL INEQUALITY THROUGHOUT ALL AGE GROUPS IN GERMANY. THERE ARE SOCIAL GRADIENTS OF MENTAL HEALTH ON THE POPULATION LEVEL, I.E. THE LINEAR RELATIONSHIP BETWEEN SOCIAL CLASSES OR STATUS AND STATE OF HEALTH. FUNDAMENTAL DETERMINANTS OF HEALTH DISPARITY ARE CULTURAL, SOCIAL, POLITICAL, AND GEOGRAPHICAL CONDITIONS, WHICH INTERACT WITH THE GENETIC MAKE-UP AND EPIGENETIC PROCESSES. THESE DETERMINANTS ALSO INFLUENCE THE MANAGEMENT OF DEVELOPMENTAL TASKS DURING THE LIFE COURSE AND ARE OF UTMOST IMPORTANCE FOR THE DEVELOPMENT OF MENTAL DISORDERS. THE MALADAPTATION TO CHRONIC STRESS IS AT THE CORE OF HEALTH DISPARITY. INTERVENTIONS AT THE INDIVIDUAL BEHAVIORAL LEVEL SHOULD COMPRISE THE DEVELOPMENT OF STRESS MANAGEMENT AND COPING STRATEGIES. 2019 8 3004 19 GENETIC, EPIGENETIC, AND MECHANISTIC STUDIES OF TEMPOROMANDIBULAR DISORDERS AND OVERLAPPING PAIN CONDITIONS. LEADERS IN THE FIELDS OF TEMPOROMANDIBULAR DISORDERS (TMD) AND ITS ACCOMPANYING OVERLAPPING PAIN CONDITIONS PRESENTED THEIR LATEST FINDINGS AT THE SEVENTH SCIENTIFIC MEETING OF THE TMJ ASSOCIATION, SEPTEMBER 7-9, 2014, IN BETHESDA, MD. THE MEETING WAS CO-SPONSORED BY THE TMJ ASSOCIATION AND THE NATIONAL INSTITUTES OF HEALTH. TOPICS OF THE SCIENTIFIC SESSIONS INCLUDED EPIDEMIOLOGY AND DIAGNOSTIC CRITERIA, BASIC MECHANISMS OF CHRONIC PAIN INCLUDING THE GENETIC AND EPIGENETIC BASIS OF CHRONIC PAIN, AND THE DEVELOPMENT OF NOVEL DRUGS FOR TREATMENT OF THESE CONDITIONS. DISCUSSIONS WERE DIRECTED TOWARD FORMULATING A SET OF RECOMMENDATIONS TO ADVANCE RESEARCH IN THIS FIELD. 2014 9 3116 20 GEROSCIENCE: ADDRESSING THE MISMATCH BETWEEN ITS EXCITING RESEARCH OPPORTUNITIES, ITS ECONOMIC IMPERATIVE AND ITS CURRENT FUNDING CRISIS. THERE IS AT PRESENT A HUGE DISCONNECT BETWEEN LEVELS OF FUNDING FOR BASIC RESEARCH ON FUNDAMENTAL MECHANISMS OF BIOLOGICAL AGING AND, GIVEN DEMOGRAPHIC PROJECTIONS, THE ANTICIPATED ENORMOUS SOCIAL AND ECONOMIC IMPACTS OF A LITANY OF CHRONIC DISEASES FOR WHICH AGING IS BY FAR THE MAJOR RISK FACTOR: ONE VALUABLE APPROACH, RECENTLY INSTIGATED BY FELIPE SIERRA & COLLEAGUES AT THE US NATIONAL INSTITUTE ON AGING, IS THE DEVELOPMENT OF A GEROSCIENCE INTEREST GROUP AMONG VIRTUALLY ALL OF THE NIH INSTITUTES. A COMPLEMENTARY APPROACH WOULD BE TO SEEK MAJOR ESCALATIONS OF PRIVATE FUNDING. THE AMERICAN FEDERATION FOR AGING RESEARCH, THE PAUL GLENN FOUNDATION AND THE ELLISON MEDICAL FOUNDATION PIONEERED EFFORTS BY THE PRIVATE SECTOR TO PROVIDE SUBSTANTIAL SUPPLEMENTS TO PUBLIC SOURCES OF FUNDING. IT IS TIME FOR OUR COMMUNITY TO ORGANIZE EFFORTS TOWARDS THE ENHANCEMENTS OF SUCH CRUCIAL CONTRIBUTIONS, ESPECIALLY IN SUPPORT OF THE EMERGING GENERATION OF YOUNG INVESTIGATORS, MANY OF WHOM ARE LEAVING OUR RANKS TO SEEK ALTERNATIVE EMPLOYMENT. TO DO SO, WE MUST PROVIDE POTENTIAL DONORS WITH STRONG ECONOMIC, HUMANITARIAN AND SCIENTIFIC RATIONALES. AN INITIAL APPROACH TO SUCH EFFORTS IS BRIEFLY OUTLINED IN THIS MANUSCRIPT AS A BASIS FOR WIDER DISCUSSIONS WITHIN OUR COMMUNITY. 2017 10 114 17 A SOCIO-BIOLOGICAL EXPLANATION FOR SOCIAL DISPARITIES IN NON-COMMUNICABLE CHRONIC DISEASES: THE PRODUCT OF HISTORY? THIS STUDY PLACES SOCIAL DISPARITIES IN THE MAJOR NON-COMMUNICABLE CHRONIC DISEASES WITHIN THEIR GLOBAL ECONOMIC AND HISTORICAL CONTEXTS. RAPID ECONOMIC TRANSITION OUTSIDE THE DEVELOPED WORLD PROVIDES A UNIQUE OPPORTUNITY TO RE-EXAMINE THE ORIGINS OF, AND BIOLOGICAL MECHANISMS DRIVING, SOCIAL DISPARITIES. GAPS IN PREVAILING THEORIES FOCUSING ON MATERIAL RESOURCES, CIVIC INFRASTRUCTURE AND SOCIAL STRUCTURE ARE IDENTIFIED. USING LONGSTANDING EXPERIMENTAL EVIDENCE AND EPIGENETIC THEORIES, IT IS SUGGESTED THAT EXPOSURE TO ECONOMIC DEVELOPMENT OVER GENERATIONS (IE, IMPROVED LIVING CONDITIONS OVER HISTORICAL TIME) COULD BY ACTING ON DIFFERENT BIOLOGICAL AXES (SOMATOTROPHIC AND GONADOTROPHIC) GENERATE SPECIFIC PATTERNS OF SOCIAL DISPARITIES. MOREOVER, THESE SAME PROCESSES COULD INITIALLY GENERATE A TRANSIENT EPIDEMIC OF DIABETES AS WELL AS A PERMANENT INCREASE IN MALE RISK OF PREMATURE ISCHAEMIC HEART DISEASE. AS SUCH, THIS STUDY DEMONSTRATES THE IMPORTANCE OF CONTEXT, AND IMPLIES THAT CURRENT EVIDENCE FROM THE DEVELOPED WORLD MAY BE LARGELY UNINFORMATIVE FOR PREVENTING OR MITIGATING SOCIAL DISPARITIES IN NON-COMMUNICABLE CHRONIC DISEASES ELSEWHERE, SUGGESTING RESEARCH EFFORTS SHOULD BE FOCUSED ON DEVELOPING COUNTRIES. 2010 11 4169 24 MEETING REPORT ON THE 3RD INTERNATIONAL CONGRESS ON DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD). DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) FOCUSES ON THE EARLIEST STAGES OF HUMAN DEVELOPMENT, AND PROVIDES A NOVEL PARADIGM TO COMPLEMENT OTHER STRATEGIES FOR LIFELONG PREVENTION OF COMMON CHRONIC HEALTH CONDITIONS. THE 3 INTERNATIONAL CONGRESS ON DOHAD, HELD IN 2005, RETAINED THE MOST POPULAR FEATURES FROM THE FIRST TWO BIANNUAL CONGRESSES, WHILE ADDING A NUMBER OF INNOVATIONS, INCLUDING INCREASED EMPHASIS ON IMPLICATIONS OF DOHAD FOR THE DEVELOPING WORLD; PROGRAMS FOR TRAINEES AND YOUNG INVESTIGATORS; AND NEW PERSPECTIVES, INCLUDING DEVELOPMENTAL PLASTICITY, INFLUENCES OF SOCIAL HIERARCHIES, EFFECTS OF PREMATURITY, AND POPULATIONS IN TRANSITION. EMERGING AREAS OF SCIENCE INCLUDED, FIRST, THE CONTROVERSIAL ROLE OF INFANT WEIGHT GAIN IN PREDICTING ADULT OBESITY, DIABETES, AND CARDIOVASCULAR DISEASE. SECOND, IN THE ERA OF EPIDEMIC OBESITY, PAYING ATTENTION TO THE OVER-NOURISHED FETUS IS AS IMPORTANT AS INVESTIGATING THE GROWTH RETARDED ONE. THIRD, ENVIRONMENTAL TOXINS APPEAR TO HAVE ABROAD RANGE OF LONG-LASTING EFFECTS ON THE DEVELOPING HUMAN. FOURTH, EPIGENETIC MECHANISMS COULD UNITE SEVERAL STRANDS OF HUMAN AND ANIMAL OBSERVATIONS, AND EXPLAIN HOW GENETICALLY IDENTICAL INDIVIDUALS RAISED IN SIMILAR POSTNATAL ENVIRONMENTS CAN NONETHELESS DEVELOP WIDELY DIFFERING PHENOTYPES. IMPROVING THE ENVIRONMENT TO WHICH AN INDIVIDUAL IS EXPOSED DURING DEVELOPMENT MAY BE AS IMPORTANT AS ANY OTHER PUBLIC HEALTH EFFORT TO ENHANCE POPULATION HEALTH WORLD WIDE. 2007 12 2690 22 EVOLUTION OF DOHAD: THE IMPACT OF ENVIRONMENTAL HEALTH SCIENCES. ENVIRONMENTAL EXPOSURES HAVE A SIGNIFICANT INFLUENCE ON THE CHRONIC HEALTH CONDITIONS PLAGUING CHILDREN AND ADULTS. ALTHOUGH THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) PARADIGM HISTORICALLY HAS FOCUSED ON NUTRITION, AN EXPANDING BODY OF RESEARCH SPECIFICALLY COMMUNICATES THE EFFECTS OF CHEMICAL EXPOSURES ON EARLY-LIFE DEVELOPMENT AND THE PROPAGATION OF NON-COMMUNICABLE DISEASE ACROSS THE LIFESPAN. THIS PAPER PROVIDES AN OVERVIEW OF 20 YEARS OF RESEARCH EFFORTS AIMED AT IDENTIFYING CRITICAL WINDOWS OF SUSCEPTIBILITY TO ENVIRONMENTAL EXPOSURES AND THE SIGNALING CHANGES AND EPIGENETIC INFLUENCES ASSOCIATED WITH DISEASE PROGRESSION. DOHAD GRANTS FUNDED BY THE NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES (NIEHS) IN 1991, 2001 AND 2011 ARE IDENTIFIED BY GRANT-ANALYSIS SOFTWARE, AND EACH PORTFOLIO IS ANALYZED FOR EXPOSURES, DISEASE ENDPOINTS, WINDOWS OF EXPOSURE, STUDY DESIGN AND IMPACT ON THE FIELD BASED ON PUBLICATION DATA. RESULTS SHOW THAT THE 1991 AND 2001 PORTFOLIOS COMPRISED METALS, PCBS AND AIR POLLUTANTS; HOWEVER, BY 2011, THE PORTFOLIO HAS EVOLVED TO INCLUDE OR EXPAND THE VARIETY OF ENDOCRINE DISRUPTORS, PESTICIDES/PERSISTENT ORGANIC POLLUTANTS AND METALS. AN ASSORTMENT OF BRAIN-HEALTH ENDPOINTS IS MOST TARGETED ACROSS THE PORTFOLIOS, WHEREAS REPRODUCTION AND CANCER INCREASE STEADILY OVER THE SAME TIME PERIOD, AND NEW ENDPOINTS LIKE OBESITY ARE INTRODUCED BY 2011. WITH MOUNTING EVIDENCE CONNECTING EARLY-LIFE EXPOSURES TO LATER-LIFE DISEASE, WE CONCLUDE THAT IT IS CRITICAL TO EXPAND THE ORIGINAL DOHAD CONCEPT TO INCLUDE ENVIRONMENTAL CHEMICAL EXPOSURES, AND TO CONTINUE A RESEARCH AGENDA THAT EMPHASIZES DEFINING SENSITIVE WINDOWS OF EXPOSURE AND THE MECHANISMS THAT CAUSE DISEASE. 2015 13 2724 25 EXPERIENCE-SENSITIVE EPIGENETIC MECHANISMS, DEVELOPMENTAL PLASTICITY, AND THE BIOLOGICAL EMBEDDING OF CHRONIC DISEASE RISK. A WIDE RANGE OF DEVELOPMENTAL, NUTRITIONAL, ENVIRONMENTAL, AND SOCIAL FACTORS AFFECT THE BIOLOGICAL ACTIVITIES OF EPIGENETIC MECHANISMS. THESE FACTORS CHANGE SPATIOTEMPORAL PATTERNS OF GENE EXPRESSION IN A VARIETY OF DIFFERENT WAYS AND BRING SIGNIFICANT IMPACTS TO BEAR ON DEVELOPMENT, PHYSIOLOGY, AND DISEASE RISK THROUGHOUT THE LIFE COURSE. ABUNDANT EVIDENCE DEMONSTRATES THAT BEHAVIORAL STRESSORS AND ADVERSE NUTRITIONAL CONDITIONS ARE PARTICULARLY POTENT INDUCERS OF EPIGENETIC CHANGES AND ENHANCERS OF CHRONIC DISEASE RISKS. RECENT INSIGHTS FROM BOTH HUMAN CLINICAL STUDIES AND RESEARCH WITH MODEL ORGANISMS FURTHER INDICATE THAT SUCH EXPERIENCE-DEPENDENT CHANGES TO THE EPIGENOME CAN BE TRANSMITTED THROUGH THE GERMLINE ACROSS MULTIPLE GENERATIONS, WITH IMPORTANT CONSEQUENCES FOR THE HERITABILITY OF BOTH ADAPTIVE AND MALADAPTIVE PHENOTYPES. EPIGENETICS RESEARCH THUS OFFERS MANY POSSIBILITIES FOR DEVELOPING INFORMATIVE BIOMARKERS OF ACQUIRED CHRONIC DISEASE RISK AND DETERMINING THE EFFECTIVENESS OF PREVENTIVE AND THERAPEUTIC INTERVENTIONS. MOREOVER, THE EXPERIENCE-SENSITIVE NATURE OF THESE DISEASE RISKS RAISES IMPORTANT QUESTIONS ABOUT SOCIETAL AND INDIVIDUAL RESPONSIBILITIES FOR THE PREVENTION OF ILL-HEALTH AND THE PROMOTION OF WELL-BEING DURING DEVELOPMENT, ACROSS THE LIFE COURSE AND BETWEEN GENERATIONS. BETTER UNDERSTANDING OF HOW EPIGENETIC MECHANISMS REGULATE DEVELOPMENTAL PLASTICITY AND MEDIATE THE BIOLOGICAL EMBEDDING OF CHRONIC DISEASE RISKS IS THEREFORE LIKELY TO SHED IMPORTANT NEW LIGHT ON THE NATURE OF THE PATHOPHYSIOLOGICAL MECHANISMS LINKING SOCIAL AND HEALTH INEQUALITIES, AND WILL HELP TO INFORM PUBLIC POLICY INITIATIVES IN THIS AREA. CONFLICT OF INTEREST: THE AUTHOR HAS DECLARED NO CONFLICTS OF INTEREST FOR THIS ARTICLE. 2015 14 5466 20 RESILIENCE: SAFETY IN THE AFTERMATH OF TRAUMATIC STRESSOR EXPERIENCES. THE RELATIONSHIP BETWEEN ADVERSE EXPERIENCES AND THE EMERGENCE OF PATHOLOGY HAS OFTEN FOCUSED ON CHARACTERISTICS OF THE STRESSOR OR OF THE INDIVIDUAL (STRESSOR APPRAISALS, COPING STRATEGIES). THESE FEATURES ARE THOUGHT TO INFLUENCE MULTIPLE BIOLOGICAL PROCESSES THAT FAVOR THE DEVELOPMENT OF MENTAL AND PHYSICAL ILLNESSES. LESS OFTEN HAS ATTENTION FOCUSED ON THE AFTERMATH OF TRAUMATIC EXPERIENCES, AND THE IMPORTANCE OF SAFETY AND REASSURANCE THAT IS NECESSARY FOR LONGER-TERM WELL-BEING. IN SOME CASES (E.G., POST-TRAUMATIC STRESS DISORDER) THIS MAY BE REFLECTED BY A FAILURE OF FEAR EXTINCTION, WHEREAS IN OTHER INSTANCES (E.G., HISTORICAL TRAUMA), THE UNCERTAINTY ABOUT THE FUTURE MIGHT FOSTER CONTINUED ANXIETY. IN ESSENCE, THE QUESTION BECOMES ONE OF HOW INDIVIDUALS ATTAIN FEELINGS OF SAFETY WHEN IT IS FULLY UNDERSTOOD THAT THE WORLD IS NOT NECESSARILY A SAFE PLACE, UNCERTAINTIES ABOUND, AND FEELINGS OF AGENCY ARE OFTEN ILLUSORY. WE CONSIDER HOW INDIVIDUALS ACQUIRE RESILIENCE IN THE AFTERMATH OF TRAUMATIC AND CHRONIC STRESSORS. IN THIS RESPECT, WE REVIEW CHARACTERISTICS OF STRESSORS THAT MAY TRIGGER PARTICULAR BIOLOGICAL AND BEHAVIORAL COPING RESPONSES, AS WELL AS FACTORS THAT UNDERMINE THEIR EFFICACY. TO THIS END, WE EXPLORE STRESSOR DYNAMICS AND SOCIAL PROCESSES THAT FOSTER RESILIENCE IN RESPONSE TO SPECIFIC TRAUMATIC, CHRONIC, AND UNCONTROLLABLE STRESSOR CONTEXTS (INTIMATE PARTNER ABUSE; REFUGEE MIGRATION; COLLECTIVE HISTORICAL TRAUMA). WE POINT TO RESILIENCE FACTORS THAT MAY COMPRISE NEUROBIOLOGICAL CHANGES, SUCH AS THOSE RELATED TO VARIOUS STRESSOR-PROVOKED HORMONES, NEUROTROPHINS, INFLAMMATORY IMMUNE, MICROBIAL, AND EPIGENETIC PROCESSES. THESE BEHAVIORAL AND BIOLOGICAL STRESS RESPONSES MAY INFLUENCE, AND BE INFLUENCED BY, FEELINGS OF SAFETY THAT COME ABOUT THROUGH RELATIONSHIPS WITH OTHERS, SPIRITUAL AND PLACE-BASED CONNECTIONS. 2020 15 4067 18 MATERNAL AND PEDIATRIC HEALTH AND DISEASE: INTEGRATING BIOPSYCHOSOCIAL MODELS AND EPIGENETICS. THE CONCEPTS OF ALLOSTASIS (STABILITY THROUGH ADAPTATION) AND ACCUMULATED LIFE STRESS (MCEWEN'S ALLOSTATIC LOAD) AIM TO UNDERSTAND CHILDHOOD AND ADULT OUTCOMES. CHRONIC MALNUTRITION, CHANGES IN SOCIAL CONDITION, AND ADVERSE EARLY-LIFE EXPERIENCES MAY PROGRAM PHENOTYPES AND CONTRIBUTE TO LONG-LASTING DISEASE RISK. HOWEVER, INTEGRATION OF LIFE COURSE APPROACHES, SOCIAL AND ECONOMIC CONTEXTS, AND COMPARISON AMONG DIFFERENT BIOPSYCHOSOCIAL MODELS HAS NOT GENERALLY BEEN EXPLORED. THIS REVIEW CRITICALLY EXAMINES THE LITERATURE AND EVALUATES RECENT INSIGHTS INTO HOW ENVIRONMENTAL STRESS CAN ALTER LIFELONG HYPOTHALAMIC-PITUITARY-ADRENAL AXIS AND IMMUNE SYSTEM RESPONSIVENESS AND INDUCE METABOLIC AND NEURODEVELOPMENTAL MALADAPTATION. MODELS OF BIOPSYCHOSOCIAL STRESS OVERLAP BUT MAY CONSIDER DIFFERENT CONDITIONS. CONCEPTS INCLUDE ALLOSTASIS, WHICH INCORPORATES HORMONAL RESPONSES TO PREDICTABLE ENVIRONMENTAL CHANGES, AND GERONIMUS'S "WEATHERING," WHICH AIMS TO EXPLAIN HOW SOCIALLY STRUCTURED, REPEATED STRESS CAN ACCUMULATE AND INCREASE DISEASE VULNERABILITY. WEATHERING EMPHASIZES ROLES OF INTERNALIZED/INTERPERSONAL RACISM IN OUTCOMES DISPARITIES. FOR MEXICAN IMMIGRANTS AND MEXICAN AMERICANS, THE "ACCULTURATION" FRAMEWORK HAS PROVEN ESPECIALLY USEFUL TO EXPLORE DISPARITIES, INCLUDING PRETERM BIRTH AND NEUROPSYCHIATRIC RISKS IN CHILDHOOD. COMPLEXITIES OF STRESS ASSESSMENTS AND RECENT RESEARCH INTO EPIGENETIC MECHANISMS MEDIATING EFFECTS OF PHYSICAL, NUTRITIONAL, PSYCHOLOGICAL, AND SOCIAL STRESS ARE REVIEWED. 2016 16 3630 29 INCLUSION OF SOCIAL AND STRUCTURAL DETERMINANTS OF HEALTH TO ADVANCE UNDERSTANDING OF THEIR INFLUENCE ON THE BIOLOGY OF CHRONIC DISEASE. SOCIAL DETERMINANTS OF HEALTH (SDOH) CONSIDER SOCIAL, POLITICAL, AND ECONOMIC FACTORS THAT CONTRIBUTE TO HEALTH DISPARITIES IN PATIENTS AND POPULATIONS. THE MOST COMMON HEALTH-RELATED SDOH EXPOSURES ARE FOOD AND HOUSING INSECURITY, FINANCIAL INSTABILITY, TRANSPORTATION NEEDS, LOW LEVELS OF EDUCATION, AND PSYCHOSOCIAL STRESS. THESE DOMAINS DESCRIBE RISKS THAT CAN IMPACT HEALTH OUTCOMES MORE THAN HEALTH CARE. EPIDEMIOLOGIC AND TRANSLATIONAL RESEARCH DEMONSTRATES THAT SDOH FACTORS REPRESENT EXPOSURES THAT PREDICT HARM AND IMPACT THE HEALTH OF INDIVIDUALS. INTERNATIONAL AND NATIONAL GUIDELINES URGE HEALTH PROFESSIONALS TO ADDRESS SDOH IN CLINICAL PRACTICE AND PUBLIC HEALTH. THE FURTHER IMPLEMENTATION OF THESE RECOMMENDATIONS INTO BASIC AND TRANSLATIONAL RESEARCH, HOWEVER, IS LAGGING. HEREIN, WE CONSIDER A PRECISION HEALTH FRAMEWORK TO DESCRIBE HOW SDOH CONTRIBUTES TO THE EXPOSOME AND EXACERBATES PHYSIOLOGIC PATHWAYS THAT LEAD TO CHRONIC DISEASE. SDOH FACTORS ARE ASSOCIATED WITH VARIOUS FORMS OF STRESSORS THAT IMPACT PHYSIOLOGICAL PROCESSES THROUGH EPIGENETIC, INFLAMMATORY, AND REDOX REGULATION. MANY SDOH EXPOSURES MAY ADD TO OR POTENTIATE THE PATHOLOGIC EFFECTS OF ADDITIONAL ENVIRONMENTAL EXPOSURES. THIS OVERVIEW AIMS TO INFORM BASIC LIFE SCIENCE AND TRANSLATIONAL RESEARCHERS ABOUT SDOH EXPOSURES THAT CAN CONFOUND ASSOCIATIONS BETWEEN CLASSIC BIOMEDICAL DETERMINANTS OF DISEASE AND HEALTH OUTCOMES. TO ADVANCE THE STUDY OF TOXICOLOGY THROUGH EITHER QUALITATIVE OR QUANTITATIVE ASSESSMENT OF EXPOSURES TO CHEMICAL AND BIOLOGICAL SUBSTANCES, A MORE COMPLETE ENVIRONMENTAL EVALUATION SHOULD INCLUDE SDOH EXPOSURES. WE DISCUSS COMMON APPROACHES TO MEASURE SDOH FACTORS AT INDIVIDUAL AND POPULATION LEVELS AND REVIEW THE ASSOCIATIONS BETWEEN SDOH RISK FACTORS AND PHYSIOLOGIC MECHANISMS THAT INFLUENCE CHRONIC DISEASE. WE PROVIDE CLINICAL AND POLICY-BASED MOTIVATION TO ENCOURAGE RESEARCHERS TO CONSIDER THE IMPACT OF SDOH EXPOSURES ON STUDY RESULTS AND DATA INTERPRETATION. WITH VALID MEASURES OF SDOH FACTORS INCORPORATED INTO STUDY DESIGN AND ANALYSES, FUTURE TOXICOLOGICAL RESEARCH MAY CONTRIBUTE TO AN EVIDENCE BASE THAT CAN BETTER INFORM PREVENTION AND TREATMENT OPTIONS, TO IMPROVE EQUITABLE CLINICAL CARE AND POPULATION HEALTH. (C) 2022 WILEY PERIODICALS LLC. 2022 17 46 26 A CONCEPTUAL FRAMEWORK FOR THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE. IN THE LAST DECADES, THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) HAVE EMERGED AS A VIGOROUS FIELD COMBINING EXPERIMENTAL, CLINICAL, EPIDEMIOLOGICAL AND PUBLIC HEALTH RESEARCH. ITS GOAL IS TO UNDERSTAND HOW EVENTS IN EARLY LIFE SHAPE LATER MORBIDITY RISK, ESPECIALLY OF NON-COMMUNICABLE CHRONIC DISEASES. AS THESE DISEASES BECOME THE MAJOR CAUSE OF MORBIDITY AND MORTALITY WORLDWIDE, RESEARCH ARISING FROM DOHAD IS LIKELY TO GAIN SIGNIFICANCE TO PUBLIC HEALTH AND ECONOMIC DEVELOPMENT. BUT ACTION MAY BE HINDERED BY THE LACK OF A FIRM MECHANISTIC EXPLANATION AND OF A CONCEPTUAL BASIS, ESPECIALLY REGARDING THE EVOLUTIONARY SIGNIFICANCE OF THE DOHAD PHENOMENON. IN THIS ARTICLE, WE PROVIDE A SUCCINCT HISTORICAL REVIEW OF THE RESEARCH INTO THE RELATIONSHIP BETWEEN DEVELOPMENT AND LATER DISEASE, CONSIDER THE EVOLUTIONARY AND DEVELOPMENTAL SIGNIFICANCE AND DISCUSS THE UNDERLYING MECHANISMS OF THE DOHAD PHENOMENON. DOHAD SHOULD BE VIEWED AS A PART OF A BROADER BIOLOGICAL MECHANISM OF PLASTICITY BY WHICH ORGANISMS, IN RESPONSE TO CUES SUCH AS NUTRITION OR HORMONES, ADAPT THEIR PHENOTYPE TO ENVIRONMENT. THESE RESPONSES MAY BE DIVIDED INTO THOSE FOR IMMEDIATE BENEFIT AND THOSE AIMED AT PREDICTION OF A FUTURE ENVIRONMENT: DISEASE OCCURS IN THE MISMATCH BETWEEN PREDICTED AND REALIZED FUTURE. THE LIKELY MECHANISMS THAT ENABLE PLASTICITY INVOLVE EPIGENETIC PROCESSES, AFFECTING THE EXPRESSION OF GENES ASSOCIATED WITH REGULATORY PATHWAYS. THERE IS NOW EVIDENCE THAT EPIGENETIC MARKS MAY BE INHERITED AND SO CONTRIBUTE TO NON-GENOMIC HERITABLE DISEASE RISK. WE END BY DISCUSSING THE GLOBAL SIGNIFICANCE OF THE DOHAD PHENOMENON AND ITS POTENTIAL APPLICATIONS FOR PUBLIC HEALTH PURPOSES. 2010 18 6119 17 THE EPIGENETIC IMPACTS OF SOCIAL STRESS: HOW DOES SOCIAL ADVERSITY BECOME BIOLOGICALLY EMBEDDED? EPIGENETIC MECHANISMS ARE IMPLICATED IN THE PROCESSES THROUGH WHICH SOCIAL STRESSORS ERODE HEALTH IN HUMANS AND OTHER ANIMALS. HERE I REVIEW PROGRESS IN ELUCIDATING THE BIOLOGICAL PATHWAYS UNDERLYING THE SOCIAL GRADIENT IN HEALTH, WITH PARTICULAR EMPHASIS ON HOW BEHAVIORAL STRESSES INFLUENCE EPIGENOMIC VARIATION LINKED TO HEALTH. THE EVIDENCE THAT EPIGENETIC CHANGES ARE INVOLVED IN EMBEDDING OF SOCIAL STATUS-LINKED CHRONIC STRESS IS REVIEWED IN THE CONTEXT OF CURRENT KNOWLEDGE ABOUT BEHAVIOR WITHIN ANIMAL DOMINANCE HIERARCHIES AND THE IMPACTS OF SOCIAL POSITION ON BEHAVIORS THAT AFFECT HEALTH. THE ROLES OF EPIGENETIC MECHANISMS IN RESPONSES TO TRAUMA AND THE EVIDENCE FOR THEIR INVOLVEMENT IN INTERGENERATIONAL TRANSMISSION OF THE BIOLOGICAL IMPACTS OF TRAUMATIC STRESS ARE ALSO CONSIDERED. TAKEN TOGETHER, THE EMERGING INSIGHTS HAVE IMPORTANT IMPLICATIONS FOR DEVELOPMENT OF STRATEGIES TO IMPROVE SOCIETAL HEALTH AND WELL-BEING. 2016 19 1748 27 EARLY LIFE EVENTS AND THEIR CONSEQUENCES FOR LATER DISEASE: A LIFE HISTORY AND EVOLUTIONARY PERSPECTIVE. BIOMEDICAL SCIENCE HAS LITTLE CONSIDERED THE RELEVANCE OF LIFE HISTORY THEORY AND EVOLUTIONARY AND ECOLOGICAL DEVELOPMENTAL BIOLOGY TO CLINICAL MEDICINE. HOWEVER, THE OBSERVATIONS THAT EARLY LIFE INFLUENCES CAN ALTER LATER DISEASE RISK--THE "DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE" (DOHAD) PARADIGM--HAVE LED TO A RECOGNITION THAT THESE PERSPECTIVES CAN INFORM OUR UNDERSTANDING OF HUMAN BIOLOGY. WE PROPOSE THAT THE DOHAD PHENOMENON CAN BE CONSIDERED AS A SUBSET OF THE BROADER PROCESSES OF DEVELOPMENTAL PLASTICITY BY WHICH ORGANISMS ADAPT TO THEIR ENVIRONMENT DURING THEIR LIFE COURSE. SUCH ADAPTIVE PROCESSES ALLOW GENOTYPIC VARIATION TO BE PRESERVED THROUGH TRANSIENT ENVIRONMENTAL CHANGES. CUES FOR PLASTICITY OPERATE PARTICULARLY DURING EARLY DEVELOPMENT; THEY MAY AFFECT A SINGLE ORGAN OR SYSTEM, BUT GENERALLY THEY INDUCE INTEGRATED ADJUSTMENTS IN THE MATURE PHENOTYPE, A PROCESS UNDERPINNED BY EPIGENETIC MECHANISMS AND INFLUENCED BY PREDICTION OF THE MATURE ENVIRONMENT. IN MAMMALS, AN ADVERSE INTRAUTERINE ENVIRONMENT RESULTS IN AN INTEGRATED SUITE OF RESPONSES, SUGGESTING THE INVOLVEMENT OF A FEW KEY REGULATORY GENES, THAT RESETS THE DEVELOPMENTAL TRAJECTORY IN EXPECTATION OF POOR POSTNATAL CONDITIONS. MISMATCH BETWEEN THE ANTICIPATED AND THE ACTUAL MATURE ENVIRONMENT EXPOSES THE ORGANISM TO RISK OF ADVERSE CONSEQUENCES-THE GREATER THE MISMATCH, THE GREATER THE RISK. FOR HUMANS, PREDICTION IS INACCURATE FOR MANY INDIVIDUALS BECAUSE OF CHANGES IN THE POSTNATAL ENVIRONMENT TOWARD ENERGY-DENSE NUTRITION AND LOW ENERGY EXPENDITURE, CONTRIBUTING TO THE EPIDEMIC OF CHRONIC NONCOMMUNICABLE DISEASE. THIS VIEW OF HUMAN DISEASE FROM THE PERSPECTIVES OF LIFE HISTORY BIOLOGY AND EVOLUTIONARY THEORY OFFERS NEW APPROACHES TO PREVENTION, DIAGNOSIS AND INTERVENTION. 2007 20 6917 14 [WHOSE BORDERLINE IS IT? HYPOTHESIZED ETIOLOGIES OF BORDERLINE PERSONALITY]. BORDERLINE PERSONALITY IS A WELL KNOWN CONCEPT IN PSYCHIATRIC LITERATURE, HOWEVER, NOT FULLY UNDERSTOOD AS TO ITS VERY NATURE. THIS ARTICLE PRESENTS A SHORT REVIEW OF HYPOTHESIZED ETIOLOGIES OF THE BORDERLINE PERSONALITY, STARTING WITH SO CALLED TRADITIONAL THEORIES, NAMELY, BORDERLINE PERSONALITY AS A CONSOLIDATED PERSONALITY ORGANIZATION, IN WHICH THE PATIENT PATHOLOGICALLY DEALS WITH HIS OR HER INNER AGGRESSION, OR WITH AN ENDURING DEVELOPMENTAL FAILURE. MORE MODERN HYPOTHESES FOCUS ON POSSIBLE CHILDHOOD SEXUAL ABUSE AS THE ORIGIN OF THE BORDERLINE, VIEWING THE ADULT PERSONALITY AS A CHRONIC, UNRESOLVED, POST-TRAUMATIC DISORDER. ADDITIONALLY, A NEURO-EPIGENETIC VIEW HYPOTHESIZED THAT A UNIQUE CONGENITAL NEUROLOGICAL STRUCTURE INTERACTS WITH CONSEQUENTIAL EVENTS IN EARLY CHILDHOOD TO CREATE THE BORDERLINE PERSONALITY. 2008