1 2995 210 GENETIC POLYMORPHISMS IN FOLATE PATHWAY ENZYMES, DRD4 AND GSTM1 ARE RELATED TO TEMPOROMANDIBULAR DISORDER. BACKGROUND: TEMPOROMANDIBULAR DISORDER (TMD) IS A MULTIFACTORIAL SYNDROME RELATED TO A CRITICAL PERIOD OF HUMAN LIFE. TMD HAS BEEN ASSOCIATED WITH PSYCHOLOGICAL DYSFUNCTIONS, OXIDATIVE STATE AND SEXUAL DIMORPHISM WITH COINCIDENTAL OCCURRENCE ALONG THE PUBERTAL DEVELOPMENT. IN THIS WORK WE STUDY THE ASSOCIATION BETWEEN TMD AND GENETIC POLYMORPHISMS OF FOLATE METABOLISM, NEUROTRANSMISSION, OXIDATIVE AND HORMONAL METABOLISM. FOLATE METABOLISM, WHICH DEPENDS ON GENES VARIATIONS AND DIET, IS DIRECTLY INVOLVED IN GENETIC AND EPIGENETIC VARIATIONS THAT CAN INFLUENCE THE CHANGES OF LAST GROWING PERIOD OF DEVELOPMENT IN HUMAN AND THE APPEARANCE OF THE TMD. METHODS: A CASE-CONTROL STUDY WAS DESIGNED TO EVALUATE THE IMPACT OF GENETIC POLYMORPHISMS ABOVE DESCRIBED ON TMD. A TOTAL OF 229 INDIVIDUALS (69% WOMEN) WERE INCLUDED AT THE STUDY; 86 WERE PATIENTS WITH TMD AND 143 WERE HEALTHY CONTROL SUBJECTS. SUBJECTS UNDERWENT TO A CLINICAL EXAMINATION FOLLOWING THE GUIDELINES BY THE RESEARCH DIAGNOSTIC CRITERIA FOR TEMPOROMANDIBULAR DISORDERS (RDC/TMD). GENOTYPING OF 20 SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS), DIVIDED IN TWO GROUPS, WAS PERFORMED BY MULTIPLEX MINISEQUENCING PRECEDED BY MULTIPLEX PCR. OTHER SEVEN GENETIC POLYMORPHISMS DIFFERENT FROM SNPS (DELETIONS, INSERTIONS, TANDEM REPEAT, NULL GENOTYPE) WERE ACHIEVED BY A MULTIPLEX-PCR. A CHI-SQUARE TEST WAS PERFORMED TO DETERMINE THE DIFFERENCES IN GENOTYPE AND ALLELIC FREQUENCIES BETWEEN TMD PATIENTS AND HEALTHY SUBJECTS. TO ESTIMATE TMD RISK, IN THOSE POLYMORPHISMS THAT SHOWN SIGNIFICANT DIFFERENCES, ODDS RATIO (OR) WITH A 95% OF CONFIDENCE INTERVAL WERE CALCULATED. RESULTS: SIX OF THE POLYMORPHISMS SHOWED STATISTICAL ASSOCIATIONS WITH TMD. FOUR OF THEM ARE RELATED TO ENZYMES OF FOLATES METABOLISM: ALLELE G OF SERINE HYDOXYMETHYLTRANSFERASE 1 (SHMT1) RS1979277 (OR = 3.99; 95%CI 1.72, 9.25; P = 0.002), ALLELE G OF SHMT1 RS638416 (OR = 2.80; 95%CI 1.51, 5.21; P = 0.013), ALLELE T OF METHYLENTETRAHYDROFOLATE DEHYDROGENASE (MTHFD) RS2236225 (OR = 3.09; 95%CI 1.27, 7.50; P = 0.016) AND ALLELE A OF METHIONINE SYNTHASE REDUCTASE (MTRR) RS1801394 (OR = 2.35; 95CI 1.10, 5.00; P = 0.037). AN INFLAMMATORY OXIDATIVE STRESS ENZYME, GLUTHATIONE S-TRANFERASE MU-1(GSTM1), NULL ALLELE (OR = 2.21; 95%CI 1.24, 4.36; P = 0.030) AND A NEUROTRANSMISSION RECEPTOR, DOPAMINE RECEPTOR D4 (DRD4), LONG ALLELE OF 48 BP-REPEAT (OR = 3.62; 95%CI 0.76, 17.26; P = 0.161). CONCLUSIONS: SOME GENETIC POLYMORPHISMS RELATED TO FOLATES METABOLISM, INFLAMMATORY OXIDATIVE STRESS, AND NEUROTRANSMISSION RESPONSES TO PAIN, HAS BEEN SIGNIFICANTLY ASSOCIATED TO TMD SYNDROME. 2011 2 1147 40 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 3 5615 36 SAHA INHIBITS SOMATIC HYPERALGESIA INDUCED BY STRESS COMBINED WITH OROFACIAL INFLAMMATION THROUGH TARGETING DIFFERENT SPINAL 5-HT RECEPTOR SUBTYPES. EPIGENETIC REGULATION OF GENE EXPRESSION HAS BEEN IMPLICATED IN THE DEVELOPMENT OF CHRONIC PAIN. HOWEVER, LITTLE IS KNOWN ABOUT WHETHER THIS REGULATION IS INVOLVED IN THE DEVELOPMENT AND TREATMENT OF CHRONIC PAIN COMORBIDITIES SUCH AS FIBROMYALGIA SYNDROME (FMS) AND TEMPOROMANDIBULAR DISORDER (TMD), A COMORBIDITY PREDOMINANTLY OCCURRING AMONG WOMEN. HERE WE EXPLORED THE IMPACT OF THE HISTONE DEACETYLASE (HDAC) INHIBITOR SUBEROYLANILIDE HYDROXAMIC ACID (SAHA) ON SOMATIC HYPERALGESIA INDUCED BY STRESS OR STRESS COMBINED WITH OROFACIAL INFLAMMATION, WHICH MIMICKED THE COMORBIDITY OF FMS AND TMD IN RATS. OUR DATA SHOWED THAT SOMATIC THERMAL HYPERALGESIA AND MECHANICAL ALLODYNIA INDUCED BY BOTH CONDITIONS WERE COMPLETELY PREVENTED BY INTRATHECAL INJECTION OF SAHA, WHICH UPREGULATED 5-HT(2C) RECEPTORS BUT DOWNREGULATED 5-HT(3) RECEPTORS IN THE SPINAL DORSAL HORN. SUBSEQUENT SPINAL ADMINISTRATION OF RS102221 TO INHIBIT 5-HT(2C) RECEPTORS OR SR57227 TO ACTIVATE 5-HT(3) RECEPTORS REVERSED THE ANALGESIC EFFECT OF SAHA UNDER BOTH CONDITIONS. THESE RESULTS INDICATE THAT SAHA ATTENUATES THE PRO-NOCICEPTIVE EFFECTS OF STRESS COMBINED WITH OROFACIAL INFLAMMATION AND THE EFFECTS OF STRESS ALONE. THIS LIKELY OCCURS THROUGH EPIGENETIC REGULATION OF SPINAL 5-HT(2C) AND 5-HT(3) RECEPTOR EXPRESSION, SUGGESTING THAT SAHA HAS POTENTIAL THERAPEUTIC VALUE IN FMS OR COMORBID FMS-TMD PATIENTS WITH SOMATIC HYPERALGESIA. 2022 4 3004 24 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 4865 31 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 6 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 7 514 47 ASSOCIATION OF SHMT1, MAZ, ERG, AND L3MBTL3 GENE POLYMORPHISMS WITH SUSCEPTIBILITY TO MULTIPLE SCLEROSIS. MULTIPLE SCLEROSIS (MS) IS THE MOST COMMON INFLAMMATORY AND CHRONIC DISEASE OF THE CENTRAL NERVOUS SYSTEM (CNS). A COMPLEX INTERACTION BETWEEN GENETIC, ENVIRONMENTAL, AND EPIGENETIC FACTORS IS INVOLVED IN THE PATHOGENESIS OF MS. WITH THE ADVANCEMENT OF GWAS, VARIOUS VARIANTS ASSOCIATED WITH MS HAVE BEEN IDENTIFIED. THIS STUDY AIMED TO EVALUATE THE ASSOCIATION OF SINGLE-NUCLEOTIDE POLYMORPHISMS (SNPS) RS4925166 AND RS1979277 IN THE SHMT1, MAZ RS34286592, ERG RS2836425, AND L3MBTL3 RS4364506 WITH MS. IN THIS CASE-CONTROL STUDY, THE ASSOCIATION OF FIVE SNPS IN SHMT1, MAZ, ERG, AND L3MBTL3 GENES WITH RELAPSING-REMITTING MS (RR-MS) WAS INVESTIGATED IN 190 PATIENTS AND 200 HEALTHY INDIVIDUALS. FOUR SNPS INCLUDING SHMT1 RS4925166, SHMT1 RS1979277, MAZ RS34286592, AND L3MBTL3 RS4364506 WERE GENOTYPED USING PCR-RFLP AND GENOTYPING OF ERG RS2836425 WAS PERFORMED BY TETRA-PRIMER ARMS PCR. OUR FINDINGS SHOWED A SIGNIFICANT DIFFERENCE IN THE ALLELIC FREQUENCIES FOR THE FOUR SNPS OF SHMT1 RS4925166, SHMT1 RS1979277, MAZ RS34286592, AND ERG RS2836425, WHILE THERE WERE NO DIFFERENCES IN THE ALLELE AND GENOTYPE FREQUENCIES FOR L3MBTL3 RS4364506. THESE SIGNIFICANT ASSOCIATIONS WERE OBSERVED FOR THE FOLLOWING GENOTYPES: TT AND GG GENOTYPES OF SHMT1 RS4925166 (OR 0.47 AND 1.90, RESPECTIVELY) GENOTYPE GG OF SHMT1 RS1979277 (OR 0.63), GENOTYPE GG OF MAZ RS34286592 (OR 0.61), TC AND CC GENOTYPES OF ERG RS2836425 (OR 1.89 AND 0.50, RESPECTIVELY). OUR STUDY HIGHLIGHTED THAT PEOPLE WHO ARE CARRYING GENOTYPES INCLUDING GG (SHMT1 RS4925166) AND TC (ERG RS2836425) HAVE THE HIGHEST SUSCEPTIBILITY CHANCE FOR MS, RESPECTIVELY. HOWEVER, GENOTYPES TT (SHMT1 RS4925166), CC (ERG RS2836425), GG (MAZ RS34286592), AND GG (SHMT1 RS1979277) HAD THE HIGHEST NEGATIVE ASSOCIATION (PROTECTIVE EFFECT) WITH MS, RESPECTIVELY. L3MBTL3 RS4364506 WAS FOUND NEITHER AS A PREDISPOSING NOR A PROTECTIVE VARIANT. 2019 8 1037 20 CLASSIFICATION AND DIAGNOSIS OF TEMPOROMANDIBULAR DISORDERS AND TEMPOROMANDIBULAR DISORDER PAIN. DESIGNING CLASSIFICATION SYSTEMS AND DEVELOPING DIAGNOSTIC CRITERIA FOR TEMPOROMANDIBULAR DISORDERS IS DIFFICULT. AN APPRECIATION OF THE UTILITY AND APPLICABILITY OF THESE ENTITIES REQUIRES AN UNDERSTANDING OF THE IMPORTANCE OF EACH, THE DIFFERENCES BETWEEN THE TWO, AND HOW THEY MAY BE OPTIMALLY OPERATIONALIZED FOR BOTH CLINICAL AND RESEARCH ACTIVITIES IN LIGHT OF THEIR INHERENT ADVANTAGES AND LIMITATIONS. IN ADDITION, CONSIDERATION FOR ADOPTING NEWER APPROACHES, SUCH AS FOLLOWING ONTOLOGICAL AND PRECISION-BASED MEDICINE PRINCIPLES, ACCOUNTING FOR GENETICS/EPIGENETIC AND NEUROBIOLOGICAL FACTORS, AND THE INCLUSION OF BIOMARKERS WILL POTENTIALLY RESULT IN MORE THOROUGH AND COMPREHENSIVE CLASSIFICATION SYSTEMS AND DIAGNOSTIC CRITERIA. 2023 9 6779 18 [BIO-PSYCHO-SOCIAL THERAPY FOR STRESS-INDUCED CHRONIC PAIN]. BIO-PSYCHO-SOCIAL THERAPY FOR STRESS-INDUCED CHRONIC PAIN ABSTRACT. AGAINST THE BACKGROUND OF LATEST NEUROBIOLOGICAL AND EPIGENETIC FINDINGS THE BIO-PSYCHO-SOCIAL MODEL OF DISEASE IS OUTLINED OFTEN MISINTERPRETED IN THE CONTEXT OF CHRONIC PAIN. IT REPRESENTS THE BASIC PRINCIPLE FOR A PERSONALIZED TREATMENT OF STRESS-INDUCED CHRONIC PAIN. CONSEQUENCES FOR DIAGNOSTIC PROCEDURES ARE DELINEATED TO DETECT THIS PATHOGENETIC SUBGROUP OF CHRONIC PAIN PATIENTS (E.G. FIBROMYALGIA, BACK PAIN, TEMPOROMANDIBULAR DYSFUNCTION, TENSION HEADACHE). FINALLY, THE PRINCIPLES OF A BIO-PSYCHO-SOCIAL TREATMENT PROGRAM WITH HIGH EFFICIENCY ARE PRESENTED. 2020 10 3574 51 IMPACT OF METHIONINE SYNTHASE REDUCTASE POLYMORPHISMS IN CHRONIC MYELOID LEUKEMIA PATIENTS. INTRODUCTION: METABOLISM METHIONINE AND OF FOLATE PLAY A VITAL FUNCTION IN CELLULAR METHYLATION REACTIONS, DNA SYNTHESIS AND EPIGENETIC PROCESS.HOWEVER, POLYMORPHISMS OF METHIONINE HAVE RECEIVED MUCH ATTENTION IN RECENT MEDICAL GENETICS RESEARCH. OBJECTIVES: TO ASCERTAIN WHETHER THE COMMON POLYMORPHISMS OF THE MTRR (METHIONINE SYNTHASE REDUCTASE) A66G GENE COULD PLAY A ROLE IN AFFECTING SUSCEPTIBILITY TO CHRONIC MYELOID LEUKEMIA (CML) IN SUDANESE INDIVIDUALS. METHODS: IN A CASE-CONTROLLED STUDY, WE EXTRACTED AND ANALYZED DNA FROM 200 CML PATIENTS AND 100 HEALTHY CONTROL SUBJECTS BY THE PCR-RFLP METHOD. RESULTS: WE FOUND NO SIGNIFICANT DIFFERENCE IN AGE ORGENDER BETWEEN THE PATIENT GROUP AND CONTROLS. THE MTRR A66G GENOTYPES WERE DISTRIBUTED BASED ON THE HARDY-WEINBERG EQUILIBRIUM (P > 0.05). THE VARIATION OF MTRR A66G WAS LESS SIGNIFICANTLY FREQUENT IN CASES WITH CML (68.35%) THAN IN CONTROLS (87%) (OR = 0.146, 95% CI = 0.162-0.662, P < 0.002). ADDITIONALLY, AG AND GG GENOTYPES AND G ALLELE WERE REDUCING THE CML RISK (ODDS RATIO [OR] = 0.365; 95% CI [0.179-0.746]; P = 0.006; OR = 0.292; 95% CI [0.145-0.590]; P = 0.001 AND OR = 0.146; 95% CI [0.162-0.662]; P = 0.002 AND OR = 2.0; 95% CI [1.3853-2.817]; RESPECTIVELY, (P = 0.000)). CONCLUSIONS: OUR DATA DEMONSTRATED THAT HETEROZYGOUS AND HOMOZYGOUS MUTANT GENOTYPES OF MTRR POLYMORPHISMS WERE ASSOCIATED WITH DECREASED RISK OF DEVELOPING CML IN THE SUDANESE POPULATION. 2022 11 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 12 6472 31 TNFALPHA IN THE TRIGEMINAL NOCICEPTIVE SYSTEM IS CRITICAL FOR TEMPOROMANDIBULAR JOINT PAIN. PREVIOUS STUDIES HAVE SHOWN THAT TUMOR NECROSIS FACTOR ALPHA (TNFALPHA) IS SIGNIFICANTLY INCREASED IN COMPLETE FREUND'S ADJUVANT (CFA)-TREATED TEMPOROMANDIBULAR JOINT (TMJ) TISSUES. HOWEVER, IT IS UNCLEAR WHETHER TNFALPHA IN THE TRIGEMINAL NOCICEPTIVE SYSTEM CONTRIBUTES TO THE DEVELOPMENT OF TMJ PAIN. IN THE PRESENT STUDY, WE INVESTIGATED THE ROLE OF TNFALPHA IN TRIGEMINAL GANGLIA (TG) AND SPINAL TRIGEMINAL NUCLEUS CAUDALIS (SP5C) IN CFA-INDUCED INFLAMMATORY TMJ PAIN. INTRA-TMJ INJECTION OF CFA (10 MUL, 5 MG/ML) INDUCED INFLAMMATORY PAIN IN THE TRIGEMINAL NERVE V2- AND V3-INNERVATED SKIN AREAS OF WT MICE, WHICH WAS PRESENT ON DAY 1 AFTER CFA AND PERSISTED FOR AT LEAST 10 DAYS. TNFALPHA IN BOTH TG AND SP5C OF WT MICE WAS UPREGULATED AFTER CFA INJECTION. THE CFA-INDUCED TMJ PAIN WAS SIGNIFICANTLY INHIBITED IN TNFALPHA KO MICE. THE IMMUNOFLUORESCENCE STAINING SHOWED THAT INTRA-TMJ CFA INJECTION NOT ONLY ENHANCED CO-LOCALIZATION OF TNFALPHA WITH IBA1 (A MARKER FOR MICROGLIA) IN BOTH TG AND SP5C BUT ALSO MARKEDLY INCREASED THE EXPRESSION OF TNFALPHA IN THE SP5C NEURONS. BY THE METHYLATED DNA IMMUNOPRECIPITATION ASSAY, WE ALSO FOUND THAT DNA METHYLATION AT THE TNF GENE PROMOTER REGION IN THE TG WAS DRAMATICALLY DIMINISHED AFTER CFA INJECTION, INDICATING THAT EPIGENETIC REGULATION MAY BE INVOLVED IN THE CFA-ENHANCED TNFALPHA EXPRESSION IN OUR MODEL. OUR RESULTS SUGGEST THAT TNFALPHA IN THE TRIGEMINAL NOCICEPTIVE SYSTEM PLAYS A CRITICAL ROLE IN CFA-INDUCED INFLAMMATORY TMJ PAIN. 2019 13 1969 40 EPIGENETIC ALTERATIONS AND AN INCREASED FREQUENCY OF MICRONUCLEI IN WOMEN WITH FIBROMYALGIA. FIBROMYALGIA (FM), CHARACTERIZED BY CHRONIC WIDESPREAD PAIN, FATIGUE, AND COGNITIVE/MOOD DISTURBANCES, LEADS TO REDUCED WORKPLACE PRODUCTIVITY AND INCREASED HEALTHCARE EXPENSES. TO DETERMINE IF ACQUIRED EPIGENETIC/GENETIC CHANGES ARE ASSOCIATED WITH FM, WE COMPARED THE FREQUENCY OF SPONTANEOUSLY OCCURRING MICRONUCLEI (MN) AND GENOME-WIDE METHYLATION PATTERNS IN WOMEN WITH FM (N = 10) TO THOSE SEEN IN COMPARABLY AGED HEALTHY CONTROLS (N = 42 (MN); N = 8 (METHYLATION)). THE MEAN (SD) MN FREQUENCY OF WOMEN WITH FM (51.4 (21.9)) WAS SIGNIFICANTLY HIGHER THAN THAT OF CONTROLS (15.8 (8.5)) (CHI (2) = 45.552; DF = 1; P = 1.49 X 10(-11)). SIGNIFICANT DIFFERENCES (N = 69 SITES) IN METHYLATION PATTERNS WERE OBSERVED BETWEEN CASES AND CONTROLS CONSIDERING A 5% FALSE DISCOVERY RATE. THE MAJORITY OF DIFFERENTIALLY METHYLATED (DM) SITES (91%) WERE ATTRIBUTABLE TO INCREASED VALUES IN THE WOMEN WITH FM. THE DM SITES INCLUDED SIGNIFICANT BIOLOGICAL CLUSTERS INVOLVED IN NEURON DIFFERENTIATION/NERVOUS SYSTEM DEVELOPMENT, SKELETAL/ORGAN SYSTEM DEVELOPMENT, AND CHROMATIN COMPACTION. GENES ASSOCIATED WITH DM SITES WHOSE FUNCTION HAS PARTICULAR RELEVANCE TO FM INCLUDED BDNF, NAT15, HDAC4, PRKCA, RTN1, AND PRKG1. RESULTS SUPPORT THE NEED FOR FUTURE RESEARCH TO FURTHER EXAMINE THE POTENTIAL ROLE OF EPIGENETIC AND ACQUIRED CHROMOSOMAL ALTERATIONS AS A POSSIBLE BIOLOGICAL MECHANISM UNDERLYING FM. 2013 14 1672 36 DRD4 METHYLATION AS A POTENTIAL BIOMARKER FOR PHYSICAL AGGRESSION: AN EPIGENOME-WIDE, CROSS-TISSUE INVESTIGATION. EPIGENETIC PROCESSES THAT REGULATE GENE EXPRESSION, SUCH AS DNA METHYLATION (DNAM), HAVE BEEN LINKED TO INDIVIDUAL DIFFERENCES IN PHYSICAL AGGRESSION. YET, IT IS CURRENTLY UNCLEAR WHETHER: (A) DNAM PATTERNS IN HUMANS ASSOCIATE WITH PHYSICAL AGGRESSION INDEPENDENTLY OF OTHER CO-OCCURRING PSYCHIATRIC AND BEHAVIORAL SYMPTOMS; (B) WHETHER THESE PATTERNS ARE OBSERVABLE ACROSS MULTIPLE TISSUES; AND (C) WHETHER THEY MAY FUNCTION AS A CAUSAL VERSUS NONCAUSAL BIOMARKER OF PHYSICAL AGGRESSION. HERE, WE USED A MULTISAMPLE, CROSS-TISSUE DESIGN TO ADDRESS THESE QUESTIONS. FIRST, WE EXAMINED GENOME-WIDE DNAM PATTERNS (BUCCAL SWABS; ILLUMINA 450K) ASSOCIATED WITH ENGAGEMENT IN PHYSICAL FIGHTS IN A SAMPLE OF HIGH-RISK YOUTH (N = 119; AGE = 16-24 YEARS; 53% FEMALE). WE IDENTIFIED ONE DIFFERENTIALLY METHYLATED REGION IN DRD4, WHICH SURVIVED GENOME-WIDE CORRECTION, ASSOCIATED WITH PHYSICAL AGGRESSION ABOVE AND BEYOND CO-OCCURRING SYMPTOMATOLOGY (E.G., ADHD, SUBSTANCE USE), AND SHOWED STRONG CROSS-TISSUE CONCORDANCE WITH BOTH BLOOD AND BRAIN. SECOND, WE FOUND THAT DNAM SITES WITHIN THIS REGION WERE ALSO DIFFERENTIALLY METHYLATED IN AN INDEPENDENT SAMPLE OF YOUNG ADULTS, BETWEEN INDIVIDUALS WITH A HISTORY OF CHRONIC-HIGH VERSUS LOW PHYSICAL AGGRESSION (PERIPHERAL T CELLS; AGES 26-28). FINALLY, WE RAN A MENDELIAN RANDOMIZATION ANALYSIS USING GWAS DATA FROM THE EAGLE CONSORTIUM TO TEST FOR A CAUSAL ASSOCIATION OF DRD4 METHYLATION WITH PHYSICAL AGGRESSION. ONLY ONE GENETIC INSTRUMENT WAS ELIGIBLE FOR THE ANALYSIS, AND RESULTS PROVIDED NO EVIDENCE FOR A CAUSAL ASSOCIATION. OVERALL, OUR FINDINGS LEND SUPPORT FOR PERIPHERAL DRD4 METHYLATION AS A POTENTIAL BIOMARKER OF PHYSICALLY AGGRESSIVE BEHAVIOR, WITH NO EVIDENCE YET OF A CAUSAL RELATIONSHIP. 2018 15 5005 35 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 16 190 32 ACETYL-L-CARNITINE IN PAINFUL PERIPHERAL NEUROPATHY: A SYSTEMATIC REVIEW. ACETYL-L-CARNITINE (ALC) HAS SHOWN A NEUROPROTECTIVE EFFECT IN PATIENTS WITH PERIPHERAL NEUROPATHIES OF DIFFERENT ETIOLOGIES. PRECLINICAL STUDIES DEMONSTRATED A CENTRAL ANTI-NOCICEPTIVE ACTION, BOTH IN NEUROPATHIC AND NOCICEPTIVE PAIN MODELS. THE PRESENT REVIEW AIMS TO PROVIDE THE KNOWLEDGE ON THE EFFICACY OF ALC IN PATIENTS WITH PAINFUL PERIPHERAL NEUROPATHY, BASED ON THE EVIDENCE. CONSISTENT WITH THE PRISMA STATEMENT, AUTHORS SEARCHED PUBMED, EMBASE AND THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS FOR RELEVANT PAPERS, INCLUDING THOSE ISSUED BEFORE APRIL 2018. TWO AUTHORS INDEPENDENTLY SELECTED STUDIES FOR INCLUSION AND DATA EXTRACTION: ONLY TRIALS INCLUDING PATIENTS WITH A DIAGNOSIS OF PERIPHERAL NEUROPATHY AND INVOLVING AT LEAST 10 PATIENTS WERE CONSIDERED FOR THE PURPOSES OF THIS REVIEW. FOURTEEN CLINICAL TRIALS WERE REVISED, TO PROVIDE THE LEVEL OF EVIDENCE FOR NEUROPATHY. TO ASSESS THE GLOBAL EFFICACY OF ALC IN PAINFUL PERIPHERAL NEUROPATHY, A META-ANALYSIS OF FOUR RANDOMIZED CONTROLLED TRIALS WAS PERFORMED. MEAN DIFFERENCE IN PAIN REDUCTION AS MEASURED ON A 10-CM VAS, AND 95% CIS WERE USED FOR POOLING CONTINUOUS DATA FROM EACH TRIAL. FOUR RANDOMIZED CONTROLLED TRIALS TESTED ALC IN PATIENTS WITH NEUROPATHY SECONDARY TO DIABETES AND TO ANTIRETROVIRAL THERAPY FOR HIV. COMPARED TO PLACEBO, ALC PRODUCED A SIGNIFICANT PAIN REDUCTION EQUAL TO 20.2% (95% CI: 8.3%-32.1%, P<0.0001) WITH RESPECT TO BASELINE. CLINICAL TRIALS ALSO SHOWED BENEFICIAL EFFECTS ON NERVE CONDUCTION PARAMETERS AND NERVE FIBER REGENERATION, WITH A GOOD SAFETY PROFILE. THESE DATA INDICATE THAT ALC PROVIDES AN EFFECTIVE AND SAFE TREATMENT IN PATIENTS WITH PAINFUL PERIPHERAL NEUROPATHY. WE RECOMMEND FURTHER STUDIES TO ASSESS THE OPTIMAL DOSE AND DURATION OF THE THERAPEUTIC EFFECT (ALSO AFTER TREATMENT WITHDRAWAL). 2019 17 4612 33 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 18 1120 28 COMPARISON OF DIFFERENT HISTONE DEACETYLASE INHIBITORS IN ATTENUATING INFLAMMATORY PAIN IN RATS. HISTONE DEACETYLASE INHIBITORS (HDACIS), WHICH INTERFERE WITH THE EPIGENETIC PROCESS OF HISTONE ACETYLATION, HAVE SHOWN ANALGESIC EFFECTS IN ANIMAL MODELS OF PERSISTENT PAIN. THE HDAC FAMILY COMPRISES 18 GENES; HOWEVER, THE DIFFERENT EFFECTS OF DISTINCT CLASSES OF HDACIS ON PAIN RELIEF REMAIN UNCLEAR. THE AIM OF THIS STUDY WAS TO DETERMINE THE EFFICACY OF THESE HDACIS ON ATTENUATING THERMAL HYPERALGESIA IN PERSISTENT INFLAMMATORY PAIN. PERSISTENT INFLAMMATORY PAIN WAS INDUCED BY INJECTING COMPLETE FREUND'S ADJUVANT (CFA) INTO THE LEFT HIND PAW OF RATS. THEN, HDACIS TARGETING CLASS I (ENTINOSTAT (MS-275)) AND CLASS IIA (SODIUM BUTYRATE, VALPROIC ACID (VPA), AND 4-PHENYLBUTYRIC ACID (4-PBA)), OR CLASS II (SUBEROYLANILIDE HYDOXAMIC ACID (SAHA), TRICHOSTATIN A (TSA), AND DACINOSTAT (LAQ824)) WERE ADMINISTERED INTRAPERITONEALLY ONCE DAILY FOR 3 OR 4 DAYS. WE FOUND THAT THE INJECTION OF SAHA ONCE A DAY FOR 3 DAYS SIGNIFICANTLY ATTENUATED CFA-INDUCED THERMAL HYPERALGESIA FROM DAY 4 AND LASTED 7 DAYS. IN COMPARISON WITH SAHA, SUPPRESSION OF HYPERALGESIA BY 4-PBA PEAKED ON DAY 2, WHEREAS THAT BY MS-275 OCCURRED ON DAYS 5 AND 6. FATIGUE WAS A SERIOUS SIDE EFFECT SEEN WITH MS-275. THESE FINDINGS WILL BE BENEFICIAL FOR OPTIMIZING THE SELECTION OF SPECIFIC HDACIS IN MEDICAL FIELDS SUCH AS PAIN MEDICINE AND NEUROPSYCHIATRY. 2019 19 4708 44 NO ASSOCIATION OF POLYMORPHISMS IN NAV1.7 OR NERVE GROWTH FACTOR RECEPTOR GENES WITH TRIGEMINAL NEURALGIA. OBJECTIVE: TRIGEMINAL NEURALGIA IS DEFINED AS A SUDDEN SEVERE SHOCK-LIKE PAIN WITHIN THE DISTRIBUTION OF THE TRIGEMINAL NERVE. PAIN IS A SUBJECTIVE EXPERIENCE THAT IS INFLUENCED BY GENDER, CULTURE, ENVIRONMENT, PSYCHOLOGICAL TRAITS, AND GENES. SODIUM CHANNELS AND NERVE GROWTH FACTOR PLAY IMPORTANT ROLES IN THE TRANSMISSION OF NOCICEPTIVE SIGNALS AND PAIN. THE AIM OF THIS STUDY WAS TO INVESTIGATE THE OCCURRENCE OF NAV1.7 SODIUM CHANNEL AND NERVE GROWTH FACTOR RECEPTOR TRKA GENE POLYMORPHISMS (SCN9A/RS6746030 AND NTRK1/RS633, RESPECTIVELY) IN TRIGEMINAL NEURALGIA PATIENTS. METHODS: NINETY-SIX SUBJECTS FROM PAIN SPECIALTY CENTERS IN THE SOUTHEASTERN REGION OF BRAZIL WERE DIVIDED INTO 2 GROUPS: 48 WITH CLASSICAL TRIGEMINAL NEURALGIA DIAGNOSIS AND 48 CONTROLS. PAIN WAS EVALUATED USING THE VISUAL ANALOG SCALE AND MULTIDIMENSIONAL MCGILL PAIN QUESTIONNAIRE. GENOMIC DNA WAS OBTAINED FROM ORAL SWABS IN ALL INDIVIDUALS AND WAS ANALYZED BY REAL-TIME POLYMERASE CHAIN REACTION. RESULTS: NO ASSOCIATION WAS OBSERVED BETWEEN EVALUATED POLYMORPHISMS AND TRIGEMINAL NEURALGIA. FOR ALLELE ANALYSES, PATIENTS AND CONTROLS HAD SIMILAR FREQUENCIES FOR BOTH GENES. GENOTYPE DISTRIBUTION OR ALLELE FREQUENCIES OF POLYMORPHISMS ANALYZED HERE DID NOT CORRELATE TO PAIN SCORES. CONCLUSIONS: ALTHOUGH NO ASSOCIATION OF EVALUATED POLYMORPHISMS AND TRIGEMINAL NEURALGIA DIAGNOSIS OR PAIN SEVERITY WAS OBSERVED, OUR DATA DO NOT EXCLUDE THE POSSIBILITY THAT OTHER GENOTYPES AFFECTING THE EXPRESSION OF NAV1.7 OR TRKA ARE ASSOCIATED WITH THE DISEASE. FURTHER STUDIES SHOULD INVESTIGATE DISTINCT GENETIC POLYMORPHISMS AND EPIGENETIC FACTORS THAT MAY BE IMPORTANT IN EXPRESSION OF THESE MOLECULES. 2019 20 4916 30 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