1 4572 154 MYELOPEROXIDASE IMMUNOHISTOCHEMISTRY AS A MEASURE OF DISEASE ACTIVITY IN ULCERATIVE COLITIS: ASSOCIATION WITH ULCERATIVE COLITIS-COLORECTAL CANCER, TUMOR NECROSIS FACTOR POLYMORPHISM AND RUNX3 METHYLATION. BACKGROUND: PATIENTS WITH EXTENSIVE, LONGSTANDING ULCERATIVE COLITIS (UC), A DISEASE OF CHRONIC COLONIC INFLAMMATION, ARE AT RISK FOR COLORECTAL CANCER (CRC). ELUCIDATING THE MECHANISM AND FULLY CHARACTERIZING THE NATURE OF THIS CHRONIC INFLAMMATION OFFERS THE POTENTIAL TO IDENTIFY THOSE AT GREATEST RISK. WE PERFORMED A CASE-CONTROL STUDY COMPARING HISTOLOGIC DISEASE ACTIVITY (HDA; NEUTROPHILS ON HEMATOXYLIN AND EOSIN [H&E]-STAINED SLIDES) WITH IMMUNOHISTOCHEMISTRY (IHC) DIRECTED AGAINST SPECIFIC CELL TYPES. WE CORRELATED IHC RESULTS WITH DATA PREVIOUSLY GENERATED ON METHYLATION STATUS OF RUNX3 AND SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) IN TUMOR NECROSIS FACTOR ALPHA (TNF-ALPHA). METHODS: A NONADJACENT, NONNEOPLASTIC SECTION OF BOWEL WALL WAS IDENTIFIED FOR EACH UC-CRC CASE. HDA WAS ASSESSED FOR UC-CRC CASES (N = 50) AND UC-CONTROLS (N = 50). SECTIONS WERE IMMUNOSTAINED USING ANTIBODIES AGAINST MACROPHAGES (CD68), NEUTROPHILS/MONOCYTES (MYELOPEROXIDASE, MPO), AND T CELLS (CD3). SLIDES WERE SCORED USING IMAGEJ AND RESULTS REPORTED AS THE PERCENT AREA POSITIVE FOR EACH MARKER. RESULTS: HDA DID NOT CORRELATE WITH INFILTRATE LEVELS AS MEASURED BY IHC AND INCREASING HDA WAS INVERSELY RELATED TO UC-CRC RISK. CONVERSELY, THE PERCENT AREA POSITIVE FOR CD68 AND MPO WAS SIGNIFICANTLY ELEVATED IN UC-CRC CASES VERSUS CONTROLS (P = 0.04 AND < 0.0001, RESPECTIVELY). IN AREAS DESIGNATED INACTIVE, MPO STAINING REMAINED SIGNIFICANTLY HIGHER IN UC-CRC CASES VERSUS CONTROLS (P = 0.002). INCREASED MPO STAINING WAS ASSOCIATED WITH METHYLATION OF RUNX3 AND THE TNF-ALPHA -308G>A SNP. CONCLUSIONS: HDA IS LESS SENSITIVE THAN IHC AND MAY UNDERESTIMATE INFLAMMATORY CELL POPULATIONS ASSOCIATED WITH UC-CRC. THE EPIGENETIC/GENETIC ASSOCIATIONS RELATED TO ELEVATED MPO STAINING IN UC-CRC MAY OFFER NEW METHODS FOR RISK STRATIFICATION AND ADJUNCTIVE SCREENING TOOLS. 2012 2 458 20 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 3 2083 25 EPIGENETIC DRUGS: A LONGSTANDING STORY. IN THIS CHAPTER, THE DEVELOPMENT OF DECITABINE FROM ITS SYNTHESIS IN 1964 TO THE SUBMISSION OF A REGISTRATION FILE IN 2004 IS REVIEWED. THE PROPER APPLICATION OF THE UNIQUE PROPERTIES OF DECITABINE TOOK QUITE SOME TIME TO ELUCIDATE. IN ADDITION, THE PRACTICAL HANDLING IN THE CLINIC WAS NOT EASY AS THE PROLONGED MYELOSUPPRESSION OF DECITABINE MADE IT DIFFICULT TO DETERMINE THE PREFERRED DOSE AND SCHEDULE. LABORATORY STUDIES ON DNA METHYLATION AND CELL DIFFERENTIATION SHOWED POSSIBLE APPLICATIONS IN SOLID AND HEMATOLOGIC MALIGNANCIES. HOWEVER, DESPITE MANY ATTEMPTS, RESULTS IN SOLID TUMORS HAVE BEEN DISAPPOINTING THUS FAR. AFTER THOROUGH INVESTIGATION, DECITABINE ACHIEVED THERAPEUTIC APPLICATION IN MYELODYSPLASTIC SYNDROME (MDS), IN PARTICULAR IN PATIENTS WITH A POOR PROGNOSIS. FURTHER INDICATIONS MAY INCLUDE ACUTE MYELOID LEUKEMIA (AML), CHRONIC MYELOGENOUS LEUKEMIA (CML), HEMATOPOIETIC STEM CELL TRANSPLANTATION, SICKLE CELL ANEMIA, AND THALASSEMIA. WHEREAS MOST DRUGS ARE ALREADY AT THE END OF THEIR LIFE CYCLE AFTER 40 YEARS, DECITABINE IS ONLY AT THE BEGINNING. ITS APPLICATION WILL BROADEN WITH THE INCREASE IN KNOWLEDGE OF EPIGENETIC MECHANISMS AND THEIR RELATIONSHIP TO DRUG THERAPY. 2005 4 114 25 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 5 6769 16 ["EDUCATION" IN AN AGE OF INCREASING EQUALITY--A PATH TOWARDS 'OCHLOCRACY"?]. A PHILOSOPHICAL AND SCIENTIFIC ANALYSIS OF HOW THE CONCEPT OF EQUALITY HAS DEVELOPED FROM BIOLOGICAL, POLITICAL, SOCIOLOGICAL, SOCIAL, ECONOMIC AND--NOT LEAST--CULTURAL POINTS OF VIEW. THE FOCUS HERE IS ON THE GERMAN CHRONIC SHORTAGE OF EDUCATIONAL FACILITIES CONTINUING FOR DECADES, A CULTURAL REVOLUTION WITHOUT ANY FORESEEABLE END. THESE REFLECTIONS ENCOMPASS A PERIOD OF AROUND TWO AND A HALF MILLENNIA, BEGINNING WITH THE ANCIENT GREEK STATE PHILOSOPHY, REACHING INTO OUR EPOCH OF ADVANCED GLOBALISATION WITH MOMENTOUS CHANGES IN WESTERN SOCIAL WELFARE STATES. IN CONSIDERATION OF A BIOCHEMICAL AND INTRINSIC INDIVIDUALITY BASED ON GENETIC AND EPI-GENETIC FACTORS, EQUAL OPPORTUNITIES ARE AN UNLIKELY PREREQUISITE IN EVOLUTION. WITH REGARD TO FREE EDUCATION, EQUALITY CAN ONLY BE A STARTING POINT SINCE, DUE TO INDIVIDUAL DIFFERENCES, EGALITARIAN AIMS OF EDUCATION WITHIN A "GROUP UNIVERSITY" CAN NEVER OPEN UP EQUALLY GOOD CHANCES TO EVERYBODY. BECAUSE OF A MISUNDERSTANDING OF EQUALITY, THE STUDENT REVOLT IN 1968 BROUGHT FORTH AN EGALITARIAN REMODELING OF SCHOOL AND UNIVERSITY CAREERS ACCOMPANIED BY A LEVELING, AMONG OTHER THINGS A "UNIVERSITY OF EDUCATION FOR THE MASSES". INSTEAD OF "EDUCATIONAL KNOWLEDGE" BASED ON SCIENTIFIC NATURE, AN EDUCATION TOWARDS VOCATIONAL KNOWLEDGE AND REGULATION OF STUDIES TOOK PLACE. AT PRESENT, A SOCIALISTIC REVERSAL OF THE SCHOOL SYSTEM AIMED AT LEARNING TOGETHER IN ,COMMUNITY SCHOOLS" UNTIL THE 10TH GRADE IS IN PROGRESS. THE UNITY OF (PURE) RESEARCH AND TEACHING NO LONGER EXISTS. THE CHANGE IN THE SYSTEM SUPPORTED BY A WELFARE STATE WILL HAVE CONSEQUENCES IN WORLDWIDE COMPETITION. THE FINAL POINT OF THE CULTURAL REVOLUTION, FOLLOWING HISTORICAL EXAMPLES, COULD BE THE EMERGENCE OF A DEGENERATE FORM OF DEMOCRACY: OCHLOCRACY. 2012 6 2603 29 EPIGENETICS, ENVIRONMENT AND EPIDEMIOLOGY: AN INTERVIEW WITH KARL KELSEY. IN THIS INTERVIEW, PROFESSOR KARL KELSEY SPEAKS WITH STORM JOHNSON, COMMISSIONING EDITOR FOR EPIGENOMICS, ON HIS WORK TO DATE IN THE FIELD OF ENVIRONMENTAL EPIGENOMICS AND EPIDEMIOLOGY. DR KARL KELSEY, MD, MOH IS A PROFESSOR OF EPIDEMIOLOGY AND PATHOLOGY AND LABORATORY MEDICINE AT BROWN UNIVERSITY. HE IS THE FOUNDING DIRECTOR OF THE CENTER FOR ENVIRONMENTAL HEALTH AND TECHNOLOGY AND HEAD OF THE ENVIRONMENTAL HEALTH SECTION AT THE DEPARTMENT OF EPIDEMIOLOGY. DR KELSEY IS INTERESTED IN THE APPLICATION OF LABORATORY-BASED BIOMARKERS IN ENVIRONMENTAL DISEASE, WITH EXPERIENCE IN CHRONIC DISEASE EPIDEMIOLOGY AND TUMOR BIOLOGY. THE GOALS OF HIS WORK INCLUDE A MECHANISTIC UNDERSTANDING OF INDIVIDUAL SUSCEPTIBILITY TO EXPOSURE-RELATED CANCERS. IN ADDITION, HIS LABORATORY IS INTERESTED IN TUMOR BIOLOGY, INVESTIGATING SOMATIC ALTERATIONS IN TUMOR TISSUE FROM THE PATIENTS WHO HAVE DEVELOPED EXPOSURE-RELATED CANCERS. THIS WORK INVOLVES THE USE OF AN EPIDEMIOLOGIC APPROACH TO CHARACTERIZE EPIGENETIC AND GENETIC ALTERATION OF GENES IN THE CAUSAL PATHWAY FOR MALIGNANCY. ACTIVE WORK INCLUDES SEVERAL STUDIES OF INDIVIDUAL SUSCEPTIBILITY TO CANCER. DR KELSEY'S LABORATORY MAINLY INVESTIGATES SUSCEPTIBILITY TO SMOKING-RELATED LUNG CANCER AND STUDIES MULTI-RACIAL AND ETHNIC POPULATIONS. IN ADDITION, THE LABORATORY IS ALSO INVOLVED WITH THE STUDY OF INHERITED SUSCEPTIBILITY TO BRAIN TUMORS AND PANCREATIC CANCER. MAJOR CASE CONTROL STUDIES THAT ARE ONGOING IN THE LABORATORY INCLUDE STUDIES DESIGNED TO UNDERSTAND INHERITED AND ACQUIRED SUSCEPTIBILITY IN HEAD AND NECK CANCERS. THE LABORATORY IS ALSO INVOLVED IN A CASE CONTROL STUDY OF ASBESTOS-ASSOCIATED MESOTHELIOMA, ARSENIC EXPOSURE, CIGARETTE SMOKING AND BLADDER CANCER. CONSIDERABLE WORK IS BEING DEVOTED TO UNDERSTANDING THE MECHANISMS OF ACTION OF BOTH ASBESTOS AND ARSENIC INCLUDING THEIR ABILITY TO AFFECT PROMOTER METHYLATION AND GENE SILENCING IN CARCINOGENESIS. RECENT LABORATORY STUDIES INCLUDES AN INTEREST IN USING NEWLY DEVELOPED DNA METHYLATION BIOMARKERS TO PROBE IMMUNE PROFILES FROM ARCHIVED BLOOD. DR KELSEY RECEIVED HIS MD FROM THE UNIVERSITY OF MINNESOTA AND MASTERS OF OCCUPATIONAL HEALTH FROM HARVARD UNIVERSITY. 2022 7 393 16 AN OVERVIEW OF EPIGENETICS IN NURSING. EPIGENETIC CHANGES TO THE GENOME ARE BIOCHEMICAL ALTERATIONS TO THE DNA THAT DO NOT CHANGE AN INDIVIDUAL'S GENOME BUT DO CHANGE AND INFLUENCE GENE EXPRESSION. THE NURSING PROFESSION IS QUALIFIED TO CONDUCT AND INTEGRATE EPIGENETIC-FOCUSED NURSING RESEARCH INTO PRACTICE. THIS ARTICLE DISCUSSES CURRENT EPIGENETIC NURSING RESEARCH, PROVIDES AN OVERVIEW OF HOW EPIGENETIC RESEARCH RELATES TO NURSING PRACTICE, MAKES RECOMMENDATIONS, AND PROVIDES EPIGENETIC ONLINE RESOURCES FOR NURSING RESEARCH. AN OVERVIEW OF MAJOR EPIGENETIC STUDIES IN NURSING (SPECIFIC TO CHILDBIRTH STUDIES, PREECLAMPSIA, METABOLIC SYNDROME, IMMUNOTHERAPY CANCER, AND PAIN) IS PROVIDED, WITH RECOMMENDATIONS ON NEXT STEPS. 2013 8 6073 25 THE DRESDEN BURNOUT STUDY: PROTOCOL OF A PROSPECTIVE COHORT STUDY FOR THE BIO-PSYCHOLOGICAL INVESTIGATION OF BURNOUT. OBJECTIVES: THE DRESDEN BURNOUT STUDY (DBS) IS A 12-YEAR LONGITUDINAL COHORT STUDY THAT AIMS TO PROVIDE A DESCRIPTION OF THE BURNOUT SYNDROME ON THE BASIS OF TIME AND SYMPTOM CRITERIA WITH A SPECIAL FOCUS ON THE SEARCH FOR BIOMARKERS. BIOLOGICAL AND PSYCHOSOCIAL APPROACHES ARE APPLIED TO EXAMINE THE LONG-TERM COURSE AND CONSEQUENCES OF BURNOUT WITHIN A POPULATION-BASED GERMAN-SPEAKING SAMPLE AGED 18 TO 68 YEARS. METHODS: DEMOGRAPHICS AND PSYCHOSOCIAL DATA ARE GENERATED BY ONLINE ASSESSMENTS, INCLUDING DEMOGRAPHICS AND QUESTIONNAIRES ON BURNOUT, BURNOUT-RELATED CONSTRUCTS, WORK-ENVIRONMENT, AND HEALTH-RELATED FACTORS. THE LAB-BASED BIOMARKER ASSESSMENT INCLUDES ENDOCRINE, PHYSIOLOGICAL, IMMUNOLOGICAL, AND EPIGENETIC MARKERS OBTAINED FROM BLOOD AND HAIR SAMPLES. IN ADDITION, HEART RATE VARIABILITY IS ALSO MEASURED REPEATEDLY. WITHIN THE FIRST 2 YEARS, THE DBS COLLECTED PSYCHOSOCIAL DATA FROM OVER 7,600 PARTICIPANTS WITH BIOLOGICAL DATA OBTAINED FROM MORE THAN 800 INDIVIDUALS. DURING THE FOLLOWING 10 YEARS, DETAILED ASSESSMENTS OF BIOMARKERS AND PSYCHOSOCIAL FACTORS WILL BE COLLECTED IN ANNUAL STUDY WAVES. RESULTS: RESULTS WILL BE GENERATED DURING THE FOLLOWING DECADE. CONCLUSION: THE FINDINGS OF THE DBS ARE EXPECTED TO PAVE THE ROAD FOR AN IN-DEPTH BIOPSYCHOSOCIAL CHARACTERIZATION OF BURNOUT AND TO GIVE INSIGHT INTO THE LONG-TERM COURSE AND POTENTIAL MENTAL AND PHYSICAL HEALTH CONSEQUENCES OF THE BURNOUT SYNDROME. 2018 9 6914 27 [VITAMIN D DEFICIENCY IN PREGNANCY AND ITS IMPACT ON THE FETUS, THE NEWBORN AND IN CHILDHOOD]. OBJECTIVE: VITAMIN D DEFICIENCY (VDD) IN PREGNANT WOMEN AND THEIR CHILDREN IS AN IMPORTANT HEALTH PROBLEM WITH SEVERE CONSEQUENCES FOR THE HEALTH OF BOTH. THUS, THE OBJECTIVES OF THIS REVIEW WERE TO REASSESS THE MAGNITUDE AND CONSEQUENCES OF VDD DURING PREGNANCY, LACTATION AND INFANCY, ASSOCIATED RISK FACTORS, PREVENTION METHODS, AND TO EXPLORE EPIGENETIC MECHANISMS IN EARLY FETAL LIFE CAPABLE OF EXPLAINING MANY OF THE NON-SKELETAL BENEFITS OF VITAMIN D (VID). DATA SOURCE: ORIGINAL AND REVIEW ARTICLES, AND CONSENSUS DOCUMENTS WITH ELEVATED LEVEL OF EVIDENCE FOR VDD-RELATED CLINICAL DECISIONS ON THE HEALTH OF PREGNANT WOMEN AND THEIR CHILDREN, AS WELL AS ARTICLES ON THE INFLUENCE OF VID ON EPIGENETIC MECHANISMS OF FETAL PROGRAMMING OF CHRONIC DISEASES IN ADULTHOOD WERE SELECTED AMONG ARTICLES PUBLISHED ON PUBMED OVER THE LAST 20 YEARS, USING THE SEARCH TERM VITD STATUS, IN COMBINATION WITH PREGNANCY, OFFSPRING HEALTH, CHILD OUTCOMES, AND PROGRAMMING. DATA SYNTHESIS: THE FOLLOWING ITEMS WERE ANALYZED: VID PHYSIOLOGY AND METABOLISM, RISK FACTORS FOR VDD AND IMPLICATIONS IN PREGNANCY, LACTATION AND INFANCY, CONCENTRATION CUTOFF TO DEFINE VDD, THE VARIABILITY OF METHODS FOR VDD DETECTION, RECOMMENDATIONS ON VID REPLACEMENT IN PREGNANT WOMEN, THE NEWBORN AND THE CHILD, AND THE EPIGENETIC INFLUENCE OF VID. CONCLUSIONS: VDD IS A COMMON CONDITION AMONG HIGH-RISK PREGNANT WOMEN AND THEIR CHILDREN. THE ROUTINE MONITORING OF SERUM 25(OH)D3 LEVELS IN ANTENATAL PERIOD IS MANDATORY. EARLY PREVENTIVE MEASURES SHOULD BE TAKEN AT THE SLIGHTEST SUSPICION OF VDD IN PREGNANT WOMEN, TO REDUCE MORBIDITY DURING PREGNANCY AND LACTATION, AS WELL AS ITS SUBSEQUENT IMPACT ON THE FETUS, THE NEWBORN AND THE CHILD. 2015 10 4809 23 OBESITY PREVENTION. ONCE CONSIDERED A PROBLEM ONLY IN HIGH-INCOME COUNTRIES (HICS), OBESITY HAS BECOME A MAJOR CONTRIBUTOR TO THE GLOBAL DISEASE BURDEN (FINUCANE AND OTHERS 2011; MISRA AND KHURANA 2008). EXCESS ADIPOSITY, PARTICULARLY AROUND THE VISCERAL ABDOMINAL REGION, IS AN IMPORTANT RISK FACTOR FOR MORBIDITY AND MORTALITY FROM TYPE 2 DIABETES, CARDIOVASCULAR DISEASES, AND SOME CANCERS (DANAEI AND OTHERS 2009; WHITLOCK AND OTHERS 2009; WHO 2009). ALTHOUGH SOME STUDIES HAVE SUGGESTED LOWER MORTALITY AMONG OVERWEIGHT OR OBESE PERSONS THAN AMONG HEALTHY-WEIGHT PERSONS (CARNETHON AND OTHERS 2012), THIS OUTCOME HAS NOT BEEN OBSERVED IN STUDIES THAT PROPERLY ACCOUNT FOR THE CONFOUNDING EFFECTS OF SMOKING, PREEXISTING CHRONIC CONDITIONS, AND OTHER BIASES (GLOBAL BMI MORTALITY COLLABORATION 2016; TOBIAS, PAN, AND HU 2014). THE COSTS OF OBESITY AND COMORBID CONDITIONS ARE STAGGERING AS MEASURED BY BOTH HEALTH CARE EXPENDITURES AND QUALITY OF LIFE, UNDERSCORING THE IMPORTANCE OF IMPLEMENTING OBESITY PREVENTION STRATEGIES AND TREATMENT STRATEGIES ON A GLOBAL SCALE. THE CHANGES NEEDED TO REVERSE GLOBAL TRENDS IN OBESITY WILL LIKELY REQUIRE NUMEROUS INTERVENTIONS AND POLICY RECOMMENDATIONS THAT TARGET DIET, LIFESTYLE, ACCESS TO CARE, AND ENVIRONMENTAL RISK FACTORS. IN THIS CHAPTER, WE SUMMARIZE THE GLOBAL BURDEN OF OBESITY AND THE IMPACT OF A SPECTRUM OF OBESITY RISK FACTORS, RANGING FROM SOCIOPOLITICAL AND ECONOMIC FORCES THAT ARE LARGELY BEYOND AN INDIVIDUAL'S CONTROL TO MODIFIABLE LIFESTYLE FACTORS, AND DISCUSS GENETIC AND EPIGENETIC RISKS. WE ALSO REVIEW THE EFFECTIVENESS OF POPULATION-BASED INTERVENTIONS AND POLICIES FOR PREVENTING OBESITY, SOME INDIVIDUAL-LEVEL TREATMENT OPTIONS ACROSS VARIOUS PLATFORMS, AND THE COST-EFFECTIVENESS OF SELECT INTERVENTIONS. 2017 11 6433 23 THE VINDICATION OF LAMARCK? EPIGENETICS AT THE INTERSECTION OF LAW AND MENTAL HEALTH. RESEARCH ON EPIGENETIC MECHANISMS IS GAINING TRACTION, YET IS POORLY UNDERSTOOD BY CRIMINOLOGISTS AND BEHAVIORAL SCIENTISTS. THE CURRENT OBJECTIVE IS TO REVIEW RELEVANT STUDIES OF INTEREST TO BEHAVIORAL SCIENTISTS WHO STUDY CRIME, AND TO TRANSLATE ADMITTEDLY CHALLENGING SCIENTIFIC INFORMATION INTO TEXT THAT IS DIGESTIBLE TO THE AVERAGE CRIMINOLOGIST. USING SYSTEMATIC SEARCH PROCEDURES THE AUTHORS IDENTIFIED AND REVIEWED 41 STUDIES OF EPIGENETIC MECHANISMS IN PSYCHIATRIC AND BEHAVIORAL PHENOTYPES AMONG HUMANS. FINDINGS REVEALED SIGNIFICANT EPIGENETIC EFFECTS IN AN ASSORTMENT OF GENES THAT ARE IMPLICATED IN THE ETIOLOGY OF DEPRESSION, SUICIDALITY, CALLOUS-UNEMOTIONAL TRAITS, AND CHRONIC AND INTERGENERATIONAL AGGRESSIVE BEHAVIOR. SEVERAL POLYMORPHISMS THAT MEDIATE THE HPA AXIS, NEUROTRANSMISSION, IMMUNE RESPONSE, BRAIN DEVELOPMENT, SEROTONIN SYNTHESIS, AND OTHER PROCESSES WERE FOUND. ALTHOUGH PRESCRIPTIVE KNOWLEDGE BASED ON EPIGENETIC FINDINGS TO DATE IS PREMATURE, EPIGENETICS IS A NEW AND EXCITING SCIENTIFIC FRONTIER NOT TOO DIFFERENT IN SPIRIT FROM LAMARCK'S OBSERVATIONS CENTURIES AGO. 2015 12 1145 25 CONCURRENT DIAGNOSIS OF ADENOMYOSIS AND CONGENITAL UTERINE ANOMALIES: A REVIEW. BACKGROUND: ADENOMYOSIS AND CONGENITAL UTERINE ANOMALIES (CUAS) CAN COMPROMISE REPRODUCTIVE POTENTIAL AND MAY COEXIST IN THE SAME PATIENT, ESPECIALLY IN CASES OF INFERTILITY. THIS REVIEW (CRD42022382850) AIMS TO EVALUATE THE PUBLISHED CASES OF CONCURRENT ADENOMYOSIS AND SYNDROMIC AND NONSYNDROMIC CUAS. METHODS: A LITERATURE SEARCH FOR SUITABLE ARTICLES PUBLISHED IN THE ENGLISH LANGUAGE WAS PERFORMED USING THE FOLLOWING DATABASES FROM INCEPTION TO 30 NOVEMBER 2022: MEDLINE, EMBASE, GLOBAL HEALTH, THE COCHRANE LIBRARY, HEALTH TECHNOLOGY ASSESSMENT DATABASE, AND WEB OF SCIENCE. ARTICLES INCLUDING BOTH CUAS AND ADENOMYOSIS, WITH DATA ABOUT THEIR POTENTIAL RELATIONSHIP, WERE INCLUDED. RESULTS: THE LITERATURE SEARCH RETRIEVED 14 ARTICLES THAT MET THE PURPOSE OF THIS REVIEW AND SUMMARIZED THE MOST RECENT FINDINGS REGARDING THE CONCURRENT DIAGNOSIS OF ADENOMYOSIS AND CUAS. CONCLUSIONS: ADENOMYOSIS CAN BE FOUND IN BOTH SYNDROMIC AND NONSYNDROMIC CUAS, AND MAY ARISE FROM SEVERAL ETIOLOGIES. THE HYPOTHESIS THAT OBSTRUCTIONS IN CUAS INCREASE UTERINE PRESSURE AND PROMOTE THE DEVELOPMENT OF ADENOMYOSIS REMAINS TO BE FURTHER ELUCIDATED, AND ADDITIONAL FINDINGS MAY ALSO PLAY A ROLE. THE PATIENT'S GENETIC, EPIGENETIC, AND HORMONAL PATTERNS, AS WELL AS NORMAL PHYSIOLOGICAL PROCESSES, SUCH AS PREGNANCY, MAY INFLUENCE THE GROWTH OF ADENOMYOSIS. 2023 13 5154 24 PRAKRITI-BASED MEDICINE: A STEP TOWARDS PERSONALIZED MEDICINE. THE CONCEPT OF PERSONALIZED MEDICINE HAS BEEN AROUND FOR AS LONG AS PEOPLE HAVE BEEN PRACTICING MEDICINE. FROM CHARAKA TO HIPPOCRATES, ALL HAVE PRACTICED THE PERSONALIZED APPROACH FOR TREATING A DISEASE. IN THE 21(ST) CENTURY, PERSONALIZED MEDICINE IS ALL ABOUT DNA. WHEREAS THE SINGLE NUCLEOTIDE POLYMORPHISM (SNP) AND EPIGENETIC FACTORS INFLUENCE DRUG RESPONSE AND FORM THE BASIS OF PERSONALIZED MEDICINE, THE TRIDOSHA THEORY FORMS THE BASIS OF PRAKRITI-BASED MEDICINE. IT IS WELL ESTABLISHED BY NOW THAT WESTERN ALLOPATHIC MEDICINE IS EXCELLENT IN HANDLING ACUTE MEDICAL CRISES, WHEREAS AYURVEDA HAS SUCCESSFULLY DEMONSTRATED AN ABILITY TO MANAGE CHRONIC DISORDERS THAT WESTERN MEDICINE HAS BEEN UNABLE TO CURE. WITH EFFECTIVE INTEGRATION OF 'OMICS' PRAKRITI-BASED MEDICINE CAN PLAY A VITAL ROLE IN THIS CHANGING SCENARIO OF GLOBAL HEALTH WISDOM AS AYURVEDA OFFERS ITS MODALITIES BY WAY OF AHARA (DIET), VIHARA (LIFESTYLE), AND AUSHADHI (MEDICATION), WHICH ARE THE THREE PILLARS OF PRAKRITI-BASED MEDICINE MAKING IT A HOLISTIC SCIENCE. PRAKRITI-BASED MEDICINE AND OTHER TRADITIONAL MEDICINE SYSTEMS HAVE THE POTENTIAL TO OFFER REMEDIES TO THE CHALLENGING HEALTH ISSUES LIKE ADVERSE DRUG REACTIONS, DRUG WITHDRAWALS, AND ECONOMIC DISPARITIES AMONG FEW. AN INTEGRATIVE GLOBAL APPROACH COULD DO WONDERS TO HEALTH SCIENCES BENEFITING A BROAD SPECTRUM OF PATIENTS. 2011 14 3116 23 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 15 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 16 6911 21 [TWO GERMAN BIRTH COHORTS: GINIPLUS AND LISAPLUS]. NUMEROUS CHRONIC DISEASES IN CHILDHOOD AND ADULTHOOD HAVE THEIR ORIGINS IN PERINATAL LIFE AND ARE POTENTIALLY INFLUENCED BY TRANS-GENERATIONAL EPIGENETIC PROCESSES. THEREFORE, PROSPECTIVE BIRTH COHORTS CAN SUBSTANTIALLY CONTRIBUTE TO OUR KNOWLEDGE ABOUT THE ETIOLOGY OF DISEASES INCLUDING MODIFIABLE RISK FACTORS. THE TWO POPULATION-BASED GERMAN BIRTH COHORTS GINIPLUS AND LISAPLUS AIM TO DESCRIBE THE NATURAL COURSE OF CHRONIC DISEASES AND INTERMEDIATE PHENOTYPES IN CHILDHOOD AND ITS DETERMINANTS, AND TO IDENTIFY POTENTIAL GENETIC EFFECT MODIFICATIONS. IN THE MID-1990S, 5,991 (GINIPLUS) AND 3,097 (LISAPLUS) HEALTHY, TERM NEWBORNS WERE RECRUITED FOR LONG-TERM FOLLOW-UP IN FOUR REGIONS OF GERMANY. THE FOLLOW-UP RATE FOR THE FIRST 10 YEARS WAS ABOUT 55%. WE ANALYZED THE GROWTH AND DEVELOPMENT OF OVERWEIGHT, INFECTIONS AND ALLERGIC DISEASES, MENTAL AND ORAL HEALTH, METABOLIC AND INFLAMMATORY PARAMETERS AND THE ROLE OF POTENTIAL RISK FACTORS INCLUDING GENETICS. THE RESULTS OF THESE TWO BIRTH COHORTS SUBSTANTIALLY CONTRIBUTE TO THE CURRENT KNOWLEDGE ABOUT THE NATURAL COURSE OF THESE HEALTH PARAMETERS. THESE DATA WERE INCLUDED IN MANY INTERNATIONAL PROJECTS AND CONSORTIA FOR PURPOSES OF INTERNATIONAL COMPARISONS OF PREVALENCE AND CONSISTENCY OF FINDINGS, AND TO INCREASE THE POWER OF THE ANALYSES. 2012 17 4509 28 MSELENI JOINT DISEASE: A POTENTIAL MODEL OF EPIGENETIC CHONDRODYSPLASIA. OBJECTIVE: IN THIS PAPER PAST RESEARCH ON THE NATURAL HISTORY OF MSELENI JOINT DISEASE, A CRIPPLING ENDEMIC OSTEOARTHRITIS, ITS SOCIO-ECONOMIC IMPACTS, THE DEMOGRAPHICS, DIET, GEOLOGY AND THE GENETIC BACKGROUND OF AFFECTED PEOPLE ARE REVIEWED. IN ADDITION, SOME NEW RESEARCH IDEAS ARE SUGGESTED TO CONTINUE THE SEARCH FOR ETIOLOGICAL AVENUES FOR THIS DISEASE SUCH AS STABLE ISOTOPE ANALYSIS AND EPIGENETIC MECHANISMS. RESULTS: MSELENI JOINT DISEASE IS A CHONDRODYSPLASIA FIRST DESCRIBED IN 1970. IT IS GEOGRAPHICALLY CONFINED TO A REMOTE AREA IN THE MAPUTALAND REGION IN NORTHERN KWAZULU NATAL, SOUTH AFRICA. THIS DISEASE AFFECTS MOST JOINTS BUT PRIMARILY THOSE OF THE HIP; IT IS A PROGRESSIVE CONDITION BEGINNING WITH PAIN AND STIFFNESS UNTIL THE PATIENT'S ABILITY TO WALK BECOMES COMPROMISED. MSELENI JOINT DISEASE IS CHARACTERIZED BY TWO DISTINCT ABNORMALITIES, PROTRUSIO ACETABULI THAT MAINLY AFFECTS FEMALES AND INCREASES IN FREQUENCY WITH AGE, AND HIP DYSPLASIA THAT IS MORE FREQUENT WITH AGE. MUCH RESEARCH HAS BEEN CONDUCTED ON THE PEOPLE WITH THE DISEASE AND THEIR SURROUNDING ENVIRONMENT. CONCLUSION: DESPITE INTENSIVE INVESTIGATIONS INTO THE ETIOLOGY OF MSELENI JOINT DISEASE, IT REMAINS UNKNOWN. AS A RESULT THE EXAMINATION OF EPIGENETIC MECHANISMS AND STABLE ISOTOPE ANALYSIS OF TEETH ARE SUGGESTED AS A MEANS OF PROVIDING INFORMATION ON THE ETIOLOGY OF THE DISEASE. THESE METHODS CAN ALSO BE APPLIED TO OTHER CHONDROPLASIAS OF UNKNOWN ETIOLOGY. 2010 18 464 29 ARE HEIGHT AND LEG LENGTH UNIVERSAL MARKERS OF CHILDHOOD CONDITIONS? THE GUANGZHOU BIOBANK COHORT STUDY. OBJECTIVE: IN DEVELOPED WESTERN POPULATIONS LONGER LEGS HAVE BEEN SHOWN TO BE A MARKER OF BETTER EARLY CHILDHOOD CONDITIONS. IN THE FIRST GENERATIONS TO EXPERIENCE THE EPIDEMIOLOGIC TRANSITION AND ASSOCIATED ECONOMIC DEVELOPMENT, EPIGENETIC CONSTRAINTS ON GROWTH MIGHT PRECLUDE IMPROVED CHILDHOOD CONDITIONS FROM INCREASING LEG GROWTH OR HEIGHT. DESIGN, SETTING AND PARTICIPANTS: MULTIVARIABLE LINEAR REGRESSION WAS USED TO ASSESS THE ASSOCIATION OF PARENTAL GROWTH ENVIRONMENT, PROXIED BY PARENTAL LITERACY, AND CHILDHOOD CONDITIONS, PROXIED BY PARENTAL POSSESSIONS, WITH LEG LENGTH, SITTING HEIGHT AND HEIGHT IN A CROSS-SECTIONAL SAMPLE FROM 2005-6 OF 9998 CHINESE PEOPLE AGED AT LEAST 50 YEARS FROM PHASE 2 OF THE GUANGZHOU BIOBANK COHORT STUDY. MAIN RESULTS: ADJUSTED FOR AGE AND SEX, THE ASSOCIATION OF CHILDHOOD CONDITIONS WITH LEG LENGTH AND HEIGHT VARIED WITH PARENTAL LITERACY (INTERACTION P VALUES <0.01 AND 0.03), BUT NOT FOR SITTING HEIGHT (P VALUE 0.43), WITH STATISTICALLY SIGNIFICANT TRENDS (P VALUES <0.01) FOR PARENTAL POSSESSIONS TO BE ASSOCIATED WITH LONGER LEGS AND GREATER HEIGHT ONLY IN THE OFFSPRING OF TWO LITERATE PARENTS WHERE LEGS WERE LONGER BY 0.56 CM (95% CI 0.27 TO 0.86) AND HEIGHT GREATER BY 1.16 CM (95% CI 0.74 TO 1.58) FOR PARTICIPANTS WITH MOST, COMPARED WITH LEAST, PARENTAL POSSESSIONS IN CHILDHOOD. CONCLUSIONS: EPIGENETIC INFLUENCES ORIGINATING IN EARLIER GENERATIONS MAY CONSTRAIN GROWTH DURING THE INFANCY AND/OR CHILDHOOD PHASES IN VERY RECENTLY DEVELOPED POPULATIONS. NEITHER HEIGHT NOR LEG LENGTH SHOULD BE ASSUMED TO BE CONSISTENT PROXIES OF EARLY LIFE ENVIRONMENT WITH CORRESPONDING IMPLICATIONS FOR ECONOMIC HISTORY, THE AETIOLOGY OF SOME CHRONIC DISEASES AND THE MONITORING OF POPULATION HEALTH. 2008 19 1386 32 DIABETES: AN UPDATE ON THE PANDEMIC AND POTENTIAL SOLUTIONS. DIABETES MELLITUS IS A CHRONIC METABOLIC DISEASE WITH DEADLY, DISABLING, AND COSTLY CONSEQUENCES FOR INDIVIDUALS, FAMILIES, COMMUNITIES, AND COUNTRIES. ALTHOUGH THEY ARE PHENOTYPICALLY DISTINCT, DIABETES SUBTYPES (TYPE 1, TYPE 2, GESTATIONAL, AND OTHER FORMS) ARE ALL DEFINED BY ELEVATED BLOOD GLUCOSE LEVELS. APPROXIMATELY 95 PERCENT OF DIABETES CASES WORLDWIDE ARE TYPE 2 DIABETES (PREVIOUSLY KNOWN AS ADULT-ONSET OR NON-INSULIN-DEPENDENT DIABETES), WHICH IS THE FOCUS OF THIS CHAPTER. TYPE 1 DIABETES (PREVIOUSLY KNOWN AS INSULIN-DEPENDENT DIABETES) MOST COMMONLY BEGINS IN CHILDHOOD AND ADOLESCENCE. GESTATIONAL DIABETES REFERS TO ELEVATED BLOOD GLUCOSE LEVELS DURING PREGNANCY AMONG WOMEN WITHOUT PREVIOUS DIABETES AND IS ASSOCIATED WITH FETAL, BIRTHING, AND EARLY CHILDHOOD COMPLICATIONS AS WELL AS HIGHER RISK OF THE MOTHER DEVELOPING POSTGESTATION DIABETES. THE GROWTH OF DIABETES AND ITS IMPACTS HAVE ACCELERATED WORLDWIDE SINCE THE END OF THE TWENTIETH CENTURY (NCD-RISC 2016), LIKELY CORRELATED WITH EXPANSION OF DIABETES RISK FACTORS, ESPECIALLY POPULATION AGING AND OBESITY. DIABETES IS A MULTIFACTORIAL CONDITION. BECAUSE GENETIC, EPIGENETIC, LIFESTYLE, ECONOMIC, AND PSYCHOSOCIAL FACTORS ALL CONTRIBUTE TO THE DEVELOPMENT OF DIABETES (MCCARTHY 2010; STUMVOLL, GOLDSTEIN, AND VAN HAEFTEN 2005), PREVENTING AND MANAGING THE CONDITION REQUIRE ACTION AT POLICY, PROGRAM, CLINICAL PRACTICE, AND INDIVIDUAL LEVELS (HILL AND OTHERS 2013). RELIABLE AND MEANINGFUL ESTIMATES OF BURDENS, RISK FACTORS, AND EFFECTIVENESS AND COST-EFFECTIVENESS OF INTERVENTIONS AS WELL AS EVALUATIONS OF EXISTING POLICIES, ARE LIMITED; DATA ARE ESPECIALLY SCARCE IN LOW- AND MIDDLE-INCOME COUNTRIES (LMICS). THIS CHAPTER FOCUSES ON WHAT CAN AND SHOULD BE DONE TO ADDRESS DIABETES. WE PRESENT THE AVAILABLE DATA REGARDING GLOBAL BURDENS AND TRENDS IN DIABETES; REVIEW AVAILABLE EVIDENCE AND ASSESS THE EFFECTIVENESS AND COST-EFFECTIVENESS OF INTERVENTIONS TO PREVENT, DETECT, AND CONTROL DIABETES; AND REPORT SUMMARY EXPERT OPINIONS REGARDING THE PRIORITY AND FEASIBILITY OF IMPLEMENTING THESE INTERVENTIONS. ASSIMILATING EVIDENCE FROM COUNTRIES AT DIFFERENT INCOME LEVELS, WE PROVIDE GLOBAL PERSPECTIVES ON THE DIABETES PANDEMIC, RECOMMEND PRIORITY INTERVENTIONS, AND IDENTIFY REMAINING DATA GAPS. 2017 20 6815 16 [EVOLUTIONARY ONTOGENETIC ASPECTS OF PATHOGENETICS OF CHRONIC HUMAN DISEASES]. THIS ARTICLE IS A REVIEW OF SCIENTIFIC PUBLICATIONS, IN WHICH ISSUES OF PATHOGENETICS OF MULTIFACTORIAL DISEASES (MFDS) ARE CONSIDERED FROM THE VIEWPOINT OF EVOLUTION AND ONTOGENY. CONCEPTS EXPLAINING SIGNIFICANCE OF EVOLUTIONARY PROCESSES IN THE FORMATION OF GENETIC ARCHITECTURE OF HUMAN CHRONIC DISEASES ("THRIFTY" GENOMES AND PHENOTYPES, "DRIFTING GENES," DECANALIZATION) ARE ANALYZED. THE ROLES OF NATURAL SELECTION AND GENETIC DRIFT IN THE FORMATION OF HEREDITARY DIVERSITY OF GENES FOR SUSCEPTIBILITY TO MFDS ARE CONSIDERED. THE MODERN CONCEPT OF DISEASE ONTOGENY (SOMATIC MOSAICISM, LOSS OFHETEROZYGOSITY, PARADOMINANT INHERITANCE, EPIGENETIC VARIABILITY) IS DISCUSSED. IT IS DEMONSTRATED THAT THE EVOLUTIONARY AND ONTOGENETIC APPROACHES TO ANALYSIS OF GENIMUC AND OTHER "-OMIC" DATA ARE ESSENTIAL FOR UNDERSTANDING THE BIOLOGY OF DISEASES. 2011