1   561 182 BARIATRIC SURGERY-INDUCED WEIGHT LOSS AND ASSOCIATED GENOME-WIDE DNA-METHYLATION ALTERATIONS IN OBESE INDIVIDUALS. BACKGROUND: OBESITY IS A MULTIFACTORIAL AND CHRONIC CONDITION OF GROWING UNIVERSAL CONCERN. IT HAS RECENTLY BEEN REPORTED THAT BARIATRIC SURGERY IS A MORE SUCCESSFUL TREATMENT FOR SEVERE OBESITY THAN OTHER NONINVASIVE INTERVENTIONS, RESULTING IN RAPID SIGNIFICANT WEIGHT LOSS AND ASSOCIATED CHRONIC DISEASE REMISSION. THE IDENTIFICATION OF DISTINCT EPIGENETIC PATTERNS IN PATIENTS WHO ARE OBESE OR HAVE METABOLIC IMBALANCES HAS SUGGESTED A POTENTIAL ROLE FOR EPIGENETIC ALTERATIONS IN CAUSAL OR MEDIATING PATHWAYS IN THE DEVELOPMENT OF OBESITY-RELATED PATHOLOGIES. SPECIFIC CHANGES IN THE EPIGENOME (DNA METHYLOME), ASSOCIATED WITH METABOLIC DISORDERS, CAN BE DETECTED IN THE BLOOD. WE INVESTIGATED WHETHER SUCH EPIGENETIC CHANGES ARE REVERSIBLE AFTER WEIGHT LOSS USING GENOME-WIDE DNA METHYLOME ANALYSIS OF BLOOD SAMPLES FROM INDIVIDUALS WITH SEVERE OBESITY (MEAN BMI ~ 45) UNDERGOING BARIATRIC SURGERY. RESULTS: OUR ANALYSIS REVEALED 41 SIGNIFICANT (BONFERRONI P < 0.05) AND 1169 (FALSE DISCOVERY RATE P < 0.05) SUGGESTIVE DIFFERENTIALLY METHYLATED POSITIONS (DMPS) ASSOCIATED WITH WEIGHT LOSS DUE TO BARIATRIC SURGERY. AMONG THE 41 SIGNIFICANT DMPS, 5 CPGS WERE REPLICATED IN AN INDEPENDENT COHORT OF BMI-DISCORDANT MONOZYGOTIC TWINS (THE HEAVIER TWIN UNDERWENT DIET-INDUCED WEIGHT LOSS). THE EFFECT SIZES OF THESE 5 CPGS WERE CONSISTENT ACROSS DISCOVERY AND REPLICATION SETS (P < 0.05). WE ALSO IDENTIFIED 192 DIFFERENTIALLY METHYLATED REGIONS (DMRS) AMONG WHICH SMAD6 AND PFKFB3 GENES WERE THE TOP HYPERMETHYLATED AND HYPOMETHYLATED REGIONS, RESPECTIVELY. PATHWAY ENRICHMENT ANALYSIS OF THE DMR-ASSOCIATED GENES SHOWED THAT FUNCTIONAL PATHWAYS RELATED TO IMMUNE FUNCTION AND TYPE 1 DIABETES WERE SIGNIFICANT. WEIGHT LOSS DUE TO BARIATRIC SURGERY ALSO SIGNIFICANTLY DECELERATED EPIGENETIC AGE 12 MONTHS AFTER THE INTERVENTION (MEAN = - 4.29; P = 0.02). CONCLUSIONS: WE IDENTIFIED WEIGHT LOSS-ASSOCIATED DNA-METHYLATION ALTERATIONS TARGETING IMMUNE AND INFLAMMATORY GENE PATHWAYS IN BLOOD SAMPLES FROM BARIATRIC-SURGERY PATIENTS. THE TOP HITS WERE REPLICATED IN SAMPLES FROM AN INDEPENDENT COHORT OF BMI-DISCORDANT MONOZYGOTIC TWINS FOLLOWING A HYPOCALORIC DIET. ENERGY RESTRICTION AND BARIATRIC SURGERY THUS SHARE CPGS THAT MAY REPRESENT EARLY INDICATORS OF RESPONSE TO THE METABOLIC EFFECTS OF WEIGHT LOSS. THE ANALYSIS OF BARIATRIC SURGERY-ASSOCIATED DMRS SUGGESTS THAT EPIGENETIC REGULATION OF GENES INVOLVED IN ENDOTHELIAL AND ADIPOSE TISSUE FUNCTION IS KEY IN THE PATHOPHYSIOLOGY OF OBESITY.	2022	
                                                                                                                                                                                  
2    47  41 A CONCEPTUAL MODEL OF BIOPSYCHOSOCIAL MECHANISMS OF TRANSITION FROM ACUTE TO CHRONIC POSTSURGICAL PAIN IN CHILDREN AND ADOLESCENTS. ACUTE AND CHRONIC PAIN ARE HIGHLY PREVALENT AND IMPACTFUL CONSEQUENCES OF SURGERY ACROSS THE LIFESPAN, YET A COMPREHENSIVE CONCEPTUAL MODEL ENCOMPASSING BIOPSYCHOSOCIAL FACTORS UNDERLYING ACUTE TO CHRONIC PAIN TRANSITION IS LACKING, PARTICULARLY IN YOUTH. BUILDING ON PRIOR CHRONIC POSTSURGICAL PAIN MODELS, WE PROPOSE A NEW CONCEPTUAL MODEL OF BIOPSYCHOSOCIAL MECHANISMS OF TRANSITION FROM ACUTE TO CHRONIC POSTSURGICAL PAIN. THIS REVIEW AIMS TO SUMMARIZE EXISTING RESEARCH EXAMINING KEY FACTORS UNDERLYING ACUTE TO CHRONIC POSTSURGICAL PAIN TRANSITION IN ORDER TO GUIDE PREVENTION AND INTERVENTION EFFORTS AIMED AT ADDRESSING THIS HEALTH ISSUE IN CHILDREN. AS PAIN TRANSITIONS FROM ACUTE NOCICEPTIVE PAIN TO CHRONIC PAIN, CHANGES IN THE PERIPHERAL AND CENTRAL NERVOUS SYSTEM CONTRIBUTE TO THE CHRONIFICATION OF PAIN AFTER SURGERY. THESE CHANGES INCLUDE ALTERATIONS IN SENSORY PAIN PROCESSING AND PSYCHOSOCIAL PROCESSES (PSYCHOLOGICAL, BEHAVIORAL, AND SOCIAL COMPONENTS), WHICH PROMOTE THE DEVELOPMENT OF CHRONIC PAIN. PATIENT-RELATED PREMORBID FACTORS (EG, DEMOGRAPHIC FACTORS, GENETIC PROFILE, AND MEDICAL FACTORS SUCH AS PREMORBID PAIN) MAY FURTHER MODULATE THESE CHANGES. FACTORS RELATED TO ACUTE INJURY AND RECOVERY (EG, SURGICAL AND TREATMENT FACTORS), AS WELL AS BIOLOGICAL RESPONSE TO SURGERY (EG, EPIGENETIC, INFLAMMATORY, AND ENDOCRINE FACTORS), MAY ALSO INFLUENCE THIS PROCESS. OVERALL, LONGITUDINAL STUDIES EXAMINING TEMPORAL PATHWAYS OF BIOPSYCHOSOCIAL PROCESSES INCLUDING BOTH RISK AND RESILIENCY FACTORS WILL BE ESSENTIAL TO IDENTIFY THE MECHANISMS INVOLVED IN THE TRANSITION FROM ACUTE TO CHRONIC PAIN. RESEARCH IS ALSO NEEDED TO UNRAVEL CONNECTIONS BETWEEN THE ACUTE PAIN EXPERIENCE, OPIOID EXPOSURE, AND SENSORY PAIN PROCESSING DURING ACUTE TO CHRONIC PAIN TRANSITION. FURTHERMORE, FUTURE STUDIES SHOULD INCLUDE LARGER AND MORE DIVERSE SAMPLES TO MORE FULLY EXPLORE RISK FACTORS IN A BROADER RANGE OF PEDIATRIC SURGERIES. THE USE OF CONCEPTUAL MODELS TO GUIDE INTERVENTION APPROACHES TARGETING MECHANISMS OF TRANSITION FROM ACUTE TO CHRONIC PAIN WILL SIGNIFICANTLY ADVANCE THIS FIELD AND IMPROVE OUTCOMES FOR CHILDREN AND ADOLESCENTS UNDERGOING SURGERY.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
3  2571  32 EPIGENETICS OF CHRONIC PAIN AFTER THORACIC SURGERY. PURPOSE OF REVIEW: CHRONIC PAIN AFTER SURGERY IS A MAJOR PUBLIC HEALTH PROBLEM AND A MAJOR CONCERN FOR PERIOPERATIVE PHYSICIANS. THORACIC SURGERY PRESENTS A UNIQUE CHALLENGE, AS THORACOTOMY IS AMONG THE HIGHEST RISK SURGERIES TO DEVELOP PERSISTENT POSTSURGICAL PAIN. THE PURPOSE OF THIS REVIEW IS TO DISCUSS THE RELEVANCE OF RESEARCH IN PAIN EPIGENETICS TO PATIENTS WITH PERSISTENT PAIN AFTER THORACIC SURGERY. RECENT FINDINGS: RECENT ADVANCES HAVE LINKED CHRONIC PAIN STATES TO GENETIC AND EPIGENETIC CHANGES. PROGRESS IN OUR UNDERSTANDING OF CHRONIC PAIN HAS HIGHLIGHTED THE IMPORTANCE OF IMMUNE MODULATION OF PAIN. IT IS POSSIBLE THAT EPIGENETIC CHANGES DRIVING CHRONIC PAIN OCCUR IN THE PERIOPERATIVE SETTING VIA HISTONE MODIFICATION AND DNA METHYLATION. SUMMARY: THE TRANSITION FROM ACUTE TO CHRONIC PAIN AFTER THORACIC SURGERY MAY BE MEDIATED BY EPIGENETICS. HERE, WE DISCUSS EPIGENETIC MODIFICATIONS THAT HAVE BEEN DISCOVERED IN ANIMAL MODELS OF CHRONIC PAIN THAT MAY PREDISPOSE PATIENTS TO PERSISTENT NEUROPATHIC PAIN AFTER THORACIC SURGERY.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
4  6469  54 TISSUE-SPECIFIC METHYLATION PROFILE IN OBESE PATIENTS WITH TYPE 2 DIABETES BEFORE AND AFTER ROUX-EN-Y GASTRIC BYPASS. EATING HABITS, LIFESTYLES, AND EXPOSURE TO SPECIFIC ENVIRONMENTAL FACTORS CAN GREATLY IMPACT THE RISK OF DEVELOPING TYPE 2 DIABETES (T2D), INFLUENCE THE GENOME EPIGENETICALLY, AND AFFECT THE EXPRESSION OF GENES, INCLUDING GENES RELATED TO GLYCEMIC CONTROL, AT ANY STAGE OF LIFE. THE EPIGENETIC MECHANISM UNDERLYING OBESITY AND T2D PATHOGENESIS REMAINS POORLY UNDERSTOOD. CONVENTIONAL STRATEGIES FOR THE TREATMENT OF OBESITY AND ITS COMORBIDITIES OFTEN HAVE POOR LONG-TERM ADHERENCE, AND PHARMACOLOGICAL INTERVENTIONS ARE LIMITED. BARIATRIC SURGERY IS THE MOST EFFECTIVE CURRENT OPTION TO TREAT SEVERE OBESITY, AND ROUX-EN-Y GASTRIC BYPASS (RYGB) IS THE MOST APPLIED TECHNIQUE WORLDWIDE. EPIGENETIC CHANGES DIFFER DEPENDING ON THE APPROACH USED TO TREAT OBESITY AND ITS ASSOCIATED COMORBIDITIES (CLINICAL OR SURGICAL). COMPARED TO PRIMARY CLINICAL CARE, BARIATRIC SURGERY LEADS TO MUCH GREATER LOSS OF BODY WEIGHT AND HIGHER REMISSION RATES OF T2D AND METABOLIC SYNDROME, WITH METHYLATION PROFILES IN PROMOTER REGIONS OF GENES IN OBESE INDIVIDUALS BECOMING SIMILAR TO THOSE OF NORMAL-WEIGHT INDIVIDUALS. BARIATRIC SURGERY CAN INFLUENCE DNA METHYLATION IN PARALLEL WITH CHANGES IN GENE EXPRESSION PATTERN. CHANGES IN CLINICAL BIOMARKERS THAT REFLECT IMPROVEMENTS IN GLUCOSE AND LIPID METABOLISM AFTER RYGB OFTEN OCCUR BEFORE MAJOR WEIGHT LOSS AND ARE COORDINATED BY SURGERY-INDUCED CHANGES IN INTESTINAL HORMONES. THEREFORE, THE INTESTINE METHYLATION PROFILE WOULD ASSIST IN UNDERSTANDING THE MECHANISMS INVOLVED IN IMPROVED GLYCEMIC CONTROL AFTER BARIATRIC SURGERY. THE MAIN OBJECTIVES IN THIS AREA FOR THE FUTURE ARE TO IDENTIFY EPIGENETIC MARKS THAT COULD BE USED AS EARLY INDICATORS OF METABOLIC RISK, AND TO DEVELOP TREATMENTS ABLE TO DELAY OR EVEN REVERSE THESE EPIGENETIC CHANGES. STUDIES THAT PROVIDE THE "HUMAN EPIGENETIC PROFILE" WILL BE OF CONSIDERABLE VALUE TO IDENTIFY TISSUE-SPECIFIC EPIGENETIC SIGNATURES AND THEIR ROLE IN THE DEVELOPMENT OF CHRONIC DISEASES. FURTHER STUDIES SHOULD APPLY METHODS BASED ON GLOBAL ANALYSIS OF THE GENOME TO IDENTIFY METHYLATED SITES ASSOCIATED WITH DISEASE AND EPIGENETIC MARKS ASSOCIATED WITH THE REMODELING RESPONSE TO BARIATRIC SURGERY. THIS REVIEW DESCRIBES THE MAIN EPIGENETIC ALTERATIONS ASSOCIATED WITH OBESITY AND T2D AND THE POTENTIAL ROLE OF RYGB IN REMODELING THESE CHANGES.	2017	
                                                                                                                                                                                                                                                                                                                                                         
5  5797  36 STEM CELL-BASED THERAPY FOR HIRSCHSPRUNG DISEASE, DO WE HAVE THE GUTS TO TREAT? HIRSCHSPRUNG DISEASE (HSCR) IS A CONGENITAL ANOMALY OF THE COLON THAT RESULTS FROM FAILURE OF ENTERIC NERVOUS SYSTEM FORMATION, LEADING TO A CONSTRICTED DYSFUNCTIONAL SEGMENT OF THE COLON WITH VARIABLE LENGTHS, AND NECESSITATING SURGICAL INTERVENTION. THE UNDERLYING PATHOPHYSIOLOGY INCLUDES A DEFECT IN NEURAL CREST CELLS MIGRATION, PROLIFERATION AND DIFFERENTIATION, WHICH ARE PARTIALLY EXPLAINED BY IDENTIFIED GENETIC AND EPIGENETIC ALTERATIONS. DESPITE THE HIGH SUCCESS RATE OF THE CURATIVE SURGERIES, THEY ARE ASSOCIATED WITH SIGNIFICANT ADVERSE OUTCOMES SUCH AS ENTEROCOLITIS, FECAL SOILING, AND CHRONIC CONSTIPATION. IN ADDITION, SOME PATIENTS SUFFER FROM EXTENSIVE LETHAL VARIANTS OF THE DISEASE, ALL OF WHICH JUSTIFY THE NEED FOR AN ALTERNATIVE CURE. DURING THE LAST 5 YEARS, THERE HAS BEEN CONSIDERABLE PROGRESS IN HSCR STEM CELL-BASED THERAPY RESEARCH. HOWEVER, MANY MAJOR ISSUES REMAIN UNSOLVED. THIS REVIEW WILL PROVIDE CONCISE BACKGROUND INFORMATION ON HSCR, OUTLINE THE FUTURE APPROACHES OF STEM CELL-BASED HSCR THERAPY, REVIEW RECENT KEY PUBLICATIONS, DISCUSS TECHNICAL AND ETHICAL CHALLENGES THE FIELD FACES PRIOR TO CLINICAL TRANSLATION, AND TACKLE SUCH CHALLENGES BY PROPOSING SOLUTIONS AND EVALUATING EXISTING APPROACHES TO PROGRESS FURTHER.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
6  3630  34 INCLUSION OF SOCIAL AND STRUCTURAL DETERMINANTS OF HEALTH TO ADVANCE UNDERSTANDING OF THEIR INFLUENCE ON THE BIOLOGY OF CHRONIC DISEASE. SOCIAL DETERMINANTS OF HEALTH (SDOH) CONSIDER SOCIAL, POLITICAL, AND ECONOMIC FACTORS THAT CONTRIBUTE TO HEALTH DISPARITIES IN PATIENTS AND POPULATIONS. THE MOST COMMON HEALTH-RELATED SDOH EXPOSURES ARE FOOD AND HOUSING INSECURITY, FINANCIAL INSTABILITY, TRANSPORTATION NEEDS, LOW LEVELS OF EDUCATION, AND PSYCHOSOCIAL STRESS. THESE DOMAINS DESCRIBE RISKS THAT CAN IMPACT HEALTH OUTCOMES MORE THAN HEALTH CARE. EPIDEMIOLOGIC AND TRANSLATIONAL RESEARCH DEMONSTRATES THAT SDOH FACTORS REPRESENT EXPOSURES THAT PREDICT HARM AND IMPACT THE HEALTH OF INDIVIDUALS. INTERNATIONAL AND NATIONAL GUIDELINES URGE HEALTH PROFESSIONALS TO ADDRESS SDOH IN CLINICAL PRACTICE AND PUBLIC HEALTH. THE FURTHER IMPLEMENTATION OF THESE RECOMMENDATIONS INTO BASIC AND TRANSLATIONAL RESEARCH, HOWEVER, IS LAGGING. HEREIN, WE CONSIDER A PRECISION HEALTH FRAMEWORK TO DESCRIBE HOW SDOH CONTRIBUTES TO THE EXPOSOME AND EXACERBATES PHYSIOLOGIC PATHWAYS THAT LEAD TO CHRONIC DISEASE. SDOH FACTORS ARE ASSOCIATED WITH VARIOUS FORMS OF STRESSORS THAT IMPACT PHYSIOLOGICAL PROCESSES THROUGH EPIGENETIC, INFLAMMATORY, AND REDOX REGULATION. MANY SDOH EXPOSURES MAY ADD TO OR POTENTIATE THE PATHOLOGIC EFFECTS OF ADDITIONAL ENVIRONMENTAL EXPOSURES. THIS OVERVIEW AIMS TO INFORM BASIC LIFE SCIENCE AND TRANSLATIONAL RESEARCHERS ABOUT SDOH EXPOSURES THAT CAN CONFOUND ASSOCIATIONS BETWEEN CLASSIC BIOMEDICAL DETERMINANTS OF DISEASE AND HEALTH OUTCOMES. TO ADVANCE THE STUDY OF TOXICOLOGY THROUGH EITHER QUALITATIVE OR QUANTITATIVE ASSESSMENT OF EXPOSURES TO CHEMICAL AND BIOLOGICAL SUBSTANCES, A MORE COMPLETE ENVIRONMENTAL EVALUATION SHOULD INCLUDE SDOH EXPOSURES. WE DISCUSS COMMON APPROACHES TO MEASURE SDOH FACTORS AT INDIVIDUAL AND POPULATION LEVELS AND REVIEW THE ASSOCIATIONS BETWEEN SDOH RISK FACTORS AND PHYSIOLOGIC MECHANISMS THAT INFLUENCE CHRONIC DISEASE. WE PROVIDE CLINICAL AND POLICY-BASED MOTIVATION TO ENCOURAGE RESEARCHERS TO CONSIDER THE IMPACT OF SDOH EXPOSURES ON STUDY RESULTS AND DATA INTERPRETATION. WITH VALID MEASURES OF SDOH FACTORS INCORPORATED INTO STUDY DESIGN AND ANALYSES, FUTURE TOXICOLOGICAL RESEARCH MAY CONTRIBUTE TO AN EVIDENCE BASE THAT CAN BETTER INFORM PREVENTION AND TREATMENT OPTIONS, TO IMPROVE EQUITABLE CLINICAL CARE AND POPULATION HEALTH. (C) 2022 WILEY PERIODICALS LLC.	2022	
                                                                                                                                                                                                                                                                                                                                                                                        
7  1456  46 DISCRIMINATING THE MOLECULAR BASIS OF HEPATOTOXICITY USING THE LARGE-SCALE CHARACTERISTIC MOLECULAR SIGNATURES OF TOXICANTS BY EXPRESSION PROFILING ANALYSIS. PREDICTING THE POTENTIAL HUMAN HEALTH RISK POSED BY CHEMICAL STRESSORS HAS LONG BEEN A MAJOR CHALLENGE FOR TOXICOLOGISTS, AND THE USE OF MICROARRAYS TO MEASURE RESPONSES TO TOXICOLOGICALLY RELEVANT GENES, AND TO IDENTIFY SELECTIVE, SENSITIVE BIOMARKERS OF TOXICITY IS A MAJOR APPLICATION OF PREDICTIVE AND DISCOVERY TOXICOLOGY. TO INVESTIGATE THIS POSSIBILITY, WE INVESTIGATED WHETHER CARCINOGENS (AT DOSES KNOWN TO INDUCE LIVER TUMORS IN CHRONIC EXPOSURE BIOASSAYS) DEREGULATE CHARACTERISTIC SETS OF GENES IN MICE. MALE C3H/HE MICE WERE DOSED WITH TWO HEPATOCARCINOGENS (VINYL CHLORIDE (VC, 50-25 MG/KG), ALDRIN (AD, 0.8-0.4 MG/KG)), OR TWO NON-HEPATOCARCINOGENS (COPPER SULFATE (CS, 150-60 MG/KG), 2,4,5-TRICHLOROPHENOXYACETIC ACID (2,4,5-T, 150-60 MG/KG)). LARGE-SCALE MOLECULAR CHANGES ELICITED BY THESE FOUR HEPATOTOXICANTS IN LIVER TISSUES WERE ANALYZED USING DNA MICROARRAY. THREE DAYS AFTER ADMINISTRATION, NO SIGNIFICANT PHENOTYPIC CHANGES WERE INDUCED BY THESE FOUR DIFFERENT HEPATOTOXICANTS IN TERMS OF HISTOLOGICAL EXAMINATION OR BLOOD BIOCHEMICAL ASSAY. HOWEVER, UNSUPERVISED HIERARCHICAL ANALYSIS OF GENE EXPRESSIONAL CHANGES INDUCED BY HEPATOTOXICANTS RESULTED IN TWO MAJOR GENE SUBCLUSTERS ON DENDROGRAM, I.E., A CARCINOGEN (VN, AD) AND NON-CARCINOGEN GROUP (CS, 2,4,5-T), AND ALSO REVEALED THAT DISTINCT MOLECULAR SIGNATURES EXIST. THESE SIGNATURES WERE FOUNDED ON WELL-DEFINED FUNCTIONAL GENE CATEGORIES AND MAY DIFFERENTIATE GENOTOXIC AND NON-GENOTOXIC CARCINOGENS. FURTHERMORE, VENN DIAGRAM ANALYSIS ALLOWED US TO IDENTIFY CARCINOGEN AND NON-CARCINOGEN-ASSOCIATED MOLECULAR SIGNATURES. USING STATISTICAL METHODS, WE ANALYZED OUTLIER GENES FOR FOUR DIFFERENT CLASSES (GENOTOXIC-, NON-GENOTOXIC-CARCINOGEN, GENOTOXIC-, NON-GENOTOXIC NON-CARCINOGEN) IN TERMS OF THEIR POTENTIAL TO PREDICT DIFFERENT MODES-OF-ACTION. IN CONCLUSION, THE IDENTIFICATION OF LARGE-SCALE MOLECULAR CHANGES IN DIFFERENT HEPATOCARCINOGEN EXPOSURE MODELS REVEALED THAT DIFFERENT TYPES OF HEPATOTOXICANTS ARE ASSOCIATED WITH DIFFERENT EPIGENETIC CHANGES AND MOLECULAR PATHWAYS AND THAT THESE LARGE-SCALE CHARACTERISTIC MOLECULAR CHANGES COULD BE USED AS PREDICTABLE TOXICITY MARKERS.	2008	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
8  4515  40 MULTI-OMICS APPROACHES FOR PRECISION OBESITY MANAGEMENT : POTENTIALS AND LIMITATIONS OF OMICS IN PRECISION PREVENTION, TREATMENT AND RISK REDUCTION OF OBESITY. INTRODUCTION: OBESITY IS A MULTIFACTORIAL CHRONIC DISEASE THAT CANNOT BE ADDRESSED BY SIMPLY PROMOTING BETTER DIETS AND MORE PHYSICAL ACTIVITY. TO DATE, NOT A SINGLE COUNTRY HAS SUCCESSFULLY BEEN ABLE TO CURB THE ACCUMULATING BURDEN OF OBESITY. ONE EXPLANATION FOR THE LACK OF PROGRESS IS THAT LIFESTYLE INTERVENTION PROGRAMS ARE TRADITIONALLY IMPLEMENTED WITHOUT A COMPREHENSIVE EVALUATION OF AN INDIVIDUAL'S DIAGNOSTIC BIOMARKERS. EVIDENCE FROM GENOME-WIDE ASSOCIATION STUDIES HIGHLIGHT THE IMPORTANCE OF GENETIC AND EPIGENETIC FACTORS IN THE DEVELOPMENT OF OBESITY AND HOW THEY IN TURN AFFECT THE TRANSCRIPTOME, METABOLITES, MICROBIOMES, AND PROTEOMES. OBJECTIVE: THE PURPOSE OF THIS REVIEW IS TO PROVIDE AN OVERVIEW OF THE DIFFERENT TYPES OF OMICS DATA: GENOMICS, EPIGENOMICS, TRANSCRIPTOMICS, PROTEOMICS, METABOLOMICS AND ILLUSTRATE HOW A MULTI-OMICS APPROACH CAN BE FUNDAMENTAL FOR THE IMPLEMENTATION OF PRECISION OBESITY MANAGEMENT. RESULTS: THE DIFFERENT TYPES OF OMICS DESIGNS ARE GROUPED INTO TWO CATEGORIES, THE GENOTYPE APPROACH AND THE PHENOTYPE APPROACH. WHEN APPLIED TO OBESITY PREVENTION AND MANAGEMENT, EACH OMICS TYPE COULD POTENTIALLY HELP TO DETECT SPECIFIC BIOMARKERS IN PEOPLE WITH RISK PROFILES AND GUIDE HEALTHCARE PROFESSIONALS AND DECISION MAKERS IN DEVELOPING INDIVIDUALIZED TREATMENT PLANS ACCORDING TO THE NEEDS OF THE INDIVIDUAL BEFORE THE ONSET OF OBESITY. CONCLUSION: INTEGRATING MULTI-OMICS APPROACHES WILL ENABLE A PARADIGM SHIFT FROM THE ONE SIZE FITS ALL APPROACH TOWARDS PRECISION OBESITY MANAGEMENT, I.E. (1) PRECISION PREVENTION OF THE ONSET OF OBESITY, (2) PRECISION MEDICINE AND TAILORED TREATMENT OF OBESITY, AND (3) PRECISION RISK REDUCTION AND PREVENTION OF SECONDARY DISEASES RELATED TO OBESITY.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
9  4832  26 OMICS BIOMARKERS IN OBESITY: NOVEL ETIOLOGICAL INSIGHTS AND TARGETS FOR PRECISION PREVENTION. PURPOSE OF REVIEW: OMICS-BASED TECHNOLOGIES WERE SUGGESTED TO PROVIDE AN ADVANCED UNDERSTANDING OF OBESITY ETIOLOGY AND ITS METABOLIC CONSEQUENCES. THIS REVIEW HIGHLIGHTS THE RECENT DEVELOPMENTS IN "OMICS"-BASED RESEARCH AIMED TO IDENTIFY OBESITY-RELATED BIOMARKERS. RECENT FINDINGS: RECENT ADVANCES IN OBESITY AND METABOLISM RESEARCH INCREASINGLY RELY ON NEW TECHNOLOGIES TO IDENTIFY MECHANISMS IN THE DEVELOPMENT OF OBESITY USING VARIOUS "OMICS" PLATFORMS. GENETIC AND EPIGENETIC BIOMARKERS THAT TRANSLATE INTO CHANGES IN TRANSCRIPTOME, PROTEOME, AND METABOLOME COULD SERVE AS TARGETS FOR OBESITY PREVENTION. DESPITE A NUMBER OF PROMISING CANDIDATE BIOMARKERS, THERE IS AN INCREASED DEMAND FOR LARGER PROSPECTIVE COHORT STUDIES TO VALIDATE FINDINGS AND DETERMINE BIOMARKER REPRODUCIBILITY BEFORE THEY CAN FIND APPLICATIONS IN PRIMARY CARE AND PUBLIC HEALTH. "OMICS" BIOMARKERS HAVE ADVANCED OUR KNOWLEDGE ON THE ETIOLOGY OF OBESITY AND ITS LINKS WITH CHRONIC DISEASES. THEY BRING SUBSTANTIAL PROMISE IN IDENTIFYING EFFECTIVE PUBLIC HEALTH STRATEGIES THAT PAVE THE WAY TOWARDS PATIENT STRATIFICATION AND PRECISION PREVENTION.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
10  4344  27 MINIREVIEW: TRANSLATIONAL ANIMAL MODELS OF HUMAN MENOPAUSE: CHALLENGES AND EMERGING OPPORTUNITIES. INCREASING IMPORTANCE IS PLACED ON THE TRANSLATIONAL VALIDITY OF ANIMAL MODELS OF HUMAN MENOPAUSE TO DISCERN RISK VS. BENEFIT FOR PREDICTION OF OUTCOMES AFTER THERAPEUTIC INTERVENTIONS AND TO DEVELOP NEW THERAPEUTIC STRATEGIES TO PROMOTE HEALTH. BASIC DISCOVERY RESEARCH CONDUCTED OVER MANY DECADES HAS BUILT AN EXTENSIVE BODY OF KNOWLEDGE REGARDING REPRODUCTIVE SENESCENCE ACROSS MAMMALIAN SPECIES UPON WHICH TO ADVANCE ANIMAL MODELS OF HUMAN MENOPAUSE. MODIFICATIONS TO EXISTING ANIMAL MODELS COULD RAPIDLY ADDRESS TRANSLATIONAL GAPS RELEVANT TO CLINICAL ISSUES IN HUMAN MENOPAUSAL HEALTH, WHICH INCLUDE THE IMPACT OF 1) CHRONIC OVARIAN HORMONE DEPRIVATION AND HORMONE THERAPY, 2) CLINICALLY RELEVANT HORMONE THERAPY REGIMENS (CYCLIC VS. CONTINUOUS COMBINED), 3) CLINICALLY RELEVANT HORMONE THERAPY FORMULATIONS, AND 4) WINDOWS OF OPPORTUNITY AND OPTIMAL DURATION OF INTERVENTIONS. MODIFICATIONS IN EXISTING ANIMAL MODELS TO MORE ACCURATELY REPRESENT HUMAN MENOPAUSE AND CLINICAL INTERVENTIONS COULD RAPIDLY PROVIDE PRECLINICAL TRANSLATIONAL DATA TO PREDICT OUTCOMES REGARDING UNRESOLVED CLINICAL ISSUES RELEVANT TO WOMEN'S MENOPAUSAL HEALTH. DEVELOPMENT OF THE NEXT GENERATION OF ANIMAL MODELS OF HUMAN MENOPAUSE COULD LEVERAGE ADVANCES IN IDENTIFYING GENOTYPIC VARIATIONS IN ESTROGEN AND PROGESTERONE RECEPTORS TO DEVELOP PERSONALIZED MENOPAUSAL CARE AND TO PREDICT OUTCOMES OF INTERVENTIONS FOR PROTECTION AGAINST OR VULNERABILITY TO DISEASE. KEY TO THE SUCCESS OF THESE MODELS IS THE CLOSE COUPLING BETWEEN THE TRANSLATIONAL TARGET AND THE RANGE OF PREDICTIVE VALIDITY. PRECLINICAL TRANSLATIONAL ANIMAL MODELS OF HUMAN MENOPAUSE NEED TO KEEP PACE WITH CHANGES IN CLINICAL PRACTICE. WITH FOCUS ON PREDICTIVE VALIDITY AND STRATEGIC USE OF ADVANCES IN GENETIC AND EPIGENETIC SCIENCE, NEW ANIMAL MODELS OF HUMAN MENOPAUSE HAVE THE OPPORTUNITY TO SET NEW DIRECTIONS FOR MENOPAUSAL CLINICAL CARE FOR WOMEN WORLDWIDE.	2012	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
11   103  34 A REHABILOMICS FRAMEWORK FOR PERSONALIZED AND TRANSLATIONAL REHABILITATION RESEARCH AND CARE FOR INDIVIDUALS WITH DISABILITIES: PERSPECTIVES AND CONSIDERATIONS FOR SPINAL CORD INJURY. DESPITE MANY PEOPLE HAVING SIMILAR CLINICAL PRESENTATION, DEMOGRAPHIC FACTORS, AND CLINICAL CARE, OUTCOME CAN DIFFER FOR THOSE SUSTAINING SIGNIFICANT INJURY SUCH AS SPINAL CORD INJURY (SCI) AND TRAUMATIC BRAIN INJURY (TBI). IN ADDITION TO TRADITIONAL DEMOGRAPHIC, SOCIAL, AND CLINICAL FACTORS, VARIABILITY ALSO MAY BE ATTRIBUTABLE TO INNATE (INCLUDING GENETIC, TRANSCRIPTOMIC PROTEOMIC, EPIGENETIC) BIOLOGICAL VARIATION THAT INDIVIDUALS BRING TO RECOVERY AND THEIR UNIQUE RESPONSE TO THEIR CARE AND ENVIRONMENT. TECHNOLOGIES COLLECTIVELY CALLED "-OMICS" ENABLE SIMULTANEOUS MEASUREMENT OF AN ENORMOUS NUMBER OF BIOMOLECULES THAT CAN CAPTURE MANY POTENTIAL BIOLOGICAL CONTRIBUTORS TO HETEROGENEITY OF INJURY/DISEASE COURSE AND OUTCOME. DUE TO THE NATURE OF INJURY AND COMPLEX DISEASE, AND ITS ASSOCIATIONS WITH IMPAIRMENT, DISABILITY, AND RECOVERY, REHABILITATION DOES NOT LEND ITSELF TO A SINGULAR "PROTOCOLIZED" PLAN OF THERAPY. YET, BY NATURE AND BY NECESSITY, REHABILITATION MEDICINE OPERATES AS A FUNCTIONAL MODEL OF "PERSONALIZED CARE". THUS, THE CHALLENGE FOR SUCCESSFUL PROGRAMS OF TRANSLATIONAL REHABILITATION CARE AND RESEARCH IS TO IDENTIFY VIABLE APPROACHES TO EXAMINE BROAD POPULATIONS, WITH VARIED IMPAIRMENTS AND FUNCTIONAL LIMITATIONS, AND TO IDENTIFY EFFECTIVE TREATMENT RESPONSES THAT INCORPORATE PERSONALIZED PROTOCOLS TO OPTIMIZE FUNCTIONAL RECOVERY. THE REHABILOMICS FRAMEWORK IS A TRANSLATIONAL MODEL THAT PROVIDES AN "-OMICS" OVERLAY TO THE SCIENTIFIC STUDY OF REHABILITATION PROCESSES AND MULTIDIMENSIONAL OUTCOMES. REHABILOMICS RESEARCH PROVIDES NOVEL OPPORTUNITIES TO EVALUATE THE NEUROBIOLOGY OF COMPLEX INJURY OR CHRONIC DISEASE AND CAN BE USED TO EXAMINE METHODS AND TREATMENTS FOR PERSON-CENTERED CARE AMONG POPULATIONS WITH DISABILITIES. EXEMPLARS FOR APPLICATION IN SCI AND OTHER NEUROREHABILITATION POPULATIONS ARE DISCUSSED.	2014	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
12  6462  50 TISSUE AND CIRCULATING MICRORNAS AS BIOMARKERS OF RESPONSE TO OBESITY TREATMENT STRATEGIES. BACKGROUND: OBESITY, CHARACTERIZED BY AN INCREASED AMOUNT OF ADIPOSE TISSUE, IS A METABOLIC CHRONIC ALTERATION WHICH HAS REACHED PANDEMIC PROPORTION. LIFESTYLE CHANGES ARE THE FIRST LINE THERAPY FOR OBESITY AND A LARGE VARIETY OF DIETARY APPROACHES HAVE DEMONSTRATED EFFICACY IN PROMOTING WEIGHT LOSS AND IMPROVING OBESITY-RELATED METABOLIC ALTERATIONS. BESIDES DIET AND PHYSICAL ACTIVITY, BARIATRIC SURGERY MIGHT BE AN EFFECTIVE THERAPEUTIC STRATEGY FOR MORBID OBESE PATIENTS. RESPONSE TO WEIGHT-LOSS INTERVENTIONS IS CHARACTERISED BY HIGH INTER-INDIVIDUAL VARIABILITY, WHICH MIGHT INVOLVE EPIGENETIC FACTORS. MICRORNAS HAVE CRITICAL ROLES IN METABOLIC PROCESSES AND THEIR DYSREGULATED EXPRESSION HAS BEEN REPORTED IN OBESITY. AIM: THE AIM OF THIS REVIEW IS TO PROVIDE A COMPREHENSIVE OVERVIEW OF CURRENT STUDIES EVALUATING CHANGES IN MICRORNA EXPRESSION IN OBESE PATIENTS UNDERGOING LIFESTYLE INTERVENTIONS OR BARIATRIC SURGERY. RESULTS: A CONSIDERABLE NUMBER OF STUDIES HAVE REPORTED A DIFFERENTIAL EXPRESSION OF CIRCULATING MICRORNAS BEFORE AND AFTER VARIOUS DIETARY AND BARIATRIC SURGERY APPROACHES, IDENTIFYING SEVERAL CANDIDATE BIOMARKERS OF RESPONSE TO WEIGHT LOSS. SIGNIFICANT CHANGES IN MICRORNA EXPRESSION HAVE BEEN OBSERVED AT A TISSUE LEVEL AS WELL, WITH ENTIRELY DIFFERENT PATTERNS BETWEEN VISCERAL AND SUBCUTANEOUS ADIPOSE TISSUE. INTERESTINGLY, RELEVANT DIFFERENCES IN MICRORNA EXPRESSION HAVE EMERGED BETWEEN RESPONDERS AND NON-RESPONDERS TO DIETARY OR SURGICAL INTERVENTIONS. A WIDE VARIETY OF DYSREGULATED MICRORNA TARGET PATHWAYS HAVE ALSO BEEN IDENTIFIED, HELPING TO UNDERSTAND THE PATHOPHYSIOLOGICAL MECHANISMS UNDERLYING OBESITY AND OBESITY-RELATED METABOLIC DISEASES. CONCLUSIONS: ALTHOUGH FURTHER RESEARCH IS NEEDED TO DRAW FIRM CONCLUSIONS, THERE IS INCREASING EVIDENCE ABOUT MICRORNAS AS POTENTIAL BIOMARKERS FOR WEIGHT LOSS AND RESPONSE TO INTERVENTION STRATEGIES IN OBESITY.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
13    29  28 A BIOPSYCHOSOCIAL OVERVIEW OF THE OPIOID CRISIS: CONSIDERING NUTRITION AND GASTROINTESTINAL HEALTH. THE OPIOID CRISIS HAS REACHED EPIDEMIC PROPORTIONS IN THE UNITED STATES WITH RISING OVERDOSE DEATH RATES. IDENTIFYING THE UNDERLYING FACTORS THAT CONTRIBUTE TO ADDICTION VULNERABILITY MAY LEAD TO MORE EFFECTIVE PREVENTION STRATEGIES. SUPPLY SIDE ENVIRONMENTAL FACTORS ARE A MAJOR CONTRIBUTING COMPONENT. PSYCHOSOCIAL FACTORS SUCH AS STRESS, TRAUMA, AND ADVERSE CHILDHOOD EXPERIENCES HAVE BEEN LINKED TO EMOTIONAL PAIN LEADING TO SELF-MEDICATION. GENETIC AND EPIGENETIC FACTORS ASSOCIATED WITH BRAIN REWARD PATHWAYS AND IMPULSIVITY ARE KNOWN PREDICTORS OF ADDICTION VULNERABILITY. THIS REVIEW ATTEMPTS TO PRESENT A BIOPSYCHOSOCIAL APPROACH THAT CONNECTS VARIOUS SOCIAL AND BIOLOGICAL THEORIES RELATED TO THE ADDICTION CRISIS. THE EMERGING ROLE OF NUTRITION THERAPY WITH AN EMPHASIS ON GASTROINTESTINAL HEALTH IN THE TREATMENT OF OPIOID USE DISORDER IS PRESENTED. THE BIOPSYCHOSOCIAL MODEL INTEGRATES CONCEPTS FROM SEVERAL DISCIPLINES, EMPHASIZING MULTICAUSALITY RATHER THAN A REDUCTIONIST APPROACH. POTENTIAL SOLUTIONS AT MULTIPLE LEVELS ARE PRESENTED, CONSIDERING INDIVIDUAL AS WELL AS POPULATION HEALTH. THIS SINGLE COHESIVE FRAMEWORK IS BASED ON THE INTERDEPENDENCY OF THE ENTIRE SYSTEM, IDENTIFYING RISK AND PROTECTIVE FACTORS THAT MAY INFLUENCE SUBSTANCE-SEEKING BEHAVIOR. NUTRITION SHOULD BE INCLUDED AS ONE FACET OF A MULTIDISCIPLINARY APPROACH TOWARD IMPROVED RECOVERY OUTCOMES. CROSS-DISCIPLINARY COLLABORATIVE EFFORTS, NEW IDEAS, AND FISCAL RESOURCES WILL BE CRITICAL TO ADDRESS THE EPIDEMIC.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                       
14  6478  28 TOPICAL REVIEW: THE EMERGING FIELD OF EPIGENETICS: INFORMING MODELS OF PEDIATRIC TRAUMA AND PHYSICAL HEALTH. OBJECTIVE: TRAUMA EXPERIENCED DURING CHILDHOOD AND ADOLESCENCE HAS BEEN LINKED TO A NUMBER OF CHRONIC MEDICAL CONCERNS. WE HIGHLIGHT MAJOR FINDINGS FROM THE PEDIATRIC TRAUMA LITERATURE TO PROVIDE A MODEL FOR UNDERSTANDING THIS ASSOCIATION. METHODS: STUDIES EXAMINING THE EFFECTS OF TRAUMA WERE SYSTEMATICALLY REVIEWED AND SYNTHESIZED INTO A MODEL PROPOSING A CENTRAL ROLE FOR EPIGENETICS IN THE WAYS THAT CHILDHOOD EXPERIENCES CAN AFFECT HEALTH. RESULTS: EARLY HYPOTHALAMIC PITUITARY ADRENAL (HPA) AXIS RESPONSE MAY IMPACT INITIAL TRAUMA EXPERIENCE, WITH DOWNSTREAM EFFECTS ON POSTTRAUMA ADJUSTMENT REFLECTED IN POSTTRAUMA NEUROBIOLOGY, PSYCHOLOGICAL HEALTH, AND PHYSICAL HEALTH. CONCLUSIONS: PROSPECTIVE RESEARCH WITH CHILDREN AND ADOLESCENTS EXPOSED TO TRAUMA IS NEEDED TO BETTER CHARACTERIZE THE GENETIC AND EPIGENETIC INFLUENCES ON THE COURSE OF HPA AND IMMUNE PROCESSES AS RELATED TO POSTTRAUMA PSYCHOLOGICAL AND PHYSICAL HEALTH OUTCOMES.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
15  6894  25 [SOCIAL INEQUALITY AND MENTAL HEALTH]. SOCIAL INEQUALITY REFERS TO THE INEQUITABLE DISTRIBUTION OF SOCIAL PROSPERITY INCLUDING THE RESOURCE OF HEALTH. THE RELATIONSHIP BETWEEN SOCIAL INEQUALITY AND MENTAL HEALTH CAN BE ESTABLISHED BY MEANS OF INDICATORS OF SOCIAL INEQUALITY THROUGHOUT ALL AGE GROUPS IN GERMANY. THERE ARE SOCIAL GRADIENTS OF MENTAL HEALTH ON THE POPULATION LEVEL, I.E. THE LINEAR RELATIONSHIP BETWEEN SOCIAL CLASSES OR STATUS AND STATE OF HEALTH. FUNDAMENTAL DETERMINANTS OF HEALTH DISPARITY ARE CULTURAL, SOCIAL, POLITICAL, AND GEOGRAPHICAL CONDITIONS, WHICH INTERACT WITH THE GENETIC MAKE-UP AND EPIGENETIC PROCESSES. THESE DETERMINANTS ALSO INFLUENCE THE MANAGEMENT OF DEVELOPMENTAL TASKS DURING THE LIFE COURSE AND ARE OF UTMOST IMPORTANCE FOR THE DEVELOPMENT OF MENTAL DISORDERS. THE MALADAPTATION TO CHRONIC STRESS IS AT THE CORE OF HEALTH DISPARITY. INTERVENTIONS AT THE INDIVIDUAL BEHAVIORAL LEVEL SHOULD COMPRISE THE DEVELOPMENT OF STRESS MANAGEMENT AND COPING STRATEGIES.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
16  5224  37 PRIORITIZED RESEARCH FOR THE PREVENTION, TREATMENT, AND REVERSAL OF CHRONIC DISEASE: RECOMMENDATIONS FROM THE LIFESTYLE MEDICINE RESEARCH SUMMIT. DECLINING LIFE EXPECTANCY AND INCREASING ALL-CAUSE MORTALITY IN THE UNITED STATES HAVE BEEN ASSOCIATED WITH UNHEALTHY BEHAVIORS, SOCIOECOLOGICAL FACTORS, AND PREVENTABLE DISEASE. A GROWING BODY OF BASIC SCIENCE, CLINICAL RESEARCH, AND POPULATION HEALTH EVIDENCE POINTS TO THE BENEFITS OF HEALTHY BEHAVIORS, ENVIRONMENTS AND POLICIES TO MAINTAIN HEALTH AND PREVENT, TREAT, AND REVERSE THE ROOT CAUSES OF COMMON CHRONIC DISEASES. SIMILARLY, INNOVATIONS IN RESEARCH METHODOLOGIES, STANDARDS OF EVIDENCE, EMERGENCE OF UNIQUE STUDY COHORTS, AND BREAKTHROUGHS IN DATA ANALYTICS AND MODELING CREATE NEW POSSIBILITIES FOR PRODUCING BIOMEDICAL KNOWLEDGE AND CLINICAL TRANSLATION. TO UNDERSTAND THESE ADVANCES AND INFORM FUTURE DIRECTIONS RESEARCH, THE LIFESTYLE MEDICINE RESEARCH SUMMIT WAS CONVENED AT THE UNIVERSITY OF PITTSBURGH ON DECEMBER 4-5, 2019. THE SUMMIT'S GOAL WAS TO REVIEW CURRENT STATUS AND DEFINE RESEARCH PRIORITIES IN THE SIX CORE AREAS OF LIFESTYLE MEDICINE: PLANT-PREDOMINANT NUTRITION, PHYSICAL ACTIVITY, SLEEP, STRESS, ADDICTIVE BEHAVIORS, AND POSITIVE PSYCHOLOGY/SOCIAL CONNECTION. FORTY INVITED SUBJECT MATTER EXPERTS (1) REVIEWED EXISTING KNOWLEDGE AND GAPS RELATING LIFESTYLE BEHAVIORS TO COMMON CHRONIC DISEASES, SUCH AS CARDIOVASCULAR DISEASE, DIABETES, MANY CANCERS, INFLAMMATORY- AND IMMUNE-RELATED DISORDERS AND OTHER CONDITIONS; AND (2) DISCUSSED THE POTENTIAL FOR APPLYING CUTTING-EDGE MOLECULAR, CELLULAR, EPIGENETIC AND EMERGING SCIENCE KNOWLEDGE AND COMPUTATIONAL METHODOLOGIES, RESEARCH DESIGNS, AND STUDY COHORTS TO ACCELERATE CLINICAL APPLICATIONS ACROSS ALL SIX DOMAINS OF LIFESTYLE MEDICINE. NOTABLY, FEDERAL HEALTH AGENCIES, SUCH AS THE DEPARTMENT OF DEFENSE AND VETERANS ADMINISTRATION HAVE BEGUN TO ADOPT "WHOLE-PERSON HEALTH AND PERFORMANCE" MODELS THAT ADDRESS THESE LIFESTYLE AND ENVIRONMENTAL ROOT CAUSES OF CHRONIC DISEASE AND ASSOCIATED MORBIDITY, MORTALITY, AND COST. RECOMMENDATIONS STRONGLY SUPPORT LEVERAGING EMERGING RESEARCH METHODOLOGIES, SYSTEMS BIOLOGY, AND COMPUTATIONAL MODELING IN ORDER TO ACCELERATE EFFECTIVE CLINICAL AND POPULATION SOLUTIONS TO IMPROVE HEALTH AND REDUCE SOCIETAL COSTS. NEW AND ALTERNATIVE HIERARCHIES OF EVIDENCE ARE ALSO BE NEEDED IN ORDER TO ASSESS THE QUALITY OF EVIDENCE AND DEVELOP EVIDENCE-BASED GUIDELINES ON LIFESTYLE MEDICINE. CHILDREN AND UNDERSERVED POPULATIONS WERE IDENTIFIED AS PRIORITIZED GROUPS TO STUDY. THE COVID-19 PANDEMIC, WHICH DISPROPORTIONATELY IMPACTS PEOPLE WITH CHRONIC DISEASES THAT ARE AMENABLE TO EFFECTIVE LIFESTYLE MEDICINE INTERVENTIONS, MAKES THE SUMMIT'S FINDINGS AND RECOMMENDATIONS FOR FUTURE RESEARCH PARTICULARLY TIMELY AND RELEVANT.	2020	

17  3606  29 IMPROVING TREATMENT OF NEURODEVELOPMENTAL DISORDERS: RECOMMENDATIONS BASED ON PRECLINICAL STUDIES. INTRODUCTION: NEURODEVELOPMENTAL DISORDERS (NDDS) ARE COMMON AND SEVERELY DEBILITATING. THEIR CHRONIC NATURE AND RELIANCE ON BOTH GENETIC AND ENVIRONMENTAL FACTORS MAKES STUDYING NDDS AND THEIR TREATMENT A CHALLENGING TASK. AREAS COVERED: HEREIN, THE AUTHORS DISCUSS THE NEUROBIOLOGICAL MECHANISMS OF NDDS, AND PRESENT RECOMMENDATIONS ON THEIR TRANSLATIONAL RESEARCH AND THERAPY, OUTLINED BY THE INTERNATIONAL STRESS AND BEHAVIOR SOCIETY. VARIOUS DRUGS CURRENTLY PRESCRIBED TO TREAT NDDS ALSO REPRESENT A HIGHLY DIVERSE GROUP. ACTING ON VARIOUS NEUROTRANSMITTER AND PHYSIOLOGICAL SYSTEMS, THESE DRUGS OFTEN LACK SPECIFICITY OF ACTION, AND ARE COMMONLY USED TO TREAT MULTIPLE OTHER PSYCHIATRIC CONDITIONS. THERE HAS ALSO BEEN RELATIVELY LITTLE PROGRESS IN THE DEVELOPMENT OF NOVEL MEDICATIONS TO TREAT NDDS. BASED ON CLINICAL, PRECLINICAL AND TRANSLATIONAL MODELS OF NDDS, OUR RECOMMENDATIONS COVER A WIDE RANGE OF METHODOLOGICAL APPROACHES AND CONCEPTUAL STRATEGIES. EXPERT OPINION: TO IMPROVE PHARMACOTHERAPY AND DRUG DISCOVERY FOR NDDS, WE NEED A STRONGER EMPHASIS ON TARGETING MULTIPLE ENDOPHENOTYPES, A BETTER DISSECTION OF GENETIC/EPIGENETIC FACTORS OR "HIDDEN HERITABILITY," AND A CAREFUL CONSIDERATION OF POTENTIAL DEVELOPMENTAL/TROPHIC ROLES OF BRAIN NEUROTRANSMITTERS. THE VALIDITY OF ANIMAL NDD MODELS CAN BE IMPROVED THROUGH DISCOVERY OF NOVEL (BEHAVIORAL, PHYSIOLOGICAL AND NEUROIMAGING) BIOMARKERS, APPLYING PROPER ENVIRONMENTAL ENRICHMENT, WIDENING THE SPECTRUM OF MODEL ORGANISMS, TARGETING DEVELOPMENTAL TRAJECTORIES OF NDD-RELATED BEHAVIORS AND COMORBID CONDITIONS BEYOND TRADITIONAL NDDS. WHILE THESE RECOMMENDATIONS CANNOT BE ADDRESSED ALL IN ONCE, OUR INCREASED UNDERSTANDING OF NDD PATHOBIOLOGY MAY TRIGGER INNOVATIVE CROSS-DISCIPLINARY RESEARCH EXPANDING BEYOND TRADITIONAL METHODS AND CONCEPTS.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
18  3926  33 LITERATURE REVIEW AND METHODOLOGICAL CONSIDERATIONS FOR UNDERSTANDING CIRCULATING RISK BIOMARKERS FOLLOWING TRAUMA EXPOSURE. EXPOSURE TO TRAUMATIC EVENTS IS COMMON. WHILE MANY INDIVIDUALS RECOVER FOLLOWING TRAUMA EXPOSURE, A SUBSTANTIAL SUBSET DEVELOP ADVERSE POSTTRAUMATIC NEUROPSYCHIATRIC SEQUELAE (APNS) SUCH AS POSTTRAUMATIC STRESS, MAJOR DEPRESSION, AND REGIONAL OR WIDESPREAD CHRONIC MUSCULOSKELETAL PAIN. APNS CAUSE SUBSTANTIAL BURDEN TO THE INDIVIDUAL AND TO SOCIETY, CAUSING FUNCTIONAL IMPAIRMENT AND PHYSICAL DISABILITY, RISK FOR SUICIDE, LOST WORKDAYS, AND INCREASED HEALTH CARE COSTS. CONTEMPORARY TREATMENT IS LIMITED BY AN INABILITY TO IDENTIFY INDIVIDUALS AT HIGH RISK OF APNS IN THE IMMEDIATE AFTERMATH OF TRAUMA, AND AN INABILITY TO IDENTIFY OPTIMAL TREATMENTS FOR INDIVIDUAL PATIENTS. OUR PURPOSE IS TO PROVIDE A COMPREHENSIVE REVIEW DESCRIBING CANDIDATE BLOOD-BASED BIOMARKERS THAT MAY HELP TO IDENTIFY THOSE AT HIGH RISK OF APNS AND/OR GUIDE INDIVIDUAL INTERVENTION DECISION-MAKING. SUCH BLOOD-BASED BIOMARKERS INCLUDE CIRCULATING BIOLOGICAL FACTORS SUCH AS HORMONES, PROTEINS, IMMUNE MOLECULES, NEUROPEPTIDES, NEUROTRANSMITTERS, MRNA, AND NONCODING RNA EXPRESSION SIGNATURES, WHILE WE DO NOT REVIEW GENETIC AND EPIGENETIC BIOMARKERS DUE TO OTHER RECENT REVIEWS OF THIS TOPIC. THE CURRENT STATE OF THE LITERATURE ON CIRCULATING RISK BIOMARKERS OF APNS IS SUMMARIZED, AND KEY CONSIDERATIONS AND CHALLENGES FOR THEIR DISCOVERY AND TRANSLATION ARE DISCUSSED. WE ALSO DESCRIBE THE AURORA STUDY, A SPECIFIC EXAMPLE OF CURRENT SCIENTIFIC EFFORTS TO IDENTIFY SUCH CIRCULATING RISK BIOMARKERS AND THE LARGEST STUDY TO DATE FOCUSED ON IDENTIFYING RISK AND PROGNOSTIC FACTORS IN THE AFTERMATH OF TRAUMA EXPOSURE.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                              
19   107  31 A REVIEW OF PRE-CLINICAL MODELS FOR GULF WAR ILLNESS. GULF WAR ILLNESS (GWI) IS A CHRONIC MULTISYMPTOMATIC DISORDER THAT AFFLICTS OVER 1/3RD OF THE 1991 GW VETERANS. IT SPANS MULTIPLE BODILY SYSTEMS AND PRESENTS ITSELF AS A SYNDROME EXHIBITING DIVERSE SYMPTOMS INCLUDING FATIGUE, DEPRESSION, MOOD, AND MEMORY AND CONCENTRATION DEFICITS, MUSCULOSKELETAL PAIN AND GASTROINTESTINAL DISTRESS IN GW VETERANS. THE ETIOLOGY OF GWI IS COMPLEX AND MANY FACTORS, INCLUDING CHEMICAL, PHYSIOLOGICAL, AND ENVIRONMENTAL STRESSORS PRESENT IN THE GW ARENA, HAVE BEEN IMPLICATED FOR ITS DEVELOPMENT. IT HAS BEEN OVER 30 YEARS SINCE THE END OF THE GW BUT, GWI HAS BEEN PERSISTENT IN SUFFERING VETERANS WHO ARE ALSO DEALING WITH PAUCITY OF EFFECTIVE TREATMENTS. THE MULTIFACTORIAL ASPECT OF GWI ALONG WITH GENETIC HETEROGENEITY AND LACK OF AVAILABLE DATA SURROUNDING WAR-TIME EXPOSURES HAVE PROVED TO BE CHALLENGING IN DEVELOPING PRE-CLINICAL MODELS OF GWI. DESPITE THIS, OVER A DOZEN GWI ANIMAL MODELS EXIST IN THE LITERATURE. IN THIS ARTICLE, FOLLOWING A BRIEF DISCUSSION OF GW HISTORY, GWI DEFINITIONS, AND PROBABLE CAUSES FOR ITS PATHOGENESIS, WE WILL EXPAND UPON VARIOUS EXPERIMENTAL MODELS USED IN GWI LABORATORY RESEARCH. THESE ANIMAL MODELS WILL BE DISCUSSED IN THE CONTEXT OF THEIR ATTEMPTS AT MIMICKING GW-RELATED EXPOSURES WITH REGARDS TO THE VARIATIONS IN CHEMICAL COMBINATIONS, DOSES, AND FREQUENCY OF EXPOSURES. WE WILL DISCUSS THEIR ADVANTAGES AND LIMITATIONS IN MODELING GWI FOLLOWED BY A DISCUSSION OF BEHAVIORAL AND MOLECULAR FINDINGS IN THESE MODELS. THE MECHANISTIC DATA OBTAINED FROM THESE PRECLINICAL STUDIES HAVE OFFERED MULTIPLE MOLECULAR PATHWAYS INCLUDING CHRONIC INFLAMMATION, MITOCHONDRIAL DYSFUNCTION, OXIDATIVE STRESS, LIPID DISTURBANCES, CALCIUM HOMEOSTATIC ALTERATIONS, CHANGES IN GUT MICROBIOTA, AND EPIGENETIC MODIFICATIONS, AMONGST OTHERS FOR EXPLAINING GWI DEVELOPMENT AND ITS PERSISTENCE. FINALLY, THESE FINDINGS HAVE ALSO INFORMED US ON NOVEL DRUGGABLE TARGETS IN GWI. WHILE, IT HAS BEEN DIFFICULT TO CONCEIVE A SINGLE PRE-CLINICAL MODEL THAT COULD EXPRESS ALL THE GWI SIGNS AND EXHIBIT BIOLOGICAL COMPLEXITY REFLECTIVE OF THE CLINICAL PRESENTATION IN GWI, ANIMAL MODELS HAVE BEEN CRITICAL FOR IDENTIFYING MOLECULAR UNDERPINNINGS OF GWI AND EVALUATING TREATMENT STRATEGIES FOR GWI.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
20  1058  29 CLINICAL MEASURES OF ALLOSTATIC LOAD IN CHILDREN AND ADOLESCENTS WITH FOOD ALLERGY, DEPRESSION, OR ANXIETY. PURPOSE: SUSTAINED HIGH STRESS EXPOSURE RESULTS IN CHRONIC ACTIVATION OF THE STRESS RESPONSE SYSTEM, DYSREGULATED STRESS RESPONSES, HIGH ALLOSTATIC LOAD, AND POOR LATER-LIFE HEALTH. CHILDREN AND ADOLESCENTS WITH CHRONIC HEALTH CONDITIONS FACE STRESSORS RELATED TO THEIR CONDITION IN ADDITION TO THOSE TYPICAL OF CHILDHOOD AND ADOLESCENCE, PLACING THEM AT RISK OF HIGH ALLOSTATIC LOAD. THE PURPOSE OF THIS SECONDARY ANALYSIS WAS TO EXAMINE WHETHER YOUTH WITH CHRONIC HEALTH CONDITIONS DIFFER FROM CONTROLS ON CLINICAL MEASURES OF ALLOSTATIC LOAD. DESIGN AND METHODS: A SECONDARY ANALYSIS OF TWO DATASETS, THE ELECTRONIC HEALTH RECORD OF A TERTIARY CHILDREN'S HOSPITAL AND DATA FROM THE SURVEY OF THE HEALTH OF WISCONSIN, COMPARED YOUTH WITH CHRONIC HEALTH CONDITIONS TO CONTROLS ON CLINICAL MEASURES OF ALLOSTATIC LOAD. ADDITIONAL ANALYSES EXPLORED WHETHER PARENTAL STRESS AND MENTAL HEALTH INFLUENCED THESE RELATIONSHIPS. RESULTS: ANALYSES IDENTIFIED DIFFERENCES IN BMI, BLOOD PRESSURE, AND WAIST CIRCUMFERENCE BETWEEN YOUTH WITH FOOD ALLERGY, ANXIETY, OR DEPRESSION, AND CONTROLS. THESE RELATIONSHIPS DIFFERED FOR MALES AND FEMALES AND FOR THOSE WITH COMORBID MENTAL AND PHYSICAL CONDITIONS, AND WERE INFLUENCED BY PARENT STRESS AND MENTAL HEALTH. CONCLUSIONS: RESULTS SUPPORT FUTURE STUDIES EXPLORING WHETHER HIGH STRESS IN YOUTH WITH CHRONIC HEALTH CONDITIONS LEADS TO INCREASED ALLOSTATIC LOAD. INCORPORATING BIOMARKERS AS WELL AS GENETIC AND EPIGENETIC FACTORS WILL PROVIDE CRITICAL INSIGHTS. PRACTICE IMPLICATIONS: YOUTH WITH MENTAL AND PHYSICAL CHCS MAY BE AT INCREASED RISK OF HIGH ALLOSTATIC LOAD, REFLECTED IN CLINICAL MEASURES OF METABOLISM, AND SHOULD HAVE REGULAR ASSESSMENTS OF THEIR METABOLIC HEALTH.	2021