1 6507 58 TRAINING VOCATIONAL REHABILITATION COUNSELORS WHO WORK WITH CHRONIC MENTAL PATIENTS. BECAUSE OF THE INEFFICACY OF DISPARATE PSYCHIATRIC AND REHABILITATIVE APPROACHES TO PSYCHOSOCIAL RESTORATION OF CHRONIC MENTAL PATIENTS, THE AUTHORS DESIGNED THE NEW ENGLAND PSYCHIATRIC REHABILITATION TRAINING PROGRAM FOR VOCATIONAL REHABILITATION COUNSELORS WHO WORK WITH THESE PATIENTS. THE PROGRAM EXTENDS ERIKSON'S EPIGENETIC SEQUENCE TO DEVELOPMENT OF WORK CAPACITY AND EMPHASIZES A COMPREHENSIVE, MULTIAXIAL APPROACH TO PSYCHOPATHOLOGY AND VOCATIONAL REHABILITATION. AFTER 6 WEEKS OF SEMINARS, CLINICAL WORK, AND SUPERVISION, COUNSELORS RETURN TO THEIR AGENCIES AND RECEIVE AN ADDITIONAL 8 WEEKS OF PART-TIME SUPPORT FROM FIELD FACULTY INSTRUCTORS.	1981	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
2 6769 14 ["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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
3 6911 11 [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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
4 6433 15 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
5 3899 15 LATE NEUROLOGICAL CONSEQUENCES OF ZIKA VIRUS INFECTION: RISK FACTORS AND PHARMACEUTICAL APPROACHES. ZIKA VIRUS (ZIKV) INFECTION WAS HISTORICALLY CONSIDERED A DISEASE WITH MILD SYMPTOMS AND NO MAJOR CONSEQUENCES TO HUMAN HEALTH. HOWEVER, SEVERAL LONG-TERM, LATE ONSET, AND CHRONIC NEUROLOGICAL COMPLICATIONS, BOTH IN CONGENITALLY-EXPOSED BABIES AND IN ADULT PATIENTS, HAVE BEEN REPORTED AFTER ZIKV INFECTION, ESPECIALLY AFTER THE 2015 EPIDEMICS IN THE AMERICAN CONTINENT. THE DEVELOPMENT OR SEVERITY OF THESE CONDITIONS CANNOT BE FULLY PREDICTED, BUT IT IS POSSIBLE THAT GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS MAY CONTRIBUTE TO DETERMINE ZIKV INFECTION OUTCOMES. THIS REINFORCES THE IMPORTANCE THAT INDIVIDUALS EXPOSED TO ZIKV ARE SUBMITTED TO LONG-TERM CLINICAL SURVEILLANCE AND HIGHLIGHTS THE URGENT NEED FOR THE DEVELOPMENT OF THERAPEUTIC APPROACHES TO REDUCE OR ELIMINATE THE NEUROLOGICAL BURDEN OF INFECTION. HERE, WE REVIEW THE EPIDEMIOLOGY OF ZIKV-ASSOCIATED NEUROLOGICAL COMPLICATIONS AND THE ROLE OF FACTORS THAT MAY INFLUENCE DISEASE OUTCOME. MOREOVER, WE DISCUSS EXPERIMENTAL AND CLINICAL EVIDENCE OF DRUGS THAT HAVE SHOWN PROMISING RESULTS IN VITRO OR IN VITRO AGAINST VIRAL REPLICATION AND AND/OR ZIKV-INDUCED NEUROTOXICITY.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
6 4834 13 ON THE INTERPLAY BETWEEN THE MEDICINE OF HILDEGARD OF BINGEN AND MODERN MEDICINE: THE ROLE OF ESTROGEN RECEPTOR AS AN EXAMPLE OF BIODYNAMIC INTERFACE FOR STUDYING THE CHRONIC DISEASE'S COMPLEXITY. INTRODUCTION: HILDEGARD OF BINGEN (1098-1179) INTERPRETED THE ORIGINS OF CHRONIC DISEASE HIGHLIGHTING AND ANTICIPATING, ALTHOUGH ONLY IN A LIMITED FASHION, THE IMPORTANCE THAT COMPLEX INTERACTIONS AMONG NUMEROUS GENETIC, INTERNAL MILIEU AND EXTERNAL ENVIRONMENTAL FACTORS HAVE IN DETERMINING THE DISEASE PHENOTYPE. TODAY, WE RECOGNIZE THOSE FACTORS, CAPABLE OF MEDIATING THE TRANSMISSION OF MESSAGES BETWEEN HUMAN BODY AND ENVIRONMENT AND VICE VERSA, AS BIODYNAMIC INTERFACES. AIM: WE ANALYZED, IN THE LIGHT OF MODERN SCIENTIFIC EVIDENCE, HILDEGARD OF BINGEN'S MEDICAL APPROACH AND HER ORIGINAL HUMORAL THEORY IN ORDER TO IDENTIFY POSSIBLE INSIGHTS INCLUDED IN HER MEDICINE THAT COULD BE REFERRED TO IN THE CONTEXT OF MODERN EVIDENCE-BASED MEDICINE. IN PARTICULAR, THE ABBESS'S HUMORAL THEORY SUGGESTS THE IDENTIFICATION OF BIODYNAMIC INTERFACES WITH SEX HORMONES AND THEIR RECEPTORS. FINDINGS: WE FOUND THAT THE HILDEGARDIAN HOLISTIC VISION OF THE ORGANISM-ENVIRONMENT RELATIONSHIP CAN ACTUALLY REPRESENT A VISIONARY APPROACH TO MODERN ENDOCRINOLOGY AND THAT SEX HORMONES, IN PARTICULAR ESTROGENS, COULD REPRESENT AN EXAMPLE OF A BIODYNAMIC INTERFACE. ESTROGEN RECEPTORS ARE FOUND IN REGIONS OF THE BRAIN INVOLVED IN EMOTIONAL AND COGNITIVE REGULATION, CONTROLLING THE MOLECULAR MECHANISM OF BRAIN FUNCTION. ESTROGEN RECEPTORS ARE INVOLVED IN THE REGULATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS AND IN THE EPIGENETIC REGULATION OF RESPONSES TO PHYSIOLOGICAL, SOCIAL, AND HORMONAL STIMULI. FURTHERMORE, ESTROGEN AFFECTS GENE METHYLATION ON ITS OWN AND RELATED RECEPTOR PROMOTERS IN DISCRETE REGIONS OF THE DEVELOPING BRAIN. THIS SCENARIO WAS STRIKINGLY PERCEIVED BY THE ABBESS IN THE XIITH CENTURY, AND DEPICTED AS A COMPLEX INTERPLAY AMONG DIFFERENT HUMORS AND FLEGMATA THAT SHE RECOGNIZED TO BE SEX SPECIFIC AND ENVIRONMENTALLY REGULATED. VIEWPOINT: CONSIDERING THE FUNCTION PLAYED BY HORMONES, ANALYZED THROUGH THE LAST SCIENTIFIC EVIDENCE, AND SCIENTIFIC LITERATURE ON BIODYNAMIC INTERFACES, WE COULD SUGGEST HILDEGARDIAN INSIGHTS AND THEORIES AS THE FIRST ATTEMPT TO DESCRIBE THE MODERN HOLISTIC, SEX-BASED MEDICINE. CONCLUSION: HILDEGARD ANTICIPATED A CONCEPT OF PATHOGENESIS THAT SEES A CENTRAL ROLE FOR ENDOCRINOLOGY IN SEX-SPECIFIC DISEASE. FURTHERMORE, ESTROGENS AND ESTROGEN RECEPTORS COULD REPRESENT A GOOD EXAMPLE OF MOLECULAR INTERFACES CAPABLE OF MODULATING THE INTERACTION BETWEEN THE ORGANISM INTERNAL MILIEU AND THE ENVIRONMENTAL FACTORS.	2022	

7 6785 14 [CONFLICT MEDIATION: AN ADDITIONAL OPTION FOR THE MEDICAL PRACTITIONER]. CHRONIC STRESS AFFECTS THE INDIVIDUAL AND OFFSPRING THROUGH A COMBINATION OF SOCIAL, GENETIC AND EPIGENETIC FACTORS THAT PREDISPOSE TO VARIOUS ILLNESSES. FURTHERMORE, CONFLICT UNFAVORABLY AFFECTS MENTALIZATION WHICH WOULD HELP ITS RESOLUTION. THE PSYCHOPHYSIOLOGICAL PARAMETERS OF STRESS DROP WHEN AN INDIVIDUAL GOES FROM THE STATE OF UNFORGIVENESS TO THAT OF FORGIVENESS AND THIS IS COMPARABLE TO THE FEELING OF RELIEF EXPERIENCED AFTER A SUCCESSFUL MEDIATION. THE AUTHOR BRIEFLY ILLUSTRATES CONFLICT MEDIATION FROM A PSYCHODYNAMIC POINT OF VIEW. THE MEDIATION PROCESS INSCRIBES ITSELF IN A PROLONGATION OF FREUD'S KULTURARBEIT. THE AUTHOR CONCLUDES THAT THE MEDICAL PRACTITIONER COULD IDENTIFY PATIENTS WHOSE AILMENTS ARE DIRECTLY RELATED TO EXPERIENCING RECENT CONFLICT AND FOR WHOM CONFLICT MEDIATION COULD PROVE TO BE BENEFICIAL.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
8 5213 12 PRESYMPTOMATIC RISK ASSESSMENT FOR CHRONIC NON-COMMUNICABLE DISEASES. THE PREVALENCE OF COMMON CHRONIC NON-COMMUNICABLE DISEASES (CNCDS) FAR OVERSHADOWS THE PREVALENCE OF BOTH MONOGENIC AND INFECTIOUS DISEASES COMBINED. ALL CNCDS, ALSO CALLED COMPLEX GENETIC DISEASES, HAVE A HERITABLE GENETIC COMPONENT THAT CAN BE USED FOR PRE-SYMPTOMATIC RISK ASSESSMENT. COMMON SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) THAT TAG RISK HAPLOTYPES ACROSS THE GENOME CURRENTLY ACCOUNT FOR A NON-TRIVIAL PORTION OF THE GERM-LINE GENETIC RISK AND WE WILL LIKELY CONTINUE TO IDENTIFY THE REMAINING MISSING HERITABILITY IN THE FORM OF RARE VARIANTS, COPY NUMBER VARIANTS AND EPIGENETIC MODIFICATIONS. HERE, WE DESCRIBE A NOVEL MEASURE FOR CALCULATING THE LIFETIME RISK OF A DISEASE, CALLED THE GENETIC COMPOSITE INDEX (GCI), AND DEMONSTRATE ITS PREDICTIVE VALUE AS A CLINICAL CLASSIFIER. THE GCI ONLY CONSIDERS SUMMARY STATISTICS OF THE EFFECTS OF GENETIC VARIATION AND HENCE DOES NOT REQUIRE THE RESULTS OF LARGE-SCALE STUDIES SIMULTANEOUSLY ASSESSING MULTIPLE RISK FACTORS. COMBINING GCI SCORES WITH ENVIRONMENTAL RISK INFORMATION PROVIDES AN ADDITIONAL TOOL FOR CLINICAL DECISION-MAKING. THE GCI CAN BE POPULATED WITH HERITABLE RISK INFORMATION OF ANY TYPE, AND THUS REPRESENTS A FRAMEWORK FOR CNCD PRE-SYMPTOMATIC RISK ASSESSMENT THAT CAN BE POPULATED AS ADDITIONAL RISK INFORMATION IS IDENTIFIED THROUGH NEXT-GENERATION TECHNOLOGIES.	2010	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
9 5464 10 RESILIENCE IN LONG-TERM VIRAL INFECTION: GENETIC DETERMINANTS AND INTERACTIONS. VIRUS-INDUCED NEUROLOGICAL SEQUELAE RESULTING FROM INFECTION BY THEILER'S MURINE ENCEPHALOMYELITIS VIRUS (TMEV) ARE USED FOR STUDYING HUMAN CONDITIONS RANGING FROM EPILEPTIC SEIZURES TO DEMYELINATING DISEASE. MOUSE STRAINS ARE TYPICALLY CONSIDERED SUSCEPTIBLE OR RESISTANT TO TMEV INFECTION BASED ON VIRAL PERSISTENCE AND EXTREME PHENOTYPES, SUCH AS DEMYELINATION. WE HAVE IDENTIFIED A BROADER SPECTRUM OF PHENOTYPIC OUTCOMES BY INFECTING STRAINS OF THE GENETICALLY DIVERSE COLLABORATIVE CROSS (CC) MOUSE RESOURCE. WE EVALUATED THE CHRONIC-INFECTION GENE EXPRESSION PROFILES OF HIPPOCAMPI AND THORACIC SPINAL CORDS FOR 19 CC STRAINS IN RELATION TO PHENOTYPIC SEVERITY AND TMEV PERSISTENCE. STRAINS WERE CLUSTERED BASED ON SIMILAR PHENOTYPIC PROFILES AND TMEV LEVELS AT 90 DAYS POST-INFECTION, AND WE CATEGORIZED DISTINCT TMEV RESPONSE PROFILES. THE THREE MOST COMMON PROFILES INCLUDED "RESISTANT" AND "SUSCEPTIBLE," AS BEFORE, AS WELL AS A "RESILIENT" TMEV RESPONSE GROUP WHICH EXPERIENCED BOTH TMEV PERSISTENCE AND MILD NEUROLOGICAL PHENOTYPES EVEN AT 90 DAYS POST-INFECTION. EACH PROFILE HAD A DISTINCT GENE EXPRESSION SIGNATURE, ALLOWING THE IDENTIFICATION OF PATHWAYS AND NETWORKS SPECIFIC TO EACH TMEV RESPONSE GROUP. CC FOUNDER HAPLOTYPES FOR GENES INVOLVED IN THESE PATHWAYS/NETWORKS REVEALED CANDIDATE RESPONSE-SPECIFIC ALLELES. THESE ALLELES DEMONSTRATED PLEIOTROPY AND EPIGENETIC (MIRNA) REGULATION IN LONG-TERM TMEV INFECTION, WITH PARTICULAR RELEVANCE FOR RESILIENT MOUSE STRAINS.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
10 4019 12 LOW-DOSE OR LOW-DOSE-RATE IONIZING RADIATION-INDUCED BIOEFFECTS IN ANIMAL MODELS. ANIMAL EXPERIMENTAL STUDIES INDICATE THAT ACUTE OR CHRONIC LOW-DOSE IONIZING RADIATION (LDIR) (</=100 MSV) OR LOW-DOSE-RATE IONIZING RADIATION (LDRIR) (<6 MSV/H) EXPOSURES MAY BE HARMFUL. IT INDUCES GENETIC AND EPIGENETIC CHANGES AND IS ASSOCIATED WITH A RANGE OF PHYSIOLOGICAL DISTURBANCES THAT INCLUDES ALTERED IMMUNE SYSTEM, ABNORMAL BRAIN DEVELOPMENT WITH RESULTANT COGNITIVE IMPAIRMENT, CATARACTOGENESIS, ABNORMAL EMBRYONIC DEVELOPMENT, CIRCULATORY DISEASES, WEIGHT GAIN, PREMATURE MENOPAUSE IN FEMALE ANIMALS, TUMORIGENESIS AND SHORTENED LIFESPAN. PATERNAL OR PRENATAL LDIR/LDRIR EXPOSURE IS ASSOCIATED WITH REDUCED FERTILITY AND NUMBER OF LIVE FETUSES, AND TRANSGENERATIONAL GENOMIC ABERRATIONS. ON THE OTHER HAND, IN SOME EXPERIMENTAL STUDIES, LDIR/LDRIR EXPOSURE HAS ALSO BEEN REPORTED TO BRING ABOUT BENEFICIAL EFFECTS SUCH AS REDUCTION IN TUMORIGENESIS, PROLONGED LIFESPAN AND ENHANCED FERTILITY. THE DIFFERENCES IN REPORTED EFFECTS OF LDIR/LDRIR EXPOSURE ARE DEPENDENT ON ANIMAL GENETIC BACKGROUND (SUSCEPTIBILITY), AGE (PRENATAL OR POSTNATAL DAYS), SEX, NATURE OF RADIATION EXPOSURE (I.E. ACUTE, FRACTIONATED OR CHRONIC RADIATION EXPOSURE), TYPE OF RADIATION, COMBINATION OF RADIATION WITH OTHER TOXIC AGENTS (SUCH AS SMOKING, PESTICIDES OR OTHER CHEMICAL TOXINS) OR ANIMAL EXPERIMENTAL DESIGNS. IN THIS REVIEW PAPER, WE AIMED TO UPDATE RADIATION RESEARCHERS AND RADIOLOGISTS ON THE CURRENT PROGRESS ACHIEVED IN UNDERSTANDING THE LDIR/LDRIR-INDUCED BIONEGATIVE AND BIOPOSITIVE EFFECTS REPORTED IN THE VARIOUS ANIMAL MODELS. THE ROLES PLAYED BY A VARIETY OF MOLECULES THAT ARE IMPLICATED IN LDIR/LDRIR-INDUCED HEALTH EFFECTS WILL BE ELABORATED. THE REVIEW WILL HELP IN FUTURE INVESTIGATIONS OF LDIR/LDRIR-INDUCED HEALTH EFFECTS BY PROVIDING CLUES FOR DESIGNING IMPROVED ANIMAL RESEARCH MODELS IN ORDER TO CLARIFY THE CURRENT CONTROVERSIAL/CONTRADICTORY FINDINGS FROM EXISTING STUDIES.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
11 6087 15 THE EFFECTS OF AEROBIC AND ANAEROBIC EXERCISES ON CIRCULATING SOLUBLE-KLOTHO AND IGF-I IN YOUNG AND ELDERLY ADULTS AND IN CAD PATIENTS. DIFFERENT STUDIES SUPPORT THE NOTION THAT CHRONIC AEROBIC EXERCISES TRAINING CAN INFLUENCE THE CIRCULATING LEVELS OF SOLUBLE-KLOTHO (S-KLOTHO) AND INSULIN-LIKE GROWTH FACTOR 1 (IGF-I). THE EFFECTS OF S-KLOTHO INCLUDE IMPROVING THE QUALITY OF LIFE, ALLEVIATING THE NEGATIVE IMPACT OF AGE ON THE BODY'S WORK CAPACITY, AND POSSIBLY INCREASING LONGEVITY. THIS REVIEW PROVIDES AN OVERVIEW OF THE LATEST FINDINGS IN THIS FIELD OF RESEARCH IN HUMANS. THE DIFFERENT MODES OF DYNAMIC EXERCISE AND THEIR IMPACT ON CIRCULATING LEVELS OF S-KLOTHO AND IGF-I IN YOUNG ADULT ATHLETES, UNTRAINED YOUNG ADULTS, TRAINED HEALTHY OLDER ADULTS, UNTRAINED HEALTHY OLDER ADULTS, AND CORONARY ARTERY DISEASE (CAD) PATIENTS ARE REVIEWED AND DISCUSSED. TOGETHER THESE FINDINGS SUGGEST THAT LONG-LASTING (CHRONIC) AEROBIC EXERCISE TRAINING IS PROBABLY ONE OF THE ANTIAGING FACTORS THAT COUNTERACT THE AGING AND CAD PROCESS BY INCREASING THE CIRCULATING S-KLOTHO AND LOWERING THE IGF-I LEVELS. HOWEVER, FOLLOWING ANAEROBIC EXERCISE TRAINING THE OPPOSITE OCCURS. THE EXACT METABOLIC AND PHYSIOLOGICAL PATHWAYS INVOLVED IN THE ACTIVITY OF THESE WELL-TRAINED YOUNG AND MASTER SPORTSMEN SHOULD BE FURTHER STUDIED AND ELUCIDATED. THE PURPOSE OF THIS REVIEW WAS TO PROVIDE A CLARIFICATION REGARDING THE ROLES OF S-KLOTHO AND INTENSITIES AND DURATIONS OF DIFFERENT EXERCISE ON HUMAN HEALTH.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
12 6464 13 TISSUE MISREPAIR HYPOTHESIS FOR RADIATION CARCINOGENESIS. DOSE-RESPONSE CURVES FOR CHRONIC LEUKEMIA IN A-BOMB SURVIVORS AND LIVER TUMORS IN PATIENTS GIVEN THOROTRAST (COLLOIDAL THORIUM DIOXIDE) SHOW LARGE THRESHOLD EFFECTS. THE EXISTENCE OF THESE THRESHOLD EFFECTS CAN BE EXPLAINED BY THE FOLLOWING HYPOTHESIS. A HIGH DOSE OF RADIATION CAUSES A PERSISTENT WOUND IN A CELL-RENEWABLE TISSUE. DISORDER OF THE INJURED CELL SOCIETY PARTLY FREES THE COMPONENT CELLS FROM TERRITORIAL RESTRAINTS ON THEIR PROLIFERATION, ENABLING THEM TO CONTINUE DEVELOPMENT OF THEIR CELLULAR FUNCTIONS TOWARD ADVANCED AUTONOMY. THIS PROGRESSION MIGHT BE ACHIEVED BY CONTINUED EPIGENETIC AND GENETIC CHANGES AS A RESULT OF OCCASIONAL ERRORS IN THE OTHERWISE CONCERTED HEALING ACTION OF VARIOUS ENDOGENOUS FACTORS RECRUITED FOR TISSUE REPAIR. CARCINOGENESIS IS NOT SIMPLY A SINGLE-CELL PROBLEM BUT A CELL-SOCIETY PROBLEM. THEREFORE, IT IS NOT WARRANTED TO ESTIMATE RISK AT LOW DOSES BY LINEAR EXTRAPOLATION FROM CANCER DATA AT HIGH DOSES WITHOUT KNOWLEDGE OF THE MECHANISM OF RADIATION CARCINOGENESIS.	1991	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
13 6914 12 [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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
14  227 11 ADAPTATION OF AN OUTBREAKING INSECT DEFOLIATOR TO CHRONIC NUTRITIONAL STRESS. DURING INSECT OUTBREAKS, THE HIGH NUMBER OF INDIVIDUALS FEEDING ON ITS HOST PLANT CAUSES A DEPLETION OF THE FOOD SOURCE. REDUCED AVAILABILITY AND DECREASED QUALITY OF NUTRIENTS NEGATIVELY INFLUENCE LIFE-HISTORY TRAITS OF INSECTS DRIVING THEM TO DEVELOP ADAPTIVE STRATEGIES TO PERSIST IN THE ENVIRONMENT. IN A LABORATORY EXPERIMENT WITH THREE REPETITIONS, WE TESTED THE EFFECT OF CHRONIC NUTRITIONAL STRESS ON SPRUCE BUDWORM PERFORMANCE DURING THREE GENERATIONS TO DETERMINE THE ADAPTIVE STRATEGIES EMPLOYED BY THE INSECT TO DEAL WITH A SELECTION PRESSURE PRODUCED BY LOW-QUALITY DIET. OUR RESULTS SHOW THAT ALL TESTED LIFE-HISTORY TRAITS (MORTALITY, DEVELOPMENTAL TIME, PUPAL MASS, GROWTH RATE AND FEMALE FECUNDITY) BUT FEMALE FERTILITY WERE NEGATIVELY INFLUENCED BY THE LOW-QUALITY DIET SIMULATING FOOD DEPLETION DURING OUTBREAK CONDITIONS. HOWEVER, ESPECIALLY FEMALES IN THE THIRD GENERATION UNDER CHRONIC NUTRITIONAL STRESS SHOW AN ADAPTIVE RESPONSE IN LIFE-HISTORY TRAITS WHEN COMPARED TO THOSE REARED ONLY ONE GENERATION ON LOW-QUALITY DIET. LARVAL DEVELOPMENTAL TIME SIGNIFICANTLY DECREASED AND PUPAL MASS, GROWTH RATE AND FECUNDITY SIGNIFICANTLY INCREASED. THE STUDY DEMONSTRATES THE CAPACITY OF SPRUCE BUDWORM TO REACT TO CHRONIC NUTRITIONAL STRESS WITH ADAPTATIONS THAT MAY BE CAUSED BY EPIGENETIC PARENTAL EFFECTS. THIS INFORMATION CAN HELP TO UNDERSTAND THE COURSE OF AN OUTBREAK ESPECIALLY AT PEAK DENSITIES AND DURING THE COLLAPSE.	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
15 2603 20 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	
                                                                                                                                                                                                                                                                                                                                                                                                           
16 4624 15 NEUROBIOLOGY OF KB220Z-GLUTAMINERGIC-DOPAMINERGIC OPTIMIZATION COMPLEX [GDOC] AS A LIQUID NANO: CLINICAL ACTIVATION OF BRAIN IN A HIGHLY FUNCTIONAL CLINICIAN IMPROVING FOCUS, MOTIVATION AND OVERALL SENSORY INPUT FOLLOWING CHRONIC INTAKE. BACKGROUND: WITH NEUROGENETIC AND EPIGENETIC TOOLS UTILIZED IN RESEARCH AND NEUROIMAGING, WE ARE UNRAVELING THE MYSTERIES OF BRAIN FUNCTION, ESPECIALLY AS IT RELATES TO REWARD DEFICIENCY (RDS). WE ENCOURAGE THE DEVELOPMENT OF PHARMACEUTICALS OR NUTRACEUTICALS THAT PROMOTE A REDUCTION IN DOPAMINE RESISTANCE AND BALANCE BRAIN NEUROCHEMISTRY, LEADING TO DOPAMINE HOMEOSTASIS. WE DISCLOSE SELF-ASSESSMENT OF A HIGHLY FUNCTIONAL PROFESSIONAL UNDER WORK-RELATED STRESS FOLLOWING KB220Z USE, A LIQUID (AQUA) NANO GLUTAMINERGIC-DOPAMINERGIC OPTIMIZATION COMPLEX (GDOC). CASE PRESENTATION: SUBJECT TOOK GDOC FOR ONE MONTH. SUBJECT SELF-ADMINISTERED GDOC USING ONE-HALF-OUNCE TWICE A DAY. DURING FIRST THREE DAYS, UNIQUE BRAIN ACTIVATION OCCURRED; RESEMBLING WHITE NOISE AFTER 30 MINUTES AND SENSATION WAS STRONG FOR 45 MINUTES AND THEN DISSIPATED. HE DESCRIBED EFFECT AS IF HIS EYESIGHT IMPROVED SLIGHTLY AND POINTED OUT THAT HIS SENSE OF SMELL AND SLEEP GREATLY IMPROVED. SUBJECT EXPERIENCED A CALMING EFFECT SIMILAR TO MEDITATION THAT COULD BE LINKED TO DOPAMINE RELEASE. HE ALSO REPORTED CONTROL OF GOING OVER THE EDGE AFTER A HARD DAY'S WORK, WHICH WAS COUPLED WITH A SLIGHT INCREASE IN ENERGY, INCREASED MOTIVATION TO WORK, INCREASED FOCUS AND MULTI-TASKING, WITH CLEARER PURPOSE OF TASK AT HAND. SUBJECT FELT LESS INHIBITED IN A SOCIAL SETTING AND SUGGESTED SYNDROME THAT GDOC INCREASED HIS BEHAVIOR ACTIVATING SYSTEM (REWARD), WHILE HAVING A DECREASE IN THE BEHAVIOR INHIBITION SYSTEM (CAUTION). CONCLUSION: THESE RESULTS AND OTHER RELATED STUDIES REVEAL AN IMPROVED MOOD, WORK-RELATED FOCUS, AND SLEEP. THESE EFFECTS AS A SUBJECTIVE FEELING OF BRAIN ACTIVATION MAYBE DUE TO DIRECT OR INDIRECT DOPAMINERGIC INTERACTION. WHILE THIS CASE IS ENCOURAGING, WE MUST AWAIT MORE RESEARCH IN A LARGER RANDOMIZED PLACEBO-CONTROLLED STUDY TO MAP THE ROLE OF GDOC, ESPECIALLY IN A NANO-SIZED PRODUCT, TO DETERMINE THE POSSIBLE EFFECTS ON CIRCUIT INHIBITORY CONTROL AND MEMORY BANKS AND THE INDUCTION OF DOPAMINE HOMEOSTASIS INDEPENDENT OF EITHER HYPO- OR HYPER-DOPAMINERGIC TRAITS/STATES.	2016	
                                                                                                                                                                                                                                                                                                                                                        
17 6292 17 THE PRIMACY OF PSYCHOANALYTIC INTERVENTION IN RECOVERY FROM THE PSYCHOSES AND SCHIZOPHRENIAS. FUNCTIONAL CAPACITIES, SUCH AS ATTACHMENT AND AFFECT REGULATION, OBJECT RELATIONS CAPACITY, SYMBOLIC FUNCTION AND LANGUAGE DEVELOPMENT, NOW DOCUMENTED BY NEUROSCIENTIFIC RESEARCH AND EPIGENETICS, ARE REVIEWED. RESULTS FROM THIS RESEARCH, TOGETHER WITH OTHER FACTORS, ARE POSITED TO HAVE CONTRIBUTED TO EFFECTIVE CONTEMPORARY PSYCHOANALYTIC AND PSYCHOTHERAPEUTIC TREATMENTS FOR THE PSYCHOSES AND SCHIZOPHRENIAS. ETIOLOGICAL FACTORS INVOLVING THE SCHIZOPHRENIAS AND OTHER PSYCHOSES ARE CONSIDERED BOTH IN TERMS OF AN EPIGENETIC MODEL, AND IN TERMS OF HOW ETIOLOGY MAY, OR MAY NOT, AFFECT CLINICAL TREATMENT. THE LACANIAN 388 PROGRAM IS REVIEWED IN SOME DETAIL, AS ARE SEVERAL PSYCHOANALYTIC AND PSYCHOTHERAPEUTIC CLINICAL APPROACHES USED WITH THIS POPULATION OVER THE LAST SIX DECADES. ALL TREATMENTS FOCUS ON THE PRIMACY OF PSYCHOTHERAPEUTIC INTERVENTION, AND USE MEDICATIONS MINIMALLY, NOT AT ALL, OR ONLY AS INFORMED BY AN OVER-ARCHING PSYCHODYNAMIC MODEL OF TREATMENT. THE AUTHOR ARGUES THAT THERE IS NOW SUBSTANTIAL RESEARCH AND OUTCOME DATA SUGGESTING THAT THE PSYCHOSES AND SCHIZOPHRENIAS ARE NOT CHRONIC DETERIORATING CONDITIONS. RECOVERY IS OBSERVED IN MANY PSYCHOTIC AND SCHIZOPHRENIC PATIENTS TREATED WITH APPROACHES THAT FOCUS ON THE PRIMACY OF PSYCHOTHERAPEUTIC INTERVENTION.	2007	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
18 5087 12 PIMECROLIMUS FOR THE TREATMENT OF ATOPIC DERMATITIS IN INFANTS: AN ASIAN PERSPECTIVE. ATOPIC DERMATITIS (AD) IS A COMMON CHRONIC, MULTISYSTEM INFLAMMATORY SKIN DISEASE IN PEDIATRIC PATIENTS. THERE HAS BEEN AN INCREASE IN THE INCIDENCE OF AD IN THE PEDIATRIC POPULATION OF THE ASIA-PACIFIC REGION. STUDIES HAVE SHOWN THAT GENETIC, EPIGENETIC, ENVIRONMENTAL AND CULTURAL FACTORS MAY LEAD TO DIFFERENCES IN THE CLINICAL MANIFESTATION AND PREVALENCE OF AD BETWEEN RACES. EARLY TREATMENT OF AD IS NECESSARY TO PREVENT THE ATOPIC MARCH LEADING TO COMORBIDITIES SUCH AS ASTHMA AND ALLERGIC RHINITIS. TOPICAL CORTICOSTEROIDS (TCS) ARE USED AS FIRST-LINE THERAPY FOR THE TREATMENT OF AD, BUT THEIR LONG-TERM USAGE POSES A RISK TO THE PATIENT'S HEALTH. PIMECROLIMUS (1%) IS A TOPICAL CALCINEURIN INHIBITOR (TCI) THAT IS INDICATED FOR THE TREATMENT OF MILD TO MODERATE AD. PIMECROLIMUS HAS NO APPARENT INCREASE IN ADVERSE EVENTS COMPARED TO TCS, AND IT CAUSES LESS OF A BURNING SENSATION THAN TACROLIMUS. THE SAFETY AND EFFICACY OF PIMECROLIMUS HAS BEEN ESTABLISHED THROUGH VARIOUS CLINICAL TRIALS; YET, IN MANY ASIAN COUNTRIES, THE USE OF PIMECROLIMUS IN INFANTS IS STILL RESTRICTED DUE TO SAFETY CONCERNS. BASED ON THE AVAILABLE EVIDENCE, THE EXPERT PANEL RECOMMENDS PIMECROLIMUS IN INFANTS BETWEEN 3 MONTHS AND 2 YEARS OF AGE IN THE ASIAN POPULATION.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
19 2967 12 GENETIC AND EPIGENETIC REGULATION OF CATECHOL-O-METHYLTRANSFERASE IN RELATION TO INFLAMMATION IN CHRONIC FATIGUE SYNDROME AND FIBROMYALGIA. BACKGROUND: CATECHOL-O-METHYLTRANSFERASE (COMT) HAS BEEN SHOWN TO INFLUENCE CLINICAL PAIN, DESCENDING MODULATION, AND EXERCISE-INDUCED SYMPTOM WORSENING. COMT REGULATES NOCICEPTIVE PROCESSING AND INFLAMMATION, KEY PATHOPHYSIOLOGICAL FEATURES OF CHRONIC FATIGUE SYNDROME AND FIBROMYALGIA (CFS/FM). WE AIMED TO DETERMINE THE INTERACTIONS BETWEEN GENETIC AND EPIGENETIC MECHANISMS REGULATING COMT AND ITS INFLUENCE ON INFLAMMATORY MARKERS AND SYMPTOMS IN PATIENTS WITH CFS/FM. METHODS: A CASE-CONTROL STUDY WITH REPEATED-MEASURES DESIGN WAS USED TO REDUCE THE CHANCE OF FALSE POSITIVE AND INCREASE THE POWER OF OUR FINDINGS. FIFTY-FOUR PARTICIPANTS (28 PATIENTS WITH CFS/FM AND 26 CONTROLS) WERE ASSESSED TWICE WITHIN 4 DAYS. THE ASSESSMENT INCLUDED CLINICAL QUESTIONNAIRES, NEUROPHYSIOLOGICAL ASSESSMENT (PAIN THRESHOLDS, TEMPORAL SUMMATION, AND CONDITIONED PAIN MODULATION), AND BLOOD WITHDRAWAL IN ORDER TO ASSESS RS4818, RS4633, AND RS4680 COMT POLYMORPHISMS AND PERFORM HAPLOTYPE ESTIMATION, DNA METHYLATION IN THE COMT GENE (BOTH MB-COMT AND S-COMT PROMOTERS), AND CYTOKINE EXPRESSION (TNF-ALPHA, IFN-GAMMA, IL-6, AND TGF-BETA). RESULTS: COMT HAPLOTYPES WERE ASSOCIATED WITH DNA METHYLATION IN THE S-COMT PROMOTER, TGF-BETA EXPRESSION, AND SYMPTOMS. HOWEVER, THIS WAS NOT SPECIFIC FOR ONE CONDITION. SIGNIFICANT BETWEEN-GROUP DIFFERENCES WERE FOUND FOR INCREASED DNA METHYLATION IN THE MB-COMT PROMOTER AND DECREASED IFN-GAMMA EXPRESSION IN PATIENTS. DISCUSSION: OUR RESULTS ARE CONSISTENT WITH BASIC AND CLINICAL RESEARCH, PROVIDING INTERESTING INSIGHTS INTO GENETIC-EPIGENETIC REGULATORY MECHANISMS. MB-COMT DNA METHYLATION MIGHT BE AN INDEPENDENT FACTOR CONTRIBUTING TO THE PATHOPHYSIOLOGY OF CFS/FM. FURTHER RESEARCH ON DNA METHYLATION IN COMPLEX CONDITIONS SUCH AS CFS/FM IS WARRANTED. WE RECOMMEND FUTURE RESEARCH TO EMPLOY A REPEATED-MEASURE DESIGN TO CONTROL FOR BIOMARKERS VARIABILITY AND WITHIN-SUBJECT CHANGES.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
20 6490 10 TRACING SLOW PHENOPTOSIS TO THE PRENATAL STAGE IN SOCIAL VERTEBRATES. VLADIMIR SKULACHEV'S COINING OF THE TERM "PHENOPTOSIS" 25 YEARS AGO (SKULACHEV, V. P., BIOCHEMISTRY (MOSCOW), 62, 1997) HIGHLIGHTED THE THEORETICAL POSSIBILITY THAT AGING IS A PROGRAMMED PROCESS TO SPEED THE EXIT OF INDIVIDUALS POSING SOME DANGER TO THEIR SOCIAL GROUP. WHILE RAPID "ACUTE PHENOPTOSIS" MIGHT OCCUR AT ANY AGE (E.G., TO PREVENT SPREAD OF DEADLY INFECTIONS), "SLOW PHENOPTOSIS" IS GENERALLY CONSIDERED TO OCCUR LATER IN LIFE IN THE FORM OF CHRONIC AGE-RELATED DISORDERS. HOWEVER, RECENT RESEARCH INDICATES THAT RISKS FOR SUCH CHRONIC DISORDERS CAN BE GREATLY RAISED BY EARLY LIFE ADVERSITY, ESPECIALLY DURING THE PRENATAL STAGE. MUCH OF THIS RESEARCH USES INDICATORS OF BIOLOGICAL AGING, THE SPEEDING OR SLOWING OF NATURAL PHYSIOLOGICAL DETERIORATION IN RESPONSE TO ENVIRONMENTAL INPUTS, LEADING TO DIVERGENCE FROM CHRONOLOGICAL AGE. STUDIES USING BIOLOGICAL AGING INDICATORS COMMONLY FIND IT IS ACCELERATED NOT ONLY IN OLDER INDIVIDUALS WITH CHRONIC DISORDERS, BUT ALSO IN VERY YOUNG INDIVIDUALS WITH HEALTH PROBLEMS. THIS REVIEW WILL EXPLAIN HOW ACCELERATED BIOLOGICAL AGING EQUATES TO SLOW PHENOPTOSIS. ITS OCCURRENCE EVEN IN THE PRENATAL STAGE IS THEORETICALLY SUPPORTED BY W. D. HAMILTON'S PROPOSAL THAT OFFSPRINGS DETECTING THEY HAVE DANGEROUS MUTATIONS SHOULD THEN AUTOMATICALLY SPEED THEIR DEMISE, IN ORDER TO IMPROVE THEIR INCLUSIVE FITNESS BY GIVING THEIR PARENTS THE CHANCE TO PRODUCE OTHER FITTER SIBLINGS.	2022