1 244 168 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 2 4805 38 OBESITY AND METABOLIC COMORBIDITIES: ENVIRONMENTAL DISEASES? OBESITY AND METABOLIC COMORBIDITIES REPRESENT INCREASING HEALTH PROBLEMS. ENDOCRINE DISRUPTING COMPOUNDS (EDCS) ARE EXOGENOUS AGENTS THAT CHANGE ENDOCRINE FUNCTION AND CAUSE ADVERSE HEALTH EFFECTS. MOST EDCS ARE SYNTHETIC CHEMICALS; SOME ARE NATURAL FOOD COMPONENTS AS PHYTOESTROGENS. PEOPLE ARE EXPOSED TO COMPLEX MIXTURES OF CHEMICALS THROUGHOUT THEIR LIVES. EDCS IMPACT HORMONE-DEPENDENT METABOLIC SYSTEMS AND BRAIN FUNCTION. LABORATORY AND HUMAN STUDIES PROVIDE COMPELLING EVIDENCE THAT HUMAN CHEMICAL CONTAMINATION CAN PLAY A ROLE IN OBESITY EPIDEMIC. CHEMICAL EXPOSURES MAY INCREASE THE RISK OF OBESITY BY ALTERING THE DIFFERENTIATION OF ADIPOCYTES. EDCS CAN ALTER METHYLATION PATTERNS AND NORMAL EPIGENETIC PROGRAMMING IN CELLS. OXIDATIVE STRESS MAY BE INDUCED BY MANY OF THESE CHEMICALS, AND ACCUMULATING EVIDENCE INDICATES THAT IT PLAYS IMPORTANT ROLES IN THE ETIOLOGY OF CHRONIC DISEASES. THE INDIVIDUAL SENSITIVITY TO CHEMICALS IS VARIABLE, DEPENDING ON ENVIRONMENT AND ABILITY TO METABOLIZE HAZARDOUS CHEMICALS. A NUMBER OF GENES, ESPECIALLY THOSE REPRESENTING ANTIOXIDANT AND DETOXIFICATION PATHWAYS, HAVE POTENTIAL APPLICATION AS BIOMARKERS OF RISK ASSESSMENT. THE POTENTIAL HEALTH EFFECTS OF COMBINED EXPOSURES MAKE THE RISK ASSESSMENT PROCESS MORE COMPLEX COMPARED TO THE ASSESSMENT OF SINGLE CHEMICALS. TECHNIQUES AND METHODS NEED TO BE FURTHER DEVELOPED TO FILL DATA GAPS AND INCREASE THE KNOWLEDGE ON HARMFUL EXPOSURE COMBINATIONS. 2013 3 2715 30 EXERCISE-INDUCED BIOCHEMICAL CHANGES AND THEIR POTENTIAL INFLUENCE ON CANCER: A SCIENTIFIC REVIEW. AIM: TO REVIEW AND DISCUSS THE AVAILABLE INTERNATIONAL LITERATURE REGARDING THE INDIRECT AND DIRECT BIOCHEMICAL MECHANISMS THAT OCCUR AFTER EXERCISE, WHICH COULD POSITIVELY, OR NEGATIVELY, INFLUENCE ONCOGENIC PATHWAYS. METHODS: THE PUBMED, MEDLINE, EMBASE AND COCHRANE LIBRARIES WERE SEARCHED FOR PAPERS UP TO JULY 2016 ADDRESSING BIOCHEMICAL CHANGES AFTER EXERCISE WITH A PARTICULAR REFERENCE TO CANCER. THE THREE AUTHORS INDEPENDENTLY ASSESSED THEIR APPROPRIATENESS FOR INCLUSION IN THIS REVIEW BASED ON THEIR SCIENTIFIC QUALITY AND RELEVANCE. RESULTS: 168 PAPERS WERE SELECTED AND CATEGORISED INTO INDIRECT AND DIRECT BIOCHEMICAL PATHWAYS. THE INDIRECT EFFECTS INCLUDED CHANGES IN VITAMIN D, WEIGHT REDUCTION, SUNLIGHT EXPOSURE AND IMPROVED MOOD. THE DIRECT EFFECTS INCLUDED INSULIN-LIKE GROWTH FACTOR, EPIGENETIC EFFECTS ON GENE EXPRESSION AND DNA REPAIR, VASOACTIVE INTESTINAL PEPTIDE, OXIDATIVE STRESS AND ANTIOXIDANT PATHWAYS, HEAT SHOCK PROTEINS, TESTOSTERONE, IRISIN, IMMUNITY, CHRONIC INFLAMMATION AND PROSTAGLANDINS, ENERGY METABOLISM AND INSULIN RESISTANCE. SUMMARY: EXERCISE IS ONE OF SEVERAL LIFESTYLE FACTORS KNOWN TO LOWER THE RISK OF DEVELOPING CANCER AND IS ASSOCIATED WITH LOWER RELAPSE RATES AND BETTER SURVIVAL. THIS REVIEW HIGHLIGHTS THE NUMEROUS BIOCHEMICAL PROCESSES, WHICH EXPLAIN THESE POTENTIAL ANTICANCER BENEFITS. 2017 4 5450 35 REPRODUCTIVE TOXICITY OF COMBINED EFFECTS OF ENDOCRINE DISRUPTORS ON HUMAN REPRODUCTION. CONFLUENCE OF ENVIRONMENTAL, GENETIC, AND LIFESTYLE VARIABLES IS RESPONSIBLE FOR DETERIORATION OF HUMAN FECUNDITY. ENDOCRINE DISRUPTORS OR ENDOCRINE DISRUPTING CHEMICALS (EDCS) MAY BE FOUND IN A VARIETY OF FOODS, WATER, AIR, BEVERAGES, AND TOBACCO SMOKE. IT HAS BEEN DEMONSTRATED IN EXPERIMENTAL INVESTIGATIONS THAT A WIDE RANGE OF ENDOCRINE DISRUPTING CHEMICALS HAVE NEGATIVE EFFECTS ON HUMAN REPRODUCTIVE FUNCTION. HOWEVER, EVIDENCE ON THE REPRODUCTIVE CONSEQUENCES OF HUMAN EXPOSURE TO ENDOCRINE DISRUPTING CHEMICALS IS SPARSE AND/OR CONFLICTING IN THE SCIENTIFIC LITERATURE. THE COMBINED TOXICOLOGICAL ASSESSMENT IS A PRACTICAL METHOD FOR ASSESSING THE HAZARDS OF COCKTAILS OF CHEMICALS, CO-EXISTING IN THE ENVIRONMENT. THE CURRENT REVIEW PROVIDES A COMPREHENSIVE OVERVIEW OF STUDIES EMPHASIZING THE COMBINED TOXICITY OF ENDOCRINE DISRUPTING CHEMICALS ON HUMAN REPRODUCTION. ENDOCRINE DISRUPTING CHEMICALS INTERACT WITH EACH OTHER TO DISRUPT THE DIFFERENT ENDOCRINE AXES, RESULTING IN SEVERE GONADAL DYSFUNCTIONS. TRANSGENERATIONAL EPIGENETIC EFFECTS HAVE ALSO BEEN INDUCED IN GERM CELLS, MOSTLY THROUGH DNA METHYLATION AND EPIMUTATIONS. SIMILARLY, AFTER ACUTE OR CHRONIC EXPOSURE TO ENDOCRINE DISRUPTING CHEMICALS COMBINATIONS, INCREASED OXIDATIVE STRESS (OS), ELEVATED ANTIOXIDANT ENZYMATIC ACTIVITY, DISRUPTED REPRODUCTIVE CYCLE, AND REDUCED STEROIDOGENESIS ARE OFTEN REPORTED CONSEQUENCES. THE ARTICLE ALSO DISCUSSES THE CONCENTRATION ADDITION (CA) AND INDEPENDENT ACTION (IA) PREDICTION MODELS, WHICH REVEAL THE IMPORTANCE OF VARIOUS SYNERGISTIC ACTIONS OF ENDOCRINE DISRUPTING CHEMICALS MIXTURES. MORE CRUCIALLY, THIS EVIDENCE-BASED STUDY ADDRESSES THE RESEARCH LIMITATIONS AND INFORMATION GAPS, AS WELL AS PARTICULARLY PRESENTS THE FUTURE RESEARCH VIEWS ON COMBINED ENDOCRINE DISRUPTING CHEMICALS TOXICITY ON HUMAN REPRODUCTION. 2023 5 2869 40 FUNCTIONAL FOODS AND HEALTH EFFECTS: A NUTRITIONAL BIOCHEMISTRY PERSPECTIVE. BACKGROUND: INCREASED CONSUMER S INTEREST IN HEALTH HAS DRIVEN THE DEVELOPMENT OF FOODS THAT OFFER SPECIFIC BENEFICIAL EFFECTS. THE LIST OF FOODS AND INGREDIENTS INCLUDES ESSENTIAL AND NON-ESSENTIAL NUTRIENTS, PLANT AND MARINE COMPONENTS, WHOLE FOODS, MICROORGANISMS, MICROALGAE AND TECHNOLOGICAL APPROACHES. TRADITIONALLY, HEALTH OUTCOMES FOCUSSED ON THE PREVENTION OF CHRONIC DISEASES BUT HEALTH TARGETS HAVE EXPANDED TO COVER AREAS SUCH AS BRAIN HEALTH, INFLAMMATION, EYE HEALTH, WOMEN S HEALTH, HEALTHY AGEING AND BEAUTY. OBJECTIVE: THIS REVIEW HIGHLIGHTS, FROM A NUTRITIONAL BIOCHEMISTRY PERSPECTIVE, DIFFERENTIAL ASPECTS ON DESIGNING AND INTERPRETING HUMAN STUDIES TO SUPPORT THE HEALTH EFFECTS OF FUNCTIONAL FOODS. RESULTS: DESPITE THE AVAILABLE EVIDENCE FROM IN VITRO, ANIMAL AND OBSERVATIONAL STUDIES, WELLDESIGNED HUMAN STUDIES ARE NECESSARY TO SUPPORT THE HEALTH EFFECTS OF FUNCTIONAL FOODS. INTERVENTION TRIALS WITH FOODS ARE COMPLEX AS THEY IMPLY LIMITATIONS DUE TO METHODOLOGICAL, FOOD-RELATED AND HOST-RELATED FACTORS. THE USE OF RESPONSIVE, VALIDATED AND CLINICALLY RELEVANT MARKERS BECOMES ESSENTIAL EVEN THOUGH THERE IS A LACK OF RELIABLE BIOMARKERS OF EXPOSURE FOR MANY BIOACTIVES. FURTHERMORE, THE EFFECT OF MODULATING FACTORS SUCH AS SUBCLINICAL INFLAMMATION, GUT MICROBIOTA AND GENETIC VARIABILITY SHOULD BE TAKEN INTO ACCOUNT. MULTIPLE INDICATORS MAY PROVIDE A MORE RELIABLE ALTERNATIVE TO ASSESS PHYSIOLOGICAL PROCESSES WHILE EMERGING BIOMARKERS (MICRORNAS, EPIGENETIC CHANGES) CONSTITUTE A PROMISING APPROACH. ADDITIONALLY, THE MAGNITUDE OF THE CHANGE IS CRITICAL TO SUPPORT ANY HEALTH EFFECT ALTHOUGH INTERVENTIONS MAY HAVE A LIMITED CLINICAL IMPACT BUT BE EPIDEMIOLOGICALLY RELEVANT. ALSO, BASED ON THE AVAILABLE DATA, THE PREMISE THAT BIOACTIVESCONTAINING FOODS ARE SAFE MAY BE QUESTIONABLE. CONCLUSION: AN INTEGRATED APPROACH INCLUDING MULTIPLE BIOMARKERS, GENETIC VARIABILITY, EFFECT OF GUT MICROBIOTA AND RISK/BENEFIT ASSESSMENT SHOULD BE USED TO SUPPORT THE POTENTIAL HEALTH EFFECTS OF FUNCTIONAL FOODS. 2016 6 380 35 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 7 1066 43 CLINICAL USE OF AMINO ACIDS AS DIETARY SUPPLEMENT: PROS AND CONS. NITROGEN SUPPLY IS PIVOTAL FOR THE MAINTENANCE OF LIFE. AMINO ACIDS CAN BE UTILIZED TO SYNTHESIZE BOTH GLUCOSE AND LIPIDS. THE OPPOSITE, I.E., PRODUCTION OF AMINO ACIDS FROM EITHER ONE OF THEM, IS NOT POSSIBLE IN THE ABSENCE OF OTHER AMINO ACIDS AS DONORS OF NITROGEN. THE QUALITY OF AMINO ACID CONTENT IN PROTEIN HAS BEEN RE-EVALUATED RECENTLY, AND THE RELEVANCE OF ESSENTIAL AMINO ACIDS HAS BEEN REPEATEDLY UNDERLINED. ESSENTIAL AMINO ACID REQUIREMENTS IN DIFFERENT MAMMALS ARE NOT IDENTICAL, AND RATIOS AMONG THEM SHOULD BE TAKEN INTO ACCOUNT WHEN PROJECTING AN EFFICIENT FORMULATION. RECENT RESEARCH HAS DEMONSTRATED THAT GENES RESPOND TO DIFFERENT QUALITIES AND QUANTITIES OF NUTRITIONAL SUPPLY, AND INCREASED PROVISION OF ESSENTIAL AMINO ACIDS INCREASES LIFESPAN IN ANIMAL EXPERIMENTS THROUGH MITOCHONDRIOGENESIS AND MAINTENANCE OF ELEVATED RATES OF SYNTHESIS OF ANTI-OXIDANT MOLECULES. MOREOVER, GENETIC EXPRESSION OF KEY CONTROLLERS OF SYNTHESIS, LIKE MTOR, MAY BE PARTICULARLY IMPORTANT FOR UNDERSTANDING SKELETAL MUSCLE MAINTENANCE. LOSSES OF MUSCLE MASS AND IMPAIRED IMMUNE FUNCTION ARE RELATED TO REDUCED PROTEIN SUPPLY, AND THERE IS INCREASING EVIDENCE THAT REGULAR ESSENTIAL AMINO ACID INTAKE AS PART OF AN ORAL DIET IS EFFECTIVE IN REVERSING MUSCLE CATABOLISM, PROMOTING MUSCLE ANABOLISM, AND RESTORING IMMUNOLOGICAL FUNCTION. THEREFORE, THE USE OF AMINO ACIDS AS SUPPLEMENTS TO DIET WOULD BE EXPANDING IN THE NEAR FUTURE. IS THIS SAFE? FEW DATA ARE AVAILABLE ON AMINO ACID TOXICITY, AND ONLY ONE ESSENTIAL AMINO ACID MAY BE CONSIDERED TO HAVE CLINICALLY RELEVANT TOXICITY: METHIONINE, BECAUSE IT IS TRANSFORMED INTO A TOXIC INTERMEDIATE, HOMOCYSTEINE, WHEN CYSTEINE SYNTHESIS IS REQUIRED BY METABOLIC NEEDS. MATCHING OF STOICHIOMETRIC RATIOS BETWEEN METHIONINE AND CYSTEINE MAY SOLVE THE PROBLEM OF SUPPLYING SUFFICIENT AMOUNTS OF SULFUR TO THE BODY. ARGININE AND GLUTAMINE ARE TWO NON-ESSENTIAL AMINO ACIDS THAN CAN BECOME "CONDITIONALLY ESSENTIAL" BECAUSE OF ELEVATED NEEDS DURING PATHOLOGICAL CONDITIONS, AND METABOLISM MAY NOT BE ABLE TO MAINTAIN THEIR CONCENTRATIONS AT SUFFICIENT LEVELS TO MATCH METABOLIC REQUIREMENTS. CHRONIC EXOGENOUS ARGININE SUPPLEMENTATION HAS NOT PROVEN TO EXERT POSITIVE CLINICAL EFFECTS IN DIFFERENT TRIALS, AND SEQUENTIAL ARTICULATION OF THE KNOWLEDGE OF INTRODUCTION OF ARGININE-DRIVEN TRANSCRIPTIONAL, TRANSLATIONAL, AND EPIGENETIC ADAPTATIONS MAY GIVE US A KEY FOR INTERPRETING THOSE PUZZLING RESULTS. 2011 8 3881 36 KETOGENIC DIETS AND THE NERVOUS SYSTEM: A SCOPING REVIEW OF NEUROLOGICAL OUTCOMES FROM NUTRITIONAL KETOSIS IN ANIMAL STUDIES. OBJECTIVES: KETOGENIC DIETS HAVE REPORTED EFFICACY FOR NEUROLOGICAL DYSFUNCTIONS; HOWEVER, THERE ARE LIMITED PUBLISHED HUMAN CLINICAL TRIALS ELUCIDATING THE MECHANISMS BY WHICH NUTRITIONAL KETOSIS PRODUCES THERAPEUTIC EFFECTS. THE PURPOSE OF THIS PRESENT STUDY WAS TO INVESTIGATE ANIMAL MODELS THAT REPORT VARIATIONS IN NERVOUS SYSTEM FUNCTION BY CHANGING FROM A STANDARD ANIMAL DIET TO A KETOGENIC DIET, SYNTHESISE THESE INTO BROAD THEMES, AND COMPARE THESE WITH MECHANISMS REPORTED AS TARGETS IN PAIN NEUROSCIENCE TO INFORM HUMAN CHRONIC PAIN TRIALS. METHODS: AN ELECTRONIC SEARCH OF SEVEN DATABASES WAS CONDUCTED IN JULY 2020. TWO INDEPENDENT REVIEWERS SCREENED STUDIES FOR ELIGIBILITY, AND DESCRIPTIVE OUTCOMES RELATING TO NERVOUS SYSTEM FUNCTION WERE EXTRACTED FOR A THEMATIC ANALYSIS, THEN SYNTHESISED INTO BROAD THEMES. RESULTS: IN TOTAL, 170 STUDIES FROM EIGHTEEN DIFFERENT DISEASE MODELS WERE IDENTIFIED AND GROUPED INTO FOURTEEN BROAD THEMES: ALTERATIONS IN CELLULAR ENERGETICS AND METABOLISM, BIOCHEMICAL, CORTICAL EXCITABILITY, EPIGENETIC REGULATION, MITOCHONDRIAL FUNCTION, NEUROINFLAMMATION, NEUROPLASTICITY, NEUROPROTECTION, NEUROTRANSMITTER FUNCTION, NOCICEPTION, REDOX BALANCE, SIGNALLING PATHWAYS, SYNAPTIC TRANSMISSION AND VASCULAR SUPPLY. DISCUSSION: THE MECHANISMS PRESENTED CENTRED AROUND THE REDUCTION OF INFLAMMATION AND OXIDATIVE STRESS AS WELL AS A REDUCTION IN NERVOUS SYSTEM EXCITABILITY. GIVEN THE MULTIPLE POTENTIAL MECHANISMS PRESENTED, IT IS LIKELY THAT MANY OF THESE ARE INVOLVED SYNERGISTICALLY AND UNDERGO ADAPTIVE PROCESSES WITHIN THE HUMAN BODY, AND CONTROLLED ANIMAL MODELS THAT LIMIT THE INVESTIGATION TO A PARTICULAR PATHWAY IN ISOLATION MAY REACH DIFFERING CONCLUSIONS. ATTENTION IS REQUIRED WHEN TRANSLATING THIS INFORMATION TO HUMAN CHRONIC PAIN POPULATIONS OWING TO THE LIMITATIONS OUTLINED FROM THE ANIMAL RESEARCH. 2022 9 103 38 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 10 375 29 AN ENERGETIC VIEW OF STRESS: FOCUS ON MITOCHONDRIA. ENERGY IS REQUIRED TO SUSTAIN LIFE AND ENABLE STRESS ADAPTATION. AT THE CELLULAR LEVEL, ENERGY IS LARGELY DERIVED FROM MITOCHONDRIA - UNIQUE MULTIFUNCTIONAL ORGANELLES WITH THEIR OWN GENOME. FOUR MAIN ELEMENTS CONNECT MITOCHONDRIA TO STRESS: (1) ENERGY IS REQUIRED AT THE MOLECULAR, (EPI)GENETIC, CELLULAR, ORGANELLAR, AND SYSTEMIC LEVELS TO SUSTAIN COMPONENTS OF STRESS RESPONSES; (2) GLUCOCORTICOIDS AND OTHER STEROID HORMONES ARE PRODUCED AND METABOLIZED BY MITOCHONDRIA; (3) RECIPROCALLY, MITOCHONDRIA RESPOND TO NEUROENDOCRINE AND METABOLIC STRESS MEDIATORS; AND (4) EXPERIMENTALLY MANIPULATING MITOCHONDRIAL FUNCTIONS ALTERS PHYSIOLOGICAL AND BEHAVIORAL RESPONSES TO PSYCHOLOGICAL STRESS. THUS, MITOCHONDRIA ARE ENDOCRINE ORGANELLES THAT PROVIDE BOTH THE ENERGY AND SIGNALS THAT ENABLE AND DIRECT STRESS ADAPTATION. NEURAL CIRCUITS REGULATING SOCIAL BEHAVIOR - AS WELL AS PSYCHOPATHOLOGICAL PROCESSES - ARE ALSO INFLUENCED BY MITOCHONDRIAL ENERGETICS. AN INTEGRATIVE VIEW OF STRESS AS AN ENERGY-DRIVEN PROCESS OPENS NEW OPPORTUNITIES TO STUDY MECHANISMS OF ADAPTATION AND REGULATION ACROSS THE LIFESPAN. 2018 11 4652 29 NEUROPROTECTION WITH NATURAL ANTIOXIDANTS AND NUTRACEUTICALS IN THE CONTEXT OF BRAIN CELL DEGENERATION: THE EPIGENETIC CONNECTION. BIOACTIVE ANTIOXIDANT AGENTS PRESENT IN SELECTED PLANTS ARE KNOWN TO PROVIDE THE FIRST LINE OF BIOLOGICAL DEFENSE AGAINST OXIDATIVE STRESS. IN PARTICULAR, SOLUBLE VITAMIN C, E, CAROTENOIDS AND PHENOLIC COMPOUNDS HAVE DEMONSTRATED CRUCIAL BIOLOGICAL EFFECTS IN CELLS AGAINST OXIDATIVE DAMAGE, PREVENTING PREVALENT CHRONIC DISEASES, SUCH AS DIABETES, CANCER AND CARDIOVASCULAR DISEASE. THE REPORTED WIDE RANGE OF EFFECTS THAT INCLUDED ANTI-AGING, ANTI-ATHEROSCLEROSIS, ANTI-INFLAMMATORY AND ANTICANCER ACTIVITY WERE STUDIED AGAINST DEGENERATIVE PATHOLOGIES OF THE BRAIN. VITAMINS AND DIFFERENT PHYTOCHEMICALS ARE IMPORTANT EPIGENETIC MODIFIERS THAT PREVENT NEURODEGENERATION. IN ORDER TO EXPLORE THE POTENTIAL ANTIOXIDANT SOURCES IN FUNCTIONAL FOODS AND NUTRACEUTICALS AGAINST NEURODEGENERATION, THE PRESENT PAPER AIMS TO SHOW A COMPREHENSIVE ASSESSMENT OF ANTIOXIDANT ACTIVITY AT CHEMICAL AND CELLULAR LEVELS. THE EFFECTS OF THE DIFFERENT BIOACTIVE COMPOUNDS AVAILABLE AND THEIR ANTIOXIDANT ACTIVITY THROUGH AN EPIGENETIC POINT OF VIEW ARE ALSO DISCUSSED. 2019 12 367 37 AMPLIFIED PAIN SYNDROMES IN CHILDREN: TREATMENT AND NEW INSIGHTS INTO DISEASE PATHOGENESIS. PURPOSE OF REVIEW: ALTHOUGH MANY DIAGNOSTIC TERMS ARE USED FOR PEDIATRIC CHRONIC PAIN, EVIDENCE SUGGESTS A COMMON THREAD OF SIGNAL AMPLIFICATION, LEADING TO THE UNIFYING TERM 'AMPLIFIED PAIN SYNDROMES'. ONGOING RESEARCH PROVIDES NEW INSIGHTS INTO BIOPSYCHOSOCIAL CONTRIBUTORS AND TREATMENTS FOR PEDIATRIC AMPLIFIED PAIN SYNDROMES. RECENT FINDINGS: BASIC SCIENCE INDICATES A COMPLEX INTERPLAY OF GENETIC, EPIGENETIC, NEUROCHEMICAL, ENDOCRINE, AND INFLAMMATORY CONTRIBUTORS, ALONG WITH ENVIRONMENTAL AND PSYCHOLOGICAL FACTORS. ALTHOUGH MEDICATIONS AND INTERVENTIONS REMAIN COMMON APPROACHES TO CHILDREN WITH CHRONIC PAIN, THEIR EVIDENCE IS LIMITED. PRELIMINARY EVIDENCE EXISTS FOR MINDFULNESS-BASED THERAPIES, YOGA, AND OTHER COMPLEMENTARY/ALTERNATIVE MEDICINE APPROACHES. THE STRONGEST EVIDENCE IS FOR EXERCISE-BASED AND COGNITIVE-BEHAVIORAL TREATMENTS, IN PARTICULAR, WHEN COMBINED IN A MULTIDISCIPLINARY FORMAT. INTENSIVE APPROACHES (PAIN REHABILITATION) HAVE THE POTENTIAL TO EFFECTIVELY AND EFFICIENTLY TREAT THOSE MOST DISABLED BY AMPLIFIED PAIN SYNDROMES, AND LEAD TO SUSTAINED IMPROVEMENT IN PAIN, FUNCTIONING, AND MEDICAL UTILIZATION. SUMMARY: ALTHOUGH UNDERSTANDING OF THE MECHANISMS UNDERLYING PEDIATRIC AMPLIFIED PAIN SYNDROMES EVOLVES, STANDARD OF CARE IS MULTIDISCIPLINARY EMPHASIZING EXERCISE THERAPY, COGNITIVE-BEHAVIORAL TREATMENT, AND SELF-REGULATION. TREATMENT SHOULD TARGET FULL RETURN TO PHYSICAL FUNCTION, WHICH LEADS TO SUBSEQUENT IMPROVEMENT OR RESOLUTION OF PAIN. MULTIDISCIPLINARY CARE CAN BE COORDINATED BY A RHEUMATOLOGIST OR OTHER PHYSICIAN WITH APPROPRIATE REFERRALS, OR THROUGH A MULTIDISCIPLINARY TEAM. 2014 13 2900 34 GENDER BIAS IN THERAPEUTIC EFFORT: FROM RESEARCH TO HEALTH CARE. THERE ARE RELEVANT DIMENSIONS FROM A GENDER PERSPECTIVE RELATED TO THERAPEUTIC EFFORT. TO ILLUSTRATE AND DISCUSS POSSIBLE GENDER BIAS RELATED TO MEDICINES, THROUGH THE CONSUMPTION ANALYSIS IN WOMEN, THE PRESCRIPTION OF BIOLOGICAL DRUGS ACCORDING TO SEX, THE POTENTIAL GENDER INEQUALITY IN ADVERSE DRUG REACTIONS, AND RESEARCH WITH CLINICAL TRIALS, AS WELL AS THE DECISIONS OF INTERNATIONAL INSTITUTIONS IN THE MARKETING OF MEDICINAL PRODUCTS. THERE IS GREATER TENDENCY TO PRESCRIBE PAIN RELIEVERS, REGARDLESS OF PAIN, AND DRUGS FOR LOW INTENSITY DEPRESSIVE SYMPTOMS IN WOMEN THAN IN MEN. THE OPPOSITE OCCURS IN THE PRESCRIPTION OF STATINS AND ADEQUATE DOSES, AND WITH THE GREATER PROBABILITY OF PRESCRIBING ANTI-TUMOR NECROSIS FACTOR IN MEN THAN IN WOMEN WITH ANKYLOSING SPONDYLITIS, DESPITE A SIMILAR DISEASE BURDEN. ADVERSE DRUG REACTIONS ARE OBSERVED MORE FREQUENTLY IN WOMEN THAN IN MEN, WHERE DETERMINANTS SUCH AS BODY WEIGHT ARE HAVING LITTLE INFLUENCE ON THE DOSAGE. IT IS CURRENTLY SCARCELY CONSIDERED IN THE PRESCRIPTION THAT WOMEN HAVE DIFFERENCES IN THE ACTIVITY OF CYTOCHROME CYPP450 ENZYMES, WHICH CAN AFFECT THE LIVER'S METABOLISM RATE. THERE ARE EVEN IMMUNOLOGICAL, GENETIC AND EPIGENETIC EFFECTS (DUE TO HEREDITY AND UNEVEN GENE DOSING LOCATED IN THE X AND Y CHROMOSOMES) THAT CAN INFLUENCE THESE DIFFERENCES BY SEX. FINALLY, THROUGH CASES OF HORMONAL THERAPY CLINICAL TRIALS, A DRUG FOR WOMEN'S INHIBITED SEXUAL DESIRE AND A CONTRACEPTIVE FOR MEN, GENDER BIAS AND STEREOTYPES ARE SHOWN TO INFLUENCE A POTENTIAL GENERATION OF INEQUALITIES, ESPECIALLY IN ADVERSE DRUG REACTIONS TO THE DETRIMENT OF WOMEN. IN CONCLUSION, HEALTH PROFESSIONALS FREQUENTLY ATTRIBUTE PHYSICAL SYMPTOMS TO WOMEN'S EMOTIONALITY, INFLUENCING THEIR GREATER PRESCRIPTION OF SYMPTOMATIC DRUGS. WHETHER THE SAME REASON INFLUENCES THE LOWER PRESCRIPTION OF THERAPEUTIC DRUGS IN WOMEN THAN IN MEN SHOULD BE ANALYZED. THERE ARE BIOLOGICAL DETERMINANTS TO CONSIDER DUE TO THEIR INFLUENCE ON A GREATER PHARMACOLOGICAL TOXICITY IN WOMEN. CLINICAL TRIALS SHOULD IMPROVE ACCORDING TO THE GENDER RECOMMENDATIONS BY THE FOOD AND DRUGS ADMINISTRATION. 2020 14 6329 42 THE ROLE OF CHILDHOOD TRAUMA IN BIPOLAR DISORDERS. THIS REVIEW WILL DISCUSS THE ROLE OF CHILDHOOD TRAUMA IN BIPOLAR DISORDERS. RELEVANT STUDIES WERE IDENTIFIED VIA MEDLINE (PUBMED) AND PSYCINFO DATABASES PUBLISHED UP TO AND INCLUDING JULY 2015. THIS REVIEW CONTRIBUTES TO A NEW UNDERSTANDING OF THE NEGATIVE CONSEQUENCES OF EARLY LIFE STRESS, AS WELL AS SETTING CHILDHOOD TRAUMA IN A BIOLOGICAL CONTEXT OF SUSCEPTIBILITY AND DISCUSSING NOVEL LONG-TERM PATHOPHYSIOLOGICAL CONSEQUENCES IN BIPOLAR DISORDERS. CHILDHOOD TRAUMATIC EVENTS ARE RISK FACTORS FOR DEVELOPING BIPOLAR DISORDERS, IN ADDITION TO A MORE SEVERE CLINICAL PRESENTATION OVER TIME (PRIMARILY AN EARLIER AGE AT ONSET AND AN INCREASED RISK OF SUICIDE ATTEMPT AND SUBSTANCE MISUSE). CHILDHOOD TRAUMA LEADS TO ALTERATIONS OF AFFECT REGULATION, IMPULSE CONTROL, AND COGNITIVE FUNCTIONING THAT MIGHT DECREASE THE ABILITY TO COPE WITH LATER STRESSORS. CHILDHOOD TRAUMA INTERACTS WITH SEVERAL GENES BELONGING TO SEVERAL DIFFERENT BIOLOGICAL PATHWAYS [HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS, SEROTONERGIC TRANSMISSION, NEUROPLASTICITY, IMMUNITY, CALCIUM SIGNALING, AND CIRCADIAN RHYTHMS] TO DECREASE THE AGE AT THE ONSET OF THE DISORDER OR INCREASE THE RISK OF SUICIDE. EPIGENETIC FACTORS MAY ALSO BE INVOLVED IN THE NEUROBIOLOGICAL CONSEQUENCES OF CHILDHOOD TRAUMA IN BIPOLAR DISORDER. BIOLOGICAL SEQUELAE SUCH AS CHRONIC INFLAMMATION, SLEEP DISTURBANCE, OR TELOMERE SHORTENING ARE POTENTIAL MEDIATORS OF THE NEGATIVE EFFECTS OF CHILDHOOD TRAUMA IN BIPOLAR DISORDERS, IN PARTICULAR WITH REGARD TO PHYSICAL HEALTH. THE MAIN CLINICAL IMPLICATION IS TO SYSTEMATICALLY ASSESS CHILDHOOD TRAUMA IN PATIENTS WITH BIPOLAR DISORDERS, OR AT LEAST IN THOSE WITH A SEVERE OR INSTABLE COURSE. THE CHALLENGE FOR THE NEXT YEARS WILL BE TO FILL THE GAP BETWEEN CLINICAL AND FUNDAMENTAL RESEARCH AND ROUTINE PRACTICE, SINCE RECOMMENDATIONS FOR MANAGING THIS SPECIFIC POPULATION ARE LACKING. IN PARTICULAR, LITTLE IS KNOWN ON WHICH PSYCHOTHERAPIES SHOULD BE PROVIDED OR WHICH TARGETS THERAPISTS SHOULD FOCUS ON, AS WELL AS HOW CHILDHOOD TRAUMA COULD EXPLAIN THE RESISTANCE TO MOOD STABILIZERS. 2016 15 5792 44 STAGING IN BIPOLAR DISORDER: FROM THEORETICAL FRAMEWORK TO CLINICAL UTILITY. ILLNESS STAGING IS WIDELY UTILIZED IN SEVERAL MEDICAL DISCIPLINES TO HELP PREDICT COURSE OR PROGNOSIS, AND OPTIMIZE TREATMENT. STAGING MODELS IN PSYCHIATRY IN GENERAL, AND BIPOLAR DISORDER IN PARTICULAR, DEPEND ON THE PREMISE THAT PSYCHOPATHOLOGY MOVES ALONG A PREDICTABLE PATH: AN AT-RISK OR LATENCY STAGE, A PRODROME PROGRESSING TO A FIRST CLINICAL THRESHOLD EPISODE, AND ONE OR MORE RECURRENCES WITH THE POTENTIAL TO REVERT OR PROGRESS TO LATE OR END-STAGE MANIFESTATIONS. THE UTILITY AND VALIDITY OF A STAGING MODEL FOR BIPOLAR DISORDER DEPEND ON ITS LINKING TO CLINICAL OUTCOME, TREATMENT RESPONSE AND NEUROBIOLOGICAL MEASURES. THESE INCLUDE PROGRESSIVE BIOCHEMICAL, NEUROIMAGING AND COGNITIVE CHANGES, AND POTENTIALLY STAGE-SPECIFIC DIFFERENCES IN RESPONSE TO PHARMACOLOGICAL AND PSYCHOSOCIAL TREATMENTS. MECHANISTICALLY, STAGING MODELS IMPLY THE PRESENCE OF AN ACTIVE DISEASE PROCESS THAT, IF NOT REMEDIATED, CAN LEAD TO NEUROPROGRESSION, A MORE MALIGNANT DISEASE COURSE AND FUNCTIONAL DETERIORATION. BIOLOGICAL ELEMENTS THOUGHT TO BE OPERATIVE IN BIPOLAR DISORDER INCLUDE A GENETIC DIATHESIS, PHYSICAL AND PSYCHIC TRAUMA, EPIGENETIC CHANGES, ALTERED NEUROGENESIS AND APOPTOSIS, MITOCHONDRIAL DYSFUNCTION, INFLAMMATION, AND OXIDATIVE STRESS. MANY AVAILABLE AGENTS, SUCH AS LITHIUM, HAVE EFFECTS ON THESE TARGETS. STAGING MODELS ALSO SUGGEST THE UTILITY OF STAGE-SPECIFIC TREATMENT APPROACHES THAT MAY NOT ONLY TARGET SYMPTOM REDUCTION, BUT ALSO IMPEDE ILLNESS NEUROPROGRESSION. THESE TREATMENT APPROACHES RANGE FROM PREVENTION FOR AT-RISK INDIVIDUALS, TO EARLY INTERVENTION STRATEGIES FOR PRODROMAL AND NEWLY DIAGNOSED INDIVIDUALS, COMPLEX COMBINATION THERAPY FOR RAPIDLY RECURRENT ILLNESS, AND PALLIATIVE-TYPE APPROACHES FOR THOSE AT CHRONIC, LATE STAGES OF ILLNESS. THERE IS HOPE THAT PROMPT INITIATION OF POTENTIALLY DISEASE MODIFYING THERAPIES MAY PRECLUDE OR ATTENUATE THE COGNITIVE AND STRUCTURAL CHANGES SEEN IN THE LATER STAGES OF BIPOLAR DISORDER. THE AIMS OF THIS PAPER ARE TO: A) EXPLORE THE CURRENT LEVEL OF EVIDENCE SUPPORTING THE DESCRIPTIVE STAGING OF THE SYNDROMAL PATTERN OF BIPOLAR DISORDER; B) DESCRIBE PRELIMINARY ATTEMPTS AT VALIDATION; C) MAKE RECOMMENDATIONS FOR THE DIRECTION OF FURTHER STUDIES; AND D) PROVIDE A DISTILLATION OF THE POTENTIAL CLINICAL IMPLICATIONS OF STAGING IN BIPOLAR DISORDER WITHIN A BROADER TRANSDIAGNOSTIC FRAMEWORK. 2017 16 682 38 BRAIN ON STRESS: HOW THE SOCIAL ENVIRONMENT GETS UNDER THE SKIN. STRESS IS A STATE OF THE MIND, INVOLVING BOTH BRAIN AND BODY AS WELL AS THEIR INTERACTIONS; IT DIFFERS AMONG INDIVIDUALS AND REFLECTS NOT ONLY MAJOR LIFE EVENTS BUT ALSO THE CONFLICTS AND PRESSURES OF DAILY LIFE THAT ALTER PHYSIOLOGICAL SYSTEMS TO PRODUCE A CHRONIC STRESS BURDEN THAT, IN TURN, IS A FACTOR IN THE EXPRESSION OF DISEASE. THIS BURDEN REFLECTS THE IMPACT OF NOT ONLY LIFE EXPERIENCES BUT ALSO GENETIC VARIATIONS AND INDIVIDUAL HEALTH BEHAVIORS SUCH AS DIET, PHYSICAL ACTIVITY, SLEEP, AND SUBSTANCE ABUSE; IT ALSO REFLECTS STABLE EPIGENETIC MODIFICATIONS IN DEVELOPMENT THAT SET LIFELONG PATTERNS OF PHYSIOLOGICAL REACTIVITY AND BEHAVIOR THROUGH BIOLOGICAL EMBEDDING OF EARLY ENVIRONMENTS INTERACTING WITH CUMULATIVE CHANGE FROM EXPERIENCES OVER THE LIFESPAN. HORMONES ASSOCIATED WITH THE CHRONIC STRESS BURDEN PROTECT THE BODY IN THE SHORT RUN AND PROMOTE ADAPTATION (ALLOSTASIS), BUT IN THE LONG RUN, THE BURDEN OF CHRONIC STRESS CAUSES CHANGES IN THE BRAIN AND BODY THAT CAN LEAD TO DISEASE (ALLOSTATIC LOAD AND OVERLOAD). BRAIN CIRCUITS ARE PLASTIC AND REMODELED BY STRESS TO CHANGE THE BALANCE BETWEEN ANXIETY, MOOD CONTROL, MEMORY, AND DECISION MAKING. SUCH CHANGES MAY HAVE ADAPTIVE VALUE IN PARTICULAR CONTEXTS, BUT THEIR PERSISTENCE AND LACK OF REVERSIBILITY CAN BE MALADAPTIVE. HOWEVER, THE CAPACITY OF BRAIN PLASTICITY TO EFFECTS OF STRESSFUL EXPERIENCES IN ADULT LIFE HAS ONLY BEGUN TO BE EXPLORED ALONG WITH THE EFFICACY OF TOP-DOWN STRATEGIES FOR HELPING THE BRAIN CHANGE ITSELF, SOMETIMES AIDED BY PHARMACEUTICAL AGENTS AND OTHER TREATMENTS. 2012 17 108 26 A REVIEW OF THE PROTECTIVE EFFECT OF MELATONIN IN PESTICIDE-INDUCED TOXICITY. PESTICIDES ARE AMONG THE MOST IMPORTANT CHEMICALS USED IN AGRICULTURE SECTOR. HOWEVER, THEIR EXTENSIVE USE HAS POLLUTED THE ENVIRONMENT AND INCREASED HUMAN VULNERABILITY TO VARIOUS CHRONIC DISEASES. PESTICIDE EXPOSURE CAUSES GENETIC AND EPIGENETIC MODIFICATIONS, ENDOCRINE DISRUPTION, MITOCHONDRIAL DYSFUNCTION AND OXIDATIVE STRESS. AREAS COVERED: THIS REVIEW IS BASED ON THE LITERATURE STUDIES CURRENTLY REPORTED ON PESTICIDE-INDUCED TOXICITY AND THE PROTECTIVE ROLE OF MELATONIN. SCIENTIFIC DATABASES SUCH AS PUBMED, SCOPUS AND WEB OF SCIENCE WERE SEARCHED USING KEYWORDS 'PESTICIDE' AND 'MELATONIN' UP TO JANUARY 2016. FULL LENGTH ARTICLES RELATED TO ANIMAL AND HUMAN EXPOSURE WERE RETRIEVED. A TOTAL NUMBER OF 181 RECORDS WERE OBTAINED, AND AFTER EXCLUDING THE DUPLICATES, 97 PAPERS WERE FURTHER SCREENED ON THE BASIS OF RELEVANCE TO THE TOPIC. EXPERT OPINION: MELATONIN AS A BROAD-SPECTRUM ANTIOXIDANT IS ABLE TO PENETRATE CELLULAR COMPARTMENTS SPECIFICALLY THE MITOCHONDRIA. IT IS A POTENT FREE RADICAL SCAVENGER WITH LOW TOXICITY AND DESIRABLE SOLUBILITY IN ORGANIC AND AQUEOUS PHASES. WE ARE OF THE OPINION THAT MELATONIN IS A PROMISING AGENT IN MINIMIZING ORGAN INJURIES INDUCED BY PESTICIDES. 2017 18 5280 33 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 19 6406 35 THE SEARCH FOR RELIABLE BIOMARKERS OF DISEASE IN MULTIPLE CHEMICAL SENSITIVITY AND OTHER ENVIRONMENTAL INTOLERANCES. WHILST FACING A WORLDWIDE FAST INCREASE OF FOOD AND ENVIRONMENTAL ALLERGIES, THE MEDICAL COMMUNITY IS ALSO CONFRONTED WITH ANOTHER INHOMOGENEOUS GROUP OF ENVIRONMENT-ASSOCIATED DISABLING CONDITIONS, INCLUDING MULTIPLE CHEMICAL SENSITIVITY (MCS), FIBROMYALGIA, CHRONIC FATIGUE SYNDROME, ELECTRIC HYPERSENSITIVITY, AMALGAM DISEASE AND OTHERS. THESE SHARE THE FEATURES OF POLY-SYMPTOMATIC MULTI-ORGAN CUTANEOUS AND SYSTEMIC MANIFESTATIONS, WITH POSTULATED INHERITED/ACQUIRED IMPAIRED METABOLISM OF CHEMICAL/PHYSICAL/NUTRITIONAL XENOBIOTICS, TRIGGERING ADVERSE REACTIONS AT EXPOSURE LEVELS FAR BELOW TOXICOLOGICALLY-RELEVANT VALUES, OFTEN IN THE ABSENCE OF CLEAR-CUT ALLERGOLOGIC AND/OR IMMUNOLOGIC INVOLVEMENT. DUE TO THE LACK OF PROVEN PATHOGENIC MECHANISMS GENERATING MEASURABLE DISEASE BIOMARKERS, THESE ENVIRONMENTAL HYPERSENSITIVITIES ARE GENERALLY IGNORED BY SANITARY AND SOCIAL SYSTEMS, AS PSYCHOGENIC OR "MEDICALLY UNEXPLAINED SYMPTOMS". THE UNCONTROLLED APPLICATION OF DIAGNOSTIC AND TREATMENT PROTOCOLS NOT CORRESPONDING TO ACCEPTABLE LEVELS OF VALIDATION, SAFETY, AND CLINICAL EFFICACY, TO A STEADILY INCREASING NUMBER OF PATIENTS DEMANDING ASSISTANCE, OCCURS IN MANY COUNTRIES IN THE ABSENCE OF EVIDENCE-BASED GUIDELINES. HERE WE REVISE AVAILABLE INFORMATION SUPPORTING THE ORGANIC NATURE OF THESE CLINICAL CONDITIONS. FOLLOWING INTENSE RESEARCH ON GENE POLYMORPHISMS OF PHASE I/II DETOXIFICATION ENZYME GENES, SO FAR STATISTICALLY INCONCLUSIVE, EPIGENETIC AND METABOLIC FACTORS ARE UNDER INVESTIGATION, IN PARTICULAR FREE RADICAL/ANTIOXIDANT HOMEOSTASIS DISTURBANCES. THE FINDING OF RELEVANT ALTERATIONS OF CATALASE, GLUTATHIONE-TRANSFERASE AND PEROXIDASE DETOXIFYING ACTIVITIES SIGNIFICANTLY CORRELATING WITH CLINICAL MANIFESTATIONS OF MCS, HAS RECENTLY REGISTERED SOME PROGRESS TOWARDS THE IDENTIFICATION OF RELIABLE BIOMARKERS OF DISEASE ONSET, PROGRESSION, AND TREATMENT OUTCOMES. 2011 20 6742 68 WHITHER THE ETIOPATHOGENESIS (AND SCOLIOGENY) OF ADOLESCENT IDIOPATHIC SCOLIOSIS? ALTHOUGH CONSIDERABLE PROGRESS HAD BEEN MADE IN THE PAST TWO DECADES IN UNDERSTANDING THE ETIOPATHOGENESIS OF ADOLESCENT IDIOPATHIC SCOLIOSIS (AIS), IT STILL LACKS AN AGREED THEORY OF ETIOPATHOGENESIS. ONE PROBLEM MAY BE THAT AIS RESULTS NOT FROM ONE CAUSE, BUT SEVERAL THAT INTERACT WITH VARIOUS GENETIC PREDISPOSING FACTORS. THERE IS A VIEW THERE ARE TWO OTHER PATHOGENIC PROCESSES FOR IDIOPATHIC SCOLIOSIS NAMELY, INITIATING (OR INDUCING), AND THOSE THAT CAUSE CURVE PROGRESSION. TWIN STUDIES AND OBSERVATIONS OF FAMILY AGGREGATION HAVE REVEALED SIGNIFICANT GENETIC CONTRIBUTIONS TO IDIOPATHIC SCOLIOSIS, THAT PLACE AIS AMONG OTHER COMMON DISEASE OR COMPLEX TRAITS WITH A HIGH HERITABILITY INTERPRETED BY THE GENETIC VARIANT HYPOTHESIS OF DISEASE. WE SUMMARIZE ETIOPATHOGENETIC KNOWLEDGE OF AIS AS THEORIES OF PATHOGENESIS INCLUDING RECENT MULTIPLE CONCEPTS, AND BLOOD TESTS FOR AIS BASED ON PREDICTIVE BIOMARKERS AND GENETIC VARIANTS THAT SIGNIFY DISEASE RISK. THERE IS INCREASING EVIDENCE FOR THE POSSIBILITY OF AN UNDERLYING NEUROLOGICAL DISORDER FOR AIS, RESEARCH WHICH HOLDS PROMISE. LIKE BRAIN RESEARCH, MOST AIS WORKERS FOCUS ON THEIR OWN CORNER AND THERE IS A NEED FOR GREATER INTEGRATION OF RESEARCH EFFORT. EPIGENETICS, A RELATIVELY RECENT FIELD, EVALUATES FACTORS CONCERNED WITH GENE EXPRESSION IN RELATION TO ENVIRONMENT, DISEASE, NORMAL DEVELOPMENT AND AGING, WITH A COMPLEX REGULATION ACROSS THE GENOME DURING THE FIRST DECADE OF LIFE. RESEARCH ON THE ROLE OF ENVIRONMENTAL FACTORS, EPIGENETICS AND CHRONIC NON-COMMUNICABLE DISEASES (NCDS) INCLUDING ADIPOSITY, AFTER A SLOW START, HAS EXPLODED IN THE LAST DECADE. NOT SO FOR AIS RESEARCH AND THE ENVIRONMENT WHERE, EXCEPT FOR MONOZYGOTIC TWIN STUDIES, THERE ARE ONLY SPORADIC REPORTS TO SUGGEST THAT ENVIRONMENTAL FACTORS ARE AT WORK IN ETIOLOGY. HERE, WE EXAMINE EPIGENETIC CONCEPTS AS THEY MAY RELATE TO HUMAN DEVELOPMENT, NORMAL LIFE HISTORY PHASES AND AIS PATHOGENESIS. ALTHOUGH AIS IS NOT REGARDED AS AN NCD, LIKE THEM, IT IS ASSOCIATED WITH WHOLE ORGANISM METABOLIC PHENOMENA, INCLUDING LOWER BODY MASS INDEX, LOWER CIRCULATING LEPTIN LEVELS AND OTHER SYSTEMIC DISORDERS. SOME EPIGENETIC RESEARCH APPLIED TO SILVER-RUSSELL SYNDROME AND ADIPOSITY IS EXAMINED, FROM WHICH SUGGESTIONS ARE MADE FOR CONSIDERATION OF AIS EPIGENETIC RESEARCH, CROSS-SECTIONAL AND LONGITUDINAL. THE WORD SCOLIOGENY IS SUGGESTED TO INCLUDE ETIOLOGY, PATHOGENESIS AND PATHOMECHANISM. 2012