1 6096 215 THE EFFECTS OF STRESS AND MEDITATION ON THE IMMUNE SYSTEM, HUMAN MICROBIOTA, AND EPIGENETICS. CONTEXT * GLOBALLY, MORE THAN 25% OF INDIVIDUALS ARE AFFECTED BY ANXIETY AND DEPRESSION DISORDERS. MEDITATION IS GAINING POPULARITY IN CLINICAL SETTINGS AND ITS TREATMENT EFFICACY IS BEING STUDIED FOR A WIDE ARRAY OF PSYCHOLOGICAL AND PHYSIOLOGICAL AILMENTS. AN EXPLORATION OF STRESS PHYSIOLOGY IS AN ESSENTIAL PRECURSOR TO DELINEATION OF THE MECHANISMS UNDERLYING THE BENEFICIAL EFFECTS OF MEDITATION PRACTICES. OBJECTIVE * THE REVIEW OUTLINES A MODEL OF INTERCONNECTED PHYSIOLOGICAL PROCESSES THAT MIGHT SUPPORT THE CONTINUED INCLUSION AND EXPANSION OF MEDITATION IN THE TREATMENT OF DIVERSE MEDICAL CONDITIONS AND TO INVESTIGATE THE ROLE THAT GUT MICROBIOTA MAY PLAY IN REALIZING WELL-BEING THROUGH MEDITATION. DESIGN * THE AUTHORS CONDUCTED A SCIENTIFIC LITERATURE DATABASE SEARCH WITH THE GOAL OF REVIEWING THE LINK BETWEEN STRESS MANAGEMENT TECHNIQUES AND HUMAN MICROBIOTA. THEIR GOAL WAS ALSO TO IDENTIFY THE EXTENT OF UNDERLYING EPIGENETIC REACTIONS IN THESE PROCESSES. THE REVIEW WAS COMPLETED IN APPROXIMATELY 2 Y. DATABASES SEARCHED INCLUDED MEDLINE VIA PUBMED AND OVID, PSYCINFO VIA OVID, SPINET, PROQUEST CENTRAL, SAGE RESEARCH METHODS ONLINE, CINAHL PLUS WITH FULL TEXT, SCIENCE DIRECT, SPRINGER LINK, AND WILEY ONLINE LIBRARY. KEYWORDS SEARCHED INCLUDED, BUT WERE NOT LIMITED TO, STRESS, MEDITATION, MINDFULNESS, IMMUNE SYSTEM, HPA AXIS, SYMPATHETIC NERVOUS SYSTEM, PARASYMPATHETIC NERVOUS SYSTEM, MICROBIOTA, MICROBIOME, GUT-BARRIER FUNCTION, LEAKY GUT, VAGUS NERVE, PSYCHONEUROIMMUNOLOGY, EPIGENETIC, AND NF-KAPPAB. SETTING * THE STUDY TOOK PLACE AT NEW YORK UNIVERSITY (NEW YORK, NY, USA), THE UNIVERSITY OF CALIFORNIA, SAN DIEGO (LA JOLLA, CA, USA), AND THE CHOPRA FOUNDATION (CARLSBAD, CA, USA). RESULTS * PSYCHOLOGICAL STRESS TYPICALLY TRIGGERS A FIGHT-OR-FLIGHT RESPONSE, PROMPTING CORTICOTROPIN-RELEASING HORMONE AND CATECHOLAMINE PRODUCTION IN VARIOUS PARTS OF THE BODY, WHICH ULTIMATELY DISTURBS THE MICROBIOTA. IN THE ABSENCE OF STRESS, A HEALTHY MICROBIOTA PRODUCES SHORT-CHAIN FATTY ACIDS THAT EXERT ANTI-INFLAMMATORY AND ANTITUMOR EFFECTS. DURING STRESS, AN ALTERED GUT MICROBIAL POPULATION AFFECTS THE REGULATION OF NEUROTRANSMITTERS MEDIATED BY THE MICROBIOME AND GUT BARRIER FUNCTION. MEDITATION HELPS REGULATE THE STRESS RESPONSE, THEREBY SUPPRESSING CHRONIC INFLAMMATION STATES AND MAINTAINING A HEALTHY GUT-BARRIER FUNCTION. CONCLUSIONS * THE CURRENT RESEARCH TEAM RECOMMENDS THE INTEGRATION OF MEDITATION INTO CONVENTIONAL HEALTH CARE AND WELLNESS MODELS. CONCURRENTLY, STUDIES TO EXPLORE THE EFFECTS OF MEDITATION ON HUMAN MICROBIOTA ARE WARRANTED. 2017 2 5725 50 SKIN MANIFESTATIONS OF INSULIN RESISTANCE: FROM A BIOCHEMICAL STANCE TO A CLINICAL DIAGNOSIS AND MANAGEMENT. WORLDWIDE, MORE THAN 1.9 BILLION ADULTS ARE OVERWEIGHT, AND AROUND 600 MILLION PEOPLE SUFFER FROM OBESITY. SIMILARLY, ~382 MILLION INDIVIDUALS LIVE WITH DIABETES, AND 40-50% OF THE GLOBAL POPULATION IS LABELED AT "HIGH RISK" (I.E., PREDIABETES). THE IMPACT OF THESE TWO CHRONIC CONDITIONS RELIES NOT ONLY ON THE BURDEN OF ILLNESSES PER SE (I.E., ASSOCIATED INCREASED MORBIDITY AND MORTALITY), BUT ALSO ON THEIR INCREASED COST, BURDEN OF TREATMENT, AND DECREASED HEALTH-RELATED QUALITY OF LIFE. FOR THIS REVIEW A COMPREHENSIVE SEARCH IN SEVERAL DATABASES INCLUDING PUBMED (MEDLINE), OVID EMBASE, WEB OF SCIENCE, AND SCOPUS WAS CONDUCTED. IN BOTH DIABETES AND OBESITY, GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS OVERLAP AND ARE INCLUSIVE RATHER THAN EXCLUSIVE. DE FACTO, 70-80% OF THE PATIENTS WITH OBESITY AND VIRTUALLY EVERY PATIENT WITH TYPE 2 DIABETES HAVE INSULIN RESISTANCE. INSULIN RESISTANCE IS A WELL-KNOWN PATHOPHYSIOLOGIC FACTOR IN THE DEVELOPMENT OF TYPE 2 DIABETES, CHARACTERISTICALLY APPEARING YEARS BEFORE ITS DIAGNOSIS. THE GOLD STANDARD FOR INSULIN RESISTANCE DIAGNOSIS (THE EUGLYCEMIC INSULIN CLAMP) IS A COMPLEX, INVASIVE, COSTLY, AND HENCE UNFEASIBLE TEST TO IMPLEMENT IN CLINICAL PRACTICE. LIKEWISE, LABORATORY MEASURES AND DERIVED INDEXES [E.G., HOMEOSTASIS MODEL ASSESSMENT OF INSULIN RESISTANCE (HOMA-IR-)] ARE INDIRECT, IMPRECISE, AND NOT HIGHLY ACCURATE AND REPRODUCIBLE TESTS. HOWEVER, SKIN MANIFESTATIONS OF INSULIN RESISTANCE (E.G., ACROCHORDONS, ACANTHOSIS NIGRICANS, ANDROGENETIC ALOPECIA, ACNE, HIRSUTISM) OFFER A RELIABLE, STRAIGHTFORWARD, AND REAL-TIME WAY TO DETECT INSULIN RESISTANCE. THE OBJECTIVE OF THIS REVIEW IS TO AID CLINICIANS IN RECOGNIZING SKIN MANIFESTATIONS OF INSULIN RESISTANCE. DIAGNOSING THESE SKIN MANIFESTATIONS ACCURATELY MAY CASCADE POSITIVELY IN THE PATIENT'S HEALTH BY TRIGGERING AN ADEQUATE METABOLIC EVALUATION, A TIMELY TREATMENT OR REFERRAL WITH THE ULTIMATE OBJECTIVE OF DECREASING DIABETES AND OBESITY BURDEN, AND IMPROVING THE HEALTH AND THE QUALITY OF CARE FOR THESE PATIENTS. 2017 3 5137 43 POTENTIAL MECHANISMS OF NON-SUICIDAL SELF-INJURY (NSSI) IN MAJOR DEPRESSIVE DISORDER: A SYSTEMATIC REVIEW. BACKGROUND: NON-SUICIDAL SELF-INJURY (NSSI) IS A FREQUENT AND PROMINENT PHENOMENON IN MAJOR DEPRESSIVE DISORDER (MDD). EVEN THOUGH ITS PREVALENCE AND RISK FACTORS ARE RELATIVELY WELL UNDERSTOOD, THE POTENTIAL MECHANISMS OF NSSI IN MDD REMAIN ELUSIVE. AIMS: TO REVIEW PRESENT EVIDENCE RELATED TO THE POTENTIAL MECHANISMS OF NSSI IN MDD. METHODS: ACCORDING TO PREFERRED REPORTING ITEMS FOR SYSTEMATIC REVIEWS AND META-ANALYSES 2020 GUIDELINES, ARTICLES FOR THIS SYSTEMATIC REVIEW WERE SEARCHED ON MEDLINE (THROUGH PUBMED), EMBASE (THROUGH ELSEVIER), PSYCINFO (THROUGH OVID) AND WEB OF SCIENCE DATABASES FOR ENGLISH ARTICLES, AS WELL AS CHINA NATIONAL KNOWLEDGE INFRASTRUCTURE (CNKI), SINOMED, WANFANG DATA, AND THE CHONGQING VIP CHINESE SCIENCE AND TECHNOLOGY PERIODICAL (VIP) DATABASES FOR CHINESE ARTICLES PUBLISHED FROM THE DATE OF INCEPTION TO 2 AUGUST 2022. TWO RESEARCHERS (BW, HZ) INDEPENDENTLY SCREENED STUDIES BASED ON INCLUSION AND EXCLUSION CRITERIA AND ASSESSED THEIR QUALITY. RESULTS: A TOTAL OF 25 157 STUDIES WERE SEARCHED. ONLY 25 OF THEM WERE ULTIMATELY INCLUDED, CONTAINING 3336 SUBJECTS (1535 PATIENTS WITH MDD AND NSSI, 1403 PATIENTS WITH MDD WITHOUT NSSI AND 398 HCS). INCLUDED STUDIES WERE DIVIDED INTO 6 CATEGORIES: PSYCHOSOCIAL FACTORS (11 STUDIES), NEUROIMAGING (8 STUDIES), STRESS AND HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS (2 STUDIES), PAIN PERCEPTION (1 STUDY), ELECTROENCEPHALOGRAM (EEG) (2 STUDIES) AND EPIGENETICS (1 STUDY). CONCLUSIONS: THIS SYSTEMATIC REVIEW INDICATES THAT PATIENTS WITH MDD AND NSSI MIGHT HAVE SPECIFIC PSYCHOSOCIAL FACTORS, ABERRANT BRAIN FUNCTIONS AND NEUROCHEMICAL METABOLISMS, HPA AXIS DYSFUNCTIONS, ABNORMAL PAIN PERCEPTIONS AND EPIGENETIC ALTERATIONS. 2023 4 639 46 BIOMARKERS FOR MYALGIC ENCEPHALOMYELITIS/CHRONIC FATIGUE SYNDROME (ME/CFS): A SYSTEMATIC REVIEW. BACKGROUND: MYALGIC ENCEPHALOMYELITIS/CHRONIC FATIGUE SYNDROME (ME/CFS) IS A MULTIFACETED CONDITION THAT AFFECTS MOST BODY SYSTEMS. THERE IS CURRENTLY NO KNOWN DIAGNOSTIC BIOMARKER; INSTEAD, DIAGNOSIS IS DEPENDENT ON APPLICATION OF SYMPTOM-BASED CASE CRITERIA FOLLOWING EXCLUSION OF ANY OTHER POTENTIAL MEDICAL CONDITIONS. WHILE THERE ARE SOME STUDIES THAT REPORT POTENTIAL BIOMARKERS FOR ME/CFS, THEIR EFFICACY HAS NOT BEEN VALIDATED. THE AIM OF THIS SYSTEMATIC REVIEW IS TO COLLATE AND APPRAISE LITERATURE PERTAINING TO A POTENTIAL BIOMARKER(S) WHICH MAY EFFECTIVELY DIFFERENTIATE ME/CFS PATIENTS FROM HEALTHY CONTROLS. METHODS: THIS SYSTEMATIC REVIEW WAS CONDUCTED ACCORDING TO THE PREFERRED REPORTING ITEMS FOR SYSTEMATIC REVIEWS AND META-ANALYSES AND COCHRANE REVIEW GUIDELINES. PUBMED, EMBASE AND SCOPUS WERE SYSTEMATICALLY SEARCHED FOR ARTICLES CONTAINING "BIOMARKER" AND "ME/CFS" KEYWORDS IN THE ABSTRACT OR TITLE AND IF THEY INCLUDED THE FOLLOWING CRITERIA: (1) WERE OBSERVATIONAL STUDIES PUBLISHED BETWEEN DECEMBER 1994 AND APRIL 2022; (2) INVOLVED ADULT HUMAN PARTICIPANTS; (3) FULL TEXT IS AVAILABLE IN ENGLISH (4) ORIGINAL RESEARCH; (5) DIAGNOSIS OF ME/CFS PATIENTS MADE ACCORDING TO THE FUKUDA CRITERIA (1994), CANADIAN CONSENSUS CRITERIA (2003), INTERNATIONAL CONSENSUS CRITERIA (2011) OR INSTITUTE OF MEDICINE CRITERIA (2015); (6) STUDY INVESTIGATED POTENTIAL BIOMARKERS OF ME/CFS COMPARED TO HEALTHY CONTROLS. QUALITY AND BIAS WERE ASSESSED USING THE JOANNA BRIGGS INSTITUTE CRITICAL APPRAISAL CHECKLIST FOR CASE CONTROL STUDIES. RESULTS: A TOTAL OF 101 PUBLICATIONS WERE INCLUDED IN THIS SYSTEMATIC REVIEW. POTENTIAL BIOMARKERS RANGED FROM GENETIC/EPIGENETIC (19.8%), IMMUNOLOGICAL (29.7%), METABOLOMICS/MITOCHONDRIAL/MICROBIOME (14.85%), ENDOVASCULAR/CIRCULATORY (17.82%), NEUROLOGICAL (7.92%), ION CHANNEL (8.91%) AND PHYSICAL DYSFUNCTION BIOMARKERS (8.91%). MOST OF THE POTENTIAL BIOMARKERS REPORTED WERE BLOOD-BASED (79.2%). USE OF LYMPHOCYTES AS A MODEL TO INVESTIGATE ME/CFS PATHOLOGY WAS PROMINENT AMONG IMMUNE-BASED BIOMARKERS. MOST BIOMARKERS HAD SECONDARY (43.56%) OR TERTIARY (54.47%) SELECTIVITY, WHICH IS THE ABILITY FOR THE BIOMARKER TO IDENTIFY A DISEASE-CAUSING AGENT, AND A MODERATE (59.40%) TO COMPLEX (39.60%) EASE-OF-DETECTION, INCLUDING THE REQUIREMENT OF SPECIALISED EQUIPMENT. CONCLUSIONS: ALL POTENTIAL ME/CFS BIOMARKERS DIFFERED IN EFFICIENCY, QUALITY, AND TRANSLATABILITY AS A DIAGNOSTIC MARKER. REPRODUCIBILITY OF FINDINGS BETWEEN THE INCLUDED PUBLICATIONS WERE LIMITED, HOWEVER, SEVERAL STUDIES VALIDATED THE INVOLVEMENT OF IMMUNE DYSFUNCTION IN THE PATHOLOGY OF ME/CFS AND THE USE OF LYMPHOCYTES AS A MODEL TO INVESTIGATE THE PATHOMECHANISM OF ILLNESS. THE HETEROGENEITY SHOWN ACROSS MANY OF THE INCLUDED STUDIES HIGHLIGHTS THE NEED FOR MULTIDISCIPLINARY RESEARCH AND UNIFORM PROTOCOLS IN ME/CFS BIOMARKER RESEARCH. 2023 5 455 44 APPLICATIONS OF YOGA IN ORAL ONCOLOGY: A SYSTEMATIC SCOPING REVIEW. BACKGROUND AND AIMS: YOGA IS WELL-THOUGHT-OUT AS AN ALL-INCLUSIVE APPROACH GLOBALLY AND CAN BE ADMINISTERED IN CLINICAL CARE AS AN INTEGRATIVE OR ALTERNATE APPROACH TO REGULAR TREATMENT. YOGA EXERCISE HAS BEEN DISCLOSED TO INFLUENCE REMISSION FROM CANCER CELLS OVER A LONG PERIOD OF TIME AND ALSO REVERSES EPIGENETIC ALTERATIONS. APPLICATIONS OF YOGA IN THE MANAGEMENT OF ORAL ONCOLOGY PATIENTS ARE SCARCE, HENCE THE NEED FOR A SCOPING REVIEW OF THE LITERATURE. HENCE, THIS STUDY AIMED TO CONDUCT A SCOPING REVIEW OF THE EXISTING EMPIRICAL EVIDENCE ON THE APPLICATIONS OF YOGA IN ORAL ONCOLOGY. METHODS: THE REVIEW METHODOLOGY WAS INFORMED BY JOANNA BRIGG'S INSTITUTE GUIDELINES FOR SYSTEMATIC SCOPING REVIEWS, AND THE REVIEW WAS REPORTED IN ACCORDANCE WITH THE PREFERRED REPORTING ITEMS FOR SYSTEMATIC REVIEWS AND META-ANALYSES EXTENSION FOR SCOPING REVIEWS. TEN DATABASES WERE SEARCHED. THE RECORDS OF ALL THE LITERATURE RETRIEVED FROM THE SEARCH WERE IMPORTED INTO THE RAYYAN SOFTWARE FOR DEDUPLICATION. AFTER THE FULL-TEXT SCREENING, ONLY TWO WERE FOUND ELIGIBLE FOR INCLUSION IN THE SCOPING REVIEW. DATA OBTAINED IN THE INCLUDED LITERATURE WERE EXTRACTED AND SYNTHESIZED. RESULTS: THIS REVIEW FOUND THAT YOGA WAS NOT SIGNIFICANTLY EFFECTIVE IN THE MANAGEMENT OF STRESS AMONG ORAL CANCER PATIENTS (P-VALUES > 0.04). HOWEVER, IT WAS FOUND THAT YOGA SIGNIFICANTLY REDUCED ANXIETY, SALIVA STICKINESS, AND EPISODES OF FALLING ILL (P-VALUES < 0.05) WHILE IT IMPROVED MENTAL WELL-BEING, COGNITIVE FUNCTIONING, EMOTIONAL FUNCTIONING, AND HEAD AND NECK PAIN OF THOSE ORAL CANCER PATIENTS THAT RECEIVED IT (P-VALUES < 0.05). CONCLUSION: AN INTEGRATIVE CARE APPROACH THAT CONSIDERS NONPHARMACEUTICAL TECHNIQUES SUCH AS YOGA COULD HELP TO REDUCE CARE COST WHILE IMPROVING CARE OUTCOMES AND QUALITY OF LIFE OF ORAL CANCER PATIENTS. HENCE, IT IS IMPERATIVE TO CONSIDER YOGA ALONG WITH ITS POTENTIAL BENEFITS, AND WE RECOMMEND GRADUAL INCORPORATION OF YOGA INTO ORAL CANCER CARE. 2023 6 5882 41 SYSTEMATIC REVIEW OF LUNG FUNCTION AND COPD WITH PERIPHERAL BLOOD DNA METHYLATION IN POPULATION BASED STUDIES. BACKGROUND: EPIGENETIC VARIATIONS IN PERIPHERAL BLOOD HAVE POTENTIAL AS BIOMARKERS FOR DISEASE. THIS SYSTEMATIC REVIEW ASSESSES THE ASSOCIATION OF LUNG FUNCTION AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD) WITH DNA METHYLATION PROFILES IN PERIPHERAL BLOOD FROM POPULATION-BASED STUDIES. METHODS: ONLINE DATABASES MEDLINE, EMBASE, AND WEB OF SCIENCE WERE SEARCHED. GOOGLE SCHOLAR WAS SEARCHED TO IDENTIFY GREY LITERATURE. AFTER REMOVING DUPLICATE ARTICLES, 1155 ARTICLES WERE INDEPENDENTLY SCREENED BY TWO INVESTIGATORS. PEER REVIEWED REPORTS ON POPULATION-BASED STUDIES THAT EXAMINED PERIPHERAL BLOOD DNA METHYLATION IN PARTICIPANTS WITH MEASURED LUNG FUNCTION (FEV1, FEV1/FVC RATIO) OR KNOWN COPD STATUS WERE SELECTED FOR FULL-TEXT REVIEW. SIX ARTICLES WERE SUITABLE FOR INCLUSION. INFORMATION REGARDING STUDY CHARACTERISTICS, DESIGNS, METHODOLOGIES AND CONCLUSIONS WAS EXTRACTED. A NARRATIVE SYNTHESIS WAS PERFORMED BASED ON PUBLISHED RESULTS. RESULTS: THREE OF THE SIX ARTICLES ASSESSED THE ASSOCIATION OF COPD WITH DNA METHYLATION, AND TWO OF THESE ALSO INCLUDED ASSOCIATIONS WITH LUNG FUNCTION. OVERALL, FIVE REPORTS EXAMINED THE ASSOCIATION OF LUNG FUNCTION WITH DNA METHYLATION PROFILES. FIVE OF THE SIX ARTICLES REPORTED 'SIGNIFICANT' RESULTS. HOWEVER, NO CONSISTENT CPG SITES WERE IDENTIFIED ACROSS STUDIES FOR COPD STATUS OR LUNG FUNCTION VALUES. CONCLUSIONS: DNA METHYLATION PATTERNS IN PERIPHERAL BLOOD FROM INDIVIDUALS WITH REDUCED LUNG FUNCTION OR COPD MAY BE DIFFERENT TO THOSE IN PEOPLE WITH NORMAL LUNG FUNCTION. HOWEVER, THIS SYSTEMATIC REVIEW DID NOT FIND ANY CONSISTENT ASSOCIATIONS OF LUNG FUNCTION OR COPD WITH DIFFERENTIALLY METHYLATED CPG SITES. LARGE STUDIES WITH A LONGITUDINAL DESIGN TO ADDRESS REVERSE CAUSALITY MAY PROVE A MORE FRUITFUL AREA OF RESEARCH. TRIAL REGISTRATION: PROSPERO 2016: CRD42016037352 . 2017 7 6047 35 THE COMPUTATIONAL ANALYSIS CONDUCTED ON MIRNA TARGET SITES IN ASSOCIATION WITH SNPS AT 3'UTR OF ADHD-IMPLICATED GENES. BACKGROUND: ATTENTION-DEFICIT/HYPERACTIVITY DISORDER (ADHD) IS A FREQUENT CHRONIC NEUROPSYCHIATRIC DISORDER IN WHICH DIFFERENT FACTORS INCLUDING ENVIRONMENTAL, GENETIC, AND EPIGENETIC FACTORS PLAY AN IMPORTANT ROLE IN ITS PATHOGENESIS. ONE OF THE EFFECTIVE EPIGENETIC FACTORS IS RECOGNIZED AS MICRORNAS (MIRNAS). ON THE OTHER HAND, IT HAS BEEN INDICATED THAT THE SINGLE NUCLEOTIDE POLYMORPHISM (SNPS) PRESENT WITHIN 3'UTR (3' UNTRANSLATED REGION) OF MRNAS CAN INFLUENCE THE REGULATION OF MIRNA-MEDIATED GENE AND SUSCEPTIBILITY TO A DIVERSITY OF HUMAN DISEASES. METHODS: THE PURPOSE OF THIS STUDY WAS TO ANALYZE THE SNPS WITHIN THE 3'UTR OF MIRNA TARGET GENES ASSOCIATED WITH ADHD. 3'UTR GENETIC VARIANTS WERE IDENTIFIED IN ALL GENES ASSOCIATED WITH ADHD USING DISGENET, DBGAP, OVID, DAVID, WEB OF KNOWLEDGE, AND SNPS DATABASES. MIRNA'S TARGET PREDICTION DATABASES WERE APPLIED IN ORDER TO PREDICT THE MIRNA BINDING SITES. 124 SNPS WITH MAF>0.05 WERE IDENTIFIED LOCATED IN THE BINDING SITE OF THE MIRNA OF 35 GENES AMONGST 51 GENES ASSOCIATED WITH ADHD. RESULTS: BIOINFORMATICS ANALYSIS PREDICTED 81 MRE (MIRNA RECOGNITION ELEMENTS)-CREATING SNPS, 101 MRE-BREAKING SNPS, 61 MRE-ENHANCING SNPS, AND FINALLY PREDICTED 41 MREDECREASING SNPS IN THE 3'UTR OF ADHD-IMPLICATED GENES. THESE CANDIDATE SNPS WITHIN THESE GENES MIRNA BINDING SITES CAN ALTER THE MIRNAS BINDING, AND CONSEQUENTLY, LEAD TO MRNA GENE REGULATION. CONCLUSION: THEREFORE, THESE MIRNA AND MRE-SNPS MAY PLAY IMPORTANT ROLES IN ADHD, AND BECAUSE OF THAT, THEY WOULD BE VALUABLE FOR FURTHER INVESTIGATION IN THE FIELD OF FUNCTIONAL VERIFICATION. 2020 8 6112 44 THE EPIGENETIC CLOCK AS A PREDICTOR OF DISEASE AND MORTALITY RISK: A SYSTEMATIC REVIEW AND META-ANALYSIS. BACKGROUND: AGEING IS ONE OF THE PRINCIPAL RISK FACTORS FOR MANY CHRONIC DISEASES. HOWEVER, THERE IS CONSIDERABLE BETWEEN-PERSON VARIATION IN THE RATE OF AGEING AND INDIVIDUAL DIFFERENCES IN THEIR SUSCEPTIBILITY TO DISEASE AND DEATH. EPIGENETIC MECHANISMS MAY PLAY A ROLE IN HUMAN AGEING, AND DNA METHYLATION AGE BIOMARKERS MAY BE GOOD PREDICTORS OF AGE-RELATED DISEASES AND MORTALITY RISK. THE AIMS OF THIS SYSTEMATIC REVIEW WERE TO IDENTIFY AND SYNTHESISE THE EVIDENCE FOR AN ASSOCIATION BETWEEN PERIPHERALLY MEASURED DNA METHYLATION AGE AND LONGEVITY, AGE-RELATED DISEASE, AND MORTALITY RISK. METHODS: A SYSTEMATIC SEARCH WAS CONDUCTED IN LINE WITH THE PREFERRED REPORTING ITEMS FOR SYSTEMATIC REVIEWS AND META-ANALYSES (PRISMA) GUIDELINES. USING RELEVANT SEARCH TERMS, MEDLINE, EMBASE, COCHRANE CENTRAL REGISTER OF CONTROLLED TRIALS, AND PSYCHINFO DATABASES WERE SEARCHED TO IDENTIFY ARTICLES MEETING THE INCLUSION CRITERIA. STUDIES WERE ASSESSED FOR BIAS USING JOANNA BRIGGS INSTITUTE CRITICAL APPRAISAL CHECKLISTS. DATA WAS EXTRACTED FROM STUDIES MEASURING AGE ACCELERATION AS A PREDICTOR OF AGE-RELATED DISEASES, MORTALITY OR LONGEVITY, AND THE FINDINGS FOR SIMILAR OUTCOMES COMPARED. USING REVIEW MANAGER 5.3 SOFTWARE, TWO META-ANALYSES (ONE PER EPIGENETIC CLOCK) WERE CONDUCTED ON STUDIES MEASURING ALL-CAUSE MORTALITY. RESULTS: TWENTY-THREE RELEVANT ARTICLES WERE IDENTIFIED, INCLUDING A TOTAL OF 41,607 PARTICIPANTS. FOUR STUDIES FOCUSED ON AGEING AND LONGEVITY, 11 ON AGE-RELATED DISEASE (CANCER, CARDIOVASCULAR DISEASE, AND DEMENTIA), AND 11 ON MORTALITY. THERE WAS SOME, ALTHOUGH INCONSISTENT, EVIDENCE FOR AN ASSOCIATION BETWEEN INCREASED DNA METHYLATION AGE AND RISK OF DISEASE. META-ANALYSES INDICATED THAT EACH 5-YEAR INCREASE IN DNA METHYLATION AGE WAS ASSOCIATED AN 8 TO 15% INCREASED RISK OF MORTALITY. CONCLUSION: DUE TO THE SMALL NUMBER OF STUDIES AND HETEROGENEITY IN STUDY DESIGN AND OUTCOMES, THE ASSOCIATION BETWEEN DNA METHYLATION AGE AND AGE-RELATED DISEASE AND LONGEVITY IS INCONCLUSIVE. INCREASED EPIGENETIC AGE WAS ASSOCIATED WITH MORTALITY RISK, BUT POSITIVE PUBLICATION BIAS NEEDS TO BE CONSIDERED. FURTHER RESEARCH IS NEEDED TO DETERMINE THE EXTENT TO WHICH DNA METHYLATION AGE CAN BE USED AS A CLINICAL BIOMARKER. 2019 9 1151 46 CONNECTIONS AMONG BIOLOGIC EMBEDDING OF CHILDHOOD ADVERSITY, ADULT CHRONIC ILLNESS, AND WOUND CARE: A REVIEW OF THE LITERATURE. ADVERSE CHILDHOOD EXPERIENCES (ACES) BIOLOGICALLY EMBED BY ALTERING BRAIN DEVELOPMENT AND INFLUENCING EPIGENETIC MECHANISMS. THESE EXPERIENCES MAY GENERATE HEALTH RISK FACTORS. PURPOSE: A LITERATURE REVIEW WAS CONDUCTED TO COMPARE ACE-GENERATED HEALTH RISK FACTORS WITH RISK FACTORS FOR WOUND DEVELOPMENT AND ABERRANT HEALING, AS WELL AS TO IDENTIFY A GAP IN LITERATURE REGARDING CRITICAL CONNECTIONS BETWEEN ACES, CHRONIC ILLNESS, AND WOUND DEVELOPMENT/HEALING, WITH ASSOCIATED PRACTICE IMPLICATIONS. METHODOLOGY: A LITERATURE SEARCH OF ENGLISH-LANGUAGE ARTICLES WAS CONDUCTED USING THE CUMULATIVE INDEX OF NURSING AND ALLIED HEALTH LITERATURE, MEDLINE, AND PUBMED USING THE SEARCH TERMS ADVERSE CHILDHOOD EXPERIENCES, ADULTS, WOUNDS, CHRONIC DISEASE OR ILLNESS, AND EPIGENETICS. THE SEARCHES YIELDED 561 PUBLICATIONS REGARDING ACES, CHRONIC ILLNESS OR DISEASE, AND ADULT; 182 FOR ACES; AND 547 FOR EPIGENETICS AND WOUNDS. ABSTRACTS WERE REVIEWED TO REMOVE DUPLICATES AND STUDIES WITH PARTICIPANTS WHO WERE <18 YEARS OLD. PUBLICATIONS WERE REVIEWED FOR SALIENCE; THOSE DISCUSSING THE BIOLOGIC PLAUSIBILITY OF ACES CONTRIBUTING TO ADULT ILLNESSES AND ASSOCIATED WOUND DEVELOPMENT AND HEALING WERE REVIEWED FOR INCLUSION. RESULTS: SIXTY-EIGHT (68) PUBLICATIONS WERE FOUND APPROPRIATE FOR REVIEW AND INCLUDED POPULATION-BASED STUDIES; LITERATURE REVIEWS; EPIDEMIOLOGIC DATA; META-ANALYSES; AND SYSTEMATIC, CROSS-SECTIONAL, OBSERVATIONAL, AND PROSPECTIVE STUDIES AS SINGULAR OR MIXED METHODS DESIGNS. A SUBSTANTIAL OVERLAP WAS FOUND IN TERMS OF RISK FACTORS GENERATED BY ACE EXPOSURE AND RISK FACTORS FOR WOUND DEVELOPMENT/HEALING, AS WAS A GAP IN THE LITERATURE REGARDING THIS RELATIONSHIP. EPIGENETIC MECHANISMS AND ALTERED BRAIN DEVELOPMENT ARE IMPLICATED IN PROCESSES THROUGH WHICH CHILDHOOD ADVERSITY ERODES HUMAN HEALTH. CONCLUSION: ADULT HEALTH RISKS AS A RESULT OF EXPOSURE TO ACES AND CRITICAL CONNECTIONS WITH RISKS FOR WOUND DEVELOPMENT AND DISRUPTED WOUND HEALING VIA EPIGENETIC INFLUENCES ARE RECOGNIZED IN THE LITERATURE. PRACTICE IMPLICATIONS INCLUDE CONSIDERING SCREENING FOR THE RISK FACTOR OF ACES EXPOSURE IN ADULT PATIENTS TO IDENTIFY THIS ADDITIONAL RISK FACTOR AND PRACTICING PATIENT-CENTERED, TRAUMA-INFORMED CARE. FURTHER RESEARCH INTO THE INTEGRATIVE ROLES OF THESE FACTORS IS WARRANTED. 2019 10 2646 44 EPIGENOMIC LINKS BETWEEN SOCIAL DETERMINANTS OF HEALTH AND SYMPTOMS: A SCOPING REVIEW. SOCIAL DETERMINANTS OF HEALTH (SDOH) IMPACT HEALTH AND WELLNESS. THE LINK BETWEEN SDOH AND ADVERSE HEALTH OUTCOMES, INCLUDING SYMPTOM OCCURRENCE AND SEVERITY, MAY BE EXPLAINED BY AN INDIVIDUAL'S PHYSIOLOGIC RESPONSE TO ONE OR MORE SDOH. ONE POTENTIAL MECHANISM UNDERLYING THIS PHYSIOLOGIC RESPONSE LINKING SDOH AND SYMPTOMS IS THE DYNAMIC EPIGENOME. THE PURPOSE OF THIS SCOPING REVIEW OF THE LITERATURE WAS TO EXAMINE DIFFERENTIAL SUSCEPTIBILITY FOR SYMPTOMS BY IDENTIFYING AND SUMMARIZING RESEARCH LINKING SDOH AND SYMPTOMS THROUGH EPIGENOMIC MECHANISMS. PUBMED WAS SEARCHED TO IDENTIFY EMPIRICAL RESEARCH WHERE AT LEAST ONE SDOH WAS AN INDEPENDENT OR DEPENDENT VARIABLE, AT LEAST ONE SYMPTOM WAS INVESTIGATED, AND THE INVESTIGATION INCLUDED AN EPIGENOMIC MEASURE. OF THE 484 ARTICLES INITIALLY RETRIEVED, AFTER THOROUGH VETTING, 41 ARTICLES MET ELIGIBILITY. THE MOST STUDIED SYMPTOM WAS DEPRESSIVE SYMPTOMS FOLLOWED BY ANXIETY, COGNITIVE FUNCTION, SLEEP DYSFUNCTION, AND PAIN. THE MOST FREQUENTLY STUDIED SDOH WERE: 1) STRESS, PARTICULARLY EARLY LIFE STRESS AND ACCULTURATIVE STRESS; AND 2) TRAUMA, PREDOMINANTLY CHILDHOOD TRAUMA. DNA METHYLATION AND TELOMERE LENGTH WERE THE MOST STUDIED EPIGENOMIC MEASURES. FOUR GENES (SLC6A4, BDNF, NR3C1, OXTR) HAD EVIDENCE FROM MULTIPLE STUDIES AND ACROSS METHODOLOGICAL APPROACHES LINKING SDOH TO SYMPTOMS. THIS REVIEW SUPPORTS THE INCLUSION OF EPIGENOMIC APPROACHES TO BETTER UNDERSTAND THE LINK BETWEEN SDOH AND SYMPTOMS AND PROVIDES EVIDENCE THAT SDOH IMPACT TELOMERE LENGTH AND THE METHYLATION OF GENES INVOLVED IN NEUROTRANSMITTER SIGNALING, NEURONAL SURVIVAL, BEHAVIOR, INFLAMMATION AND STRESS RESPONSE. 2023 11 108 30 A REVIEW OF THE PROTECTIVE EFFECT OF MELATONIN IN PESTICIDE-INDUCED TOXICITY. PESTICIDES ARE AMONG THE MOST IMPORTANT CHEMICALS USED IN AGRICULTURE SECTOR. HOWEVER, THEIR EXTENSIVE USE HAS POLLUTED THE ENVIRONMENT AND INCREASED HUMAN VULNERABILITY TO VARIOUS CHRONIC DISEASES. PESTICIDE EXPOSURE CAUSES GENETIC AND EPIGENETIC MODIFICATIONS, ENDOCRINE DISRUPTION, MITOCHONDRIAL DYSFUNCTION AND OXIDATIVE STRESS. AREAS COVERED: THIS REVIEW IS BASED ON THE LITERATURE STUDIES CURRENTLY REPORTED ON PESTICIDE-INDUCED TOXICITY AND THE PROTECTIVE ROLE OF MELATONIN. SCIENTIFIC DATABASES SUCH AS PUBMED, SCOPUS AND WEB OF SCIENCE WERE SEARCHED USING KEYWORDS 'PESTICIDE' AND 'MELATONIN' UP TO JANUARY 2016. FULL LENGTH ARTICLES RELATED TO ANIMAL AND HUMAN EXPOSURE WERE RETRIEVED. A TOTAL NUMBER OF 181 RECORDS WERE OBTAINED, AND AFTER EXCLUDING THE DUPLICATES, 97 PAPERS WERE FURTHER SCREENED ON THE BASIS OF RELEVANCE TO THE TOPIC. EXPERT OPINION: MELATONIN AS A BROAD-SPECTRUM ANTIOXIDANT IS ABLE TO PENETRATE CELLULAR COMPARTMENTS SPECIFICALLY THE MITOCHONDRIA. IT IS A POTENT FREE RADICAL SCAVENGER WITH LOW TOXICITY AND DESIRABLE SOLUBILITY IN ORGANIC AND AQUEOUS PHASES. WE ARE OF THE OPINION THAT MELATONIN IS A PROMISING AGENT IN MINIMIZING ORGAN INJURIES INDUCED BY PESTICIDES. 2017 12 6478 38 TOPICAL REVIEW: THE EMERGING FIELD OF EPIGENETICS: INFORMING MODELS OF PEDIATRIC TRAUMA AND PHYSICAL HEALTH. OBJECTIVE: TRAUMA EXPERIENCED DURING CHILDHOOD AND ADOLESCENCE HAS BEEN LINKED TO A NUMBER OF CHRONIC MEDICAL CONCERNS. WE HIGHLIGHT MAJOR FINDINGS FROM THE PEDIATRIC TRAUMA LITERATURE TO PROVIDE A MODEL FOR UNDERSTANDING THIS ASSOCIATION. METHODS: STUDIES EXAMINING THE EFFECTS OF TRAUMA WERE SYSTEMATICALLY REVIEWED AND SYNTHESIZED INTO A MODEL PROPOSING A CENTRAL ROLE FOR EPIGENETICS IN THE WAYS THAT CHILDHOOD EXPERIENCES CAN AFFECT HEALTH. RESULTS: EARLY HYPOTHALAMIC PITUITARY ADRENAL (HPA) AXIS RESPONSE MAY IMPACT INITIAL TRAUMA EXPERIENCE, WITH DOWNSTREAM EFFECTS ON POSTTRAUMA ADJUSTMENT REFLECTED IN POSTTRAUMA NEUROBIOLOGY, PSYCHOLOGICAL HEALTH, AND PHYSICAL HEALTH. CONCLUSIONS: PROSPECTIVE RESEARCH WITH CHILDREN AND ADOLESCENTS EXPOSED TO TRAUMA IS NEEDED TO BETTER CHARACTERIZE THE GENETIC AND EPIGENETIC INFLUENCES ON THE COURSE OF HPA AND IMMUNE PROCESSES AS RELATED TO POSTTRAUMA PSYCHOLOGICAL AND PHYSICAL HEALTH OUTCOMES. 2016 13 6743 43 WHITHER THE ETIOPATHOGENESIS (AND SCOLIOGENY) OF ADOLESCENT IDIOPATHIC SCOLIOSIS? INCORPORATING PRESENTATIONS ON SCOLIOGENY AT THE 2012 IRSSD AND SRS MEETINGS. THIS PAPER AIMS TO INTEGRATE INTO CURRENT UNDERSTANDING OF AIS CAUSATION, ETIOPATHOGENETIC INFORMATION PRESENTED AT TWO MEETINGS DURING 2012 NAMELY, THE INTERNATIONAL RESEARCH SOCIETY OF SPINAL DEFORMITIES (IRSSD) AND THE SCOLIOSIS RESEARCH SOCIETY (SRS). THE ULTIMATE HOPE IS TO PREVENT THE OCCURRENCE OR PROGRESSION OF THE SPINAL DEFORMITY OF AIS WITH NON-INVASIVE TREATMENT, POSSIBLY MEDICAL. THIS MIGHT BE ATTAINED BY PERSONALISED POLYMECHANISTIC PREVENTIVE THERAPY TARGETING THE APPROPRIATE ETIOLOGY AND/OR ETIOPATHOGENETIC PATHWAYS, TO AVOID FUSION AND MAINTAIN SPINAL MOBILITY. ALTHOUGH CONSIDERABLE PROGRESS HAD BEEN MADE IN THE PAST TWO DECADES IN UNDERSTANDING THE ETIOPATHOGENESIS OF ADOLESCENT IDIOPATHIC SCOLIOSIS (AIS), IT STILL LACKS AN AGREED THEORY OF ETIOPATHOGENESIS. ONE PROBLEM MAY BE THAT AIS RESULTS NOT FROM ONE CAUSE, BUT SEVERAL THAT INTERACT WITH VARIOUS GENETIC PREDISPOSING FACTORS. THERE IS A VIEW THERE ARE TWO OTHER PATHOGENIC PROCESSES FOR IDIOPATHIC SCOLIOSIS NAMELY, INITIATING (OR INDUCING), AND THOSE THAT CAUSE CURVE PROGRESSION. TWIN STUDIES AND OBSERVATIONS OF FAMILY AGGREGATION HAVE REVEALED SIGNIFICANT GENETIC CONTRIBUTIONS TO IDIOPATHIC SCOLIOSIS, THAT PLACE AIS AMONG OTHER COMMON DISEASE OR COMPLEX TRAITS WITH A HIGH HERITABILITY INTERPRETED BY THE GENETIC VARIANT HYPOTHESIS OF DISEASE. WE SUMMARIZE ETIOPATHOGENETIC KNOWLEDGE OF AIS AS THEORIES OF PATHOGENESIS INCLUDING RECENT MULTIPLE CONCEPTS, AND BLOOD TESTS FOR AIS BASED ON PREDICTIVE BIOMARKERS AND GENETIC VARIANTS THAT SIGNIFY DISEASE RISK. THERE IS INCREASING EVIDENCE FOR THE POSSIBILITY OF AN UNDERLYING NEUROLOGICAL DISORDER FOR AIS, RESEARCH WHICH HOLDS PROMISE. LIKE BRAIN RESEARCH, MOST AIS WORKERS FOCUS ON THEIR OWN CORNER AND THERE IS A NEED FOR GREATER INTEGRATION OF RESEARCH EFFORT. EPIGENETICS, A RELATIVELY RECENT FIELD, EVALUATES FACTORS CONCERNED WITH GENE EXPRESSION IN RELATION TO ENVIRONMENT, DISEASE, NORMAL DEVELOPMENT AND AGING, WITH A COMPLEX REGULATION ACROSS THE GENOME DURING THE FIRST DECADE OF LIFE. RESEARCH ON THE ROLE OF ENVIRONMENTAL FACTORS, EPIGENETICS AND CHRONIC NON-COMMUNICABLE DISEASES (NCDS) INCLUDING ADIPOSITY, AFTER A SLOW START, HAS EXPLODED IN THE LAST DECADE. NOT SO FOR AIS RESEARCH AND THE ENVIRONMENT WHERE, EXCEPT FOR MONOZYGOTIC TWIN STUDIES, THERE ARE ONLY SPORADIC REPORTS TO SUGGEST THAT ENVIRONMENTAL FACTORS ARE AT WORK IN ETIOLOGY. HERE, WE EXAMINE EPIGENETIC CONCEPTS AS THEY MAY RELATE TO HUMAN DEVELOPMENT, NORMAL LIFE HISTORY PHASES AND AIS PATHOGENESIS. ALTHOUGH AIS IS NOT REGARDED AS AN NCD, LIKE THEM, IT IS ASSOCIATED WITH WHOLE ORGANISM METABOLIC PHENOMENA, INCLUDING LOWER BODY MASS INDEX, LOWER CIRCULATING LEPTIN LEVELS AND OTHER SYSTEMIC DISORDERS. SOME EPIGENETIC RESEARCH APPLIED TO SILVER-RUSSELL SYNDROME AND ADIPOSITY IS EXAMINED, FROM WHICH SUGGESTIONS ARE MADE FOR CONSIDERATION OF AIS EPIGENETIC RESEARCH, CROSS-SECTIONAL AND LONGITUDINAL. THE WORD SCOLIOGENY IS SUGGESTED TO INCLUDE ETIOLOGY, PATHOGENESIS AND PATHOMECHANISM. 2013 14 3797 21 INTERNATIONAL BREAST CANCER AND NUTRITION: A MODEL FOR RESEARCH, TRAINING AND POLICY IN DIET, EPIGENETICS, AND CHRONIC DISEASE PREVENTION. THIS ARTICLE SUMMARIZES PRESENTATIONS FROM THE INTERNATIONAL BREAST CANCER AND NUTRITION WORKSHOP HELD DURING THE ASN SCIENTIFIC SESSIONS AND ANNUAL MEETING AT EXPERIMENTAL BIOLOGY 2014 IN SAN DIEGO, CA, ON 28 APRIL 2014. AN INTERNATIONAL COLLABORATION WAS DESCRIBED AMONG TEAMS FROM LOW-, MIDDLE-, AND HIGH-INCOME COUNTRIES ADDRESSING ENVIRONMENTAL FACTORS, ESPECIALLY DIET, AND EPIGENETIC INTERACTIONS THAT AFFECT THE RISK OF CHRONIC DISEASE. SPEAKERS ADDRESSED OPPORTUNITIES AND CHALLENGES INVOLVED IN THIS TYPE OF INTERNATIONAL COLLABORATION, ASSESSING DIET AND NUTRITIONAL STATUS ACROSS A WIDE RANGE OF CULTURES, AND RESEARCH TOOLS AND DISCOVERIES FROM THIS GROUP. 2014 15 5224 46 PRIORITIZED RESEARCH FOR THE PREVENTION, TREATMENT, AND REVERSAL OF CHRONIC DISEASE: RECOMMENDATIONS FROM THE LIFESTYLE MEDICINE RESEARCH SUMMIT. DECLINING LIFE EXPECTANCY AND INCREASING ALL-CAUSE MORTALITY IN THE UNITED STATES HAVE BEEN ASSOCIATED WITH UNHEALTHY BEHAVIORS, SOCIOECOLOGICAL FACTORS, AND PREVENTABLE DISEASE. A GROWING BODY OF BASIC SCIENCE, CLINICAL RESEARCH, AND POPULATION HEALTH EVIDENCE POINTS TO THE BENEFITS OF HEALTHY BEHAVIORS, ENVIRONMENTS AND POLICIES TO MAINTAIN HEALTH AND PREVENT, TREAT, AND REVERSE THE ROOT CAUSES OF COMMON CHRONIC DISEASES. SIMILARLY, INNOVATIONS IN RESEARCH METHODOLOGIES, STANDARDS OF EVIDENCE, EMERGENCE OF UNIQUE STUDY COHORTS, AND BREAKTHROUGHS IN DATA ANALYTICS AND MODELING CREATE NEW POSSIBILITIES FOR PRODUCING BIOMEDICAL KNOWLEDGE AND CLINICAL TRANSLATION. TO UNDERSTAND THESE ADVANCES AND INFORM FUTURE DIRECTIONS RESEARCH, THE LIFESTYLE MEDICINE RESEARCH SUMMIT WAS CONVENED AT THE UNIVERSITY OF PITTSBURGH ON DECEMBER 4-5, 2019. THE SUMMIT'S GOAL WAS TO REVIEW CURRENT STATUS AND DEFINE RESEARCH PRIORITIES IN THE SIX CORE AREAS OF LIFESTYLE MEDICINE: PLANT-PREDOMINANT NUTRITION, PHYSICAL ACTIVITY, SLEEP, STRESS, ADDICTIVE BEHAVIORS, AND POSITIVE PSYCHOLOGY/SOCIAL CONNECTION. FORTY INVITED SUBJECT MATTER EXPERTS (1) REVIEWED EXISTING KNOWLEDGE AND GAPS RELATING LIFESTYLE BEHAVIORS TO COMMON CHRONIC DISEASES, SUCH AS CARDIOVASCULAR DISEASE, DIABETES, MANY CANCERS, INFLAMMATORY- AND IMMUNE-RELATED DISORDERS AND OTHER CONDITIONS; AND (2) DISCUSSED THE POTENTIAL FOR APPLYING CUTTING-EDGE MOLECULAR, CELLULAR, EPIGENETIC AND EMERGING SCIENCE KNOWLEDGE AND COMPUTATIONAL METHODOLOGIES, RESEARCH DESIGNS, AND STUDY COHORTS TO ACCELERATE CLINICAL APPLICATIONS ACROSS ALL SIX DOMAINS OF LIFESTYLE MEDICINE. NOTABLY, FEDERAL HEALTH AGENCIES, SUCH AS THE DEPARTMENT OF DEFENSE AND VETERANS ADMINISTRATION HAVE BEGUN TO ADOPT "WHOLE-PERSON HEALTH AND PERFORMANCE" MODELS THAT ADDRESS THESE LIFESTYLE AND ENVIRONMENTAL ROOT CAUSES OF CHRONIC DISEASE AND ASSOCIATED MORBIDITY, MORTALITY, AND COST. RECOMMENDATIONS STRONGLY SUPPORT LEVERAGING EMERGING RESEARCH METHODOLOGIES, SYSTEMS BIOLOGY, AND COMPUTATIONAL MODELING IN ORDER TO ACCELERATE EFFECTIVE CLINICAL AND POPULATION SOLUTIONS TO IMPROVE HEALTH AND REDUCE SOCIETAL COSTS. NEW AND ALTERNATIVE HIERARCHIES OF EVIDENCE ARE ALSO BE NEEDED IN ORDER TO ASSESS THE QUALITY OF EVIDENCE AND DEVELOP EVIDENCE-BASED GUIDELINES ON LIFESTYLE MEDICINE. CHILDREN AND UNDERSERVED POPULATIONS WERE IDENTIFIED AS PRIORITIZED GROUPS TO STUDY. THE COVID-19 PANDEMIC, WHICH DISPROPORTIONATELY IMPACTS PEOPLE WITH CHRONIC DISEASES THAT ARE AMENABLE TO EFFECTIVE LIFESTYLE MEDICINE INTERVENTIONS, MAKES THE SUMMIT'S FINDINGS AND RECOMMENDATIONS FOR FUTURE RESEARCH PARTICULARLY TIMELY AND RELEVANT. 2020 16 5655 31 SEX-BASED MEDICINE MEETS PSORIATIC ARTHRITIS: LESSONS LEARNED AND TO LEARN. HUMORALLY ASSOCIATED AUTOIMMUNE DISEASES GENERALLY SHOW A FEMALE PREDOMINANCE WHEREAS ANKYLOSING SPONDYLITIS, A DISEASE THAT OVERLAPS WITH PSORIATIC ARTHRITIS (PSA), SHOWS A MALE PREDOMINANCE. THE PRESENT REVIEW ASCERTAINS THE CURRENT KNOWLEDGE OF SEX-SPECIFIC DIFFERENCES RELATED TO PSORIATIC ARTHRITIS (PSA), A CHRONIC, INFLAMMATORY CONDITION ASSOCIATED WITH PSORIASIS. SEX DIFFERENCES MAY HAVE IMPORTANT IMPLICATIONS FOR CLINICAL RESEARCH IN PSA AND IN TERMS OF EPIDEMIOLOGY (INCIDENCE, PREVALENCE, LIFETIME RISK, SURVIVAL, AND MORTALITY), CLINICAL, RADIOLOGICAL, AND LABORATORY FEATURES, AND RESPONSE TO TREATMENT. WHILE NATIONWIDE SURVEYS AND LARGE-SCALE DATABASES AND REGISTRIES SHOW NO SEX-SPECIFIC DIFFERENCES, VARYING MALE/FEMALE RATIOS HAVE BEEN REPORTED, RANGING FROM 0.42 TO 2.75 (COMPARABLE WITH THOSE REPORTED FOR PSORIASIS VULGARIS: RANGING FROM 0.28 TO 2.38). THIS MAY REFLECT SUBTLE, COMPLEX, NONLINEAR INTERACTIONS BETWEEN THE BIOLOGICAL MAKE-UP OF THE INDIVIDUAL (GENETIC AND EPIGENETIC DIFFERENCES), HORMONAL COMPONENTS INCLUDING MENOPAUSAL STATUS, ENVIRONMENTAL EXPOSURES INCLUDING SKELETAL PHYSICAL STRESSING, AND PSYCHOLOGICAL VARIABLES. THERE EXISTS METHODOLOGICAL HETEROGENEITY AND PAUCITY OF DATA CONCERNING SEX-SPECIFIC DIFFERENCES, IN TERMS OF THE SPECIFIC POPULATION STUDIED, STUDY DESIGN, AND THE DIAGNOSTIC CRITERIA UTILIZED. HARMONIZING AND RECONCILING THESE DISCREPANCIES WOULD BE OF CRUCIAL IMPORTANCE IN ACHIEVING THE AMBITIOUS GOALS OF PERSONALIZED/INDIVIDUALIZED MEDICINE AND FURTHER STANDARDIZED META-DATA AND BIG DATA COULD HELP DISENTANGLE AND ELUCIDATE THE PRECISE MECHANISMS OF UNDERLYING POTENTIAL PSA SEX-SPECIFIC DIFFERENCES. 2022 17 6329 50 THE ROLE OF CHILDHOOD TRAUMA IN BIPOLAR DISORDERS. THIS REVIEW WILL DISCUSS THE ROLE OF CHILDHOOD TRAUMA IN BIPOLAR DISORDERS. RELEVANT STUDIES WERE IDENTIFIED VIA MEDLINE (PUBMED) AND PSYCINFO DATABASES PUBLISHED UP TO AND INCLUDING JULY 2015. THIS REVIEW CONTRIBUTES TO A NEW UNDERSTANDING OF THE NEGATIVE CONSEQUENCES OF EARLY LIFE STRESS, AS WELL AS SETTING CHILDHOOD TRAUMA IN A BIOLOGICAL CONTEXT OF SUSCEPTIBILITY AND DISCUSSING NOVEL LONG-TERM PATHOPHYSIOLOGICAL CONSEQUENCES IN BIPOLAR DISORDERS. CHILDHOOD TRAUMATIC EVENTS ARE RISK FACTORS FOR DEVELOPING BIPOLAR DISORDERS, IN ADDITION TO A MORE SEVERE CLINICAL PRESENTATION OVER TIME (PRIMARILY AN EARLIER AGE AT ONSET AND AN INCREASED RISK OF SUICIDE ATTEMPT AND SUBSTANCE MISUSE). CHILDHOOD TRAUMA LEADS TO ALTERATIONS OF AFFECT REGULATION, IMPULSE CONTROL, AND COGNITIVE FUNCTIONING THAT MIGHT DECREASE THE ABILITY TO COPE WITH LATER STRESSORS. CHILDHOOD TRAUMA INTERACTS WITH SEVERAL GENES BELONGING TO SEVERAL DIFFERENT BIOLOGICAL PATHWAYS [HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS, SEROTONERGIC TRANSMISSION, NEUROPLASTICITY, IMMUNITY, CALCIUM SIGNALING, AND CIRCADIAN RHYTHMS] TO DECREASE THE AGE AT THE ONSET OF THE DISORDER OR INCREASE THE RISK OF SUICIDE. EPIGENETIC FACTORS MAY ALSO BE INVOLVED IN THE NEUROBIOLOGICAL CONSEQUENCES OF CHILDHOOD TRAUMA IN BIPOLAR DISORDER. BIOLOGICAL SEQUELAE SUCH AS CHRONIC INFLAMMATION, SLEEP DISTURBANCE, OR TELOMERE SHORTENING ARE POTENTIAL MEDIATORS OF THE NEGATIVE EFFECTS OF CHILDHOOD TRAUMA IN BIPOLAR DISORDERS, IN PARTICULAR WITH REGARD TO PHYSICAL HEALTH. THE MAIN CLINICAL IMPLICATION IS TO SYSTEMATICALLY ASSESS CHILDHOOD TRAUMA IN PATIENTS WITH BIPOLAR DISORDERS, OR AT LEAST IN THOSE WITH A SEVERE OR INSTABLE COURSE. THE CHALLENGE FOR THE NEXT YEARS WILL BE TO FILL THE GAP BETWEEN CLINICAL AND FUNDAMENTAL RESEARCH AND ROUTINE PRACTICE, SINCE RECOMMENDATIONS FOR MANAGING THIS SPECIFIC POPULATION ARE LACKING. IN PARTICULAR, LITTLE IS KNOWN ON WHICH PSYCHOTHERAPIES SHOULD BE PROVIDED OR WHICH TARGETS THERAPISTS SHOULD FOCUS ON, AS WELL AS HOW CHILDHOOD TRAUMA COULD EXPLAIN THE RESISTANCE TO MOOD STABILIZERS. 2016 18 6598 31 TWINSUK: THE UK ADULT TWIN REGISTRY UPDATE. TWINSUK IS THE LARGEST COHORT OF COMMUNITY-DWELLING ADULT TWINS IN THE UK. THE REGISTRY COMPRISES OVER 14,000 VOLUNTEER TWINS (14,838 INCLUDING MIXED, SINGLE AND TRIPLETS); IT IS PREDOMINANTLY FEMALE (82%) AND MIDDLE-AGED (MEAN AGE 59). IN ADDITION, OVER 1800 PARENTS AND SIBLINGS OF TWINS ARE REGISTERED VOLUNTEERS. DURING THE LAST 27 YEARS, TWINSUK HAS COLLECTED NUMEROUS QUESTIONNAIRE RESPONSES, PHYSICAL/COGNITIVE MEASURES AND BIOLOGICAL MEASURES ON OVER 8500 SUBJECTS. DATA WERE COLLECTED ALONGSIDE FOUR COMPREHENSIVE PHENOTYPING CLINICAL VISITS TO THE DEPARTMENT OF TWIN RESEARCH AND GENETIC EPIDEMIOLOGY, KING'S COLLEGE LONDON. SUCH COLLECTION METHODS HAVE RESULTED IN VERY DETAILED LONGITUDINAL CLINICAL, BIOCHEMICAL, BEHAVIORAL, DIETARY AND SOCIOECONOMIC COHORT CHARACTERIZATION; IT PROVIDES A MULTIDISCIPLINARY PLATFORM FOR THE STUDY OF COMPLEX DISEASE DURING THE ADULT LIFE COURSE, INCLUDING THE PROCESS OF HEALTHY AGING. THE MAJOR STRENGTH OF TWINSUK IS THE AVAILABILITY OF SEVERAL 'OMIC' TECHNOLOGIES FOR A RANGE OF SAMPLE TYPES FROM PARTICIPANTS, WHICH INCLUDES GENOMEWIDE SCANS OF SINGLE-NUCLEOTIDE VARIANTS, NEXT-GENERATION SEQUENCING, METABOLOMIC PROFILES, MICROBIOMICS, EXOME SEQUENCING, EPIGENETIC MARKERS, GENE EXPRESSION ARRAYS, RNA SEQUENCING AND TELOMERE LENGTH MEASURES. TWINSUK FACILITATES AND ACTIVELY ENCOURAGES SHARING THE 'TWINSUK' RESOURCE WITH THE SCIENTIFIC COMMUNITY - INTERESTED RESEARCHERS MAY REQUEST DATA VIA THE TWINSUK WEBSITE (HTTP://TWINSUK.AC.UK/RESOURCES-FOR-RESEARCHERS/ACCESS-OUR-DATA/) FOR THEIR OWN USE OR FUTURE COLLABORATION WITH THE STUDY TEAM. IN ADDITION, FURTHER COHORT DATA COLLECTION IS PLANNED VIA THE WELLCOME OPEN RESEARCH GATEWAY (HTTPS://WELLCOMEOPENRESEARCH.ORG/GATEWAYS). THE CURRENT ARTICLE PRESENTS AN UP-TO-DATE REPORT ON THE APPLICATION OF TECHNOLOGICAL ADVANCES, NEW STUDY PROCEDURES IN THE COHORT AND FUTURE DIRECTION OF TWINSUK. 2019 19 6742 36 WHITHER THE ETIOPATHOGENESIS (AND SCOLIOGENY) OF ADOLESCENT IDIOPATHIC SCOLIOSIS? ALTHOUGH CONSIDERABLE PROGRESS HAD BEEN MADE IN THE PAST TWO DECADES IN UNDERSTANDING THE ETIOPATHOGENESIS OF ADOLESCENT IDIOPATHIC SCOLIOSIS (AIS), IT STILL LACKS AN AGREED THEORY OF ETIOPATHOGENESIS. ONE PROBLEM MAY BE THAT AIS RESULTS NOT FROM ONE CAUSE, BUT SEVERAL THAT INTERACT WITH VARIOUS GENETIC PREDISPOSING FACTORS. THERE IS A VIEW THERE ARE TWO OTHER PATHOGENIC PROCESSES FOR IDIOPATHIC SCOLIOSIS NAMELY, INITIATING (OR INDUCING), AND THOSE THAT CAUSE CURVE PROGRESSION. TWIN STUDIES AND OBSERVATIONS OF FAMILY AGGREGATION HAVE REVEALED SIGNIFICANT GENETIC CONTRIBUTIONS TO IDIOPATHIC SCOLIOSIS, THAT PLACE AIS AMONG OTHER COMMON DISEASE OR COMPLEX TRAITS WITH A HIGH HERITABILITY INTERPRETED BY THE GENETIC VARIANT HYPOTHESIS OF DISEASE. WE SUMMARIZE ETIOPATHOGENETIC KNOWLEDGE OF AIS AS THEORIES OF PATHOGENESIS INCLUDING RECENT MULTIPLE CONCEPTS, AND BLOOD TESTS FOR AIS BASED ON PREDICTIVE BIOMARKERS AND GENETIC VARIANTS THAT SIGNIFY DISEASE RISK. THERE IS INCREASING EVIDENCE FOR THE POSSIBILITY OF AN UNDERLYING NEUROLOGICAL DISORDER FOR AIS, RESEARCH WHICH HOLDS PROMISE. LIKE BRAIN RESEARCH, MOST AIS WORKERS FOCUS ON THEIR OWN CORNER AND THERE IS A NEED FOR GREATER INTEGRATION OF RESEARCH EFFORT. EPIGENETICS, A RELATIVELY RECENT FIELD, EVALUATES FACTORS CONCERNED WITH GENE EXPRESSION IN RELATION TO ENVIRONMENT, DISEASE, NORMAL DEVELOPMENT AND AGING, WITH A COMPLEX REGULATION ACROSS THE GENOME DURING THE FIRST DECADE OF LIFE. RESEARCH ON THE ROLE OF ENVIRONMENTAL FACTORS, EPIGENETICS AND CHRONIC NON-COMMUNICABLE DISEASES (NCDS) INCLUDING ADIPOSITY, AFTER A SLOW START, HAS EXPLODED IN THE LAST DECADE. NOT SO FOR AIS RESEARCH AND THE ENVIRONMENT WHERE, EXCEPT FOR MONOZYGOTIC TWIN STUDIES, THERE ARE ONLY SPORADIC REPORTS TO SUGGEST THAT ENVIRONMENTAL FACTORS ARE AT WORK IN ETIOLOGY. HERE, WE EXAMINE EPIGENETIC CONCEPTS AS THEY MAY RELATE TO HUMAN DEVELOPMENT, NORMAL LIFE HISTORY PHASES AND AIS PATHOGENESIS. ALTHOUGH AIS IS NOT REGARDED AS AN NCD, LIKE THEM, IT IS ASSOCIATED WITH WHOLE ORGANISM METABOLIC PHENOMENA, INCLUDING LOWER BODY MASS INDEX, LOWER CIRCULATING LEPTIN LEVELS AND OTHER SYSTEMIC DISORDERS. SOME EPIGENETIC RESEARCH APPLIED TO SILVER-RUSSELL SYNDROME AND ADIPOSITY IS EXAMINED, FROM WHICH SUGGESTIONS ARE MADE FOR CONSIDERATION OF AIS EPIGENETIC RESEARCH, CROSS-SECTIONAL AND LONGITUDINAL. THE WORD SCOLIOGENY IS SUGGESTED TO INCLUDE ETIOLOGY, PATHOGENESIS AND PATHOMECHANISM. 2012 20 2093 37 EPIGENETIC EFFECTS FOLLOWING ACUTE AND CHRONIC EXERCISE IN CARDIOVASCULAR DISEASE: A SYSTEMATIC REVIEW. INTRODUCTION: ACUTE EXERCISE AND EXERCISE TRAINING MAY CONFER EPIGENETIC MODIFICATIONS IN HEALTHY SUBJECTS. EPIGENETIC EFFECTS AFTER EXERCISE HAVE BEEN SHOWED IN PATIENTS WITH CARDIOVASCULAR DISEASE. THE AIM OF THIS SYSTEMATIC REVIEW WAS TO SUMMARIZE THE EVIDENCE FROM AVAILABLE CLINICAL TRIALS THAT STUDY EPIGENETIC ADAPTATIONS AFTER EXERCISE IN PATIENTS WITH CARDIOVASCULAR DISEASE. METHODS: THE SEARCH STRATEGY WAS PERFORMED IN PUBMED AND CENTRAL DATABASES ON ARTICLES PUBLISHED UNTIL SEPTEMBER 2020. STUDIES WITH TITLES AND ABSTRACTS RELEVANT TO EXERCISE EPIGENETIC MODIFICATION APPLIED TO CARDIOVASCULAR PATIENTS WERE FULLY EXAMINED. INCLUSION AND EXCLUSION CRITERIA WERE UTILIZED FOR STUDIES SCREENING. QUALITY ASSESSMENT WITH PEDRO SCALE AND EVALUATION BY TWO INDEPENDENT REVIEWERS WAS PERFORMED. RESULTS: OF THE 1714 ARTICLES RETRIEVED, 88 ARTICLES WERE ASSESSED FOR ELIGIBILITY CRITERIA AND 8 ARTICLES MATCHED OUR SEARCH CRITERIA AND FINALLY INCLUDED IN THE SYSTEMATIC ANALYSIS. THE ACUTE EXERCISE EPIGENETIC (MIRNAS) EFFECTS WERE ASSESSED IN THREE STUDIES AND THE CHRONIC EXERCISE TRAINING EFFECTS (MIRNAS AND DNA METHYLATION) IN SIX STUDIES. THE RESULTS HAVE SHOWN THAT THERE IS POSSIBLY AN ACUTE SIGNIFICANT EXERCISE EFFECT ON EPIGENETIC TARGETS WHICH IS MORE EVIDENT AFTER CHRONIC EXERCISE TRAINING. CONCLUSIONS: BY THE PRESENT SYSTEMATIC REVIEW, WE PROVIDE PRELIMINARY EVIDENCE OF BENEFICIAL EPIGENETIC ADAPTATIONS FOLLOWING ACUTE AND CHRONIC EXERCISE IN PATIENTS WITH CARDIOVASCULAR DISEASE. MORE CONTROLLED STUDIES ARE NEEDED TO CONFIRM SUCH EVIDENCE. 2021