1 3400 121 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 2 3004 38 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 3 1037 21 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 4 1377 25 DEVELOPMENTAL PROGRAMMING: STATE-OF-THE-SCIENCE AND FUTURE DIRECTIONS-SUMMARY FROM A PENNINGTON BIOMEDICAL SYMPOSIUM. OBJECTIVE: ON DECEMBER 8-9, 2014, THE PENNINGTON BIOMEDICAL RESEARCH CENTER CONVENED A SCIENTIFIC SYMPOSIUM TO REVIEW THE STATE-OF-THE-SCIENCE AND FUTURE DIRECTIONS FOR THE STUDY OF DEVELOPMENTAL PROGRAMMING OF OBESITY AND CHRONIC DISEASE. THE OBJECTIVES OF THE SYMPOSIUM WERE TO DISCUSS: (I) PAST AND CURRENT SCIENTIFIC ADVANCES IN ANIMAL MODELS, POPULATION-BASED COHORT STUDIES, AND HUMAN CLINICAL TRIALS, (II) THE STATE-OF-THE-SCIENCE OF EPIGENETIC-BASED RESEARCH, AND (III) CONSIDERATIONS FOR FUTURE STUDIES. RESULTS: THIS SYMPOSIUM PROVIDED A COMPREHENSIVE ASSESSMENT OF THE STATE OF THE SCIENTIFIC FIELD AND IDENTIFIED RESEARCH GAPS AND OPPORTUNITIES FOR FUTURE RESEARCH IN ORDER TO UNDERSTAND THE MECHANISMS CONTRIBUTING TO THE DEVELOPMENTAL PROGRAMMING OF HEALTH AND DISEASE. CONCLUSIONS: IDENTIFYING THE MECHANISMS WHICH CAUSE OR CONTRIBUTE TO DEVELOPMENTAL PROGRAMMING OF FUTURE GENERATIONS WILL BE INVALUABLE TO THE SCIENTIFIC AND MEDICAL COMMUNITY. THE ABILITY TO INTERVENE DURING CRITICAL PERIODS OF PRENATAL AND EARLY POSTNATAL LIFE TO PROMOTE LIFELONG HEALTH IS THE ULTIMATE GOAL. CONSIDERATIONS FOR FUTURE RESEARCH INCLUDING THE USE OF ANIMAL MODELS, THE STUDY DESIGN IN HUMAN COHORTS WITH CONSIDERATIONS ABOUT THE TIMING OF THE INTRAUTERINE EXPOSURE, AND THE RESULTING TISSUE-SPECIFIC EPIGENETIC SIGNATURE WERE EXTENSIVELY DISCUSSED AND ARE PRESENTED IN THIS MEETING SUMMARY. 2016 5 1248 23 CURRENT EVIDENCE FOR BIOLOGICAL BIOMARKERS AND MECHANISMS UNDERLYING ACUTE TO CHRONIC PAIN TRANSITION ACROSS THE PEDIATRIC AGE SPECTRUM. CHRONIC PAIN IS HIGHLY PREVALENT IN THE PEDIATRIC POPULATION. MANY FACTORS ARE INVOLVED IN THE TRANSITION FROM ACUTE TO CHRONIC PAIN. CURRENTLY, THERE ARE CONCEPTUAL MODELS PROPOSED, BUT THEY LACK A MECHANISTICALLY SOUND INTEGRATED THEORY CONSIDERING THE STAGES OF CHILD DEVELOPMENT. OBJECTIVE BIOMARKERS ARE CRITICALLY NEEDED FOR THE DIAGNOSIS, RISK STRATIFICATION, AND PROGNOSIS OF THE PATHOLOGICAL STAGES OF PAIN CHRONIFICATION. IN THIS ARTICLE, WE SUMMARIZE THE CURRENT EVIDENCE ON MECHANISMS AND BIOMARKERS OF ACUTE TO CHRONIC PAIN TRANSITIONS IN INFANTS AND CHILDREN THROUGH THE DEVELOPMENTAL LENS. THE GOAL IS TO IDENTIFY GAPS AND OUTLINE FUTURE DIRECTIONS FOR BASIC AND CLINICAL RESEARCH TOWARD A DEVELOPMENTALLY INFORMED THEORY OF PAIN CHRONIFICATION IN THE PEDIATRIC POPULATION. AT THE OUTSET, THE IMPORTANCE OF OBJECTIVE BIOMARKERS FOR CHRONIFICATION OF PAIN IN CHILDREN IS OUTLINED, FOLLOWED BY A SUMMARY OF THE CURRENT EVIDENCE ON THE MECHANISMS OF ACUTE TO CHRONIC PAIN TRANSITION IN ADULTS, IN ORDER TO CONTRAST WITH THE DEVELOPMENTAL MECHANISMS OF PAIN CHRONIFICATION IN THE PEDIATRIC POPULATION. EVIDENCE IS PRESENTED TO SHOW THAT CHRONIC PAIN MAY HAVE ITS ORIGIN FROM INSULTS EARLY IN LIFE, WHICH PRIME THE CHILD FOR THE DEVELOPMENT OF CHRONIC PAIN IN LATER LIFE. FURTHERMORE, AVAILABLE GENETIC, EPIGENETIC, PSYCHOPHYSICAL, ELECTROPHYSIOLOGICAL, NEUROIMAGING, NEUROIMMUNE, AND SEX MECHANISMS ARE DESCRIBED IN INFANTS AND OLDER CHILDREN. IN CONCLUSION, FUTURE DIRECTIONS ARE DISCUSSED WITH A FOCUS ON RESEARCH GAPS, TRANSLATIONAL AND CLINICAL IMPLICATIONS. UTILIZATION OF DEVELOPMENTAL MECHANISMS FRAMEWORK TO INFORM CLINICAL DECISION-MAKING AND STRATEGIES FOR PREVENTION AND MANAGEMENT OF ACUTE TO CHRONIC PAIN TRANSITIONS IN CHILDREN, IS HIGHLIGHTED. 2023 6 421 29 ANIMAL MODELS IN EPIGENETIC RESEARCH: INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE CONSIDERATIONS ACROSS THE LIFESPAN. THE RAPID EXPANSION AND EVOLUTION OF EPIGENETICS AS A CORE SCIENTIFIC DISCIPLINE HAVE RAISED NEW QUESTIONS ABOUT HOW ENDOGENOUS AND ENVIRONMENTAL FACTORS CAN INFORM THE MECHANISMS THROUGH WHICH BIOLOGICAL FORM AND FUNCTION ARE REGULATED. EXISTING AND PROPOSED ANIMAL MODELS USED FOR EPIGENETIC RESEARCH HAVE TARGETED A MYRIAD OF HEALTH AND DISEASE ENDPOINTS THAT MAY BE ACUTE, CHRONIC, AND TRANSGENERATIONAL IN NATURE. INITIATING EVENTS AND OUTCOMES MAY EXTEND ACROSS THE ENTIRE LIFESPAN TO ELICIT UNANTICIPATED PHENOTYPES THAT ARE OF PARTICULAR CONCERN TO INSTITUTIONAL ANIMAL CARE AND USE COMMITTEES (IACUCS). THE DYNAMICS AND PLASTICITY OF EPIGENETIC MECHANISMS PRODUCE EFFECTS AND CONSEQUENCES THAT ARE MANIFEST DIFFERENTIALLY WITHIN DISCREET SPATIAL AND TEMPORAL CONTEXTS, INCLUDING PRENATAL DEVELOPMENT, STEM CELLS, ASSISTED REPRODUCTIVE TECHNOLOGIES, PRODUCTION OF SEXUAL DIMORPHISMS, SENESCENCE, AND OTHERS. MANY DIETARY AND NUTRITIONAL INTERVENTIONS HAVE ALSO BEEN SHOWN TO HAVE A SIGNIFICANT IMPACT ON BIOLOGICAL FUNCTIONS AND DISEASE SUSCEPTIBILITIES THROUGH ALTERED EPIGENETIC PROGRAMMING. THE ENVIRONMENTAL, CHEMICAL, TOXIC, THERAPEUTIC, AND PSYCHOSOCIAL STRESSORS USED IN ANIMAL STUDIES TO ELICIT EPIGENETIC CHANGES CAN BECOME EXTREME AND SHOULD RAISE IACUC CONCERNS FOR THE WELL-BEING AND PROPER CARE OF ALL RESEARCH ANIMALS INVOLVED. EPIGENETICS RESEARCH IS RAPIDLY BECOMING AN INTEGRAL PART OF THE SEARCH FOR MECHANISMS IN EVERY MAJOR AREA OF BIOMEDICAL AND BEHAVIORAL RESEARCH AND WILL FOSTER THE CONTINUED DEVELOPMENT OF NEW ANIMAL MODELS. FROM THE IACUC PERSPECTIVE, CARE MUST BE TAKEN TO ACKNOWLEDGE THE PARTICULAR NEEDS AND CONCERNS CREATED BY SUPERIMPOSITION OF EPIGENETIC MECHANISMS OVER DIVERSE FIELDS OF INVESTIGATION TO ENSURE THE PROPER CARE AND USE OF ANIMALS WITHOUT IMPEDING SCIENTIFIC PROGRESS. 2012 7 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 8 2521 37 EPIGENETICS AND THE INTERNATIONAL CLASSIFICATION OF FUNCTIONING, DISABILITY AND HEALTH MODEL: BRIDGING NATURE, NURTURE, AND PATIENT-CENTERED POPULATION HEALTH. EPIGENETIC PROCESSES ENABLE ENVIRONMENTAL INPUTS SUCH AS DIET, EXERCISE, AND HEALTH BEHAVIORS TO REVERSIBLY TAG DNA WITH CHEMICAL "MARKS" THAT INCREASE OR DECREASE THE EXPRESSION OF AN INDIVIDUAL'S GENETIC TEMPLATE. OVER TIME, EPIGENETIC ADAPTATIONS ENABLE THE EFFECTS OF HEALTHY OR UNHEALTHY STRESSES TO BECOME STABLY EXPRESSED IN THE TISSUE OF AN ORGANISM, WITH IMPORTANT CONSEQUENCES FOR HEALTH AND DISEASE. NEW RESEARCH INDICATES THAT SEEMINGLY NON-BIOLOGICAL FACTORS SUCH AS SOCIAL STRESS, POVERTY, AND CHILDHOOD HARDSHIP INITIATE EPIGENETIC ADAPTATIONS IN GENE PATHWAYS THAT GOVERN INFLAMMATION AND IMMUNITY, TWO OF THE GREATEST CONTRIBUTORS TO CHRONIC DISEASES SUCH AS DIABETES AND OBESITY. EPIGENETIC PROCESSES THEREFORE PROVIDE A BIOLOGICAL BRIDGE BETWEEN THE GENOME-AN INDIVIDUAL'S GENETIC INHERITANCE-AND THE SOCIAL DETERMINANTS OF HEALTH-THE CONDITIONS IN WHICH THEY ARE BORN, GROW, LIVE, WORK, AND AGE. THIS PERSPECTIVE PAPER ARGUES THAT PHYSICAL THERAPY CLINICIANS, RESEARCHERS, AND EDUCATORS CAN USE THE THEORETICAL FRAMEWORK PROVIDED BY THE INTERNATIONAL CLASSIFICATION OF FUNCTIONING, DISABILITY, AND HEALTH (ICF MODEL) TO HARMONIZE NEW DISCOVERIES FROM BOTH PUBLIC HEALTH RESEARCH AND MEDICALLY FOCUSED GENOMIC RESEARCH. THE ICF MODEL LIKEWISE CAPTURES THE ESSENTIAL ROLE PLAYED BY PHYSICAL ACTIVITY AND EXERCISE, WHICH INITIATE POWERFUL AND WIDESPREAD EPIGENETIC ADAPTATIONS THAT PROMOTE HEALTH AND FUNCTIONING. IN THIS PROPOSED FRAMEWORK, EPIGENETIC PROCESSES TRANSDUCE THE EFFECTS OF THE SOCIAL DETERMINANTS OF HEALTH AND BEHAVIORS SUCH AS EXERCISE INTO STABLE BIOLOGICAL ADAPTATIONS THAT AFFECT AN INDIVIDUAL'S DAILY ACTIVITIES AND THEIR PARTICIPATION IN SOCIAL ROLES. BY HARMONIZING "NATURE" AND "NURTURE," PHYSICAL THERAPISTS CAN APPROACH PATIENT CARE WITH A MORE INTEGRATED PERSPECTIVE, CAPITALIZING ON NOVEL DISCOVERIES IN PRECISION MEDICINE, REHABILITATION SCIENCE, AND IN POPULATION-LEVEL RESEARCH. AS THE EXPERTS IN PHYSICAL ACTIVITY AND EXERCISE, PHYSICAL THERAPISTS ARE IDEALLY POSITIONED TO DRIVE PROGRESS IN THE NEW ERA OF PATIENT-CENTERED POPULATION HEALTH CARE. 2022 9 5028 32 PERSONALIZING PEDIATRIC PAIN MEDICINE: USING POPULATION-SPECIFIC PHARMACOGENETICS, GENOMICS, AND OTHER -OMICS APPROACHES TO PREDICT RESPONSE. PERSONALIZED MEDICINE IS THE SCIENCE OF INDIVIDUALIZED PREVENTION AND THERAPY. THE NOTION THAT "ONE SIZE FITS ALL" HAS BEEN REPLACED BY THE IDEA OF PATIENT-TAILORED HEALTH CARE. WITHIN THIS PARADIGM, THE RESEARCH COMMUNITY HAS TURNED TO EXAMINE GENETIC PREDICTORS OF DISEASE AND TREATMENT RESPONSES. PAIN RESEARCHERS HAVE PRODUCED GENETIC STUDIES OVER THE LAST DECADE THAT EVALUATE THE ASSOCIATION OF GENETIC VARIABILITY WITH PAIN SENSITIVITY AND ANALGESIC RESPONSE. WHILE MOST OF THESE STUDIES HAVE BEEN CONDUCTED AMONG COHORTS OF SUBJECTS OF EUROPEAN DESCENT, SOME HAVE INCLUDED OTHER RACIAL AND ETHNIC GROUPS, PROVIDING EVIDENCE OF VARIABLE RESPONSES TO ANALGESICS. SIMULTANEOUSLY, THERE IS AN INCREASED RECOGNITION REGARDING THE COMPLEXITY OF PAIN RESEARCH, ACKNOWLEDGING THE ADDITIONAL ROLE OF EPIGENETIC, TRANSCRIPTOMIC, PROTEOMIC, AND METABOLOMIC FACTORS IN THE DEVELOPMENT, EXPERIENCE, AND TREATMENT OF PAIN. THIS ARTICLE PROVIDES AN INTRODUCTION TO POPULATION-SPECIFIC PHARMACOGENETICS, PROTEOMICS AND OTHER "-OMICS" TECHNOLOGIES TO PREDICT DRUG RESPONSE TO PAIN MEDICATIONS IN CHILDREN. IT AIMS TO PROVIDE ANESTHESIOLOGISTS WITH THE BASIC KNOWLEDGE TO UNDERSTAND THE POTENTIAL IMPLICATIONS OF GENETIC AND EPIGENETIC FACTORS MANAGING THE PAIN OF PEDIATRIC PATIENTS. 2015 10 5038 19 PHARMACOGENETICS OF CHRONIC PAIN AND ITS TREATMENT. THIS PAPER REVIEWS THE IMPACT OF GENETIC VARIABILITY OF DRUG METABOLIZING ENZYMES, TRANSPORTERS, RECEPTORS, AND PATHWAYS INVOLVED IN CHRONIC PAIN PERCEPTION ON THE EFFICACY AND SAFETY OF ANALGESICS AND OTHER DRUGS USED FOR CHRONIC PAIN TREATMENT. SEVERAL CANDIDATE GENES HAVE BEEN IDENTIFIED IN THE LITERATURE, WHILE THERE IS USUALLY ONLY LIMITED CLINICAL EVIDENCE SUBSTANTIATING FOR THE PENETRATION OF THE TESTING FOR THESE CANDIDATE BIOMARKERS INTO THE CLINICAL PRACTICE. FURTHER, THE PAIN-PERCEPTION REGULATION AND MODULATION ARE STILL NOT FULLY UNDERSTOOD, AND THUS MORE COMPLEX KNOWLEDGE OF GENETIC AND EPIGENETIC BACKGROUND FOR ANALGESIA WILL BE NEEDED PRIOR TO THE CLINICAL USE OF THE CANDIDATE GENETIC BIOMARKERS. 2013 11 13 34 360-DEGREE PERSPECTIVES ON OBESITY. ALARMING STATISTICS SHOW THAT THE NUMBER OF PEOPLE AFFECTED BY EXCESSIVE WEIGHT HAS SURPASSED 2 BILLION, REPRESENTING APPROXIMATELY 30% OF THE WORLD'S POPULATION. THE AIM OF THIS REVIEW IS TO PROVIDE A COMPREHENSIVE OVERVIEW OF ONE OF THE MOST SERIOUS PUBLIC HEALTH PROBLEMS, CONSIDERING THAT OBESITY REQUIRES AN INTEGRATIVE APPROACH THAT TAKES INTO ACCOUNT ITS COMPLEX ETIOLOGY, INCLUDING GENETIC, ENVIRONMENTAL, AND LIFESTYLE FACTORS. ONLY AN UNDERSTANDING OF THE CONNECTIONS BETWEEN THE MANY CONTRIBUTORS TO OBESITY AND THE SYNERGY BETWEEN TREATMENT INTERVENTIONS CAN ENSURE SATISFACTORY OUTCOMES IN REDUCING OBESITY. MECHANISMS SUCH AS OXIDATIVE STRESS, CHRONIC INFLAMMATION, AND DYSBIOSIS PLAY A CRUCIAL ROLE IN THE PATHOGENESIS OF OBESITY AND ITS ASSOCIATED COMPLICATIONS. COMPOUNDING FACTORS SUCH AS THE DELETERIOUS EFFECTS OF STRESS, THE NOVEL CHALLENGE POSED BY THE OBESOGENIC DIGITAL (FOOD) ENVIRONMENT, AND THE STIGMA ASSOCIATED WITH OBESITY SHOULD NOT BE OVERLOOKED. PRECLINICAL RESEARCH IN ANIMAL MODELS HAS BEEN INSTRUMENTAL IN ELUCIDATING THESE MECHANISMS, AND TRANSLATION INTO CLINICAL PRACTICE HAS PROVIDED PROMISING THERAPEUTIC OPTIONS, INCLUDING EPIGENETIC APPROACHES, PHARMACOTHERAPY, AND BARIATRIC SURGERY. HOWEVER, MORE STUDIES ARE NECESSARY TO DISCOVER NEW COMPOUNDS THAT TARGET KEY METABOLIC PATHWAYS, INNOVATIVE WAYS TO DELIVER THE DRUGS, THE OPTIMAL COMBINATIONS OF LIFESTYLE INTERVENTIONS WITH ALLOPATHIC TREATMENTS, AND, LAST BUT NOT LEAST, EMERGING BIOLOGICAL MARKERS FOR EFFECTIVE MONITORING. WITH EACH PASSING DAY, THE OBESITY CRISIS TIGHTENS ITS GRIP, THREATENING NOT ONLY INDIVIDUAL LIVES BUT ALSO BURDENING HEALTHCARE SYSTEMS AND SOCIETIES AT LARGE. IT IS HIGH TIME WE TOOK ACTION AS WE CONFRONT THE URGENT IMPERATIVE TO ADDRESS THIS ESCALATING GLOBAL HEALTH CHALLENGE HEAD-ON. 2023 12 4156 26 MECHANOBIOLOGY AND ADAPTIVE PLASTICITY THEORY AS A POTENTIAL CONFOUNDING FACTOR IN PREDICTING MUSCULOSKELETAL FOOT FUNCTION. THERE ARE MANY THEORETICAL MODELS THAT ATTEMPT TO ACCURATELY AND CONSISTENTLY LINK KINEMATIC AND KINETIC INFORMATION TO MUSCULOSKELETAL PAIN AND DEFORMITY OF THE FOOT. BIOMECHANICAL THEORY OF THE FOOT LACKS A CONSENSUAL MODEL: CLINICIANS ARE ENTICED TO DRAW FROM NUMEROUS PARADIGMS, EACH HAVING DIFFERENT LEVELS OF SUPPORTIVE EVIDENCE AND CONTRASTING METHODS OF EVALUATION, IN ORDER TO ENGAGE IN CLINICAL DEDUCTION AND TREATMENT PLANNING. CONTRIVING TO FIND A LINK BETWEEN FORM AND FUNCTION LIES AT THE HEART OF MOST OF THESE COMPETING THEORIES AND THE PHYSICAL NATURE OF THE DISCIPLINE HAS PROMPTED AN ENGINEERING APPROACH. PHYSICS IS OF GREAT IMPORTANCE IN BIOLOGY AND HELPS US TO MODEL THE FORCES THAT THE FOOT HAS TO DEAL WITH IN ORDER FOR IT TO WORK EFFECTIVELY. HOWEVER, THE TISSUES OF THE BODY HAVE COMPLEX PROCESSES THAT ARE IN PLACE TO PROTECT THEM AND THEY ARE VARIABLE BETWEEN INDIVIDUALS. RESEARCH IS UNCOVERING WHY THESE DIFFERENCES EXIST AND HOW THESE PROCESSES ARE GOVERNED. THE EMERGING EXPLANATIONS FOR ADAPTABILITY OF FOOT STRUCTURE AND MUSCULOSKELETAL HOMEOSTASIS OFFER NEW INSIGHTS INTO HOW CLINICAL VARIATION IN OUTCOMES AND TREATMENT EFFECTS MIGHT ARISE. THESE BIOLOGICAL PROCESSES UNDERLIE HOW VARIATION IN THE PERFORMANCE AND USE OF COMMON TRAITS, EVEN WITHIN APPARENTLY SIMILAR SUBGROUPS, MAKE ANATOMICAL DISTINCTION LESS MEANINGFUL AND ARE LIKELY TO UNDERMINE THE JUSTIFICATION OF A "FOOT TYPE." FURTHERMORE, MECHANOBIOLOGY INTRODUCES A PROBABILISTIC ELEMENT TO MORPHOLOGY BASED ON GENETIC AND EPIGENETIC FACTORS. 2021 13 5161 37 PRECISION AND PERSONALIZED MEDICINE: HOW GENOMIC APPROACH IMPROVES THE MANAGEMENT OF CARDIOVASCULAR AND NEURODEGENERATIVE DISEASE. LIFE EXPECTANCY HAS GRADUALLY GROWN OVER THE LAST CENTURY. THIS HAS DEEPLY AFFECTED HEALTHCARE COSTS, SINCE THE GROWTH OF AN AGING POPULATION IS CORRELATED TO THE INCREASING BURDEN OF CHRONIC DISEASES. THIS REPRESENTS THE INTERESTING CHALLENGE OF HOW TO MANAGE PATIENTS WITH CHRONIC DISEASES IN ORDER TO IMPROVE HEALTH CARE BUDGETS. EFFECTIVE PRIMARY PREVENTION COULD REPRESENT A PROMISING ROUTE. TO THIS END, PRECISION, TOGETHER WITH PERSONALIZED MEDICINE, ARE USEFUL INSTRUMENTS IN ORDER TO INVESTIGATE PATHOLOGICAL PROCESSES BEFORE THE APPEARANCE OF CLINICAL SYMPTOMS AND TO GUIDE PHYSICIANS TO CHOOSE A TARGETED THERAPY TO MANAGE THE PATIENT. CARDIOVASCULAR AND NEURODEGENERATIVE DISEASES REPRESENT SUITABLE MODELS FOR TAKING FULL ADVANTAGE OF PRECISION MEDICINE TECHNOLOGIES APPLIED TO ALL STAGES OF DISEASE DEVELOPMENT. THE AVAILABILITY OF HIGH TECHNOLOGY INCORPORATING ARTIFICIAL INTELLIGENCE AND ADVANCEMENT PROGRESS MADE IN THE FIELD OF BIOMEDICAL RESEARCH HAVE BEEN SUBSTANTIAL TO UNDERSTAND HOW GENES, EPIGENETIC MODIFICATIONS, AGING, NUTRITION, DRUGS, MICROBIOME AND OTHER ENVIRONMENTAL FACTORS CAN IMPACT HEALTH AND CHRONIC DISORDERS. THE AIM OF THE PRESENT REVIEW IS TO ADDRESS HOW PRECISION AND PERSONALIZED MEDICINE CAN BRING GREATER CLARITY TO THE CLINICAL AND BIOLOGICAL COMPLEXITY OF THESE TYPES OF DISORDERS ASSOCIATED WITH HIGH MORTALITY, INVOLVING TREMENDOUS HEALTH CARE COSTS, BY DESCRIBING IN DETAIL THE METHODS THAT CAN BE APPLIED. THIS MIGHT OFFER PRECIOUS TOOLS FOR PREVENTIVE STRATEGIES AND POSSIBLE CLUES ON THE EVOLUTION OF THE DISEASE AND COULD HELP IN PREDICTING MORBIDITY, MORTALITY AND DETECTING CHRONIC DISEASE INDICATORS MUCH EARLIER IN THE DISEASE COURSE. THIS, OF COURSE, WILL HAVE A MAJOR EFFECT ON BOTH IMPROVING THE QUALITY OF CARE AND QUALITY OF LIFE OF THE PATIENTS AND REDUCING TIME EFFORTS AND HEALTHCARE COSTS. 2020 14 6480 32 TOWARDS PRECISION MEDICINE IN GENERALIZED ANXIETY DISORDER: REVIEW OF GENETICS AND PHARMACO(EPI)GENETICS. GENERALIZED ANXIETY DISORDER (GAD) IS A PREVALENT AND CHRONIC MENTAL DISORDER THAT ELICITS WIDESPREAD FUNCTIONAL IMPAIRMENT. GIVEN THE HIGH DEGREE OF NON-RESPONSE/PARTIAL RESPONSE AMONG PATIENTS WITH GAD TO AVAILABLE PHARMACOLOGICAL TREATMENTS, THERE IS A STRONG NEED FOR NOVEL APPROACHES THAT CAN OPTIMIZE OUTCOMES, AND LEAD TO MEDICATIONS THAT ARE SAFER AND MORE EFFECTIVE. ALTHOUGH INVESTIGATIONS HAVE IDENTIFIED INTERESTING TARGETS PREDICTING TREATMENT RESPONSE THROUGH PHARMACOGENETICS (PGX), PHARMACO-EPIGENETICS, AND NEUROIMAGING METHODS, THESE STUDIES ARE OFTEN SOLITARY, NOT REPLICATED, AND CARRY SEVERAL LIMITATIONS. THIS REVIEW PROVIDES AN OVERVIEW OF THE CURRENT STATUS OF GAD GENETICS AND PGX AND PRESENTS POTENTIAL STRATEGIES TO IMPROVE TREATMENT RESPONSE BY COMBINING BETTER PHENOTYPING WITH PGX AND IMPROVED ANALYTICAL METHODS. THESE STRATEGIES CARRY THE DUAL BENEFIT OF DELIVERING DATA ON BIOMARKERS OF TREATMENT RESPONSE AS WELL AS POINTING TO DISEASE MECHANISMS THROUGH THE BIOLOGY OF THE MARKERS ASSOCIATED WITH RESPONSE. OVERALL, THESE EFFORTS CAN SERVE TO IDENTIFY CLINICAL, GENETIC, AND EPIGENETIC FACTORS THAT CAN BE INCORPORATED INTO A PHARMACO(EPI)GENETIC TEST THAT MAY ULTIMATELY IMPROVE TREATMENT RESPONSE AND REDUCE THE SOCIOECONOMIC BURDEN OF GAD. 2019 15 2586 23 EPIGENETICS OF PAIN MEDIATORS. PURPOSE OF REVIEW: THE FIELD OF EPIGENETICS CONTINUES ITS INFLUENTIAL RISE AS A MEANS TO BETTER UNDERSTAND AN ORGANISM'S UNIQUE DEVELOPMENTAL IDENTITY OVER A LIFESPAN. WHEREAS A GENOME IS CONSTANT AND UNCHANGING, AN EPIGENOME IS DYNAMIC AND ALTERABLE. EPIGENETIC CHANGES ARE IN RESPONSE TO INNUMERABLE INTERNAL AND EXTERNAL INFLUENCES INCLUDING ENVIRONMENTAL CHANGES SUCH AS DIET, EXERCISE, DISEASE, TOXINS, AND STRESS. EPIGENETICS IS OF PARTICULAR INTEREST IN THE MEDICAL RESEARCH COMMUNITY BOTH FOR THE POTENTIAL TO CAUSE DISEASE AND AS A TARGET FOR THERAPEUTIC INTERVENTIONS. THIS ARTICLE PROVIDES A SUCCINCT EXPLANATION OF THE POTENTIAL FOR EPIGENETICS TO INFLUENCE THE UNDERSTANDING OF PAIN AS WELL AS A REVIEW OF RELEVANT RESEARCH ON THE TOPIC. RECENT FINDINGS: STUDIES ON EPIGENETICS AND PAIN REMAIN LARGELY PRECLINICAL AND INVESTIGATE THE THEORETICAL ABILITY OF EPIGENETICS TO ALTER THE NOCICEPTIVE PATHWAYS BOTH IN THE PERIPHERY AND CENTRALLY. SIGNIFICANT EVIDENCE NOW EXISTS FOR THE ABILITY OF EPIGENETICS TO MODIFY BROADLY CATEGORIZED PAIN TYPES, INCLUDING INFLAMMATORY, NEUROPATHIC, VISCERAL, AND CANCER RELATED. SUMMARY: BOTH PATIENTS AND PROVIDERS RECOGNIZE THAT NOVEL MEDICATIONS FOR THE TREATMENT OF BOTH ACUTE AND CHRONIC PAIN CONDITIONS ARE SORELY NEEDED. THE UNDERSTANDING OF EPIGENETICS AND ITS INFLUENCE ON NOCICEPTION REMAINS IN RELATIVE INFANCY BUT EARLY EVIDENCE IS STRONG FOR POTENTIAL THERAPEUTIC BENEFITS TO TREAT THESE CONDITIONS. 2018 16 3007 27 GENETIC, IMMUNOLOGIC, AND ENVIRONMENTAL BASIS OF SARCOIDOSIS. SARCOIDOSIS IS A MULTISYSTEM DISEASE WITH TREMENDOUS HETEROGENEITY IN DISEASE MANIFESTATIONS, SEVERITY, AND CLINICAL COURSE THAT VARIES AMONG DIFFERENT ETHNIC AND RACIAL GROUPS. TO BETTER UNDERSTAND THIS DISEASE AND TO IMPROVE THE OUTCOMES OF PATIENTS, A NATIONAL HEART, LUNG, AND BLOOD INSTITUTE WORKSHOP WAS CONVENED TO ASSESS THE CURRENT STATE OF KNOWLEDGE, GAPS, AND RESEARCH NEEDS ACROSS THE CLINICAL, GENETIC, ENVIRONMENTAL, AND IMMUNOLOGIC ARENAS. WE ALSO EXPLORED TO WHAT EXTENT THE INTERPLAY OF THE GENETIC, ENVIRONMENTAL, AND IMMUNOLOGIC FACTORS COULD EXPLAIN THE DIFFERENT PHENOTYPES AND OUTCOMES OF PATIENTS WITH SARCOIDOSIS, INCLUDING THE CHRONIC PHENOTYPES THAT HAVE THE GREATEST HEALTHCARE BURDEN. THE POTENTIAL USE OF CURRENT GENETIC, EPIGENETIC, AND IMMUNOLOGIC TOOLS ALONG WITH STUDY APPROACHES THAT INTEGRATE ENVIRONMENTAL EXPOSURES AND PRECISE CLINICAL PHENOTYPING WERE ALSO EXPLORED. FINALLY, WE MADE EXPERT PANEL-BASED CONSENSUS RECOMMENDATIONS FOR RESEARCH APPROACHES AND PRIORITIES TO IMPROVE OUR UNDERSTANDING OF THE EFFECT OF THESE FACTORS ON THE HEALTH OUTCOMES IN SARCOIDOSIS. 2017 17 5650 31 SEX DIFFERENCES IN THE DEVELOPMENT OF PHYSICAL AGGRESSION: AN INTERGENERATIONAL PERSPECTIVE AND IMPLICATIONS FOR PREVENTIVE INTERVENTIONS. THIS ARTICLE REVIEWS THE STATE OF KNOWLEDGE ON THE DEVELOPMENT OF CHRONIC PHYSICAL AGGRESSION (CPA), WITH THE AIM OF IDENTIFYING THE MOST EFFECTIVE PREVENTION STRATEGIES. WE SPECIFICALLY FOCUS ON THE EARLY DEVELOPMENT OF PHYSICAL AGGRESSION, ON SEX DIFFERENCES IN THE USE OF PHYSICAL AGGRESSION, AND ON THE TRANSMISSION OF BEHAVIOR PROBLEMS FROM ONE GENERATION TO THE OTHER. THE BODY OF RESEARCH ON THE DEVELOPMENT OF CPA FROM THE PAST THREE DECADES THAT WE REVIEW SHOWS INCREASING EVIDENCE THAT ITS PREVENTION REQUIRES A LONG-TERM BIOPSYCHOSOCIAL DEVELOPMENTAL APPROACH WHICH ALSO MUST INCLUDE AN INTERGENERATIONAL PERSPECTIVE. RECENT GENETIC AND EPIGENETIC RESEARCH HAS INDICATED THAT THERE ARE BOTH IMPORTANT GENETIC AND ENVIRONMENTAL EFFECTS ON GENE EXPRESSION WHICH START AT CONCEPTION. WE CONCLUDE THAT ONE OF THE MOST EFFECTIVE STRATEGIES TO BREAK THE INTERGENERATIONAL TRANSMISSION OF CPA INVOLVES GIVING LONG-TERM SUPPORT TO PREGNANT WOMEN WITH A HISTORY OF BEHAVIOR PROBLEMS, THEIR SPOUSE, AND THEIR OFFSPRING. 2019 18 6760 30 WORKGROUP ON NAPA'S SCIENTIFIC AGENDA FOR A NATIONAL INITIATIVE ON ALZHEIMER'S DISEASE. THIS REPORT OUTLINES A GOAL-DIRECTED SCIENTIFIC AGENDA FOR A NATIONAL INITIATIVE TO OVERCOME THE ALZHEIMER'S DISEASE (AD) CRISIS. THE STATEMENT, WHICH REFLECTS THE COLLECTIVE VIEWS AND RECOMMENDATIONS OF LEADERS IN AD RESEARCH, IS INTENDED TO AID THE IMPLEMENTATION OF THE NATIONAL ALZHEIMER'S PROJECT ACT (NAPA)'S NATIONAL PLAN TO DEFEAT AD. THE PRIMARY PUBLIC POLICY AIMS OF THIS 10-YEAR SCIENTIFIC AGENDA ARE TO DISCOVER, VALIDATE, AND DEVELOP: (1) A BROAD RANGE OF TECHNOLOGIES, TOOLS AND ALGORITHMS FOR EARLY DETECTION OF PEOPLE WITH SYMPTOMATIC AD, AND ASYMPTOMATIC INDIVIDUALS AT ELEVATED RISK FOR AD AND OTHER DEMENTIAS; AND (2) A WIDE RANGE OF INTERVENTIONS TO PRESERVE AND/OR RESTORE HEALTH AND NORMAL NEURAL FUNCTION, AIMING TO MAINTAIN INDEPENDENT FUNCTIONING FOR AS LONG AS POSSIBLE. THE LONG-TERM SCIENTIFIC PUBLIC HEALTH OBJECTIVES OF THIS COMPREHENSIVE PLAN ARE TO: (1) REDUCE THE NUMBER OF PEOPLE WITH CHRONIC DISABLING SYMPTOMS WHO WILL REQUIRE PROLONGED CARE AND, EVENTUALLY, REDUCE THE NUMBER OF ASYMPTOMATIC PEOPLE AT ELEVATED RISK FOR AD/DEMENTIA; (2) DELAY THE ONSET OF CHRONIC DISABILITY FOR PEOPLE WITH AD AND OTHER DEGENERATIVE BRAIN DISORDERS; AND (3) LOWER THE COST AND BURDEN OF CARE. THE PLAN CALLS FOR SIGNIFICANT EXPANSION OF RESEARCH PROGRAMS TO IDENTIFY AND VALIDATE THE CAUSE(S) AND PATHOGENESIS OF AD, GENETIC AND EPIGENETIC FACTORS THAT CONTRIBUTE TO AD RISK, THERAPEUTIC TARGETS THAT AFFECT DISEASE PROGRESSION, SURROGATE BIOMARKERS OF AD PATHOBIOLOGY, AND TECHNOLOGIES FOR EARLY DETECTION OF AD. 2012 19 6863 28 [ONE AUTISM, SEVERAL AUTISMS. PHENOTYPICAL VARIABILITY IN AUTISM SPECTRUM DISORDERS]. INTRODUCTION: AUTISM SPECTRUM DISORDERS (ASD) ARE A HETEROGENEOUS GROUP OF DISORDERS THAT BEGIN IN THE EARLY MONTHS OF LIFE AND FOLLOW A CHRONIC PROGRESSION. THEY HAVE A BIOLOGICAL ORIGIN, WITH COMPLEX AETIOLOGICAL FACTORS THAT INVOLVE DIFFERENT GENETIC, EPIGENETIC AND ENVIRONMENTAL MECHANISMS THAT INTERACT WITH ONE ANOTHER. AIM: TO REVIEW THE MAIN FACTORS THAT VARY THE PRESENTATION OF AUTISM TAKING INTO ACCOUNT THE MOST RECENT SCIENTIFIC EVIDENCE. DEVELOPMENT: ASPECTS RELATED WITH THE DEVELOPMENT OF SYMPTOMS, GENDER, COMORBIDITY, AGE AND AETIOLOGY DETERMINE THE VARIABILITY IN THE CLINICAL PRESENTATION OF ASD. CONCLUSIONS: AUTISM IS HIGHLY HETEROGENEOUS AND IS PHENOTYPICALLY RELATED, AT LEAST IN PART, WITH A WIDE RANGE OF CAUSATIONS, WHICH RESEARCHERS HAVE BEGUN TO UNRAVEL BUT WHICH ARE STILL LARGELY UNKNOWN. AETIOLOGICAL RESEARCH, ESPECIALLY IN THE AREA OF GENETICS, WILL MAKE IT POSSIBLE TO IDENTIFY DIFFERENT HOMOGENEOUS SUBGROUPS WITH THEIR CORRESPONDING PHENOTYPES, WHILE ALSO OPENING UP THE WAY TO POSSIBLE THERAPEUTIC ALTERNATIVES IN THE FUTURE. 2016 20 3472 28 IDENTIFICATION AND MANAGEMENT OF PAIN MEDICATION ABUSE AND MISUSE: CURRENT STATE AND FUTURE DIRECTIONS. LONG-TERM OPIOID THERAPY POSES A RISK FOR ABUSE AND MISUSE IN SOME PATIENTS. IDENTIFYING WHICH PATIENTS MAY POTENTIALLY BE AT RISK PRIOR TO INITIATION OF THERAPY, AND IDENTIFYING PATIENTS IN WHOM THESE PROBLEMS DEVELOP DURING THERAPY, ARE SIGNIFICANT CHALLENGES. OUTCOME PREDICTION IS IMPEDED BY THE COMPLEXITY OF THE PROBLEM, WHERE CONSIDERABLE HETEROGENEITY RESULTS FROM PSYCHOLOGICAL AND SOCIOECONOMIC FACTORS, AS WELL AS INTERINDIVIDUAL VARIATION IN BIOLOGICAL PATHWAYS DUE TO GENETIC AND EPIGENETIC FACTORS. SCREENING TOOLS DESIGNED TO DETECT OPIOID MISUSE AND URINE DRUG TESTING ARE BOTH USED CLINICALLY; SCANT EVIDENCE CURRENTLY EXISTS TO ALLOW THE FORMULATION OF AN ALGORITHM FOR JUDICIOUS USE OF THESE TOOLS. MOREOVER, THESE TOOLS MAY NOT BE ADDRESSING THE UNDERLYING ALTERATIONS IN BIOLOGICAL PATHWAYS THAT OCCUR OWING TO THE DEVELOPMENT OF CHRONIC PAIN OR IN RESPONSE TO CHRONIC OPIOID ADMINISTRATION. AN EVIDENCE-BASED ALGORITHMIC APPROACH TO RISK MITIGATION THAT CAN BE APPLIED IN A COST-EFFECTIVE MANNER TO GUIDE THERAPY IS URGENTLY NEEDED. 2012