1 3377 118 HISTORICAL APPROACH AND EVOLUTION OF THE STRESS CONCEPT: A PERSONAL ACCOUNT. AS A MATTER OF RESEARCH OR AS A PROCESS, STRESS REMAINS ONE OF THE MOST CITED CONSTRUCT IN BIOMEDICAL LITERATURE; A MEDLINE SURVEY ACCOUNTS FOR MORE THAN 210,000 CITATIONS SINCE 1970. IT IS DIFFICULT TO DEFINE. IT IS FREQUENTLY USED IN A VAGUE MANNER, INCLUDING UNDIFFERENTLY THE AGENT, THE PROCESS, AND THE RESPONSE. THE CONCEPT IS MULTIDIMENSIONAL AND COMPOSITE, INCLUDING EMOTION AND AROUSAL. STRESS HAS AN IMPLICIT: IT IMPLIES ALTERATION OF A THEORETICAL BALANCE OR EQUILIBRIUM WITHIN PHYSIOLOGICAL SYSTEMS, AND IT SEEMS TO CHARACTERIZE A PROCESS LEADING TO DISEASE. LARGE INDIVIDUAL DIFFERENCES EXIST IN THE WAY TO REACT TO A STRESSOR. PSYCHOLOGICAL AND COGNITIVE DETERMINANTS ARE CENTRAL FOR THE COURSE OF THE PROCESS. THE HOMEOSTASIS CONCEPT IS NOT USEFUL ANYMORE AND HAS BEEN REPLACED BY THE MORE ACCURATE AND FLEXIBLE CONCEPT OF ALLOSTASIS. THE PHYSIOLOGICAL HORMONAL AND NEURAL BASES OF THIS PROCESS ARE NOW IDENTIFIED. NEW PERSPECTIVES IDENTIFY STRESSORS, CHRONIC OR NOT, TO BE A SOURCE OF VULNERABILITIES THROUGH EPIGENETIC MECHANISMS AND A SERIES OF BIOBEHAVIORAL DISORDERS CHARACTERISTIC OF OUR MODERN CIVILIZATIONS. THE EVOLUTION OF THE CONCEPT IS NOT LINEAR. IT HAS BEEN ENRICHED BY RECENT NEUROBIOLOGICAL-NEUROENDOCRINOLOGICAL DISCOVERIES AND ALSO BY BEHAVIORAL-COGNITIVE SCIENCES. 2007 2 29 26 A BIOPSYCHOSOCIAL OVERVIEW OF THE OPIOID CRISIS: CONSIDERING NUTRITION AND GASTROINTESTINAL HEALTH. THE OPIOID CRISIS HAS REACHED EPIDEMIC PROPORTIONS IN THE UNITED STATES WITH RISING OVERDOSE DEATH RATES. IDENTIFYING THE UNDERLYING FACTORS THAT CONTRIBUTE TO ADDICTION VULNERABILITY MAY LEAD TO MORE EFFECTIVE PREVENTION STRATEGIES. SUPPLY SIDE ENVIRONMENTAL FACTORS ARE A MAJOR CONTRIBUTING COMPONENT. PSYCHOSOCIAL FACTORS SUCH AS STRESS, TRAUMA, AND ADVERSE CHILDHOOD EXPERIENCES HAVE BEEN LINKED TO EMOTIONAL PAIN LEADING TO SELF-MEDICATION. GENETIC AND EPIGENETIC FACTORS ASSOCIATED WITH BRAIN REWARD PATHWAYS AND IMPULSIVITY ARE KNOWN PREDICTORS OF ADDICTION VULNERABILITY. THIS REVIEW ATTEMPTS TO PRESENT A BIOPSYCHOSOCIAL APPROACH THAT CONNECTS VARIOUS SOCIAL AND BIOLOGICAL THEORIES RELATED TO THE ADDICTION CRISIS. THE EMERGING ROLE OF NUTRITION THERAPY WITH AN EMPHASIS ON GASTROINTESTINAL HEALTH IN THE TREATMENT OF OPIOID USE DISORDER IS PRESENTED. THE BIOPSYCHOSOCIAL MODEL INTEGRATES CONCEPTS FROM SEVERAL DISCIPLINES, EMPHASIZING MULTICAUSALITY RATHER THAN A REDUCTIONIST APPROACH. POTENTIAL SOLUTIONS AT MULTIPLE LEVELS ARE PRESENTED, CONSIDERING INDIVIDUAL AS WELL AS POPULATION HEALTH. THIS SINGLE COHESIVE FRAMEWORK IS BASED ON THE INTERDEPENDENCY OF THE ENTIRE SYSTEM, IDENTIFYING RISK AND PROTECTIVE FACTORS THAT MAY INFLUENCE SUBSTANCE-SEEKING BEHAVIOR. NUTRITION SHOULD BE INCLUDED AS ONE FACET OF A MULTIDISCIPLINARY APPROACH TOWARD IMPROVED RECOVERY OUTCOMES. CROSS-DISCIPLINARY COLLABORATIVE EFFORTS, NEW IDEAS, AND FISCAL RESOURCES WILL BE CRITICAL TO ADDRESS THE EPIDEMIC. 2019 3 585 27 BEHAVIORAL PERINATOLOGY: BIOBEHAVIORAL PROCESSES IN HUMAN FETAL DEVELOPMENT. BEHAVIORAL PERINATOLOGY IS AS AN INTERDISCIPLINARY AREA OF RESEARCH THAT INVOLVES CONCEPTUALIZATION OF THEORETICAL MODELS AND CONDUCT OF EMPIRICAL STUDIES OF THE DYNAMIC TIME-, PLACE-, AND CONTEXT-DEPENDENT INTERPLAY BETWEEN BIOLOGICAL AND BEHAVIORAL PROCESSES IN FETAL, NEONATAL, AND INFANT LIFE USING AN EPIGENETIC FRAMEWORK OF DEVELOPMENT. THE BIOBEHAVIORAL PROCESSES OF PARTICULAR INTEREST TO OUR RESEARCH GROUP RELATE TO THE EFFECTS OF MATERNAL PRE- AND PERINATAL STRESS AND MATERNAL-PLACENTAL-FETAL STRESS PHYSIOLOGY. WE PROPOSE THAT BEHAVIORAL PERINATOLOGY RESEARCH MAY HAVE IMPORTANT IMPLICATIONS FOR A BETTER UNDERSTANDING OF THE PROCESSES THAT UNDERLIE OR CONTRIBUTE TO THE RISK OF THREE SETS OF OUTCOMES: PREMATURITY, ADVERSE NEURODEVELOPMENT, AND CHRONIC DEGENERATIVE DISEASES IN ADULTHOOD. BASED ON OUR UNDERSTANDING OF THE ONTOGENY OF HUMAN FETAL DEVELOPMENT AND THE PHYSIOLOGY OF PREGNANCY AND FETAL DEVELOPMENT, WE HAVE ARTICULATED A NEUROBIOLOGICAL MODEL OF PRE- AND PERINATAL STRESS. OUR MODEL PROPOSES THAT CHRONIC MATERNAL STRESS MAY EXERT A SIGNIFICANT INFLUENCE ON FETAL DEVELOPMENTAL OUTCOMES. MATERNAL STRESS MAY ACT VIA ONE OR MORE OF THREE MAJOR PHYSIOLOGICAL PATHWAYS: NEUROENDOCRINE, IMMUNE/INFLAMMATORY, AND VASCULAR. WE FURTHER SUGGEST THAT PLACENTAL CORTICOTROPIN-RELEASING HORMONE (CRH) MAY PLAY A CENTRAL ROLE IN COORDINATING THE EFFECTS OF ENDOCRINE, IMMUNE/INFLAMMATORY, AND VASCULAR PROCESSES ON FETAL DEVELOPMENTAL OUTCOMES. FINALLY, WE HYPOTHESIZE THAT THE EFFECTS OF MATERNAL STRESS ARE MODULATED BY THE NATURE, DURATION, AND TIMING OF OCCURRENCE OF STRESS DURING GESTATION. IN THIS PAPER, WE ELABORATE ON THE CONCEPTUAL AND EMPIRICAL BASIS FOR THIS MODEL, HIGHLIGHT SOME RELEVANT ISSUES AND QUESTIONS, AND MAKE RECOMMENDATIONS FOR FUTURE RESEARCH IN THIS AREA. 2002 4 2521 27 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 5 5457 20 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 6 4006 26 LOST AMONG THE TREES? THE AUTONOMIC NERVOUS SYSTEM AND PAEDIATRICS. THE AUTONOMIC NERVOUS SYSTEM (ANS) HAS BEEN STRIKINGLY NEGLECTED IN WESTERN MEDICINE. DESPITE ITS PROFOUND IMPORTANCE FOR REGULATION, ADJUSTMENT AND COORDINATION OF BODY SYSTEMS, IT LACKS PRIORITY IN TRAINING AND PRACTICE AND RECEIVES SCANT ATTENTION IN NUMEROUS MAJOR TEXTBOOKS. THE ANS IS INTEGRAL TO MANIFESTATIONS OF ILLNESS, UNDERLYING FAMILIAR PHYSICAL AND PSYCHOLOGICAL SYMPTOMS. WHEN ANS ACTIVITY IS ITSELF DYSFUNCTIONAL, USUAL INDICATORS OF ACUTE ILLNESS MAY PROVE DECEPTIVE. RECOGNISING THE RELEVANCE OF THE ANS CAN INVOLVE SEEING THE FAMILIAR THROUGH FRESH EYES, CHALLENGING ASSUMPTIONS IN CLINICAL ASSESSMENT AND IN APPROACHES TO PRACTICE. ITS IMPORTANCE EXTENDS FROM PHYSICAL AND PSYCHOLOGICAL WELL-BEING TO PARENTING AND SAFEGUARDING, PUBLIC SERVICES AND THE FUNCTIONING OF SOCIETY. EXPLORATION OF ITS ROLE IN CONDITIONS RANGING FROM NEUROLOGICAL, GASTROINTESTINAL AND CONNECTIVE TISSUE DISORDERS, DIABETES AND CHRONIC FATIGUE SYNDROME, TO AUTISM, BEHAVIOURAL AND MENTAL HEALTH DIFFICULTIES MAY OPEN THERAPEUTIC AVENUES. THE ANS OFFERS A MECHANISM FOR SO-CALLED FUNCTIONAL ILLNESSES AND ILLUSTRATES THE IMPORTANCE OF RECOGNISING THAT 'STRESS' TAKES MANY FORMS, PHYSICAL, PSYCHOLOGICAL AND ENVIRONMENTAL, DESIRABLE AND OTHERWISE. EVIDENCE OF INTRAUTERINE AND POST-NATAL PROGRAMMING OF ANS REACTIVITY SUGGESTS THAT NEONATAL CARE AND SAFEGUARDING PRACTICE MAY OFFER PREVENTIVE OPPORTUNITY, AS MAY GREATER UNDERSTANDING OF EPIGENETIC CHANGE OF ANS ACTIVITY THROUGH, FOR EXAMPLE, ACCIDENTAL OR PSYCHOLOGICAL TRAUMA OR INFECTION. THE AIM OF THIS ARTICLE IS TO ACCELERATE RECOGNITION OF THE IMPORTANCE OF THE ANS THROUGHOUT PAEDIATRICS, AND OF THE POTENTIAL PHYSICAL AND PSYCHOLOGICAL COST OF NEGLECTING IT. 2014 7 2860 21 FROM SOCIAL DETERMINANTS TO SOCIAL EPIGENETICS: HEALTH GEOGRAPHIES OF CHRONIC DISEASE. SOCIAL EPIGENETICS EXPLORES RELATIONSHIPS BETWEEN SOCIAL FACTORS AND HEALTH INEQUITIES EMBODIED AT THE MOLECULAR LEVEL. THROUGH MODULATING GENE EXPRESSION, EPIGENETIC CHANGES RESULTING FROM HUMAN-ENVIRONMENT INTERACTIONS MAY PLAY A ROLE IN SHAPING HEALTH TRAJECTORIES. THIS PAPER APPLIES A HEALTH GEOGRAPHY LENS TO EXPLORE THE POTENTIAL AND SUPPORT FOR CONDUCTING SOCIAL EPIGENETIC STUDIES OF CHRONIC DISEASES WITH COMPLEX AND DYNAMIC ETIOLOGIES. IN SO DOING, WE ARGUE THAT SOCIAL EPIGENETICS PRESENTS A NOVEL SPACE FOR INVESTIGATIONS OF HEALTH AND DISEASE THAT IS TRANSDISCIPLINARY AND BUILDS UPON NEW UNDERSTANDINGS OF BODIES AND PLACE-BASED EXPERIENCES. GIVEN GENDER DISPARITIES IN CHRONIC DISEASES, WE ADOPT A FEMINIST PERSPECTIVE THAT COGITATES THE TRANSACTIVE RELATIONSHIPS BETWEEN GENDER AND HEALTH/ILL-HEALTH AS MEDIATED BY BIOSOCIAL PROCESSES AT A VARIETY OF SCALES. LOOKING FORWARD TO THE PRACTICAL UNDERTAKING OF SOCIAL EPIGENETIC STUDIES, WE ASSESS EXISTING THEORETICAL AND METHODOLOGICAL SUPPORT AS WELL AS INSIGHTS TO BE GAINED. REFLECTING UPON THE CENTRAL TENETS OF HEALTH GEOGRAPHY, WE PROPOSE A UNIQUE POSITIONALITY FOR HEALTH GEOGRAPHERS TO DRIVE THIS FIELD FORWARD. 2021 8 4156 25 MECHANOBIOLOGY AND ADAPTIVE PLASTICITY THEORY AS A POTENTIAL CONFOUNDING FACTOR IN PREDICTING MUSCULOSKELETAL FOOT FUNCTION. THERE ARE MANY THEORETICAL MODELS THAT ATTEMPT TO ACCURATELY AND CONSISTENTLY LINK KINEMATIC AND KINETIC INFORMATION TO MUSCULOSKELETAL PAIN AND DEFORMITY OF THE FOOT. BIOMECHANICAL THEORY OF THE FOOT LACKS A CONSENSUAL MODEL: CLINICIANS ARE ENTICED TO DRAW FROM NUMEROUS PARADIGMS, EACH HAVING DIFFERENT LEVELS OF SUPPORTIVE EVIDENCE AND CONTRASTING METHODS OF EVALUATION, IN ORDER TO ENGAGE IN CLINICAL DEDUCTION AND TREATMENT PLANNING. CONTRIVING TO FIND A LINK BETWEEN FORM AND FUNCTION LIES AT THE HEART OF MOST OF THESE COMPETING THEORIES AND THE PHYSICAL NATURE OF THE DISCIPLINE HAS PROMPTED AN ENGINEERING APPROACH. PHYSICS IS OF GREAT IMPORTANCE IN BIOLOGY AND HELPS US TO MODEL THE FORCES THAT THE FOOT HAS TO DEAL WITH IN ORDER FOR IT TO WORK EFFECTIVELY. HOWEVER, THE TISSUES OF THE BODY HAVE COMPLEX PROCESSES THAT ARE IN PLACE TO PROTECT THEM AND THEY ARE VARIABLE BETWEEN INDIVIDUALS. RESEARCH IS UNCOVERING WHY THESE DIFFERENCES EXIST AND HOW THESE PROCESSES ARE GOVERNED. THE EMERGING EXPLANATIONS FOR ADAPTABILITY OF FOOT STRUCTURE AND MUSCULOSKELETAL HOMEOSTASIS OFFER NEW INSIGHTS INTO HOW CLINICAL VARIATION IN OUTCOMES AND TREATMENT EFFECTS MIGHT ARISE. THESE BIOLOGICAL PROCESSES UNDERLIE HOW VARIATION IN THE PERFORMANCE AND USE OF COMMON TRAITS, EVEN WITHIN APPARENTLY SIMILAR SUBGROUPS, MAKE ANATOMICAL DISTINCTION LESS MEANINGFUL AND ARE LIKELY TO UNDERMINE THE JUSTIFICATION OF A "FOOT TYPE." FURTHERMORE, MECHANOBIOLOGY INTRODUCES A PROBABILISTIC ELEMENT TO MORPHOLOGY BASED ON GENETIC AND EPIGENETIC FACTORS. 2021 9 6892 18 [SIGNIFICANCE OF PREVENTING DEVELOPMENTAL ORIGINS OF DISEASES IN IMPROVING POPULATION QUALITY]. MORE STUDIES SHOW THAT VARIOUS DISEASES, ESPECIALLY CHRONIC NON-INFECTIOUS DISEASES, HAVE DEVELOPMENTAL ORIGIN. DEVELOPMENTAL ORIGINS OF DISEASES ARE MAINLY DUE TO GAMETES AND EARLY LIFE DEVELOPMENT STAGE BEING EXPOSED TO ADVERSE ENVIRONMENT, RESULTING IN ABNORMAL MODIFICATION OF EPIGENETIC AND STABLE INHERITANCE TO THE ADULT STAGE, WHICH COULD MAKE THE RISK OF VARIOUS LONG-TERM DISEASES OF INDIVIDUALS HIGH. THE THEORY OF DEVELOPMENTAL ORIGIN PROVIDES A NEW PERSPECTIVE FOR THE OCCURRENCE AND DEVELOPMENT OF DISEASES, AND ALSO PROVIDES A THEORETICAL BASIS FOR DISEASE PREVENTION. ATTACHING IMPORTANCE TO MATERNAL AND CHILD HEALTH CARE AND LIFE-CYCLE MANAGEMENT IS CONDUCIVE TO THE PREVENTION OF DEVELOPMENTAL DISEASES AND IS OF GREAT SIGNIFICANCE TO THE IMPROVEMENT OF POPULATION QUALITY. 2023 10 5315 31 PSYCHOLOGICAL STRESS IN CHILDHOOD AND SUSCEPTIBILITY TO THE CHRONIC DISEASES OF AGING: MOVING TOWARD A MODEL OF BEHAVIORAL AND BIOLOGICAL MECHANISMS. AMONG PEOPLE EXPOSED TO MAJOR PSYCHOLOGICAL STRESSORS IN EARLY LIFE, THERE ARE ELEVATED RATES OF MORBIDITY AND MORTALITY FROM CHRONIC DISEASES OF AGING. THE MOST COMPELLING DATA COME FROM STUDIES OF CHILDREN RAISED IN POVERTY OR MALTREATED BY THEIR PARENTS, WHO SHOW HEIGHTENED VULNERABILITY TO VASCULAR DISEASE, AUTOIMMUNE DISORDERS, AND PREMATURE MORTALITY. THESE FINDINGS RAISE CHALLENGING THEORETICAL QUESTIONS. HOW DOES CHILDHOOD STRESS GET UNDER THE SKIN, AT THE MOLECULAR LEVEL, TO AFFECT RISK FOR LATER DISEASES? AND HOW DOES IT INCUBATE THERE, GIVING RISE TO DISEASES SEVERAL DECADES LATER? HERE WE PRESENT A BIOLOGICAL EMBEDDING MODEL, WHICH ATTEMPTS TO ADDRESS THESE QUESTIONS BY SYNTHESIZING KNOWLEDGE ACROSS SEVERAL BEHAVIORAL AND BIOMEDICAL LITERATURES. THIS MODEL MAINTAINS THAT CHILDHOOD STRESS GETS "PROGRAMMED" INTO MACROPHAGES THROUGH EPIGENETIC MARKINGS, POSTTRANSLATIONAL MODIFICATIONS, AND TISSUE REMODELING. AS A CONSEQUENCE THESE CELLS ARE ENDOWED WITH PROINFLAMMATORY TENDENCIES, MANIFEST IN EXAGGERATED CYTOKINE RESPONSES TO CHALLENGE AND DECREASED SENSITIVITY TO INHIBITORY HORMONAL SIGNALS. THE MODEL GOES ON TO PROPOSE THAT OVER THE LIFE COURSE, THESE PROINFLAMMATORY TENDENCIES ARE EXACERBATED BY BEHAVIORAL PROCLIVITIES AND HORMONAL DYSREGULATION, THEMSELVES THE PRODUCTS OF EXPOSURE TO EARLY STRESS. BEHAVIORALLY, THE MODEL POSITS THAT CHILDHOOD STRESS GIVES RISE TO EXCESSIVE THREAT VIGILANCE, MISTRUST OF OTHERS, POOR SOCIAL RELATIONSHIPS, IMPAIRED SELF-REGULATION, AND UNHEALTHY LIFESTYLE CHOICES. HORMONALLY, EARLY STRESS CONFERS ALTERED PATTERNS OF ENDOCRINE AND AUTONOMIC DISCHARGE. THIS MILIEU AMPLIFIES THE PROINFLAMMATORY ENVIRONMENT ALREADY INSTANTIATED BY MACROPHAGES. ACTING IN CONCERT WITH OTHER EXPOSURES AND GENETIC LIABILITIES, THE RESULTING INFLAMMATION DRIVES FORWARD PATHOGENIC MECHANISMS THAT ULTIMATELY FOSTER CHRONIC DISEASE. 2011 11 380 28 AN EPIGENETIC PERSPECTIVE ON LIFESTYLE MEDICINE FOR DEPRESSION: IMPLICATIONS FOR PRIMARY CARE PRACTICE. DEPRESSION IS THE MOST COMMON PRESENTING MENTAL HEALTH DISORDER IN PRIMARY CARE. IT IS ALSO A MAJOR CONTRIBUTOR TO SOMATIC COMPLAINTS, WORSENING OF CHRONIC MEDICAL CONDITIONS, POOR QUALITY OF LIFE, AND SUICIDE. CURRENT PHARMACOLOGIC AND PSYCHOTHERAPEUTIC APPROACHES AVERT LESS THAN HALF OF DEPRESSION'S CUMULATIVE BURDEN ON SOCIETY. HOWEVER, THERE IS A GROWING BODY OF RESEARCH DESCRIBING BOTH HOW MALADAPTIVE LIFESTYLE CHOICES CONTRIBUTE TO THE DEVELOPMENT AND WORSENING OF DEPRESSION AND HOW LIFESTYLE-ORIENTED MEDICAL INTERVENTIONS CAN REDUCE THE INCIDENCE AND SEVERITY OF DEPRESSION. THIS RESEARCH, LARGELY DERIVED FROM AN EMERGING FIELD CALLED EPIGENETICS, ELUCIDATES THE INTERACTIONS BETWEEN OUR LIFESTYLE CHOICES AND THOSE EPIGENETIC FACTORS WHICH MEDIATE OUR TENDENCIES TOWARD EITHER HEALTH, OR THE ONSET, IF NOT WORSENING OF DISEASE. THE PRESENT REVIEW HIGHLIGHTS HOW LIFESTYLE CHOICES INVOLVING DIET, PHYSICAL ACTIVITY, SLEEP, SOCIAL RELATIONSHIPS, AND STRESS INFLUENCE EPIGENETIC PROCESSES POSITIVELY OR NEGATIVELY, AND THEREBY PLAY A SIGNIFICANT ROLE IN DETERMINING WHETHER ONE DOES OR DOES NOT SUFFER FROM DEPRESSION. THE AUTHORS PROPOSE THAT MEDICAL TRAINING PROGRAMS CONSIDER AND ADOPT LIFESTYLE MEDICINE ORIENTED INSTRUCTIONAL INITIATIVES THAT WILL ENABLE TOMORROW'S PRIMARY CARE PROVIDERS TO MORE EFFECTIVELY IDENTIFY AND THERAPEUTICALLY INTERVENE IN THE MALADAPTIVE CHOICES CONTRIBUTING TO THEIR PATIENTS' DEPRESSION. 2022 12 2724 27 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 13 5316 26 PSYCHOLOGICAL STRESS IN EARLY LIFE AS A PREDISPOSING FACTOR FOR THE DEVELOPMENT OF CHRONIC PAIN: CLINICAL AND PRECLINICAL EVIDENCE AND NEUROBIOLOGICAL MECHANISMS. A WEALTH OF RESEARCH OVER THE PAST 2 DECADES HAS EXPANDED OUR UNDERSTANDING OF THE IMPACT OF EARLY-LIFE ADVERSITY ON PHYSIOLOGICAL FUNCTION AND, CONSEQUENTLY, HEALTH AND WELLBEING IN LATER LIFE. EARLY-LIFE ADVERSITY INCREASES THE RISK OF DEVELOPING A NUMBER OF DISORDERS, SUCH AS CHRONIC PAIN, FIBROMYALGIA, AND IRRITABLE BOWEL SYNDROME. ALTHOUGH MUCH OF THE RESEARCH HAS EXAMINED THE IMPACT OF PHYSICAL MALTREATMENT, AN INCREASING NUMBER OF STUDIES HAVE BEEN PUBLISHED OVER THE PAST FEW YEARS EXAMINING THE EFFECT OF CHILDHOOD PSYCHOLOGICAL STRESS AND TRAUMA ON THE DEVELOPMENT OF VARIOUS TYPES OF CHRONIC PAIN CONDITIONS. WE REVIEW THE CLINICAL AND PRECLINICAL DATA EXAMINING THE LINK AMONG EARLY-LIFE PSYCHOLOGICAL STRESS, ALTERED NOCICEPTIVE BEHAVIOR, AND CHRONIC PAIN IN LATER LIFE. EVIDENCE SUPPORTING A ROLE FOR CERTAIN KEY NEUROBIOLOGICAL SUBSTRATES, INCLUDING THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS; MONOAMINERGIC, OPIOIDERGIC, ENDOCANNABINOID AND IMMUNE SYSTEMS; AND EPIGENETIC MECHANISMS IN THE ASSOCIATION BETWEEN EARLY-LIFE PSYCHOLOGICAL STRESS AND CHRONIC PAIN, IS PROVIDED. GREATER UNDERSTANDING OF THE IMPACT OF EARLY-LIFE STRESS MAY INFORM THE DEVELOPMENT OF PERSONALIZED TREATMENTS FOR CHRONIC PAIN IN LATER LIFE AND STRATEGIES TO PREVENT ITS ONSET IN SUSCEPTIBLE INDIVIDUALS. (C) 2016 WILEY PERIODICALS, INC. 2017 14 458 25 APPLYING MINIMALLY INVASIVE BIOMARKERS OF CHRONIC STRESS ACROSS COMPLEX ECOLOGICAL CONTEXTS. CHRONIC STRESS IS BOTH THEORETICALLY AND METHODOLOGICALLY CHALLENGING TO OPERATIONALIZE THROUGH BIOMARKERS. YET MINIMALLY INVASIVE, FIELD-FRIENDLY BIOMARKERS OF CHRONIC STRESS ARE VALUABLE IN RESEARCH LINKING BIOLOGY AND CULTURE, SEEKING TO UNDERSTAND DIFFERENTIAL PATTERNS OF HUMAN DEVELOPMENT ACROSS ECOLOGICAL CONTEXTS, AND EXPLORING THE EVOLUTION OF HUMAN SOCIALITY. FOR HUMAN BIOLOGISTS, A CENTRAL QUESTION IN MEASUREMENT AND INTERPRETATION OF BIOMARKERS IS HOW STRESS-RESPONSIVE PHYSIOLOGICAL SYSTEMS ARE REGULATED ACROSS DIVERSE HUMAN ECOLOGIES. THIS ARTICLE AIMS TO DESCRIBE A CONDITIONAL TOOLKIT FOR HUMAN BIOLOGISTS INTERESTED IN THE STUDY OF CHRONIC STRESS, HIGHLIGHTING A MIX OF LONGSTANDING AND NOVEL BIOMARKERS, WITH SPECIAL FOCUS ON HAIR/FINGERNAIL CORTISOL, LATENT HERPESVIRUS ANTIBODIES, ALLOSTATIC LOAD INDICES, AND SERIAL/AMBULATORY DATA COLLECTION APPROACHES. FUTURE TRENDS IN CHRONIC STRESS BIOMARKER RESEARCH, INCLUDING EPIGENETIC APPROACHES, ARE BRIEFLY CONSIDERED. THIS OVERVIEW CONSIDERS: (1) CHALLENGES IN SEPARATING A DISTINCTLY PSYCHOSOCIAL DIMENSION OF CHRONIC STRESS FROM ADVERSITY MORE BROADLY; (2) ESSENTIAL CHARACTERISTICS OF HUMAN ECOLOGY THAT SHAPE INTERPRETATION; (3) RETROSPECTIVE VS. LONGITUDINAL SAMPLING; (4) THE ROLE OF AGE, DEVELOPMENTAL EFFECTS, AND LOCAL BIOLOGIES; (5) DIFFERENT TIMESCALES OF CHRONICITY; AND (6) THE ROLE OF CULTURE. 2022 15 4985 26 PATHWAYS TO AGING: THE MITOCHONDRION AT THE INTERSECTION OF BIOLOGICAL AND PSYCHOSOCIAL SCIENCES. COMPELLING EVIDENCE SUGGESTS THAT BOTH BIOLOGICAL AND PSYCHOSOCIAL FACTORS IMPACT THE PROCESS OF AGING. HOWEVER, OUR UNDERSTANDING OF THE DYNAMIC INTERPLAY AMONG BIOLOGICAL AND PSYCHOSOCIAL FACTORS ACROSS THE LIFE COURSE IS STILL FRAGMENTARY. FOR EXAMPLE, IT NEEDS TO BE ESTABLISHED HOW THE INTERACTION OF INDIVIDUAL FACTORS (E.G., GENETIC AND EPIGENETIC ENDOWMENT AND PERSONALITY), BEHAVIORAL FACTORS (E.G., PHYSICAL ACTIVITY, DIET, AND STRESS MANAGEMENT), AND PSYCHOSOCIAL EXPERIENCES (E.G., SOCIAL SUPPORT, WELL-BEING, SOCIOECONOMIC STATUS, AND MARRIAGE) IN PERINATAL, CHILDHOOD, AND ADULTHOOD INFLUENCE HEALTH ACROSS THE AGING CONTINUUM. THIS PAPER AIMS TO OUTLINE POTENTIAL INTERSECTION POINTS SERVING AS AN INTERFACE BETWEEN BIOLOGICAL AND PSYCHOSOCIAL FACTORS, WITH AN EMPHASIS ON THE MITOCHONDRION. MITOCHONDRIA ARE CELLULAR ORGANELLES WHICH PLAY A CRITICAL ROLE IN CELLULAR SENESCENCE. BOTH CHRONIC EXPOSURE TO PSYCHOSOCIAL STRESS AND GENETIC-BASED MITOCHONDRIAL DYSFUNCTION HAVE STRIKINGLY SIMILAR BIOLOGICAL CONSEQUENCES; BOTH PREDISPOSE INDIVIDUALS TO ADVERSE AGE-RELATED HEALTH DISORDERS AND EARLY MORTALITY. EXPLORING THE INTERACTIVE NATURE OF THE FACTORS RESULTING IN PATHWAYS TO NORMAL HEALTHY AGING, AS WELL AS THOSE LEADING TO MORBIDITY AND EARLY MORTALITY, WILL CONTINUE TO ENHANCE OUR ABILITY TO TRANSLATE RESEARCH INTO EFFECTIVE PRACTICES THAT CAN BE IMPLEMENTED THROUGHOUT THE LIFE COURSE TO OPTIMISE THE AGING PROCESS. 2011 16 114 24 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 17 707 27 BY WHAT MOLECULAR MECHANISMS DO SOCIAL DETERMINANTS IMPACT CARDIOMETABOLIC RISK? WHILE IT IS WELL KNOWN FROM NUMEROUS EPIDEMIOLOGIC INVESTIGATIONS THAT SOCIAL DETERMINANTS (SOCIOECONOMIC, ENVIRONMENTAL, AND PSYCHOSOCIAL FACTORS EXPOSED TO OVER THE LIFE-COURSE) CAN DRAMATICALLY IMPACT CARDIOVASCULAR HEALTH, THE MOLECULAR MECHANISMS BY WHICH SOCIAL DETERMINANTS LEAD TO POOR CARDIOMETABOLIC OUTCOMES ARE NOT WELL UNDERSTOOD. THIS REVIEW COMPREHENSIVELY SUMMARIZES A VARIETY OF CURRENT TOPICS SURROUNDING THE BIOLOGICAL EFFECTS OF ADVERSE SOCIAL DETERMINANTS (I.E., THE BIOLOGY OF ADVERSITY), LINKING TRANSLATIONAL AND LABORATORY STUDIES WITH EPIDEMIOLOGIC FINDINGS. WITH A STRONG FOCUS ON THE BIOLOGICAL EFFECTS OF CHRONIC STRESS, WE HIGHLIGHT AN ARRAY OF STUDIES ON MOLECULAR AND IMMUNOLOGICAL SIGNALING IN THE CONTEXT OF SOCIAL DETERMINANTS OF HEALTH (SDOH). THE MAIN TOPICS COVERED INCLUDE BIOMARKERS OF SYMPATHETIC NERVOUS SYSTEM AND HYPOTHALAMIC-PITUITARY-ADRENAL AXIS ACTIVATION, AND THE ROLE OF INFLAMMATION IN THE BIOLOGY OF ADVERSITY FOCUSING ON GLUCOCORTICOID RESISTANCE AND KEY INFLAMMATORY CYTOKINES LINKED TO PSYCHOSOCIAL AND ENVIRONMENTAL STRESSORS (PSES). WE THEN FURTHER DISCUSS THE EFFECT OF SDOH ON IMMUNE CELL DISTRIBUTION AND CHARACTERIZATION BY SUBSET, RECEPTOR EXPRESSION, AND FUNCTION. LASTLY, WE DESCRIBE EPIGENETIC REGULATION OF THE CHRONIC STRESS RESPONSE AND EFFECTS OF SDOH ON TELOMERE LENGTH AND AGING. ULTIMATELY, WE HIGHLIGHT CRITICAL KNOWLEDGE GAPS FOR FUTURE RESEARCH AS WE STRIVE TO DEVELOP MORE TARGETED INTERVENTIONS THAT ACCOUNT FOR SDOH TO IMPROVE CARDIOMETABOLIC HEALTH FOR AT-RISK, VULNERABLE POPULATIONS. 2023 18 3630 27 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 19 5466 29 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 20 6792 28 [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