1 5280 106 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 2 6026 24 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 3 6375 35 THE ROLE OF NEURO-IMMUNE INTERACTION IN CHRONIC PAIN CONDITIONS; FUNCTIONAL SOMATIC SYNDROME, NEUROGENIC INFLAMMATION, AND PERIPHERAL NEUROPATHY. FUNCTIONAL SOMATIC SYNDROMES ARE INCREASINGLY DIAGNOSED IN CHRONICALLY ILL PATIENTS PRESENTING WITH AN ARRAY OF SYMPTOMS NOT ATTRIBUTED TO PHYSICAL AILMENTS. CONDITIONS SUCH AS CHRONIC FATIGUE SYNDROME, FIBROMYALGIA SYNDROME, OR IRRITABLE BOWEL SYNDROME ARE COMMON DISORDERS THAT BELONG IN THIS BROAD CATEGORY. SUCH SYNDROMES ARE CHARACTERISED BY THE PRESENCE OF ONE OR MULTIPLE CHRONIC SYMPTOMS INCLUDING WIDESPREAD MUSCULOSKELETAL PAIN, FATIGUE, SLEEP DISORDERS, AND ABDOMINAL PAIN, AMONGST OTHER ISSUES. SYMPTOMS ARE BELIEVED TO RELATE TO A COMPLEX INTERACTION OF BIOLOGICAL AND PSYCHOSOCIAL FACTORS, WHERE A DEFINITE AETIOLOGY HAS NOT BEEN ESTABLISHED. THEORIES SUGGEST CAUSATIVE PATHWAYS BETWEEN THE IMMUNE AND NERVOUS SYSTEMS OF AFFECTED INDIVIDUALS WITH SEVERAL RISK FACTORS IDENTIFIED IN PATIENTS PRESENTING WITH ONE OR MORE FUNCTIONAL SYNDROMES. RISK FACTORS INCLUDING STRESS AND CHILDHOOD TRAUMA ARE NOW RECOGNISED AS IMPORTANT CONTRIBUTORS TO CHRONIC PAIN CONDITIONS. EMOTIONAL, PHYSICAL, AND SEXUAL ABUSE DURING CHILDHOOD IS CONSIDERED A SEVERE STRESSOR HAVING A HIGH PREVALENCE IN FUNCTIONAL SOMATIC SYNDROME SUFFERS. SUCH TRAUMA PERMANENTLY ALTERS THE BIOLOGICAL STRESS RESPONSE OF THE SUFFERS LEADING TO NEUROEXCITATORY AND OTHER NERVE ISSUES ASSOCIATED WITH CHRONIC PAIN IN ADULTS. TRAUMATIC AND CHRONIC STRESS RESULTS IN EPIGENETIC CHANGES IN STRESS RESPONSE GENES, WHICH ULTIMATELY LEADS TO DYSREGULATION OF THE HYPOTHALAMIC-PITUITARY AXIS, THE AUTONOMIC NERVOUS SYSTEM, AND THE IMMUNE SYSTEM MANIFESTING IN A BROAD ARRAY OF SYMPTOMS. IMPORTANTLY, THESE SYSTEMS ARE KNOWN TO BE DYSREGULATED IN PATIENTS SUFFERING FROM FUNCTIONAL SOMATIC SYNDROME. FUNCTIONAL SOMATIC SYNDROMES ARE ALSO HIGHLY PREVALENT CO-MORBIDITIES OF PSYCHIATRIC CONDITIONS, MOOD DISORDERS, AND ANXIETY. CONSEQUENTLY, THIS REVIEW AIMS TO PROVIDE INSIGHT INTO THE ROLE OF THE NERVOUS SYSTEM AND IMMUNE SYSTEM IN CHRONIC PAIN DISORDERS ASSOCIATED WITH THE MUSCULOSKELETAL SYSTEM, AND CENTRAL AND PERIPHERAL NERVOUS SYSTEMS. 2022 4 6021 30 THE BENEFICIAL AND DEBILITATING EFFECTS OF ENVIRONMENTAL AND MICROBIAL TOXINS, DRUGS, ORGANIC SOLVENTS AND HEAVY METALS ON THE ONSET AND PROGRESSION OF MULTIPLE SCLEROSIS. MULTIPLE SCLEROSIS (MS), A CHRONIC INFLAMMATORY DISEASE OF THE CENTRAL NERVOUS SYSTEM IS COMMON AMONGST YOUNG ADULTS, LEADING TO MAJOR PERSONAL AND SOCIOECONOMIC BURDENS. HOWEVER, IT IS STILL CONSIDERED COMPLEX AND CHALLENGING TO UNDERSTAND AND TREAT, IN SPITE OF THE EFFORTS MADE TO EXPLAIN ITS ETIOPATHOLOGY. DESPITE THE DISCOVERY OF MANY GENETIC AND ENVIRONMENTAL FACTORS THAT MIGHT BE RELATED TO ITS ETIOLOGY, NO CLEAR ANSWER WAS FOUND ABOUT THE CAUSES OF THE ILLNESS AND NEITHER ABOUT THE DETAILED MECHANISM OF THESE ENVIRONMENTAL TRIGGERS THAT MAKE INDIVIDUALS SUSCEPTIBLE TO MS. IN THIS REVIEW, WE WILL ATTEMPT TO EXPLORE THE MAJOR CONTRIBUTORS TO MS AUTOIMMUNITY INCLUDING GENETIC, EPIGENETIC AND ECOLOGICAL FACTORS WITH A PARTICULAR FOCUS ON TOXINS, CHEMICALS OR DRUGS THAT MAY TRIGGER, MODIFY OR PREVENT MS DISEASE. 2019 5 6211 29 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 6 2404 33 EPIGENETIC RESEARCH IN MULTIPLE SCLEROSIS: PROGRESS, CHALLENGES, AND OPPORTUNITIES. MULTIPLE SCLEROSIS (MS) IS A CHRONIC INFLAMMATORY AND DEMYELINATING DISEASE OF THE CENTRAL NERVOUS SYSTEM. MS LIKELY RESULTS FROM A COMPLEX INTERPLAY BETWEEN PREDISPOSING CAUSAL GENE VARIANTS (THE STRONGEST INFLUENCE COMING FROM HLA CLASS II LOCUS) AND ENVIRONMENTAL RISK FACTORS SUCH AS SMOKING, INFECTIOUS MONONUCLEOSIS, AND LACK OF SUN EXPOSURE/VITAMIN D. HOWEVER, LITTLE IS KNOWN ABOUT THE MECHANISMS UNDERLYING MS DEVELOPMENT AND PROGRESSION. MOREOVER, THE CLINICAL HETEROGENEITY AND VARIABLE RESPONSE TO TREATMENT REPRESENT ADDITIONAL CHALLENGES TO A COMPREHENSIVE UNDERSTANDING AND EFFICIENT TREATMENT OF DISEASE. EPIGENETIC PROCESSES, SUCH AS DNA METHYLATION AND HISTONE POSTTRANSLATIONAL MODIFICATIONS, INTEGRATE INFLUENCES FROM THE GENES AND THE ENVIRONMENT TO REGULATE GENE EXPRESSION ACCORDINGLY. STUDYING EPIGENETIC MODIFICATIONS, WHICH ARE STABLE AND REVERSIBLE, MAY PROVIDE AN ALTERNATIVE APPROACH TO BETTER UNDERSTAND AND MANAGE DISEASE. WE HERE AIM TO REVIEW FINDINGS FROM EPIGENETIC STUDIES IN MS AND FURTHER DISCUSS THE CHALLENGES AND CLINICAL OPPORTUNITIES ARISING FROM EPIGENETIC RESEARCH, MANY OF WHICH APPLY TO OTHER DISEASES WITH SIMILAR COMPLEX ETIOLOGY. A GROWING BODY OF EVIDENCE SUPPORTS A ROLE OF EPIGENETIC PROCESSES IN THE MECHANISMS UNDERLYING IMMUNE PATHOGENESIS AND NERVOUS SYSTEM DYSFUNCTION IN MS. HOWEVER, DISPARITIES BETWEEN STUDIES SHED LIGHT ON THE NEED TO CONSIDER POSSIBLE CONFOUNDERS AND METHODOLOGICAL LIMITATIONS FOR A BETTER INTERPRETATION OF THE DATA. NEVERTHELESS, TRANSLATIONAL USE OF EPIGENETICS MIGHT OFFER NEW OPPORTUNITIES IN EPIGENETIC-BASED DIAGNOSTICS AND THERAPEUTIC TOOLS FOR A PERSONALIZED CARE OF MS PATIENTS. 2017 7 1329 32 DEPRESSION ASSOCIATED WITH DIABETES: FROM PATHOPHYSIOLOGY TO TREATMENT. DIABETES IS A CHRONIC AND PROGRESSIVE SYNDROME COMMONLY ASSOCIATED WITH SEVERAL NEUROPSYCHIATRIC COMORBITIES, OF WHICH DEPRESSION IS THE MOST STUDIED. THE PREVALENCE OF DEPRESSION IS ABOUT TWO OR THREE TIMES HIGHER IN DIABETIC PATIENTS COMPARED TO THE GENERAL POPULATION. IT IS BELIEVED THAT THE DIABETES - DEPRESSION RELATION MAY BE BIDIRECTIONAL, I.E., THE DEPRESSION CAN LEAD TO DIABETES AND CONVERSELY DIABETES COULD FACILITATE THE EMERGENCE OF DEPRESSION. DEPRESSION IS ONE OF THE MOST NEGLECTED SYMPTOMS IN DIABETIC PATIENTS AND IS DIRECTLY LINKED WITH LOWERING OF QUALITY OF LIFE. THE TREATMENT OF DEPRESSION IN THESE PATIENTS IS STILL QUITE INEFFECTIVE AND IN MANY CASES TREATMENTREFRACTORY. FURTHERMORE, SOME OF THE FIRST CHOICE DRUGS USED TO TREAT THE DEPRESSION AFFECT THE BLOOD GLUCOSE CONTROL, AGGRAVATING THE HYPERGLYCEMIC STATE. THESE ISSUES UNDERSCORE THE URGENCY IN STUDIES SEARCHING FOR NEW PHARMACOLOGICAL TARGETS FOR THE TREATMENT OF DEPRESSION ASSOCIATED WITH DIABETES. FOR THIS, A BETTER UNDERSTANDING OF THE PATHOPHYSIOLOGY THAT RELATES THIS COMORBIDITY BECOMES CRITICAL. IN THIS RESPECT, THIS REVIEW WILL FOCUS ON SOME HYPOTHESES THAT HAVE BEEN PROPOSED TO EXPLAIN THE MECHANISMS UNDERLYING DEPRESSION ASSOCIATED WITH DIABETES, HIGHLIGHTING THE TREATMENT OPTIONS CURRENTLY AVAILABLE AND THEIR LIMITATIONS. AMONG THESE HYPOTHESES, WE WILL POINT OUT THE HYPERGLYCEMIA AS A PRIMARY METABOLIC CAUSE OF THE DEPRESSION DEVELOPMENT, THE INVOLVEMENT OF THE DYSREGULATION OF HYPOTHALAMIC PITUITARY-ADRENAL (HPA) AXIS AND OF NEUROTRANSMITTER SYSTEMS, SPECIALLY MONOAMINERGIC SYSTEM. BESIDES, THE ROLE OF OXIDATIVE STRESS, NEUROINFLAMMATION AND CELL DEATH, ESPECIALLY IN HIPPOCAMPUS AND PREFRONTAL CORTEX, BRAIN AREAS IMPORTANT FOR THE MEDIATION AND MODULATION OF EMOTIONAL BEHAVIOR WILL ALSO BE DISCUSSED. FINALLY, WE WILL BRING UP THE INFLUENCE OF THE EPIGENETIC REGULATION WITH RESPECT TO NEUROPSYCHIATRIC DISORDERS. 2016 8 724 25 CAN GENETICS GUIDE EXERCISE PRESCRIPTIONS IN OSTEOARTHRITIS? OSTEOARTHRITIS (OA) IS THE MOST COMMON FORM OF ARTHRITIS AND HAS A MULTIFACTORIAL ETIOLOGY. CURRENT MANAGEMENT FOR OA FOCUSES ON MINIMIZING PAIN AND FUNCTIONAL LOSS, TYPICALLY INVOLVING PHARMACOLOGICAL, PHYSICAL, PSYCHOSOCIAL, AND MIND-BODY INTERVENTIONS. HOWEVER, THERE REMAIN CHALLENGES IN DETERMINING WHICH PATIENTS WILL BENEFIT MOST FROM WHICH INTERVENTIONS. ALTHOUGH EXERCISE-BASED INTERVENTIONS ARE RECOMMENDED AS FIRST-LINE TREATMENTS AND ARE KNOWN TO BE BENEFICIAL FOR MANAGING BOTH THE DISEASE AND ILLNESS OF OA, THE OPTIMAL EXERCISE "PRESCRIPTION" IS UNKNOWN, DUE IN PART TO OUR LIMITED UNDERSTANDING OF THE PRECISE MECHANISMS UNDERLYING ITS ACTION. HERE WE PRESENT OUR PERSPECTIVE ON THE POTENTIAL ROLE OF GENETICS IN GUIDING EXERCISE PRESCRIPTION FOR PERSONS WITH OA. WE DESCRIBE KEY PUBLICATIONS IN THE AREAS OF EXERCISE AND OA, GENETICS AND OA, AND EXERCISE AND GENETICS, AND POINT TO A PAUCITY OF KNOWLEDGE AT THE INTERSECTION OF EXERCISE, GENETICS, AND OA. WE SUGGEST THERE IS EMERGING EVIDENCE TO SUPPORT THE USE OF GENETICS AND EPIGENETICS TO EXPLAIN THE BENEFICIAL EFFECTS OF EXERCISE FOR OA. WE IDENTIFY MISSING LINKS IN THE EXISTING RESEARCH RELATING TO EXERCISE, GENETICS, AND OA, AND HIGHLIGHT EPIGENETICS AS A PROMISING MECHANISM THROUGH WHICH ENVIRONMENTAL EXPOSURES SUCH AS EXERCISE MAY IMPACT OA OUTCOMES. WE ANTICIPATE FUTURE STUDIES WILL IMPROVE OUR UNDERSTANDING OF HOW GENETIC AND EPIGENETIC FACTORS MEDIATE EXERCISE-BASED INTERVENTIONS TO SUPPORT IMPLEMENTATION AND ULTIMATELY IMPROVE OA PATIENT CARE. 2022 9 6260 25 THE MOLECULAR NEUROBIOLOGY OF CHRONIC PAIN-INDUCED DEPRESSION. THE INCREASING NUMBER OF INDIVIDUALS WITH COMORBIDITIES POSES AN URGENT NEED TO IMPROVE THE MANAGEMENT OF PATIENTS WITH MULTIPLE CO-EXISTING DISEASES. AMONG THESE COMORBIDITIES, CHRONIC PAIN AND MOOD DISORDERS, TWO LONG-LASTING DISABLING CONDITIONS THAT SIGNIFICANTLY REDUCE THE QUALITY OF LIFE, COULD BE CITED FIRST. THE RECENT DEVELOPMENT OF ANIMAL MODELS ACCELERATED THE STUDIES FOCUSING ON THE UNDERLYING MECHANISMS OF THE CHRONIC PAIN AND DEPRESSION/ANXIETY COMORBIDITY. THIS REVIEW PROVIDES AN OVERVIEW OF CLINICAL AND PRE-CLINICAL STUDIES PERFORMED OVER THE PAST TWO DECADES ADDRESSING THE MOLECULAR ASPECTS OF THE COMORBID RELATIONSHIP OF CHRONIC PAIN AND DEPRESSION. WE THUS FOCUSED ON THE STUDIES THAT INVESTIGATED THE MOLECULAR CHARACTERISTICS OF THE COMORBID RELATIONSHIP BETWEEN CHRONIC PAIN AND MOOD DISORDERS, ESPECIALLY MAJOR DEPRESSIVE DISORDERS, FROM THE GENETIC AND EPIGENETIC POINT OF VIEW TO KEY NEUROMODULATORS WHICH HAVE BEEN SHOWN TO PLAY AN IMPORTANT ROLE IN THIS COMORBIDITY. 2019 10 5069 23 PHYSICAL ACTIVITY IN THE PREVENTION OF HUMAN DISEASES: ROLE OF EPIGENETIC MODIFICATIONS. EPIGENETIC MODIFICATION REFERS TO HERITABLE CHANGES IN GENE FUNCTION THAT CANNOT BE EXPLAINED BY ALTERATIONS IN THE DNA SEQUENCE. THE CURRENT LITERATURE CLEARLY DEMONSTRATES THAT THE EPIGENETIC RESPONSE IS HIGHLY DYNAMIC AND INFLUENCED BY DIFFERENT BIOLOGICAL AND ENVIRONMENTAL FACTORS SUCH AS AGING, NUTRIENT AVAILABILITY AND PHYSICAL EXERCISE. AS SUCH, IT IS WELL ACCEPTED THAT PHYSICAL ACTIVITY AND EXERCISE CAN MODULATE GENE EXPRESSION THROUGH EPIGENETIC ALTERNATIONS ALTHOUGH THE TYPE AND DURATION OF EXERCISE ELICITING SPECIFIC EPIGENETIC EFFECTS THAT CAN RESULT IN HEALTH BENEFITS AND PREVENT CHRONIC DISEASES REMAINS TO BE DETERMINED. THIS REVIEW HIGHLIGHTS THE MOST SIGNIFICANT FINDINGS FROM EPIGENETIC STUDIES INVOLVING PHYSICAL ACTIVITY/EXERCISE INTERVENTIONS KNOWN TO BENEFIT CHRONIC DISEASES SUCH AS METABOLIC SYNDROME, DIABETES, CANCER, CARDIOVASCULAR AND NEURODEGENERATIVE DISEASES. 2017 11 4591 24 NARRATIVE REVIEW OF THE COMPLEX INTERACTION BETWEEN PAIN AND TRAUMA IN CHILDREN: A FOCUS ON BIOLOGICAL MEMORY, PRECLINICAL DATA, AND EPIGENETIC PROCESSES. THE INCIDENCE AND COLLECTIVE IMPACT OF EARLY ADVERSE EXPERIENCES, TRAUMA, AND PAIN CONTINUE TO INCREASE. THIS UNDERSCORES THE URGENT NEED FOR TRANSLATIONAL EFFORTS BETWEEN CLINICAL AND PRECLINICAL RESEARCH TO BETTER UNDERSTAND THE UNDERLYING MECHANISMS AND DEVELOP EFFECTIVE THERAPEUTIC APPROACHES. AS OUR UNDERSTANDING OF THESE ISSUES IMPROVES FROM STUDIES IN CHILDREN AND ADOLESCENTS, WE CAN CREATE MORE PRECISE PRECLINICAL MODELS AND ULTIMATELY TRANSLATE OUR FINDINGS BACK TO CLINICAL PRACTICE. A MULTIDISCIPLINARY APPROACH IS ESSENTIAL FOR ADDRESSING THE COMPLEX AND WIDE-RANGING EFFECTS OF THESE EXPERIENCES ON INDIVIDUALS AND SOCIETY. THIS NARRATIVE REVIEW AIMS TO (1) DEFINE PAIN AND TRAUMA EXPERIENCES IN CHILDHOOD AND ADOLESCENTS, (2) DISCUSS THE RELATIONSHIP BETWEEN PAIN AND TRAUMA, (3) CONSIDER THE ROLE OF BIOLOGICAL MEMORY, (4) DECIPHER THE RELATIONSHIP BETWEEN PAIN AND TRAUMA USING PRECLINICAL DATA, AND (5) EXAMINE THE ROLE OF THE ENVIRONMENT BY INTRODUCING THE IMPORTANCE OF EPIGENETIC PROCESSES. THE ULTIMATE SCOPE IS TO BETTER UNDERSTAND THE WIDE-RANGING EFFECTS OF TRAUMA, ABUSE, AND CHRONIC PAIN ON CHILDREN AND ADOLESCENTS, HOW THEY OCCUR, AND HOW TO PREVENT OR MITIGATE THEIR EFFECTS AND DEVELOP EFFECTIVE TREATMENT STRATEGIES THAT ADDRESS BOTH THE UNDERLYING CAUSES AND THE ASSOCIATED PHYSIOLOGICAL AND PSYCHOLOGICAL EFFECTS. 2023 12 6739 25 WHEN ENVIRONMENT MEETS GENETICS: A CLINICAL REVIEW OF THE EPIGENETICS OF PAIN, PSYCHOLOGICAL FACTORS, AND PHYSICAL ACTIVITY. EPIGENETIC MECHANISMS REPRESENT A LINK BETWEEN THE ENVIRONMENT AND GENE FUNCTION. RECENT RESEARCH SHOWS HOW EARLY LIFE STRESS, INFLAMMATION, AND PHYSICAL ACTIVITY CAN INFLUENCE GENE EXPRESSION THROUGH EPIGENETIC MECHANISMS. EPIGENETIC CHANGES-SUCH AS DNA METHYLATION AND MICRORNA INTERFERENCE-CAN BE MEASURED IN HUMANS AND MIGHT SOON BECOME IMPORTANT BIOLOGICAL MARKERS. EPIGENETIC MARKS CAN ACCOMPANY CLINICAL ASSESSMENT TO MEASURE THE EFFECTIVENESS OF VARIOUS INTERVENTIONS, SUCH AS EXERCISE THERAPY. IN ADDITION, EPIGENETICS IS IMPROVING THE UNDERSTANDING OF IMPORTANT UNDERLYING MECHANISMS RELATED TO THE CENTRAL NERVOUS SYSTEM, THE OPIOIDERGIC SYSTEM, AND STRESS RESPONSES. EPIGENETICS IS CLOSING A GAP IN OUR EXPLANATORY ABILITIES AND SHOULD BE IMPLEMENTED TO BROADEN THE FIELD OF REHABILITATION SCIENCES, PROMOTE A MECHANISM-BASED CLINICAL REASONING, AND DEVELOP NEW TREATMENTS. IN THE PRESENT REVIEW, WE FOCUSED ON EPIGENETIC MECHANISMS RELATED TO PAIN, PSYCHOLOGICAL FACTORS (SUCH AS FEAR AND ANXIETY), AND PHYSICAL ACTIVITY, TRANSLATING RELEVANT FINDINGS FROM THESE 3 DIFFERENT, YET RELATED, AREAS OF CARDINAL IMPORTANCE FOR CLINICIANS. 2019 13 3676 31 INFLAMMATION AND NEUTROPHIL IMMUNOSENESCENCE IN HEALTH AND DISEASE: TARGETED TREATMENTS TO IMPROVE CLINICAL OUTCOMES IN THE ELDERLY. DESPITE INCREASING LONGEVITY, MANY OLD PEOPLE ARE NOT IN GOOD HEALTH. THERE HAS BEEN AN INCREASE IN THE PREVALENCE OF AGE-ASSOCIATED MULTI-MORBIDITY (TWO OR MORE CHRONIC CONDITIONS IN THE SAME PERSON). ALSO, SEVERE INFECTIONS, SUCH AS PNEUMONIA, REMAIN SIGNIFICANT CAUSES OF MORTALITY AND MORBIDITY IN THIS AGING GROUP. MANY CHRONIC HEALTH CONDITIONS SHARE RISK FACTORS SUCH AS INCREASING AGE, SMOKING, A SEDENTARY LIFE STYLE AND BEING PART OF A LOWER SOCIOECONOMIC GROUP. HOWEVER, DESPITE THIS, MULTI-MORBIDITIES OFTEN CO-OCCUR MORE COMMONLY THAN WOULD BE PREDICTED. THIS HAS LED TO THE HYPOTHESIS THAT THEY SHARE COMMON UNDERLYING MECHANISMS. THIS IS AN IMPORTANT CONCEPT, FOR IF IT WERE TRUE, TREATMENTS COULD BE DEVISED WHICH TARGET THESE COMMON PATHWAYS AND IMPROVE A NUMBER OF AGE-ASSOCIATED HEALTH CONDITIONS. MANY CHRONIC ILLNESSES ASSOCIATED WITH MULTI-MORBIDITY AND SEVERE INFECTIONS ARE CHARACTERIZED BY AN ABNORMAL AND SUSTAINED INFLAMMATORY RESPONSE, WITH NEUTROPHILS BEING KEY EFFECTOR CELLS IN THE PATHOLOGICAL PROCESS. STUDIES HAVE DESCRIBED ABERRANT NEUTROPHIL FUNCTIONS ACROSS THESE CONDITIONS, AND SOME HAVE HIGHLIGHTED POTENTIAL MECHANISMS FOR ALTERED CELL BEHAVIOURS WHICH APPEAR SHARED ACROSS DISEASE STATES. IT HAS BEEN SUGGESTED THAT ALTERED FUNCTIONS MAY REPRESENT NEUTROPHIL "SENESCENCE". THIS REVIEW CONSIDERS HOW AND WHY NEUTROPHIL FUNCTIONS CHANGE AS THE CELL AGES, AND HOW AND WHY NEUTROPHIL FUNCTIONS CHANGE AS THE HOST AGES IN HEALTH AND DISEASE AND DISCUSSES WHETHER NEUTROPHIL FUNCTIONS COULD BE TARGETED TO IMPROVE HEALTH OUTCOMES IN OLDER ADULTS. 2018 14 4914 22 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 15 4716 22 NON-GENETIC RATS MODELS FOR ATHEROSCLEROSIS RESEARCH: FROM PAST TO PRESENT. ATHEROSCLEROSIS IS AN INFLAMMATORY, PROGRESSIVE, AND CHRONIC ILLNESS THAT INVOLVES SEVERAL MOLECULAR AND EPIGENETIC FACTORS. DESPITE TREATMENT LIMITATIONS, CLINICAL AND THERAPEUTIC APPROACHES HAVE UNDENIABLY CHANGED RADICALLY IN RECENT DECADES THROUGH BETTER KNOWLEDGE OF THE PATHOPHYSIOLOGICAL BASIS OF THE DISEASE, WHICH HAS CONSIDERABLY IMPROVED PATIENTS' SURVIVAL AND QUALITY OF LIFE. SOME OF THESE ADVANCES ARE ATTRIBUTABLE TO BASIC BIOMEDICAL RESEARCH THAT PROVIDES INSIGHTS INTO A BETTER UNDERSTANDING AND IDENTIFICATION OF NEW MOLECULAR AND CELLULAR TARGETS FOR ATHEROSCLEROSIS TREATMENT. ALTHOUGH RODENT MODELS HAVE CONTRIBUTED SUBSTANTIALLY TO A BETTER UNDERSTANDING OF THE DEVELOPMENT OF ATHEROSCLEROSIS, THE ACCURACY OF THESE MODELS REMAINS CONTROVERSIAL. RESEARCH THAT UTILIZES GENETIC RODENT MODELS IS WELL ESTABLISHED, BUT THE USE OF SPECIFIC DIETS THAT ARE ASSOCIATED WITH OTHER RISK FACTORS (E.G., HYPERTENSION, HORMONE DEPRIVATION, AND PHARMACOLOGICAL TOOLS) IS STILL DEBATABLE. THE PRESENT REVIEW PROVIDES AN UPDATE ON NON-GENETIC RAT MODELS OF ATHEROSCLEROSIS AND AN OVERVIEW OF THE MAIN METHODOLOGIES THAT ARE CURRENTLY AVAILABLE. 2019 16 5829 22 STRESS, PSYCHIATRIC DISORDERS, MOLECULAR TARGETS, AND MORE. MENTAL HEALTH IS CENTRAL TO NORMAL HEALTH OUTCOMES. A WIDELY ACCEPTED THEORY IS THAT CHRONIC PERSISTENT STRESS DURING ADULTHOOD AS WELL AS DURING EARLY LIFE TRIGGERS ONSET OF NEUROPSYCHIATRIC AILMENTS. HOWEVER, QUESTIONS RELATED TO HOW THAT OCCURS, AND WHY ARE SOME INDIVIDUALS RESISTANT TO STRESS WHILE OTHERS ARE NOT, REMAIN UNANSWERED. AN INTEGRATED, MULTISYSTEMIC STRESS RESPONSE INVOLVING NEUROINFLAMMATORY, NEUROENDOCRINE, EPIGENETIC AND METABOLIC CASCADES HAVE BEEN SUGGESTED TO HAVE CAUSATIVE LINKS. SEVERAL THEORIES HAVE BEEN PROPOSED OVER THE YEARS TO CONCEPTUALIZE THIS LINK INCLUDING THE CYTOKINE HYPOTHESIS, THE ENDOCRINE HYPOTHESIS, THE OXIDATIVE STRESS HYPOTHESIS AND THE OXIDO-NEUROINFLAMMATION HYPOTHESIS. THE DATA DISCUSSED IN THIS REVIEW DESCRIBES POTENTIAL BIOCHEMICAL BASIS OF THE LINK BETWEEN STRESS, AND STRESS-INDUCED NEURONAL, BEHAVIORAL AND EMOTIONAL DEFICITS, PROVIDING INSIGHTS INTO POTENTIALLY NOVEL DRUG TARGETS. 2019 17 5136 30 POTENTIAL MECHANISMS LINKING PSYCHOLOGICAL STRESS TO BONE HEALTH. CHRONIC PSYCHOLOGICAL STRESS AFFECTS MANY BODY SYSTEMS, INCLUDING THE SKELETON, THROUGH VARIOUS MECHANISMS. THIS REVIEW AIMS TO PROVIDE AN OVERVIEW OF THE FACTORS MEDIATING THE RELATIONSHIP BETWEEN PSYCHOLOGICAL STRESS AND BONE HEALTH. THESE FACTORS CAN BE DIVIDED INTO PHYSIOLOGICAL AND BEHAVIOURAL CHANGES INDUCED BY PSYCHOLOGICAL STRESS. THE PHYSIOLOGICAL FACTORS INVOLVE ENDOCRINOLOGICAL CHANGES, SUCH AS INCREASED GLUCOCORTICOIDS, PROLACTIN, LEPTIN AND PARATHYROID HORMONE LEVELS AND REDUCED GONADAL HORMONES. LOW-GRADE INFLAMMATION AND HYPERACTIVATION OF THE SYMPATHETIC NERVOUS SYSTEM DURING PSYCHOLOGICAL STRESS ARE ALSO PHYSIOLOGICAL CHANGES DETRIMENTAL TO BONE HEALTH. THE BEHAVIOURAL CHANGES DURING MENTAL STRESS, SUCH AS ALTERED DIETARY PATTERN, CIGARETTE SMOKING, ALCOHOLISM AND PHYSICAL INACTIVITY, ALSO THREATEN THE SKELETAL SYSTEM. PSYCHOLOGICAL STRESS MAY BE PARTLY RESPONSIBLE FOR EPIGENETIC REGULATION OF SKELETAL DEVELOPMENT. IT MAY ALSO MEDIATE THE RELATIONSHIP BETWEEN SOCIOECONOMIC STATUS AND BONE HEALTH. HOWEVER, MORE DIRECT EVIDENCE IS REQUIRED TO PROVE THESE HYPOTHESES. IN CONCLUSION, CHRONIC PSYCHOLOGICAL STRESS SHOULD BE RECOGNISED AS A RISK FACTOR OF OSTEOPOROSIS AND STRESS-COPING METHODS SHOULD BE INCORPORATED AS PART OF THE COMPREHENSIVE OSTEOPOROSIS-PREVENTING STRATEGY. 2021 18 2526 28 EPIGENETICS APPLIED TO PSYCHIATRY: CLINICAL OPPORTUNITIES AND FUTURE CHALLENGES. PSYCHIATRIC DISORDERS ARE CLINICALLY HETEROGENEOUS AND DEBILITATING CHRONIC DISEASES RESULTING FROM A COMPLEX INTERPLAY BETWEEN GENE VARIANTS AND ENVIRONMENTAL FACTORS. EPIGENETIC PROCESSES, SUCH AS DNA METHYLATION AND HISTONE POSTTRANSLATIONAL MODIFICATIONS, INSTRUCT THE CELL/TISSUE TO CORRECTLY INTERPRET EXTERNAL SIGNALS AND ADJUST ITS FUNCTIONS ACCORDINGLY. GIVEN THAT EPIGENETIC MODIFICATIONS ARE SENSITIVE TO ENVIRONMENT, STABLE, AND REVERSIBLE, EPIGENETIC STUDIES IN PSYCHIATRY COULD REPRESENT A PROMISING APPROACH TO BETTER UNDERSTANDING AND TREATING DISEASE. IN THE PRESENT REVIEW, WE AIM TO DISCUSS THE CLINICAL OPPORTUNITIES AND CHALLENGES ARISING FROM THE EPIGENETIC RESEARCH IN PSYCHIATRY. USING SELECTED EXAMPLES, WE FIRST RECAPITULATE KEY FINDINGS SUPPORTING THE ROLE OF ADVERSE LIFE EVENTS, ALONE OR IN COMBINATION WITH GENETIC RISK, IN EPIGENETIC PROGRAMMING OF NEUROPSYCHIATRIC SYSTEMS. EPIGENETIC STUDIES FURTHER REPORT ENCOURAGING FINDINGS ABOUT THE USE OF METHYLATION CHANGES AS DIAGNOSTIC MARKERS OF DISEASE PHENOTYPE AND PREDICTIVE TOOLS OF PROGRESSION AND RESPONSE TO TREATMENT. THEN WE DISCUSS THE POTENTIAL OF USING TARGETED EPIGENETIC PHARMACOTHERAPY, COMBINED WITH PSYCHOSOCIAL INTERVENTIONS, FOR FUTURE PERSONALIZED MEDICINE FOR PATIENTS. FINALLY, WE REVIEW THE METHODOLOGICAL LIMITATIONS THAT COULD HINDER INTERPRETATION OF EPIGENETIC DATA IN PSYCHIATRY. THEY MAINLY ARISE FROM HETEROGENEITY AT THE INDIVIDUAL AND TISSUE LEVEL AND REQUIRE FUTURE STRATEGIES IN ORDER TO REINFORCE THE BIOLOGICAL RELEVANCE OF EPIGENETIC DATA AND ITS TRANSLATIONAL USE IN PSYCHIATRY. OVERALL, WE SUGGEST THAT EPIGENETICS COULD PROVIDE NEW INSIGHTS INTO A MORE COMPREHENSIVE INTERPRETATION OF MENTAL ILLNESS AND MIGHT EVENTUALLY IMPROVE THE NOSOLOGY, TREATMENT, AND PREVENTION OF PSYCHIATRIC DISORDERS. 2018 19 6252 29 THE MICROBIOME AND CANCER: IMPLICATIONS FOR ONCOLOGY NURSING SCIENCE. BACKGROUND: APPROXIMATELY 1.6 MILLION AMERICANS WERE DIAGNOSED WITH CANCER IN 2014. TO COMBAT THEIR DISEASE, MANY INDIVIDUALS RECEIVED EITHER CURATIVE OR PALLIATIVE TREATMENTS THAT PRODUCED UNDESIRED SYMPTOMS. THESE SYMPTOMS, WHICH OFTEN CAUSE SIGNIFICANT DISTRESS FOR INDIVIDUALS COPING WITH CANCER, MAY SHARE BIOLOGIC UNDERPINNINGS SUCH AS EPIGENETIC CHANGES AND IMMUNE DYSREGULATION. ALTERATIONS IN THE NORMAL FLORA OF THE GUT MAY ALSO INFLUENCE CANCER SYMPTOMS. OBJECTIVE: THE AIM OF THIS REVIEW IS TO DESCRIBE THE EMERGING ROLE FOR THE GUT MICROBIOME IN CANCER RESEARCH, ESPECIALLY THE POTENTIAL RELATIONSHIP BETWEEN THE GUT MICROBIOME AND CANCER SYMPTOMS. METHODS: EXTANT LITERATURE WAS REVIEWED AND SYNTHESIZED. RESULTS: THE MAJORITY OF STUDIES LINKING THE GUT MICROBIOTA AND CANCER ARE ANIMAL MODELS AND FOCUS ON THE RELATIONSHIP BETWEEN DYSBIOSIS AND COLORECTAL CANCER. EMERGING EVIDENCE SUPPORTS THAT THE "GUT-BRAIN" CONNECTION IS A PLAUSIBLE MECHANISM FOR "PSYCHONEUROLOGICAL" CANCER SYMPTOMS SUCH AS DEPRESSION, PAIN, AND FATIGUE. CONCLUSIONS: THERE IS COMPELLING EVIDENCE THAT THE GUT MICROBIOTA AFFECTS CANCER VIA SEVERAL MECHANISMS, INCLUDING MICROBIAL DIVERSITY AND NUMBER, METABOLISM, AND/OR IMMUNE INITIATION. HOWEVER, MORE RESEARCH IS NECESSARY TO ELUCIDATE THESE MECHANISMS, PARTICULARLY AMONG A VARIETY OF CANCERS AND CANCER-RELATED SYMPTOMS. IMPLICATIONS FOR PRACTICE: A BETTER UNDERSTANDING OF THE ROLE OF THE GUT MICROBIOTA IN CANCER SYMPTOMS MAY LEAD TO THE DEVELOPMENT OF TARGETED INDIVIDUALIZED INTERVENTIONS AFFECTING THE GUT MICROBIOTA THAT PREVENT OR AMELIORATE DYSBIOSIS, THEREBY REDUCING SYMPTOMS. THESE INTERVENTIONS MAY EMPHASIZE SELF-CARE MANAGEMENT STRATEGIES ESSENTIAL FOR WELLNESS, SUCH AS DIET, NUTRITION, AND STRESS REDUCTION. 2016 20 4985 30 PATHWAYS TO AGING: THE MITOCHONDRION AT THE INTERSECTION OF BIOLOGICAL AND PSYCHOSOCIAL SCIENCES. COMPELLING EVIDENCE SUGGESTS THAT BOTH BIOLOGICAL AND PSYCHOSOCIAL FACTORS IMPACT THE PROCESS OF AGING. HOWEVER, OUR UNDERSTANDING OF THE DYNAMIC INTERPLAY AMONG BIOLOGICAL AND PSYCHOSOCIAL FACTORS ACROSS THE LIFE COURSE IS STILL FRAGMENTARY. FOR EXAMPLE, IT NEEDS TO BE ESTABLISHED HOW THE INTERACTION OF INDIVIDUAL FACTORS (E.G., GENETIC AND EPIGENETIC ENDOWMENT AND PERSONALITY), BEHAVIORAL FACTORS (E.G., PHYSICAL ACTIVITY, DIET, AND STRESS MANAGEMENT), AND PSYCHOSOCIAL EXPERIENCES (E.G., SOCIAL SUPPORT, WELL-BEING, SOCIOECONOMIC STATUS, AND MARRIAGE) IN PERINATAL, CHILDHOOD, AND ADULTHOOD INFLUENCE HEALTH ACROSS THE AGING CONTINUUM. THIS PAPER AIMS TO OUTLINE POTENTIAL INTERSECTION POINTS SERVING AS AN INTERFACE BETWEEN BIOLOGICAL AND PSYCHOSOCIAL FACTORS, WITH AN EMPHASIS ON THE MITOCHONDRION. MITOCHONDRIA ARE CELLULAR ORGANELLES WHICH PLAY A CRITICAL ROLE IN CELLULAR SENESCENCE. BOTH CHRONIC EXPOSURE TO PSYCHOSOCIAL STRESS AND GENETIC-BASED MITOCHONDRIAL DYSFUNCTION HAVE STRIKINGLY SIMILAR BIOLOGICAL CONSEQUENCES; BOTH PREDISPOSE INDIVIDUALS TO ADVERSE AGE-RELATED HEALTH DISORDERS AND EARLY MORTALITY. EXPLORING THE INTERACTIVE NATURE OF THE FACTORS RESULTING IN PATHWAYS TO NORMAL HEALTHY AGING, AS WELL AS THOSE LEADING TO MORBIDITY AND EARLY MORTALITY, WILL CONTINUE TO ENHANCE OUR ABILITY TO TRANSLATE RESEARCH INTO EFFECTIVE PRACTICES THAT CAN BE IMPLEMENTED THROUGHOUT THE LIFE COURSE TO OPTIMISE THE AGING PROCESS. 2011