1 1221 146 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
2 1151  61 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	

3 6127  40 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
4 6853  35 [NEUROBIOLOGY OF EARLY LIFE TRAUMATIC STRESS AND TRAUMA: PROLONGED NEUROENDOCRINE DYSREGULATION AS A NEURODEVELOPMENTAL RISK FACTOR]. EARLY LIFE STRESSORS DISPLAY A HIGH UNIVERSAL PREVALENCE AND CONSTITUTE A MAJOR PUBLIC HEALTH PROBLEM WITH TWO THIRDS OF YOUTH BEING EXPOSED TO POTENTIALLY TRAUMATIC EXPERIENCES BY THE AGE OF 17. TRAUMATIC STRESS EXPOSURE DURING CRITICAL PERIODS OF DEVELOPMENT MAY HAVE ESSENTIAL AND LONG-LASTING EFFECTS ON THE PHYSICAL AND MENTAL HEALTH OF INDIVIDUALS AND REPRESENTS A DEVELOPMENTAL RISK FACTOR MEDIATING RISK FOR DISEASE. EARLY-LIFE STRESS (ELS) AND CHILDHOOD TRAUMA (CT) CAN BOTH HAVE AN IMPACT ON SENSITIVE NEURONAL BRAIN NETWORKS INVOLVED IN STRESS REACTIONS, AND COULD EXERT A PROGRAMMING EFFECT ON GLUCOCORTICOID SIGNALING LEADING TO CHRONIC HYPER- OR HYPO-ACTIVATION OF THE STRESS SYSTEM. IN ADDITION, ALTERATIONS IN EMOTIONAL AND AUTONOMIC REACTIVITY, CIRCADIAN RHYTHM DISRUPTION, FUNCTIONAL AND STRUCTURAL CHANGES IN THE BRAIN, AS WELL AS IMMUNE AND METABOLIC DYSREGULATION HAVE BEEN LATELY IDENTIFIED AS IMPORTANT RISK FACTORS FOR A CHRONICALLY IMPAIRED HOMEOSTATIC BALANCE AFTER ELS/CT. FURTHERMORE, HUMAN GENETIC BACKGROUND AND EPIGENETIC MODIFICATIONS THROUGH STRESS-RELATED GENE EXPRESSION COULD INTERACT WITH THESE ALTERATIONS AND EXPLAIN INTER-INDIVIDUAL VARIATION IN VULNERABILITY OR RESILIENCE TO STRESS. THIS NARRATIVE REVIEW PRESENTS RELEVANT EVIDENCE FROM MAINLY HUMAN RESEARCH ON THE MOST ACKNOWLEDGED NEUROBIOLOGICAL ALLOSTATIC PATHWAYS EXERTING ENDURING ADVERSE EFFECTS OF ELS/CT EVEN DECADES LATER. FUTURE STUDIES SHOULD PROSPECTIVELY INVESTIGATE POTENTIAL CONFOUNDERS, THEIR TEMPORAL SEQUENCE AND COMBINED EFFECTS AT THE BIOLOGICAL LEVEL, WHILE CONSIDERING THE POTENTIALLY DELAYED TIME-FRAME FOR THE EXPRESSION OF THEIR EFFECTS. FINALLY, SCREENING STRATEGIES FOR ELS/CT AND TRAUMA NEED TO BE IMPROVED. INFORMATION ABOUT ELS/CT HISTORY AND THE NUMBER OF ADVERSE EXPERIENCES COULD HELP TO BETTER IDENTIFY THE INDIVIDUAL RISK FOR DISEASE DEVELOPMENT, PREDICT INDIVIDUAL TREATMENT RESPONSE AND DESIGN PREVENTION STRATEGIES TO REDUCE THE NEGATIVE EFFECTS OF ELS/CT.	2023	
                                                                                                                                                                                                                                                                                                                           
5  247  34 ADULTHOOD ASTHMA AS A CONSEQUENCE OF CHILDHOOD ADVERSITY: A SYSTEMATIC REVIEW OF EPIGENETICALLY AFFECTED GENES. THERE IS AN ACCUMULATING DATA THAT SHOWS RELATION BETWEEN CHILDHOOD ADVERSITY AND VULNERABILITY TO CHRONIC DISEASES AS WELL AS EPIGENETIC INFLUENCES THAT IN TURN GIVE RISE TO THESE DISEASES. ASTHMA IS ONE OF THE CHRONIC DISEASES THAT IS INFLUENCED FROM GENETIC REGULATION OF THE INFLAMMATORY BIOMOLECULES AND THEREFORE THE HYPOTHESIS IN THIS RESEARCH WAS CHILDHOOD ADVERSITY MIGHT HAVE CAUSED EPIGENETIC DIFFERENTIATION IN THE ASTHMA-RELATED GENES IN THE POPULATION WHO HAD CHILDHOOD TRAUMA. TO TEST THIS HYPOTHESIS, THE LITERATURE WAS SYSTEMATICALLY REVIEWED TO EXTRACT EPIGENETICALLY MODIFIED GENE DATA OF THE ADULTS WHO HAD CHILDHOOD ADVERSITY, AND AFFECTED GENES WERE FURTHER EVALUATED FOR THEIR ASSOCIATION WITH ASTHMA. PRISMA GUIDELINES WERE ADOPTED AND PUBMED AND GOOGLE SCHOLAR WERE INCLUDED IN THE SEARCHED DATABASES, TO EVALUATE EPIGENETIC MODIFICATIONS IN ASTHMA-RELATED GENES OF PHYSICALLY, EMOTIONALLY OR SEXUALLY ABUSED CHILDREN. AFTER RETRIEVING A TOTAL OF 5245 ARTICLES, 36 OF THEM WERE INCLUDED IN THE STUDY. SEVERAL GENES AND PATHWAYS THAT MAY CONTRIBUTE TO PATHOGENESIS OF ASTHMA DEVELOPMENT, INCREASED INFLAMMATION, OR RESPONSE TO ASTHMA TREATMENT WERE FOUND EPIGENETICALLY AFFECTED BY CHILDHOOD TRAUMAS. CHILDHOOD ADVERSITY, CAUSING EPIGENETIC CHANGES IN DNA, MAY LEAD TO ASTHMA DEVELOPMENT OR INFLUENCE THE COURSE OF THE DISEASE AND THEREFORE SHOULD BE TAKEN INTO ACCOUNT FOR THE PROLONGED HEALTH CONSEQUENCES.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
6 2999  37 GENETIC VARIATION, STRESS, AND PHYSIOLOGICAL STRESS RESPONSE IN ADULTS WITH FOOD ALLERGY OR CELIAC DISEASE. BACKGROUND: PERSISTENTLY HIGH CHRONIC STRESS CAN LEAD TO MALADAPTIVE PSYCHOLOGICAL, BEHAVIORAL, AND PHYSIOLOGICAL STRESS RESPONSES AND POOR MENTAL AND PHYSICAL HEALTH, HIGHLIGHTING THE IMPORTANCE OF IDENTIFYING INDIVIDUALS AT INCREASED RISK. CHRONIC HEALTH CONDITION DIAGNOSIS AND GENETICS ARE 2 CHARACTERISTICS THAT CAN INFLUENCE STRESS, STRESS RESPONSE, AND HEALTH OUTCOMES. PURPOSE: FOOD ALLERGY (FA) AND CELIAC DISEASE (CD) REQUIRE CONSTANT VIGILANCE IN DAILY LIFE AND CAN LEAD TO INCREASED STRESS. THE PURPOSE OF THIS EXPLORATORY ANALYSIS WAS TO EXAMINE THE ASSOCIATION OF VARIANTS IN SELECTED STRESS-RELATED GENES WITH STRESS EXPOSURES, STRESS, CLINICAL MEASURES OF PHYSIOLOGICAL STRESS RESPONSE, AND MENTAL HEALTH SYMPTOMS IN ADULTS WITH AND WITHOUT FA OR CD. METHODS: WE COMPARED STRESS EXPOSURES, SYMPTOMS OF PTSD, DEPRESSION, ANXIETY, AND STRESS, BMI, AND WAIST-HIP RATIO BETWEEN CASES AND CONTROLS. WE ANALYZED THE ASSOCIATION OF SNPS IN GENES WITH KNOWN OR HYPOTHESIZED ASSOCIATIONS WITH STRESS-RELATED MEASURES IN 124 CASES AND 124 MATCHED CONTROLS: CRHBP (RS7718461, RS10474485), CRHR1 (RS242940) AND OXTR (RS2268490). FOR THIS EXPLORATORY STUDY, P-VALUES </= 0.10 WERE CONSIDERED SUGGESTIVE. RESULTS: FOR CASES AND CONTROLS, RS7718461 WAS ASSOCIATED WITH STRESS SYMPTOMS, RS2268490 WITH SYMPTOMS OF STRESS AND PTSD, AND RS242940 WITH SYMPTOMS OF STRESS, PTSD, ANXIETY, AND DEPRESSION. FURTHER ANALYSES FOUND THAT STRESS-RELATED OUTCOMES IN INDIVIDUALS WITH FA OR CD MAY BE INFLUENCED BY SNP GENOTYPE. CONCLUSIONS: GIVEN THESE SUGGESTIVE FINDINGS, LARGER PROSPECTIVE STUDIES SHOULD EXAMINE SIMILAR RELATIONSHIPS IN INDIVIDUALS WITH OTHER CHRONIC HEALTH CONDITIONS, INCORPORATING FACTORS SUCH AS ENVIRONMENTAL EXPOSURES, INDIVIDUAL EXPERIENCES, AND EPIGENETIC MODIFICATIONS.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
7 2901  31 GENDER DIFFERENCES IN GERM-CELL MUTAGENESIS AND GENETIC RISK. CURRENT INTERNATIONAL CLASSIFICATION SYSTEMS FOR CHEMICAL MUTAGENS ARE HAZARD-BASED RATHER THAN AIMED AT ASSESSING RISKS QUANTITATIVELY. IN THE PAST, GERM-CELL TESTS HAVE BEEN MAINLY PERFORMED WITH A LIMITED NUMBER OF SOMATIC CELL MUTAGENS, AND RARELY UNDER CONDITIONS AIMED AT COMPARING GENDER-SPECIFIC DIFFERENCES IN SUSCEPTIBILITY TO MUTAGEN EXPOSURES. THERE ARE PROFOUND DIFFERENCES IN THE GENETIC CONSTITUTION, AND IN HORMONAL, STRUCTURAL, AND FUNCTIONAL ASPECTS OF DIFFERENTIATION AND CONTROL OF GAMETOGENESIS BETWEEN THE SEXES. A CRITICAL REVIEW OF THE LITERATURE SUGGESTS THAT THESE DIFFERENCES MAY HAVE A PROFOUND IMPACT ON THE RELATIVE SUSCEPTIBILITY, STAGE OF HIGHEST SENSITIVITY AND THE RELATIVE RISK FOR THE GENESIS OF GENE MUTATION, AS WELL AS STRUCTURAL AND NUMERICAL CHROMOSOMAL ABERRATIONS IN MALE AND FEMALE GERM CELLS. TRANSMISSION OF GERM-CELL MUTATIONS TO THE OFFSPRING MAY ALSO ENCOUNTER GENDER-SPECIFIC INFLUENCES. GENDER DIFFERENCES IN SUSCEPTIBILITY TO CHEMICALLY DERIVED ALTERATIONS IN IMPRINTING PATTERNS MAY POSE A THREAT FOR THE HEALTH OF THE OFFSPRING AND MAY ALSO BE TRANSMITTED TO FUTURE GENERATIONS. RECENT REPORTS ON DIFFERENT GENETIC EFFECTS FROM HIGH ACUTE AND FROM CHRONIC LOW-DOSE EXPOSURES CHALLENGE THE VALIDITY OF CONCLUSIONS DRAWN FROM STANDARD METHODS OF MUTAGENICITY TESTING. IN CONCLUSION, RESEARCH IS URGENTLY NEEDED TO IDENTIFY GENETIC HAZARDS FOR A LARGER RANGE OF CHEMICAL COMPOUNDS, INCLUDING THOSE SUSPECTED TO DISTURB PROPER CHROMOSOME SEGREGATION. ALTERATIONS IN EPIGENETIC PROGRAMMING AND THEIR HEALTH CONSEQUENCES WILL HAVE TO BE INVESTIGATED. MORE ATTENTION SHOULD BE PAID TO GENDER-SPECIFIC GENETIC EFFECTS. FINALLY, THE DATABASE FOR GERM-CELL MUTAGENS SHOULD BE ENLARGED USING MOLECULAR METHODOLOGIES, AND GENETIC EPIDEMIOLOGY STUDIES SHOULD BE PERFORMED WITH THESE TECHNIQUES TO VERIFY HUMAN GENETIC RISK.	2007	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
8 1045  40 CLINICAL CORRELATION AMONG MALE INFERTILITY AND OVERALL MALE HEALTH: A SYSTEMATIC REVIEW OF THE LITERATURE. PURPOSE: ONGOING EVIDENCE HAS SUGGESTED THE ROLE OF MALE FACTOR INFERTILITY AS A POTENTIAL PREDICTOR OF MORTALITY AND GENERAL HEALTH STATUS. THE AIM OF THE PRESENT REVIEW IS TO UPDATE THE CURRENT KNOWLEDGE BASE REGARDING THE ASSOCIATION BETWEEN MALE FACTOR INFERTILITY AND GENERAL HEALTH THROUGH A CRITICAL REVIEW OF THE LITERATURE. MATERIALS AND METHODS: A SYSTEMATIC REVIEW OF THE LITERATURE WAS CARRIED OUT FROM INCEPTION TO NOVEMBER 2019 IN ORDER TO EVALUATE SIGNIFICANT ASSOCIATIONS BETWEEN MALE INFERTILITY AND ADVERSE HEALTH OUTCOMES SUCH AS CARDIOVASCULAR, ONCOLOGIC, METABOLIC AND AUTOIMMUNE DISEASES AS WELL AS OVERALL MORTALITY. RESULTS: IN ALL, 27 STUDIES MET INCLUSION CRITERIA AND WERE CRITICALLY EXAMINED. FIVE STUDIES EXAMINED MALE INFERTILITY AND CARDIOVASCULAR DISEASE RISK, 11 EXAMINED ONCOLOGIC RISK (E.G., OVERALL CANCER RISK, TESTIS AND PROSTATE CANCER), 8 EXAMINED AGGREGATE CHRONIC MEDICAL DISEASES AND 5 INFERTILITY RELATED TO INCIDENCE OF MORTALITY, FOR A TOTAL OF 599,807 MEN DIAGNOSED WITH ANY MALE FACTOR INFERTILITY COVERING A PERIOD FROM 1916 TO 2016. CONCLUSIONS: A MAN'S FERTILITY AND OVERALL HEALTH APPEAR TO BE INTERCONNECTED. THEREFORE, A DIAGNOSIS OF MALE INFERTILITY MAY ALLOW A WINDOW INTO FUTURE COMORBIDITY AND/OR MORTALITY WHICH MAY HELP GUIDE CLINICAL DECISIONS AND COUNSELING. SEVERAL POSSIBLE ETIOLOGIES SUCH AS GENETIC, EPIGENETIC, DEVELOPMENTAL, AND LIFESTYLE-BASED FACTORS NEED TO BE FURTHER EVALUATED IN ORDER TO ESTABLISH THE UNDERLYING MECHANISMS BETWEEN MALE INFERTILITY AND HEALTH.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
9   14  32 3RD COLLEGE OF PAEDIATRICS AND CHILD HEALTH LECTURE--THE PAST, THE PRESENT AND THE SHAPE OF THINGS TO COME.. THE GROWTH TRENDS OF SINGAPORE CHILDREN SPANNING 5 DECADES ARE REVIEWED, BASED ON 8 ANTHROPOMETRIC STUDIES FROM 1957 TILL 2002. THE HEIGHTS OF PRE-SCHOOL CHILDREN AND SCHOOL AGE CHILDREN APPEAR TO HAVE OPTIMISED ACCORDING TO THEIR GENETIC POTENTIAL, BUT THE WEIGHTS AND BODY MASS INDICES OF CHILDREN STILL APPEAR TO BE INCREASING FROM 6 TO 18 YEARS FOR BOTH SEXES, PROBABLY AS A CONSEQUENCE OF INCREASING AFFLUENCE. THIS TREND IS REFLECTED IN THE INCREASING OBESITY PREVALENCE IN SCHOOL CHILDREN OVER THE PAST 30 YEARS, AND THE CONCOMITANT INCREASED MORBIDITY ASSOCIATED WITH THE METABOLIC SYNDROME, NECESSITATES FURTHER RESEARCH INTO THE CAUSES OF OBESITY. BARKER'S HYPOTHESIS FIRST SUGGESTED THAT CHANGES IN THE INTRA-UTERINE ENVIRONMENT CAN CAUSE FETAL ADAPTATIONS WHICH PERSIST INTO ADULTHOOD, AND ARE RESPONSIBLE FOR MANY CHRONIC DISEASES OF ADULT LIFE. MORE RECENTLY, INTENSE RESEARCH IN THE FIELD OF EPIGENETICS SUGGESTS THAT THE ENVIRONMENT CAN ALSO INFLUENCE THE PHENOTYPE THROUGH GENE EXPRESSION, THROUGH MODIFICATION OF DNA METHYLATION AND HISTONES WHICH, IN TURN, INFLUENCES GENE EXPRESSION. THE CHALLENGE FOR THE FUTURE IS TO DETERMINE IF THERE ARE CLEAR EPIGENETIC CHANGES, WHICH ARE RESPONSIBLE FOR THE INCREASED PREVALENCE OF CHILDHOOD AND ADOLESCENT OBESITY, AND WHETHER THESE CHANGES ARE TRANSMITTED THROUGH GENERATIONS. UNRAVELLING THESE EPIGENETIC MECHANISMS MAY BE THE KEY TO THE PREVENTION OF OBESITY AND THE METABOLIC SYNDROME.	2008	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
10 5810  27 STRESS & SLEEP: A RELATIONSHIP LASTING A LIFETIME. STRESS IS AN ADAPTATIVE RESPONSE AIMED AT RESTORING BODY HOMEOSTASIS. THE CLASSICAL NEUROENDOCRINE STRESS RESPONSE INVOLVING THE ACTIVATION OF THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS MODULATES MANY PHYSIOLOGICAL ASPECTS, SUCH AS THE WAKE-SLEEP CYCLE. IN THE PRESENT REVIEW, WE WILL FIRST REPORT A SERIES OF HUMAN AND RODENT STUDIES SHOWING THAT EACH ACTOR OF THE HPA AXIS HAS THE POTENTIAL TO INTERFERE WITH SLEEP HOMEOSTASIS AND, THEN, WE WILL HIGHLIGHT HOW ACUTE OR CHRONIC STRESS DIFFERENTLY MODULATES THE WAKE-SLEEP CYCLE. MOREOVER, WE WILL PRESENT NEW AND INTERESTING STUDIES DEALING WITH THE RELATIONSHIP BETWEEN SLEEP AND STRESS ON A DIFFERENT (LONGER) TIME SCALE. PARTICULARLY, WE WILL DISCUSS HOW THE EXPOSURE TO PERINATAL STRESS, PROBABLY THROUGH EPIGENETIC MODULATIONS, IS SUFFICIENT TO CAUSE PERSISTENT SLEEP DERANGEMENTS DURING ADULT LIFE. IN LIGHT OF THIS EVIDENCE, THE MAIN MESSAGE OF THE PRESENT REVIEW IS THAT THE COMPLEX RELATIONSHIP BETWEEN SLEEP AND STRESS CHANGES DRAMATICALLY ON THE BASIS OF THE TIME SCALE CONSIDERED AND, CONSEQUENTLY, "TIME" SHOULD BE CONSIDERED AS A CRITICAL FACTOR WHEN FACING THIS TOPIC.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
11 6730  23 WALK MORE, EAT LESS, DON'T STRESS. UNHEALTHY DIET, OBESITY, LACK OF PHYSICAL ACTIVITY, AND PSYCHOLOGIC STRESS ARE ASSOCIATED WITH INCREASED INFLAMMATION, OXIDATIVE STRESS, INSULIN RESISTANCE, AND DNA METHYLATION, WHICH ARE THE MAIN MECHANISMS OF CHRONIC DISEASES SUCH AS CANCER, HYPERTENSION, DIABETES, CARDIOVASCULAR DISEASE, AND ALZHEIMER'S DISEASE. IT HAS RECENTLY BEEN FOUND THAT HEALTHY DIET AND PHYSICAL ACTIVITY CAN REDUCE INFLAMMATORY MARKERS AND IMPROVE INSULIN SENSITIVITY RESULTING IN BETTER SURVIVORSHIP OUTCOMES IN PATIENTS WITH PROSTATE CANCER. AN "ANTI-INFLAMMATORY" LIFESTYLE, INCLUDING PHYSICAL ACTIVITY, HEALTHY BODY WEIGHT, HEALTHY DIET, AND STRESS REDUCTION, HAS BEEN ASSOCIATED WITH DECREASED CANCER RISK AND PROGRESSION. EPIGENETIC CHANGES DUE TO DNA METHYLATION AND ALTERED GENE EXPRESSION ASSOCIATED WITH UNHEALTHY LIFESTYLE CAN BE MODULATED BY HEALTHY BEHAVIORS. NATIONAL CENTER FOR COMPLEMENTARY AND INTEGRATIVE HEALTH (NCCIH) FOCUSES ON HEALTHY LIFESTYLE, AND IT SUPPORTS RESEARCH ON PSYCHOLOGIC AND PHYSICAL APPROACHES INCLUDING DIETARY SUPPLEMENTS AND PLANT-BASED PRODUCTS, AS WELL AS MIND AND BODY APPROACHES, SUCH AS YOGA, MASSAGE, MEDITATION, MINDFULNESS-BASED STRESS REDUCTION, AND ACUPUNCTURE. SEE RELATED ARTICLE BY LANGLAIS ET AL., P. 1760.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
12  844  31 CHILDHOOD ALLERGY DISEASE, EARLY DIAGNOSIS, AND THE POTENTIAL OF SALIVARY PROTEIN BIOMARKERS. ALLERGIC DISEASE HAS RISEN TO EPIDEMIC PROPORTIONS SINCE THE LAST DECADE AND IS AMONG THE MOST COMMON NONCOMMUNICABLE, CHRONIC DISEASES IN CHILDREN AND ADOLESCENTS WORLDWIDE. ALLERGIC DISEASE USUALLY OCCURS IN EARLY LIFE; THUS, EARLY BIOMARKERS OF ALLERGIC SUSCEPTIBILITY ARE REQUIRED FOR PREVENTIVE MEASURES TO HIGH-RISK INFANTS WHICH ENABLE EARLY INTERVENTIONS TO DECREASE ALLERGIC SEVERITY. HOWEVER, TO DATE, THERE IS NO RELIABLE GENERAL OR SPECIFIC ALLERGY PHENOTYPE DETECTION METHOD THAT IS EASY AND NONINVASIVE FOR CHILDREN. MOST REPORTED ALLERGIC PHENOTYPE DETECTION METHODS ARE INVASIVE, SUCH AS THE SKIN PRICK TEST (SPT), ORAL FOOD CHALLENGE (OFC), AND BLOOD TEST, AND MANY INVOLVE NOT READILY ACCESSIBLE BIOLOGICAL SAMPLES, SUCH AS CORD BLOOD (CB), MATERNAL BLOOD, OR NEWBORN VERNIX. SALIVA IS A BIOLOGICAL SAMPLE THAT HAS GREAT POTENTIAL AS A BIOMARKER MEASUREMENT AS IT CONSISTS OF AN ABUNDANCE OF BIOMARKERS, SUCH AS GENETIC MATERIAL AND PROTEINS. IT IS EASILY ACCESSIBLE, NONINVASIVE, COLLECTED VIA A PAINLESS PROCEDURE, AND AN EASY BEDSIDE SCREENING FOR REAL-TIME MEASUREMENT OF THE ONGOING HUMAN PHYSIOLOGICAL SYSTEM. ALL THESE ADVANTAGES EMPHASISE SALIVA AS A VERY PROMISING DIAGNOSTIC CANDIDATE FOR THE DETECTION AND MONITORING OF DISEASE BIOMARKERS, ESPECIALLY IN CHILDREN. FURTHERMORE, PROTEIN BIOMARKERS HAVE THE ADVANTAGES AS MODIFIABLE INFLUENCING FACTORS RATHER THAN GENETIC AND EPIGENETIC FACTORS THAT ARE MOSTLY NONMODIFIABLE FACTORS FOR ALLERGIC DISEASE SUSCEPTIBILITY IN CHILDHOOD. SALIVA HAS GREAT POTENTIAL TO REPLACE SERUM AS A BIOLOGICAL FLUID BIOMARKER IN DIAGNOSING CLINICAL ALLERGY. HOWEVER, TO DATE, SALIVA IS NOT CONSIDERED AS AN ESTABLISHED MEDICALLY ACCEPTABLE BIOMARKER. THIS REVIEW CONSIDERS WHETHER THE SALIVA COULD BE SUITABLE BIOLOGICAL SAMPLES FOR EARLY DETECTION OF ALLERGIC RISK. SUCH TOOLS MAY BE USED AS JUSTIFICATION FOR TARGETED INTERVENTIONS IN EARLY CHILDHOOD FOR DISEASE PREVENTION AND ASSISTING IN REDUCING MORBIDITY AND MORTALITY CAUSED BY CHILDHOOD ALLERGY.	2021	
                                                                                                                                                                                                                                                                                                                                        
13 2585  47 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	
                                                                                                                                                                                                                                                            
14  120  30 A SYSTEMATIC REVIEW OF CHILDHOOD MALTREATMENT AND DNA METHYLATION: CANDIDATE GENE AND EPIGENOME-WIDE APPROACHES. CHILDHOOD MALTREATMENT IS A MAJOR RISK FACTOR FOR CHRONIC AND SEVERE MENTAL AND PHYSICAL HEALTH PROBLEMS ACROSS THE LIFESPAN. INCREASING EVIDENCE SUPPORTS THE HYPOTHESIS THAT MALTREATMENT IS ASSOCIATED WITH EPIGENETIC CHANGES THAT MAY SUBSEQUENTLY SERVE AS MECHANISMS OF DISEASE. THE CURRENT REVIEW USES A SYSTEMATIC APPROACH TO IDENTIFY AND SUMMARIZE THE LITERATURE RELATED TO CHILDHOOD MALTREATMENT AND ALTERATIONS IN DNA METHYLATION IN HUMANS. A TOTAL OF 100 EMPIRICAL ARTICLES WERE IDENTIFIED IN OUR SYSTEMATIC REVIEW OF RESEARCH PUBLISHED PRIOR TO OR DURING MARCH 2020, INCLUDING STUDIES THAT FOCUSED ON CANDIDATE GENES AND STUDIES THAT LEVERAGED EPIGENOME-WIDE DATA IN BOTH CHILDREN AND ADULTS. THEMES ARISING FROM THE LITERATURE, INCLUDING CONSISTENT AND INCONSISTENT PATTERNS OF RESULTS, ARE PRESENTED. SEVERAL DIRECTIONS FOR FUTURE RESEARCH, INCLUDING IMPORTANT METHODOLOGICAL CONSIDERATIONS FOR FUTURE STUDY DESIGN, ARE DISCUSSED. TAKEN TOGETHER, THE LITERATURE ON CHILDHOOD MALTREATMENT AND DNA METHYLATION UNDERSCORES THE COMPLEXITY OF TRANSACTIONS BETWEEN THE ENVIRONMENT AND BIOLOGY ACROSS DEVELOPMENT.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
15 2093  32 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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
16 2047  30 EPIGENETIC CLOCKS MAY COME OUT OF RHYTHM-IMPLICATIONS FOR THE ESTIMATION OF CHRONOLOGICAL AGE IN FORENSIC CASEWORK. THERE IS A GROWING PERCEPTION THAT DNA METHYLATION MAY BE INFLUENCED BY EXOGENOUS AND ENDOGENOUS PARAMETERS. KNOWLEDGE OF THESE FACTORS IS OF GREAT RELEVANCE FOR THE INTERPRETATION OF DNA-METHYLATION DATA FOR THE ESTIMATION OF CHRONOLOGICAL AGE IN FORENSIC CASEWORK. WE PERFORMED A LITERATURE REVIEW TO IDENTIFY PARAMETERS, WHICH MIGHT BE OF RELEVANCE FOR THE PREDICTION OF CHRONOLOGICAL AGE BASED ON DNA METHYLATION. THE QUALITY OF AGE PREDICTIONS MIGHT PARTICULARLY BE INFLUENCED BY LIFETIME ADVERSITIES (CHRONIC STRESS, TRAUMA/POST-TRAUMATIC STRESS DISORDER (PTSD), VIOLENCE, LOW SOCIOECONOMIC STATUS/EDUCATION), CANCER, OBESITY AND RELATED DISEASES, INFECTIOUS DISEASES (ESPECIALLY HIV AND CYTOMEGALOVIRUS (CMV) INFECTIONS), SEX, ETHNICITY AND EXPOSURE TO TOXINS (ALCOHOL, SMOKING, AIR POLLUTION, PESTICIDES). SUCH FACTORS MAY ALTER THE DNA METHYLATION PATTERN AND MAY EXPLAIN THE PARTLY HIGH DEVIATIONS BETWEEN EPIGENETIC AGE AND CHRONOLOGICAL AGE IN SINGLE CASES (DESPITE OF LOW MEAN ABSOLUTE DEVIATIONS) THAT CAN ALSO BE OBSERVED WITH "EPIGENETIC CLOCKS" COMPRISING A HIGH NUMBER OF CPG SITES. SO FAR, ONLY FEW PUBLICATIONS DEALING WITH FORENSIC AGE ESTIMATION ADDRESS THESE CONFOUNDING FACTORS. FUTURE RESEARCH SHOULD FOCUS ON THE IDENTIFICATION OF FURTHER RELEVANT CONFOUNDING FACTORS AND THE DEVELOPMENT OF MODELS THAT ARE "ROBUST" AGAINST THE INFLUENCE OF SUCH BIOLOGICAL FACTORS BY SYSTEMATIC INVESTIGATIONS UNDER TARGETED INCLUSION OF DIVERSE AND DEFINED COHORTS.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
17 5737  37 SMOKING AND HEALTH: ASSOCIATION BETWEEN TELOMERE LENGTH AND FACTORS IMPACTING ON HUMAN DISEASE, QUALITY OF LIFE AND LIFE SPAN IN A LARGE POPULATION-BASED COHORT UNDER THE EFFECT OF SMOKING DURATION. REACTIVE OXYGEN SPECIES (ROS) ARE OF PRIMARY IMPORTANCE AS THEY CAUSE DAMAGE TO LIPIDS, PROTEINS, AND DNA EITHER ENDOGENOUSLY BY CELLULAR MECHANISM, OR THROUGH EXOGENOUS EXPOSURE TO ENVIRONMENTAL INJURY FACTORS, INCLUDING OXIDATION INSULT FACTORS, SUCH AS TOBACCO SMOKE. CURRENTLY 46.3 MILLION ADULTS (25.7 PERCENT OF THE POPULATION) ARE SMOKERS. THIS INCLUDES 24 MILLION MEN (28.1 PERCENT OF THE TOTAL) AND MORE THAN 22 MILLION WOMEN (23.5 PERCENT). THE PREVALENCE IS HIGHEST AMONG PERSONS 25-44 YEARS OF AGE. CIGARETTE SMOKERS HAVE A HIGHER RISK OF DEVELOPING SEVERAL CHRONIC DISORDERS. THESE INCLUDE FATTY BUILDUPS IN ARTERIES, SEVERAL TYPES OF CANCER AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (LUNG PROBLEMS). AS PERIPHERAL LEUKOCYTES HAVE BEEN THE MAIN TARGET OF HUMAN TELOMERE RESEARCH, MOST OF WHAT IS KNOWN ABOUT HUMAN TELOMERE DYNAMICS IN VIVO IS BASED ON THESE CELLS. LEUKOCYTE TELOMERE LENGTH (TL) IS A COMPLEX TRAIT THAT IS SHAPED BY GENETIC, EPIGENETIC, AND ENVIRONMENTAL DETERMINANTS. IN THIS ARTICLE, WE CONSIDER THAT SMOKING MODIFIES LEUKOCYTE TL IN HUMANS AND CONTRIBUTES TO ITS VARIABILITY AMONG INDIVIDUALS, ALTHOUGH THE SMOKING EFFECT ON TL AND ITS RELATION WITH OTHER METABOLIC INDICES MAY ACCELERATE BIOLOGICAL AGING AND DEVELOPMENT OF SMOKING-INDUCED CHRONIC DISEASES IN A LARGE HUMAN POPULATION-BASED COHORTS WITH SMOKING BEHAVIOR. RECENT STUDIES CONFIRMED THAT INDIVIDUALS WITH SHORTER TELOMERES PRESENT A HIGHER PREVALENCE OF ARTERIAL LESIONS AND HIGHER RISK OF CARDIOVASCULAR DISEASE MORTALITY. THIS STUDY ORIGINALLY SUGGESTS THAT EFFICIENT THERAPEUTIC PROTECTION OF TL AND STRUCTURE IN RESPONSE TO STRESSES THAT ARE KNOWN TO REDUCE TL, SUCH AS OXIDATIVE DAMAGE OR INFLAMMATION ASSOCIATED WITH TOBACCO SMOKING, WOULD LEAD TO BETTER TELOMERE MAINTENANCE. RECENTLY, WE HAVE DISCOVERED THE POTENTIAL USE OF TELOMERE-RESTORATIVE IMIDAZOLE-CONTAINING DIPEPTIDE (NON-HYDROLIZED CARNOSINE, CARCININE) BASED THERAPY FOR BETTER SURVIVAL OF SMOKERS. WE CONCLUDE THAT A BETTER THERAPEUTIC OR NUTRITIONAL MAINTENANCE OF TL MAY CONFER HEALTHY AGING IN SMOKERS AND EXCEPTIONAL LONGEVITY IN REGULARLY ROS-EXPOSED HUMAN SURVIVORS.	2011	
                                                                                                
18 2638  20 EPIGENOME: BIOSENSOR OF CUMULATIVE EXPOSURE TO CHEMICAL AND NONCHEMICAL STRESSORS RELATED TO ENVIRONMENTAL JUSTICE. UNDERSTANDING DIFFERENTIAL DISEASE SUSCEPTIBILITY REQUIRES NEW TOOLS TO QUANTIFY THE CUMULATIVE EFFECTS OF ENVIRONMENTAL STRESS. EVIDENCE SUGGESTS THAT SOCIAL, PHYSICAL, AND CHEMICAL STRESSORS CAN INFLUENCE DISEASE THROUGH THE ACCUMULATION OF EPIGENETIC MODIFICATIONS. GEOGRAPHICALLY STABLE EPIGENETIC ALTERATIONS COULD IDENTIFY PLAUSIBLE MECHANISMS FOR HEALTH DISPARITIES AMONG THE DISADVANTAGED AND POOR. RELATIONS BETWEEN NEIGHBORHOOD-SPECIFIC EPIGENETIC MARKERS AND DISEASE WOULD IDENTIFY THE MOST APPROPRIATE TARGETS FOR MEDICAL AND ENVIRONMENTAL INTERVENTION. COMPLEX INTERACTIONS AMONG GENES, THE ENVIRONMENT, AND DISEASE REQUIRE THE EXAMINATION OF HOW EPIGENETIC CHANGES REGULATE SUSCEPTIBILITY TO ENVIRONMENTAL STRESSORS. PROGRESS IN UNDERSTANDING DISPARITIES IN DISEASE SUSCEPTIBILITY MAY DEPEND ON ASSESSING THE CUMULATIVE EFFECT OF ENVIRONMENTAL STRESSORS ON GENETIC SUBSTRATES. WE HIGHLIGHT KEY CONCEPTS REGARDING THE INTERFACE BETWEEN ENVIRONMENTAL STRESS, EPIGENETICS, AND CHRONIC DISEASE.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
19 5194  34 PRENATAL EXPOSURE TO POTENTIALLY TOXIC METALS AND THEIR EFFECTS ON GENETIC MATERIAL IN OFFSPRING: A SYSTEMATIC REVIEW. IN RECENT YEARS, THE BACKGROUND LEVEL OF ENVIRONMENTAL POLLUTANTS, INCLUDING METALS, HAS INCREASED. POLLUTANT EXPOSURE DURING THE EARLIEST STAGES OF LIFE MAY DETERMINE CHRONIC DISEASE SUSCEPTIBILITY IN ADULTHOOD BECAUSE OF GENETIC OR EPIGENETIC CHANGES. THE OBJECTIVE OF THIS REVIEW WAS TO IDENTIFY THE ASSOCIATION BETWEEN PRENATAL AND EARLY POSTNATAL EXPOSURE TO POTENTIALLY TOXIC METALS (PTMS) AND THEIR ADVERSE EFFECTS ON THE GENETIC MATERIAL OF OFFSPRING. A SYSTEMATIC REVIEW WAS CARRIED OUT FOLLOWING THE COCHRANE METHODOLOGY IN FOUR DATABASES: PUBMED, SCOPUS, WEB OF SCIENCE, AND THE COCHRANE LIBRARY. ELIGIBLE PAPERS WERE THOSE CONDUCTED IN HUMANS AND PUBLISHED IN ENGLISH BETWEEN 2010/01/01 AND 2021/04/30. A TOTAL OF 57 ARTICLES WERE INCLUDED, MOST OF WHICH EVALUATED PRENATAL EXPOSURE. MOST COMMONLY EVALUATED PTMS WERE AS, CD, AND PB. MAIN ADVERSE EFFECTS ON THE GENETIC MATERIAL OF NEWBORNS ASSOCIATED WITH PTM PRENATAL EXPOSURE WERE ALTERATIONS IN TELOMERE LENGTH, GENE OR PROTEIN EXPRESSION, MITOCHONDRIAL DNA CONTENT, METABOLOMICS, DNA DAMAGE, AND EPIGENETIC MODIFICATIONS. MANY OF THESE EFFECTS WERE SEX-SPECIFIC, BEING PREDOMINANT IN BOYS. ONE ARTICLE REPORTED A SYNERGISTIC INTERACTION BETWEEN AS AND HG, AND TWO ARTICLES OBSERVED ANTAGONISTIC INTERACTIONS BETWEEN PTMS AND ESSENTIAL METALS, SUCH AS CU, SE, AND ZN. THE FINDINGS IN THIS REVIEW HIGHLIGHT THAT THE PROBLEM OF PTM EXPOSURE PERSISTS, AFFECTING THE MOST SUSCEPTIBLE POPULATIONS, SUCH AS NEWBORNS. SOME OF THESE ASSOCIATIONS WERE OBSERVED AT LOW CONCENTRATIONS OF PTMS. MOST OF THE STUDIES HAVE FOCUSED ON SINGLE EXPOSURES; HOWEVER, THREE INTERACTIONS BETWEEN ESSENTIAL AND NONESSENTIAL METALS WERE OBSERVED, HIGHLIGHTING THAT METAL MIXTURES NEED MORE ATTENTION.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
20 6678  30 USING GENETIC BURDEN SCORES FOR GENE-BY-METHYLATION INTERACTION ANALYSIS ON METABOLIC SYNDROME IN AFRICAN AMERICANS. WITH THE RAPID ADVANCEMENT OF OMICS-BASED RESEARCH, PARTICULARLY BIG DATA SUCH AS GENOME- AND EPIGENOME-WIDE ASSOCIATION STUDIES THAT INCLUDE EXTENSIVE ENVIRONMENTAL AND CLINICAL VARIABLES, DATA ANALYTICS HAVE BECOME INCREASINGLY COMPLEX. RESEARCHERS FACE SIGNIFICANT CHALLENGES REGARDING HOW TO ANALYZE MULTIFACTORIAL DATA AND MAKE USE OF THE FINDINGS FOR CLINICAL TRANSLATION. THE PURPOSE OF THIS ARTICLE IS TO PROVIDE A SCIENTIFIC EXEMPLAR FOR USE OF GENETIC BURDEN SCORES AS A DATA ANALYSIS METHOD FOR STUDIES WITH BOTH GENOTYPE AND DNA METHYLATION DATA IN WHICH THE GOAL IS TO EVALUATE ASSOCIATIONS WITH CHRONIC CONDITIONS SUCH AS METABOLIC SYNDROME (METS). THIS STUDY INCLUDED 739 AFRICAN AMERICAN MEN AND WOMEN FROM THE GENETIC EPIDEMIOLOGY NETWORK OF ARTERIOPATHY STUDY WHO MET DIAGNOSTIC CRITERIA FOR METS AND HAD AVAILABLE GENETIC AND EPIGENETIC DATA. GENETIC BURDEN SCORES FOR EVALUATED GENES WERE NOT SIGNIFICANT AFTER MULTIPLE TESTING CORRECTIONS, BUT DNA METHYLATION AT 2 CPG SITES (DIHYDROOROTATE DEHYDROGENASE CG22381196 PFDR = .014; CTNNA3 CG00132141 PFDR = .043) WAS SIGNIFICANTLY ASSOCIATED WITH METS AFTER CONTROLLING FOR MULTIPLE COMPARISONS. INTERACTIONS BETWEEN THE MARGINALLY SIGNIFICANT CPG SITES AND BURDEN SCORES, HOWEVER, WERE NOT SIGNIFICANT. MORE WORK IS REQUIRED IN THIS AREA TO IDENTIFY INTERMEDIATE BIOLOGICAL PATHWAYS INFLUENCED BY ENVIRONMENTAL, GENETIC, AND EPIGENETIC VARIATION THAT MAY EXPLAIN THE HIGH PREVALENCE OF METS AMONG AFRICAN AMERICANS. THIS STUDY DOES SERVE, HOWEVER, AS AN EXAMPLE OF THE USE OF THE GENETIC BURDEN SCORE AS AN ALTERNATIVE DATA ANALYSIS APPROACH FOR COMPLEX STUDIES INVOLVING THE ANALYSIS OF GENETIC AND EPIGENETIC DATA SIMULTANEOUSLY.	2019