1 380 133 AN EPIGENETIC PERSPECTIVE ON LIFESTYLE MEDICINE FOR DEPRESSION: IMPLICATIONS FOR PRIMARY CARE PRACTICE. DEPRESSION IS THE MOST COMMON PRESENTING MENTAL HEALTH DISORDER IN PRIMARY CARE. IT IS ALSO A MAJOR CONTRIBUTOR TO SOMATIC COMPLAINTS, WORSENING OF CHRONIC MEDICAL CONDITIONS, POOR QUALITY OF LIFE, AND SUICIDE. CURRENT PHARMACOLOGIC AND PSYCHOTHERAPEUTIC APPROACHES AVERT LESS THAN HALF OF DEPRESSION'S CUMULATIVE BURDEN ON SOCIETY. HOWEVER, THERE IS A GROWING BODY OF RESEARCH DESCRIBING BOTH HOW MALADAPTIVE LIFESTYLE CHOICES CONTRIBUTE TO THE DEVELOPMENT AND WORSENING OF DEPRESSION AND HOW LIFESTYLE-ORIENTED MEDICAL INTERVENTIONS CAN REDUCE THE INCIDENCE AND SEVERITY OF DEPRESSION. THIS RESEARCH, LARGELY DERIVED FROM AN EMERGING FIELD CALLED EPIGENETICS, ELUCIDATES THE INTERACTIONS BETWEEN OUR LIFESTYLE CHOICES AND THOSE EPIGENETIC FACTORS WHICH MEDIATE OUR TENDENCIES TOWARD EITHER HEALTH, OR THE ONSET, IF NOT WORSENING OF DISEASE. THE PRESENT REVIEW HIGHLIGHTS HOW LIFESTYLE CHOICES INVOLVING DIET, PHYSICAL ACTIVITY, SLEEP, SOCIAL RELATIONSHIPS, AND STRESS INFLUENCE EPIGENETIC PROCESSES POSITIVELY OR NEGATIVELY, AND THEREBY PLAY A SIGNIFICANT ROLE IN DETERMINING WHETHER ONE DOES OR DOES NOT SUFFER FROM DEPRESSION. THE AUTHORS PROPOSE THAT MEDICAL TRAINING PROGRAMS CONSIDER AND ADOPT LIFESTYLE MEDICINE ORIENTED INSTRUCTIONAL INITIATIVES THAT WILL ENABLE TOMORROW'S PRIMARY CARE PROVIDERS TO MORE EFFECTIVELY IDENTIFY AND THERAPEUTICALLY INTERVENE IN THE MALADAPTIVE CHOICES CONTRIBUTING TO THEIR PATIENTS' DEPRESSION. 2022 2 5280 27 PROMOTING SYMPATHOVAGAL BALANCE IN MULTIPLE SCLEROSIS; PHARMACOLOGICAL, NON-PHARMACOLOGICAL, AND SURGICAL STRATEGIES. ACCUMULATED EVIDENCE SUGGESTS THAT CARDIOVASCULAR AUTONOMIC NERVOUS SYSTEM (ANS) DYSFUNCTION MAY BE THE UNDERLYING CAUSE OF MANY MS CLINICAL PRESENTATIONS, INCLUDING NEURODEGENERATION AND REDUCED RESPONSE TO IMMUNOMODULATORY THERAPIES, DEPRESSION, FATIGUE AND SLEEP DISORDERS, MIGRAINE, OSTEOPOROSIS, AND CHRONIC CEREBROSPINAL VENOUS INSUFFICIENCY, THE NEWER MS VASCULAR ETIOLOGY. WE HAVE RECENTLY DESCRIBED THE GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS WITH THE POTENTIAL INFLUENCING ANS ACTIVITY, AND THE INTERACTIONS AMONG THESE FACTORS. THIS REVIEW EXPANDS UPON PREVIOUS ONES, DESCRIBING THE PHARMACOLOGICAL, NON-PHARMACOLOGICAL, AND SURGICAL STRATEGIES THAT COULD BE ADOPTED TO PREVENT AND MINIMIZE THE DETERIORATION IN ANS FUNCTION, PROMOTING A STATE OF SYMPATHOVAGAL BALANCE. HOWEVER, THESE STRATEGIES SHOULD NOT BE APPLIED AS "ONE SIZE FITS ALL", BUT SHOULD TAKE INTO ACCOUNT THE NATURE AND THE DEGREE OF ANS DYSFUNCTION. THESE STRATEGIES WOULD BE EFFECTIVE IN IMPROVING ANS FUNCTION NOT ONLY IN MS, BUT ALSO IN OTHER AUTOIMMUNE AND NEURODEGENERATIVE DISEASES, WHERE THE DYSFUNCTION OF THIS SYSTEM PLAYS A ROLE. 2016 3 2724 37 EXPERIENCE-SENSITIVE EPIGENETIC MECHANISMS, DEVELOPMENTAL PLASTICITY, AND THE BIOLOGICAL EMBEDDING OF CHRONIC DISEASE RISK. A WIDE RANGE OF DEVELOPMENTAL, NUTRITIONAL, ENVIRONMENTAL, AND SOCIAL FACTORS AFFECT THE BIOLOGICAL ACTIVITIES OF EPIGENETIC MECHANISMS. THESE FACTORS CHANGE SPATIOTEMPORAL PATTERNS OF GENE EXPRESSION IN A VARIETY OF DIFFERENT WAYS AND BRING SIGNIFICANT IMPACTS TO BEAR ON DEVELOPMENT, PHYSIOLOGY, AND DISEASE RISK THROUGHOUT THE LIFE COURSE. ABUNDANT EVIDENCE DEMONSTRATES THAT BEHAVIORAL STRESSORS AND ADVERSE NUTRITIONAL CONDITIONS ARE PARTICULARLY POTENT INDUCERS OF EPIGENETIC CHANGES AND ENHANCERS OF CHRONIC DISEASE RISKS. RECENT INSIGHTS FROM BOTH HUMAN CLINICAL STUDIES AND RESEARCH WITH MODEL ORGANISMS FURTHER INDICATE THAT SUCH EXPERIENCE-DEPENDENT CHANGES TO THE EPIGENOME CAN BE TRANSMITTED THROUGH THE GERMLINE ACROSS MULTIPLE GENERATIONS, WITH IMPORTANT CONSEQUENCES FOR THE HERITABILITY OF BOTH ADAPTIVE AND MALADAPTIVE PHENOTYPES. EPIGENETICS RESEARCH THUS OFFERS MANY POSSIBILITIES FOR DEVELOPING INFORMATIVE BIOMARKERS OF ACQUIRED CHRONIC DISEASE RISK AND DETERMINING THE EFFECTIVENESS OF PREVENTIVE AND THERAPEUTIC INTERVENTIONS. MOREOVER, THE EXPERIENCE-SENSITIVE NATURE OF THESE DISEASE RISKS RAISES IMPORTANT QUESTIONS ABOUT SOCIETAL AND INDIVIDUAL RESPONSIBILITIES FOR THE PREVENTION OF ILL-HEALTH AND THE PROMOTION OF WELL-BEING DURING DEVELOPMENT, ACROSS THE LIFE COURSE AND BETWEEN GENERATIONS. BETTER UNDERSTANDING OF HOW EPIGENETIC MECHANISMS REGULATE DEVELOPMENTAL PLASTICITY AND MEDIATE THE BIOLOGICAL EMBEDDING OF CHRONIC DISEASE RISKS IS THEREFORE LIKELY TO SHED IMPORTANT NEW LIGHT ON THE NATURE OF THE PATHOPHYSIOLOGICAL MECHANISMS LINKING SOCIAL AND HEALTH INEQUALITIES, AND WILL HELP TO INFORM PUBLIC POLICY INITIATIVES IN THIS AREA. CONFLICT OF INTEREST: THE AUTHOR HAS DECLARED NO CONFLICTS OF INTEREST FOR THIS ARTICLE. 2015 4 5161 40 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 5 2504 27 EPIGENETICS AND MODULATIONS OF EARLY FLAVOR EXPERIENCES: CAN METABOLOMICS CONTRIBUTE TO PREVENTION DURING WEANING? THE SIGNIFICANT INCREASE IN CHRONIC NON-COMMUNICABLE DISEASES HAS CHANGED THE GLOBAL EPIDEMIOLOGICAL LANDSCAPE. AMONG THESE, OBESITY IS THE MOST RELEVANT IN THE PEDIATRIC FIELD. THIS HAS PUSHED THE WORLD OF RESEARCH TOWARDS A NEW PARADIGM: PREVENTIVE AND PREDICTIVE MEDICINE. THEREFORE, THE WINDOW OF EXTREME PLASTICITY THAT CHARACTERIZES THE FIRST STAGE OF DEVELOPMENT CANNOT BE UNDERESTIMATED. IN THIS CONTEXT, NUTRITION CERTAINLY PLAYS A PRIMARY ROLE, BEING ONE OF THE MOST IMPORTANT EPIGENETIC MODULATORS KNOWN TO DATE. WEANING, THEREFORE, HAS A CRUCIAL ROLE THAT MUST BE ANALYZED FAR BEYOND THE SIMPLE ACHIEVEMENT OF NUTRITIONAL NEEDS. FURTHERMORE, THE TASTE EXPERIENCE AND THE FAMILY CONTEXT ARE FUNDAMENTAL FOR FUTURE FOOD CHOICES AND CAN NO LONGER BE UNDERESTIMATED. THE USE OF METABOLOMICS ALLOWS, THROUGH THE RECOGNITION OF EARLY DISEASE MARKERS AND FOOD-SPECIFIC METABOLITES, THE PLANNING OF AN INDIVIDUALIZED AND PRECISE DIET. IN ADDITION, THE POSSIBILITY OF IDENTIFYING PARTICULAR GROUPS OF SUBJECTS AT RISK AND THE CAREFUL MONITORING OF ADHERENCE TO DIETARY THERAPY MAY REPRESENT THE BASIS FOR THIS CHANGE. 2021 6 5163 26 PRECISION/PERSONALIZED MEDICINE IN ALLERGIC DISEASES AND ASTHMA. LIKE MANY OTHER CHRONIC DISEASES, EVERY ALLERGIC PATIENT HAS DIFFERENT CHARACTERISTICS BASED ON CLINICAL COURSE, TREATMENT RESPONSIVENESS AND DISEASE OUTCOMES, WHICH ARE ASSOCIATED WITH THE GENETIC AND EPIGENETIC CONTROL OF MOLECULAR MECHANISMS AND ENVIRONMENT. THIS VARIABILITY NECESSITATES THE ESTABLISHMENT OF PATIENT-TAILORED AND PRECISION APPROACHES IN HANDLING ALLERGIC DISORDERS. BETTER UNDERSTANDING OF THE UNDERLYING PATHOPHYSIOLOGICAL MECHANISMS FOR THE DEVELOPMENT OF ALLERGIC DISORDERS WILL PROVIDE MORE RATIONALE STRATEGIES BASED ON INDIVIDUAL CASES IN CONTROLLING AND TREATING THESE DISORDERS. ENDOTYPING, PHENOTYPING, GENOTYPING AND THERATYPING, AND BIOMARKERS ARE KEYWORDS IN THIS AREA AND HAVE BEEN GAINING LOTS OF ATTENTION IN THE FIELD OF PRECISION MEDICINE, WHICH AIMS TO REVOLUTIONIZE PATIENT CARE AND DEVELOP BETTER PREVENTION AND TREATMENT STRATEGIES. IN ADDITION, PRECISION HEALTH IS A NEW CONCEPT THAT BRINGS PRECISE APPROACHES TO THE SCENE FOR BEING HEALTHY AND PREVENTION OF ALLERGIC DISEASE AND ASTHMA. THE SPECIALTY OF ALLERGY HAS A LEADING ROLE IN THE FIELD, BECAUSE ALLERGEN-SPECIFIC IMMUNOTHERAPY STARTED 105 YEARS AGO, AND IS HISTORICALLY A LEADING PERSONALIZED/PRECISION MEDICINE APPROACH IN ALL MEDICINE DISCIPLINES PROVIDING THE POSSIBILITY OF CURE IN AN INDIVIDUALIZED MANNER INSTEAD OF CONVENTIONAL SYMPTOMATIC TREATMENTS. 2018 7 2496 29 EPIGENETICS AND EARLY LIFE ORIGINS OF CHRONIC NONCOMMUNICABLE DISEASES. IN LIGHT OF THE INCREASING THREATS OF CHRONIC NONCOMMUNICABLE DISEASES IN DEVELOPING COUNTRIES, THE GROWING RECOGNITION OF THE EARLY LIFE ORIGINS OF CHRONIC DISEASE, AND INNOVATIVE BREAKTHROUGHS IN BIOMEDICAL RESEARCH AND TECHNOLOGY, IT IS IMPERATIVE THAT WE HARNESS CUTTING-EDGE DATA TO IMPROVE HEALTH PROMOTION AND MAINTENANCE. IT IS WELL RECOGNIZED THAT CHRONIC DISEASES ARE COMPLEX TRAITS AFFECTED BY A WIDE RANGE OF ENVIRONMENTAL AND GENETIC FACTORS; HOWEVER, THE ROLE OF EPIGENETIC FACTORS, PARTICULARLY WITH REGARD TO EARLY LIFE ORIGINS, REMAINS LARGELY UNEXPLORED. GIVEN THE UNIQUE PROPERTIES OF THE EPIGENOME-FUNCTIONALITY DURING CRITICAL TIME WINDOWS, SUCH AS THE INTRAUTERINE PERIOD, HERITABILITY, AND REVERSIBILITY-ENHANCING OUR UNDERSTANDING OF EPIGENETIC MECHANISMS MAY OFFER NEW OPPORTUNITIES FOR THE DEVELOPMENT OF NOVEL EARLY PREDICTION AND PREVENTION PARADIGMS. THIS MAY PRESENT AN UNPARALLELED OPPORTUNITY TO OFFER MATERNAL AND CHILD HEALTH PROFESSIONALS IMPORTANT TOOLS WITH THE TRANSLATIONAL VALUE TO PREDICT, DETECT, AND PREVENT DISEASE AT AN EARLY AGE, LONG BEFORE ITS CLINICAL OCCURRENCE, AND AS SUCH, BREAK LIFELONG AND TRANSGENERATIONAL CYCLES OF DISEASE. IN DOING SO, MODERN TECHNOLOGY CAN BE LEVERAGED TO MAKE GREAT CONTRIBUTIONS TO POPULATION HEALTH, QUALITY OF LIFE, AND REDUCING THE BURDENSOME ECONOMIC COSTS OF NONCOMMUNICABLE DISEASES IN DEVELOPING COUNTRIES. 2013 8 30 42 A BRIEF LOOK AT HASHIMOTO'S DISEASE, ADRENAL INCIDENTALOMAS, OBESITY AND INSULIN RESISTANCE-COULD ENDOCRINE DISRUPTORS BE THE OTHER SIDE OF THE SAME COIN? HASHIMOTO'S DISEASE (HD) IS THE MOST COMMON CAUSE OF HYPOTHYROIDISM IN DEVELOPED COUNTRIES. THE EXACT PATHOMECHANISM BEHIND IT HAS NOT BEEN CLEARLY ESTABLISHED; HOWEVER, AN INTERPLAY OF GENETIC SUSCEPTIBILITY, ENVIRONMENTAL TRIGGERS (INCLUDING DIET) AND EPIGENETIC FACTORS SEEMS TO BE INVOLVED. AMONG THE LATTER, INCREASINGLY MORE ATTENTION HAS BEEN PAID TO SOME HORMONALLY ACTIVE SUBSTANCES, KNOWN AS ENDOCRINE DISRUPTORS, WHICH ARE COMMONLY USED WORLDWIDE. HD HAS BECOME A CONDITION WIDELY REPORTED IN THE MEDIA, ACTING AS A CULPRIT FOR INEXPLICABLE WEIGHT GAIN, CHRONIC FATIGUE OR WEAKNESS. NEVERTHELESS, THE RECOGNITION OF HD IS UNDENIABLY INCREASING AND REPRESENTS A MAJOR PUBLIC HEALTH BURDEN. AT THE SAME TIME, IMPROVING ACCESS TO IMAGING TESTS HAS INCREASED THE NUMBER OF INCIDENTALLY DIAGNOSED ADRENAL TUMORS. ABOVE ALL, THE WIDESPREAD USE OF CHEST COMPUTED TOMOGRAPHY (CT) DUE TO THE COVID-19 PANDEMIC HAS CONTRIBUTED TO FREQUENT INCIDENTAL DETECTION OF ADRENAL LESIONS. FORTUNATELY, A VAST MAJORITY OF THESE FINDINGS ARE ASYMPTOMATIC BENIGN TUMORS WITH NO EXCESSIVE HORMONAL ACTIVITY, AND THEREFORE, THEY ARE DEFINED AS ADRENAL INCIDENTALOMAS (AIS). INTERESTINGLY, RECENT STUDIES HAVE INDICATED THAT PATIENTS WITH AIS ARE MORE PRONE TO OBESITY AND INSULIN RESISTANCE. ALTHOUGH MUTUAL RELATIONSHIPS BETWEEN THE THYROID AND THE ADRENAL GLANDS HAVE BEEN STUDIED WIDELY, STILL, LITTLE IS KNOWN ABOUT THE POSSIBLE PATHOPHYSIOLOGICAL ASSOCIATIONS BETWEEN THYROID AUTOIMMUNITY AND THE OCCURRENCE OF ADRENAL INCIDENTALOMAS. THIS ARTICLE PRESENTS A BRIEF REVIEW OF THE COMMON ENDOCRINE DISORDERS WITH A SPECIAL FOCUS ON THE FREQUENTLY COEXISTING INSULIN RESISTANCE AND/OR OBESITY. FURTHERMORE, IN RESPONSE TO THE RECENT GROWING INTEREST IN ENDOCRINE DISRUPTORS, WITH THEIR TRANSGENERATIONAL EPIGENETIC EFFECTS THAT INFLUENCE HORMONAL SYSTEM FUNCTION, A CONCISE OVERVIEW OF THE TOPIC HAS ALSO BEEN INCLUDED. 2023 9 2662 29 EPSTEIN-BARR VIRUS AND MULTIPLE SCLEROSIS: A CONVOLUTED INTERACTION AND THE OPPORTUNITY TO UNRAVEL PREDICTIVE BIOMARKERS. SINCE THE EARLY 1980S, EPSTEIN-BARR VIRUS (EBV) INFECTION HAS BEEN DESCRIBED AS ONE OF THE MAIN RISK FACTORS FOR DEVELOPING MULTIPLE SCLEROSIS (MS), AND RECENTLY, NEW EPIDEMIOLOGICAL EVIDENCE HAS REINFORCED THIS PREMISE. EBV SEROCONVERSION PRECEDES ALMOST 99% OF THE NEW CASES OF MS AND LIKELY PREDATES THE FIRST CLINICAL SYMPTOMS. THE MOLECULAR MECHANISMS OF THIS ASSOCIATION ARE COMPLEX AND MAY INVOLVE DIFFERENT IMMUNOLOGICAL ROUTES, PERHAPS ALL RUNNING IN PARALLEL (I.E., MOLECULAR MIMICRY, THE BYSTANDER DAMAGE THEORY, ABNORMAL CYTOKINE NETWORKS, AND COINFECTION OF EBV WITH RETROVIRUSES, AMONG OTHERS). HOWEVER, DESPITE THE LARGE AMOUNT OF EVIDENCE AVAILABLE ON THESE TOPICS, THE ULTIMATE ROLE OF EBV IN THE PATHOGENESIS OF MS IS NOT FULLY UNDERSTOOD. FOR INSTANCE, IT IS UNCLEAR WHY AFTER EBV INFECTION SOME INDIVIDUALS DEVELOP MS WHILE OTHERS EVOLVE TO LYMPHOPROLIFERATIVE DISORDERS OR SYSTEMIC AUTOIMMUNE DISEASES. IN THIS REGARD, RECENT STUDIES SUGGEST THAT THE VIRUS MAY EXERT EPIGENETIC CONTROL OVER MS SUSCEPTIBILITY GENES BY MEANS OF SPECIFIC VIRULENCE FACTORS. SUCH GENETIC MANIPULATION HAS BEEN DESCRIBED IN VIRALLY-INFECTED MEMORY B CELLS FROM PATIENTS WITH MS AND ARE THOUGHT TO BE THE MAIN SOURCE OF AUTOREACTIVE IMMUNE RESPONSES. YET, THE ROLE OF EBV INFECTION IN THE NATURAL HISTORY OF MS AND IN THE INITIATION OF NEURODEGENERATION IS EVEN LESS CLEAR. IN THIS NARRATIVE REVIEW, WE WILL DISCUSS THE AVAILABLE EVIDENCE ON THESE TOPICS AND THE POSSIBILITY OF HARNESSING SUCH IMMUNOLOGICAL ALTERATIONS TO UNCOVER PREDICTIVE BIOMARKERS FOR THE ONSET OF MS AND PERHAPS FACILITATE PROGNOSTICATION OF THE CLINICAL COURSE. 2023 10 244 35 ADOLESCENT IDIOPATHIC SCOLIOSIS (AIS), ENVIRONMENT, EXPOSOME AND EPIGENETICS: A MOLECULAR PERSPECTIVE OF POSTNATAL NORMAL SPINAL GROWTH AND THE ETIOPATHOGENESIS OF AIS WITH CONSIDERATION OF A NETWORK APPROACH AND POSSIBLE IMPLICATIONS FOR MEDICAL THERAPY. GENETIC FACTORS ARE BELIEVED TO PLAY AN IMPORTANT ROLE IN THE ETIOLOGY OF ADOLESCENT IDIOPATHIC SCOLIOSIS (AIS). DISCORDANT FINDINGS FOR MONOZYGOTIC (MZ) TWINS WITH AIS SHOW THAT ENVIRONMENTAL FACTORS INCLUDING DIFFERENT INTRAUTERINE ENVIRONMENTS ARE IMPORTANT IN ETIOLOGY, BUT WHAT THESE ENVIRONMENTAL FACTORS MAY BE IS UNKNOWN. RECENT EVIDENCE FOR COMMON CHRONIC NON-COMMUNICABLE DISEASES SUGGESTS EPIGENETIC DIFFERENCES MAY UNDERLIE MZ TWIN DISCORDANCE, AND BE THE LINK BETWEEN ENVIRONMENTAL FACTORS AND PHENOTYPIC DIFFERENCES. DNA METHYLATION IS ONE IMPORTANT EPIGENETIC MECHANISM OPERATING AT THE INTERFACE BETWEEN GENOME AND ENVIRONMENT TO REGULATE PHENOTYPIC PLASTICITY WITH A COMPLEX REGULATION ACROSS THE GENOME DURING THE FIRST DECADE OF LIFE. THE WORD EXPOSOME REFERS TO THE TOTALITY OF ENVIRONMENTAL EXPOSURES FROM CONCEPTION ONWARDS, COMPRISING FACTORS IN EXTERNAL AND INTERNAL ENVIRONMENTS. THE WORD EXPOSOME IS USED HERE ALSO IN RELATION TO PHYSIOLOGIC AND ETIOPATHOGENETIC FACTORS THAT AFFECT NORMAL SPINAL GROWTH AND MAY INDUCE THE DEFORMITY OF AIS. IN NORMAL POSTNATAL SPINAL GROWTH WE PROPOSE A NEW TERM AND CONCEPT, PHYSIOLOGIC GROWTH-PLATE EXPOSOME FOR THE NORMAL PROCESSES PARTICULARLY OF THE INTERNAL ENVIRONMENTS THAT MAY HAVE EPIGENETIC EFFECTS ON GROWTH PLATES OF VERTEBRAE. IN AIS, WE PROPOSE A NEW TERM AND CONCEPT PATHOPHYSIOLOGIC SCOLIOGENIC EXPOSOME FOR THE ABNORMAL PROCESSES IN MOLECULAR PATHWAYS PARTICULARLY OF THE INTERNAL ENVIRONMENT CURRENTLY EXPRESSED AS ETIOPATHOGENETIC HYPOTHESES; THESE ARE SUGGESTED TO HAVE DEFORMING EFFECTS ON THE GROWTH PLATES OF VERTEBRAE AT CELL, TISSUE, STRUCTURE AND/OR ORGAN LEVELS THAT ARE CONSIDERED TO BE EPIGENETIC. NEW RESEARCH IS REQUIRED FOR CHROMATIN MODIFICATIONS INCLUDING DNA METHYLATION IN AIS SUBJECTS AND VERTEBRAL GROWTH PLATES EXCISED AT SURGERY. IN ADDITION, CONSIDERATION IS NEEDED FOR A POSSIBLE NETWORK APPROACH TO ETIOPATHOGENESIS BY CONSTRUCTING AIS DISEASOMES. THESE APPROACHES MAY LEAD THROUGH SCREENING, GENETIC, EPIGENETIC, BIOCHEMICAL, METABOLIC PHENOTYPES AND PHARMACOGENOMIC RESEARCH TO IDENTIFY SUSCEPTIBLE INDIVIDUALS AT RISK AND MODULATE ABNORMAL MOLECULAR PATHWAYS OF AIS. THE POTENTIAL OF EPIGENETIC-BASED MEDICAL THERAPY FOR AIS CANNOT BE ASSESSED AT PRESENT, AND MUST AWAIT NEW RESEARCH DERIVED FROM THE EVALUATION OF EPIGENETIC CONCEPTS OF SPINAL GROWTH IN HEALTH AND DEFORMITY. THE TENETS OUTLINED HERE FOR AIS ARE APPLICABLE TO OTHER MUSCULOSKELETAL GROWTH DISORDERS INCLUDING INFANTILE AND JUVENILE IDIOPATHIC SCOLIOSIS. 2011 11 2881 30 FUTURE PERSPECTIVES OF PERSONALIZED WEIGHT LOSS INTERVENTIONS BASED ON NUTRIGENETIC, EPIGENETIC, AND METAGENOMIC DATA. AS OBESITY HAS BECOME A MAJOR GLOBAL PUBLIC HEALTH CHALLENGE, A LARGE NUMBER OF STUDIES HAVE ANALYZED DIFFERENT STRATEGIES AIMED AT INDUCING A NEGATIVE ENERGY BALANCE AND, CONSEQUENTLY, BODY WEIGHT LOSS. HOWEVER, MOST EXISTING WEIGHT LOSS PROGRAMS ARE GENERALLY UNSUCCESSFUL, SO SEVERAL INTERVENTIONS HAVE BEEN CARRIED OUT TO IDENTIFY PHYSIOLOGIC AND BEHAVIORAL FACTORS CONCERNING THIS VARIABILITY IN ORDER TO IMPLEMENT MORE PERSONALIZED TREATMENT. NOWADAYS, AN INDIVIDUALIZED APPROACH IS BEING PROPOSED THROUGH SO-CALLED PERSONALIZED NUTRITION, WHEREBY NOT ONLY THE PHENOTYPE BUT ALSO THE GENOTYPE IS USED FOR CUSTOMIZED NUTRITION TREATMENT. REGARDING BODY WEIGHT REGULATION, APPROXIMATELY 70 POLYMORPHISMS HAVE BEEN IDENTIFIED IN OR NEAR GENES RELATED TO ENERGY EXPENDITURE, APPETITE, ADIPOGENESIS, INSULIN RESISTANCE, AND LIPID METABOLISM. ALTHOUGH PERSONALIZED NUTRITION REFERS MAINLY TO GENETIC MAKEUP, RECENT ADVANCES IN THE INVESTIGATION OF THE EPIGENOME AND THE MICROBIOME OPEN THE DOOR TO IMPLEMENT MORE PERSONALIZED RECOMMENDATIONS FOR BODY WEIGHT MANAGEMENT. IN THIS CONTEXT, RECENT STUDIES HAVE DEMONSTRATED THE EXISTENCE OF SEVERAL EPIGENETIC MARKERS THAT MAY MODIFY GENE EXPRESSION AND COULD BE INVOLVED IN THE OUTCOME OF WEIGHT LOSS INTERVENTIONS. MOREOVER, DIFFERENT STUDIES HAVE SHOWN THAT DIETARY INTERVENTIONS COULD AFFECT THE COMPOSITION OF GUT MICROBIOTA AND HAVE AN IMPACT ON BODY WEIGHT. THE INTEGRATION OF NUTRIGENETIC, EPIGENETIC, AND METAGENOMIC DATA MAY LEAD TO THE DESIGN OF MORE PERSONALIZED DIETARY TREATMENTS TO PREVENT CHRONIC DISEASES AND TO OPTIMIZE THE INDIVIDUAL'S RESPONSE TO DIETARY INTERVENTIONS. 2015 12 6026 37 THE BIOLOGY OF STRESS INTOLERANCE IN PATIENTS WITH CHRONIC PAIN-STATE OF THE ART AND FUTURE DIRECTIONS. STRESS HAS BEEN CONSISTENTLY LINKED TO NEGATIVE IMPACTS ON PHYSICAL AND MENTAL HEALTH. MORE SPECIFICALLY, PATIENTS WITH CHRONIC PAIN EXPERIENCE STRESS INTOLERANCE, WHICH IS AN EXACERBATION OR OCCURRENCE OF SYMPTOMS IN RESPONSE TO ANY TYPE OF STRESS. THE PATHOPHYSIOLOGICAL MECHANISMS UNDERLYING THIS PHENOMENON REMAIN UNSOLVED. IN THIS STATE-OF-THE-ART PAPER, WE SUMMARISED THE ROLE OF THE AUTONOMIC NERVOUS SYSTEM (ANS) AND HYPOTHALAMUS-PITUITARY-ADRENAL (HPA) AXIS, THE TWO MAJOR STRESS RESPONSE SYSTEMS IN STRESS INTOLERANCE. WE PROVIDED INSIGHTS INTO SUCH MECHANISMS BASED ON EVIDENCE FROM CLINICAL STUDIES IN BOTH PATIENTS WITH CHRONIC PAIN, SHOWING DYSREGULATED STRESS SYSTEMS, AND HEALTHY CONTROLS SUPPORTED BY PRECLINICAL STUDIES, HIGHLIGHTING THE LINK BETWEEN THESE SYSTEMS AND SYMPTOMS OF STRESS INTOLERANCE. FURTHERMORE, WE EXPLORED THE POSSIBLE REGULATING ROLE FOR (EPI)GENETIC MECHANISMS INFLUENCING THE ANS AND HPA AXIS. THE LINK BETWEEN STRESS AND CHRONIC PAIN HAS BECOME AN IMPORTANT AREA OF RESEARCH AS IT HAS THE POTENTIAL TO INFORM THE DEVELOPMENT OF INTERVENTIONS TO IMPROVE THE QUALITY OF LIFE FOR INDIVIDUALS LIVING WITH CHRONIC PAIN. AS STRESS HAS BECOME A PREVALENT CONCERN IN MODERN SOCIETY, UNDERSTANDING THE CONNECTION BETWEEN STRESS, HPA AXIS, ANS, AND CHRONIC HEALTH CONDITIONS SUCH AS CHRONIC PAIN IS CRUCIAL TO IMPROVE PUBLIC HEALTH AND WELL-BEING. 2023 13 2459 27 EPIGENETIC THERAPIES FOR NON-ONCOLOGY INDICATIONS. CHRONIC AND DEGENERATIVE DISORDERS ARE A MAJOR, AND GROWING, HUMAN HEALTH BURDEN, AND CURRENT TREATMENTS ARE IN MANY CASES INADEQUATE OR VERY EXPENSIVE. EPIGENETIC THERAPIES ARE ATTRACTIVE OPTIONS FOR TREATING SUCH DISORDERS BECAUSE THEY MANIPULATE THE PROCESSES THAT MAINTAIN CELLS IN AN ABNORMAL TRANSCRIPTIONAL STATE. THE CHALLENGES LIE IN IDENTIFYING THE MOST APPROPRIATE DISEASES AND THE ENZYMES THAT SHOULD BE TARGETED. THIS REVIEW DESCRIBES THE DIFFERENT APPROACHES THAT CAN BE USED TO ADDRESS THIS PROBLEM, FOCUSING PARTICULARLY ON CNS DISORDERS (ESPECIALLY MENTAL RETARDATION, NEURODEGENERATIVE DISEASE, PSYCHIATRIC DISORDERS AND DRUG ADDICTION), DIABETES AND DIABETIC COMPLICATIONS, AND AUTOIMMUNITY AND INFLAMMATORY DISEASES. 2010 14 4006 33 LOST AMONG THE TREES? THE AUTONOMIC NERVOUS SYSTEM AND PAEDIATRICS. THE AUTONOMIC NERVOUS SYSTEM (ANS) HAS BEEN STRIKINGLY NEGLECTED IN WESTERN MEDICINE. DESPITE ITS PROFOUND IMPORTANCE FOR REGULATION, ADJUSTMENT AND COORDINATION OF BODY SYSTEMS, IT LACKS PRIORITY IN TRAINING AND PRACTICE AND RECEIVES SCANT ATTENTION IN NUMEROUS MAJOR TEXTBOOKS. THE ANS IS INTEGRAL TO MANIFESTATIONS OF ILLNESS, UNDERLYING FAMILIAR PHYSICAL AND PSYCHOLOGICAL SYMPTOMS. WHEN ANS ACTIVITY IS ITSELF DYSFUNCTIONAL, USUAL INDICATORS OF ACUTE ILLNESS MAY PROVE DECEPTIVE. RECOGNISING THE RELEVANCE OF THE ANS CAN INVOLVE SEEING THE FAMILIAR THROUGH FRESH EYES, CHALLENGING ASSUMPTIONS IN CLINICAL ASSESSMENT AND IN APPROACHES TO PRACTICE. ITS IMPORTANCE EXTENDS FROM PHYSICAL AND PSYCHOLOGICAL WELL-BEING TO PARENTING AND SAFEGUARDING, PUBLIC SERVICES AND THE FUNCTIONING OF SOCIETY. EXPLORATION OF ITS ROLE IN CONDITIONS RANGING FROM NEUROLOGICAL, GASTROINTESTINAL AND CONNECTIVE TISSUE DISORDERS, DIABETES AND CHRONIC FATIGUE SYNDROME, TO AUTISM, BEHAVIOURAL AND MENTAL HEALTH DIFFICULTIES MAY OPEN THERAPEUTIC AVENUES. THE ANS OFFERS A MECHANISM FOR SO-CALLED FUNCTIONAL ILLNESSES AND ILLUSTRATES THE IMPORTANCE OF RECOGNISING THAT 'STRESS' TAKES MANY FORMS, PHYSICAL, PSYCHOLOGICAL AND ENVIRONMENTAL, DESIRABLE AND OTHERWISE. EVIDENCE OF INTRAUTERINE AND POST-NATAL PROGRAMMING OF ANS REACTIVITY SUGGESTS THAT NEONATAL CARE AND SAFEGUARDING PRACTICE MAY OFFER PREVENTIVE OPPORTUNITY, AS MAY GREATER UNDERSTANDING OF EPIGENETIC CHANGE OF ANS ACTIVITY THROUGH, FOR EXAMPLE, ACCIDENTAL OR PSYCHOLOGICAL TRAUMA OR INFECTION. THE AIM OF THIS ARTICLE IS TO ACCELERATE RECOGNITION OF THE IMPORTANCE OF THE ANS THROUGHOUT PAEDIATRICS, AND OF THE POTENTIAL PHYSICAL AND PSYCHOLOGICAL COST OF NEGLECTING IT. 2014 15 4914 26 PAIN VULNERABILITY: A NEUROBIOLOGICAL PERSPECTIVE. THERE ARE MANY KNOWN RISK FACTORS FOR CHRONIC PAIN CONDITIONS, YET THE BIOLOGICAL UNDERPINNINGS THAT LINK THESE FACTORS TO ABNORMAL PROCESSING OF PAINFUL SIGNALS ARE ONLY JUST BEGINNING TO BE EXPLORED. THIS REVIEW WILL DISCUSS THE POTENTIAL MECHANISMS THAT HAVE BEEN PROPOSED TO UNDERLIE VULNERABILITY AND RESILIENCE TOWARD DEVELOPING CHRONIC PAIN. PARTICULAR FOCUS WILL BE GIVEN TO GENETIC AND EPIGENETIC PROCESSES, PRIMING EFFECTS ON A CELLULAR LEVEL, AND ALTERATIONS IN BRAIN NETWORKS CONCERNED WITH REWARD, MOTIVATION/LEARNING AND DESCENDING MODULATORY CONTROL. ALTHOUGH RESEARCH IN THIS AREA IS STILL IN ITS INFANCY, A BETTER UNDERSTANDING OF HOW PAIN VULNERABILITY EMERGES HAS THE POTENTIAL TO HELP IDENTIFY INDIVIDUALS AT RISK AND MAY OPEN UP NEW THERAPEUTIC AVENUES. 2014 16 46 34 A CONCEPTUAL FRAMEWORK FOR THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE. IN THE LAST DECADES, THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) HAVE EMERGED AS A VIGOROUS FIELD COMBINING EXPERIMENTAL, CLINICAL, EPIDEMIOLOGICAL AND PUBLIC HEALTH RESEARCH. ITS GOAL IS TO UNDERSTAND HOW EVENTS IN EARLY LIFE SHAPE LATER MORBIDITY RISK, ESPECIALLY OF NON-COMMUNICABLE CHRONIC DISEASES. AS THESE DISEASES BECOME THE MAJOR CAUSE OF MORBIDITY AND MORTALITY WORLDWIDE, RESEARCH ARISING FROM DOHAD IS LIKELY TO GAIN SIGNIFICANCE TO PUBLIC HEALTH AND ECONOMIC DEVELOPMENT. BUT ACTION MAY BE HINDERED BY THE LACK OF A FIRM MECHANISTIC EXPLANATION AND OF A CONCEPTUAL BASIS, ESPECIALLY REGARDING THE EVOLUTIONARY SIGNIFICANCE OF THE DOHAD PHENOMENON. IN THIS ARTICLE, WE PROVIDE A SUCCINCT HISTORICAL REVIEW OF THE RESEARCH INTO THE RELATIONSHIP BETWEEN DEVELOPMENT AND LATER DISEASE, CONSIDER THE EVOLUTIONARY AND DEVELOPMENTAL SIGNIFICANCE AND DISCUSS THE UNDERLYING MECHANISMS OF THE DOHAD PHENOMENON. DOHAD SHOULD BE VIEWED AS A PART OF A BROADER BIOLOGICAL MECHANISM OF PLASTICITY BY WHICH ORGANISMS, IN RESPONSE TO CUES SUCH AS NUTRITION OR HORMONES, ADAPT THEIR PHENOTYPE TO ENVIRONMENT. THESE RESPONSES MAY BE DIVIDED INTO THOSE FOR IMMEDIATE BENEFIT AND THOSE AIMED AT PREDICTION OF A FUTURE ENVIRONMENT: DISEASE OCCURS IN THE MISMATCH BETWEEN PREDICTED AND REALIZED FUTURE. THE LIKELY MECHANISMS THAT ENABLE PLASTICITY INVOLVE EPIGENETIC PROCESSES, AFFECTING THE EXPRESSION OF GENES ASSOCIATED WITH REGULATORY PATHWAYS. THERE IS NOW EVIDENCE THAT EPIGENETIC MARKS MAY BE INHERITED AND SO CONTRIBUTE TO NON-GENOMIC HERITABLE DISEASE RISK. WE END BY DISCUSSING THE GLOBAL SIGNIFICANCE OF THE DOHAD PHENOMENON AND ITS POTENTIAL APPLICATIONS FOR PUBLIC HEALTH PURPOSES. 2010 17 1859 39 EMBEDDING THE COMMUNITY AND INDIVIDUALS IN DISEASE PREVENTION. THE PRIMARY PREVENTION OF NON-COMMUNICABLE DISEASES IS ONE OF THE MOST CHALLENGING AND EXCITING ASPECTS OF MEDICINE AND PRIMARY CARE THIS CENTURY. FOR CANCER, IT IS AN URGENT MATTER IN LIGHT OF THE INCREASING BURDEN OF THE DISEASE AMONG YOUNGER PEOPLE AND THE HIGHER FREQUENCY OF MORE AGGRESSIVE FORMS OF THE DISEASE FOR ALL AGES. MOST CHRONIC DISORDERS RESULT FROM THE INFLUENCE OF THE ENVIRONMENT ON THE EXPRESSION OF GENES WITHIN AN INDIVIDUAL. THE ENVIRONMENT AT-LARGE ENCOMPASSES LIFESTYLE (INCLUDING NUTRITION), AND CHEMICAL/PHYSICAL AND SOCIAL EXPOSURES. IN CANCER, THE INTERACTION BETWEEN THE (EPI)GENETIC MAKEUP OF AN INDIVIDUAL AND A MULTIPLICITY OF ENVIRONMENTAL RISK AND PROTECTING FACTORS IS CONSIDERED KEY TO DISEASE ONSET. THUS, LIKE FOR PRECISION THERAPY DEVELOPED FOR PATIENTS, PERSONALIZED OR PRECISION PREVENTION IS ENVISIONED FOR INDIVIDUALS AT RISK. PREVENTION MEANS IDENTIFYING PEOPLE AT HIGHER RISK AND INTERVENING TO REDUCE THE RISK. IT REQUIRES BIOLOGICAL MARKERS OF RISK AND NON-AGGRESSIVE PREVENTIVE ACTIONS FOR THE INDIVIDUAL, BUT IT ALSO INVOLVES ACTING ON THE ENVIRONMENT AND THE COMMUNITY. SOCIAL SCIENTISTS ARE CONSIDERING MICRO (INDIVIDUAL/FAMILY), MESO (COMMUNITY), AND MACRO (COUNTRY POPULATION) LEVELS OF CARE TO ILLUSTRATE THAT PROBLEMS AND SOLUTIONS EXIST ON DIFFERENT SCALES. IDEALLY, THE DESIGN OF INTERVENTIONS IN PREVENTION SHOULD INTEGRATE ALL THESE LEVELS. IN THIS PERSPECTIVE ARTICLE, USING THE EXAMPLE OF BREAST CANCER, WE ARE DISCUSSING CHALLENGES AND POSSIBLE SOLUTIONS FOR A MULTIDISCIPLINARY COMMUNITY OF SCIENTISTS, PRIMARY HEALTH CARE PRACTITIONERS AND CITIZENS TO DEVELOP A HOLISTIC APPROACH OF PRIMARY PREVENTION, KEEPING IN MIND EQUITABLE ACCESS TO CARE. 2022 18 5224 41 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 19 727 27 CAN VITAMINS, AS EPIGENETIC MODIFIERS, ENHANCE IMMUNITY IN COVID-19 PATIENTS WITH NON-COMMUNICABLE DISEASE? PURPOSE OF REVIEW: THE HIGHLY INFECTIOUS TRANSMISSIBLE DISEASE, THE NOVEL SARS-COV-2, CAUSING THE CORONAVIRUS DISEASE (COVID-19), HAS A MEDIAN INCUBATION TIME OF 5 TO 15 DAYS. THE SYMPTOMS VARY FROM PERSON TO PERSON AND MANY ARE "HIDDEN CARRIERS." FEW PEOPLE EXPERIENCE IMMEDIATE REACTION AND EVEN DEATH WITHIN 48 H OF INFECTION. HOWEVER, MANY SHOW MILD TO CHRONIC SYMPTOMS AND RECOVER. NEVERTHELESS, THE DEATH RATE DUE TO COVID-19 TRANSMISSION IS HIGH ESPECIALLY AMONG PATIENTS WITH NON-COMMUNICABLE DISEASES. THE PURPOSE OF THIS REVIEW IS TO PROVIDE EVIDENCE TO CONSIDER VITAMINS AS EPIGENETIC MODIFIERS TO ENHANCE IMMUNITY AND REDUCE INFLAMMATORY RESPONSE IN COVID-19 PATIENTS WITH NON-COMMUNICABLE DISEASES. RECENT FINDINGS: CLINICAL EVIDENCE HAS SUGGESTED THE RISK OF GETTING INFECTED IS HIGH AMONG INDIVIDUALS WITH NON-COMMUNICABLE DISEASES SUCH AS CARDIOVASCULAR DISEASE, TYPE-2 DIABETES, CANCER, ACUTE RESPIRATORY DISTRESS SYNDROME, AND RENAL DISEASE, AS WELL AS THE ELDERLY WITH HIGH MORTALITY RATE AMONG THE COHORT. THE IMPACT IS DUE TO AN ALREADY COMPROMISED IMMUNE SYSTEM OF PATIENTS. EVERY PATIENT HAS A DIFFERENT RESPONSE TO COVID-19, WHICH SHOWS THAT THE ABILITY TO COMBAT THE DEADLY VIRUS VARIES INDIVIDUALLY. THUS, TREATMENT CAN BE PERSONALIZED AND ADJUSTED TO HELP PROTECT AND COMBAT COVID-19 INFECTIONS, ESPECIALLY IN INDIVIDUALS WITH NON-COMMUNICABLE DISEASES. BASED ON CURRENT PUBLISHED SCIENTIFIC AND MEDICAL EVIDENCE, THE SUGGESTIONS MADE IN THIS ARTICLE FOR COMBINATION OF VITAMIN THERAPY AS EPIGENETIC MODIFIERS TO CONTROL THE UNREGULATED INFLAMMATORY AND CYTOKINE MARKER EXPRESSIONS, FURTHER NEEDS TO BE CLINICALLY PROVEN. FUTURE RESEARCH AND CLINICAL TRIALS CAN APPLY THE SUGGESTIONS GIVEN IN THIS ARTICLE TO SUPPORT METABOLIC ACTIVITIES IN PATIENTS AND ENHANCE THE IMMUNE RESPONSE. 2020 20 6211 32 THE INTERPLAY BETWEEN OXIDATIVE STRESS, EXERCISE, AND PAIN IN HEALTH AND DISEASE: POTENTIAL ROLE OF AUTONOMIC REGULATION AND EPIGENETIC MECHANISMS. OXIDATIVE STRESS CAN BE INDUCED BY VARIOUS STIMULI AND ALTERED IN CERTAIN CONDITIONS, INCLUDING EXERCISE AND PAIN. ALTHOUGH MANY STUDIES HAVE INVESTIGATED OXIDATIVE STRESS IN RELATION TO EITHER EXERCISE OR PAIN, THE LITERATURE PRESENTS CONFLICTING RESULTS. THEREFORE, THIS REVIEW CRITICALLY DISCUSSES EXISTING LITERATURE ABOUT THIS TOPIC, AIMING TO PROVIDE A CLEAR OVERVIEW OF KNOWN INTERACTIONS BETWEEN OXIDATIVE STRESS, EXERCISE, AND PAIN IN HEALTHY PEOPLE AS WELL AS IN PEOPLE WITH CHRONIC PAIN, AND TO HIGHLIGHT POSSIBLE CONFOUNDING FACTORS TO KEEP IN MIND WHEN REFLECTING ON THESE INTERACTIONS. IN ADDITION, AUTONOMIC REGULATION AND EPIGENETIC MECHANISMS ARE PROPOSED AS POTENTIAL MECHANISMS OF ACTION UNDERLYING THE INTERPLAY BETWEEN OXIDATIVE STRESS, EXERCISE, AND PAIN. THIS REVIEW HIGHLIGHTS THAT THE RELATION BETWEEN OXIDATIVE STRESS, EXERCISE, AND PAIN IS POORLY UNDERSTOOD AND NOT STRAIGHTFORWARD, AS IT IS DEPENDENT ON THE CHARACTERISTICS OF EXERCISE, BUT ALSO ON WHICH POPULATION IS INVESTIGATED. TO BE ABLE TO COMPARE STUDIES ON THIS TOPIC, STRICT GUIDELINES SHOULD BE DEVELOPED TO LIMIT THE EFFECT OF SEVERAL CONFOUNDING FACTORS. THIS WAY, THE TRUE INTERPLAY BETWEEN OXIDATIVE STRESS, EXERCISE, AND PAIN, AND THE UNDERLYING MECHANISMS OF ACTION CAN BE REVEALED AND VALIDATED VIA INDEPENDENT STUDIES. 2020