1 6792 104 [DOHAD AND EPIGENETIC INFORMATION: SOCIETAL CHALLENGES]. THE CONCEPT OF THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) ALTERS OUR UNDERSTANDING OF WHAT CONSTITUTES "HEALTH" OR "DISEASE" INTENDED AS CHRONIC, NON-COMMUNICABLE DISEASES, WHICH DEVELOP OVER THE LIFE COURSE IN HIGH INCOME AND EMERGING COUNTRIES. IT IMPLIES A CHANGE IN PARADIGM FORMING A BASIS FOR PREVENTION POLICIES ACROSS THE GLOBE. IT ALSO IMPACTS PSYCHOLOGICAL, SOCIAL, ECONOMIC, ETHICAL AND LEGAL SCIENCES. IN LINE WITH THE UNANTICIPATED UNDERPINNING EPIGENETIC MECHANISMS ARE ALSO THE SOCIAL ISSUES (INCLUDING PUBLIC POLICIES) THAT COULD BE PRODUCED BY THE KNOWLEDGE RELATED TO DOHAD THAT OPENS A WIDE FIELD OF INQUIRY. THE INFORMATION UNVEILED BY EPIGENETICS COUPLED WITH INFORMATION ON LIFESTYLE INCLUDING DURING THE DEVELOPMENT PHASE, IS OF UNFORESEEN NATURE, RAISING ISSUES OF DIFFERENT NATURE. THEREFORE IT REQUIRES SPECIFIC ATTENTION AND RESEARCH, AND A SPECIFIC SUPPORT BY A PLURIDISCIPLINARY REFLECTION SINCE THE VERY BEGINNING OF ITS PRODUCTION, TO ANTICIPATE THE QUESTIONS THAT MIGHT BE RAISED IN THE FUTURE. 2016 2 3116 31 GEROSCIENCE: ADDRESSING THE MISMATCH BETWEEN ITS EXCITING RESEARCH OPPORTUNITIES, ITS ECONOMIC IMPERATIVE AND ITS CURRENT FUNDING CRISIS. THERE IS AT PRESENT A HUGE DISCONNECT BETWEEN LEVELS OF FUNDING FOR BASIC RESEARCH ON FUNDAMENTAL MECHANISMS OF BIOLOGICAL AGING AND, GIVEN DEMOGRAPHIC PROJECTIONS, THE ANTICIPATED ENORMOUS SOCIAL AND ECONOMIC IMPACTS OF A LITANY OF CHRONIC DISEASES FOR WHICH AGING IS BY FAR THE MAJOR RISK FACTOR: ONE VALUABLE APPROACH, RECENTLY INSTIGATED BY FELIPE SIERRA & COLLEAGUES AT THE US NATIONAL INSTITUTE ON AGING, IS THE DEVELOPMENT OF A GEROSCIENCE INTEREST GROUP AMONG VIRTUALLY ALL OF THE NIH INSTITUTES. A COMPLEMENTARY APPROACH WOULD BE TO SEEK MAJOR ESCALATIONS OF PRIVATE FUNDING. THE AMERICAN FEDERATION FOR AGING RESEARCH, THE PAUL GLENN FOUNDATION AND THE ELLISON MEDICAL FOUNDATION PIONEERED EFFORTS BY THE PRIVATE SECTOR TO PROVIDE SUBSTANTIAL SUPPLEMENTS TO PUBLIC SOURCES OF FUNDING. IT IS TIME FOR OUR COMMUNITY TO ORGANIZE EFFORTS TOWARDS THE ENHANCEMENTS OF SUCH CRUCIAL CONTRIBUTIONS, ESPECIALLY IN SUPPORT OF THE EMERGING GENERATION OF YOUNG INVESTIGATORS, MANY OF WHOM ARE LEAVING OUR RANKS TO SEEK ALTERNATIVE EMPLOYMENT. TO DO SO, WE MUST PROVIDE POTENTIAL DONORS WITH STRONG ECONOMIC, HUMANITARIAN AND SCIENTIFIC RATIONALES. AN INITIAL APPROACH TO SUCH EFFORTS IS BRIEFLY OUTLINED IN THIS MANUSCRIPT AS A BASIS FOR WIDER DISCUSSIONS WITHIN OUR COMMUNITY. 2017 3 3011 20 GENETICS AND EPIGENETICS IN THE FIBROGENIC EVOLUTION OF CHRONIC LIVER DISEASES. RECENT YEARS HAVE SEEN UNPRECEDENTED PROGRESS IN THE IDENTIFICATION AND CHARACTERIZATION OF GENETIC INFORMATION RELATED TO CHRONIC LIVER DISEASES (CLDS). HOWEVER, DESPITE THE CONCEPTUAL BENEFIT IN EARLY RECOGNITION OF AT-RISK POPULATIONS AMENABLE TO PRE-EMPTIVE TREATMENT AND/OR SURVEILLANCE STRATEGIES, RECENT GENOMIC RESEARCH IN THE FIELD HAS PLACED FOCUS ON UNRAVELLING THE GENETIC ARCHITECTURE OF DISEASE SUSCEPTIBILITY, WHILE DATA ON GENETIC MARKERS ANTICIPATING AN ACCELERATED FIBROGENESIS IN AN INDIVIDUAL ARE STILL LIMITED. LIKEWISE, SEQUENCE VARIATION ASSIGNING RAPID FIBROGENIC EVOLUTION COMMON TO CLDS IRRESPECTIVE OF ETIOLOGY ARE POORLY DEFINED ASIDE FROM PNPLA3 (ADIPONUTRIN) AS A PROMINENT EXCEPTION. THE EMERGING FIELD OF EPIGENETICS IN HEPATOLOGY HAS MOSTLY BEEN STUDIED UNDER THE PERSPECTIVE OF GENE REGULATION, LESS SO AS A HERITABLE ALTERATION IN GENE ACTIVITY. IN THIS ARTICLE WE WILL CRITICALLY DISCUSS RECENT FINDINGS IN GENOMIC HEPATOLOGY WITH SPECIAL FOCUS ON THE (EPI)GENETIC CONTRIBUTION TO THE FIBROGENIC EVOLUTION OF CLDS. 2011 4 1374 33 DEVELOPMENTAL PROGRAMMING OF ADULT DISEASE: REPROGRAMMING BY MELATONIN? ADULT-ONSET CHRONIC NON-COMMUNICABLE DISEASES (NCDS) CAN ORIGINATE FROM EARLY LIFE THROUGH SO-CALLED THE "DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE" (DOHAD) OR "DEVELOPMENTAL PROGRAMMING". THE DOHAD CONCEPT OFFERS THE "REPROGRAMMING" STRATEGY TO SHIFT THE TREATMENT FROM ADULTHOOD TO EARLY LIFE, BEFORE CLINICAL DISEASE IS APPARENT. MELATONIN, AN ENDOGENOUS INDOLEAMINE PRODUCED BY THE PINEAL GLAND, HAS PLEIOTROPIC BIOACTIVITIES THOSE ARE BENEFICIAL IN A VARIETY OF HUMAN DISEASES. EMERGING EVIDENCE SUPPORT THAT MELATONIN IS CLOSELY INTER-RELATED TO OTHER PROPOSED MECHANISMS CONTRIBUTING TO THE DEVELOPMENTAL PROGRAMMING OF A VARIETY OF CHRONIC NCDS. RECENT ANIMAL STUDIES HAVE BEGUN TO UNRAVEL THE MULTIFUNCTIONAL ROLES OF MELATONIN IN MANY EXPERIMENTAL MODELS OF DEVELOPMENTAL PROGRAMMING. EVEN THOUGH SOME PROGRESS HAS BEEN MADE IN RESEARCH ON MELATONIN AS A REPROGRAMMING STRATEGY TO PREVENT DOHAD-RELATED NCDS, FUTURE HUMAN STUDIES SHOULD AIM AT FILLING THE TRANSLATIONAL GAP BETWEEN ANIMAL MODELS AND CLINICAL TRIALS. HERE, WE REVIEW SEVERAL KEY THEMES ON THE REPROGRAMMING EFFECTS OF MELATONIN IN DOHAD RESEARCH. WE HAVE PARTICULARLY FOCUSED ON THE FOLLOWING AREAS: MECHANISMS OF DEVELOPMENTAL PROGRAMMING; THE INTERRELATIONSHIP BETWEEN MELATONIN AND MECHANISMS UNDERLYING DEVELOPMENTAL PROGRAMMING; PATHOPHYSIOLOGICAL ROLES OF MELATONIN IN PREGNANCY AND FETAL DEVELOPMENT; AND INSIGHT PROVIDED BY ANIMAL MODELS TO SUPPORT MELATONIN AS A REPROGRAMMING THERAPY. RATES OF NCDS ARE INCREASING FASTER THAN ANTICIPATED ALL OVER THE WORLD. HENCE, THERE IS AN URGENT NEED TO UNDERSTAND REPROGRAMMING MECHANISMS OF MELATONIN AND TO TRANSLATE EXPERIMENTAL RESEARCH INTO CLINICAL PRACTICE FOR HALTING A GROWING LIST OF DOHAD-RELATED NCDS. 2017 5 5161 32 PRECISION AND PERSONALIZED MEDICINE: HOW GENOMIC APPROACH IMPROVES THE MANAGEMENT OF CARDIOVASCULAR AND NEURODEGENERATIVE DISEASE. LIFE EXPECTANCY HAS GRADUALLY GROWN OVER THE LAST CENTURY. THIS HAS DEEPLY AFFECTED HEALTHCARE COSTS, SINCE THE GROWTH OF AN AGING POPULATION IS CORRELATED TO THE INCREASING BURDEN OF CHRONIC DISEASES. THIS REPRESENTS THE INTERESTING CHALLENGE OF HOW TO MANAGE PATIENTS WITH CHRONIC DISEASES IN ORDER TO IMPROVE HEALTH CARE BUDGETS. EFFECTIVE PRIMARY PREVENTION COULD REPRESENT A PROMISING ROUTE. TO THIS END, PRECISION, TOGETHER WITH PERSONALIZED MEDICINE, ARE USEFUL INSTRUMENTS IN ORDER TO INVESTIGATE PATHOLOGICAL PROCESSES BEFORE THE APPEARANCE OF CLINICAL SYMPTOMS AND TO GUIDE PHYSICIANS TO CHOOSE A TARGETED THERAPY TO MANAGE THE PATIENT. CARDIOVASCULAR AND NEURODEGENERATIVE DISEASES REPRESENT SUITABLE MODELS FOR TAKING FULL ADVANTAGE OF PRECISION MEDICINE TECHNOLOGIES APPLIED TO ALL STAGES OF DISEASE DEVELOPMENT. THE AVAILABILITY OF HIGH TECHNOLOGY INCORPORATING ARTIFICIAL INTELLIGENCE AND ADVANCEMENT PROGRESS MADE IN THE FIELD OF BIOMEDICAL RESEARCH HAVE BEEN SUBSTANTIAL TO UNDERSTAND HOW GENES, EPIGENETIC MODIFICATIONS, AGING, NUTRITION, DRUGS, MICROBIOME AND OTHER ENVIRONMENTAL FACTORS CAN IMPACT HEALTH AND CHRONIC DISORDERS. THE AIM OF THE PRESENT REVIEW IS TO ADDRESS HOW PRECISION AND PERSONALIZED MEDICINE CAN BRING GREATER CLARITY TO THE CLINICAL AND BIOLOGICAL COMPLEXITY OF THESE TYPES OF DISORDERS ASSOCIATED WITH HIGH MORTALITY, INVOLVING TREMENDOUS HEALTH CARE COSTS, BY DESCRIBING IN DETAIL THE METHODS THAT CAN BE APPLIED. THIS MIGHT OFFER PRECIOUS TOOLS FOR PREVENTIVE STRATEGIES AND POSSIBLE CLUES ON THE EVOLUTION OF THE DISEASE AND COULD HELP IN PREDICTING MORBIDITY, MORTALITY AND DETECTING CHRONIC DISEASE INDICATORS MUCH EARLIER IN THE DISEASE COURSE. THIS, OF COURSE, WILL HAVE A MAJOR EFFECT ON BOTH IMPROVING THE QUALITY OF CARE AND QUALITY OF LIFE OF THE PATIENTS AND REDUCING TIME EFFORTS AND HEALTHCARE COSTS. 2020 6 1748 30 EARLY LIFE EVENTS AND THEIR CONSEQUENCES FOR LATER DISEASE: A LIFE HISTORY AND EVOLUTIONARY PERSPECTIVE. BIOMEDICAL SCIENCE HAS LITTLE CONSIDERED THE RELEVANCE OF LIFE HISTORY THEORY AND EVOLUTIONARY AND ECOLOGICAL DEVELOPMENTAL BIOLOGY TO CLINICAL MEDICINE. HOWEVER, THE OBSERVATIONS THAT EARLY LIFE INFLUENCES CAN ALTER LATER DISEASE RISK--THE "DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE" (DOHAD) PARADIGM--HAVE LED TO A RECOGNITION THAT THESE PERSPECTIVES CAN INFORM OUR UNDERSTANDING OF HUMAN BIOLOGY. WE PROPOSE THAT THE DOHAD PHENOMENON CAN BE CONSIDERED AS A SUBSET OF THE BROADER PROCESSES OF DEVELOPMENTAL PLASTICITY BY WHICH ORGANISMS ADAPT TO THEIR ENVIRONMENT DURING THEIR LIFE COURSE. SUCH ADAPTIVE PROCESSES ALLOW GENOTYPIC VARIATION TO BE PRESERVED THROUGH TRANSIENT ENVIRONMENTAL CHANGES. CUES FOR PLASTICITY OPERATE PARTICULARLY DURING EARLY DEVELOPMENT; THEY MAY AFFECT A SINGLE ORGAN OR SYSTEM, BUT GENERALLY THEY INDUCE INTEGRATED ADJUSTMENTS IN THE MATURE PHENOTYPE, A PROCESS UNDERPINNED BY EPIGENETIC MECHANISMS AND INFLUENCED BY PREDICTION OF THE MATURE ENVIRONMENT. IN MAMMALS, AN ADVERSE INTRAUTERINE ENVIRONMENT RESULTS IN AN INTEGRATED SUITE OF RESPONSES, SUGGESTING THE INVOLVEMENT OF A FEW KEY REGULATORY GENES, THAT RESETS THE DEVELOPMENTAL TRAJECTORY IN EXPECTATION OF POOR POSTNATAL CONDITIONS. MISMATCH BETWEEN THE ANTICIPATED AND THE ACTUAL MATURE ENVIRONMENT EXPOSES THE ORGANISM TO RISK OF ADVERSE CONSEQUENCES-THE GREATER THE MISMATCH, THE GREATER THE RISK. FOR HUMANS, PREDICTION IS INACCURATE FOR MANY INDIVIDUALS BECAUSE OF CHANGES IN THE POSTNATAL ENVIRONMENT TOWARD ENERGY-DENSE NUTRITION AND LOW ENERGY EXPENDITURE, CONTRIBUTING TO THE EPIDEMIC OF CHRONIC NONCOMMUNICABLE DISEASE. THIS VIEW OF HUMAN DISEASE FROM THE PERSPECTIVES OF LIFE HISTORY BIOLOGY AND EVOLUTIONARY THEORY OFFERS NEW APPROACHES TO PREVENTION, DIAGNOSIS AND INTERVENTION. 2007 7 46 34 A CONCEPTUAL FRAMEWORK FOR THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE. IN THE LAST DECADES, THE DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) HAVE EMERGED AS A VIGOROUS FIELD COMBINING EXPERIMENTAL, CLINICAL, EPIDEMIOLOGICAL AND PUBLIC HEALTH RESEARCH. ITS GOAL IS TO UNDERSTAND HOW EVENTS IN EARLY LIFE SHAPE LATER MORBIDITY RISK, ESPECIALLY OF NON-COMMUNICABLE CHRONIC DISEASES. AS THESE DISEASES BECOME THE MAJOR CAUSE OF MORBIDITY AND MORTALITY WORLDWIDE, RESEARCH ARISING FROM DOHAD IS LIKELY TO GAIN SIGNIFICANCE TO PUBLIC HEALTH AND ECONOMIC DEVELOPMENT. BUT ACTION MAY BE HINDERED BY THE LACK OF A FIRM MECHANISTIC EXPLANATION AND OF A CONCEPTUAL BASIS, ESPECIALLY REGARDING THE EVOLUTIONARY SIGNIFICANCE OF THE DOHAD PHENOMENON. IN THIS ARTICLE, WE PROVIDE A SUCCINCT HISTORICAL REVIEW OF THE RESEARCH INTO THE RELATIONSHIP BETWEEN DEVELOPMENT AND LATER DISEASE, CONSIDER THE EVOLUTIONARY AND DEVELOPMENTAL SIGNIFICANCE AND DISCUSS THE UNDERLYING MECHANISMS OF THE DOHAD PHENOMENON. DOHAD SHOULD BE VIEWED AS A PART OF A BROADER BIOLOGICAL MECHANISM OF PLASTICITY BY WHICH ORGANISMS, IN RESPONSE TO CUES SUCH AS NUTRITION OR HORMONES, ADAPT THEIR PHENOTYPE TO ENVIRONMENT. THESE RESPONSES MAY BE DIVIDED INTO THOSE FOR IMMEDIATE BENEFIT AND THOSE AIMED AT PREDICTION OF A FUTURE ENVIRONMENT: DISEASE OCCURS IN THE MISMATCH BETWEEN PREDICTED AND REALIZED FUTURE. THE LIKELY MECHANISMS THAT ENABLE PLASTICITY INVOLVE EPIGENETIC PROCESSES, AFFECTING THE EXPRESSION OF GENES ASSOCIATED WITH REGULATORY PATHWAYS. THERE IS NOW EVIDENCE THAT EPIGENETIC MARKS MAY BE INHERITED AND SO CONTRIBUTE TO NON-GENOMIC HERITABLE DISEASE RISK. WE END BY DISCUSSING THE GLOBAL SIGNIFICANCE OF THE DOHAD PHENOMENON AND ITS POTENTIAL APPLICATIONS FOR PUBLIC HEALTH PURPOSES. 2010 8 2496 33 EPIGENETICS AND EARLY LIFE ORIGINS OF CHRONIC NONCOMMUNICABLE DISEASES. IN LIGHT OF THE INCREASING THREATS OF CHRONIC NONCOMMUNICABLE DISEASES IN DEVELOPING COUNTRIES, THE GROWING RECOGNITION OF THE EARLY LIFE ORIGINS OF CHRONIC DISEASE, AND INNOVATIVE BREAKTHROUGHS IN BIOMEDICAL RESEARCH AND TECHNOLOGY, IT IS IMPERATIVE THAT WE HARNESS CUTTING-EDGE DATA TO IMPROVE HEALTH PROMOTION AND MAINTENANCE. IT IS WELL RECOGNIZED THAT CHRONIC DISEASES ARE COMPLEX TRAITS AFFECTED BY A WIDE RANGE OF ENVIRONMENTAL AND GENETIC FACTORS; HOWEVER, THE ROLE OF EPIGENETIC FACTORS, PARTICULARLY WITH REGARD TO EARLY LIFE ORIGINS, REMAINS LARGELY UNEXPLORED. GIVEN THE UNIQUE PROPERTIES OF THE EPIGENOME-FUNCTIONALITY DURING CRITICAL TIME WINDOWS, SUCH AS THE INTRAUTERINE PERIOD, HERITABILITY, AND REVERSIBILITY-ENHANCING OUR UNDERSTANDING OF EPIGENETIC MECHANISMS MAY OFFER NEW OPPORTUNITIES FOR THE DEVELOPMENT OF NOVEL EARLY PREDICTION AND PREVENTION PARADIGMS. THIS MAY PRESENT AN UNPARALLELED OPPORTUNITY TO OFFER MATERNAL AND CHILD HEALTH PROFESSIONALS IMPORTANT TOOLS WITH THE TRANSLATIONAL VALUE TO PREDICT, DETECT, AND PREVENT DISEASE AT AN EARLY AGE, LONG BEFORE ITS CLINICAL OCCURRENCE, AND AS SUCH, BREAK LIFELONG AND TRANSGENERATIONAL CYCLES OF DISEASE. IN DOING SO, MODERN TECHNOLOGY CAN BE LEVERAGED TO MAKE GREAT CONTRIBUTIONS TO POPULATION HEALTH, QUALITY OF LIFE, AND REDUCING THE BURDENSOME ECONOMIC COSTS OF NONCOMMUNICABLE DISEASES IN DEVELOPING COUNTRIES. 2013 9 421 32 ANIMAL MODELS IN EPIGENETIC RESEARCH: INSTITUTIONAL ANIMAL CARE AND USE COMMITTEE CONSIDERATIONS ACROSS THE LIFESPAN. THE RAPID EXPANSION AND EVOLUTION OF EPIGENETICS AS A CORE SCIENTIFIC DISCIPLINE HAVE RAISED NEW QUESTIONS ABOUT HOW ENDOGENOUS AND ENVIRONMENTAL FACTORS CAN INFORM THE MECHANISMS THROUGH WHICH BIOLOGICAL FORM AND FUNCTION ARE REGULATED. EXISTING AND PROPOSED ANIMAL MODELS USED FOR EPIGENETIC RESEARCH HAVE TARGETED A MYRIAD OF HEALTH AND DISEASE ENDPOINTS THAT MAY BE ACUTE, CHRONIC, AND TRANSGENERATIONAL IN NATURE. INITIATING EVENTS AND OUTCOMES MAY EXTEND ACROSS THE ENTIRE LIFESPAN TO ELICIT UNANTICIPATED PHENOTYPES THAT ARE OF PARTICULAR CONCERN TO INSTITUTIONAL ANIMAL CARE AND USE COMMITTEES (IACUCS). THE DYNAMICS AND PLASTICITY OF EPIGENETIC MECHANISMS PRODUCE EFFECTS AND CONSEQUENCES THAT ARE MANIFEST DIFFERENTIALLY WITHIN DISCREET SPATIAL AND TEMPORAL CONTEXTS, INCLUDING PRENATAL DEVELOPMENT, STEM CELLS, ASSISTED REPRODUCTIVE TECHNOLOGIES, PRODUCTION OF SEXUAL DIMORPHISMS, SENESCENCE, AND OTHERS. MANY DIETARY AND NUTRITIONAL INTERVENTIONS HAVE ALSO BEEN SHOWN TO HAVE A SIGNIFICANT IMPACT ON BIOLOGICAL FUNCTIONS AND DISEASE SUSCEPTIBILITIES THROUGH ALTERED EPIGENETIC PROGRAMMING. THE ENVIRONMENTAL, CHEMICAL, TOXIC, THERAPEUTIC, AND PSYCHOSOCIAL STRESSORS USED IN ANIMAL STUDIES TO ELICIT EPIGENETIC CHANGES CAN BECOME EXTREME AND SHOULD RAISE IACUC CONCERNS FOR THE WELL-BEING AND PROPER CARE OF ALL RESEARCH ANIMALS INVOLVED. EPIGENETICS RESEARCH IS RAPIDLY BECOMING AN INTEGRAL PART OF THE SEARCH FOR MECHANISMS IN EVERY MAJOR AREA OF BIOMEDICAL AND BEHAVIORAL RESEARCH AND WILL FOSTER THE CONTINUED DEVELOPMENT OF NEW ANIMAL MODELS. FROM THE IACUC PERSPECTIVE, CARE MUST BE TAKEN TO ACKNOWLEDGE THE PARTICULAR NEEDS AND CONCERNS CREATED BY SUPERIMPOSITION OF EPIGENETIC MECHANISMS OVER DIVERSE FIELDS OF INVESTIGATION TO ENSURE THE PROPER CARE AND USE OF ANIMALS WITHOUT IMPEDING SCIENTIFIC PROGRESS. 2012 10 4871 24 OUR GENES ARE NOT OUR DESTINY: INCORPORATING MOLECULAR MEDICINE INTO CLINICAL PRACTICE. IN MANY DEVELOPED NATIONS, THE STATE OF PUBLICLY ADMINISTERED HEALTH CARE IS INCREASINGLY PRECARIOUS AS A RESULT OF ESCALATING NUMBERS OF CHRONICALLY ILL PATIENTS, INADEQUATE MEDICAL PERSONNEL AND HOSPITAL FACILITIES, AS WELL AS SPARSE FUNDING FOR ONGOING UPGRADES TO STATE-OF-THE-ART DIAGNOSTIC AND THERAPEUTIC TECHNOLOGY - AN INCREASED EMPHASIS ON AETIOLOGY-CENTRED MEDICINE SHOULD BE CONSIDERED IN ORDER TO ACHIEVE IMPROVED HEALTH FOR PATIENTS AND POPULATIONS. MEDICAL PRACTICE PATTERNS WHICH ARE DESIGNED TO PROVIDE QUICK AND EFFECTIVE AMELIORATION OF SIGNS AND SYMPTOMS ARE FREQUENTLY NOT AN ENDURING SOLUTION TO MANY HEALTH AFFLICTIONS AND CHRONIC DISEASE STATES. RECENT SCIENTIFIC DISCOVERY HAS RENDERED THE DRUG-ORIENTED ALGORITHMIC PARADIGM COMMONLY FOUND IN CONTEMPORARY EVIDENCE-BASED MEDICINE TO BE A REDUCTIONIST APPROACH TO CLINICAL PRACTICE. UNFOLDING EVIDENCE APPEARS TO SUPPORT A GENETIC PREDISPOSITION MODEL OF HEALTH AND ILLNESS RATHER THAN A FATALISTIC PREDESTINATION CONSTRUCT - MODIFIABLE EPIGENETIC AND ENVIRONMENTAL FACTORS HAVE ENORMOUS POTENTIAL TO INFLUENCE CLINICAL OUTCOMES. BY UNDERSTANDING AND APPLYING FUNDAMENTAL CLINICAL PRINCIPLES RELATING TO THE EMERGING FIELDS OF MOLECULAR MEDICINE, NUTRIGENOMICS AND HUMAN EXPOSURE ASSESSMENT, DOCTORS WILL BE EMPOWERED TO ADDRESS CAUSALITY OF AFFLICTION WHEN POSSIBLE AND ACHIEVE SUSTAINED REPRIEVE FOR MANY SUFFERING PATIENTS. 2008 11 3910 30 LIFE COURSE OF ASTHMA. ASTHMA IS A HETEROGENEOUS CHRONIC AIRWAY DISEASE THAT CAN VARY OVER A LIFETIME. ALTHOUGH BROAD CATEGORIES OF ASTHMA BY SEVERITY AND TYPE HAVE BEEN CONSTRUCTED, THERE REMAINS A TREMENDOUS OPPORTUNITY TO DISCOVER AN APPROACH TO MANAGING ASTHMA WITH ADDITIONAL FACTORS IN MIND. MANY IN THE FIELD HAVE SUGGESTED AND ARE PURSUING A NOVEL PARADIGM SHIFT IN HOW ASTHMA MIGHT BE BETTER MANAGED, CONSIDERING THE LIFE COURSE OF EXPOSURES, MANAGEMENT PRIORITIES, AND PREDICTED TRAJECTORY OF LUNG FUNCTION GROWTH. THIS APPROACH WILL REQUIRE A MORE HOLISTIC VIEW OF PRENATAL, POSTNATAL, ADOLESCENCE, HORMONAL AND GENDER ASPECTS, AND THE AGING PROCESS. IN ADDITION, THE ENVIRONMENT, EXTERNALLY AND INTERNALLY, INCLUDING IN ONE'S GENETIC CODE AND EPIGENETIC CHANGES, ARE FACTORS THAT AFFECT HOW ASTHMA PROGRESSES OR BECOMES MORE STABLE IN INDIVIDUALS. THIS CHAPTER FOCUSES ON THE VARIOUS INFLUENCES THAT MAY, TO DIFFERING DEGREES, AFFECT PEOPLE WITH ASTHMA, WHICH CAN DEVELOP AT ANY TIME IN THEIR LIVES. SHIFTING THE PARADIGM OF THOUGHT AND STRATEGIES FOR CARE AND ADVOCATING FOR PUBLIC POLICIES AND HEALTH DELIVERY THAT FOCUS ON THIS PHILOSOPHY IS PARAMOUNT TO ADVANCE ASTHMA CARE FOR ALL. 2023 12 4813 26 OBSTRUCTIVE SLEEP APNEA AND HALLMARKS OF AGING. OBSTRUCTIVE SLEEP APNEA (OSA) IS ONE OF THE MOST COMMON SLEEP DISORDERS. SINCE AGING IS A RISK FACTOR FOR OSA DEVELOPMENT, IT IS EXPECTED THAT ITS PREVALENCE WILL INCREASE WITH THE CURRENT INCREASE IN LIFE SPAN. IN RECENT YEARS, SEVERAL STUDIES HAVE SHOWN THAT OSA POTENTIALLY CONTRIBUTES TO FUNCTIONAL DECLINE, MAINLY PROMPTED BY CHRONIC INTERMITTENT HYPOXIA AND SLEEP FRAGMENTATION. HERE, WE PROPOSE THAT OSA MIGHT ANTICIPATE/AGGRAVATE AGING BY INDUCING CELLULAR AND MOLECULAR IMPAIRMENTS THAT CHARACTERIZE THE AGING PROCESS, SUCH AS STEM CELL EXHAUSTION, TELOMERE ATTRITION AND EPIGENETIC CHANGES. WE SUGGEST THAT FURTHER KNOWLEDGE ON THE IMPACT OF OSA ON AGING MECHANISMS MIGHT CONTRIBUTE TO A BETTER UNDERSTANDING OF HOW OSA MIGHT PUTATIVELY ACCELERATE AGING AND AGING-RELATED DISEASES. 2017 13 5263 28 PROMISING BIOMARKERS OF HUMAN AGING: IN SEARCH OF A MULTI-OMICS PANEL TO UNDERSTAND THE AGING PROCESS FROM A MULTIDIMENSIONAL PERSPECTIVE. THE AGING PROCESS HAS BEEN LINKED TO THE OCCURRENCE OF CHRONIC DISEASES AND FUNCTIONAL IMPAIRMENTS, INCLUDING CANCER, SARCOPENIA, FRAILTY, METABOLIC, CARDIOVASCULAR, AND NEURODEGENERATIVE DISEASES. NONETHELESS, AGING IS HIGHLY VARIABLE AND HETEROGENEOUS AND REPRESENTS A CHALLENGE FOR ITS CHARACTERIZATION. IN THIS SENSE, INTRINSIC CAPACITY (IC) STANDS AS A NOVEL PERSPECTIVE BY THE WORLD HEALTH ORGANIZATION, WHICH INTEGRATES THE INDIVIDUAL WELLBEING, ENVIRONMENT, AND RISK FACTORS TO UNDERSTAND AGING. HOWEVER, THERE IS A LACK OF QUANTITATIVE AND QUALITATIVE ATTRIBUTES TO DEFINE IT OBJECTIVELY. THEREFORE, IN THIS REVIEW WE ATTEMPT TO SUMMARIZE THE MOST RELEVANT AND PROMISING BIOMARKERS DESCRIBED IN CLINICAL STUDIES AT DATE OVER DIFFERENT MOLECULAR LEVELS, INCLUDING EPIGENOMICS, TRANSCRIPTOMICS, PROTEOMICS, METABOLOMICS, AND THE MICROBIOME. TO AID GERONTOLOGISTS, GERIATRICIANS, AND BIOMEDICAL RESEARCHERS TO UNDERSTAND THE AGING PROCESS THROUGH THE IC. AGING BIOMARKERS REFLECT THE PHYSIOLOGICAL STATE OF INDIVIDUALS AND THE UNDERLYING MECHANISMS RELATED TO HOMEOSTATIC CHANGES THROUGHOUT AN INDIVIDUAL LIFESPAN; THEY DEMONSTRATED THAT AGING COULD BE MEASURED INDEPENDENTLY OF TIME (THAT MAY EXPLAIN ITS HETEROGENEITY) AND TO BE HELPFUL TO PREDICT AGE-RELATED SYNDROMES AND MORTALITY. IN SUMMARY, WE HIGHLIGHT THE AREAS OF OPPORTUNITY AND GAPS OF KNOWLEDGE THAT MUST BE ADDRESSED TO FULLY INTEGRATE BIOMEDICAL FINDINGS INTO CLINICALLY USEFUL TOOLS AND INTERVENTIONS. 2020 14 264 25 ADVANCING ASTHMA CARE: THE GLASS IS ONLY HALF FULL! OVER THE PAST 20 YEARS, THERE HAS BEEN A CONCERTED EFFORT IN THE UNITED STATES TO REDUCE MORBIDITY RELATED TO CHRONIC DISEASE, INCLUDING ASTHMA. ATTENTION WAS INITIALLY DIRECTED TOWARD ASTHMA IN RESPONSE TO THE RECOGNITION THAT ASTHMA MORTALITY WAS INCREASING AND THAT THE BURDEN OF DISEASE WAS SIGNIFICANT. THESE EFFORTS TO ADDRESS ASTHMA MORTALITY LED TO MANY NEW INITIATIVES TO DEVELOP CLINICAL PRACTICE GUIDELINES, IMPLEMENT THE ASTHMA GUIDELINES INTO CLINICAL PRACTICE, CONDUCT RESEARCH TO FILL THE GAPS IN THE GUIDELINES, AND CONTINUOUSLY REVISE THE ASTHMA GUIDELINES AS MORE INFORMATION BECAME AVAILABLE. AN ASSESSMENT OF OUR PROGRESS SHOWS SIGNIFICANT ACCOMPLISHMENTS IN RELATION TO REDUCING ASTHMA MORTALITY AND HOSPITALIZATIONS. CONSEQUENTLY, WE ARE NOW AT A CROSSROADS IN ASTHMA CARE. ALTHOUGH WE HAVE RECOGNIZED SOME REMARKABLE ACCOMPLISHMENTS IN REDUCING ASTHMA MORTALITY AND MORBIDITY, THE AVAILABILITY OF NEW TOOLS TO MONITOR DISEASE ACTIVITY, INCLUDING BIOMARKERS AND EPIGENETIC MARKERS, ALONG WITH INFORMATION TECHNOLOGY SYSTEMS TO MONITOR ASTHMA CONTROL HOLD SOME PROMISE IN IDENTIFYING GAPS IN DISEASE MANAGEMENT. THESE ADVANCES SHOULD PROMPT THE EVOLUTION OF NEW STRATEGIES AND NEW TREATMENTS TO FURTHER REDUCE DISEASE BURDEN. IT NOW BECOMES IMPERATIVE TO CONTINUE A FOCUS ON WAYS TO FURTHER REDUCE THE BURDEN OF ASTHMA AND PREVENT ITS ONSET. 2011 15 3399 22 HOW CAN GENETICS AND EPIGENETICS HELP THE NEPHROLOGIST IMPROVE THE DIAGNOSIS AND TREATMENT OF CHRONIC KIDNEY DISEASE PATIENTS? DISCOVERY OF NOVEL IMPROVED TOOLS FOR DIAGNOSIS, PREVENTION AND THERAPY OF CHRONIC KIDNEY DISEASE (CKD) IS AN IMPORTANT TASK FOR THE NEPHROLOGY COMMUNITY AND IT IS LIKELY THAT SCIENTIFIC BREAKTHROUGHS, TO A LARGE EXTENT, WILL BE BASED ON GENOMICS. THE RAPID GROWTH OF THE NUMBER OF GENOME-WIDE ASSOCIATION STUDIES, MAJOR ADVANCES IN DNA SEQUENCING AND OMICS PROFILING, AND ACCELERATING BIOMEDICAL RESEARCH EFFORTS IN THIS AREA HAVE GREATLY EXPANDED THE KNOWLEDGE BASE NEEDED FOR APPLIED GENOMICS. HOWEVER, TRANSLATING AND IMPLEMENTING GENOTYPE-PHENOTYPE DATA INTO GENE-BASED MEDICINE IN CKD POPULATIONS IS STILL IN AN EARLY PHASE AND WILL REQUIRE CONTINUOUS RESEARCH EFFORTS WITH INTEGRATED APPROACHES AND INTENSIFIED INVESTIGATIONS THAT FOCUS ON THE BIOLOGICAL PATHWAYS, WHICH CAUSATIVELY LINK A GENETIC VARIANT WITH THE DISEASE PHENOTYPE. IN THIS ARTICLE, WE REVIEW SOME CURRENT STRATEGIES TO UNRAVEL THESE TRANSLATIONAL GAPS AS WELL AS PROSPECTS FOR THE IMPLEMENTATION OF GENETIC AND EPIGENETIC METHODS INTO NOVEL CLINICAL PRACTICE. 2014 16 7 32 'BIOLOGIZING' PSYCHOPATHY: ETHICAL, LEGAL, AND RESEARCH IMPLICATIONS AT THE INTERFACE OF EPIGENETICS AND CHRONIC ANTISOCIAL CONDUCT. EPIGENETICS, A FIELD THAT LINKS GENETICS AND ENVIRONMENTAL INFLUENCES ON THE EXPRESSION OF PHENOTYPIC TRAITS, OFFERS TO INCREASE OUR UNDERSTANDING OF THE DEVELOPMENT AND TRAJECTORY OF DISEASE AND PSYCHOLOGICAL DISORDERS BEYOND THAT THOUGHT OF TRADITIONAL GENETIC RESEARCH AND BEHAVIOURAL MEASURES. BY EXTENSION, THIS NEW PERSPECTIVE HAS IMPLICATIONS FOR RISK AND RISK MANAGEMENT OF ANTISOCIAL BEHAVIOUR WHERE THERE IS A BIOLOGICAL COMPONENT, SUCH AS PSYCHOPATHY. PSYCHOPATHY IS A PERSONALITY DISORDER ASSOCIATED WITH REPEAT DISPLAYS OF ANTISOCIAL BEHAVIOUR, AND IS ASSOCIATED WITH THE DISPROPORTIONATE IMPOSITION OF HARM ON COMMUNITIES. DESPITE ADVANCES IN OUR KNOWLEDGE OF PSYCHOPATHIC INDIVIDUALS, THE CONSTRUCT REMAINS COMPLEX AND IS HAMPERED BY A LACK OF INTEGRATION ACROSS A RANGE OF FUNDAMENTAL DOMAINS. THE CLINICAL AND FORENSIC RESEARCH ON PSYCHOPATHY IS BROUGHT INTO CONVERSATION WITH THE EMERGING FIELD OF EPIGENETICS TO HIGHLIGHT CRITICAL ISSUES OF (1) CLINICAL DEFINITION AND DIAGNOSIS, (2) ASSESSMENT, (3) AETIOLOGY OF PSYCHOPATHIC PHENOTYPES, AND (4) TREATMENT AND REHABILITATION APPROACHES. BROADER ETHICAL AND LEGAL QUESTIONS OF THE ROLE OF EPIGENETIC MECHANISMS IN THE MANAGEMENT OF PSYCHOPATHY BEYOND THE CRIMINAL JUSTICE ARENA ARE ALSO OUTLINED. 2015 17 5163 29 PRECISION/PERSONALIZED MEDICINE IN ALLERGIC DISEASES AND ASTHMA. LIKE MANY OTHER CHRONIC DISEASES, EVERY ALLERGIC PATIENT HAS DIFFERENT CHARACTERISTICS BASED ON CLINICAL COURSE, TREATMENT RESPONSIVENESS AND DISEASE OUTCOMES, WHICH ARE ASSOCIATED WITH THE GENETIC AND EPIGENETIC CONTROL OF MOLECULAR MECHANISMS AND ENVIRONMENT. THIS VARIABILITY NECESSITATES THE ESTABLISHMENT OF PATIENT-TAILORED AND PRECISION APPROACHES IN HANDLING ALLERGIC DISORDERS. BETTER UNDERSTANDING OF THE UNDERLYING PATHOPHYSIOLOGICAL MECHANISMS FOR THE DEVELOPMENT OF ALLERGIC DISORDERS WILL PROVIDE MORE RATIONALE STRATEGIES BASED ON INDIVIDUAL CASES IN CONTROLLING AND TREATING THESE DISORDERS. ENDOTYPING, PHENOTYPING, GENOTYPING AND THERATYPING, AND BIOMARKERS ARE KEYWORDS IN THIS AREA AND HAVE BEEN GAINING LOTS OF ATTENTION IN THE FIELD OF PRECISION MEDICINE, WHICH AIMS TO REVOLUTIONIZE PATIENT CARE AND DEVELOP BETTER PREVENTION AND TREATMENT STRATEGIES. IN ADDITION, PRECISION HEALTH IS A NEW CONCEPT THAT BRINGS PRECISE APPROACHES TO THE SCENE FOR BEING HEALTHY AND PREVENTION OF ALLERGIC DISEASE AND ASTHMA. THE SPECIALTY OF ALLERGY HAS A LEADING ROLE IN THE FIELD, BECAUSE ALLERGEN-SPECIFIC IMMUNOTHERAPY STARTED 105 YEARS AGO, AND IS HISTORICALLY A LEADING PERSONALIZED/PRECISION MEDICINE APPROACH IN ALL MEDICINE DISCIPLINES PROVIDING THE POSSIBILITY OF CURE IN AN INDIVIDUALIZED MANNER INSTEAD OF CONVENTIONAL SYMPTOMATIC TREATMENTS. 2018 18 3169 29 GUIDE FOR CURRENT NUTRIGENETIC, NUTRIGENOMIC, AND NUTRIEPIGENETIC APPROACHES FOR PRECISION NUTRITION INVOLVING THE PREVENTION AND MANAGEMENT OF CHRONIC DISEASES ASSOCIATED WITH OBESITY. CHRONIC DISEASES, INCLUDING OBESITY, ARE MAJOR CAUSES OF MORBIDITY AND MORTALITY IN MOST COUNTRIES. THE ADVERSE IMPACTS OF OBESITY AND ASSOCIATED COMORBIDITIES ON HEALTH REMAIN A MAJOR CONCERN DUE TO THE LACK OF EFFECTIVE INTERVENTIONS FOR PREVENTION AND MANAGEMENT. PRECISION NUTRITION IS AN EMERGING THERAPEUTIC APPROACH THAT TAKES INTO ACCOUNT AN INDIVIDUAL'S GENETIC AND EPIGENETIC INFORMATION, AS WELL AS AGE, GENDER, OR PARTICULAR PHYSIOPATHOLOGICAL STATUS. ADVANCES IN GENOMIC SCIENCES ARE CONTRIBUTING TO A BETTER UNDERSTANDING OF THE ROLE OF GENETIC VARIANTS AND EPIGENETIC SIGNATURES AS WELL AS GENE EXPRESSION PATTERNS IN THE DEVELOPMENT OF DIVERSE CHRONIC CONDITIONS, AND HOW THEY MAY MODIFY THERAPEUTIC RESPONSES. THIS KNOWLEDGE HAS LED TO THE SEARCH FOR GENETIC AND EPIGENETIC BIOMARKERS TO PREDICT THE RISK OF DEVELOPING CHRONIC DISEASES AND PERSONALIZING THEIR PREVENTION AND TREATMENT. ADDITIONALLY, ORIGINAL NUTRITIONAL INTERVENTIONS BASED ON NUTRIENTS AND BIOACTIVE DIETARY COMPOUNDS THAT CAN MODIFY EPIGENETIC MARKS AND GENE EXPRESSION HAVE BEEN IMPLEMENTED. ALTHOUGH CAUTION MUST BE EXERCISED, THESE SCIENTIFIC INSIGHTS ARE PAVING THE WAY FOR THE DESIGN OF INNOVATIVE STRATEGIES FOR THE CONTROL OF CHRONIC DISEASES ACCOMPANYING OBESITY. THIS DOCUMENT PROVIDES A NUMBER OF EXAMPLES OF THE HUGE POTENTIAL OF UNDERSTANDING NUTRIGENETIC, NUTRIGENOMIC, AND NUTRIEPIGENETIC ROLES IN PRECISION NUTRITION. 2017 19 2693 24 EVOLUTION, KIDNEY DEVELOPMENT, AND CHRONIC KIDNEY DISEASE. THERE IS A GLOBAL EPIDEMIC OF CHRONIC KIDNEY DISEASE (CKD) CHARACTERIZED BY A PROGRESSIVE LOSS OF NEPHRONS, ASCRIBED IN LARGE PART TO A RISING INCIDENCE OF HYPERTENSION, METABOLIC SYNDROME, AND TYPE 2 DIABETES MELLITUS. THERE IS A TEN-FOLD VARIATION IN NEPHRON NUMBER AT BIRTH IN THE GENERAL POPULATION, AND A 50% OVERALL DECREASE IN NEPHRON NUMBER IN THE LAST DECADES OF LIFE. THE VICIOUS CYCLE OF NEPHRON LOSS STIMULATING HYPERTROPHY BY REMAINING NEPHRONS AND RESULTING IN GLOMERULOSCLEROSIS HAS BEEN REGARDED AS MALADAPTIVE, AND ONLY PARTIALLY RESPONSIVE TO ANGIOTENSIN INHIBITION. ADVANCES OVER THE PAST CENTURY IN KIDNEY PHYSIOLOGY, GENETICS, AND DEVELOPMENT HAVE ELUCIDATED MANY ASPECTS OF NEPHRON FORMATION, STRUCTURE AND FUNCTION. PARALLEL ADVANCES HAVE BEEN ACHIEVED IN EVOLUTIONARY BIOLOGY, WITH THE EMERGENCE OF EVOLUTIONARY MEDICINE, A DISCIPLINE THAT PROMISES TO PROVIDE NEW INSIGHT INTO THE TREATMENT OF CHRONIC DISEASE. THIS REVIEW PROVIDES A FRAMEWORK FOR UNDERSTANDING THE ORIGINS OF CONTEMPORARY DEVELOPMENTAL NEPHROLOGY, AND RECENT PROGRESS IN EVOLUTIONARY BIOLOGY. THE ESTABLISHMENT OF EVOLUTIONARY DEVELOPMENTAL BIOLOGY (EVO-DEVO), ECOLOGICAL DEVELOPMENTAL BIOLOGY (ECO-DEVO), AND DEVELOPMENTAL ORIGINS OF HEALTH AND DISEASE (DOHAD) FOLLOWED THE DISCOVERY OF THE HOX GENE FAMILY, THE RECOGNITION OF THE CONTRIBUTION OF CUMULATIVE ENVIRONMENTAL STRESSORS TO THE CHANGING PHENOTYPE OVER THE LIFE CYCLE, AND MECHANISMS OF EPIGENETIC REGULATION. THE MATURATION OF EVOLUTIONARY MEDICINE HAS CONTRIBUTED TO NEW INVESTIGATIVE APPROACHES TO CARDIOVASCULAR DISEASE, CANCER, AND INFECTIOUS DISEASE, AND PROMISES THE SAME FOR CKD. BY INCORPORATING THESE PRINCIPLES, DEVELOPMENTAL NEPHROLOGY IS IDEALLY POSITIONED TO ANSWER IMPORTANT QUESTIONS REGARDING THE FATE OF NEPHRONS FROM EMBRYO THROUGH SENESCENCE. 2019 20 4832 26 OMICS BIOMARKERS IN OBESITY: NOVEL ETIOLOGICAL INSIGHTS AND TARGETS FOR PRECISION PREVENTION. PURPOSE OF REVIEW: OMICS-BASED TECHNOLOGIES WERE SUGGESTED TO PROVIDE AN ADVANCED UNDERSTANDING OF OBESITY ETIOLOGY AND ITS METABOLIC CONSEQUENCES. THIS REVIEW HIGHLIGHTS THE RECENT DEVELOPMENTS IN "OMICS"-BASED RESEARCH AIMED TO IDENTIFY OBESITY-RELATED BIOMARKERS. RECENT FINDINGS: RECENT ADVANCES IN OBESITY AND METABOLISM RESEARCH INCREASINGLY RELY ON NEW TECHNOLOGIES TO IDENTIFY MECHANISMS IN THE DEVELOPMENT OF OBESITY USING VARIOUS "OMICS" PLATFORMS. GENETIC AND EPIGENETIC BIOMARKERS THAT TRANSLATE INTO CHANGES IN TRANSCRIPTOME, PROTEOME, AND METABOLOME COULD SERVE AS TARGETS FOR OBESITY PREVENTION. DESPITE A NUMBER OF PROMISING CANDIDATE BIOMARKERS, THERE IS AN INCREASED DEMAND FOR LARGER PROSPECTIVE COHORT STUDIES TO VALIDATE FINDINGS AND DETERMINE BIOMARKER REPRODUCIBILITY BEFORE THEY CAN FIND APPLICATIONS IN PRIMARY CARE AND PUBLIC HEALTH. "OMICS" BIOMARKERS HAVE ADVANCED OUR KNOWLEDGE ON THE ETIOLOGY OF OBESITY AND ITS LINKS WITH CHRONIC DISEASES. THEY BRING SUBSTANTIAL PROMISE IN IDENTIFYING EFFECTIVE PUBLIC HEALTH STRATEGIES THAT PAVE THE WAY TOWARDS PATIENT STRATIFICATION AND PRECISION PREVENTION. 2020