1 5655 148 SEX-BASED MEDICINE MEETS PSORIATIC ARTHRITIS: LESSONS LEARNED AND TO LEARN. HUMORALLY ASSOCIATED AUTOIMMUNE DISEASES GENERALLY SHOW A FEMALE PREDOMINANCE WHEREAS ANKYLOSING SPONDYLITIS, A DISEASE THAT OVERLAPS WITH PSORIATIC ARTHRITIS (PSA), SHOWS A MALE PREDOMINANCE. THE PRESENT REVIEW ASCERTAINS THE CURRENT KNOWLEDGE OF SEX-SPECIFIC DIFFERENCES RELATED TO PSORIATIC ARTHRITIS (PSA), A CHRONIC, INFLAMMATORY CONDITION ASSOCIATED WITH PSORIASIS. SEX DIFFERENCES MAY HAVE IMPORTANT IMPLICATIONS FOR CLINICAL RESEARCH IN PSA AND IN TERMS OF EPIDEMIOLOGY (INCIDENCE, PREVALENCE, LIFETIME RISK, SURVIVAL, AND MORTALITY), CLINICAL, RADIOLOGICAL, AND LABORATORY FEATURES, AND RESPONSE TO TREATMENT. WHILE NATIONWIDE SURVEYS AND LARGE-SCALE DATABASES AND REGISTRIES SHOW NO SEX-SPECIFIC DIFFERENCES, VARYING MALE/FEMALE RATIOS HAVE BEEN REPORTED, RANGING FROM 0.42 TO 2.75 (COMPARABLE WITH THOSE REPORTED FOR PSORIASIS VULGARIS: RANGING FROM 0.28 TO 2.38). THIS MAY REFLECT SUBTLE, COMPLEX, NONLINEAR INTERACTIONS BETWEEN THE BIOLOGICAL MAKE-UP OF THE INDIVIDUAL (GENETIC AND EPIGENETIC DIFFERENCES), HORMONAL COMPONENTS INCLUDING MENOPAUSAL STATUS, ENVIRONMENTAL EXPOSURES INCLUDING SKELETAL PHYSICAL STRESSING, AND PSYCHOLOGICAL VARIABLES. THERE EXISTS METHODOLOGICAL HETEROGENEITY AND PAUCITY OF DATA CONCERNING SEX-SPECIFIC DIFFERENCES, IN TERMS OF THE SPECIFIC POPULATION STUDIED, STUDY DESIGN, AND THE DIAGNOSTIC CRITERIA UTILIZED. HARMONIZING AND RECONCILING THESE DISCREPANCIES WOULD BE OF CRUCIAL IMPORTANCE IN ACHIEVING THE AMBITIOUS GOALS OF PERSONALIZED/INDIVIDUALIZED MEDICINE AND FURTHER STANDARDIZED META-DATA AND BIG DATA COULD HELP DISENTANGLE AND ELUCIDATE THE PRECISE MECHANISMS OF UNDERLYING POTENTIAL PSA SEX-SPECIFIC DIFFERENCES. 2022 2 456 42 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 3 6822 38 [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 4 5643 37 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 5 5217 33 PREVALENCE AND CHARACTERISTICS OF PSORIASIS IN ROMANIA-FIRST STUDY IN OVERALL POPULATION. BACKGROUND: PSORIASIS IS A CHRONIC INFLAMMATORY DISEASE CHARACTERIZED BY AN EXCESSIVE HYPERPROLIFERATION OF KERATINOCYTES AND A COMBINATION OF GENETIC, EPIGENETIC, AND ENVIRONMENTAL INFLUENCES. THE PATHOGENESIS OF PSORIASIS IS COMPLEX AND THE EXACT MECHANISM REMAINS ELUSIVE. OBJECTIVES: THE STUDY OF THE PREVALENCE OF PSORIASIS WILL ALLOW THE ESTIMATION OF THE NUMBER OF PEOPLE SUFFERING FROM THIS CONDITION AT THE NATIONAL LEVEL, AS WELL AS THE DEVELOPMENT AND VALIDATION OF A QUESTIONNAIRE TO ESTIMATE THE PREVALENCE AND THE RISK FACTORS ASSOCIATED WITH THE DISEASE. METHODS: A QUANTITATIVE RESEARCH WAS CONDUCTED AT A NATIONAL LEVEL AMONG THE TARGET POPULATION IN ORDER TO VALIDATE THE QUESTIONNAIRE AND ESTIMATE THE NATIONAL PREVALENCE. RESULTS: DECLARATIVELY, THE PREVALENCE OF PSORIASIS IN THE STUDIED GROUP (N = 1500) IS 4%, THE FIRST SYMPTOMS APPEARING AROUND THE AGE OF 50, WITH A CERTIFIED DIAGNOSIS BEING MADE ON AVERAGE AT 55 YEARS. THE PREVALENCE OF PSORIASIS VULGARIS WAS 4.99%. CONCLUSIONS: THE RESULTS OBTAINED WILL BE USEFUL IN GUIDING FUTURE INITIATIVES AND COMMUNICATION CAMPAIGNS RELATED TO THIS CONDITION, AND THE METHODOLOGICAL APPROACH USED WILL PROVIDE THE OPPORTUNITY TO MAKE RECOMMENDATIONS FOR IMPROVING SIMILAR INITIATIVES IN THE FUTURE. 2021 6 6159 33 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 7 728 29 CAN WE IDENTIFY PATIENTS WITH HIGH RISK OF OSTEOARTHRITIS PROGRESSION WHO WILL RESPOND TO TREATMENT? A FOCUS ON BIOMARKERS AND FRAILTY. OSTEOARTHRITIS (OA), A DISEASE AFFECTING DIFFERENT PATIENT PHENOTYPES, APPEARS AS AN OPTIMAL CANDIDATE FOR PERSONALIZED HEALTHCARE. THE AIM OF THE DISCUSSIONS OF THE EUROPEAN SOCIETY FOR CLINICAL AND ECONOMIC ASPECTS OF OSTEOPOROSIS AND OSTEOARTHRITIS (ESCEO) WORKING GROUP WAS TO EXPLORE THE VALUE OF MARKERS OF DIFFERENT SOURCES IN DEFINING DIFFERENT PHENOTYPES OF PATIENTS WITH OA. THE ESCEO ORGANIZED A SERIES OF MEETINGS TO EXPLORE THE POSSIBILITY OF IDENTIFYING PATIENTS WHO WOULD MOST BENEFIT FROM TREATMENT FOR OA, ON THE BASIS OF RECENT DATA AND EXPERT OPINION. IN THE FIRST MEETING, PATIENT PHENOTYPES WERE IDENTIFIED ACCORDING TO THE NUMBER OF AFFECTED JOINTS, BIOMECHANICAL FACTORS, AND THE PRESENCE OF LESIONS IN THE SUBCHONDRAL BONE. IN THE SECOND MEETING, SUMMARIZED IN THE PRESENT ARTICLE, THE WORKING GROUP EXPLORED OTHER MARKERS INVOLVED IN OA. PROFILES OF PATIENTS MAY BE DEFINED ACCORDING TO THEIR LEVEL OF PAIN, FUNCTIONAL LIMITATION, AND PRESENCE OF COEXISTENT CHRONIC CONDITIONS INCLUDING FRAILTY STATUS. A CONSIDERABLE AMOUNT OF DATA SUGGESTS THAT MAGNETIC RESONANCE IMAGING MAY ALSO ASSIST IN DELINEATING DIFFERENT PHENOTYPES OF PATIENTS WITH OA. AMONG MULTIPLE BIOCHEMICAL BIOMARKERS IDENTIFIED, NONE IS SUFFICIENTLY VALIDATED AND RECOGNIZED TO IDENTIFY PATIENTS WHO SHOULD BE TREATED. CONSIDERABLE EFFORTS ARE ALSO BEING MADE TO IDENTIFY GENETIC AND EPIGENETIC FACTORS INVOLVED IN OA, BUT RESULTS ARE STILL LIMITED. THE MANY POTENTIAL BIOMARKERS THAT COULD BE USED AS POTENTIAL STRATIFIERS ARE PROMISING, BUT MORE RESEARCH IS NEEDED TO CHARACTERIZE AND QUALIFY THE EXISTING BIOMARKERS AND TO IDENTIFY NEW CANDIDATES. 2015 8 1045 38 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 9 2900 30 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 10 1736 29 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 11 5028 28 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 1248 31 CURRENT EVIDENCE FOR BIOLOGICAL BIOMARKERS AND MECHANISMS UNDERLYING ACUTE TO CHRONIC PAIN TRANSITION ACROSS THE PEDIATRIC AGE SPECTRUM. CHRONIC PAIN IS HIGHLY PREVALENT IN THE PEDIATRIC POPULATION. MANY FACTORS ARE INVOLVED IN THE TRANSITION FROM ACUTE TO CHRONIC PAIN. CURRENTLY, THERE ARE CONCEPTUAL MODELS PROPOSED, BUT THEY LACK A MECHANISTICALLY SOUND INTEGRATED THEORY CONSIDERING THE STAGES OF CHILD DEVELOPMENT. OBJECTIVE BIOMARKERS ARE CRITICALLY NEEDED FOR THE DIAGNOSIS, RISK STRATIFICATION, AND PROGNOSIS OF THE PATHOLOGICAL STAGES OF PAIN CHRONIFICATION. IN THIS ARTICLE, WE SUMMARIZE THE CURRENT EVIDENCE ON MECHANISMS AND BIOMARKERS OF ACUTE TO CHRONIC PAIN TRANSITIONS IN INFANTS AND CHILDREN THROUGH THE DEVELOPMENTAL LENS. THE GOAL IS TO IDENTIFY GAPS AND OUTLINE FUTURE DIRECTIONS FOR BASIC AND CLINICAL RESEARCH TOWARD A DEVELOPMENTALLY INFORMED THEORY OF PAIN CHRONIFICATION IN THE PEDIATRIC POPULATION. AT THE OUTSET, THE IMPORTANCE OF OBJECTIVE BIOMARKERS FOR CHRONIFICATION OF PAIN IN CHILDREN IS OUTLINED, FOLLOWED BY A SUMMARY OF THE CURRENT EVIDENCE ON THE MECHANISMS OF ACUTE TO CHRONIC PAIN TRANSITION IN ADULTS, IN ORDER TO CONTRAST WITH THE DEVELOPMENTAL MECHANISMS OF PAIN CHRONIFICATION IN THE PEDIATRIC POPULATION. EVIDENCE IS PRESENTED TO SHOW THAT CHRONIC PAIN MAY HAVE ITS ORIGIN FROM INSULTS EARLY IN LIFE, WHICH PRIME THE CHILD FOR THE DEVELOPMENT OF CHRONIC PAIN IN LATER LIFE. FURTHERMORE, AVAILABLE GENETIC, EPIGENETIC, PSYCHOPHYSICAL, ELECTROPHYSIOLOGICAL, NEUROIMAGING, NEUROIMMUNE, AND SEX MECHANISMS ARE DESCRIBED IN INFANTS AND OLDER CHILDREN. IN CONCLUSION, FUTURE DIRECTIONS ARE DISCUSSED WITH A FOCUS ON RESEARCH GAPS, TRANSLATIONAL AND CLINICAL IMPLICATIONS. UTILIZATION OF DEVELOPMENTAL MECHANISMS FRAMEWORK TO INFORM CLINICAL DECISION-MAKING AND STRATEGIES FOR PREVENTION AND MANAGEMENT OF ACUTE TO CHRONIC PAIN TRANSITIONS IN CHILDREN, IS HIGHLIGHTED. 2023 13 1935 32 ENVIRONMENTAL RISK FACTORS AND EPIGENETIC ALTERNATIONS IN PSORIASIS. INTRODUCTION AND OBJECTIVE: PSORIASIS ISA QUITE COMMON, CHRONIC AND IMMUNE-MEDIATED SKIN DISORDER. THE PREVALENCE OF PSORIASIS DIFFERS IN VARIOUS COUNTRIES, BUT IT IS SAID TO AFFECT 2% OF THE WORLD'S POPULATION IN GENERAL. PSORIASIS HAS MANY DIFFERENT CLINICAL FEATURES BUT ALL LESIONS HAVE THE SAME CHARACTERISTIC: ERYTHEMA, THICKENING AND SCALE, ALTHOUGH OTHER CLINICAL FEATURES ARE ALSO CONNECTED, SUCH AS PSORIATIC ARTHRITIS, OBESITY AND METABOLIC SYNDROME. ALL OF THESE MAY LEAD TO CONDITIONS IMPAIRING THE QUALITY OF LIFE. THIS REVIEW IS AN ATTEMPT TO SUMMARIZE RECENT DATA REGARDING ENVIRONMENTAL FACTORS, TOGETHER WITH EPIGENETIC MARKERS AND PROCESSES PLAYING AN IMPORTANT ROLE IN PSORIASIS. STATE OF KNOWLEDGE: MANY DIFFERENT ENVIRONMENTAL FACTORS PLAY A ROLE IN GENETICALLY PREDISPOSED PATIENTS. THIS IS CAUSES EPIGENETIC ALTERNATIONS WHICH MAY BE A LINKING PART IN THE WHOLE PROCESS. MANY STUDIES HAVE INDICATED A CONNECTION BETWEEN PSORIASIS AND VARIOUS GENES AND ANTIGENS. THE PRESENCE OF HLA-CW6 IS COMMON AS WELL A STRONG LINK BETWEEN ITS PRESENCE AND THE ONSET OF PSORIASIS BEING OBSERVED. THE MAIN ALTERNATIONS ARE DNA METHYLATION, HISTONE'S MODIFICATIONS AND THE ROLE OF MICRORNA. EXCESSIVE REACTION IS USUALLY NOT PRESENT WITHOUT A TRIGGERING FACTOR. ENVIRONMENTAL FACTORS ARE MOSTLY RATED, SUCH AS DRUGS, LIFE STYLE AND HABITS (SMOKING, ALCOHOL), DIET, PHYSICAL TRAUMA (SKIN INJURY PROVOKING KOEBNER PHENOMENON), STRESS, MICROORGANISM AND INFECTIONS. CONCLUSIONS: THE CORRELATION BETWEEN PATHOGENESIS OF PSORIASIS AND ENVIRONMENTAL RISK FACTORS, TOGETHER WITH EPIGENETIC ALTERNATIONS STILL REQUIRE MORE INVESTIGATION. EDUCATION ABOUT DIET HABITS, NUTRITION, WEIGHT LOSS AND HEALTHY LIFESTYLE SEEMS TO BE IMPORTANT DURING THE TREATMENT OF PSORIASIS. 2020 14 5175 22 PREDICTORS OF BIOLOGICAL AGE: THE IMPLICATIONS FOR WELLNESS AND AGING RESEARCH. AS HEALTHSPAN AND LIFESPAN RESEARCH BREAKTHROUGHS HAVE BECOME MORE COMMONPLACE, THE NEED FOR VALID, PRACTICAL MARKERS OF BIOLOGICAL AGE IS BECOMING INCREASINGLY PARAMOUNT. THE ACCESSIBILITY AND AFFORDABILITY OF BIOLOGICAL AGE PREDICTORS THAT CAN REVEAL INFORMATION ABOUT MORTALITY AND MORBIDITY RISK, AS WELL AS REMAINING YEARS OF LIFE, HAS PROFOUND CLINICAL AND RESEARCH IMPLICATIONS. IN THIS REVIEW, WE EXAMINE 5 GROUPS OF AGING BIOMARKERS CAPABLE OF PROVIDING ACCURATE BIOLOGICAL AGE ESTIMATIONS. THE UNIQUE CAPABILITIES OF THESE BIOMARKERS HAVE FAR REACHING IMPLICATIONS FOR THE TESTING OF BOTH PHARMACEUTICAL AND NON-PHARMACEUTICAL INTERVENTIONS DESIGNED TO SLOW OR REVERSE BIOLOGICAL AGING. ADDITIONALLY, THE ENHANCED VALIDITY AND AVAILABILITY OF THESE TOOLS MAY HAVE INCREASINGLY RELEVANT CLINICAL VALUE. THE AUTHORS OF THIS REVIEW EXPLORE THOSE IMPLICATIONS, WITH AN EMPHASIS ON LIFESTYLE MODIFICATION RESEARCH, AND PROVIDE AN OVERVIEW OF THE CURRENT EVIDENCE REGARDING 5 BIOLOGICAL AGE PREDICTOR CATEGORIES: TELOMERE LENGTH, COMPOSITE BIOMARKERS, DNA METHYLATION "EPIGENETIC CLOCKS," TRANSCRIPTIONAL PREDICTORS OF BIOLOGICAL AGE, AND FUNCTIONAL AGE PREDICTORS. 2021 15 120 30 A SYSTEMATIC REVIEW OF CHILDHOOD MALTREATMENT AND DNA METHYLATION: CANDIDATE GENE AND EPIGENOME-WIDE APPROACHES. CHILDHOOD MALTREATMENT IS A MAJOR RISK FACTOR FOR CHRONIC AND SEVERE MENTAL AND PHYSICAL HEALTH PROBLEMS ACROSS THE LIFESPAN. INCREASING EVIDENCE SUPPORTS THE HYPOTHESIS THAT MALTREATMENT IS ASSOCIATED WITH EPIGENETIC CHANGES THAT MAY SUBSEQUENTLY SERVE AS MECHANISMS OF DISEASE. THE CURRENT REVIEW USES A SYSTEMATIC APPROACH TO IDENTIFY AND SUMMARIZE THE LITERATURE RELATED TO CHILDHOOD MALTREATMENT AND ALTERATIONS IN DNA METHYLATION IN HUMANS. A TOTAL OF 100 EMPIRICAL ARTICLES WERE IDENTIFIED IN OUR SYSTEMATIC REVIEW OF RESEARCH PUBLISHED PRIOR TO OR DURING MARCH 2020, INCLUDING STUDIES THAT FOCUSED ON CANDIDATE GENES AND STUDIES THAT LEVERAGED EPIGENOME-WIDE DATA IN BOTH CHILDREN AND ADULTS. THEMES ARISING FROM THE LITERATURE, INCLUDING CONSISTENT AND INCONSISTENT PATTERNS OF RESULTS, ARE PRESENTED. SEVERAL DIRECTIONS FOR FUTURE RESEARCH, INCLUDING IMPORTANT METHODOLOGICAL CONSIDERATIONS FOR FUTURE STUDY DESIGN, ARE DISCUSSED. TAKEN TOGETHER, THE LITERATURE ON CHILDHOOD MALTREATMENT AND DNA METHYLATION UNDERSCORES THE COMPLEXITY OF TRANSACTIONS BETWEEN THE ENVIRONMENT AND BIOLOGY ACROSS DEVELOPMENT. 2021 16 1385 38 DIABETES IN CHILDHOOD CANCER SURVIVORS: EMERGING CONCEPTS IN PATHOPHYSIOLOGY AND FUTURE DIRECTIONS. WITH ADVANCEMENTS IN CANCER TREATMENT AND SUPPORTIVE CARE, THERE IS A GROWING POPULATION OF CHILDHOOD CANCER SURVIVORS WHO EXPERIENCE A SUBSTANTIAL BURDEN OF COMORBIDITIES RELATED TO HAVING RECEIVED CANCER TREATMENT AT A YOUNG AGE. DESPITE AN OVERALL REDUCTION IN THE INCIDENCE OF MOST CHRONIC HEALTH CONDITIONS IN CHILDHOOD CANCER SURVIVORS OVER THE PAST SEVERAL DECADES, THE CUMULATIVE INCIDENCE OF CERTAIN LATE EFFECTS, IN PARTICULAR DIABETES MELLITUS (DM), HAS INCREASED. THE IMPLICATIONS ARE SIGNIFICANT, BECAUSE DM IS A KEY RISK FACTOR FOR CARDIOVASCULAR DISEASE, A LEADING CAUSE OF PREMATURE DEATH IN CHILDHOOD CANCER SURVIVORS. THE UNDERLYING PATHOPHYSIOLOGY OF DM IN CANCER SURVIVORS IS MULTIFACTORIAL. DM DEVELOPS AT YOUNGER AGES IN SURVIVORS COMPARED TO CONTROLS, WHICH MAY REFLECT AN "ACCELERATED AGING" PHENOTYPE IN THESE INDIVIDUALS. THE TREATMENT-RELATED EXPOSURES (I.E., CHEMOTHERAPY, RADIATION) THAT INCREASE RISK FOR DM IN CHILDHOOD CANCER SURVIVORS MAY BE MORE THAN ADDITIVE WITH ESTABLISHED DM RISK FACTORS (E.G., OLDER AGE, OBESITY, RACE, AND ETHNICITY). EMERGING RESEARCH ALSO POINTS TO PARALLELS IN CELLULAR PROCESSES IMPLICATED IN AGING- AND CANCER TREATMENT-RELATED DM. STILL, THERE REMAINS MARKED INTER-INDIVIDUAL VARIABILITY REGARDING RISK OF DM THAT IS NOT EXPLAINED BY DEMOGRAPHIC AND THERAPEUTIC RISK FACTORS ALONE. RECENT STUDIES HAVE HIGHLIGHTED THE ROLE OF GERMLINE GENETIC RISK FACTORS AND EPIGENETIC MODIFICATIONS THAT ARE ASSOCIATED WITH RISK OF DM IN BOTH THE GENERAL AND ONCOLOGY POPULATIONS. THIS REVIEW SUMMARIZES OUR CURRENT UNDERSTANDING OF RECOGNIZED RISK FACTORS FOR DM IN CHILDHOOD CANCER SURVIVORS TO HELP INFORM TARGETED APPROACHES FOR DISEASE SCREENING, PREVENTION, AND TREATMENT. FURTHERMORE, IT HIGHLIGHTS THE EXISTING SCIENTIFIC GAPS IN UNDERSTANDING THE RELATIVE CONTRIBUTIONS OF INDIVIDUAL THERAPEUTIC EXPOSURES AND THE MECHANISMS BY WHICH THEY EXERT THEIR EFFECTS THAT UNIQUELY PREDISPOSE THIS POPULATION TO DM FOLLOWING CANCER TREATMENT. 2023 17 2651 32 EPIGENOMICS AND TRANSCRIPTOMICS IN THE PREDICTION AND DIAGNOSIS OF CHILDHOOD ASTHMA: ARE WE THERE YET? ASTHMA IS THE MOST COMMON NON-COMMUNICABLE CHRONIC DISEASE OF CHILDHOOD. DESPITE ITS HIGH PREVALENCE, TO DATE WE LACK METHODS THAT ARE BOTH EFFICIENT AND ACCURATE IN DIAGNOSING ASTHMA. MOST TRADITIONAL APPROACHES HAVE BEEN BASED ON GARNERING CLINICAL EVIDENCE, SUCH AS RISK FACTORS AND EXPOSURES. GIVEN THE HIGH HERITABILITY OF ASTHMA, MORE RECENT APPROACHES HAVE LOOKED AT GENETIC POLYMORPHISMS AS POTENTIAL "RISK FACTORS." HOWEVER, GENETIC VARIANTS EXPLAIN ONLY A SMALL PROPORTION OF ASTHMA RISK, AND HAVE BEEN LESS THAN OPTIMAL AT PREDICTING RISK FOR INDIVIDUAL SUBJECTS. EPIGENOMIC STUDIES OFFER SIGNIFICANT ADVANTAGES OVER PREVIOUS APPROACHES. EPIGENETIC REGULATION IS HIGHLY TISSUE-SPECIFIC, AND CAN INDUCE BOTH SHORT- AND LONG-TERM CHANGES IN GENE EXPRESSION. SUCH CHANGES CAN START IN UTERO, CAN VARY THROUGHOUT THE LIFE SPAN, AND IN SOME INSTANCES CAN BE PASSED ON FROM ONE GENERATION TO ANOTHER. MOST IMPORTANTLY, THE EPIGENOME CAN BE MODIFIED BY ENVIRONMENTAL FACTORS AND EXPOSURES, AND THUS EPIGENETIC AND TRANSCRIPTOMIC PROFILING MAY YIELD THE MOST ACCURATE RISK ESTIMATES FOR A GIVEN PATIENT BY INCORPORATING ENVIRONMENTAL (AND TREATMENT) EFFECTS THROUGHOUT THE LIFESPAN. HERE WE WILL REVIEW THE MOST RECENT ADVANCES IN THE USE OF EPIGENETIC AND TRANSCRIPTOMIC ANALYSIS FOR THE EARLY DIAGNOSIS OF ASTHMA AND ATOPY, AS WELL AS CHALLENGES AND FUTURE DIRECTIONS IN THE FIELD AS IT MOVES FORWARD. WE WILL PARTICULARLY FOCUS ON DNA METHYLATION, THE MOST STUDIED MECHANISM OF EPIGENETIC REGULATION. 2019 18 637 27 BIOLOGY OF PREMATURE AGEING IN SURVIVORS OF CANCER. OVER 30 MILLION CANCER SURVIVORS EXIST WORLDWIDE. SURVIVORS HAVE AN EARLIER ONSET AND HIGHER INCIDENCE OF CHRONIC COMORBIDITIES, INCLUDING ENDOCRINOPATHIES, CARDIAC DYSFUNCTION, OSTEOPOROSIS, PULMONARY FIBROSIS, SECONDARY CANCERS AND FRAILTY THAN THE GENERAL POPULATION; HOWEVER, THE FUNDAMENTAL BASIS OF THESE CHANGES AT THE CELLULAR LEVEL IS UNKNOWN. AN ELECTRONIC SEARCH WAS PERFORMED ON EMBASE, MEDLINE IN-PROCESS & OTHER NON-INDEXED CITATIONS, AND THE COCHRANE CENTRAL REGISTER OF CONTROLLED TRIALS. ORIGINAL ARTICLES ADDRESSING THE CELLULAR BIOLOGY OF AGEING AND/OR THE MECHANISMS OF CANCER THERAPIES SIMILAR TO AGEING MECHANISMS WERE INCLUDED, AND REFERENCES OF THESE ARTICLES WERE REVIEWED FOR FURTHER SEARCH. WE FOUND MULTIPLE BIOLOGICAL PROCESS OF AGEING AT THE CELLULAR LEVEL AND THEIR ASSOCIATION WITH CANCER THERAPIES, AS WELL AS WITH CLINICAL EFFECTS. THE DIRECT EFFECTS OF VARIOUS CHEMOTHERAPIES AND RADIATION ON TELOMERE LENGTH, SENESCENT CELLS, EPIGENETIC MODIFICATIONS AND MICRORNA WERE FOUND. WE REVIEW THE EFFECTS OF CANCER THERAPIES ON RECOGNISED HALLMARKS OF AGEING. LONG-TERM COMORBIDITIES SEEN IN CANCER SURVIVORS MIMIC THE PHENOTYPES OF AGEING AND LIKELY RESULT FROM THE INTERACTION BETWEEN THERAPEUTIC EXPOSURES AND THE UNDERLYING BIOLOGY OF AGEING. LONG-TERM FOLLOW-UP OF CANCER SURVIVORS AND RESEARCH ON PREVENTION STRATEGIES SHOULD BE PURSUED TO INCREASE THE LENGTH AND QUALITY OF LIFE AMONG THE GROWING POPULATION OF CANCER SURVIVORS. 2017 19 5185 36 PREMATURE PHYSIOLOGIC AGING AS A PARADIGM FOR UNDERSTANDING INCREASED RISK OF ADVERSE HEALTH ACROSS THE LIFESPAN OF SURVIVORS OF CHILDHOOD CANCER. THE IMPROVEMENT IN SURVIVAL OF CHILDHOOD CANCER OBSERVED ACROSS THE PAST 50 YEARS HAS RESULTED IN A GROWING ACKNOWLEDGMENT THAT SIMPLY EXTENDING THE LIFESPAN OF SURVIVORS IS NOT ENOUGH. IT IS INCUMBENT ON BOTH THE CANCER RESEARCH AND THE CLINICAL CARE COMMUNITIES TO ALSO IMPROVE THE HEALTH SPAN OF SURVIVORS. IT IS WELL ESTABLISHED THAT AGING ADULT SURVIVORS OF CHILDHOOD CANCER ARE AT INCREASED RISK OF CHRONIC HEALTH CONDITIONS, RELATIVE TO THE GENERAL POPULATION. HOWEVER, AS THE FIRST GENERATION OF SURVIVORS AGE INTO THEIR 50S AND 60S, IT HAS BECOME INCREASINGLY EVIDENT THAT THIS POPULATION IS ALSO AT RISK OF EARLY ONSET OF PHYSIOLOGIC AGING. GERIATRIC MEASURES HAVE UNCOVERED EVIDENCE OF REDUCED STRENGTH AND SPEED AND INCREASED FATIGUE, ALL COMPONENTS OF FRAILTY, AMONG SURVIVORS WITH A MEDIAN AGE OF 33 YEARS, WHICH IS SIMILAR TO ADULTS OLDER THAN 65 YEARS OF AGE IN THE GENERAL POPULATION. FURTHERMORE, FRAILTY IN SURVIVORS INDEPENDENTLY INCREASED THE RISK OF MORBIDITY AND MORTALITY. ALTHOUGH THERE HAS BEEN A PAUCITY OF RESEARCH INVESTIGATING THE UNDERLYING BIOLOGIC MECHANISMS FOR ADVANCED PHYSIOLOGIC AGE IN SURVIVORS, RESULTS FROM GERIATRIC POPULATIONS SUGGEST FIVE BIOLOGICALLY PLAUSIBLE MECHANISMS THAT MAY BE POTENTIATED BY EXPOSURE TO CANCER THERAPIES: INCREASED CELLULAR SENESCENCE, REDUCED TELOMERE LENGTH, EPIGENETIC MODIFICATIONS, SOMATIC MUTATIONS, AND MITOCHONDRIAL DNA INFIDELITY. THERE IS NOW A CRITICAL NEED FOR RESEARCH TO ELUCIDATE THE BIOLOGIC MECHANISMS OF PREMATURE AGING IN SURVIVORS OF CHILDHOOD CANCER. THIS RESEARCH COULD PAVE THE WAY FOR NEW FRONTIERS IN THE PREVENTION OF THESE LIFE-CHANGING OUTCOMES. 2018 20 3676 34 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