1 2900 156 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 2 6822 48 [GENDER MEDICINE. SEX- AND GENDER-SPECIFIC ASPECTS OF CLINICAL MEDICINE]. GENDER MEDICINE STUDIES SEX- AND GENDER-BASED DIFFERENCES IN THE DEVELOPMENT AND PREVENTION OF DISEASES, THE AWARENESS AND PRESENTATION OF SYMPTOMS, AND THE EFFECTIVENESS OF THERAPY. GENDER MEDICINE IS PART OF PERSONALIZED MEDICINE, CONSIDERING DIFFERENCES IN BIOLOGICAL AND PSYCHOSOCIAL FACTORS INDIVIDUALLY. THERE ARE DIFFERENCES IN GENES, CHROMOSOMES, HORMONES, AND METABOLISM AS WELL AS DIFFERENCES IN CULTURE, ENVIRONMENT, AND SOCIETY. LIFELONG INTERACTIONS BETWEEN PHYSICAL AND PSYCHOSOCIAL FACTORS WILL INFLUENCE THE HEALTH AND ILL-HEALTH OF MEN AND WOMEN IN DIFFERENT WAYS. EPIGENETIC MODIFICATIONS PROVIDE EVIDENCE OF THE IMPACT OF ENVIRONMENT AND LIFESTYLE DURING VULNERABLE PHASES ON BIOLOGICAL PROCESSES, EFFECTING FUTURE GENERATIONS. MATERNAL LIFESTYLE AND ENVIRONMENTAL FACTORS DURING PREGNANCY CAN IMPACT THE HEALTH OF OFFSPRING IN LATER LIFE ALREADY IN UTERO IN A SEX-SPECIFIC WAY. PAIN, STRESS, AND COPING STYLES DIFFER BETWEEN MEN AND WOMEN. WOMEN EXPERIENCE MORE DRAMATIC PHYSICAL CHANGES DURING THEIR LIFETIME, WHICH ARE ASSOCIATED WITH SPECIFIC BURDENS AND PSYCHOSOCIAL ALTERATIONS. WOMEN WITH MULTIPLE ROLES AND RESPONSIBILITIES SUFFERING FROM STRESS DEVELOP DEPRESSION MORE FREQUENTLY. HOWEVER, MEN ARE OFTEN NOT DIAGNOSED AND TREATED APPROPRIATELY IN CASES OF DEPRESSION OR OSTEOPOROSIS, DISEASES THAT ARE TYPICALLY CONSIDERED "FEMALE." THERE ARE PROMINENT DIFFERENCES BETWEEN MEN AND WOMEN IN MEDICINE REGARDING THE IMMUNE SYSTEM, INFLAMMATION, AND NONCOMMUNICABLE DISEASES SUCH AS OBESITY, TYPE 2 DIABETES, HYPERTENSION, AND CARDIOVASCULAR DISEASE. WOMEN EXPERIENCE MORE OFTEN AUTOIMMUNE DISEASES AND SUFFER MORE FREQUENTLY FROM (CHRONIC) PAIN, NEURODEGENERATIVE CHANGES, AND FUNCTIONAL DISABILITIES. MEN HAVE SHORTER LIFE EXPECTANCY BUT RELATIVELY MORE HEALTHY YEARS OF LIFE, WHICH IS IN GREATER PART ASCRIBED TO PSYCHOSOCIAL DETERMINANTS. STATE-OF-THE-ART CLINICAL MEDICINE COMPRISES INDIVIDUAL RISK FACTORS BASED ON SEX- AND GENDER-SENSITIVE HEALTH PROGRAMS IN ORDER TO IMPROVE THE HEALTH-RELATED QUALITY OF LIFE FOR MEN AND WOMEN. 2014 3 6159 32 THE GENETICS AND EPIGENETICS OF FATIGUE. FATIGUE IS A COMMON SYMPTOM AND INCLUDES BOTH PHYSICAL AND MENTAL COMPONENTS. IT CAN BE ASSOCIATED WITH A VARIETY OF DIFFERENT SYNDROMES AND DISEASES, BUT IN MANY CASES IS NOT ASSOCIATED WITH OTHER COMORBID CONDITIONS. MOST HUMANS HAVE EXPERIENCED ACUTE FATIGUE IN RELATION TO DIFFERENT STRESSORS. ACUTE FATIGUE TYPICALLY DECREASES AS THE EFFECT OF THE TRIGGERING FACTOR IS REDUCED AND A NORMAL HOMEOSTATIC BALANCE IS RESTORED. FATIGUE THAT PERSISTS FOR 6 MONTHS OR MORE IS TERMED CHRONIC FATIGUE. CHRONIC FATIGUE (CF) IN COMBINATION WITH A MINIMUM OF 4 OF 8 SYMPTOMS AND THE ABSENCE OF DISEASES THAT COULD EXPLAIN THESE SYMPTOMS, CONSTITUTE THE CASE DEFINITION FOR CHRONIC FATIGUE SYNDROME. IN SPITE OF ITS PREVALENCE, THE BIOLOGY OF FATIGUE IS RELATIVELY POORLY UNDERSTOOD AND BIOLOGICAL MARKERS HAVE NOT YET BEEN IDENTIFIED. THIS LITERATURE SEARCH WAS PERFORMED IN PUBMED TO IDENTIFY RESEARCH ON THE GENETICS AND EPIGENETICS OF FATIGUE. PUBLICATIONS WERE INCLUDED IF FATIGUE WAS A MAJOR TOPIC AND THE TOPIC WAS COMBINED WITH GENETIC AND/OR EPIGENETIC MEASUREMENTS IN ADULT HUMANS. A TOTAL OF 40 PUBLICATIONS WERE IDENTIFIED. ALTHOUGH ALTERED FUNCTIONING IN THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS, THE SEROTONERGIC SYSTEM, AND ASSOCIATIONS WITH INFECTIOUS AGENTS HAVE BEEN IDENTIFIED, THE SEARCH FOR GENETIC OR EPIGENETIC MARKERS OF FATIGUE, EITHER IN THE CONTEXT OF CF OR CHRONIC FATIGUE SYNDROME (CFS) HAS BEEN RELATIVELY UNPRODUCTIVE OR, IN THE CASE OF EPIGENETICS, NONEXISTENT. ALTHOUGH SEVERAL STUDIES, BOTH HYPOTHESIS-TESTING AND HYPOTHESIS-GENERATING, HAVE BEEN PERFORMED TO SEARCH FOR BIOMARKERS, THEY HAVE MOSTLY BEEN UNDERPOWERED, RESTRICTED BY THE HETEROGENEITY OF THE PHENOTYPE, OR LIMITED BY AN UNSYSTEMATIC STUDY DESIGN. TO BE ABLE TO CONFIRM THE HYPOTHESIS THAT RISK FOR, OR LEVELS OF, FATIGUE ARE INFLUENCED BY THE GENETIC OR EPIGENETIC BACKGROUND OF AN INDIVIDUAL, STUDIES NEED TO BE BASED ON LARGER SAMPLE SIZES WITH A MORE CLEARLY DEFINED PHENOTYPE. STUDIES NEED TO FOCUS NOT ONLY ON THE INFLUENCE OF A SINGLE ASPECT SUCH AS SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) OR DIFFERENTIAL GENE EXPRESSION ON DISEASE RISK OR STATE, BUT ALSO ON THE SYSTEMS BIOLOGY BEHIND THE DISEASE IN COMBINATION WITH INFORMATION ON ENVIRONMENTAL INFLUENCES AND VALIDATION OF FINDINGS IN FUNCTIONAL STUDIES. 2010 4 4915 37 PAIN, ANALGESIA AND GENETICS. OBJECTIVES: IN THE CLINICAL SETTING, THERE IS MARKED INTERSUBJECT VARIABILITY IN THE INTENSITY OF PAIN REPORTED BY PATIENTS WITH APPARENTLY SIMILAR PAIN STATES, AS WELL AS WIDELY DIFFERING ANALGESIC DOSING REQUIREMENTS BETWEEN INDIVIDUALS TO PRODUCE SATISFACTORY PAIN RELIEF WITH TOLERABLE SIDE-EFFECTS. GENETIC AND ENVIRONMENTAL FACTORS AS WELL AS THEIR INTERACTION ARE IMPLICATED, AND THESE ARE DISCUSSED IN THIS REVIEW. KEY FINDINGS: PIONEERING WORK UNDERTAKEN IN MICE MORE THAN A DECADE AGO, SHOWED A STRONG GENETIC CONTRIBUTION TO LEVELS OF NOCICEPTION/HYPERSENSITIVITY AS WELL AS LEVELS OF ANTINOCICEPTION PRODUCED BY COMMONLY AVAILABLE ANALGESIC AGENTS. TO DATE MORE THAN 300 CANDIDATE 'PAIN' GENES HAVE BEEN IDENTIFIED AS POTENTIALLY CONTRIBUTING TO HERITABLE DIFFERENCES IN PAIN SENSITIVITY AND ANALGESIC RESPONSIVENESS IN ANIMALS AND HUMANS, WITH THIS INFORMATION AVAILABLE IN A PUBLICLY ACCESSIBLE DATABASE HTTP://WWW.JBLDESIGN.COM/JMOGIL/ENTER.HTML. SINCE THEN, MANY GENETIC ASSOCIATION STUDIES HAVE BEEN CONDUCTED IN HUMANS TO INVESTIGATE THE POSSIBILITY THAT SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS) IN AN INDIVIDUAL GENE MAY EXPLAIN DRUG INEFFICACY OR EXCESSIVE TOXICITY EXPERIENCED BY A SMALL SUBSET OF THE WHOLE POPULATION WHO HAVE THE RARE ALLELE FOR A PARTICULAR SNP. SUMMARY: DESPITE THE FACT THAT SNPS IN MORE THAN 20 GENES THAT AFFECT PAIN SENSITIVITY OR CONTRIBUTE TO INTERINDIVIDUAL VARIABILITY IN RESPONSES TO ANALGESIC MEDICATIONS HAVE BEEN IDENTIFIED IN THE HUMAN GENOME, MUCH OF THE DATA IS CONFLICTING. APART FROM DEFICIENCIES IN THE DESIGN AND CONDUCT OF HUMAN GENETIC ASSOCIATION STUDIES, RECENT RESEARCH FROM OTHER FIELDS HAS IMPLICATED EPIGENETIC MECHANISMS THAT FACILITATE DYNAMIC GENE-ENVIRONMENT COMMUNICATION, AS A POSSIBLE EXPLANATION. 2011 5 4803 25 OBESITY AND MALE INFERTILITY. THE WORLDWIDE PREVALENCE OF OBESITY IS INCREASING AMONG BOTH SEXES, WITH ASSOCIATED IMPACTS ON CHRONIC HEALTH AND MEDICAL COMORBIDITIES. SIMILARLY, THE EFFECTS OF OBESITY ON REPRODUCTIVE HEALTH ARE INCREASINGLY BEING RECOGNIZED. ADIPOSITY IS ASSOCIATED WITH REDUCED FERTILITY IN MEN, WITH A COMPLEX AND MULTIFACTORIAL ETIOLOGY. THE REPORTED EFFECTS OF OBESITY ON SEMEN PARAMETERS AND IMPAIRED FERTILITY ARE CONTRASTING, WITH SOME STUDIES SHOWING A CLEAR REDUCTION IN REPRODUCTIVE OUTCOMES ASSOCIATED WITH INCREASED BODY MASS INDEX, WHILE OTHERS DO NOT SHOW SUCH IMPACTS. THESE CONTROVERSIES MAY BE DUE TO THE COMPLEX PATHOPHYSIOLOGY AND INTERPLAY BETWEEN GONADOTROPINS AND END ORGANS, AS WELL AS GENETIC AND EPIGENETIC CHANGES AND OXIDATIVE STRESS ON MALE FERTILITY AND FUNCTION. THESE DIFFERENT ASPECTS HAVE LED TO HETEROGENEOUS PARTICIPANTS IN STUDIES AND VARYING IMPLICATIONS FOR ASSISTED REPRODUCTIVE OUTCOMES AS WELL AS OFFSPRING HEALTH. TREATMENT MODALITIES TO MANAGE OBESITY INCLUDE LIFESTYLE, MEDICAL, AND SURGICAL OPTIONS, WITH EMERGING AND EFFECTIVE MEDICAL TREATMENTS SHOWING PROMISE IN REPRODUCTIVE OUTCOMES. 2023 6 5643 38 SEX AND AUTOIMMUNITY: PROPOSED MECHANISMS OF DISEASE ONSET AND SEVERITY. CHRONIC AUTOIMMUNE DISEASES AFFECT 5-10% OF THE POPULATION WORLDWIDE AND ARE LARGELY PREDOMINANT IN WOMEN. SEX HORMONE CHANGES HAVE BEEN WIDELY INVESTIGATED BASED ON CHANGES IN THE CLINICAL PHENOTYPES OBSERVED DURING PREGNANCY AND MENOPAUSE. IT IS KNOWN THAT FEMALES WITH AUTOIMMUNE DISEASES MANIFEST A HIGHER RATE OF CIRCULATING LEUKOCYTES WITH A SINGLE X CHROMOSOME, AND THERE HAVE BEEN SEVERAL REPORTS ON THE ROLE OF X CHROMOSOME GENE DOSAGE THROUGH INACTIVATION OR DUPLICATION IN AUTOIMMUNITY. HOWEVER, IT IS ALSO IMPORTANT NOT TO OVERLOOK MEN WITH AUTOIMMUNE DISEASES, WHO MIGHT MANIFEST A MORE FREQUENT LOSS OF THE Y CHROMOSOME IN CIRCULATING LEUKOCYTES. AREAS COVERED: IN THE PRESENT REVIEW, WE WILL DISCUSS THE CURRENT EVIDENCE SUPPORTING THE MECHANISMS OF FEMALE PREDOMINANCE IN RHEUMATIC DISEASES, BY DISCUSSING THE ROLE OF REPRODUCTIVE HISTORY, SEX HORMONES AND ABNORMALITIES RELATED TO THEM, CLINICAL DIFFERENCES BETWEEN MALE AND FEMALE PATIENTS, AND EPIGENETIC CHANGES THAT HAVE BEEN EVALUATED THROUGH TWIN STUDIES ON GENETIC AND ENVIRONMENTAL CHANGES IN RHEUMATIC PATIENTS. EXPERT OPINION: THE INFLUENCE OF SEX HORMONES AND CHROMOSOMES ON THE FUNCTION OF THE INNATE AND ADAPTIVE IMMUNE SYSTEMS NEEDS TO BE CLARIFIED, TO BETTER UNDERSTAND THE RISK OF AUTOIMMUNE DISEASES, EARLY DIAGNOSTIC TOOLS, AND THERAPEUTIC RESPONSE. 2019 7 5605 30 ROUTINE ASSESSMENT AND PROMOTION OF PHYSICAL ACTIVITY IN HEALTHCARE SETTINGS: A SCIENTIFIC STATEMENT FROM THE AMERICAN HEART ASSOCIATION. PHYSICAL INACTIVITY IS ONE OF THE MOST PREVALENT MAJOR HEALTH RISK FACTORS, WITH 8 IN 10 US ADULTS NOT MEETING AEROBIC AND MUSCLE-STRENGTHENING GUIDELINES, AND IS ASSOCIATED WITH A HIGH BURDEN OF CARDIOVASCULAR DISEASE. IMPROVING AND MAINTAINING RECOMMENDED LEVELS OF PHYSICAL ACTIVITY LEADS TO REDUCTIONS IN METABOLIC, HEMODYNAMIC, FUNCTIONAL, BODY COMPOSITION, AND EPIGENETIC RISK FACTORS FOR NONCOMMUNICABLE CHRONIC DISEASES. PHYSICAL ACTIVITY ALSO HAS A SIGNIFICANT ROLE, IN MANY CASES COMPARABLE OR SUPERIOR TO DRUG INTERVENTIONS, IN THE PREVENTION AND MANAGEMENT OF >40 CONDITIONS SUCH AS DIABETES MELLITUS, CANCER, CARDIOVASCULAR DISEASE, OBESITY, DEPRESSION, ALZHEIMER DISEASE, AND ARTHRITIS. WHEREAS MOST OF THE MODIFIABLE CARDIOVASCULAR DISEASE RISK FACTORS INCLUDED IN THE AMERICAN HEART ASSOCIATION'S MY LIFE CHECK - LIFE'S SIMPLE 7 ARE EVALUATED ROUTINELY IN CLINICAL PRACTICE (GLUCOSE AND LIPID PROFILES, BLOOD PRESSURE, OBESITY, AND SMOKING), PHYSICAL ACTIVITY IS TYPICALLY NOT ASSESSED. THE PURPOSE OF THIS STATEMENT IS TO PROVIDE A COMPREHENSIVE REVIEW OF THE EVIDENCE ON THE FEASIBILITY, VALIDITY, AND EFFECTIVENESS OF ASSESSING AND PROMOTING PHYSICAL ACTIVITY IN HEALTHCARE SETTINGS FOR ADULT PATIENTS. IT ALSO ADDS CONCRETE RECOMMENDATIONS FOR HEALTHCARE SYSTEMS, CLINICAL AND COMMUNITY CARE PROVIDERS, FITNESS PROFESSIONALS, THE TECHNOLOGY INDUSTRY, AND OTHER STAKEHOLDERS IN ORDER TO CATALYZE INCREASED ADOPTION OF PHYSICAL ACTIVITY ASSESSMENT AND PROMOTION IN HEALTHCARE SETTINGS AND TO CONTRIBUTE TO MEETING THE AMERICAN HEART ASSOCIATION'S 2020 IMPACT GOALS. 2018 8 4591 27 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 9 1736 30 EARLY DETECTION AND PREVENTION OF SCHIZOPHRENIC PSYCHOSIS-A REVIEW. PSYCHOTIC DISORDERS OFTEN RUN A CHRONIC COURSE AND ARE ASSOCIATED WITH A CONSIDERABLE EMOTIONAL AND SOCIAL IMPACT FOR PATIENTS AND THEIR RELATIVES. THEREFORE, EARLY RECOGNITION, COMBINED WITH THE POSSIBILITY OF PREVENTIVE INTERVENTION, IS URGENTLY WARRANTED SINCE THE DURATION OF UNTREATED PSYCHOSIS (DUP) SIGNIFICANTLY DETERMINES THE FURTHER COURSE OF THE DISEASE. IN ADDITION TO ESTABLISHED DIAGNOSTIC TOOLS, NEUROBIOLOGICAL FACTORS IN THE DEVELOPMENT OF SCHIZOPHRENIC PSYCHOSES ARE INCREASINGLY BEING INVESTIGATED. IT IS SHOWN THAT NUMEROUS MOLECULAR ALTERATIONS ALREADY EXIST BEFORE THE CLINICAL ONSET OF THE DISEASE. AS SCHIZOPHRENIC PSYCHOSES ARE NOT ELICITED BY A SINGLE MUTATION IN THE DEOXYRIBONUCLEIC ACID (DNA) SEQUENCE, EPIGENETICS LIKELY CONSTITUTE THE MISSING LINK BETWEEN ENVIRONMENTAL INFLUENCES AND DISEASE DEVELOPMENT AND COULD POTENTIALLY SERVE AS A BIOMARKER. THE RESULTS FROM TRANSCRIPTOMIC AND PROTEOMIC STUDIES POINT TO A DYSREGULATED IMMUNE SYSTEM, LIKELY EVOKED BY EPIGENETIC ALTERATIONS. DESPITE THE INCREASING KNOWLEDGE OF THE NEUROBIOLOGICAL MECHANISMS INVOLVED IN THE DEVELOPMENT OF PSYCHOTIC DISORDERS, FURTHER RESEARCH EFFORTS WITH LARGE POPULATION-BASED STUDY DESIGNS ARE NEEDED TO IDENTIFY SUITABLE BIOMARKERS. IN CONCLUSION, A COMBINATION OF BLOOD EXAMINATIONS, FUNCTIONAL IMAGING TECHNIQUES, ELECTROENCEPHALOGRAPHY (EEG) INVESTIGATIONS AND POLYGENIC RISK SCORES SHOULD BE CONSIDERED AS THE BASIS FOR PREDICTING HOW SUBJECTS WILL TRANSITION INTO MANIFEST PSYCHOSIS. 2021 10 456 39 APPLYING A LIFE COURSE BIOLOGICAL AGE FRAMEWORK TO IMPROVING THE CARE OF INDIVIDUALS WITH ADULT CANCERS: REVIEW AND RESEARCH RECOMMENDATIONS. IMPORTANCE: THE PRACTICE OF ONCOLOGY WILL INCREASINGLY INVOLVE THE CARE OF A GROWING POPULATION OF INDIVIDUALS WITH MIDLIFE AND LATE-LIFE CANCERS. MANAGING CANCER IN THESE INDIVIDUALS IS COMPLEX, BASED ON DIFFERENCES IN BIOLOGICAL AGE AT DIAGNOSIS. BIOLOGICAL AGE IS A MEASURE OF ACCUMULATED LIFE COURSE DAMAGE TO BIOLOGICAL SYSTEMS, LOSS OF RESERVE, AND VULNERABILITY TO FUNCTIONAL DETERIORATION AND DEATH. BIOLOGICAL AGE IS IMPORTANT BECAUSE IT AFFECTS THE ABILITY TO MANAGE THE RIGORS OF CANCER THERAPY, SURVIVORS' FUNCTION, AND CANCER PROGRESSION. HOWEVER, BIOLOGICAL AGE IS NOT ALWAYS CLINICALLY APPARENT. THIS REVIEW PRESENTS A CONCEPTUAL FRAMEWORK OF LIFE COURSE BIOLOGICAL AGING, SUMMARIZES CANDIDATE MEASURES, AND DESCRIBES A RESEARCH AGENDA TO FACILITATE CLINICAL TRANSLATION TO ONCOLOGY PRACTICE. OBSERVATIONS: MIDLIFE AND LATE-LIFE CANCERS ARE CHRONIC DISEASES THAT MAY ARISE FROM CUMULATIVE PATTERNS OF BIOLOGICAL AGING OCCURRING OVER THE LIFE COURSE. BEFORE DIAGNOSIS, EACH NEW PATIENT WAS ON A DISTINCT COURSE OF BIOLOGICAL AGING RELATED TO PAST EXPOSURES, LIFE EXPERIENCES, GENETICS, AND NONCANCER CHRONIC DISEASE. CANCER AND ITS TREATMENTS MAY ALSO BE ASSOCIATED WITH BIOLOGICAL AGING. SEVERAL MEASURES OF BIOLOGICAL AGE, INCLUDING P16INK4A, EPIGENETIC AGE, TELOMERE LENGTH, AND INFLAMMATORY AND BODY COMPOSITION MARKERS, HAVE BEEN USED IN ONCOLOGY RESEARCH. ONE OR MORE OF THESE MEASURES MAY BE USEFUL IN CANCER CARE, EITHER ALONE OR IN COMBINATION WITH CLINICAL HISTORY AND GERIATRIC ASSESSMENTS. HOWEVER, FURTHER RESEARCH WILL BE NEEDED BEFORE BIOLOGICAL AGE ASSESSMENT CAN BE RECOMMENDED IN ROUTINE PRACTICE, INCLUDING DETERMINATION OF SITUATIONS IN WHICH KNOWLEDGE ABOUT BIOLOGICAL AGE WOULD CHANGE TREATMENT, ASCERTAINING WHETHER TREATMENT EFFECTS ON BIOLOGICAL AGING ARE SHORT-LIVED OR PERSISTENT, AND TESTING INTERVENTIONS TO MODIFY BIOLOGICAL AGE, DECREASE TREATMENT TOXIC EFFECTS, AND MAINTAIN FUNCTIONAL ABILITIES. CONCLUSIONS AND RELEVANCE: UNDERSTANDING DIFFERENCES IN BIOLOGICAL AGING COULD ULTIMATELY ALLOW CLINICIANS TO BETTER PERSONALIZE TREATMENT AND SUPPORTIVE CARE, DEVELOP TAILORED SURVIVORSHIP CARE PLANS, AND PRESCRIBE PREVENTIVE OR AMELIORATIVE THERAPIES AND BEHAVIORS INFORMED BY AGING MECHANISMS. 2021 11 5028 26 PERSONALIZING PEDIATRIC PAIN MEDICINE: USING POPULATION-SPECIFIC PHARMACOGENETICS, GENOMICS, AND OTHER -OMICS APPROACHES TO PREDICT RESPONSE. PERSONALIZED MEDICINE IS THE SCIENCE OF INDIVIDUALIZED PREVENTION AND THERAPY. THE NOTION THAT "ONE SIZE FITS ALL" HAS BEEN REPLACED BY THE IDEA OF PATIENT-TAILORED HEALTH CARE. WITHIN THIS PARADIGM, THE RESEARCH COMMUNITY HAS TURNED TO EXAMINE GENETIC PREDICTORS OF DISEASE AND TREATMENT RESPONSES. PAIN RESEARCHERS HAVE PRODUCED GENETIC STUDIES OVER THE LAST DECADE THAT EVALUATE THE ASSOCIATION OF GENETIC VARIABILITY WITH PAIN SENSITIVITY AND ANALGESIC RESPONSE. WHILE MOST OF THESE STUDIES HAVE BEEN CONDUCTED AMONG COHORTS OF SUBJECTS OF EUROPEAN DESCENT, SOME HAVE INCLUDED OTHER RACIAL AND ETHNIC GROUPS, PROVIDING EVIDENCE OF VARIABLE RESPONSES TO ANALGESICS. SIMULTANEOUSLY, THERE IS AN INCREASED RECOGNITION REGARDING THE COMPLEXITY OF PAIN RESEARCH, ACKNOWLEDGING THE ADDITIONAL ROLE OF EPIGENETIC, TRANSCRIPTOMIC, PROTEOMIC, AND METABOLOMIC FACTORS IN THE DEVELOPMENT, EXPERIENCE, AND TREATMENT OF PAIN. THIS ARTICLE PROVIDES AN INTRODUCTION TO POPULATION-SPECIFIC PHARMACOGENETICS, PROTEOMICS AND OTHER "-OMICS" TECHNOLOGIES TO PREDICT DRUG RESPONSE TO PAIN MEDICATIONS IN CHILDREN. IT AIMS TO PROVIDE ANESTHESIOLOGISTS WITH THE BASIC KNOWLEDGE TO UNDERSTAND THE POTENTIAL IMPLICATIONS OF GENETIC AND EPIGENETIC FACTORS MANAGING THE PAIN OF PEDIATRIC PATIENTS. 2015 12 2213 35 EPIGENETIC MODIFICATIONS AS OUTCOMES OF EXERCISE INTERVENTIONS RELATED TO SPECIFIC METABOLIC ALTERATIONS: A SYSTEMATIC REVIEW. BACKGROUND: CHRONIC DISEASES ARISE AS A CONSEQUENCE OF AN UNHEALTHY LIFESTYLE PRIMARILY CHARACTERIZED BY PHYSICAL INACTIVITY AND UNBALANCED DIETS. REGULAR PHYSICAL ACTIVITY CAN IMPROVE HEALTH, AND THERE IS CONSISTENT EVIDENCE THAT THESE IMPROVEMENTS MAY BE THE RESULT OF EPIGENETIC MODIFICATIONS. OBJECTIVE: TO IDENTIFY EPIGENETIC MODIFICATIONSAS OUTCOMES OF EXERCISE INTERVENTIONS RELATED TO SPECIFIC METABOLIC ALTERATIONS. METHODS: THE PREFERRED REPORTING ITEMS FOR SYSTEMATIC REVIEWS AND META-ANALYSES PROTOCOLS (PRISMA-P) METHODOLOGY FOR MANUSCRIPT RESEARCH AND PREPARATION WAS FOLLOWED USING PUBMED AND EBSCO DATABASES FOR LITERATURE REVIEW. OUT OF 2,638 ARTICLES IDENTIFIED, ONLY 34 ARTICLES MET THE INCLUSION CRITERIA. RESULTS: THE SECTIONS OF THE REVIEW WERE ORGANIZED BY METABOLIC ALTERATIONS IN WHICH STUDIES WERE GROUPED ACCORDING TO HEALTHY, DISEASED, AND TRAINED INDIVIDUALS. RESISTANCE EXERCISE IN HUMANS INDUCED EPIGENETIC CHANGES IN PATHWAYS ASSOCIATED WITH ENERGY METABOLISM AND INSULIN SENSITIVITY, CONTRIBUTING TO HEALTHY SKELETAL MUSCLE. ENDURANCE EXERCISE ALSO CAUSED MODIFICATIONS IN BIOMARKERS ASSOCIATED TO METABOLIC ALTERATIONS THROUGH CHANGES IN DNA METHYLATION AND THE EXPRESSION OF SPECIFIC MIRNAS. HOWEVER, BOTH RESISTANCE AND ENDURANCE EXERCISE ARE NECESSARY TO OBTAIN A BETTER PHYSIOLOGICAL ADAPTATION AND A COMBINATION OF BOTH SEEMS TO BE NEEDED TO PROPERLY TACKLE THE INCREASING PREVALENCE OF NON-COMMUNICABLE PATHOLOGIES. CONCLUSION: GIVEN THE HETEROGENEITY AND COMPLEXITY OF THE EXISTING LITERATURE, IT IS CURRENTLY NOT POSSIBLE TO PROPOSE A SPECIFIC RECOMMENDATION ABOUT THE TYPE, INTENSITY, OR DURATION OF EXERCISE THAT COULD BE BENEFICIAL FOR DIFFERENT SUBSETS OF THE POPULATION (HEALTHY, DISEASED, AND/OR TRAINED). NEVERTHELESS, THIS REVIEW HIGHLIGHTS THE IMPORTANCE OF EXERCISE FOR HEALTH AND SHOWS THE NEED TO PERFORM MORE RESEARCH IN THIS EMERGING AREA TO IDENTIFY EPIGENETIC BIOMARKERS THAT COULD SERVE AS INDICATORS OF EXERCISE ADAPTATIONS. 2019 13 3676 32 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 5072 34 PHYSICAL EXERCISE POSITIVELY INFLUENCES BREAST CANCER EVOLUTION. BREAST CANCER IS ONE OF THE MOST COMMONLY DIAGNOSED TYPES OF CANCER IN WOMEN. ITS PATHOGENESIS INVOLVES GENETIC, HORMONAL, AND ENVIRONMENTAL FACTORS. A LARGE BODY OF EVIDENCE INDICATES THAT PHYSICAL ACTIVITY HAS POSITIVE EFFECTS ON EVERY ASPECT OF BREAST CANCER EVOLUTION, INCLUDING PREVENTION, MEDICAL TREATMENT, AND AFTERCARE CLINICAL SETTINGS. THUS, DIFFERENT TYPES OF EXERCISE CAN INFLUENCE THE PREVENTION AND PROGRESSION OF THE DISEASE THROUGH SEVERAL COMMON MECHANISMS, SUCH AS REDUCTION OF INSULIN RESISTANCE AND IMPROVEMENT OF IMMUNITY AND CARDIOVASCULAR FUNCTION. FURTHERMORE, ACUTE AND CHRONIC SYMPTOMS OF BREAST CANCER, SUCH AS CACHEXIA, MUSCLE MASS LOSS, FATIGUE, CARDIOTOXICITY, WEIGHT GAIN, HORMONE ALTERATIONS, BONE LOSS, AND PSYCHOLOGIC ADVERSE EFFECTS, MAY ALL BE FAVORABLY INFLUENCED BY REGULAR EXERCISE. WE REVIEW THE RELATION OF INTENSITY AND DURATION OF EXERCISE WITH POTENTIAL PATHOPHYSIOLOGIC PATHWAYS, INCLUDING OBESITY-RELATED HORMONES AND SEX STEROID HORMONE PRODUCTION, OXIDATIVE STRESS, EPIGENETIC ALTERATIONS SUCH AS DNA HYPOMETHYLATION, AND CHANGES IN TELOMERE LENGTH, WITHIN THE CONTEXT OF THE BENEFICIAL EFFECTS OF EXERCISE. THE POTENTIAL ROLE OF EXERCISE IN REDUCING THE INTENSITY OF THE ADVERSE EFFECTS THAT RESULT FROM BREAST CANCER AND ANTICANCER TREATMENT IS ALSO DISCUSSED. 2017 15 1932 27 ENVIRONMENTAL EXPOSURES: AN UNDERRECOGNIZED CONTRIBUTION TO NONCOMMUNICABLE DISEASES. PREVIOUS ATTEMPTS TO DETERMINE THE DEGREE TO WHICH EXPOSURE TO ENVIRONMENTAL FACTORS CONTRIBUTE TO NONCOMMUNICABLE DISEASES (NCDS) HAVE BEEN VERY CONSERVATIVE AND HAVE SIGNIFICANTLY UNDERESTIMATED THE ACTUAL CONTRIBUTION OF THE ENVIRONMENT FOR AT LEAST TWO REASONS. FIRSTLY, MOST PREVIOUS REPORTS HAVE EXCLUDED THE CONTRIBUTION OF LIFESTYLE BEHAVIORAL RISK FACTORS, BUT THESE USUALLY INVOLVE SIGNIFICANT EXPOSURE TO ENVIRONMENTAL CHEMICALS THAT INCREASE RISK OF DISEASE. SECONDLY, EARLY LIFE EXPOSURE TO CHEMICAL CONTAMINANTS IS NOW CLEARLY ASSOCIATED WITH AN ELEVATED RISK OF SEVERAL DISEASES LATER IN LIFE, BUT THESE CONNECTIONS ARE OFTEN DIFFICULT TO DISCERN. THIS IS ESPECIALLY TRUE FOR ASTHMA AND NEURODEVELOPMENTAL CONDITIONS, BUT THERE IS ALSO A MAJOR CONTRIBUTION TO THE DEVELOPMENT OF OBESITY AND CHRONIC DISEASES. MOST CANCERS ARE CAUSED BY ENVIRONMENTAL EXPOSURES IN GENETICALLY SUSCEPTIBLE INDIVIDUALS. IN ADDITION, NEW INFORMATION SHOWS SIGNIFICANT ASSOCIATIONS BETWEEN CARDIOVASCULAR DISEASES AND DIABETES AND EXPOSURE TO ENVIRONMENTAL CHEMICALS PRESENT IN AIR, FOOD, AND WATER. THESE RELATIONSHIPS LIKELY REFLECT THE COMBINATION OF EPIGENETIC EFFECTS AND GENE INDUCTION. ENVIRONMENTAL FACTORS CONTRIBUTE SIGNIFICANTLY MORE TO NCDS THAN PREVIOUS REPORTS HAVE SUGGESTED. PREVENTION NEEDS TO SHIFT FOCUS FROM INDIVIDUAL RESPONSIBILITY TO SOCIETAL RESPONSIBILITY AND AN UNDERSTANDING THAT EFFECTIVE PREVENTION OF NCDS ULTIMATELY RELIES ON IMPROVED ENVIRONMENTAL MANAGEMENT TO REDUCE EXPOSURE TO MODIFIABLE RISKS. 2013 16 6211 27 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 17 1045 30 CLINICAL CORRELATION AMONG MALE INFERTILITY AND OVERALL MALE HEALTH: A SYSTEMATIC REVIEW OF THE LITERATURE. PURPOSE: ONGOING EVIDENCE HAS SUGGESTED THE ROLE OF MALE FACTOR INFERTILITY AS A POTENTIAL PREDICTOR OF MORTALITY AND GENERAL HEALTH STATUS. THE AIM OF THE PRESENT REVIEW IS TO UPDATE THE CURRENT KNOWLEDGE BASE REGARDING THE ASSOCIATION BETWEEN MALE FACTOR INFERTILITY AND GENERAL HEALTH THROUGH A CRITICAL REVIEW OF THE LITERATURE. MATERIALS AND METHODS: A SYSTEMATIC REVIEW OF THE LITERATURE WAS CARRIED OUT FROM INCEPTION TO NOVEMBER 2019 IN ORDER TO EVALUATE SIGNIFICANT ASSOCIATIONS BETWEEN MALE INFERTILITY AND ADVERSE HEALTH OUTCOMES SUCH AS CARDIOVASCULAR, ONCOLOGIC, METABOLIC AND AUTOIMMUNE DISEASES AS WELL AS OVERALL MORTALITY. RESULTS: IN ALL, 27 STUDIES MET INCLUSION CRITERIA AND WERE CRITICALLY EXAMINED. FIVE STUDIES EXAMINED MALE INFERTILITY AND CARDIOVASCULAR DISEASE RISK, 11 EXAMINED ONCOLOGIC RISK (E.G., OVERALL CANCER RISK, TESTIS AND PROSTATE CANCER), 8 EXAMINED AGGREGATE CHRONIC MEDICAL DISEASES AND 5 INFERTILITY RELATED TO INCIDENCE OF MORTALITY, FOR A TOTAL OF 599,807 MEN DIAGNOSED WITH ANY MALE FACTOR INFERTILITY COVERING A PERIOD FROM 1916 TO 2016. CONCLUSIONS: A MAN'S FERTILITY AND OVERALL HEALTH APPEAR TO BE INTERCONNECTED. THEREFORE, A DIAGNOSIS OF MALE INFERTILITY MAY ALLOW A WINDOW INTO FUTURE COMORBIDITY AND/OR MORTALITY WHICH MAY HELP GUIDE CLINICAL DECISIONS AND COUNSELING. SEVERAL POSSIBLE ETIOLOGIES SUCH AS GENETIC, EPIGENETIC, DEVELOPMENTAL, AND LIFESTYLE-BASED FACTORS NEED TO BE FURTHER EVALUATED IN ORDER TO ESTABLISH THE UNDERLYING MECHANISMS BETWEEN MALE INFERTILITY AND HEALTH. 2020 18 38 29 A COMMON ROLE FOR PSYCHOTROPIC MEDICATIONS: MEMORY IMPAIRMENT. THE PSYCHOPATHOLOGIC PROFILE OF MENTAL DISORDERS IS VERY DIVERSE AND PSYCHOTROPIC MEDICATIONS USED TO TREAT THEM DIFFER IN THEIR CHEMICAL STRUCTURE. NEVERTHELESS, THESE DRUGS SHARE THESE FOUR CHARACTERISTICS: DELAYED ONSET OF CLINICAL RESPONSE, NOT ONE OF THEM CAN BE SAID TO CURE, THERE IS A HIGH NUMBER OF NON-RESPONDERS, AND THE MECHANISM RESPONSIBLE FOR THEIR THERAPEUTIC ACTION IS NOT KNOWN. IT IS HYPOTHESIZED THAT THE ACTION OF PSYCHOTROPIC MEDICATIONS IS MEMORY IMPAIRMENT, UNDERSTANDING MEMORY AS THE TRACE LEFT IN THE NERVOUS SYSTEM NOT ONLY BY INDIVIDUAL EXPERIENCES BUT ALSO BY GENETIC AND EPIGENETIC PHENOMENA. IT IS SUGGESTED THAT IT WOULD BE BENEFICIAL TO TRANSLATE SOME RESEARCH STRATEGIES FROM THE NEUROBIOLOGY OF LEARNING AND MEMORY TO THE STUDY OF THE EFFECTS OF PSYCHOTROPIC MEDICATIONS. THE HYPOTHESIS IS BRIEFLY ASSESSED ACCORDING TO THE FOLLOWING THREE CRITERIA: (A). THE COMPARISON BETWEEN THE MOLECULAR EFFECTS OF PSYCHOTROPIC MEDICATIONS AND THE SO-CALLED MOLECULAR BIOLOGY OF LEARNING AND MEMORY, (B). THE EFFECTS OF THESE DRUGS, PREFERENTIALLY AFTER CHRONIC USE, ON MEMORY TESTS, AND (C). THE EFFECTS OF DRUGS THAT IMPAIR MEMORY ON TESTS USED FOR SCREENING PSYCHOTROPIC MEDICATIONS. FINALLY, SOME GENERAL SUGGESTIONS FOR FUTURE RESEARCH ARE POINTED OUT. 2003 19 2816 38 FIBROMYALGIA: PATHOGENESIS, MECHANISMS, DIAGNOSIS AND TREATMENT OPTIONS UPDATE. FIBROMYALGIA IS A SYNDROME CHARACTERIZED BY CHRONIC AND WIDESPREAD MUSCULOSKELETAL PAIN, OFTEN ACCOMPANIED BY OTHER SYMPTOMS, SUCH AS FATIGUE, INTESTINAL DISORDERS AND ALTERATIONS IN SLEEP AND MOOD. IT IS ESTIMATED THAT TWO TO EIGHT PERCENT OF THE WORLD POPULATION IS AFFECTED BY FIBROMYALGIA. FROM A MEDICAL POINT OF VIEW, THIS PATHOLOGY STILL PRESENTS INEXPLICABLE ASPECTS. IT IS KNOWN THAT FIBROMYALGIA IS CAUSED BY A CENTRAL SENSITIZATION PHENOMENON CHARACTERIZED BY THE DYSFUNCTION OF NEURO-CIRCUITS, WHICH INVOLVES THE PERCEPTION, TRANSMISSION AND PROCESSING OF AFFERENT NOCICEPTIVE STIMULI, WITH THE PREVALENT MANIFESTATION OF PAIN AT THE LEVEL OF THE LOCOMOTOR SYSTEM. IN RECENT YEARS, THE PATHOGENESIS OF FIBROMYALGIA HAS ALSO BEEN LINKED TO OTHER FACTORS, SUCH AS INFLAMMATORY, IMMUNE, ENDOCRINE, GENETIC AND PSYCHOSOCIAL FACTORS. A RHEUMATOLOGIST TYPICALLY MAKES A DIAGNOSIS OF FIBROMYALGIA WHEN THE PATIENT DESCRIBES A HISTORY OF PAIN SPREADING IN ALL QUADRANTS OF THE BODY FOR AT LEAST THREE MONTHS AND WHEN PAIN IS CAUSED BY DIGITAL PRESSURE IN AT LEAST 11 OUT OF 18 ALLOGENIC POINTS, CALLED TENDER POINTS. FIBROMYALGIA DOES NOT INVOLVE ORGANIC DAMAGE, AND SEVERAL DIAGNOSTIC APPROACHES HAVE BEEN DEVELOPED IN RECENT YEARS, INCLUDING THE ANALYSIS OF GENETIC, EPIGENETIC AND SEROLOGICAL BIOMARKERS. SYMPTOMS OFTEN BEGIN AFTER PHYSICAL OR EMOTIONAL TRAUMA, BUT IN MANY CASES, THERE APPEARS TO BE NO OBVIOUS TRIGGER. WOMEN ARE MORE PRONE TO DEVELOPING THE DISEASE THAN MEN. UNFORTUNATELY, THE CONVENTIONAL MEDICAL THERAPIES THAT TARGET THIS PATHOLOGY PRODUCE LIMITED BENEFITS. THEY REMAIN LARGELY PHARMACOLOGICAL IN NATURE AND TEND TO TREAT THE SYMPTOMATIC ASPECTS OF VARIOUS DISORDERS REPORTED BY THE PATIENT. THE STATISTICS, HOWEVER, HIGHLIGHT THE FACT THAT 90% OF PEOPLE WITH FIBROMYALGIA ALSO TURN TO COMPLEMENTARY MEDICINE TO MANAGE THEIR SYMPTOMS. 2021 20 625 26 BIOLOGICAL AGE AND ENVIRONMENTAL RISK FACTORS FOR DEMENTIA AND STROKE: MOLECULAR MECHANISMS. SINCE THE DEVELOPMENT OF ANTIBIOTICS AND VACCINATION, AS WELL AS MAJOR IMPROVEMENTS IN PUBLIC HYGIENE, THE MAIN RISK FACTORS FOR MORBIDITY AND MORTALITY ARE AGE AND CHRONIC EXPOSURE TO ENVIRONMENTAL FACTORS, BOTH OF WHICH CAN INTERACT WITH GENETIC PREDISPOSITIONS. AS THE AVERAGE AGE OF THE POPULATION INCREASES, THE PREVALENCE AND COSTS OF CHRONIC DISEASES, ESPECIALLY NEUROLOGICAL CONDITIONS, ARE RAPIDLY INCREASING. THE DELETERIOUS EFFECTS OF AGE AND ENVIRONMENTAL RISK FACTORS, DEVELOP CHRONICALLY OVER RELATIVELY LONG PERIODS OF TIME, IN CONTRAST TO THE RELATIVELY RAPID DELETERIOUS EFFECTS OF INFECTIOUS DISEASES OR ACCIDENTS. OF PARTICULAR INTEREST IS THE HYPOTHESIS THAT THE DELETERIOUS EFFECTS OF ENVIRONMENTAL FACTORS MAY BE MEDIATED BY ACCELERATION OF BIOLOGICAL AGE. THIS HYPOTHESIS IS SUPPORTED BY EVIDENCE THAT DIETARY RESTRICTION, WHICH UNIVERSALLY DELAYS AGE-RELATED DISEASES, ALSO AMELIORATES DELETERIOUS EFFECTS OF ENVIRONMENTAL FACTORS. CONVERSELY, BOTH AGE AND ENVIRONMENTAL RISK FACTORS ARE ASSOCIATED WITH THE ACCUMULATION OF SOMATIC MUTATIONS IN MITOTIC CELLS AND EPIGENETIC MODIFICATIONS THAT ARE A MEASURE OF "BIOLOGICAL AGE", A BETTER PREDICTOR OF AGE-RELATED MORBIDITY AND MORTALITY THAN CHRONOLOGICAL AGE. HERE WE REVIEW EVIDENCE THAT ENVIRONMENTAL RISK FACTORS SUCH AS SMOKING AND AIR POLLUTION MAY ALSO DRIVE NEUROLOGICAL CONDITIONS, INCLUDING ALZHEIMER'S DISEASE, BY THE ACCELERATION OF BIOLOGICAL AGE, MEDIATED BY CUMULATIVE AND PERSISTENT EPIGENETIC EFFECTS AS WELL AS SOMATIC MUTATIONS. ELUCIDATION OF SUCH MECHANISMS COULD PLAUSIBLY ALLOW THE DEVELOPMENT OF INTERVENTIONS WHICH DELAY DELETERIOUS EFFECTS OF BOTH AGING AND ENVIRONMENTAL RISK FACTORS. 2022