1   639 208 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
2  5882  45 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
3  6112  65 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
4   455  50 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
5  1145  39 CONCURRENT DIAGNOSIS OF ADENOMYOSIS AND CONGENITAL UTERINE ANOMALIES: A REVIEW. BACKGROUND: ADENOMYOSIS AND CONGENITAL UTERINE ANOMALIES (CUAS) CAN COMPROMISE REPRODUCTIVE POTENTIAL AND MAY COEXIST IN THE SAME PATIENT, ESPECIALLY IN CASES OF INFERTILITY. THIS REVIEW (CRD42022382850) AIMS TO EVALUATE THE PUBLISHED CASES OF CONCURRENT ADENOMYOSIS AND SYNDROMIC AND NONSYNDROMIC CUAS. METHODS: A LITERATURE SEARCH FOR SUITABLE ARTICLES PUBLISHED IN THE ENGLISH LANGUAGE WAS PERFORMED USING THE FOLLOWING DATABASES FROM INCEPTION TO 30 NOVEMBER 2022: MEDLINE, EMBASE, GLOBAL HEALTH, THE COCHRANE LIBRARY, HEALTH TECHNOLOGY ASSESSMENT DATABASE, AND WEB OF SCIENCE. ARTICLES INCLUDING BOTH CUAS AND ADENOMYOSIS, WITH DATA ABOUT THEIR POTENTIAL RELATIONSHIP, WERE INCLUDED. RESULTS: THE LITERATURE SEARCH RETRIEVED 14 ARTICLES THAT MET THE PURPOSE OF THIS REVIEW AND SUMMARIZED THE MOST RECENT FINDINGS REGARDING THE CONCURRENT DIAGNOSIS OF ADENOMYOSIS AND CUAS. CONCLUSIONS: ADENOMYOSIS CAN BE FOUND IN BOTH SYNDROMIC AND NONSYNDROMIC CUAS, AND MAY ARISE FROM SEVERAL ETIOLOGIES. THE HYPOTHESIS THAT OBSTRUCTIONS IN CUAS INCREASE UTERINE PRESSURE AND PROMOTE THE DEVELOPMENT OF ADENOMYOSIS REMAINS TO BE FURTHER ELUCIDATED, AND ADDITIONAL FINDINGS MAY ALSO PLAY A ROLE. THE PATIENT'S GENETIC, EPIGENETIC, AND HORMONAL PATTERNS, AS WELL AS NORMAL PHYSIOLOGICAL PROCESSES, SUCH AS PREGNANCY, MAY INFLUENCE THE GROWTH OF ADENOMYOSIS.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
6  5137  54 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
7   497  38 ASSOCIATION BETWEEN BMI AND DNA METHYLATION IN BLOOD OR NORMAL ADULT BREAST TISSUE: A SYSTEMATIC REVIEW. BACKGROUND/AIM: SEVERAL STUDIES HAVE INVESTIGATED THE INFLUENCE OF OBESITY ON DNA METHYLATION (DNAM) TO FIND BIOMARKERS ASSOCIATED WITH THE DETECTION OF CHRONIC DISEASES, INCLUDING BREAST CANCER. THE AIM OF THE STUDY WAS TO SYSTEMATICALLY REVIEW STUDIES EXAMINING THE ASSOCIATION OF BODY MASS INDEX (BMI) AND DNAM IN BLOOD OR NORMAL BREAST TISSUE. MATERIALS AND METHODS: THREE SCIENTIFIC LITERATURE DATABASES (PUBMED, EMBASE AND WEB OF SCIENCE) WERE SCREENED UNTIL MAY 2018. RESULTS: TWENTY-FOUR STUDIES WERE INCLUDED ALONG WITH OURS IN WHICH WE INVESTIGATED THIS RELATION IN THE NORMAL BREAST TISSUE OF 40 BREAST CANCER PATIENTS. CONCLUSION: BMI-ASSOCIATED CPG SITES WERE HIGHLY VARIABLE WITH FEW IDENTIFIED IN LESS THAN HALF OF THE STUDIES. NEVERTHELESS, A FEW GENES POTENTIALLY ASSOCIATED WITH BMI WERE HIGHLIGHTED IN BLOOD (CPT1A, ABCG1, SREBF1 AND LGALS3BP) AND IN NORMAL BREAST TISSUE (PTPRN2 AND ABLIM2). THE VARIABILITY OF THE RESULTS COULD BE EXPLAINED BY THE TISSUE AND CELL-SPECIFICITY OF METHYLATION AND DIFFERENCES IN METHODOLOGY.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
8  1517  40 DNA METHYLATION AS A MEDIATOR OF ASSOCIATIONS BETWEEN THE ENVIRONMENT AND CHRONIC DISEASES: A SCOPING REVIEW ON APPLICATION OF MEDIATION ANALYSIS. DNA METHYLATION (DNAM) IS ONE OF THE MOST STUDIED EPIGENETIC MODIFICATIONS. DNAM HAS EMERGED AS A KEY BIOLOGICAL MECHANISM AND BIOMARKERS TO TEST ASSOCIATIONS BETWEEN ENVIRONMENTAL EXPOSURE AND OUTCOMES IN EPIDEMIOLOGICAL STUDIES. ALTHOUGH PREVIOUS STUDIES HAVE FOCUSED ON ASSOCIATIONS BETWEEN DNAM AND EITHER EXPOSURE/OUTCOMES, IT IS USEFUL TO TEST FOR MEDIATION OF THE ASSOCIATION BETWEEN EXPOSURE AND OUTCOME BY DNAM. THE PURPOSE OF THIS SCOPING REVIEW IS TO INTRODUCE THE METHODOLOGICAL ESSENCE OF STATISTICAL MEDIATION ANALYSIS AND TO EXAMINE EMERGING EPIDEMIOLOGICAL RESEARCH APPLYING MEDIATION ANALYSES. WE CONDUCTED THIS SCOPING REVIEW FOR PUBLISHED PEER-REVIEWED JOURNALS ON THIS TOPIC USING ONLINE DATABASES (PUBMED, SCOPUS, COCHRANE, AND CINAHL) ENDING IN DECEMBER 2020. WE EXTRACTED A TOTAL OF 219 ARTICLES BY INITIAL SCREENING. AFTER REVIEWING TITLES, ABSTRACTS, AND FULL TEXTS, A TOTAL OF 69 ARTICLES WERE ELIGIBLE FOR THIS REVIEW. THE BREAKDOWN OF STUDIES ASSIGNED TO EACH CATEGORY WAS 13 FOR SMOKING (18.8%), 8 FOR DIETARY INTAKE AND FAMINE (11.6%), 6 FOR OTHER LIFESTYLE FACTORS (8.7%), 8 FOR CLINICAL ENDPOINTS (11.6%), 22 FOR ENVIRONMENTAL CHEMICAL EXPOSURES (31.9%), 2 FOR SOCIOECONOMIC STATUS (SES) (2.9%), AND 10 FOR GENETIC FACTORS AND RACE (14.5%). IN THIS REVIEW, WE PROVIDE AN EXPOSURE-WIDE SUMMARY FOR THE MEDIATION ANALYSIS USING DNAM LEVELS. HOWEVER, WE FOUND HETEROGENOUS METHODS AND INTERPRETATIONS IN MEDIATION ANALYSIS WITH TYPICAL ISSUES SUCH AS DIFFERENT CELL COMPOSITIONS AND TISSUE-SPECIFICITY. FURTHER ACCUMULATION OF EVIDENCE WITH DIVERSE EXPOSURES, POPULATIONS AND WITH RIGOROUS METHODOLOGY WILL BE EXPECTED TO PROVIDE FURTHER INSIGHT IN THE ROLE OF DNAM IN DISEASE SUSCEPTIBILITY.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
9  2093  41 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
10  1151  43 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
11   108  37 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  2585  55 EPIGENETICS OF OBSTRUCTIVE SLEEP APNEA SYNDROME: A SYSTEMATIC REVIEW. STUDY OBJECTIVES: OBSTRUCTIVE SLEEP APNEA (OSA) IS A CHRONIC AND WIDELY PREVALENT DISEASE ASSOCIATED WITH MULTIPLE HEALTH DISORDERS. CURRENT DIAGNOSTIC STRATEGIES FOR OSA ARE LIMITED BECAUSE OF COST, TIME, AND ACCESS. EPIGENETIC SIGNATURES OFFER INSIGHT INTO THE RELATIONSHIPS BETWEEN DISEASE AND ENVIRONMENT AND COULD PLAY A SIGNIFICANT ROLE IN DEVELOPING BOTH DIAGNOSTIC AND THERAPEUTIC TOOLS FOR OSA. IN THE CURRENT STUDY, A SYSTEMATIC LITERATURE SEARCH WAS CONDUCTED TO INVESTIGATE THE EXISTING EVIDENCE OF OSA-ASSOCIATED EPIGENETIC MODIFICATIONS. METHODS: A SYSTEMATIC LITERATURE SEARCH WAS PERFORMED USING ELECTRONIC ACADEMIC DATABASES INCLUDING PUBMED, CINAHL, SCOPUS, EMBASE, EBM REVIEWS, AND WEB OF SCIENCE. HOWEVER, THE CURRENT STUDY FOCUSED ON SCREENING FOR ORIGINAL, ENGLISH-LANGUAGE ARTICLES PERTAINING TO OSA AND ASSOCIATED EPIGENETIC MECHANISMS. TO PRODUCE UNBIASED RESULTS, SCREENING WAS PERFORMED INDEPENDENTLY BY AUTHORS. RESULTS: WE IDENTIFIED 2,944 PUBLICATIONS IN OUR SYSTEMATIC SEARCH. AMONG THEM, 65 RESEARCH ARTICLES WERE RELATED TO OS A-ASSOCIATED DIFFERENTIAL GENE EXPRESSION, GENETIC VARIATION, AND EPIGENETIC MODIFICATIONS. ALTHOUGH THESE 65 ARTICLES WERE CONSIDERED FOR FULL MANUSCRIPT REVIEW, ONLY 12 ARTICLES MET THE CRITERIA OF OSA-ASSOCIATED EPIGENETIC MODIFICATIONS IN HUMAN AND ANIMAL MODELS. HUMAN PATIENTS WITH OSA HAD UNIQUE EPIGENETIC CHANGES COMPARED TO HEALTHY CONTROL PATIENTS AND, INTERESTINGLY, EPIGENETIC SIGNATURES WERE COMMONLY IDENTIFIED IN GENES ASSOCIATED WITH METABOLIC AND INFLAMMATORY PATHWAYS. CONCLUSIONS: ALTHOUGH THE AVAILABLE STUDIES ARE LIMITED, THIS RESEARCH PROVIDES NOVEL INSIGHTS FOR THE DEVELOPMENT OF EPIGENETIC MARKERS FOR THE DIAGNOSIS AND TREATMENT OF OSA. THOROUGH GENOME-WIDE INVESTIGATIONS WILL BE REQUIRED TO DEVELOP COST-EFFECTIVE, ROBUST BIOMARKERS FOR THE IDENTIFICATION OF OSA AMONG CHILDREN AND ADULTS. HERE, WE OFFER A STUDY DESIGN FOR SUCH EFFORTS. CITATION: LEADER BA, KORITALA BSC, MOORE CA, DEAN EG, KOTTYAN LC, SMITH DF. EPIGENETICS OF OBSTRUCTIVE SLEEP APNEA SYNDROME: A SYSTEMATIC REVIEW. J CLIN SLEEP MED. 2021;17(12):2533-2541.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
13  2622  47 EPIGENOME-WIDE ASSOCIATION STUDIES IN ASTHMA: A SYSTEMATIC REVIEW. OBJECTIVE: ASTHMA IS A COMMON CHRONIC RESPIRATORY AIRWAY DISEASE INFLUENCED BY ENVIRONMENTAL FACTORS AND POSSIBLY THEIR INTERACTION WITH THE HUMAN GENOME CAUSING EPIGENETIC CHANGES. EPIGENOME-WIDE ASSOCIATION STUDIES (EWAS) HAVE MAINLY INVESTIGATED DNA METHYLATION AND ITS ASSOCIATION WITH DISEASE OR TRAITS, EXPOSURE FACTORS OR GENE EXPRESSION. THIS SYSTEMATIC REVIEW AIMED TO IDENTIFY ALL EWAS ASSESSING DIFFERENTIALLY METHYLATED SITES ASSOCIATED WITH ASTHMA IN HUMANS. DESIGN: STRUCTURED SYSTEMATIC LITERATURE SEARCH FOLLOWING PRISMA GUIDELINES, NEWCASTLE-OTTAWA SCALE (NOS) FOR COHORT STUDIES WAS USED FOR BIAS ASSESSMENT. DATA SOURCES: WE SEARCHED PUBMED AND EMBASE DATABASES FROM 2005 TO 2019. ELIGIBILITY CRITERIA: EPIGENOME-WIDE ASSOCIATION STUDIES TESTING ASSOCIATION BETWEEN DIFFERENTIAL METHYLATION AND ASTHMA IN HUMANS. RESULTS: OVERALL, WE IDENTIFIED 16 EWAS STUDIES COMPLYING WITH OUR SEARCH CRITERIA. TWELVE STUDIES WERE CONDUCTED ON CHILDREN, AND 10 WERE CONDUCTED ON SAMPLE SIZES <150 SUBJECTS. FOUR HUNDRED AND NINETEEN CPGS WERE REPORTED IN CHILDREN STUDIES AFTER CORRECTION FOR MULTIPLE TESTING. IN THE ADULT STUDIES, THOUSANDS OF DIFFERENTIALLY METHYLATED SITES WERE IDENTIFIED. DIFFERENTIAL METHYLATION IN INFLAMMATORY-RELATED GENES CORRELATED WITH HIGHER LEVELS OF GENE EXPRESSIONS OF INFLAMMATORY MODULATORS IN ASTHMA. DIFFERENTIALLY METHYLATED GENES ASSOCIATED WITH ASTHMA INCLUDED SMAD3, SERPINC1, PROK1, IL13, RUNX3 AND TIGIT. FORTY-ONE CPGS WERE REPLICATED AT LEAST ONCE IN BLOOD SAMPLES, AND 28 CPGS WERE REPLICATED IN NASAL SAMPLES. CONCLUSION: ALTHOUGH MANY DIFFERENTIALLY METHYLATED CPGS IN GENES KNOWN TO BE INVOLVED IN ASTHMA HAVE BEEN IDENTIFIED IN EWAS TO DATE, WE CONCLUDE THAT FURTHER STUDIES OF LARGER SAMPLE SIZES AND ANALYSES OF DIFFERENTIAL METHYLATION BETWEEN DIFFERENT PHENOTYPES ARE NEEDED IN ORDER TO COMPREHENSIVELY EVALUATE THE ROLE OF EPIGENETIC FACTORS IN THE PATHOPHYSIOLOGY AND HETEROGENEITY OF ASTHMA, AND THE POTENTIAL CLINICAL UTILITY TO PREDICT OR CLASSIFY PATIENTS WITH ASTHMA.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
14  6127  39 THE EPIGENETIC OVERLAP BETWEEN OBESITY AND MOOD DISORDERS: A SYSTEMATIC REVIEW. (1) BACKGROUND: OBESITY AND MOOD DISORDERS ARE CONSIDERED AS THE MOST PREVALENT MORBIDITIES IN MANY COUNTRIES. WE SUPPOSE THAT EPIGENETIC MECHANISMS MAY INDUCE HIGHER RATES OF OBESITY IN SUBJECTS WHO SUFFER FROM MOOD DISORDERS. IN THIS SYSTEMATIC REVIEW, WE FOCUSED ON THE POTENTIAL ROLES OF DNA METHYLATION ON MOOD DISORDERS AND OBESITY DEVELOPMENT. (2) METHODS: THIS SYSTEMATIC REVIEW WAS CONDUCTED IN ACCORDANCE WITH THE PRISMA STATEMENT AND REGISTERED IN PROSPERO. A SYSTEMATIC SEARCH WAS CONDUCTED IN MEDLINE, SCOPUS, WEB OF SCIENCE, COCHRANE CENTRAL DATABASE, EMBASE, AND CINHAL. WE ALSO CONDUCTED A GREY LITERATURE SEARCH, SUCH AS GOOGLE SCHOLAR. (3) RESULTS: AFTER DEDUPLICATION, WE IDENTIFIED 198 POTENTIALLY RELATED CITATIONS. FINALLY, TEN UNIQUE STUDIES MET OUR INCLUSION CRITERIA. WE HAVE FOUND THREE OVERLAP GENES THAT SHOW SIGNIFICANT DNA METHYLATION CHANGES, BOTH IN OBESITY AND DEPRESSION. PATHWAY ANALYSIS INTERACTION FOR TAPBP, BDNF, AND SORBS2 CONFIRMED THE RELATION OF THESE GENES IN BOTH OBESITY AND MOOD DISORDERS. (4) CONCLUSIONS: WHILE MECHANISMS LINKING BOTH OBESITY AND MOOD DISORDERS TO EPIGENETIC RESPONSE ARE STILL UNKNOWN, WE HAVE ALREADY KNOWN CHRONIC INFLAMMATION INDUCES A NOVEL EPIGENETIC PROGRAM. AS THE RESULTS OF GENE ENRICHMENT, PATHWAYS ANALYSIS SHOWED THAT TAPBP, BDNF, AND SORBS2 LINKED TOGETHER BY INFLAMMATORY PATHWAYS. HYPERMETHYLATION IN THESE GENES MIGHT PLAY A CRUCIAL RULE IN THE CO-OCCURRENCE OF OBESITY AND MOOD DISORDERS.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
15  4607  39 NEIGHBORHOOD ENVIRONMENT AND DNA METHYLATION: IMPLICATIONS FOR CARDIOVASCULAR DISEASE RISK. EXPOSURE TO CHRONIC STRESS SUCH AS LIVING IN DISADVANTAGED NEIGHBORHOODS HAS BEEN RELATED TO CARDIOVASCULAR DISEASE (CVD). CHRONIC STRESS MAY INCREASE THE RISK FOR CVD BY INCREASING LEVELS OF SYSTEMIC INFLAMMATION (E.G., HIGHER LEVELS OF PRO-INFLAMMATORY CYTOKINES). DIFFERENTIAL DNA METHYLATION OF INFLAMMATION-RELATED CANDIDATE GENES IS ALSO RELATED TO HIGHER RISK FOR CVD. THUS, THE PURPOSE OF THIS REVIEW WAS TO EXAMINE THE ASSOCIATION OF NEIGHBORHOOD DISADVANTAGE WITH DNA METHYLATION. A SEARCH OF LITERATURE WAS CONDUCTED USING SCOPUS, CINAHL, PUBMED, MEDLINE, AND EMBASE DATABASES. THE KEYWORDS NEIGHBORHOOD, NEIGHBORHOOD DISORDER, NEIGHBORHOOD CRIME, NEIGHBORHOOD VIOLENCE, NEIGHBORHOOD SAFETY, BUILT ENVIRONMENT, AND HOUSING VACANCY WERE COMBINED WITH THE KEYWORDS DNA METHYLATION AND EPIGENETICS. FIVE STUDIES WERE INCLUDED IN THIS REVIEW (N = 3 ADULT BLOOD SAMPLES AND N = 2 FETAL BLOOD SAMPLES). FOUR OF THE FIVE STUDIES REPORTED AN ASSOCIATION OF NEIGHBORHOOD SOCIOECONOMIC STATUS, SOCIAL ENVIRONMENT, AND CRIME WITH EITHER GLOBAL OR GENE-SPECIFIC DNA METHYLATION. ONLY TWO STUDIES EXAMINED THE ASSOCIATION OF NEIGHBORHOOD DISADVANTAGE WITH INFLAMMATION-RELATED CANDIDATE GENES. ONE OF THESE STUDIES FOUND A SIGNIFICANT ASSOCIATION OF NEIGHBORHOOD SOCIOECONOMIC DISADVANTAGE AND SOCIAL ENVIRONMENT WITH DNA METHYLATION IN INFLAMMATION-RELATED CANDIDATE GENES. THUS, DATA ARE LIMITED ON THE ASSOCIATION BETWEEN NEIGHBORHOOD DISADVANTAGE AND DNA METHYLATION OF INFLAMMATION-RELATED CANDIDATE GENES, AS WELL AS GENES IN OTHER POTENTIAL MECHANISTIC PATHWAYS INCLUDING PSYCHOSOCIAL STRESS, TOXIN RESPONSE, AND ADIPOSITY. FUTURE STUDIES SHOULD EXAMINE THESE ASSOCIATIONS AND THE POTENTIAL EPIGENETIC MECHANISMS BY WHICH NEIGHBORHOOD DISADVANTAGE INCREASES THE RISK FOR CVD.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
16   667  61 BLOOD-BASED EPIGENOME-WIDE ANALYSES OF 19 COMMON DISEASE STATES: A LONGITUDINAL, POPULATION-BASED LINKED COHORT STUDY OF 18,413 SCOTTISH INDIVIDUALS. BACKGROUND: DNA METHYLATION IS A DYNAMIC EPIGENETIC MECHANISM THAT OCCURS AT CYTOSINE-PHOSPHATE-GUANINE DINUCLEOTIDE (CPG) SITES. EPIGENOME-WIDE ASSOCIATION STUDIES (EWAS) INVESTIGATE THE STRENGTH OF ASSOCIATION BETWEEN METHYLATION AT INDIVIDUAL CPG SITES AND HEALTH OUTCOMES. ALTHOUGH BLOOD METHYLATION MAY ACT AS A PERIPHERAL MARKER OF COMMON DISEASE STATES, PREVIOUS EWAS HAVE TYPICALLY FOCUSED ONLY ON INDIVIDUAL CONDITIONS AND HAVE HAD LIMITED POWER TO DISCOVER DISEASE-ASSOCIATED LOCI. THIS STUDY EXAMINED THE ASSOCIATION OF BLOOD DNA METHYLATION WITH THE PREVALENCE OF 14 DISEASE STATES AND THE INCIDENCE OF 19 DISEASE STATES IN A SINGLE POPULATION OF OVER 18,000 SCOTTISH INDIVIDUALS. METHODS AND FINDINGS: DNA METHYLATION WAS ASSAYED AT 752,722 CPG SITES IN WHOLE-BLOOD SAMPLES FROM 18,413 VOLUNTEERS IN THE FAMILY-STRUCTURED, POPULATION-BASED COHORT STUDY GENERATION SCOTLAND (AGE RANGE 18 TO 99 YEARS). EWAS TESTED FOR CROSS-SECTIONAL ASSOCIATIONS BETWEEN BASELINE CPG METHYLATION AND 14 PREVALENT DISEASE STATES, AND FOR LONGITUDINAL ASSOCIATIONS BETWEEN BASELINE CPG METHYLATION AND 19 INCIDENT DISEASE STATES. PREVALENT CASES WERE SELF-REPORTED ON HEALTH QUESTIONNAIRES AT THE BASELINE. INCIDENT CASES WERE IDENTIFIED USING LINKAGE TO SCOTTISH PRIMARY (READ 2) AND SECONDARY (ICD-10) CARE RECORDS, AND THE CENSORING DATE WAS SET TO OCTOBER 2020. THE MEAN TIME-TO-DIAGNOSIS RANGED FROM 5.0 YEARS (FOR CHRONIC PAIN) TO 11.7 YEARS (FOR CORONAVIRUS DISEASE 2019 (COVID-19) HOSPITALISATION). THE 19 DISEASE STATES CONSIDERED IN THIS STUDY WERE SELECTED IF THEY WERE PRESENT ON THE WORLD HEALTH ORGANISATION'S 10 LEADING CAUSES OF DEATH AND DISEASE BURDEN OR INCLUDED IN BASELINE SELF-REPORT QUESTIONNAIRES. EWAS MODELS WERE ADJUSTED FOR AGE AT METHYLATION TYPING, SEX, ESTIMATED WHITE BLOOD CELL COMPOSITION, POPULATION STRUCTURE, AND 5 COMMON LIFESTYLE RISK FACTORS. A STRUCTURED LITERATURE REVIEW WAS ALSO CONDUCTED TO IDENTIFY EXISTING EWAS FOR ALL 19 DISEASE STATES TESTED. THE MEDLINE, EMBASE, WEB OF SCIENCE, AND PREPRINT SERVERS WERE SEARCHED TO RETRIEVE RELEVANT ARTICLES INDEXED AS OF MARCH 27, 2023. FIFTY-FOUR OF APPROXIMATELY 2,000 INDEXED ARTICLES MET OUR INCLUSION CRITERIA: ASSAYED BLOOD-BASED DNA METHYLATION, HAD >20 INDIVIDUALS IN EACH COMPARISON GROUP, AND EXAMINED ONE OF THE 19 CONDITIONS CONSIDERED. FIRST, WE ASSESSED WHETHER THE ASSOCIATIONS IDENTIFIED IN OUR STUDY WERE REPORTED IN PREVIOUS STUDIES. WE IDENTIFIED 69 ASSOCIATIONS BETWEEN CPGS AND THE PREVALENCE OF 4 CONDITIONS, OF WHICH 58 WERE NEWLY DESCRIBED. THE CONDITIONS WERE BREAST CANCER, CHRONIC KIDNEY DISEASE, ISCHEMIC HEART DISEASE, AND TYPE 2 DIABETES MELLITUS. WE ALSO UNCOVERED 64 CPGS THAT ASSOCIATED WITH THE INCIDENCE OF 2 DISEASE STATES (COPD AND TYPE 2 DIABETES), OF WHICH 56 WERE NOT REPORTED IN THE SURVEYED LITERATURE. SECOND, WE ASSESSED REPLICATION ACROSS EXISTING STUDIES, WHICH WAS DEFINED AS THE REPORTING OF AT LEAST 1 COMMON SITE IN >2 STUDIES THAT EXAMINED THE SAME CONDITION. ONLY 6/19 DISEASE STATES HAD EVIDENCE OF SUCH REPLICATION. THE LIMITATIONS OF THIS STUDY INCLUDE THE NONCONSIDERATION OF MEDICATION DATA AND A POTENTIAL LACK OF GENERALIZABILITY TO INDIVIDUALS THAT ARE NOT OF SCOTTISH AND EUROPEAN ANCESTRY. CONCLUSIONS: WE DISCOVERED OVER 100 ASSOCIATIONS BETWEEN BLOOD METHYLATION SITES AND COMMON DISEASE STATES, INDEPENDENTLY OF MAJOR CONFOUNDING RISK FACTORS, AND A NEED FOR GREATER STANDARDISATION AMONG EWAS ON HUMAN DISEASE.	2023	

17  1221  40 CRITICAL CONNECTIONS AMONG EMBEDDING OF CHILDHOOD ADVERSITY AND ADULT CHRONIC GASTROINTESTINAL AND GENITOURINARY DISORDERS: A REVIEW OF THE LITERATURE. BACKGROUND: A GAP IN THE LITERATURE EXISTS DEMONSTRATING ASSOCIATIONS BETWEEN ADVERSE CHILD EXPERIENCES (ACES) AS POTENTIAL A PRIORI CONTRIBUTING FACTORS AND GASTROINTESTINAL (GI)/GENITOURINARY (GU) DISORDERS. PURPOSE: A NARRATIVE REVIEW OF THE LITERATURE WAS CONDUCTED TO EXPLORE CRITICAL CONNECTIONS BETWEEN ACES AND GI/GU DISORDERS WITH A WORKING HYPOTHESIS OF A DOSE-RESPONSIVE RELATIONSHIP EXISTING AMONG THEM. METHODS: A LITERATURE SEARCH WAS CONDUCTED USING MEDLINE, CUMULATIVE INDEX OF NURSING AND ALLIED HEALTH LITERATURE, PUBMED, AND WEB OF SCIENCE USING SEARCH TERMS ADVERSE CHILDHOOD EXPERIENCES, CHILDHOOD ADVERSITY, OBESITY, GASTROINTESTINAL DISORDERS, AND GENITOURINARY DISORDERS, AND SECONDARY SEARCHES OF OBESITY AND SPECIFIC GI/GU DISORDERS (EG, IRRITABLE BOWEL SYNDROME, PELVIC PAIN). DUPLICATES AND ARTICLES WITH INAPPROPRIATE FOCUS WERE DISCARDED AFTER REVIEW. RESULTS: A TOTAL OF 58 ARTICLES WERE INCLUDED. RESEARCH IDENTIFIED SHOWED THAT ACES DO PLAY A ROLE IN ADULT GI AND GU MORBIDITIES IN A DOSE-RESPONSE MANNER, AND SELECTED FACTORS SUCH AS SOCIOECONOMIC STATUS, RACE, GENDER IDENTITY, AND PHYSIOLOGIC STATE (EG, OBESITY) CONFER HIGHER RISK. RESEARCH ALSO SUGGESTED THAT GENETIC/EPIGENETIC MECHANISMS ARE AT PLAY IN DISEASE OCCURRENCE, AND THE IMPACT OF ACES MAY BE MITIGATED WITH POSITIVE LIFE EXPERIENCES. CONCLUSION: RESEARCH ON THE RELATIONSHIP BETWEEN ACES AND GI/GU DISORDERS IS HETEROGENEOUS, NOTABLY DUE TO WIDE VARIATIONS IN HOW TYPES OF ACES ARE DEFINED AND SCREENING METHODS USED. DESPITE THIS LIMITATION, ASSOCIATIONS ARE DEMONSTRATED. AWARENESS OF A POSSIBLE CORRELATION BETWEEN ACES AND RISK OF GI/GU DISORDERS HAS THE POTENTIAL TO IMPROVE PATIENT CARE, ESPECIALLY THROUGH TRAUMA-INFORMED STRATEGIES.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
18  2510  41 EPIGENETICS AND POSTSURGICAL PAIN: A SCOPING REVIEW. OBJECTIVE: MULTIPLE FACTORS ARE INVOLVED IN THE PHYSIOLOGY AND VARIABILITY OF POSTSURGICAL PAIN, A GREAT PART OF WHICH CAN BE EXPLAINED BY GENETIC AND ENVIRONMENTAL FACTORS AND THEIR INTERACTION. EPIGENETICS REFERS TO THE MECHANISM BY WHICH THE ENVIRONMENT ALTERS THE STABILITY AND EXPRESSION OF GENES. WE CONDUCTED A SCOPING REVIEW TO EXAMINE THE AVAILABLE EVIDENCE IN BOTH ANIMAL MODELS AND CLINICAL STUDIES ON EPIGENETIC MECHANISMS INVOLVED IN THE REGULATION OF POSTSURGICAL AND CHRONIC POSTSURGICAL PAIN. METHODS: THE ARKSEY AND O'MALLEY FRAMEWORK AND THE PRISMA-SCR (PREFERRED REPORTING ITEMS FOR SYSTEMATIC REVIEW AND META-ANALYSIS, SCOPING REVIEWS EXTENSION) GUIDELINES WERE USED. THE PUBMED, WEB OF SCIENCE, AND GOOGLE SCHOLAR DATABASES WERE SEARCHED, AND THE ORIGINAL ARTICLES CITED IN REVIEWS LOCATED THROUGH THE SEARCH WERE ALSO REVIEWED. ENGLISH-LANGUAGE ARTICLES WITHOUT TIME LIMITS WERE RETRIEVED. ARTICLES WERE SELECTED IF THE ABSTRACT ADDRESSED INFORMATION ON THE EPIGENETIC OR EPIGENOMIC MECHANISMS, HISTONE, OR DNA METHYLATION AND MICRORIBONUCLEIC ACIDS INVOLVED IN POSTSURGICAL AND CHRONIC POSTSURGICAL PAIN IN ANIMAL MODELS AND CLINICAL STUDIES. RESULTS: THE INITIAL SEARCH PROVIDED 174 ARTICLES, AND 95 WERE USED. THE AVAILABLE STUDIES TO DATE, MOSTLY IN ANIMAL MODELS, HAVE SHOWN THAT EPIGENETICS CONTRIBUTES TO THE REGULATION OF GENE EXPRESSION IN THE PATHWAYS INVOLVED IN POSTSURGICAL PAIN AND IN MAINTAINING LONG-TERM PAIN. CONCLUSION: RESEARCH ON POSSIBLE EPIGENETIC MECHANISMS INVOLVED IN POSTSURGICAL PAIN AND CHRONIC POSTSURGICAL PAIN IN HUMANS IS SCARCE. IN VIEW OF THE EVIDENCE AVAILABLE IN ANIMAL MODELS, THERE IS A NEED TO EVALUATE EPIGENETIC PAIN MECHANISMS IN THE CONTEXT OF HUMAN AND CLINICAL STUDIES.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
19   190  35 ACETYL-L-CARNITINE IN PAINFUL PERIPHERAL NEUROPATHY: A SYSTEMATIC REVIEW. ACETYL-L-CARNITINE (ALC) HAS SHOWN A NEUROPROTECTIVE EFFECT IN PATIENTS WITH PERIPHERAL NEUROPATHIES OF DIFFERENT ETIOLOGIES. PRECLINICAL STUDIES DEMONSTRATED A CENTRAL ANTI-NOCICEPTIVE ACTION, BOTH IN NEUROPATHIC AND NOCICEPTIVE PAIN MODELS. THE PRESENT REVIEW AIMS TO PROVIDE THE KNOWLEDGE ON THE EFFICACY OF ALC IN PATIENTS WITH PAINFUL PERIPHERAL NEUROPATHY, BASED ON THE EVIDENCE. CONSISTENT WITH THE PRISMA STATEMENT, AUTHORS SEARCHED PUBMED, EMBASE AND THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS FOR RELEVANT PAPERS, INCLUDING THOSE ISSUED BEFORE APRIL 2018. TWO AUTHORS INDEPENDENTLY SELECTED STUDIES FOR INCLUSION AND DATA EXTRACTION: ONLY TRIALS INCLUDING PATIENTS WITH A DIAGNOSIS OF PERIPHERAL NEUROPATHY AND INVOLVING AT LEAST 10 PATIENTS WERE CONSIDERED FOR THE PURPOSES OF THIS REVIEW. FOURTEEN CLINICAL TRIALS WERE REVISED, TO PROVIDE THE LEVEL OF EVIDENCE FOR NEUROPATHY. TO ASSESS THE GLOBAL EFFICACY OF ALC IN PAINFUL PERIPHERAL NEUROPATHY, A META-ANALYSIS OF FOUR RANDOMIZED CONTROLLED TRIALS WAS PERFORMED. MEAN DIFFERENCE IN PAIN REDUCTION AS MEASURED ON A 10-CM VAS, AND 95% CIS WERE USED FOR POOLING CONTINUOUS DATA FROM EACH TRIAL. FOUR RANDOMIZED CONTROLLED TRIALS TESTED ALC IN PATIENTS WITH NEUROPATHY SECONDARY TO DIABETES AND TO ANTIRETROVIRAL THERAPY FOR HIV. COMPARED TO PLACEBO, ALC PRODUCED A SIGNIFICANT PAIN REDUCTION EQUAL TO 20.2% (95% CI: 8.3%-32.1%, P<0.0001) WITH RESPECT TO BASELINE. CLINICAL TRIALS ALSO SHOWED BENEFICIAL EFFECTS ON NERVE CONDUCTION PARAMETERS AND NERVE FIBER REGENERATION, WITH A GOOD SAFETY PROFILE. THESE DATA INDICATE THAT ALC PROVIDES AN EFFECTIVE AND SAFE TREATMENT IN PATIENTS WITH PAINFUL PERIPHERAL NEUROPATHY. WE RECOMMEND FURTHER STUDIES TO ASSESS THE OPTIMAL DOSE AND DURATION OF THE THERAPEUTIC EFFECT (ALSO AFTER TREATMENT WITHDRAWAL).	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
20   642  45 BIOMARKERS OF PARTICULATE MATTER EXPOSURE IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE: A SYSTEMATIC REVIEW. BACKGROUND: IN RECENT YEARS, AMBIENT PARTICULATE MATTER (PM) EXPOSURE HAS BEEN STRONGLY LINKED WITH HEALTH EFFECTS. ELEVATED LEVELS OF PM IN POLLUTED AIR HAVE BEEN CORRELATED WITH THE ONSET AND DEVELOPMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). THIS SYSTEMATIC REVIEW WAS CONDUCTED TO EVALUATE BIOMARKERS THAT COULD REFLECT THE EFFECTS OF PM EXPOSURE IN PATIENTS WITH COPD. METHODS: WE PERFORMED A SYSTEMATIC REVIEW OF STUDIES PUBLISHED ON BIOMARKERS ASSOCIATED WITH PM EXPOSURE IN PATIENTS WITH COPD BETWEEN JANUARY 01, 2012 AND JUNE 30, 2022 IN PUBMED/MEDLINE, EMBASE, AND COCHRANE DATABASES. STUDIES THAT INCLUDED DATA ON BIOMARKERS WITH COPD EXPOSED PM WERE ELIGIBLE FOR INCLUSION. BIOMARKERS WERE CLASSIFIED INTO 4 GROUPS ACCORDING TO THEIR MECHANISMS. RESULTS: OF THE 105 STUDIES IDENTIFIED, 22 WERE INCLUDED IN THIS STUDY. NEARLY 50 BIOMARKERS HAVE BEEN PROPOSED IN THE STUDIES INCLUDED IN THIS REVIEW, AND THE MOST STUDIED IN RELATION TO PM ARE SEVERAL INTERLEUKINS. VARIOUS MECHANISMS HAVE BEEN REPORTED BY WHICH PM INDUCES AND AGGRAVATES COPD. SIX STUDIES RELATED TO OXIDATIVE STRESS, ONE RELATED TO DIRECT EFFECT OF INNATE AND ADAPTIVE IMMUNE SYSTEMS, 16 ASSOCIATED WITH GENETIC REGULATION OF INFLAMMATION, AND TWO RELATED TO EPIGENETIC REGULATION OF PHYSIOLOGY AND SUSCEPTIBILITY WERE FOUND. BIOMARKERS RELATED TO THESE MECHANISMS WERE DETECTED IN SERUM, SPUTUM, URINE, EXHALED BREATH CONCENTRATION (EBC), AND SHOWED VARIOUS CORRELATIONS WITH PM IN COPD. CONCLUSIONS: VARIOUS BIOMARKERS HAVE SHOWN POTENTIAL IN PREDICTING THE EXTENT OF PM EXPOSURE IN COPD PATIENTS. FUTURE STUDIES ARE NEEDED TO ESTABLISH RECOMMENDATIONS FOR REGULATION TO REDUCE AIRBORNE PM, WHICH COULD BE USED TO DEVELOP STRATEGIES FOR PREVENTION AND MANAGEMENT OF ENVIRONMENTAL RESPIRATORY DISEASES.	2023