1  1147 152 CONDYLE MODELING STABILITY, CRANIOFACIAL ASYMMETRY AND ACTN3 GENOTYPES: CONTRIBUTION TO TMD PREVALENCE IN A COHORT OF DENTOFACIAL DEFORMITIES. CRANIOFACIAL ASYMMETRY, MANDIBULAR CONDYLAR MODELING AND TEMPOROMANDIBULAR JOINT DISORDERS ARE COMMON COMORBIDITIES OF SKELETALLY DISPROPORTIONATE MALOCCLUSIONS, BUT ETIOLOGY OF OCCURRENCE TOGETHER IS POORLY UNDERSTOOD. WE COMPARED ASYMMETRY, CONDYLE MODELING STABILITY AND TEMPOROMANDIBULAR HEALTH IN A COHORT OF 128 PATIENTS HAVING ORTHODONTICS AND ORTHOGNATHIC SURGERY TO CORRECT DENTOFACIAL DEFORMITY MALOCCLUSIONS. WE ALSO COMPARED ACTN3 AND ENPP1 GENOTYPES FOR ASSOCIATION TO CLINICAL CONDITIONS. PRE-SURGICAL POSTERIOR-ANTERIOR CEPHALOMETRIC AND PANOMETRIC RADIOGRAPHIC ANALYSES; JAW PAIN AND FUNCTION QUESTIONNAIRE AND CLINICAL EXAMINATION OF TMD; AND SNP-GENOTYPE ANALYSIS FROM SALIVA SAMPLES WERE COMPARED TO ASSESS INTERRELATIONSHIPS. ALMOST HALF HAD ASYMMETRIES IN NEED OF SURGICAL CORRECTION, WHICH COULD BE SUBDIVIDED INTO FOUR DISTINCT MORPHOLOGICAL PATTERNS. ASYMMETRIC CONDYLE MODELING BETWEEN SIDES WAS SIGNIFICANTLY GREATER IN CRANIOFACIAL ASYMMETRY, BUT MOST COMMONLY HAD AN UNANTICIPATED PATTERN. OFTEN, LONGER OR LARGER CONDYLES OCCURRED ON THE SHORTER MANDIBULAR RAMUS SIDE. SUBJECTS WITH LONGER RAMUS BUT DIMENSIONALLY SMALLER CONDYLES WERE MORE LIKELY TO HAVE SELF-REPORTED TMD SYMPTOMS (P = 0.023) AND SIGNIFICANTLY GREATER CLINICAL DIAGNOSIS OF TMD (P = 0 .000001), WITH MASTICATORY MYALGIA MOST PROMINENT. GENOTYPING FOUND TWO SIGNIFICANT GENOTYPE ASSOCIATIONS FOR ACTN3 RS1671064 (Q523R MISSENSE) P = 0.02; RS678397 (INTRONIC SNP) P = 0.04 AND ONE SIGNIFICANT ALLELE ASSOCIATION RS1815739 (R577X NONSENSE) P = 0.00. SKELETAL ASYMMETRY, UNUSUAL CONDYLE MODELING AND TMD ARE COMMON AND INTERRELATED COMPONENTS OF MANY DENTOFACIAL DEFORMITIES. IMBALANCED MUSCULOSKELETAL FUNCTIONAL ADAPTATIONS AND GENETIC OR EPIGENETIC INFLUENCES CONTRIBUTE TO THE ETIOLOGY, AND REQUIRE FURTHER INVESTIGATION.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
2  5176  26 PREFACE TO COAST 2016 INNOVATORS' WORKSHOP ON PERSONALIZED AND PRECISION ORTHODONTIC THERAPY. OBJECTIVE: A SECOND FOCUSED WORKSHOP EXPLORED HOW TO TRANSFER NOVEL FINDINGS INTO CLINICAL ORTHODONTIC PRACTICE. SETTING AND SAMPLE POPULATION: PARTICIPANTS MET IN WEST PALM BEACH (FLORIDA, USA), ON 9-11 SEPTEMBER 2016 FOR THE CONSORTIUM FOR ORTHODONTIC ADVANCES IN SCIENCE AND TECHNOLOGY 2016 INNOVATORS' WORKSHOP (COAST). APPROXIMATELY 65 REGISTERED ATTENDEES CONSIDERED AND DISCUSSED INFORMATION FROM 27 TO 34 SPEAKERS, 8 TO 15 POSTER PRESENTERS AND FOUR LUNCH-HOUR FOCUS GROUP LEADERS. MATERIAL AND METHODS: THE INNOVATORS' WORKSHOPS WERE ORGANIZED ACCORDING TO FIVE THEMED SESSIONS. THE AIMS OF THE DISCUSSION SESSIONS WERE TO IDENTIFY THE FOLLOWING: I) THE STRENGTH AND IMPACT OF THE EVIDENCED-BASED DISCOVERIES, II) REQUIRED STEPS TO ENABLE FURTHER DEVELOPMENT AND III) REQUIRED STEPS TO TRANSLATE THESE NEW DISCOVERIES INTO ORTHODONTIC PRACTICE. RESULTS: THE ROLE OF GENE-ENVIRONMENT INTERACTIONS THAT UNDERLIE COMPLEX CRANIOFACIAL TRAITS WAS THE FOCUS OF SEVERAL SESSIONS. IT WAS AGREED THAT DIVERSE APPROACHES ARE CALLED FOR, SUCH AS (I) LARGE-SCALE COLLABORATIVE EFFORTS FOR FUTURE GENETIC STUDIES OF COMPLEX TRAITS; (II) DEEP GENOME SEQUENCING TO ADDRESS THE ISSUES OF ISOLATED MUTATIONS; (III) QUANTIFYING EPIGENETIC-ENVIRONMENTAL VARIABLES IN DIVERSE AREAS MYOFASCIAL PAIN, ALVEOLAR REMODELLING AND MANDIBULAR GROWTH. COMMON NEEDS IDENTIFIED FROM THE THEMED SESSIONS WERE MULTISCALE/MULTISPECIES MODELLING AND EXPERIMENTATION USING CONTROLLED AND QUANTIFIED MECHANICS AND TRANSLATION OF THE FINDINGS IN BONE BIOLOGY BETWEEN SPECIES. PANEL DISCUSSIONS LED TO THE CONSENSUS THAT A CONSORTIUM APPROACH TO ESTABLISH STANDARDS FOR INTRA-ORAL SCANNING AND 3D IMAGING SHOULD BE INITIATED. CONCLUSIONS: CURRENT AND EMERGING TECHNOLOGIES STILL REQUIRE SUPPORTED RESEARCH TO TRANSLATE NEW FINDINGS FROM THE LABORATORY TO ORTHODONTIC PRACTICE.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
3  3400  32 HOW CAN PRECISION MEDICINE BE APPLIED TO TEMPOROMANDIBULAR DISORDERS AND ITS COMORBIDITIES? THE EIGHTH SCIENTIFIC MEETING OF THE TMJ ASSOCIATION, LTD. WAS HELD IN BETHESDA, MARYLAND, SEPTEMBER 11-13, 2016. AS IN THE PAST, THE MEETING WAS COSPONSORED BY COMPONENTS OF THE NATIONAL INSTITUTES OF HEALTH WITH SPEAKERS INVITED TO REVIEW THE STATE OF TEMPOROMANDIBULAR DISORDER SCIENCE AND PROPOSE RECOMMENDATIONS TO FURTHER PROGRESS. THE THEME OF PRECISION MEDICINE, WHICH AIMS TO TAILOR DISEASE TREATMENT AND PREVENTION TO MATCH THE CHARACTERISTICS OF AN INDIVIDUAL PATIENT (GENETIC, EPIGENETIC, ENVIRONMENTAL, LIFESTYLE) UNDERSCORED THE CURRENT CONSENSUS THAT TEMPOROMANDIBULAR DISORDERS ARE NO LONGER VIEWED AS LOCAL CONDITIONS OF JAW PAIN AND DYSFUNCTION. RATHER, THEY REPRESENT A COMPLEX FAMILY OF BIOPSYCHOSOCIAL DISORDERS THAT CAN PROGRESS TO CHRONIC PAIN, MOST OFTEN ACCOMPANIED BY ONE OR MORE OTHER CHRONIC PAIN CONDITIONS. TEMPOROMANDIBULAR DISORDERS AND THESE COMORBIDITIES, CALLED CHRONIC OVERLAPPING PAIN CONDITIONS, PREDOMINANTLY OR EXCLUSIVELY AFFECT WOMEN IN THEIR CHILDBEARING YEARS AND REFLECT CENTRAL NERVOUS SYSTEM SENSITIZATION. PRESENTERS AT THE MEETING INCLUDED LEADERS IN TEMPOROMANDIBULAR DISORDER AND PAIN RESEARCH, TEMPOROMANDIBULAR DISORDER PATIENTS AND ADVOCATES, AND EXPERTS IN OTHER FIELDS OR IN THE USE OF TECHNOLOGIES THAT COULD FACILITATE THE DEVELOPMENT OF PRECISION MEDICINE APPROACHES IN TEMPOROMANDIBULAR DISORDERS.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
4  3004  19 GENETIC, EPIGENETIC, AND MECHANISTIC STUDIES OF TEMPOROMANDIBULAR DISORDERS AND OVERLAPPING PAIN CONDITIONS. LEADERS IN THE FIELDS OF TEMPOROMANDIBULAR DISORDERS (TMD) AND ITS ACCOMPANYING OVERLAPPING PAIN CONDITIONS PRESENTED THEIR LATEST FINDINGS AT THE SEVENTH SCIENTIFIC MEETING OF THE TMJ ASSOCIATION, SEPTEMBER 7-9, 2014, IN BETHESDA, MD. THE MEETING WAS CO-SPONSORED BY THE TMJ ASSOCIATION AND THE NATIONAL INSTITUTES OF HEALTH. TOPICS OF THE SCIENTIFIC SESSIONS INCLUDED EPIDEMIOLOGY AND DIAGNOSTIC CRITERIA, BASIC MECHANISMS OF CHRONIC PAIN INCLUDING THE GENETIC AND EPIGENETIC BASIS OF CHRONIC PAIN, AND THE DEVELOPMENT OF NOVEL DRUGS FOR TREATMENT OF THESE CONDITIONS. DISCUSSIONS WERE DIRECTED TOWARD FORMULATING A SET OF RECOMMENDATIONS TO ADVANCE RESEARCH IN THIS FIELD.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
5  4612  30 NEONATAL PAIN AND COMT VAL158MET GENOTYPE IN RELATION TO SEROTONIN TRANSPORTER (SLC6A4) PROMOTER METHYLATION IN VERY PRETERM CHILDREN AT SCHOOL AGE. CHILDREN BORN VERY PRETERM ARE EXPOSED TO REPEATED NEONATAL PROCEDURES THAT INDUCE PAIN AND STRESS DURING HOSPITALIZATION IN THE NEONATAL INTENSIVE CARE UNIT (NICU). THE COMT VAL158MET GENOTYPE IS INVOLVED WITH PAIN SENSITIVITY, AND EARLY LIFE STRESS IS IMPLICATED IN ALTERED EXPRESSION OF METHYLATION OF THE SEROTONIN TRANSPORTER. WE EXAMINED: (1) WHETHER METHYLATION OF THE SEROTONIN TRANSPORTER GENE (SLC6A4) PROMOTER DIFFERS BETWEEN VERY PRETERM CHILDREN AND FULL-TERM CONTROLS AT SCHOOL AGE, (2) RELATIONSHIPS WITH CHILD BEHAVIOR PROBLEMS, AND (3) WHETHER THE EXTENT OF NEONATAL PAIN EXPOSURE INTERACTS WITH THE COMT VAL158MET GENOTYPE TO PREDICT SLC6A4 METHYLATION AT 7 YEARS IN THE VERY PRETERM CHILDREN. WE EXAMINED THE ASSOCIATIONS BETWEEN THE COMT GENOTYPES, NEONATAL PAIN EXPOSURE (ADJUSTED FOR NEONATAL CLINICAL CONFOUNDERS), SLC6A4 METHYLATION AND BEHAVIOR PROBLEMS. VERY PRETERM CHILDREN HAD SIGNIFICANTLY HIGHER METHYLATION AT 7/10 CPG SITES IN THE SLC6A4 PROMOTER COMPARED TO FULL-TERM CONTROLS AT 7 YEARS. NEONATAL PAIN (ADJUSTED FOR CLINICAL CONFOUNDERS) WAS SIGNIFICANTLY ASSOCIATED WITH TOTAL CHILD BEHAVIOR PROBLEMS ON THE CHILD BEHAVIOR CHECKLIST (CBCL) QUESTIONNAIRE (ADJUSTED FOR CONCURRENT STRESSORS AND 5HTTLPR GENOTYPE) (P = 0.035). CBCL TOTAL PROBLEMS WAS SIGNIFICANTLY ASSOCIATED WITH GREATER SLC6A4 METHYLATION IN VERY PRETERM CHILDREN (P = 0.01). NEONATAL PAIN (ADJUSTED FOR CLINICAL CONFOUNDERS) AND COMT MET/MET GENOTYPE WERE ASSOCIATED WITH SLC6A4 PROMOTER METHYLATION IN VERY PRETERM CHILDREN AT 7 YEARS (P = 0.001). THESE FINDINGS PROVIDE EVIDENCE THAT BOTH GENETIC PREDISPOSITION AND EARLY ENVIRONMENT NEED TO BE CONSIDERED IN UNDERSTANDING SUSCEPTIBILITY FOR DEVELOPING BEHAVIORAL PROBLEMS IN THIS VULNERABLE POPULATION.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
6  5612  35 SAFETY AND ACTIVITY OF RRX-001 IN PATIENTS WITH ADVANCED CANCER: A FIRST-IN-HUMAN, OPEN-LABEL, DOSE-ESCALATION PHASE 1 STUDY. BACKGROUND: EPIGENETIC ALTERATIONS HAVE BEEN STRONGLY ASSOCIATED WITH TUMOUR FORMATION AND RESISTANCE TO CHEMOTHERAPEUTIC DRUGS, AND EPIGENETIC MODIFICATIONS ARE AN ATTRACTIVE TARGET IN CANCER RESEARCH. RRX-001 IS ACTIVATED BY HYPOXIA AND INDUCES THE GENERATION OF REACTIVE OXYGEN AND NITROGEN SPECIES THAT CAN EPIGENETICALLY MODULATE DNA METHYLATION, HISTONE DEACETYLATION, AND LYSINE DEMETHYLATION. THE AIM OF THIS PHASE 1 STUDY WAS TO ASSESS THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF RRX-001. METHODS: IN THIS OPEN-LABEL, DOSE-ESCALATION, PHASE 1 STUDY, WE RECRUITED ADULT PATIENTS (AGED >18 YEARS) WITH HISTOLOGICALLY OR CYTOLOGICALLY CONFIRMED DIAGNOSIS OF ADVANCED, MALIGNANT, INCURABLE SOLID TUMOURS FROM UNIVERSITY OF CALIFORNIA AT SAN DIEGO, CA, USA, AND SARAH CANNON RESEARCH INSTITUTE, NASHVILLE, TN, USA. KEY ELIGIBILITY CRITERIA INCLUDED EVALUABLE DISEASE, EASTERN COOPERATIVE GROUP PERFORMANCE STATUS OF 2 OR LESS, AN ESTIMATED LIFE EXPECTANCY OF AT LEAST 12 WEEKS, ADEQUATE LABORATORY PARAMETERS, DISCONTINUATION OF ALL PREVIOUS ANTINEOPLASTIC THERAPIES AT LEAST 6 WEEKS BEFORE INTERVENTION, AND NO RESIDUAL SIDE-EFFECTS FROM PREVIOUS THERAPIES. PATIENTS WERE ASSIGNED TO RECEIVE INTRAVENOUS INFUSIONS OF RRX-001 AT INCREASING DOSES (10 MG/M(2), 16.7 MG/M(2), 24.6 MG/M(2), 33 MG/M(2), 55 MG/M(2), AND 83 MG/M(2)) EITHER ONCE OR TWICE-WEEKLY FOR AT LEAST 4 WEEKS, WITH AT LEAST THREE PATIENTS PER DOSE COHORT AND ALLOWING A 2-WEEK OBSERVATION PERIOD BEFORE DOSE ESCALATION. SAMPLES FOR SAFETY AND PHARMACOKINETICS ANALYSIS, INCLUDING STANDARD CHEMISTRY AND HAEMATOLOGICAL PANELS, WERE TAKEN ON EACH TREATMENT DAY. THE PRIMARY OBJECTIVE WAS TO ASSESS SAFETY, TOLERABILITY, AND DOSE-LIMITING TOXIC EFFECTS OF RRX-001, TO DETERMINE SINGLE-DOSE PHARMACOKINETICS, AND TO IDENTIFY A RECOMMENDED DOSE FOR PHASE 2 TRIALS. ALL ANALYSES WERE DONE PER PROTOCOL. ACCRUAL IS COMPLETE AND FOLLOW-UP IS STILL ON-GOING. THIS TRIAL IS REGISTERED WITH CLINICALTRIALS.GOV, NUMBER NCT01359982. FINDINGS: BETWEEN OCT 10, 2011, AND MARCH 18, 2013, WE ENROLLED 25 PATIENTS AND TREATED SIX PATIENTS IN THE 10 MG/M(2) COHORT, THREE PATIENTS IN THE 16.7 MG/M(2) COHORT, THREE PATIENTS IN THE 24.6 MG/M(2) COHORT, FOUR PATIENTS IN THE 33 MG/M(2) COHORT, THREE PATIENTS IN THE 55 MG/M(2), AND SIX PATIENTS IN THE 83 MG/M(2) COHORT. PAIN AT THE INJECTION SITE, MOSTLY GRADE 1 AND GRADE 2, WAS THE MOST COMMON ADVERSE EVENT RELATED TO TREATMENT, EXPERIENCED BY 21 (84%) PATIENTS. OTHER COMMON DRUG-RELATED ADVERSE EVENTS INCLUDED ARM SWELLING OR OEDEMA (EIGHT [32%] PATIENTS), AND VEIN HARDENING (SEVEN [28%] PATIENTS). NO DOSE-LIMITING TOXICITIES WERE OBSERVED. TIME CONSTRAINTS RELATED TO MANAGEMENT OF INFUSION PAIN FROM RRX-001 RESULTED IN A MAXIMALLY FEASIBLE DOSE OF 83 MG/M(2). OF THE 21 EVALUABLE PATIENTS, ONE (5%) PATIENT HAD A PARTIAL RESPONSE, 14 (67%) PATIENTS HAD STABLE DISEASE, AND SIX (29%) PATIENTS HAD PROGRESSIVE DISEASE; ALL RESPONSES WERE ACROSS A VARIETY OF TUMOUR TYPES. FOUR PATIENTS WHO HAD RECEIVED RRX-001 WERE SUBSEQUENTLY RECHALLENGED WITH A TREATMENT THAT THEY HAD BECOME REFRACTORY TO; ALL FOUR RESPONDED TO THE RECHALLENGE. INTERPRETATION: RRX-001 IS A WELL-TOLERATED NOVEL COMPOUND WITHOUT CLINICALLY SIGNIFICANT TOXIC EFFECTS AT THE TESTED DOSES. PRELIMINARY EVIDENCE OF ACTIVITY IS PROMISING AND, ON THE BASIS OF ALL FINDINGS, A DOSE OF 16.7 MG/M(2) WAS RECOMMENDED AS THE TARGETED DOSE FOR PHASE 2 TRIALS. FUNDING: EPICENTRX (FORMERLY RADIORX).	2015	

7  3797  11 INTERNATIONAL BREAST CANCER AND NUTRITION: A MODEL FOR RESEARCH, TRAINING AND POLICY IN DIET, EPIGENETICS, AND CHRONIC DISEASE PREVENTION. THIS ARTICLE SUMMARIZES PRESENTATIONS FROM THE INTERNATIONAL BREAST CANCER AND NUTRITION WORKSHOP HELD DURING THE ASN SCIENTIFIC SESSIONS AND ANNUAL MEETING AT EXPERIMENTAL BIOLOGY 2014 IN SAN DIEGO, CA, ON 28 APRIL 2014. AN INTERNATIONAL COLLABORATION WAS DESCRIBED AMONG TEAMS FROM LOW-, MIDDLE-, AND HIGH-INCOME COUNTRIES ADDRESSING ENVIRONMENTAL FACTORS, ESPECIALLY DIET, AND EPIGENETIC INTERACTIONS THAT AFFECT THE RISK OF CHRONIC DISEASE. SPEAKERS ADDRESSED OPPORTUNITIES AND CHALLENGES INVOLVED IN THIS TYPE OF INTERNATIONAL COLLABORATION, ASSESSING DIET AND NUTRITIONAL STATUS ACROSS A WIDE RANGE OF CULTURES, AND RESEARCH TOOLS AND DISCOVERIES FROM THIS GROUP.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
8  4916  22 PAIN-RELATED INCREASE IN SEROTONIN TRANSPORTER GENE METHYLATION ASSOCIATES WITH EMOTIONAL REGULATION IN 4.5-YEAR-OLD PRETERM-BORN CHILDREN. AIM: THE MAIN GOAL OF THIS STUDY WAS TO ASSESS THE ASSOCIATION BETWEEN PAIN-RELATED INCREASE IN SEROTONIN TRANSPORTER GENE (SLC6A4) METHYLATION AND EMOTIONAL DYSREGULATION IN 4.5-YEAR-OLD PRETERM CHILDREN COMPARED WITH FULL-TERM MATCHED COUNTERPARTS. METHODS: PRETERM (N = 29) AND FULL-TERM (N = 26) CHILDREN RECRUITED FROM TWO ITALIAN HOSPITALS WERE FOLLOWED-UP FROM OCTOBER 2011 TO DECEMBER 2017. SLC6A4 METHYLATION WAS ASSESSED FROM CORD BLOOD AT BIRTH FROM BOTH GROUPS AND PERIPHERAL BLOOD AT DISCHARGE FOR PRETERM ONES. AT 4.5 YEARS, EMOTIONAL REGULATION (IE, ANGER, FEAR AND SADNESS) WAS ASSESSED THROUGH AN OBSERVATIONAL STANDARDISED PROCEDURE. RESULTS: PRETERM CHILDREN (18 FEMALES; MEAN AGE = 4.5, RANGE = 4.3-4.8) SHOWED GREATER ANGER DISPLAY COMPARED WITH FULL-TERM CONTROLS (14 FEMALES; MEAN AGE = 4.5, RANGE = 4.4-4.9) IN RESPONSE TO EMOTIONAL STRESS. CONTROLLING FOR ADVERSE LIFE EVENTS OCCURRENCE FROM DISCHARGE TO 4.5 YEARS AND SLC6A4 METHYLATION AT BIRTH, CPG-SPECIFIC SLC6A4 METHYLATION IN THE NEONATAL PERIOD WAS PREDICTIVE OF GREATER ANGER DISPLAY IN PRETERM CHILDREN BUT NOT IN FULL-TERM ONES. CONCLUSION: THESE FINDINGS CONTRIBUTE TO HIGHLIGHT HOW EPIGENETIC REGULATION OF SEROTONIN TRANSPORTER GENE IN RESPONSE TO NICU PAIN EXPOSURE CONTRIBUTES TO LONG-LASTING PROGRAMMING OF ANGER REGULATION IN PRETERM CHILDREN.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
9  3559  28 IMPACT OF CHRONIC CONDITIONS AND DEMENTIA IN RURAL WEST TEXAS: A HEALTHY AGING STUDY. ALZHEIMER'S DISEASE (AD) IS A DEVASTATING ILLNESS IN ELDERLY INDIVIDUALS, THAT CURRENTLY HAS NO KNOWN CURE. CAUSAL GENETIC FACTORS ONLY ACCOUNT FOR 1-2% OF AD PATIENTS. HOWEVER, OTHER CAUSAL FACTORS ARE STILL UNKNOWN FOR A MAJORITY OF AD PATIENTS. CURRENTLY, MULTIPLE FACTORS ARE IMPLICATED IN LATE-ONSET AD, INCLUDING UNHEALTHY DIET, PHYSICAL INACTIVITY, TRAUMATIC BRAIN INJURY, CHRONIC CONDITIONS, EPIGENETIC FACTORS, AND ENVIRONMENTAL EXPOSURES. ALTHOUGH CLINICAL SYMPTOMS OF DEMENTIA ARE COMMON TO ALL RACES AND ETHNIC GROUPS, CONDITIONS THAT LEAD TO DEMENTIA ARE DIFFERENT IN TERMS OF LIFESTYLE, GENETIC PROFILE, AND SOCIO-ECONOMIC CONDITIONS. INCREASING EVIDENCE ALSO SUGGESTS THAT SOME ELDERLY INDIVIDUALS AGE WITHOUT COGNITIVE IMPAIRMENTS IN THEIR 60-90S AS SEEN IN RURAL WEST TEXAS, WHILE SOME INDIVIDUALS PROGRESS WITH CHRONIC CONDITIONS AND COGNITIVE IMPAIRMENTS INTO THEIR 60S. TO UNDERSTAND THESE DISCRIMINATIONS, WE ASSESSED CURRENT LITERATURE ON DEMOGRAPHIC FEATURES OF HEALTH IN RURAL WEST TEXAS. THIS PAPER ALSO OUTLINES OUR INITIATED CLINICAL STUDY WITH A PURPOSE OF UNDERSTANDING THE FACTORS THAT ALLOW SOME INDIVIDUALS TO LIVE WITHOUT COGNITIVE IMPAIRMENTS AT THE AGE OF 60-90 YEARS, WHEREAS OTHERS DEVELOP DEFICITS IN COGNITIVE FUNCTION AROUND OR ABOVE 60 YEARS. OUR ONGOING STUDY HOPES TO DETERMINE THE FACTORS THAT DELAY AGING IN SOME INDIVIDUALS BY INVESTIGATING VARIOUS ASPECTS INCLUDING GENETICS, EPIGENETICS, ETHNICITY, BIOLOGY, CULTURE, AND LIFESTYLE. THIS WILL BE ACHIEVED BY GATHERING INFORMATION ABOUT PARTICIPANTS' ETHNOGRAPHIC PROFILES, COGNITIVE ASSESSMENTS, BLOOD-PROFILES, BRAIN SCANS, AND BLOOD-BASED GENOMIC ANALYSES IN RELATION TO LIFESTYLE. THE OUTCOMES OF OUR STUDY WILL PROVIDE INSIGHTS INTO HEALTHY AGING IN RURAL WEST TEXAS.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
10   180  28 ACCELERATED EPIGENETIC AGING IN OLDER ADULTS WITH HIV DISEASE: ASSOCIATIONS WITH SEROSTATUS, HIV CLINICAL FACTORS, AND HEALTH LITERACY. THE PREVALENCE OF OLDER PERSONS WITH HIV (PWH) DISEASE HAS INCREASED CONSIDERABLY IN THE LAST 20 YEARS, BUT OUR UNDERSTANDING OF BIOLOGICAL FACTORS OF AGING AND THEIR CLINICAL CORRELATES AMONG PWH REMAINS LIMITED. STUDY PARTICIPANTS WERE 149 PERSONS AGED 50 AND OLDER, INCLUDING 107 PWH AND 42 SERONEGATIVES. ALL PARTICIPANTS COMPLETED A BLOOD DRAW, RESEARCH MEDICAL EVALUATION, STRUCTURED PSYCHIATRIC INTERVIEW, NEUROCOGNITIVE ASSESSMENT, QUESTIONNAIRES, AND MEASURES OF HEALTH LITERACY. FOUR EPIGENETIC CLOCKS WERE GENERATED FROM STORED BLOOD SAMPLES USING STANDARDIZED LABORATORY METHODS. IN REGRESSION MODELS ADJUSTING FOR SEX AND SMOKING STATUS, PWH HAD SIGNIFICANTLY HIGHER EPIGENETIC AGING ACCELERATION VALUES THAN SERONEGATIVES ON ALL FOUR INDICATORS. WITHIN THE PWH SAMPLE, HIGHER LEVELS OF EPIGENETIC AGING ACCELERATION WERE MODERATELY ASSOCIATED WITH LOWER CURRENT CD4 COUNT, AIDS DIAGNOSES, HIGHER SCORES ON THE VETERANS AGING COHORT STUDY INDEX, AND LOWER TELOMERE VALUES. HIGHER EPIGENETIC AGING ACCELERATION INDICES WERE ALSO ASSOCIATED WITH LOWER HEALTH LITERACY AMONG PWH. PWH EXPERIENCE ACCELERATED AGING AS MEASURED BY A SERIES OF EPIGENETIC CLOCKS, WHICH MAY BE LINKED TO IMMUNE COMPROMISE AND RISK OF ALL-CAUSE MORTALITY. HEALTH LITERACY MAY BE A MODIFIABLE TARGET FOR MITIGATING THE RISK OF ACCELERATED AGING AMONG OLDER PWH.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
11  5005  26 PERIPHERAL BLOOD DNA METHYLATION-BASED MACHINE LEARNING MODELS FOR PREDICTION OF KNEE OSTEOARTHRITIS PROGRESSION: BIOLOGIC SPECIMENS AND DATA FROM THE OSTEOARTHRITIS INITIATIVE AND JOHNSTON COUNTY OSTEOARTHRITIS PROJECT. OBJECTIVE: THE LACK OF ACCURATE BIOMARKERS TO PREDICT KNEE OSTEOARTHRITIS (OA) PROGRESSION IS A KEY UNMET NEED IN OA CLINICAL RESEARCH. THE OBJECTIVE OF THIS STUDY WAS TO DEVELOP BASELINE PERIPHERAL BLOOD EPIGENETIC BIOMARKER MODELS TO PREDICT KNEE OA PROGRESSION. METHODS: GENOME-WIDE BUFFY COAT DNA METHYLATION PATTERNS FROM 554 INDIVIDUALS FROM THE OSTEOARTHRITIS BIOMARKERS CONSORTIUM (OABC) WERE DETERMINED USING ILLUMINA INFINIUM METHYLATIONEPIC 850K ARRAYS. DATA WERE DIVIDED INTO MODEL DEVELOPMENT AND VALIDATION SETS, AND MACHINE LEARNING MODELS WERE TRAINED TO CLASSIFY FUTURE OA PROGRESSION BY KNEE PAIN, RADIOGRAPHIC IMAGING, KNEE PAIN PLUS RADIOGRAPHIC IMAGING, AND ANY PROGRESSION (PAIN, RADIOGRAPHIC, OR BOTH). PARSIMONIOUS MODELS USING THE TOP 13 CPG SITES MOST FREQUENTLY SELECTED DURING DEVELOPMENT WERE TESTED ON INDEPENDENT SAMPLES FROM PARTICIPANTS IN THE JOHNSTON COUNTY OSTEOARTHRITIS (JOCO OA) PROJECT (N = 128) AND A PREVIOUSLY PUBLISHED OSTEOARTHRITIS INITIATIVE (OAI) DATA SET (N = 55). RESULTS: FULL MODELS ACCURATELY CLASSIFIED FUTURE RADIOGRAPHIC-ONLY PROGRESSION (MEAN +/- SEM ACCURACY 87 +/- 0.8%, AREA UNDER THE CURVE [AUC] 0.94 +/- 0.004), PAIN-ONLY PROGRESSION (ACCURACY 89 +/- 0.9%, AUC 0.97 +/- 0.004), PAIN PLUS RADIOGRAPHIC PROGRESSION (ACCURACY 72 +/- 0.7%, AUC 0.79 +/- 0.006), AND ANY PROGRESSION (ACCURACY 78 +/- 0.4%, AUC 0.86 +/- 0.004). PAIN-ONLY AND RADIOGRAPHIC-ONLY PROGRESSORS WERE NOT DISTINGUISHABLE (MEAN +/- SEM ACCURACY 58 +/- 1%, AUC 0.62 +/- 0.001). PARSIMONIOUS MODELS SHOWED SIMILAR PERFORMANCE AND ACCURATELY CLASSIFIED FUTURE RADIOGRAPHIC PROGRESSORS IN THE OABC COHORT AND IN BOTH VALIDATION COHORTS (MEAN +/- SEM ACCURACY 80 +/- 0.3%, AUC 0.88 +/- 0.003 [USING JOCO OA PROJECT DATA], ACCURACY 80 +/- 0.8%, AUC 0.89 +/- 0.002 [USING PREVIOUS OAI DATA]). CONCLUSION: OUR DATA SUGGEST THAT PAIN AND STRUCTURAL PROGRESSION SHARE SIMILAR EARLY SYSTEMIC IMMUNE EPIGENOTYPES. FURTHER STUDIES SHOULD FOCUS ON EVALUATING THE PATHOPHYSIOLOGIC CONSEQUENCES OF DIFFERENTIAL DNA METHYLATION AND PERIPHERAL BLOOD CELL EPIGENOTYPES IN INDIVIDUALS WITH KNEE OA.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
12  5085  29 PILOT STUDY OF ABSOLUTE TELOMERE LENGTHS IN PRETERM INFANTS. BACKGROUND: ANNUALLY, APPROXIMATELY 15 MILLION BABIES ARE BORN PRETERM (<37 WEEKS GESTATIONAL AGE) GLOBALLY. IN THE NEONATAL INTENSIVE CARE UNIT (NICU) ENVIRONMENT, INFANTS ARE EXPOSED TO REPEATED STRESSFUL OR PAINFUL PROCEDURES AS PART OF ROUTINE LIFESAVING CARE. THESE PROCEDURES HAVE BEEN ASSOCIATED WITH EPIGENETIC ALTERATIONS THAT MAY LEAD TO AN INCREASED RISK OF NEURODEVELOPMENTAL DISORDERS. TELOMERE LENGTH HAS BEEN NEGATIVELY ASSOCIATED WITH ADVERSE LIFE EXPERIENCES IN STUDIES OF ADULTS. OBJECTIVES: THIS PILOT STUDY AIMED TO DESCRIBE TELOMERE LENGTH IN A SAMPLE OF PRETERM INFANTS AT NICU DISCHARGE AND EXAMINE ANY ASSOCIATIONS WITH PAIN, FEEDING METHOD, AND NEURODEVELOPMENT. METHODS: THIS DESCRIPTIVE PILOT STUDY SAMPLE INCLUDES BASELINE ABSOLUTE TELOMERE LENGTH (ATL) OF 36 PRETERM INFANTS IMMEDIATELY PRIOR TO DISCHARGE. QUANTITATIVE POLYMERASE CHAIN REACTION WAS USED TO DETERMINE ATL. INFANT DEMOGRAPHICS, PAIN/STRESS, TYPE OF FEEDING, ANTIBIOTIC USE, NEURODEVELOPMENT, AND BUCCAL SWAB DATA WERE COLLECTED. DESCRIPTIVE DATA ANALYSIS WAS USED TO DESCRIBE THE TELOMERE LENGTH USING GRAPHS. RESULTS: AMONG OUR PRETERM INFANT SAMPLES, THE MEAN ATL WAS FAR GREATER THAN THE AVERAGE ADULT TELOMERE LENGTH. ALTHOUGH NO SIGNIFICANT ASSOCIATIONS WERE FOUND BETWEEN ATL AND PAIN, FEEDING METHOD, AND NEURODEVELOPMENT, A TREND BETWEEN SEX WAS NOTED WHERE MALE TELOMERE LENGTHS WERE SHORTER THAN FEMALES AS THEY AGED. DISCUSSION: THIS IS ONE OF FEW STUDIES TO EVALUATE PRETERM INFANT TELOMERE LENGTH. ALTHOUGH OTHER RESEARCHERS HAVE USED RELATIVE TELOMERE LENGTH, WE USED THE MORE ACCURATE ATL. WE FOUND NONSIGNIFICANT SHORTER TELOMERE LENGTHS AMONG MALES. ADDITIONAL LARGE-SCALE, LONGITUDINAL STUDIES ARE NEEDED TO BETTER IDENTIFY THE PREDICTORS OF TELOMERE LENGTH AT THE TIME OF DISCHARGE FROM NICU.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                    
13  6598  25 TWINSUK: THE UK ADULT TWIN REGISTRY UPDATE. TWINSUK IS THE LARGEST COHORT OF COMMUNITY-DWELLING ADULT TWINS IN THE UK. THE REGISTRY COMPRISES OVER 14,000 VOLUNTEER TWINS (14,838 INCLUDING MIXED, SINGLE AND TRIPLETS); IT IS PREDOMINANTLY FEMALE (82%) AND MIDDLE-AGED (MEAN AGE 59). IN ADDITION, OVER 1800 PARENTS AND SIBLINGS OF TWINS ARE REGISTERED VOLUNTEERS. DURING THE LAST 27 YEARS, TWINSUK HAS COLLECTED NUMEROUS QUESTIONNAIRE RESPONSES, PHYSICAL/COGNITIVE MEASURES AND BIOLOGICAL MEASURES ON OVER 8500 SUBJECTS. DATA WERE COLLECTED ALONGSIDE FOUR COMPREHENSIVE PHENOTYPING CLINICAL VISITS TO THE DEPARTMENT OF TWIN RESEARCH AND GENETIC EPIDEMIOLOGY, KING'S COLLEGE LONDON. SUCH COLLECTION METHODS HAVE RESULTED IN VERY DETAILED LONGITUDINAL CLINICAL, BIOCHEMICAL, BEHAVIORAL, DIETARY AND SOCIOECONOMIC COHORT CHARACTERIZATION; IT PROVIDES A MULTIDISCIPLINARY PLATFORM FOR THE STUDY OF COMPLEX DISEASE DURING THE ADULT LIFE COURSE, INCLUDING THE PROCESS OF HEALTHY AGING. THE MAJOR STRENGTH OF TWINSUK IS THE AVAILABILITY OF SEVERAL 'OMIC' TECHNOLOGIES FOR A RANGE OF SAMPLE TYPES FROM PARTICIPANTS, WHICH INCLUDES GENOMEWIDE SCANS OF SINGLE-NUCLEOTIDE VARIANTS, NEXT-GENERATION SEQUENCING, METABOLOMIC PROFILES, MICROBIOMICS, EXOME SEQUENCING, EPIGENETIC MARKERS, GENE EXPRESSION ARRAYS, RNA SEQUENCING AND TELOMERE LENGTH MEASURES. TWINSUK FACILITATES AND ACTIVELY ENCOURAGES SHARING THE 'TWINSUK' RESOURCE WITH THE SCIENTIFIC COMMUNITY - INTERESTED RESEARCHERS MAY REQUEST DATA VIA THE TWINSUK WEBSITE (HTTP://TWINSUK.AC.UK/RESOURCES-FOR-RESEARCHERS/ACCESS-OUR-DATA/) FOR THEIR OWN USE OR FUTURE COLLABORATION WITH THE STUDY TEAM. IN ADDITION, FURTHER COHORT DATA COLLECTION IS PLANNED VIA THE WELLCOME OPEN RESEARCH GATEWAY (HTTPS://WELLCOMEOPENRESEARCH.ORG/GATEWAYS). THE CURRENT ARTICLE PRESENTS AN UP-TO-DATE REPORT ON THE APPLICATION OF TECHNOLOGICAL ADVANCES, NEW STUDY PROCEDURES IN THE COHORT AND FUTURE DIRECTION OF TWINSUK.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                          
14   464  31 ARE HEIGHT AND LEG LENGTH UNIVERSAL MARKERS OF CHILDHOOD CONDITIONS? THE GUANGZHOU BIOBANK COHORT STUDY. OBJECTIVE: IN DEVELOPED WESTERN POPULATIONS LONGER LEGS HAVE BEEN SHOWN TO BE A MARKER OF BETTER EARLY CHILDHOOD CONDITIONS. IN THE FIRST GENERATIONS TO EXPERIENCE THE EPIDEMIOLOGIC TRANSITION AND ASSOCIATED ECONOMIC DEVELOPMENT, EPIGENETIC CONSTRAINTS ON GROWTH MIGHT PRECLUDE IMPROVED CHILDHOOD CONDITIONS FROM INCREASING LEG GROWTH OR HEIGHT. DESIGN, SETTING AND PARTICIPANTS: MULTIVARIABLE LINEAR REGRESSION WAS USED TO ASSESS THE ASSOCIATION OF PARENTAL GROWTH ENVIRONMENT, PROXIED BY PARENTAL LITERACY, AND CHILDHOOD CONDITIONS, PROXIED BY PARENTAL POSSESSIONS, WITH LEG LENGTH, SITTING HEIGHT AND HEIGHT IN A CROSS-SECTIONAL SAMPLE FROM 2005-6 OF 9998 CHINESE PEOPLE AGED AT LEAST 50 YEARS FROM PHASE 2 OF THE GUANGZHOU BIOBANK COHORT STUDY. MAIN RESULTS: ADJUSTED FOR AGE AND SEX, THE ASSOCIATION OF CHILDHOOD CONDITIONS WITH LEG LENGTH AND HEIGHT VARIED WITH PARENTAL LITERACY (INTERACTION P VALUES <0.01 AND 0.03), BUT NOT FOR SITTING HEIGHT (P VALUE 0.43), WITH STATISTICALLY SIGNIFICANT TRENDS (P VALUES <0.01) FOR PARENTAL POSSESSIONS TO BE ASSOCIATED WITH LONGER LEGS AND GREATER HEIGHT ONLY IN THE OFFSPRING OF TWO LITERATE PARENTS WHERE LEGS WERE LONGER BY 0.56 CM (95% CI 0.27 TO 0.86) AND HEIGHT GREATER BY 1.16 CM (95% CI 0.74 TO 1.58) FOR PARTICIPANTS WITH MOST, COMPARED WITH LEAST, PARENTAL POSSESSIONS IN CHILDHOOD. CONCLUSIONS: EPIGENETIC INFLUENCES ORIGINATING IN EARLIER GENERATIONS MAY CONSTRAIN GROWTH DURING THE INFANCY AND/OR CHILDHOOD PHASES IN VERY RECENTLY DEVELOPED POPULATIONS. NEITHER HEIGHT NOR LEG LENGTH SHOULD BE ASSUMED TO BE CONSISTENT PROXIES OF EARLY LIFE ENVIRONMENT WITH CORRESPONDING IMPLICATIONS FOR ECONOMIC HISTORY, THE AETIOLOGY OF SOME CHRONIC DISEASES AND THE MONITORING OF POPULATION HEALTH.	2008	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
15  1956  28 EPIGENETIC AGE IN PERIPHERAL BLOOD AMONG CHILDREN, ADOLESCENT, AND ADULT SURVIVORS OF CHILDHOOD CANCER. IMPORTANCE: CERTAIN CANCER THERAPIES ARE RISK FACTORS FOR EPIGENETIC AGE ACCELERATION (EAA) AMONG SURVIVORS OF CHILDHOOD CANCER, AND EAA IS ASSOCIATED WITH CHRONIC HEALTH CONDITIONS (CHCS). HOWEVER, SMALL NUMBERS OF YOUNGER SURVIVORS (AGED <20 YEARS) PREVIOUSLY EVALUATED HAVE LIMITED THE ABILITY TO CALCULATE EAA AMONG THIS AGE GROUP. OBJECTIVE: TO EVALUATE THE CHANGE RATE OF EPIGENETIC AGE (EA) AND EAA IN YOUNGER COMPARED WITH OLDER SURVIVORS AND THE POSSIBLE ASSOCIATION OF EAA WITH EARLY-ONSET OBESITY (AGED <20 YEARS), SEVERITY/BURDEN OF CHCS, AND LATE MORTALITY (>5 YEARS FROM CANCER DIAGNOSIS). DESIGN, SETTING, AND PARTICIPANTS: STUDY PARTICIPANTS WERE FROM THE ST JUDE LIFETIME COHORT, INITIATED IN 2007 WITH ONGOING FOLLOW-UP. THE PRESENT STUDY WAS CONDUCTED FROM APRIL 17, 2022, TO MARCH 23, 2023. SURVIVORS IN THIS COHORT OF EUROPEAN ANCESTRY WITH DNA METHYLATION DATA WERE INCLUDED. CROSS-SECTIONAL ANNUAL CHANGES IN EA AND EAA WERE COMPARED ACROSS 5 DIFFERENT CHRONOLOGIC AGE GROUPS: AGE 0 TO 9 (CHILDREN), 10 TO 19 (ADOLESCENTS), 20 TO 34 (YOUNGER ADULTS), 35 TO 49 (MIDDLE-AGED ADULTS), AND GREATER THAN OR EQUAL TO 50 (OLDER ADULTS) YEARS. LOGISTIC REGRESSION EVALUATED THE ASSOCIATION BETWEEN EAA AND EARLY-ONSET OBESITY OR SEVERITY/BURDEN OF CHCS. COX PROPORTIONAL HAZARDS REGRESSION ASSESSED THE ASSOCIATION BETWEEN EAA AND LATE MORTALITY. MAIN OUTCOMES AND MEASURES: EARLY-ONSET OBESITY, SEVERITY/BURDEN OF CHCS (GRADED USING THE COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (GRADE 1, MILD; 2, MODERATE; 3, SEVERE/DISABLING; 4, LIFE-THREATENING) AND WERE COMBINED INTO HIGH VS LOW SEVERITY/BURDEN BASED ON FREQUENCY AND GRADE), AND LATE MORTALITY WERE THE OUTCOMES BASED ON FOLLOW-UP UNTIL APRIL 2020. EXPANDED DNA METHYLATION PROFILING INCREASED THE NUMBER OF SURVIVORS YOUNGER THAN 20 YEARS (N = 690). EPIGENETIC AGE WAS CALCULATED PRIMARILY USING THE LEVINE CLOCK, AND EAA WAS DERIVED FROM LEAST SQUARES REGRESSION OF EA AGAINST CHRONOLOGIC AGE AND WAS STANDARDIZED TO A Z SCORE (LEVINE EEA). RESULTS: AMONG 2846 PARTICIPANTS (MEDIAN AGE, 30.3 [IQR, 9.3-41.5] YEARS; 53% MALES), THE CROSS-SECTIONAL ANNUAL CHANGE IN EA_LEVINE WAS HIGHER IN CHILDREN (1.63 YEARS) AND ADOLESCENTS (1.14 YEARS), AND THE ADJUSTED LEAST-SQUARES MEAN OF LEVINE EEA WAS LOWER IN CHILDREN (-0.22 YEARS) AND OLDER ADULTS (-1.70 YEARS). EACH 1-SD INCREASE IN LEVINE EEA WAS ASSOCIATED WITH INCREASED RISK OF DEVELOPING EARLY-ONSET OBESITY (ODDS RATIO [OR], 1.46; 95% CI, 1.19-1.78), HIGH SEVERITY/BURDEN OF CHCS (OR, 1.13; 95% CI, 1.03-1.24), AND LATE MORTALITY (HAZARD RATIO, 1.75; 95% CI, 1.35-2.26). CONCLUSIONS AND RELEVANCE: THE FINDINGS OF THIS STUDY SUGGEST THAT EAA MEASURED IN CHILDREN AND ADOLESCENT SURVIVORS OF CHILDHOOD CANCER IS ASSOCIATED WITH EARLY-ONSET OBESITY, SEVERITY/BURDEN OF ALL CHCS, AND LATE MORTALITY. EVALUATING EAA MAY HELP IDENTIFY SURVIVORS OF CHILDHOOD CANCER AT INCREASED RISK FOR EARLY-ONSET OBESITY, MORBIDITY IN GENERAL, AND MORTALITY.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           
16   325  30 ALLELE-SPECIFIC DNA METHYLATION LEVEL OF FKBP5 IS ASSOCIATED WITH POST-TRAUMATIC STRESS DISORDER. BACKGROUND: FK506-BINDING PROTEIN 5 (FKBP5) BINDS TO GLUCOCORTICOID RECEPTORS AND MODULATES GLUCOCORTICOID SENSITIVITY. THE FKBP5 GENE HAS BEEN IMPLICATED IN THE DYSREGULATION OF HUMAN STRESS RESPONSES, CONTRIBUTING TO THE RISK AND TREATMENT RESPONSE OF STRESS-RELATED DISORDERS. THE PRESENT STUDY EXAMINED WHETHER EPIGENETIC CHANGES IN FKBP5 ARE ASSOCIATED WITH CHRONIC POST-TRAUMATIC STRESS DISORDER (PTSD) STATUS IN THE CONTEXT OF FKBP5 GENETIC VARIATION (RS1360780 POLYMORPHISM) AMONG MALE VETERANS EXPOSED TO COMBAT TRAUMA. METHODS: KOREAN MALE VETERANS WHO SERVED ON ACTIVE DUTY DURING THE VIETNAM WAR WERE CATEGORIZED INTO 2 GROUPS: WITH PTSD (N = 123) AND WITHOUT PTSD (N = 116). THE GENOTYPE OF FKBP5 RS1360780 AND DNA METHYLATION LEVELS OF TWO CPG SITES AT THE FKBP5 INTRON 7 REGION WERE ASSESSED IN PERIPHERAL BLOOD. ANALYSIS OF COVARIANCE WAS PERFORMED TO EXAMINE MAIN AND INTERACTION EFFECTS OF PTSD STATUS AND FKBP5 GENOTYPE ON FKBP5 DNA METHYLATION LEVEL, WITH AGE, TRAUMA LEVELS, AND ALCOHOL USE AS COVARIATES. RESULTS: A SIGNIFICANT MAIN EFFECT OF FKBP5 RS1360780 AND PTSD AND AN INTERACTION EFFECT BETWEEN GENOTYPE AND PTSD STATUS WERE FOUND ON MEAN FKBP5 DNA METHYLATION LEVEL. THE T ALLELE OF RS1360780 WAS ASSOCIATED WITH LOWER FKBP5 METHYLATION LEVEL. IN ADDITION, THE PTSD GROUP SHOWED SIGNIFICANTLY HIGHER METHYLATION THAN DID THE NON-PTSD GROUP AMONG VETERANS CARRYING THE RISK T ALLELE (N = 96), WHILE NO GROUP DIFFERENCE WAS OBSERVED ON METHYLATION LEVELS AMONG VETERANS WITH THE CC GENOTYPE (N = 143). AMONG VETERANS CARRYING THE T ALLELE, FKBP5 METHYLATION LEVELS WERE POSITIVELY CORRELATED WITH THE SEVERITY OF PTSD SYMPTOMS. CONCLUSIONS: THE PRESENT STUDY DEMONSTRATED DIFFERENT FKBP5 METHYLATION LEVELS IN PTSD DEPENDING ON FKBP5 GENETIC VARIATION AMONG VETERANS EXPOSED TO COMBAT TRAUMA. THE PRESENT FINDING SUGGESTS THAT THE GENETIC AND EPIGENETIC MODULATION OF FKBP5 IS INVOLVED IN THE PATHOPHYSIOLOGY OF PTSD. FURTHER LONGITUDINAL RESEARCH INVOLVING PEOPLE EXPOSED TO TRAUMA IS REQUIRED TO UNDERSTAND CAUSAL RELATIONSHIPS OF FKBP5 IN THE DEVELOPMENT AND RECOVERY OF PTSD.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
17  5470  26 RESOLVING THE ENIGMA OF THE MESOAMERICAN NEPHROPATHY: A RESEARCH WORKSHOP SUMMARY. THE FIRST INTERNATIONAL RESEARCH WORKSHOP ON MESOAMERICAN NEPHROPATHY (MEN) MET IN COSTA RICA IN NOVEMBER 2012 TO DISCUSS HOW TO ESTABLISH THE EXTENT AND DEGREE OF MEN, EXAMINE RELEVANT CAUSAL HYPOTHESES, AND FOCUS EFFORTS TO CONTROL OR ELIMINATE THE DISEASE BURDEN. MEN DESCRIBES A DEVASTATING EPIDEMIC OF CHRONIC KIDNEY DISEASE OF UNKNOWN ORIGIN PREDOMINANTLY OBSERVED AMONG YOUNG MALE SUGARCANE CUTTERS. THE CAUSE OF MEN REMAINS UNCERTAIN; HOWEVER, THE STRONGEST HYPOTHESIS PURSUED TO DATE IS REPEATED EPISODES OF OCCUPATIONAL HEAT STRESS AND WATER AND SOLUTE LOSS, PROBABLY IN COMBINATION WITH OTHER POTENTIAL RISK FACTOR(S), SUCH AS NONSTEROIDAL ANTI-INFLAMMATORY DRUG AND OTHER NEPHROTOXIC MEDICATION USE, INORGANIC ARSENIC, LEPTOSPIROSIS, OR PESTICIDES. AT THE RESEARCH WORKSHOP, CLINICAL AND EPIDEMIOLOGIC CASE DEFINITIONS WERE PROPOSED IN ORDER TO FACILITATE BOTH PUBLIC HEALTH AND RESEARCH EFFORTS. RECOMMENDATIONS EMANATING FROM THE WORKSHOP INCLUDED MEASURING WORKLOAD, HEAT, AND WATER AND SOLUTE LOSS AMONG WORKERS; QUANTIFYING NEPHROTOXIC AGENTS IN DRINKING WATER AND FOOD; USING BIOMARKERS OF EARLY KIDNEY INJURY TO EXPLORE POTENTIAL CAUSES OF MEN; AND CHARACTERIZING SOCIAL AND WORKING CONDITIONS TOGETHER WITH METHODS FOR VALID DATA COLLECTION OF EXPOSURES AND PERSONAL RISK FACTORS. ADVANTAGES AND DISADVANTAGES OF DIFFERENT POPULATION STUDY DESIGNS WERE DETAILED. TO ELUCIDATE THE ETIOLOGY OF MEN, MULTICOUNTRY STUDIES WITH PROSPECTIVE COHORT DESIGN, PREFERABLY INTEGRATING AN ECOSYSTEM HEALTH APPROACH, WERE CONSIDERED THE MOST PROMISING. IN ADDITION, GENETIC, EXPERIMENTAL, AND MECHANISTIC METHODS AND DESIGNS WERE ADDRESSED, SPECIFICALLY THE NEED FOR KIDNEY BIOPSY ANALYSIS, STUDIES IN ANIMAL MODELS, ADVANCES IN BIOMARKERS, GENETIC AND EPIGENETIC STUDIES, A COMMON REGISTRY AND REPOSITORY OF BIOLOGICAL AND DEMOGRAPHIC DATA AND/OR SPECIMENS, AND OTHER AREAS OF POTENTIAL CHRONIC KIDNEY DISEASE EXPERIMENTAL RESEARCH. FINALLY, IN ORDER TO IMPROVE INTERNATIONAL COLLABORATION ON MEN, WORKSHOP PARTICIPANTS AGREED TO ESTABLISH A RESEARCH CONSORTIUM TO LINK THESE MESOAMERICAN EFFORTS TO OTHER EFFORTS WORLDWIDE.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
18  4865  26 ORO-FACIAL PAIN AND TEMPOROMANDIBULAR DISORDERS CLASSIFICATION SYSTEMS: A CRITICAL APPRAISAL AND FUTURE DIRECTIONS. IT IS A DIFFICULT UNDERTAKING TO DESIGN A CLASSIFICATION SYSTEM FOR ANY DISEASE ENTITY, LET ALONE FOR ORO-FACIAL PAIN (OFP) AND MORE SPECIFICALLY FOR TEMPOROMANDIBULAR DISORDERS (TMD). A FURTHER COMPLICATION OF THIS TASK IS THAT BOTH PHYSICAL AND PSYCHOSOCIAL VARIABLES MUST BE INCLUDED. TO AUGMENT THIS PROCESS, A TWO-STEP SYSTEMATIC REVIEW, ADHERING TO PRISMA GUIDELINES, OF THE CLASSIFICATION SYSTEMS PUBLISHED DURING THE LAST 20 YEARS FOR OFP AND TMD WAS PERFORMED. THE FIRST SEARCH STEP IDENTIFIED 190 POTENTIAL CITATIONS WHICH ULTIMATELY RESULTED IN ONLY 17 ARTICLES BEING INCLUDED FOR IN-DEPTH ANALYSIS AND REVIEW. THE SECOND STEP RESULTED IN ONLY 5 ARTICLES BEING SELECTED FOR INCLUSION IN THIS REVIEW. FIVE ADDITIONAL ARTICLES AND FOUR CLASSIFICATION GUIDELINES/CRITERIA WERE ALSO INCLUDED DUE TO EXPANSION OF THE SEARCH CRITERIA. THUS, IN TOTAL, 14 DOCUMENTS COMPRISING ARTICLES AND GUIDELINES/CRITERIA (8 PROPOSALS OF CLASSIFICATION SYSTEMS FOR OFP; 6 FOR TMD) WERE SELECTED FOR INCLUSION IN THE SYSTEMATIC REVIEW. FOR EACH, A DISCUSSION AS TO THEIR ADVANTAGES, STRENGTHS AND LIMITATIONS WAS PROVIDED. SUGGESTIONS REGARDING THE FUTURE DIRECTION FOR IMPROVING THE CLASSIFICATION PROCESS WITH THE USE OF ONTOLOGICAL PRINCIPLES RATHER THAN TAXONOMY ARE DISCUSSED. FURTHERMORE, THE POTENTIAL FOR EXPANDING THE SCOPE OF AXES INCLUDED IN EXISTING CLASSIFICATION SYSTEMS, TO INCLUDE GENETIC, EPIGENETIC AND NEUROBIOLOGICAL VARIABLES, IS EXPLORED. IT IS THEREFORE RECOMMENDED THAT FUTURE CLASSIFICATION SYSTEM PROPOSALS BE BASED ON COMBINED APPROACHES AIMING TO PROVIDE ARCHETYPAL TREATMENT-ORIENTED CLASSIFICATIONS.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
19  1957  30 EPIGENETIC AGE PREDICTORS IN COMMUNITY-DWELLING ADULTS WITH HIGH IMPACT KNEE PAIN. GERONTOLOGICAL RESEARCH REVEALS CONSIDERABLE INTERINDIVIDUAL VARIABILITY IN AGING PHENOTYPES, AND EMERGING EVIDENCE SUGGESTS THAT HIGH IMPACT CHRONIC PAIN MAY BE ASSOCIATED WITH VARIOUS ACCELERATED BIOLOGICAL AGING PROCESSES. IN PARTICULAR, EPIGENETIC AGING IS A ROBUST PREDICTOR OF HEALTH-SPAN AND DISABILITY COMPARED TO CHRONOLOGICAL AGE ALONE. THE CURRENT STUDY AIMED TO DETERMINE WHETHER SEVERAL EPIGENETIC AGING BIOMARKERS WERE ASSOCIATED WITH HIGH IMPACT CHRONIC PAIN IN MIDDLE TO OLDER AGE ADULTS (44-78 YEARS OLD). PARTICIPANTS (N = 213) UNDERWENT A BLOOD DRAW, DEMOGRAPHIC, PSYCHOSOCIAL, PAIN AND FUNCTIONAL ASSESSMENTS. WE ESTIMATED FIVE EPIGENETIC CLOCKS AND CALCULATED THE DIFFERENCE BETWEEN EPIGENETIC AGE AND CHRONOLOGICAL AGE, WHICH HAS BEEN PREVIOUSLY REPORTED TO PREDICT OVERALL MORTALITY RISK, AS WELL AS INCLUDED ADDITIONAL DERIVED VARIABLES OF EPIGENETIC AGE PREVIOUSLY ASSOCIATED WITH PAIN. THERE WERE SIGNIFICANT DIFFERENCES ACROSS PAIN IMPACT GROUPS IN THREE OUT OF THE FIVE EPIGENETIC CLOCKS EXAMINED (DNAMAGE, DNAMPHENOAGE AND DNAMGRIMAGE), INDICATING THAT PAIN-RELATED DISABILITY DURING THE PAST 6 MONTHS WAS ASSOCIATED WITH MARKERS OF EPIGENETIC AGING. ONLY DNAMPHENOAGE AND DNAMGRIMAGE WERE ASSOCIATED WITH HIGHER KNEE PAIN INTENSITY DURING THE PAST 48 H. FINALLY, PAIN CATASTROPHIZING, DEPRESSIVE SYMPTOMATOLOGY AND MORE NEUROPATHIC PAIN SYMPTOMS WERE SIGNIFICANTLY ASSOCIATED WITH AN OLDER EPIGENOME IN ONLY ONE OF THE FIVE EPIGENETIC CLOCKS (I.E. DNAMGRIMAGE) AFTER CORRECTING FOR MULTIPLE COMPARISONS (CORRECTED P'S < 0.05). GIVEN THE SCANT LITERATURE IN RELATION TO EPIGENETIC AGING AND THE COMPLEX EXPERIENCE OF PAIN, ADDITIONAL RESEARCH IS NEEDED TO UNDERSTAND WHETHER EPIGENETIC AGING MAY HELP IDENTIFY PEOPLE WITH CHRONIC PAIN AT GREATER RISK OF FUNCTIONAL DECLINE AND POORER HEALTH OUTCOMES.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
20   403  31 ANALYSIS OF EPIGENETIC AGE ACCELERATION AND HEALTHY LONGEVITY AMONG OLDER US WOMEN. IMPORTANCE: ACCELERATED BIOLOGICAL AGING IS ASSOCIATED WITH DECREASED PHYSICAL CAPABILITY AND COGNITIVE FUNCTIONING, WHICH ARE ASSOCIATED WITH INCREASED RISK OF MORBIDITY AND MORTALITY. OBJECTIVE: WE INVESTIGATED ASSOCIATIONS BETWEEN EPIGENETIC AGE ACCELERATION (EAA), A BIOMARKER ASSOCIATED WITH AGING, AND HEALTHY LONGEVITY AMONG OLDER WOMEN. DESIGN, SETTING, AND PARTICIPANTS: THIS COHORT STUDY WAS A SECONDARY ANALYSIS OF PARTICIPANTS IN THE WOMEN'S HEALTH INITIATIVE (WHI) WHO WERE ELIGIBLE TO SURVIVE TO AGE 90 YEARS BY SEPTEMBER 30, 2020. PARTICIPANTS WERE LOCATED IN MULTIPLE CENTERS. THIS STUDY WAS RESTRICTED TO WOMEN WITH GENOME-WIDE DNA METHYLATION DATA, GENERATED FROM BASELINE BLOOD SAMPLES WITHIN 3 WHI ANCILLARY STUDIES. MEDIAN (IQR) FOLLOW-UP TIMES FROM BASELINE WERE 21.6 (19.6-22.9) YEARS AND 21.4 (19.8-22.7) YEARS FOR WOMEN WHO SURVIVED TO AGE 90 YEARS WITH AND WITHOUT INTACT MOBILITY, RESPECTIVELY, AND 13.2 (8.8-16.7) FOR WOMEN WHO DID NOT SURVIVE TO AGE 90 YEARS. DATA WERE ANALYZED FROM DECEMBER 2020 TO JULY 2021. EXPOSURES: EAA WAS ESTIMATED USING 4 ESTABLISHED "CLOCKS": HORVATH PANTISSUE, HANNUM, PHENO, AND GRIM. MAIN OUTCOMES AND MEASURES: USING MULTINOMIAL LOGISTIC REGRESSION, ODDS RATIOS (ORS) AND 95% CIS WERE ESTIMATED FOR 3 HEALTHY LONGEVITY OUTCOMES FOR EACH CLOCK: SURVIVAL TO AGE 90 YEARS WITH INTACT MOBILITY, SURVIVAL TO AGE 90 YEARS WITHOUT INTACT MOBILITY, AND NO SURVIVAL TO AGE 90 YEARS. RESULTS: AMONG 1813 WOMEN, THERE WERE 464 WOMEN (MEAN [SD] AGE AT BASELINE, 71.6 [3.5] YEARS) WHO SURVIVED TO AGE 90 YEARS WITH INTACT MOBILITY AND COGNITIVE FUNCTIONING, 420 WOMEN (MEAN [SD] AGE AT BASELINE, 71.3 [3.2] YEARS) WHO SURVIVED TO AGE 90 YEARS WITHOUT INTACT MOBILITY AND COGNITIVE FUNCTIONING, AND 929 WOMEN (MEAN [SD] AGE AT BASELINE, 70.2 [3.4] YEARS) WHO DID NOT SURVIVE TO AGE 90 YEARS. WOMEN WHO SURVIVED TO AGE 90 YEARS WITH INTACT MOBILITY AND COGNITIVE FUNCTION WERE HEALTHIER AT BASELINE COMPARED WITH WOMEN WHO SURVIVED WITHOUT THOSE OUTCOMES OR WHO DID NOT SURVIVE TO AGE 90 YEARS (EG, 143 WOMEN [30.8%] VS 101 WOMEN [24.0%] AND 202 WOMEN [21.7%] WITH 0 CHRONIC CONDITIONS). THE ODDS OF SURVIVING TO AGE 90 YEARS WITH INTACT MOBILITY WERE LOWER FOR EVERY 1 SD INCREASE IN EAA COMPARED WITH THOSE WHO DID NOT SURVIVE TO AGE 90 YEARS AS MEASURED BY AGEACCELHORVATH (OR, 0.82; 95% CI, 0.69-0.96; P = .01), AGEACCELHANNUM (OR, 0.67; 95% CI, 0.56-0.80; P < .001), AGEACCELPHENO (OR, 0.60; 95% CI, 0.51-0.72; P < .001), AND AGEACCELGRIM (OR, 0.68; 95% CI, 0.55-0.84; P < .001). ORS WERE SIMILAR FOR WOMEN WHO SURVIVED TO AGE 90 YEARS WITH INTACT MOBILITY AND COGNITIVE FUNCTION (EG, AGEACCELHORVATH: OR PER 1 SD INCREASE IN EAA, 0.83; 95% CI, 0.71-0.98; P = .03) COMPARED WITH WOMEN WHO DID NOT SURVIVE TO AGE 90 YEARS. CONCLUSIONS AND RELEVANCE: THESE FINDINGS SUGGEST THAT EAA MAY BE A VALID BIOMARKER ASSOCIATED WITH HEALTHY LONGEVITY AMONG OLDER WOMEN AND MAY BE USED FOR RISK STRATIFICATION AND RISK ESTIMATION OF FUTURE FUNCTIONAL AND COGNITIVE AGING. OUTCOMES SUGGEST THAT FUTURE STUDIES MAY FOCUS ON THE POTENTIAL FOR PUBLIC HEALTH INTERVENTIONS TO COUNTERACT EAA AND ITS ASSOCIATION WITH POOR HEALTH OUTCOMES TO LOWER DISEASE BURDEN WHILE INCREASING LONGEVITY.	2022