1 6808 55 [EPIGENETICS IN ALLERGIC DISEASES AND ASTHMA]. ALLERGIC DISEASES AND ASTHMA ARE THE RESULT OF COMPLEX INTERACTIONS BETWEEN GENETIC PREDISPOSITION AND ENVIRONMENTAL FACTORS. ASTHMA IS ONE OF THE MOST PREVALENT CHRONIC DISEASE AMONG CHILDREN. IN THIS ARTICLE WE REVIEW SOME ENVIRONMENTAL FACTORS LIKE: ALLERGEN EXPOSITION, TOBACCO, BACTERIA, MICROBIAL COMPONENTS, DIET, OBESITY AND STRESS, WHICH INFLUENCES DURING INTRAUTERINE AND INFANCY LIFE IN THE EPIGENETIC REGULATION OF ASTHMA AND ALLERGIC DISEASES. THE REVIEW HAS BEEN DONE IN THREE MODELS: IN-VITRO, ANIMAL AND HUMAN. 2016 2 6042 23 THE COLON REVISITED OR THE KEY TO WELLNESS, HEALTH AND DISEASE. THE HYPOTHESIS BEING ADVANCED IN THIS PAPER IS THAT THERE IS A NEW MEDICAL PARADIGM EMERGING FROM THE BIOMEDICAL RESEARCH CARRIED OUT IN THIS CENTURY, MAINLY DUE TO THE EXPLOSION OF THE SO CALLED "OMICS" AND ASSOCIATED TECHNIQUES. THE MAIN IDEA IS THAT THERE IS A COMMON PATHWAY FROM WELLBEING AND HEALTH TO CHRONIC DISEASE ("CHRONOPATHY") AND EVEN TO DEATH, WHICH COMPRISES FOLLOWING STEPS: 1) UNHEALTHY DIET, SEDENTARY LIFE STYLE AND PERMANENT EXPOSITION TO XENOBIOTICS AND ALL KINDS OF NOXIOUS STIMULI;-->2) INTESTINAL DYSBIOSIS;-->3) ALTERATION OF THE INTESTINAL MUCUS LAYER (ESPECIALLY THAT OF THE COLON);-->4) DISRUPTION OF THE ENDOTHELIAL TIGHT JUNCTIONS;-->5) METABOLIC ENDOTOXEMIA+BACTERIAL TRANSLOCATION;-->6) INFLAMMATION;-->7) EXACERBATION OF THE ENTERIC NERVOUS SYSTEM (ENS) AND CONSEQUENT MALADAPTATION AND MALFUNCTIONING OF THE COLON;-->8) EPIGENETIC MANIFESTATIONS;-->9) "CHRONOPATHY" AND PREMATURE DEATH. THEREFORE, IN ORDER TO MAINTAIN A GOOD HEALTH OR TO IMPROVE OR EVEN REVERSE CHRONIC DISEASES IN A PERSON, THE MAIN OUTCOME TO LOOK FOR IS A HOMEOSTATIC BALANCE OF THE INTESTINAL MICROBIOTA (EUBIOSIS), MOST OF WHICH IS LOCATED IN THE COLON. LYNN MARGULIS WAS ONE OF THE MAIN SCIENTISTS TO HIGHLIGHT THE IMPORTANCE OF THE ROLE PLAYED BY BACTERIA NOT ONLY IN THE ORIGIN OF ALL BIOLOGICAL SPECIES NOW PRESENT ON EARTH, BUT ALSO ON THEIR ROLE IN GLOBAL HOMEOSTASIS. BACTERIA DO NOT RELY ON OTHER LIVING BEINGS FOR THEIR EXISTENCE, WHILE THE LATTER DEPEND COMPLETELY ON THE FORMER. HUMANS ARE NO EXEMPTION, AND NEW EVIDENCE EMERGES EACH DAY ABOUT THE PIVOTAL ROLE OF INTESTINAL MICROBIOTA IN HUMAN HEALTH, DISEASE AND, IN GENERAL, IN ITS WELLBEING. THE FOLLOWING FACTS ABOUT INTESTINAL MICROBIOTA ARE NOWADAYS GENERALLY ACCEPTED: THERE ARE ABOUT 10 TIMES MORE BACTERIA IN THE GUT THAN HUMAN CELLS IN EVERY HUMAN BEING; THE MICROBIOMA IS ABOUT 100-150 TIMES BIGGER THAT THE HUMAN GENOME, AND THERE IS A CLEAR LINK BETWEEN INTESTINAL MICROBIOTA AND MANY OF THE MOST COMMON CHRONIC DISEASES, FROM OBESITY AND DIABETES TO DEPRESSION AND PARKINSON DISEASE AND DIFFERENT KINDS OF CANCER. THE MAIN IMPLICATION OF THIS THEORY IS THAT WE SHOULD BECOME A SORT OF MICROBIOTA FARMERS, THAT IS, WE OUGHT TO BE MORE CONSCIOUS OF OUR INTESTINAL MICROBIOTA, TAKE CARE OF IT AND MONITOR IT PERMANENTLY. THUS, AS PART OF OUR GOOD LIFE HABITS (HEALTHY EATING, PHYSICAL EXERCISE), WE SHOULD PROBABLY UNDERGO PERIODIC SEASONS OF FASTING AND COLON CLEANSING, AS IT WAS COMMON IN OLDER TIMES. 2017 3 6825 16 [GENETIC AND EPIGENETIC FACTORS OF POLYCYSTIC OVARY SYNDROME]. THE DEVELOPMENT OF POLYCYSTIC OVARY SYNDROME AND ITS EXACT PATHOPHYSIOLOGICAL MECHANISM IS STILL UNCLEAR, BUT ENVIRONMENTAL AND GENETIC FACTORS LIKELY PLAY A ROLE. EXPOSITION TO TERATOGENIC EFFECTS DURING THE PRENATAL DEVELOPMENT CAN LEAD TO CHRONIC DISEASES IN THE POSTNATAL PERIOD. THIS FINDING CONFIRMS THE COMMON FAMILIAL AGGREGATION AS WELL. A LITERATURE SEARCH WAS CONDUCTED UP TO JANUARY 1, 2016 FOR ARTICLES DEALING WITH THE GENETIC OR EPIGENETIC FACTORS OF POLYCYSTIC OVARY SYNDROME. THIS REVIEW WILL DISCUSS THE CURRENT UNDERSTANDING OF THE GENETIC BASIS AND CLINICAL PRESENTATION OF THIS DISEASE. ORV. HETIL., 2016, 157(32), 1275-1281. 2016 4 4894 21 OXIDATIVE STRESS CAUSED BY ACUTE AND CHRONIC EXPOSITION TO ALTITUDE. IN THIS ARTICLE, CURRENT VIEWS ON CELLULAR AND MOLECULAR BIOLOGY (BIOCHEMICAL) MECHANISMS ARE DISCUSSED UNDER THE ASPECT OF ALTITUDE EXPOSITION. THE ANDEAN, TIBETAN, AND ETHIOPIAN PATTERNS OF ADAPTATION TO HIGH-ALTITUDE HYPOXIA ARE KNOWN [BEAL ET AL. (2002) PROC NATL ACAD SCI USA 99: 17215-17218]. THE PHYLOGENETIC TREE OF THE HUMAN SPECIES SUGGESTS THAT THERE ARE GENETIC DIFFERENCES IN ADAPTATION PATTERNS TO CHRONIC HYPOXIC HYPOXIA. FIVE DEFENSE MECHANISMS ARE WELL ESTABLISHED FOR LOWLANDERS WHO ARE EXPOSED TO ACUTE HYPOXIC HYPOXIA. CONSEQUENCES OF THE CELLULAR DECREASE IN ATP ARE THE FORMATION OF HYPOXANTHINE AND XANTHINE, WHICH ARE THE SUBSTRATES FOR THE MASSIVE FORMATION OF SUPEROXIDE ANION RADICALS AND HYDROGEN PEROXIDE VIA THE OXIDASE ACTIVITY OF THE XANTHINE OXIDOREDUCTASE REACTION. UNDER SEVERE HYPOXIA, ABOUT 51 % OF THE TOTAL INHALED OXYGEN IS USED TO FORM SUPEROXIDE ANION RADICALS IN RAT LIVER [GERBER ET AL. (1989) ADV EXP MED BIOL 253B, PLENUM PRESS, NEW YORK, 497-504]. THE REACTIVITY AND SELECTIVITY OF THE SUPEROXIDE ANION RADICAL ARE MODIFIED BY SPECIFIC INTERACTIONS AND ELECTRON EXCHANGE. IT IS COMMONLY ACCEPTED THAT THE SUPEROXIDE ANION RADICAL IN AQUEOUS SOLUTIONS HAS A LIFETIME IN THE MILLISECOND RANGE. HOWEVER, ELECTRON SPIN RESONANCE SPECTROSCOPY STUDIES IN A KO2/H2O/IRON ION SYSTEM REVEALED FOR THE FIRST TIME A STABILIZATION OF A PART OF THE INITIALLY ADDED SUPEROXIDE ANION RADICALS LASTING UP TO HOURS AT ROOM TEMPERATURE [FOLDES-PAPP (1992) GEN PHYSIOL BIOPHYS 11: 3-38]. SUPEROXIDE ANION RADICALS ADSORBED ON AN OXIDIC IRON HYDRATE PHASE IN AQUEOUS SYSTEMS MIGHT FUNCTION AS A STRONG OXIDANT SIMILAR TO THAT SPECIES WHICH HAS BEEN SUGGESTED TO BE A COMPLEX BETWEEN OXYGEN AND DIFFERENT VALENCE STATES OF IRON IN THE INITIATION OF LIPID PEROXIDATION BY FERROUS IRON. THERE WERE SERIOUS DOUBTS ABOUT THE IDENTITY OF ALKOXY RADICALS. FOR THE FIRST TIME, ALKOXY RADICALS WERE DIRECTLY DEMONSTRATED IN SOLUTION BY ELECTRON SPIN RESONANCE SPECTROSCOPY [FOLDES-PAPP ET AL. (1991) ADV SYNTH CATAL 333: 293-301]. THE REDOX STATUS IN MAMMALIAN CELLS IS MAINLY DETERMINED BY THE ANTIOXIDANT GLUTATHIONE, WHICH IS A KEY PLAYER IN MAINTAINING THE INTRACELLULAR REDOX EQUILIBRIUM AND IN THE METABOLIC REGULATION OF THE CELLULAR DEFENSE AGAINST OXIDATIVE STRESS. AS REACTIVE OXYGEN SPECIES OCCUPY AN ESSENTIAL ROLE IN MEMBRANE DAMAGE, THE IDEA OF MEMBRANE-BOUND ENZYMATIC DEFENSE MECHANISMS GETS A NEW DIMENSION [FOLDES-PAPP ET AL. (1981) ACTA BIOL MED GER 40: 1129-1132; FOLDES-PAPP AND MARETZKI (1982) ACTA BIOL MED GER 41: 1003-1008]. THE STEADY-STATE BETWEEN ANTIOXIDANTS AND PRO-OXIDANTS AFFECTS THE GENE EXPRESSION VIA HYPOXIA-INDUCED TRANSCRIPTION ACTIVITIES. THE TRANSCRIPTION FACTOR HYPOXIA-INDUCIBLE FACTOR 1 (HIF-1) IS A GLOBAL REGULATOR OF OXYGEN HOMEOSTASIS. AS DISCUSSED IN THIS ARTICLE, HYPOXIA OR 'OXIDATIVE STRESS' IS ACCOMPANIED BY APPROPRIATE MOLECULAR ADAPTATION MECHANISMS AT THE ENZYMATIC OR EPIGENETIC LEVEL (ENZYMATIC AND NON-ENZYMATIC RADICAL INHIBITORS, POSTTRANSLATIONAL MODIFICATIONS) AND AT THE GENETIC LEVEL (TRANSCRIPTION, TRANSLATION). 2005 5 6811 25 [EPIGENETICS, ENVIRONMENT AND ASTHMA]. ASTHMA IS A CHRONIC INFLAMMATORY DISEASE OF THE RESPIRATORY TRACT WITH A COMPLEX GENETIC BACKGROUND INFLUENCED BY THE EXPOSITION TO A SERIES OF ENVIRONMENTAL FACTORS. GENETIC STUDIES CAN ONLY ELUCIDATE PART OF THE HERITABILITY AND SUSCEPTIBILITY OF ASTHMA AND EVEN THOUGH SEVERAL DISEASES HAVE AN EVIDENT GENETIC ETIOLOGY, ONLY A FRACTION OF THE GENES INVOLVED IN THEIR PATHOGENICITY HAVE BEEN IDENTIFIED. THE EPIGENETIC REGULATION OF THE LATTER IS A FACT ONE SHOULD BEAR IN MIND IN ORDER TO EXPLAIN THE MAJOR TRIGGERS OF DISEASES WHOSE UNDERSTANDING IS COMPLICATED, SUCH AS ALLERGIES AND ASTHMA. EXTERNAL STIMULUS SUCH AS NOURISHMENT, STRESS, PHYSICAL ACTIVITY, ATMOSPHERIC POLLUTION, TOBACCO SMOKING AND ALCOHOL DRINKING CAN INDUCE EITHER GENE SILENCING OR GENE EXPRESSION. IN THIS REGARD, EPIGENETICS CAN EXPLAIN HOW THESE ENVIRONMENTAL FACTORS INFLUENCE OUR GENETIC INHERITANCE. THERE IS GROWING EVIDENCE THAT BACKS-UP THE FACT THAT DNA METHYLATION, HISTONE POST-TRANSLATIONAL MODIFICATION AND MICRORNA EXPRESSION ARE INFLUENCED BY THE ENVIRONMENT. THIS HELPS EXPLAINING HOW SEVERAL OF THE RISK FACTORS MENTIONED CONTRIBUTE TO THE DEVELOPMENT AND INHERITANCE OF ASTHMA. IN THIS REVIEW, DIFFERENT ENVIRONMENTAL FACTORS AND THEIR RELATION WITH THE MAIN EPIGENETIC REGULATORY MECHANISMS WILL BE ANALYZED, AS WELL AS THEIR POSSIBLE ROLE IN THE DEVELOPMENT OF ASTHMA. 2014 6 2861 20 FROM TRAINED IMMUNITY IN ALLERGY TO TRAINED IMMUNITY-BASED ALLERGEN VACCINES. INNATE IMMUNE CELLS EXPERIENCE LONG LASTING METABOLIC AND EPIGENETIC CHANGES AFTER AN ENCOUNTER WITH SPECIFIC STIMULI. THIS FACILITATES ENHANCED IMMUNE RESPONSES UPON SECONDARY EXPOSITION TO BOTH THE SAME AND UNRELATED PATHOGENS, A PROCESS TERMED TRAINED IMMUNITY. TRAINED IMMUNITY-BASED VACCINES (TIBV) ARE VACCINES ABLE TO INDUCE INNATE IMMUNE MEMORY, THUS CONFERRING HETEROLOGOUS PROTECTION AGAINST A BROAD RANGE OF PATHOGENS. WHILE TRAINED IMMUNITY HAS BEEN WELL DOCUMENTED IN THE CONTEXT OF INFECTIONS AND MULTIPLE IMMUNE-MEDIATED DISEASES, THE ROLE OF INNATE IMMUNE MEMORY AND ITS CONTRIBUTION TO THE INITIATION AND MAINTENANCE OF CHRONIC ALLERGIC DISEASES REMAINS POORLY UNDERSTOOD. OVER THE LAST YEARS, DIFFERENT STUDIES ATTEMPTING TO UNCOVER THE ROLE OF TRAINED IMMUNITY IN ALLERGY HAVE EMERGED. EXPOSITION TO ENVIRONMENTAL FACTORS IMPACTING ALLERGY DEVELOPMENT SUCH AS ALLERGENS OR VIRUSES INDUCES THE REPROGRAMMING OF INNATE IMMUNE CELLS TO ACQUIRE A MORE PRO-INFLAMMATORY PHENOTYPE IN THE CONTEXT OF ASTHMA OR FOOD ALLERGY. SEVERAL STUDIES HAVE CONVINCINGLY DEMONSTRATED THAT PREVENTION OF VIRAL INFECTIONS USING TIBV CONTRIBUTES TO REDUCE WHEEZING ATTACKS IN CHILDREN, WHICH REPRESENT A HIGH-RISK FACTOR FOR ASTHMA DEVELOPMENT LATER IN LIFE. INNATE IMMUNE CELLS TRAINED WITH SPECIFIC STIMULI MIGHT ALSO ACQUIRE ANTI-INFLAMMATORY FEATURES AND PROMOTE TOLERANCE, WHICH MAY HAVE IMPORTANT IMPLICATIONS FOR CHRONIC INFLAMMATORY DISEASES SUCH AS ALLERGIES. RECENT FINDINGS SHOWED THAT ALLERGOID-MANNAN CONJUGATES, WHICH ARE NEXT GENERATION VACCINES FOR ALLERGEN-SPECIFIC IMMUNOTHERAPY (AIT), ARE ABLE TO REPROGRAM MONOCYTES INTO TOLEROGENIC DENDRITIC CELLS BY MECHANISMS DEPENDING ON METABOLIC AND EPIGENETIC REWIRING. A BETTER UNDERSTANDING OF THE UNDERLYING MECHANISMS OF TRAINED IMMUNITY IN ALLERGY WILL PAVE THE WAY FOR THE DESIGN OF NOVEL TRAINED IMMUNITY-BASED ALLERGEN VACCINES AS POTENTIAL ALTERNATIVE STRATEGIES FOR THE PREVENTION AND TREATMENT OF ALLERGIC DISEASES. 2023 7 6876 23 [PROLONGED EXPOSURE TO ATMOSPHERIC AIR POLLUTION AND MORTALITY FROM RESPIRATORY CAUSES]. DIFFERENT DESIGNS CAN BE USED TO ANALYZE THE RELATIONSHIPS BETWEEN RESPIRATORY MORTALITY AND LONG TERM EXPOSURE TO ATMOSPHERIC POLLUTION: EPIDEMIOLOGICAL STUDIES (COHORT, PREVALENCE STUDY) DEMONSTRATE THE REALITY OF THE RELATIONSHIP AND TOXICOLOGICAL STUDIES EXPLAIN IT. COHORT STUDIES HAVE THE ADVANTAGE OF BEING ABLE TO TAKE INTO ACCOUNT MANY CONFOUNDING FACTORS AND THUS AVOID BIASES (WHICH IS NOT THE CASE WITH PREVALENCE STUDIES), BUT REQUIRE SIGNIFICANT HUMAN AND FINANCIAL RESOURCES. THEY WERE FIRST ADOPTED IN THE US, BUT ARE NOW MORE OFTEN APPLIED IN EUROPE. THE RESULTS ARE RELATIVELY CONSISTENT, AS THEY ALL SHOW A STATISTICALLY SIGNIFICANT ASSOCIATION BETWEEN AN INCREASE IN PARTICULATE POLLUTION AND CARDIOPULMONARY MORTALITY. MORTALITY FROM LUNG CANCER IS ALSO ASSOCIATED WITH LONG TERM EXPOSITION TO PARTICLES AND SOMETIMES TO OZONE OR NITROGEN OXIDES. CEREBROVASCULAR DISEASES AND SUDDEN DEATH OF YOUNG CHILDREN HAVE ALSO BEEN ASSOCIATED WITH PARTICULATE POLLUTION. THE RELATIONSHIPS ARE MORE POWERFUL FOR LONG TERM THAN SHORT TERM EXPOSURE BUT ARE ALSO LINEAR AND WITHOUT THRESHOLD. IN ORDER TO EXPLAIN THESE EFFECTS (TODAY THE CAUSALITY OF THE RELATIONSHIP IS CERTAIN) THERE ARE MANY POSSIBLE FACTORS, PARTICULARLY REGARDING PARTICULATE EXPOSURES: AN INCREASE IN CARDIOVASCULAR RISK BIOMARKERS (FIBRINOGEN, WHITE BLOOD CELLS, AND PLATELETS), ATHEROSCLEROSIS, CHRONIC INFLAMMATION OF LUNG TISSUES INCREASED BY ACUTE EXPOSURE, ETC. MORE AND MORE STUDIES ADDRESS THE INTERACTION BETWEEN GENE AND ENVIRONMENT AND EVEN EPIGENETIC PHENOMENA WHICH COULD BE RESPONSIBLE OF THESE EFFECTS. PUBLIC HEALTH IMPACT COULD BE QUANTIFIED. THE EUROPEAN E&H SURVEILLANCE PROGRAM APHEIS, FOR EXAMPLE, ESTIMATED THAT IF PM2.5 LEVELS REMAINED BELOW 15 MICROG/M(3), A 30 YEAR OLD PERSON COULD SEE HIS LIFE EXPECTANCY INCREASED BY 1 MONTH TO 2 YEARS, DEPENDING ON THE STUDIED CITY. FINALLY, MORTALITY IS NOT THE ONLY RELEVANT INDICATOR FOR HEALTH EFFECTS OF AIR POLLUTION. ISAAC STUDIES ADDRESS ASTHMA, ALLERGIC RHINITIS AND ECZEMA AMONG CHILDREN. 2009 8 6792 13 [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 9 5457 18 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 10 529 19 ASTHMA IN URBAN CHILDREN: EPIDEMIOLOGY, ENVIRONMENTAL RISK FACTORS, AND THE PUBLIC HEALTH DOMAIN. ASTHMA IS THE MOST COMMONLY REPORTED CHRONIC CONDITION OF CHILDHOOD IN DEVELOPED COUNTRIES, WITH 6.5 MILLION CHILDREN AFFECTED IN THE USA. A DISPARATE BURDEN OF CHILDHOOD ASTHMA IS SEEN AMONG SOCIOECONOMICALLY DISADVANTAGED YOUTH, OFTEN CONCENTRATED IN URBAN AREAS WITH HIGH POVERTY RATES. HOST FACTORS THAT PREDISPOSE A CHILD TO ASTHMA INCLUDE ATOPY, MALE GENDER, PARENTAL HISTORY OF ASTHMA, AND ALSO RACE, ETHNICITY, AND GENETIC AND EPIGENETIC SUSCEPTIBILITIES. ENVIRONMENTAL FACTORS, SUCH AS IMPROVED HYGIENE, AMBIENT AIR POLLUTION, AND EARLY LIFE EXPOSURES TO MICROBES AND AEROALLERGENS, ALSO INFLUENCE THE DEVELOPMENT OF ASTHMA. WITH GREATER THAN 90% OF TIME SPENT INDOORS, HOME EXPOSURES (SUCH AS COCKROACH, RODENT, AND INDOOR AIR POLLUTION) ARE HIGHLY RELEVANT FOR URBAN ASTHMA. MORBIDITY REDUCTION MAY REQUIRE FOCUSED PUBLIC HEALTH INITIATIVES FOR ENVIRONMENTAL INTERVENTION IN HIGH PRIORITY RISK GROUPS AND THE ADDITION OF IMMUNE MODULATORY AGENTS IN CHILDREN WITH POORLY CONTROLLED DISEASE. 2016 11 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 12 6048 20 THE CONCEPTS OF ASTHMA ENDOTYPES AND PHENOTYPES TO GUIDE CURRENT AND NOVEL TREATMENT STRATEGIES. ASTHMA, A COMMON, NON-COMMUNICABLE CHRONIC DISEASE AFFECTS OVER 300 MILLION INDIVIDUALS WORLDWIDE. THE WESTERN WORLD LIFESTYLE IS CLAIMED TO BE RESPONSIBLE FOR THIS HIGH AND INCREASING PREVALENCE. ASTHMA HAS BEEN DEFINED AS A SYNDROME WITH VARIOUS PHENOTYPES AND ENDOTYPES, ALLERGIC ASTHMA AND TYPE 2 ASTHMA BEING THE MOST FREQUENT. A GREAT INCREASE IN PREVALENCE OF ALLERGIC DISEASES HAS NECESSITATED INTENSIVE INVESTIGATIONS BOTH FOR UNDERSTANDING THE UNDERLYING MECHANISMS AND FOR THE DEVELOPMENT OF NOVEL THERAPY OPTIONS WITH LONG-TERM EFFICACY AND LIMITED SIDE-EFFECTS. ALLERGIC PATIENTS DEMONSTRATE UNIQUE PRESENTATIONS WITH VARIABLE VISIBLE CHARACTERISTICS AND DISEASE OUTCOMES DEPENDING ON DIFFERENT MOLECULAR MECHANISMS, RELATED TO INFLUENCE OF GENES AND EPIGENETIC CONTROL BY MICRO- AND MACRO-ENVIRONMENT. AREAS COVERED: THIS ARTICLE REVIEWS THE DEFINITION OF ASTHMA PHENOTYPES AND POSSIBLE ENDOTYPES, ADVANCES IN ALLERGY-IMMUNOLOGY FIELD AND CONTEMPORARY PERSONALIZED THERAPY OPTIONS FOR ASTHMA. EXPERT COMMENTARY: BETTER UNDERSTANDING OF THE COMPLEX IMMUNE NETWORK OF ALLERGIC INFLAMMATION AND KEY PLAYERS OF IMMUNITY IS CONTINUOUSLY BEING PROVIDED FOR CLARIFICATION OF ASTHMA SUB-TYPES. SUCCESSFUL THERAPY OF ASTHMA REQUIRES BETTER DEFINITION OF UNDERLYING PATHOGENESIS, WHICH SEQUENTIALLY COULD END UP WITH 'CUSTOM-TAILORED' INDIVIDUALIZED, EVIDENCE-BASED AND MORE PRECISE THERAPY OPTIONS; A NEW ERA TERMED AS 'PRECISION MEDICINE'. ENDOTYPE, PHENOTYPE, THERATYPE AND BIOMARKER TERMS ARISE AS MAJOR KEYWORDS IN PRECISION/PERSONALIZED MEDICINE. 2018 13 6877 25 [REASONS FOR THE DEVELOPMENT OF ALLERGIES IN CHILDREN]. ALLERGIES ARE ONE OF THE MOST COMMON CHRONIC DISEASES IN CHILDHOOD, CONTRIBUTING TO A TREMENDOUS MEDICAL AND ECONOMICAL BURDEN IN HEALTH CARE SYSTEMS OF MOST INDUSTRIALIZED COUNTRIES. THE DEVELOPMENT OF ALLERGIES IS DEPENDENT ON A COMPLEX INTERACTION OF-AMONG OTHERS-ENVIRONMENTAL FACTORS, NUTRITION, GENETIC AND EPIGENETIC MECHANISMS AS WELL AS THE MICROBIOME. THESE DIVERSE FACTORS CAN INFLUENCE EARLY LIFE IMMUNE REGULATION INCLUDING INNATE AND ADAPTIVE IMMUNE MECHANISMS IN A COMPLEX FASHION. IN CASE OF ANY CHILDHOOD ALLERGIES HAVE INCREASED SIGNIFICANTLY IN PAST DECADES. IN ADDITION TO ENVIRONMENTAL FACTORS AND NUTRITION, GENETIC AND EPIGENETIC MECHANISMS AS WELL AS THE MICROBIOME OF CHILDREN PLAY AN IMPORTANT ROLE. OF RELEVANCE IS THE WAY IN WHICH THESE DIVERSE FACTORS INFLUENCE EARLY IMMUNE DEVELOPMENT OF THE INNATE AND ADAPTIVE IMMUNE SYSTEMS OF CHILDREN. THEIR COMPLEX REGULATION IS DECISIVE FOR WHETHER OR NOT A CHILD DEVELOPS AN ALLERGY THAT MANIFESTS IN MOST CASES AS ATOPIC DERMATITIS, BRONCHIAL ASTHMA, OR ALLERGIC RHINO CONJUNCTIVITIS, OR WHETHER A CHILD DEVELOPS AN IMMUNE TOLERANCE. THESE INFLUENCES CAN BEGIN PRENATALLY, ALREADY SETTING THE COURSE FOR LATER IMMUNE SYSTEM DEVELOPMENT AND OCCURRENCE OF DISEASE. 2019 14 6483 15 TOXIC STRESS, EPIGENETICS AND CHILD DEVELOPMENT. OBJECTIVES: TO DESCRIBE THE CONCEPT OF TOXIC STRESS, PRESENT THE BASICS OF EPIGENETICS AND DISCUSS THEIR RELATIONSHIP WITH CHILD DEVELOPMENT. DATA SOURCE: NARRATIVE LITERATURE REVIEW THROUGH A SEARCH IN THE SCIELO, LILACS, MEDLINE DATABASES USING THE TERMS ADVERSE CHILDHOOD EXPERIENCE OR EARLY LIFE STRESS, EPIGENOMIC OR EPIGENETIC, CHILD DEVELOPMENT OR INFANT DEVELOPMENT. DATA SYNTHESIS: CONTINUING STRESS RESPONSE, KNOWN AS TOXIC STRESS, CAN OCCUR WHEN A CHILD EXPERIENCES INTENSE, FREQUENT, AND/OR PROLONGED ADVERSITY-SUCH AS PHYSICAL OR EMOTIONAL ABUSE, CHRONIC NEGLECT, FOR EXAMPLE-WITHOUT ADEQUATE ADULT SUPPORT. THIS TOXIC STRESS CAN HAVE HARMFUL EFFECTS ON LEARNING, BEHAVIOR, AND HEALTH THROUGHOUT LIFE. EPIGENETICS, AN EMERGING SCIENTIFIC RESEARCH AREA?, SHOWS HOW ENVIRONMENTAL INFLUENCES AFFECT GENE EXPRESSIONS AND EXPLAINS HOW EARLY EXPERIENCES CAN IMPACT THROUGHOUT LIFE. CONCLUSIONS: TOXIC STRESS CAUSES CHANGES IN THE HUMAN BODY RESPONSE SYSTEMS THAT CAN BE EXPLAINED IN PART BY EPIGENETIC CHANGES, WHICH CAN BE TEMPORARY OR LONG-LASTING. PEDIATRICIANS MUST BE AWARE OF THESE MECHANISMS AND THEIR CONSEQUENCES, SEEKING TO PREVENT THEM AND THUS PROMOTE THE HEALTH, WELL-BEING, AND QUALITY OF LIFE OF CHILDREN, CONTRIBUTING TO THEIR FULL DEVELOPMENT. 2022 15 6894 16 [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 16 3910 18 LIFE COURSE OF ASTHMA. ASTHMA IS A HETEROGENEOUS CHRONIC AIRWAY DISEASE THAT CAN VARY OVER A LIFETIME. ALTHOUGH BROAD CATEGORIES OF ASTHMA BY SEVERITY AND TYPE HAVE BEEN CONSTRUCTED, THERE REMAINS A TREMENDOUS OPPORTUNITY TO DISCOVER AN APPROACH TO MANAGING ASTHMA WITH ADDITIONAL FACTORS IN MIND. MANY IN THE FIELD HAVE SUGGESTED AND ARE PURSUING A NOVEL PARADIGM SHIFT IN HOW ASTHMA MIGHT BE BETTER MANAGED, CONSIDERING THE LIFE COURSE OF EXPOSURES, MANAGEMENT PRIORITIES, AND PREDICTED TRAJECTORY OF LUNG FUNCTION GROWTH. THIS APPROACH WILL REQUIRE A MORE HOLISTIC VIEW OF PRENATAL, POSTNATAL, ADOLESCENCE, HORMONAL AND GENDER ASPECTS, AND THE AGING PROCESS. IN ADDITION, THE ENVIRONMENT, EXTERNALLY AND INTERNALLY, INCLUDING IN ONE'S GENETIC CODE AND EPIGENETIC CHANGES, ARE FACTORS THAT AFFECT HOW ASTHMA PROGRESSES OR BECOMES MORE STABLE IN INDIVIDUALS. THIS CHAPTER FOCUSES ON THE VARIOUS INFLUENCES THAT MAY, TO DIFFERING DEGREES, AFFECT PEOPLE WITH ASTHMA, WHICH CAN DEVELOP AT ANY TIME IN THEIR LIVES. SHIFTING THE PARADIGM OF THOUGHT AND STRATEGIES FOR CARE AND ADVOCATING FOR PUBLIC POLICIES AND HEALTH DELIVERY THAT FOCUS ON THIS PHILOSOPHY IS PARAMOUNT TO ADVANCE ASTHMA CARE FOR ALL. 2023 17 46 18 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 5254 25 PROGRAMMING OF RESPIRATORY HEALTH IN CHILDHOOD: INFLUENCE OF OUTDOOR AIR POLLUTION. PURPOSE OF REVIEW: THIS OVERVIEW HIGHLIGHTS RECENT EXPERIMENTAL AND EPIDEMIOLOGICAL EVIDENCE FOR THE PROGRAMMING EFFECTS OF OUTDOOR AIR POLLUTION EXPOSURES DURING EARLY DEVELOPMENT ON LUNG FUNCTION AND CHRONIC RESPIRATORY DISORDERS, SUCH AS ASTHMA AND RELATED ALLERGIC DISORDERS. RECENT FINDINGS: AIR POLLUTANTS MAY IMPACT ANATOMY AND/OR PHYSIOLOGICAL FUNCTIONING OF THE LUNG AND INTERRELATED SYSTEMS. PROGRAMMING EFFECTS MAY RESULT FROM POLLUTANT-INDUCED SHIFTS IN A NUMBER OF MOLECULAR, CELLULAR, AND PHYSIOLOGICAL STATES AND THEIR INTERACTING SYSTEMS. SPECIFIC KEY REGULATORY SYSTEMS SUSCEPTIBLE TO PROGRAMMING MAY INFLUENCE LUNG DEVELOPMENT AND VULNERABILITY TO RESPIRATORY DISEASES, INCLUDING BOTH CENTRAL AND PERIPHERAL COMPONENTS OF NEUROENDOCRINE PATHWAYS AND AUTONOMIC NERVOUS SYSTEM (ANS) FUNCTIONING WHICH, IN TURN, INFLUENCE THE IMMUNE SYSTEM. STARTING IN UTERO, ENVIRONMENTAL FACTORS, INCLUDING AIR POLLUTANTS, MAY PERMANENTLY ORGANIZE THESE SYSTEMS TOWARD TRAJECTORIES OF ENHANCED PEDIATRIC (E.G., ASTHMA, ALLERGY) AS WELL AS ADULT DISEASE RISK (E.G., CHRONIC OBSTRUCTIVE PULMONARY DISEASE). EVIDENCE SUPPORTS A CENTRAL ROLE OF OXIDATIVE STRESS IN THE TOXIC EFFECTS OF AIR POLLUTION. ADDITIONAL RESEARCH SUGGESTS XENOBIOTIC METABOLISM AND SUBCELLULAR COMPONENTS, SUCH AS MITOCHONDRIA ARE TARGETS OF AMBIENT AIR POLLUTION AND PLAY A ROLE IN ASTHMA AND ALLERGY PROGRAMMING. MECHANISMS OPERATING AT THE LEVEL OF THE PLACENTA ARE BEING ELUCIDATED. EPIGENETIC MECHANISMS MAY BE AT THE ROOTS OF ADAPTIVE DEVELOPMENTAL PROGRAMMING. SUMMARY: OPTIMAL COORDINATED FUNCTIONING OF MANY COMPLEX PROCESSES AND THEIR NETWORKS OF INTERACTION ARE NECESSARY FOR NORMAL LUNG DEVELOPMENT AND THE MAINTENANCE OF RESPIRATORY HEALTH. OUTDOOR AIR POLLUTION MAY PLAY AN IMPORTANT ROLE IN EARLY PROGRAMMING OF RESPIRATORY HEALTH AND IS POTENTIALLY AMENABLE TO INTERVENTION. 2013 19 360 14 AMBIENT AIR POLLUTION AND BIOMARKERS OF HEALTH EFFECT. RECENTLY, THE AIR POLLUTION SITUATION OF OUR COUNTRY IS VERY SERIOUS ALONG WITH THE DEVELOPMENT OF URBANIZATION AND INDUSTRIALIZATION. STUDIES INDICATE THAT THE EXPOSURE OF AIR POLLUTION CAN CAUSE A RISE OF INCIDENCE AND MORTALITY OF MANY DISEASES, SUCH AS CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), ASTHMA, MYOCARDIAL INFARCTION, AND SO ON. HOWEVER, THERE IS NOW GROWING EVIDENCE SHOWING THAT SIGNIFICANT AIR POLLUTION EXPOSURES ARE ASSOCIATED WITH EARLY BIOMARKERS IN VARIOUS SYSTEMS OF THE BODY. IN ORDER TO BETTER PREVENT AND CONTROL THE DAMAGE EFFECT OF AIR POLLUTION, THIS ARTICLE SUMMARIZES COMPREHENSIVELY EPIDEMIOLOGICAL STUDIES ABOUT THE BAD EFFECTS ON THE BIOMARKERS OF RESPIRATORY SYSTEM, CARDIOVASCULAR SYSTEM, AND GENETIC AND EPIGENETIC SYSTEM EXPOSURE TO AMBIENT AIR POLLUTION. 2017 20 2518 24 EPIGENETICS AND THE EMBODIMENT OF RACE: DEVELOPMENTAL ORIGINS OF US RACIAL DISPARITIES IN CARDIOVASCULAR HEALTH. THE RELATIVE CONTRIBUTION OF GENETIC AND ENVIRONMENTAL INFLUENCES TO THE US BLACK-WHITE DISPARITY IN CARDIOVASCULAR DISEASE (CVD) IS HOTLY DEBATED WITHIN THE PUBLIC HEALTH, ANTHROPOLOGY, AND MEDICAL COMMUNITIES. IN THIS ARTICLE, WE REVIEW EVIDENCE FOR DEVELOPMENTAL AND EPIGENETIC PATHWAYS LINKING EARLY LIFE ENVIRONMENTS WITH CVD, AND CRITICALLY EVALUATE THEIR POSSIBLE ROLE IN THE ORIGINS OF THESE RACIAL HEALTH DISPARITIES. AFRICAN AMERICANS NOT ONLY SUFFER FROM A DISPROPORTIONATE BURDEN OF CVD RELATIVE TO WHITES, BUT ALSO HAVE HIGHER RATES OF THE PERINATAL HEALTH DISPARITIES NOW KNOWN TO BE THE ANTECEDENTS OF THESE CONDITIONS. THERE IS EXTENSIVE EVIDENCE FOR A SOCIAL ORIGIN TO PREMATURITY AND LOW BIRTH WEIGHT IN AFRICAN AMERICANS, REFLECTING PATHWAYS SUCH AS THE EFFECTS OF DISCRIMINATION ON MATERNAL STRESS PHYSIOLOGY. IN LIGHT OF THE INVERSE RELATIONSHIP BETWEEN BIRTH WEIGHT AND ADULT CVD, THERE IS NOW A STRONG RATIONALE TO CONSIDER DEVELOPMENTAL AND EPIGENETIC MECHANISMS AS LINKS BETWEEN EARLY LIFE ENVIRONMENTAL FACTORS LIKE MATERNAL STRESS DURING PREGNANCY AND ADULT RACE-BASED HEALTH DISPARITIES IN DISEASES LIKE HYPERTENSION, DIABETES, STROKE, AND CORONARY HEART DISEASE. THE MODEL OUTLINED HERE BUILDS UPON SOCIAL CONSTRUCTIVIST PERSPECTIVES TO HIGHLIGHT AN IMPORTANT SET OF MECHANISMS BY WHICH SOCIAL INFLUENCES CAN BECOME EMBODIED, HAVING DURABLE AND EVEN TRANSGENERATIONAL INFLUENCES ON THE MOST PRESSING US HEALTH DISPARITIES. WE CONCLUDE THAT ENVIRONMENTALLY RESPONSIVE PHENOTYPIC PLASTICITY, IN COMBINATION WITH THE BETTER-STUDIED ACUTE AND CHRONIC EFFECTS OF SOCIAL-ENVIRONMENTAL EXPOSURES, PROVIDES A MORE PARSIMONIOUS EXPLANATION THAN GENETICS FOR THE PERSISTENCE OF CVD DISPARITIES BETWEEN MEMBERS OF SOCIALLY IMPOSED RACIAL CATEGORIES. 2009