1 5331 229 PUTTING THE PIECES TOGETHER IN GILLES DE LA TOURETTE SYNDROME: EXPLORING THE LINK BETWEEN CLINICAL OBSERVATIONS AND THE BIOLOGICAL BASIS OF DYSFUNCTION. GILLES DE LA TOURETTE SYNDROME IS A COMPLEX, IDIOPATHIC NEUROPSYCHIATRIC DISORDER WHOSE PATHOPHYSIOLOGICAL MECHANISMS HAVE YET TO BE ELUCIDATED. IT IS PHENOTYPICALLY HETEROGENEOUS AND MANIFESTS MORE OFTEN THAN NOT WITH BOTH MOTOR AND BEHAVIORAL IMPAIRMENT, ALTHOUGH TICS ARE ITS CLINICAL HALLMARK. TICS THEMSELVES PRESENT WITH A COMPLEX PROFILE AS THEY CHARACTERISTICALLY WAX AND WANE AND ARE OFTEN PRECEDED BY PREMONITORY SOMATOSENSORY SENSATIONS TO WHICH IT IS SAID A TIC IS THE RESPONSE. HIGHLY COMORBID WITH OBSESSIVE-COMPULSIVE DISORDER AND ATTENTION DEFICIT-HYPERACTIVITY DISORDER, IT IS PURPORTED TO BE AN EPIGENETIC, NEURODEVELOPMENTAL SPECTRUM DISORDER WITH A COMPLEX GENETIC PROFILE. IT HAS A CHILDHOOD ONSET, OCCURS DISPROPORTIONATELY IN MALES, AND SHOWS SPONTANEOUS SYMPTOMATIC ATTENUATION BY ADULTHOOD IN THE MAJORITY OF THOSE AFFLICTED. ALTHOUGH NOT FULLY UNDERSTOOD, ITS NEUROBIOLOGICAL BASIS IS LINKED TO DYSFUNCTION IN THE CORTICO-BASAL GANGLIA-THALAMO-CORTICAL NETWORK. TREATMENT MODALITIES FOR TOURETTE SYNDROME INCLUDE BEHAVIORAL, PHARMACOLOGICAL AND SURGICAL INTERVENTIONS, BUT THERE IS PRESENTLY NO CURE FOR THE DISORDER. FOR THOSE SEVERELY AFFECTED, DEEP BRAIN STIMULATION (DBS) HAS RECENTLY BECOME A VIABLE THERAPEUTIC OPTION. A KEY FACTOR TO ATTAINING OPTIMAL RESULTS FROM THIS SURGERY IS TARGET SELECTION, A TOPIC STILL UNDER DEBATE DUE TO THE COMPLEX CLINICAL PROFILE PRESENTED BY GTS PATIENTS. DEPENDING ON ITS PHENOTYPIC EXPRESSION AND THE MOST PROBLEMATIC ASPECT OF THE DISORDER FOR THE INDIVIDUAL, ONE OF THREE BRAIN REGIONS IS MOST COMMONLY CHOSEN FOR STIMULATION: THE THALAMUS, GLOBUS PALLIDUS, OR NUCLEUS ACCUMBENS. NEUROPHYSIOLOGICAL ANALYSES OF INTRA- AND POST-OPERATIVE HUMAN ELECTROPHYSIOLOGICAL RECORDINGS FROM CLINICAL DBS STUDIES SUGGEST A LINK BETWEEN TIC BEHAVIOR AND ACTIVITY IN BOTH THE THALAMUS AND GLOBUS PALLIDUS. IN PARTICULAR, CHRONIC RECORDINGS FROM THE THALAMUS HAVE SHOWN A CORRELATION BETWEEN SYMPTOMATOLOGY AND (1) SPECTRAL ACTIVITY IN GAMMA BAND POWER AND (2) THETA/GAMMA CROSS FREQUENCY COHERENCE. THESE RESULTS SUGGEST GAMMA OSCILLATIONS AND THETA/GAMMA CROSS CORRELATION DYNAMICS MAY SERVE AS BIOMARKERS FOR DYSFUNCTION. WHILE ACUTE AND CHRONIC RECORDINGS FROM HUMAN SUBJECTS UNDERGOING DBS HAVE PROVIDED BETTER INSIGHT INTO TIC GENESIS AND THE NEUROPATHOPHYSIOLOGICAL MECHANISMS UNDERLYING TOURETTE SYNDROME, THESE STUDIES ARE STILL SPARSE AND THE FIELD WOULD GREATLY BENEFIT FROM FURTHER INVESTIGATIONS. THIS REVIEW REPORTS DATA AND DISCOVERIES OF SCIENTIFIC AND CLINICAL RELEVANCE FROM A WIDE VARIETY OF METHODS AND PROVIDES UP-TO-DATE INFORMATION ABOUT OUR CURRENT UNDERSTANDING OF THE PATHOMECHANISMS UNDERLYING TOURETTE SYNDROME. IT GIVES A COMPREHENSIVE OVERVIEW OF THE CURRENT STATE OF KNOWLEDGE AND ADDRESSES OPEN QUESTIONS IN THE FIELD. 2017 2 5450 45 REPRODUCTIVE TOXICITY OF COMBINED EFFECTS OF ENDOCRINE DISRUPTORS ON HUMAN REPRODUCTION. CONFLUENCE OF ENVIRONMENTAL, GENETIC, AND LIFESTYLE VARIABLES IS RESPONSIBLE FOR DETERIORATION OF HUMAN FECUNDITY. ENDOCRINE DISRUPTORS OR ENDOCRINE DISRUPTING CHEMICALS (EDCS) MAY BE FOUND IN A VARIETY OF FOODS, WATER, AIR, BEVERAGES, AND TOBACCO SMOKE. IT HAS BEEN DEMONSTRATED IN EXPERIMENTAL INVESTIGATIONS THAT A WIDE RANGE OF ENDOCRINE DISRUPTING CHEMICALS HAVE NEGATIVE EFFECTS ON HUMAN REPRODUCTIVE FUNCTION. HOWEVER, EVIDENCE ON THE REPRODUCTIVE CONSEQUENCES OF HUMAN EXPOSURE TO ENDOCRINE DISRUPTING CHEMICALS IS SPARSE AND/OR CONFLICTING IN THE SCIENTIFIC LITERATURE. THE COMBINED TOXICOLOGICAL ASSESSMENT IS A PRACTICAL METHOD FOR ASSESSING THE HAZARDS OF COCKTAILS OF CHEMICALS, CO-EXISTING IN THE ENVIRONMENT. THE CURRENT REVIEW PROVIDES A COMPREHENSIVE OVERVIEW OF STUDIES EMPHASIZING THE COMBINED TOXICITY OF ENDOCRINE DISRUPTING CHEMICALS ON HUMAN REPRODUCTION. ENDOCRINE DISRUPTING CHEMICALS INTERACT WITH EACH OTHER TO DISRUPT THE DIFFERENT ENDOCRINE AXES, RESULTING IN SEVERE GONADAL DYSFUNCTIONS. TRANSGENERATIONAL EPIGENETIC EFFECTS HAVE ALSO BEEN INDUCED IN GERM CELLS, MOSTLY THROUGH DNA METHYLATION AND EPIMUTATIONS. SIMILARLY, AFTER ACUTE OR CHRONIC EXPOSURE TO ENDOCRINE DISRUPTING CHEMICALS COMBINATIONS, INCREASED OXIDATIVE STRESS (OS), ELEVATED ANTIOXIDANT ENZYMATIC ACTIVITY, DISRUPTED REPRODUCTIVE CYCLE, AND REDUCED STEROIDOGENESIS ARE OFTEN REPORTED CONSEQUENCES. THE ARTICLE ALSO DISCUSSES THE CONCENTRATION ADDITION (CA) AND INDEPENDENT ACTION (IA) PREDICTION MODELS, WHICH REVEAL THE IMPORTANCE OF VARIOUS SYNERGISTIC ACTIONS OF ENDOCRINE DISRUPTING CHEMICALS MIXTURES. MORE CRUCIALLY, THIS EVIDENCE-BASED STUDY ADDRESSES THE RESEARCH LIMITATIONS AND INFORMATION GAPS, AS WELL AS PARTICULARLY PRESENTS THE FUTURE RESEARCH VIEWS ON COMBINED ENDOCRINE DISRUPTING CHEMICALS TOXICITY ON HUMAN REPRODUCTION. 2023 3 4015 40 LOW-DOSE EXPOSURE TO BISPHENOLS A, F AND S OF HUMAN PRIMARY ADIPOCYTE IMPACTS CODING AND NON-CODING RNA PROFILES. BISPHENOL A (BPA) EXPOSURE HAS BEEN SUSPECTED TO BE ASSOCIATED WITH DELETERIOUS EFFECTS ON HEALTH INCLUDING OBESITY AND METABOLICALLY-LINKED DISEASES. ALTHOUGH BISPHENOLS F (BPF) AND S (BPS) ARE BPA STRUCTURAL ANALOGS COMMONLY USED IN MANY MARKETED PRODUCTS AS A REPLACEMENT FOR BPA, ONLY SPARSE TOXICOLOGICAL DATA ARE AVAILABLE YET. OUR OBJECTIVE WAS TO COMPREHENSIVELY CHARACTERIZE BISPHENOLS GENE TARGETS IN A HUMAN PRIMARY ADIPOCYTE MODEL, IN ORDER TO DETERMINE WHETHER THEY MAY INDUCE CELLULAR DYSFUNCTION, USING CHRONIC EXPOSURE AT TWO CONCENTRATIONS: A "LOW-DOSE" SIMILAR TO THE DOSE USUALLY ENCOUNTERED IN HUMAN BIOLOGICAL FLUIDS AND A HIGHER DOSE. THEREFORE, BPA, BPF AND BPS HAVE BEEN ADDED AT 10 NM OR 10 MUM DURING THE DIFFERENTIATION OF HUMAN PRIMARY ADIPOCYTES FROM SUBCUTANEOUS FAT OF THREE NON-DIABETIC CAUCASIAN FEMALE PATIENTS. GENE EXPRESSION (MRNA/LNCRNA) ARRAYS AND MICRORNA ARRAYS, HAVE BEEN USED TO ASSESS CODING AND NON-CODING RNA CHANGES. WE DETECTED SIGNIFICANTLY DEREGULATED MRNA/LNCRNA AND MIRNA AT LOW AND HIGH DOSES. ENRICHMENT IN "CANCER" AND "ORGANISMAL INJURY AND ABNORMALITIES" RELATED PATHWAYS WAS FOUND IN RESPONSE TO THE THREE PRODUCTS. SOME LONG INTERGENIC NON-CODING RNAS AND SMALL NUCLEOLAR RNAS WERE DIFFERENTIALLY EXPRESSED SUGGESTING THAT BISPHENOLS MAY ALSO ACTIVATE MULTIPLE CELLULAR PROCESSES AND EPIGENETIC MODIFICATIONS. THE ANALYSIS OF UPSTREAM REGULATORS OF DEREGULATED GENES HIGHLIGHTED HORMONES OR HORMONE-LIKE CHEMICALS SUGGESTING THAT BPS AND BPF CAN BE SUSPECTED TO INTERFERE, JUST LIKE BPA, WITH HORMONAL REGULATION AND HAVE TO BE CONSIDERED AS ENDOCRINE DISRUPTORS. ALL THESE RESULTS SUGGEST THAT AS BPA, ITS SUBSTITUTES BPS AND BPF SHOULD BE USED WITH THE SAME RESTRICTIONS. 2017 4 4871 37 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 5 3032 41 GENETICS OF TINNITUS: AN EMERGING AREA FOR MOLECULAR DIAGNOSIS AND DRUG DEVELOPMENT. SUBJECTIVE TINNITUS IS THE PERCEPTION OF SOUND IN THE ABSENCE OF EXTERNAL OR BODILY-GENERATED SOUNDS. CHRONIC TINNITUS IS A HIGHLY PREVALENT CONDITION AFFECTING OVER 70 MILLION PEOPLE IN EUROPE. A WIDE VARIETY OF COMORBIDITIES, INCLUDING HEARING LOSS, PSYCHIATRIC DISORDERS, NEURODEGENERATIVE DISORDERS, AND TEMPOROMANDIBULAR JOINT (TMJ) DYSFUNCTION, HAVE BEEN SUGGESTED TO CONTRIBUTE TO THE ONSET OR PROGRESSION OF TINNITUS; HOWEVER, THE PRECISE MOLECULAR MECHANISMS OF TINNITUS ARE NOT WELL UNDERSTOOD AND THE CONTRIBUTION OF GENETIC AND EPIGENETIC FACTORS REMAINS UNKNOWN. HUMAN GENETIC STUDIES COULD ENABLE THE IDENTIFICATION OF NOVEL MOLECULAR THERAPEUTIC TARGETS, POSSIBLY LEADING TO THE DEVELOPMENT OF NOVEL PHARMACEUTICAL THERAPEUTICS. IN THIS ARTICLE, WE BRIEFLY DISCUSS THE AVAILABLE EVIDENCE FOR A ROLE OF GENETICS IN TINNITUS AND CONSIDER POTENTIAL HURDLES IN DESIGNING GENETIC STUDIES FOR TINNITUS. SINCE MULTIPLE DISEASES HAVE TINNITUS AS A SYMPTOM AND THE SUPPORTING GENETIC EVIDENCE IS SPARSE, WE PROPOSE VARIOUS STRATEGIES TO INVESTIGATE THE GENETIC UNDERPINNINGS OF TINNITUS, FIRST BY SHOWING EVIDENCE OF HERITABILITY USING CONCORDANCE STUDIES IN TWINS, AND SECOND BY IMPROVING PATIENT SELECTION ACCORDING TO PHENOTYPE AND/OR ETIOLOGY IN ORDER TO CONTROL POTENTIAL BIASES AND OPTIMIZE GENETIC DATA OUTPUT. THE INCREASED KNOWLEDGE RESULTING FROM THIS ENDEAVOR COULD ULTIMATELY IMPROVE THE DRUG DEVELOPMENT PROCESS AND LEAD TO THE PREVENTIVE OR CURATIVE TREATMENT OF TINNITUS. 2016 6 6827 36 [GILLES DE LA TOURETTE'S DISEASE. SYMPTOMS, ETIOPATHOGENESIS AND THERAPEUTIC APPROACHES]. THE GILLES DE LA TOURETTE SYNDROME IS A USUALLY CHRONIC NEUROPSYCHIATRIC DISORDER WITH AN EARLY CHILDHOOD ONSET FEATURING MAINLY MOTOR AND VOCAL TICS. IT SEEMS THAT STRONG GENETIC FACTORS MAKE A MAJOR CONTRIBUTION TO THE ETIOLOGY OF THIS DISORDER, BUT THERE ARE ALSO CLUES THAT EPIGENETIC FACTORS ARE INVOLVED IN THE PATHOGENESIS OF TOURETTE'S SYNDROME, SUCH AS MATERNAL STRESS DURING PREGNANCY, BIRTH COMPLICATIONS AND HORMONAL INFLUENCES. FIRST IN LINE FOR ADEQUATE TREATMENT ARE NEUROLEPTIC COMPOUNDS OF HIGH POTENCY, BESIDES, SEVERAL OTHER PSYCHOACTIVE DRUGS HAVE SHOWN SOME THERAPEUTIC EFFECTS. LESS EVIDENT IS THE EFFICACY OF NEUROSURGICAL AND PSYCHOTHERAPEUTIC INTERVENTIONS. 1997 7 4435 44 MOLECULAR DYSREGULATIONS UNDERLYING THE PATHOGENESIS OF ENDOMETRIOSIS. ENDOMETRIOSIS IS A CRIPPLING DISEASE CHARACTERIZED BY THE PRESENCE OF ENDOMETRIUM-LIKE TISSUE OR SCAR OUTSIDE THE UTERINE CAVITY, COMMONLY CONFINED TO THE PERITONEAL AND SEROSAL SURFACES OF THE PELVIC ORGANS. 10-15% OF WOMEN IN REPRODUCTIVE AGE ARE ESTIMATED TO BE AFFECTED BY ENDOMETRIOSIS. MOST OF THESE PATIENTS PRESENT WITH INFERTILITY AND SUFFER FROM PELVIC PAIN. THE BENIGN DISEASE RARELY PROGRESSES TO MALIGNANCY. REGARDLESS OF ITS HIGH PREVALENCE, THE PATHOGENESIS OF THE DISEASE IS NOT FULLY UNDERSTOOD. TREATMENT OPTIONS FOR ENDOMETRIOSIS ARE LIMITED AND ARE OFTEN BASED ON A SYMPTOMATIC APPROACH. THE UNAVAILABILITY OF PROPER DIAGNOSTIC APPROACHES, FEWER THERAPEUTIC OPTIONS, AND SPARSE UNDERSTANDING OF MOLECULAR ALTERATIONS ARE RESPONSIBLE FOR THE CONTINUED DISEASE BURDEN. EXPLORING THE MOLECULAR ELEMENTS CAUSING THE PATHOGENESIS OF ENDOMETRIOSIS MAY LEAD TO A NUMBER OF BREAKTHROUGHS IN THE TREATMENT OF THE ILLNESS, SUCH AS THE DISCOVERY OF NEW BIOMARKERS FOR DIAGNOSIS AND THERAPEUTIC TARGETS THAT CAN BE A GUIDE TO BETTER PROGNOSIS AND REDUCED RECURRENCE. THE GOAL OF THIS REVIEW IS TO PROVIDE THE READER A CRITICAL UNDERSTANDING OF THE DISEASE BY SUMMARIZING THE GENETIC, IMMUNOLOGICAL, HORMONAL, AND EPIGENETIC DEREGULATIONS THAT SUPPORT THE MOLECULAR BASIS FOR DEVELOPMENT OF ENDOMETRIOTIC CYST, WITH A SPECIAL FOCUS ON THE STUDY MODELS NEEDED TO ANALYZE THESE CHANGES IN THE ENDOMETRIOTIC MICROENVIRONMENT. 2021 8 4344 35 MINIREVIEW: TRANSLATIONAL ANIMAL MODELS OF HUMAN MENOPAUSE: CHALLENGES AND EMERGING OPPORTUNITIES. INCREASING IMPORTANCE IS PLACED ON THE TRANSLATIONAL VALIDITY OF ANIMAL MODELS OF HUMAN MENOPAUSE TO DISCERN RISK VS. BENEFIT FOR PREDICTION OF OUTCOMES AFTER THERAPEUTIC INTERVENTIONS AND TO DEVELOP NEW THERAPEUTIC STRATEGIES TO PROMOTE HEALTH. BASIC DISCOVERY RESEARCH CONDUCTED OVER MANY DECADES HAS BUILT AN EXTENSIVE BODY OF KNOWLEDGE REGARDING REPRODUCTIVE SENESCENCE ACROSS MAMMALIAN SPECIES UPON WHICH TO ADVANCE ANIMAL MODELS OF HUMAN MENOPAUSE. MODIFICATIONS TO EXISTING ANIMAL MODELS COULD RAPIDLY ADDRESS TRANSLATIONAL GAPS RELEVANT TO CLINICAL ISSUES IN HUMAN MENOPAUSAL HEALTH, WHICH INCLUDE THE IMPACT OF 1) CHRONIC OVARIAN HORMONE DEPRIVATION AND HORMONE THERAPY, 2) CLINICALLY RELEVANT HORMONE THERAPY REGIMENS (CYCLIC VS. CONTINUOUS COMBINED), 3) CLINICALLY RELEVANT HORMONE THERAPY FORMULATIONS, AND 4) WINDOWS OF OPPORTUNITY AND OPTIMAL DURATION OF INTERVENTIONS. MODIFICATIONS IN EXISTING ANIMAL MODELS TO MORE ACCURATELY REPRESENT HUMAN MENOPAUSE AND CLINICAL INTERVENTIONS COULD RAPIDLY PROVIDE PRECLINICAL TRANSLATIONAL DATA TO PREDICT OUTCOMES REGARDING UNRESOLVED CLINICAL ISSUES RELEVANT TO WOMEN'S MENOPAUSAL HEALTH. DEVELOPMENT OF THE NEXT GENERATION OF ANIMAL MODELS OF HUMAN MENOPAUSE COULD LEVERAGE ADVANCES IN IDENTIFYING GENOTYPIC VARIATIONS IN ESTROGEN AND PROGESTERONE RECEPTORS TO DEVELOP PERSONALIZED MENOPAUSAL CARE AND TO PREDICT OUTCOMES OF INTERVENTIONS FOR PROTECTION AGAINST OR VULNERABILITY TO DISEASE. KEY TO THE SUCCESS OF THESE MODELS IS THE CLOSE COUPLING BETWEEN THE TRANSLATIONAL TARGET AND THE RANGE OF PREDICTIVE VALIDITY. PRECLINICAL TRANSLATIONAL ANIMAL MODELS OF HUMAN MENOPAUSE NEED TO KEEP PACE WITH CHANGES IN CLINICAL PRACTICE. WITH FOCUS ON PREDICTIVE VALIDITY AND STRATEGIC USE OF ADVANCES IN GENETIC AND EPIGENETIC SCIENCE, NEW ANIMAL MODELS OF HUMAN MENOPAUSE HAVE THE OPPORTUNITY TO SET NEW DIRECTIONS FOR MENOPAUSAL CLINICAL CARE FOR WOMEN WORLDWIDE. 2012 9 6847 34 [MOLECULAR DIAGNOSIS OF CHRONIC MYELOPROLIFERATIVE DISEASES AND MYELODYSPLASTIC SYNDROMES]. HISTOMORPHOLOGICAL EVALUATION OF BONE MARROW TREPHINES AND SMEARS REPRESENTS THE MAJOR APPROACH TO DIAGNOSE THE CHRONIC MYELOPROLIFERATIVE DISEASES (CMPD) AND THE MYELODYSPLASTIC SYNDROMES (MDS). HOWEVER, RISING INSIGHTS INTO MOLECULAR PATHOGENESIS OF HUMAN DISEASES STRENGTHEN THE ATTEMPT OF PATHOLOGISTS TO DEFINE AND TO DETECT UNDERLYING DEFECTS BEYOND THE MICROSCOPE. SINCE DISCOVERY OF THE PHILADELPHIA CHROMOSOME IN CHRONIC MYELOID LEUKEMIA AS THE FIRST SPECIFIC MOLECULAR ABNORMALITY EVER DETECTED IN A HUMAN NEOPLASIA THE GAIN OF KNOWLEDGE OF MOLECULAR PATHOMECHANISMS IN PHILADELPHIA CHROMOSOME NEGATIVE (PH-) CMPD WAS RATHER SPARSE. A DECISIVE BREAKTHROUGH IN PH CMPD WAS THE FINDING OF JAK2 (V617F) DERIVED FROM A SOMATIC POINT MUTATION IN THE MAJORITY OF PATIENTS WITH POLYCYTHEMIA VERA (P.VERA) AND HALF OF PATIENTS WITH ESSENTIAL THROMBOCYTHEMIA (ET) AND PRIMARY MYELOFIBROSIS (PMF). IT THEREFORE CAN NOT BE OVERESTIMATED THAT DETECTION OF JAK2 (V617F) IN A SUSPECTIVE MYELOPROLIFERATION NOW ENABLES A CLEARCUT DISCRIMINATION OF A TRUE PH CMPD FROM A REACTIVE STATE, E.G. P.VERA FROM REACTIVE ERYTHROCYTOSIS. INTERESTINGLY, A BASIC PRINCIPLE OF MOLECULAR DEFECTS DEMONSTRABLE IN CMPD AND RELATED DISORDERS SEEMS TO BE THE INVOLVEMENT OF GENES WITH KINASE ACTIVITIES. SOME OF THOSE GENES WILL BE DISCUSSED IN MORE DETAIL. IN PRIMARY MDS, KARYOTYPING VIA CLASSICAL CYTOGENETICS IS THE PREDOMINANT MOLECULAR APPROACH TO ESTIMATE PROGNOSIS, E.G. -Y, DEL(5Q) AND DEL(20Q) REPRESENT FAVOURABLE ANOMALIES. INDEED, IN 5Q- SYNDROMES KARYOTYPING ENABLES DEFINITE SUBTYPING AND ALLOWS CLINICIANS AND PATIENTS TO EXPECT A GOOD PROGNOSIS. UNTIL NOW, DOZENS OF MOLECULAR ABNORMALITIES SUCH AS MUTATIONS IN AML1, FLT3 AND RAS AS WELL AS EPIGENETIC ALTERATIONS OF GENES HAVE BEEN IDENTIFIED TO VARIOUS DEGREES IN MDS SUBTYPES. SOME OF THEM SEEM TO BE INVOLVED IN DISEASE INITIATION ("MASTER EVENT") AND OTHERS MIGHT INDICATE DISEASE PROGRESSION. HOWEVER, EVEN THOUGH USEFUL FOR FURTHER DISSECTION OF MOLECULAR PATHOMECHANISMS THE MAJORITY OF ABERRATIONS CURRENTLY DOES NOT SERVE AS POTENT MARKERS IN THE DAILY ROUTINE. NEVERTHELESS, IN CMPD AND MDS THE IMPORTANCE OF MOLECULAR ANALYSES FOR DIAGNOSIS, ESTIMATION OF PROGNOSIS, AND DISEASE MONITORING WILL FURTHER INCREASE IN A FORESEEABLE PERIOD OF TIME. 2007 10 4413 30 MOLECULAR AND CELLULAR INSIGHTS INTO THE DEVELOPMENT OF UTERINE FIBROIDS. UTERINE LEIOMYOMAS REPRESENT THE MOST COMMON BENIGN GYNECOLOGIC TUMOR. THESE HORMONE-DEPENDENT SMOOTH-MUSCLE FORMATIONS OCCUR WITH AN ESTIMATED PREVALENCE OF ~70% AMONG WOMEN OF REPRODUCTIVE AGE AND CAUSE SYMPTOMS INCLUDING PAIN, ABNORMAL UTERINE BLEEDING, INFERTILITY, AND RECURRENT ABORTION. DESPITE THE PREVALENCE AND PUBLIC HEALTH IMPACT OF UTERINE LEIOMYOMAS, AVAILABLE TREATMENTS REMAIN LIMITED. AMONG THE POTENTIAL CAUSES OF LEIOMYOMAS, EARLY HORMONAL EXPOSURE DURING PERIODS OF DEVELOPMENT MAY RESULT IN DEVELOPMENTAL REPROGRAMMING VIA EPIGENETIC CHANGES THAT PERSIST IN ADULTHOOD, LEADING TO DISEASE ONSET OR PROGRESSION. RECENT DEVELOPMENTS IN UNBIASED HIGH-THROUGHPUT SEQUENCING TECHNOLOGY ENABLE POWERFUL APPROACHES TO DETECT DRIVER MUTATIONS, YIELDING NEW INSIGHTS INTO THE GENOMIC INSTABILITY OF LEIOMYOMAS. CURRENT DATA ALSO SUGGEST THAT EACH LEIOMYOMA ORIGINATES FROM THE CLONAL EXPANSION OF A SINGLE TRANSFORMED SOMATIC STEM CELL OF THE MYOMETRIUM. IN THIS REVIEW, WE PROPOSE AN INTEGRATED CELLULAR AND MOLECULAR VIEW OF THE ORIGINS OF LEIOMYOMAS, AS WELL AS PARADIGM-SHIFTING STUDIES THAT WILL LEAD TO BETTER UNDERSTANDING AND THE FUTURE DEVELOPMENT OF NON-SURGICAL TREATMENTS FOR THESE HIGHLY FREQUENT TUMORS. 2021 11 4491 41 MONOSOMY 7 MYELOPROLIFERATIVE DISEASE IN CHILDREN WITH NEUROFIBROMATOSIS, TYPE 1: EPIDEMIOLOGY AND MOLECULAR ANALYSIS. LOSS OF CONSTITUTIONAL HETEROZYGOSITY IS A COMMON MOLECULAR FEATURE OF CANCERS IN WHICH INACTIVATION OF ONE OR MORE TUMOR SUPPRESSOR GENES IS THOUGHT TO CONTRIBUTE TO TUMORIGENESIS. RECENT EVIDENCE SUGGESTS THAT THE GENE RESPONSIBLE FOR NEUROFIBROMATOSIS, TYPE 1 (NF-1), BELONGS TO THIS CLASS OF HERITABLE CANCER GENES. CHILDREN WITH NF-1 SHOW AN INCREASED INCIDENCE OF MYELOID LEUKEMIA, INCLUDING JUVENILE CHRONIC MYELOGENOUS LEUKEMIA (JCML) AND, PERHAPS, THE MYELOPROLIFERATIVE SYNDROME (MPS) ASSOCIATED WITH BONE MARROW MONOSOMY 7 (MO 7). WE HAVE INVESTIGATED FIVE CHILDREN WITH MO 7: THREE WITH NF-1 AND TWO OTHERS WITH SUGGESTIVE EVIDENCE OF NF-1. SOUTHERN BLOTTING EXPERIMENTS PERFORMED IN FOUR PATIENTS SHOWED NO LOSS OF HETEROZYGOSITY IN BONE MARROW SPECIMENS USING PROBES LINKED TO THE NF-1 LOCUS ON THE LONG ARM OF CHROMOSOME 17. BOTH OF OUR PATIENTS WITH FAMILIAL NF-1 INHERITED THE DISEASE FROM THEIR MOTHERS, AS DID 14 OF 19 OTHER CASES OF MYELOID LEUKEMIA IN CHILDREN WITH FAMILIAL NF-1. SEVENTEEN OF THESE 21 CHILDREN WERE BOYS. MYELOID LEUKEMIA DEVELOPED IN 12 BOYS AND FOUR GIRLS WHO INHERITED NF-1 FROM THEIR MOTHERS, AND IN FIVE BOYS WHO INHERITED THE DISEASE FROM THEIR FATHERS. FATHER-TO-DAUGHTER TRANSMISSION WAS NOT OBSERVED. TAKEN TOGETHER, THE PRESENCE OF CHROMOSOME 7 DELETIONS IN THE LEUKEMIAS OF CHILDREN WITH NF-1, A PATTERN OF INHERITANCE FAVORING MATERNAL TRANSMISSION OF NF-1, AND THE MARKED PREDILECTION FOR BOYS TO DEVELOP JCML AND MO 7 SUGGEST A MULTISTEP MECHANISM OF ONCOGENESIS IN WHICH EPIGENETIC FACTORS MIGHT PLAY A ROLE. FURTHER INVESTIGATION IS REQUIRED TO DETERMINE IF THE NF-1 GENES IN THE LEUKEMIC BONE MARROWS OF THESE PATIENTS HAVE ACQUIRED POINT MUTATIONS OR SMALL DELETIONS. 1992 12 1037 22 CLASSIFICATION AND DIAGNOSIS OF TEMPOROMANDIBULAR DISORDERS AND TEMPOROMANDIBULAR DISORDER PAIN. DESIGNING CLASSIFICATION SYSTEMS AND DEVELOPING DIAGNOSTIC CRITERIA FOR TEMPOROMANDIBULAR DISORDERS IS DIFFICULT. AN APPRECIATION OF THE UTILITY AND APPLICABILITY OF THESE ENTITIES REQUIRES AN UNDERSTANDING OF THE IMPORTANCE OF EACH, THE DIFFERENCES BETWEEN THE TWO, AND HOW THEY MAY BE OPTIMALLY OPERATIONALIZED FOR BOTH CLINICAL AND RESEARCH ACTIVITIES IN LIGHT OF THEIR INHERENT ADVANTAGES AND LIMITATIONS. IN ADDITION, CONSIDERATION FOR ADOPTING NEWER APPROACHES, SUCH AS FOLLOWING ONTOLOGICAL AND PRECISION-BASED MEDICINE PRINCIPLES, ACCOUNTING FOR GENETICS/EPIGENETIC AND NEUROBIOLOGICAL FACTORS, AND THE INCLUSION OF BIOMARKERS WILL POTENTIALLY RESULT IN MORE THOROUGH AND COMPREHENSIVE CLASSIFICATION SYSTEMS AND DIAGNOSTIC CRITERIA. 2023 13 734 42 CANCER HEALTHCARE DISPARITIES AMONG AFRICAN AMERICANS IN THE UNITED STATES. A NEED EXISTS TO EXAMINE RACIAL DISPARITIES IN THE HEALTHCARE ARENA AND THE IMPACT ON PATIENTS WITH CANCER. DESPITE ONGOING EFFORTS TO INCREASE EQUITY IN PRIMARY HEALTHCARE ACCESS, RACIAL AND SOCIOECONOMIC DISPARITIES PERSIST, THUS CONTRIBUTING TO DISPROPORTIONATE TREATMENT OUTCOMES AND SURVIVORSHIP AMONG MINORITY AND LOW-INCOME PATIENTS. SUCH DISPARITIES HAVE BEEN REVEALED IN TREATMENT COHORTS OF PATIENTS WITH MULTIPLE FORMS OF CANCER, INCLUDING BREAST, CERVICAL, OVARIAN, ENDOMETRIAL, PROSTATE, LUNG, COLORECTAL, GASTROINTESTINAL, AND HEPATOCELLULAR, AND HAVE BEEN ATTRIBUTED TO A RANGE OF CO-OCCURRING BEHAVIORAL, SOCIAL DETERMINANTS OF HEALTH, UNDERLYING GENETIC FACTORS, AS WELL AS ACCESS TO EDUCATIONAL OPPORTUNITIES THAT LIMIT THE QUALITY OF INFORMED HEALTHCARE. THESE VARIOUS INTERRELATED FACTORS WIDEN CANCER HEALTHCARE DISPARITIES SYNERGISTICALLY THROUGHOUT UNDERSERVED COMMUNITIES, AND THEIR INFLUENCE HAS BEEN AMPLIFIED BY THE CORONAVIRUS DISEASE 2019 (COVID-19) PANDEMIC. FUNDAMENTALLY, A LACK OF BASIC AND CLINICAL RESEARCH EXISTS THAT FAILS TO ADEQUATELY REFLECT DIVERSITY AND MINORITY INVOLVEMENT IN DRUG DEVELOPMENT. ALTHOUGH OVERCOMING THE OBSTACLES RESPONSIBLE FOR CHRONIC TREATMENT DISPARITIES IS A FORMIDABLE TASK, PROMISING MEANS OF ACHIEVING MORE UNIFORM QUALITY HEALTHCARE ARE BECOMING MORE CLEARLY ELUCIDATED. TO REDUCE DISEASE PROGRESSION, INCREASE OVERALL SURVIVAL, AND IMPROVE THE HEALTH OF VULNERABLE POPULATIONS, IT IS NECESSARY TO IDENTIFY AND FULLY DISCLOSE ENVIRONMENTAL, BIOLOGICAL, AND ANCESTRAL FACTORS THAT IMPACT THE RISK FOR CANCER; HEAL HISTORICAL FRACTURES WITHIN COMMUNITIES; AND INCREASE PARTICIPATION OF RACIAL AND ETHNIC MINORITIES IN SCREENING EFFORTS AND RESEARCH STUDIES. THIS REQUIRES DEVELOPING A SYSTEM OF JUSTICE AND TRUST BASED ON SPECIFIC, SOLUTION-ORIENTED GRASSROOTS COMMUNITY EFFORTS WORKING IN TANDEM WITH MEDICAL AND PHARMACEUTICAL LEADERS. BY FULLY EXPLORING AND PINPOINTING THE UNDERLYING CAUSES OF HEALTHCARE DISPARITIES, IT SHOULD BE POSSIBLE TO DEFINE STRATEGIES AND INTERVENTIONS MOST LIKELY TO TRANSFORM CANCER CARE. THE ULTIMATE GOAL IS UNDERSTANDING INDIVIDUAL, CULTURAL, AND BIOLOGICAL VULNERABILITIES, INCLUDING ENVIRONMENTAL AND EPIGENETIC LIABILITIES, TO OPTIMIZE CANCER PREVENTION, DIAGNOSIS, AND TREATMENT. 2022 14 29 36 A BIOPSYCHOSOCIAL OVERVIEW OF THE OPIOID CRISIS: CONSIDERING NUTRITION AND GASTROINTESTINAL HEALTH. THE OPIOID CRISIS HAS REACHED EPIDEMIC PROPORTIONS IN THE UNITED STATES WITH RISING OVERDOSE DEATH RATES. IDENTIFYING THE UNDERLYING FACTORS THAT CONTRIBUTE TO ADDICTION VULNERABILITY MAY LEAD TO MORE EFFECTIVE PREVENTION STRATEGIES. SUPPLY SIDE ENVIRONMENTAL FACTORS ARE A MAJOR CONTRIBUTING COMPONENT. PSYCHOSOCIAL FACTORS SUCH AS STRESS, TRAUMA, AND ADVERSE CHILDHOOD EXPERIENCES HAVE BEEN LINKED TO EMOTIONAL PAIN LEADING TO SELF-MEDICATION. GENETIC AND EPIGENETIC FACTORS ASSOCIATED WITH BRAIN REWARD PATHWAYS AND IMPULSIVITY ARE KNOWN PREDICTORS OF ADDICTION VULNERABILITY. THIS REVIEW ATTEMPTS TO PRESENT A BIOPSYCHOSOCIAL APPROACH THAT CONNECTS VARIOUS SOCIAL AND BIOLOGICAL THEORIES RELATED TO THE ADDICTION CRISIS. THE EMERGING ROLE OF NUTRITION THERAPY WITH AN EMPHASIS ON GASTROINTESTINAL HEALTH IN THE TREATMENT OF OPIOID USE DISORDER IS PRESENTED. THE BIOPSYCHOSOCIAL MODEL INTEGRATES CONCEPTS FROM SEVERAL DISCIPLINES, EMPHASIZING MULTICAUSALITY RATHER THAN A REDUCTIONIST APPROACH. POTENTIAL SOLUTIONS AT MULTIPLE LEVELS ARE PRESENTED, CONSIDERING INDIVIDUAL AS WELL AS POPULATION HEALTH. THIS SINGLE COHESIVE FRAMEWORK IS BASED ON THE INTERDEPENDENCY OF THE ENTIRE SYSTEM, IDENTIFYING RISK AND PROTECTIVE FACTORS THAT MAY INFLUENCE SUBSTANCE-SEEKING BEHAVIOR. NUTRITION SHOULD BE INCLUDED AS ONE FACET OF A MULTIDISCIPLINARY APPROACH TOWARD IMPROVED RECOVERY OUTCOMES. CROSS-DISCIPLINARY COLLABORATIVE EFFORTS, NEW IDEAS, AND FISCAL RESOURCES WILL BE CRITICAL TO ADDRESS THE EPIDEMIC. 2019 15 1352 42 DEVELOPMENT AND APPLICATION OF THE ADVERSE OUTCOME PATHWAY FRAMEWORK FOR UNDERSTANDING AND PREDICTING CHRONIC TOXICITY: I. CHALLENGES AND RESEARCH NEEDS IN ECOTOXICOLOGY. TO ELUCIDATE THE EFFECTS OF CHEMICALS ON POPULATIONS OF DIFFERENT SPECIES IN THE ENVIRONMENT, EFFICIENT TESTING AND MODELING APPROACHES ARE NEEDED THAT CONSIDER MULTIPLE STRESSORS AND ALLOW RELIABLE EXTRAPOLATION OF RESPONSES ACROSS SPECIES. AN ADVERSE OUTCOME PATHWAY (AOP) IS A CONCEPT THAT PROVIDES A FRAMEWORK FOR ORGANIZING KNOWLEDGE ABOUT THE PROGRESSION OF TOXICITY EVENTS ACROSS SCALES OF BIOLOGICAL ORGANIZATION THAT LEAD TO ADVERSE OUTCOMES RELEVANT FOR RISK ASSESSMENT. IN THIS PAPER, WE FOCUS ON EXPLORING HOW THE AOP CONCEPT CAN BE USED TO GUIDE RESEARCH AIMED AT IMPROVING BOTH OUR UNDERSTANDING OF CHRONIC TOXICITY, INCLUDING DELAYED TOXICITY AS WELL AS EPIGENETIC AND TRANSGENERATIONAL EFFECTS OF CHEMICALS, AND OUR ABILITY TO PREDICT ADVERSE OUTCOMES. A BETTER UNDERSTANDING OF THE INFLUENCE OF SUBTLE TOXICITY ON INDIVIDUAL AND POPULATION FITNESS WOULD SUPPORT A BROADER INTEGRATION OF SUBLETHAL ENDPOINTS INTO RISK ASSESSMENT FRAMEWORKS. DETAILED MECHANISTIC KNOWLEDGE WOULD FACILITATE THE DEVELOPMENT OF ALTERNATIVE TESTING METHODS AS WELL AS HELP PRIORITIZE HIGHER TIER TOXICITY TESTING. WE ARGUE THAT TARGETED DEVELOPMENT OF AOPS SUPPORTS BOTH OF THESE ASPECTS BY PROMOTING THE ELUCIDATION OF MOLECULAR MECHANISMS AND THEIR CONTRIBUTION TO RELEVANT TOXICITY OUTCOMES ACROSS BIOLOGICAL SCALES. WE FURTHER DISCUSS INFORMATION REQUIREMENTS AND CHALLENGES IN APPLICATION OF AOPS FOR CHEMICAL- AND SITE-SPECIFIC RISK ASSESSMENT AND FOR EXTRAPOLATION ACROSS SPECIES. WE PROVIDE RECOMMENDATIONS FOR POTENTIAL EXTENSION OF THE AOP FRAMEWORK TO INCORPORATE INFORMATION ON EXPOSURE, TOXICOKINETICS AND SITUATION-SPECIFIC ECOLOGICAL CONTEXTS, AND DISCUSS COMMON INTERFACES THAT CAN BE EMPLOYED TO COUPLE AOPS WITH COMPUTATIONAL MODELING APPROACHES AND WITH EVOLUTIONARY LIFE HISTORY THEORY. THE EXTENDED AOP FRAMEWORK CAN SERVE AS A VENUE FOR INTEGRATION OF KNOWLEDGE DERIVED FROM VARIOUS SOURCES, INCLUDING EMPIRICAL DATA AS WELL AS MOLECULAR, QUANTITATIVE AND EVOLUTIONARY-BASED MODELS DESCRIBING SPECIES RESPONSES TO TOXICANTS. THIS WILL ALLOW A MORE EFFICIENT APPLICATION OF AOP KNOWLEDGE FOR QUANTITATIVE CHEMICAL- AND SITE-SPECIFIC RISK ASSESSMENT AS WELL AS FOR EXTRAPOLATION ACROSS SPECIES IN THE FUTURE. 2015 16 357 44 ALTERNATIVE MODELS FOR TRANSGENERATIONAL EPIGENETIC INHERITANCE: MOLECULAR PSYCHIATRY BEYOND MICE AND MAN. MENTAL ILLNESS REMAINS THE GREATEST CHRONIC HEALTH BURDEN GLOBALLY WITH FEW IN-ROADS HAVING BEEN MADE DESPITE SIGNIFICANT ADVANCES IN GENOMIC KNOWLEDGE IN RECENT DECADES. THE FIELD OF PSYCHIATRY IS CONSTANTLY CHALLENGED TO BRING NEW APPROACHES AND TOOLS TO ADDRESS AND TREAT THE NEEDS OF VULNERABLE INDIVIDUALS AND SUBPOPULATIONS, AND THAT HAS TO BE SUPPORTED BY A CONTINUOUS GROWTH IN KNOWLEDGE. THE MAJORITY OF NEUROPSYCHIATRIC SYMPTOMS REFLECT COMPLEX GENE-ENVIRONMENT INTERACTIONS, WITH EPIGENETICS BRIDGING THE GAP BETWEEN GENETIC SUSCEPTIBILITY AND ENVIRONMENTAL STRESSORS THAT TRIGGER DISEASE ONSET AND DRIVE THE ADVANCEMENT OF SYMPTOMS. IT HAS MORE RECENTLY BEEN DEMONSTRATED IN PRECLINICAL MODELS THAT EPIGENETICS UNDERPINS THE TRANSGENERATIONAL INHERITANCE OF STRESS-RELATED BEHAVIOURAL PHENOTYPES IN BOTH PATERNAL AND MATERNAL LINEAGES, PROVIDING FURTHER SUPPORTING EVIDENCE FOR HERITABILITY IN HUMANS. HOWEVER, UNBIASED PROSPECTIVE STUDIES OF THIS NATURE ARE PRACTICALLY IMPOSSIBLE TO CONDUCT IN HUMANS SO PRECLINICAL MODELS REMAIN OUR BEST OPTION FOR RESEARCHING THE MOLECULAR PATHOPHYSIOLOGIES UNDERLYING MANY NEUROPSYCHIATRIC CONDITIONS. WHILE RODENTS WILL REMAIN THE DOMINANT MODEL SYSTEM FOR PRECLINICAL STUDIES (ESPECIALLY FOR ADDRESSING COMPLEX BEHAVIOURAL PHENOTYPES), THERE IS SCOPE TO EXPAND CURRENT RESEARCH OF THE MOLECULAR AND EPIGENETIC PATHOLOGIES BY USING INVERTEBRATE MODELS. HERE, WE WILL DISCUSS THE UTILITY AND ADVANTAGES OF TWO ALTERNATIVE MODEL ORGANISMS-CAENORHABDITIS ELEGANS AND DROSOPHILA MELANOGASTER-AND SUMMARISE THE COMPELLING INSIGHTS OF THE EPIGENETIC REGULATION OF TRANSGENERATIONAL INHERITANCE THAT ARE POTENTIALLY RELEVANT TO HUMAN PSYCHIATRY. 2021 17 380 41 AN EPIGENETIC PERSPECTIVE ON LIFESTYLE MEDICINE FOR DEPRESSION: IMPLICATIONS FOR PRIMARY CARE PRACTICE. DEPRESSION IS THE MOST COMMON PRESENTING MENTAL HEALTH DISORDER IN PRIMARY CARE. IT IS ALSO A MAJOR CONTRIBUTOR TO SOMATIC COMPLAINTS, WORSENING OF CHRONIC MEDICAL CONDITIONS, POOR QUALITY OF LIFE, AND SUICIDE. CURRENT PHARMACOLOGIC AND PSYCHOTHERAPEUTIC APPROACHES AVERT LESS THAN HALF OF DEPRESSION'S CUMULATIVE BURDEN ON SOCIETY. HOWEVER, THERE IS A GROWING BODY OF RESEARCH DESCRIBING BOTH HOW MALADAPTIVE LIFESTYLE CHOICES CONTRIBUTE TO THE DEVELOPMENT AND WORSENING OF DEPRESSION AND HOW LIFESTYLE-ORIENTED MEDICAL INTERVENTIONS CAN REDUCE THE INCIDENCE AND SEVERITY OF DEPRESSION. THIS RESEARCH, LARGELY DERIVED FROM AN EMERGING FIELD CALLED EPIGENETICS, ELUCIDATES THE INTERACTIONS BETWEEN OUR LIFESTYLE CHOICES AND THOSE EPIGENETIC FACTORS WHICH MEDIATE OUR TENDENCIES TOWARD EITHER HEALTH, OR THE ONSET, IF NOT WORSENING OF DISEASE. THE PRESENT REVIEW HIGHLIGHTS HOW LIFESTYLE CHOICES INVOLVING DIET, PHYSICAL ACTIVITY, SLEEP, SOCIAL RELATIONSHIPS, AND STRESS INFLUENCE EPIGENETIC PROCESSES POSITIVELY OR NEGATIVELY, AND THEREBY PLAY A SIGNIFICANT ROLE IN DETERMINING WHETHER ONE DOES OR DOES NOT SUFFER FROM DEPRESSION. THE AUTHORS PROPOSE THAT MEDICAL TRAINING PROGRAMS CONSIDER AND ADOPT LIFESTYLE MEDICINE ORIENTED INSTRUCTIONAL INITIATIVES THAT WILL ENABLE TOMORROW'S PRIMARY CARE PROVIDERS TO MORE EFFECTIVELY IDENTIFY AND THERAPEUTICALLY INTERVENE IN THE MALADAPTIVE CHOICES CONTRIBUTING TO THEIR PATIENTS' DEPRESSION. 2022 18 103 39 A REHABILOMICS FRAMEWORK FOR PERSONALIZED AND TRANSLATIONAL REHABILITATION RESEARCH AND CARE FOR INDIVIDUALS WITH DISABILITIES: PERSPECTIVES AND CONSIDERATIONS FOR SPINAL CORD INJURY. DESPITE MANY PEOPLE HAVING SIMILAR CLINICAL PRESENTATION, DEMOGRAPHIC FACTORS, AND CLINICAL CARE, OUTCOME CAN DIFFER FOR THOSE SUSTAINING SIGNIFICANT INJURY SUCH AS SPINAL CORD INJURY (SCI) AND TRAUMATIC BRAIN INJURY (TBI). IN ADDITION TO TRADITIONAL DEMOGRAPHIC, SOCIAL, AND CLINICAL FACTORS, VARIABILITY ALSO MAY BE ATTRIBUTABLE TO INNATE (INCLUDING GENETIC, TRANSCRIPTOMIC PROTEOMIC, EPIGENETIC) BIOLOGICAL VARIATION THAT INDIVIDUALS BRING TO RECOVERY AND THEIR UNIQUE RESPONSE TO THEIR CARE AND ENVIRONMENT. TECHNOLOGIES COLLECTIVELY CALLED "-OMICS" ENABLE SIMULTANEOUS MEASUREMENT OF AN ENORMOUS NUMBER OF BIOMOLECULES THAT CAN CAPTURE MANY POTENTIAL BIOLOGICAL CONTRIBUTORS TO HETEROGENEITY OF INJURY/DISEASE COURSE AND OUTCOME. DUE TO THE NATURE OF INJURY AND COMPLEX DISEASE, AND ITS ASSOCIATIONS WITH IMPAIRMENT, DISABILITY, AND RECOVERY, REHABILITATION DOES NOT LEND ITSELF TO A SINGULAR "PROTOCOLIZED" PLAN OF THERAPY. YET, BY NATURE AND BY NECESSITY, REHABILITATION MEDICINE OPERATES AS A FUNCTIONAL MODEL OF "PERSONALIZED CARE". THUS, THE CHALLENGE FOR SUCCESSFUL PROGRAMS OF TRANSLATIONAL REHABILITATION CARE AND RESEARCH IS TO IDENTIFY VIABLE APPROACHES TO EXAMINE BROAD POPULATIONS, WITH VARIED IMPAIRMENTS AND FUNCTIONAL LIMITATIONS, AND TO IDENTIFY EFFECTIVE TREATMENT RESPONSES THAT INCORPORATE PERSONALIZED PROTOCOLS TO OPTIMIZE FUNCTIONAL RECOVERY. THE REHABILOMICS FRAMEWORK IS A TRANSLATIONAL MODEL THAT PROVIDES AN "-OMICS" OVERLAY TO THE SCIENTIFIC STUDY OF REHABILITATION PROCESSES AND MULTIDIMENSIONAL OUTCOMES. REHABILOMICS RESEARCH PROVIDES NOVEL OPPORTUNITIES TO EVALUATE THE NEUROBIOLOGY OF COMPLEX INJURY OR CHRONIC DISEASE AND CAN BE USED TO EXAMINE METHODS AND TREATMENTS FOR PERSON-CENTERED CARE AMONG POPULATIONS WITH DISABILITIES. EXEMPLARS FOR APPLICATION IN SCI AND OTHER NEUROREHABILITATION POPULATIONS ARE DISCUSSED. 2014 19 5025 39 PERSONALIZED MANAGEMENT OF CARDIOVASCULAR DISORDERS. PERSONALIZED MANAGEMENT OF CARDIOVASCULAR DISORDERS (CVD), ALSO REFERRED TO AS PERSONALIZED OR PRECISION CARDIOLOGY IN ACCORDANCE WITH GENERAL PRINCIPLES OF PERSONALIZED MEDICINE, IS SELECTION OF THE BEST TREATMENT FOR AN INDIVIDUAL PATIENT. IT INVOLVES THE INTEGRATION OF VARIOUS "OMICS" TECHNOLOGIES SUCH AS GENOMICS AND PROTEOMICS AS WELL AS OTHER NEW TECHNOLOGIES SUCH AS NANOBIOTECHNOLOGY. MOLECULAR DIAGNOSTICS AND BIOMARKERS ARE IMPORTANT FOR LINKING DIAGNOSIS WITH THERAPY AND MONITORING THERAPY. BECAUSE CVD INVOLVE PERTURBATIONS OF LARGE COMPLEX BIOLOGICAL NETWORKS, A SYSTEMS BIOLOGY APPROACH TO CVD RISK STRATIFICATION MAY BE USED FOR IMPROVING RISK-ESTIMATING ALGORITHMS, AND MODELING OF PERSONALIZED BENEFIT OF TREATMENT MAY BE HELPFUL FOR GUIDING THE CHOICE OF INTERVENTION. BIOINFORMATICS TOOLS ARE HELPFUL IN ANALYZING AND INTEGRATING LARGE AMOUNTS OF DATA FROM VARIOUS SOURCES. PERSONALIZED THERAPY IS CONSIDERED DURING DRUG DEVELOPMENT, INCLUDING METHODS OF TARGETED DRUG DELIVERY AND CLINICAL TRIALS. INDIVIDUALIZED RECOMMENDATIONS CONSIDER MULTIPLE FACTORS - GENETIC AS WELL AS EPIGENETIC - FOR PATIENTS' RISK OF HEART DISEASE. EXAMPLES OF PERSONALIZED TREATMENT ARE THOSE OF CHRONIC MYOCARDIAL ISCHEMIA, HEART FAILURE, AND HYPERTENSION. SIMILAR APPROACHES CAN BE USED FOR THE MANAGEMENT OF ATRIAL FIBRILLATION AND HYPERCHOLESTEROLEMIA, AS WELL AS THE USE OF ANTICOAGULANTS. PERSONALIZED MANAGEMENT INCLUDES PHARMACOTHERAPY, SURGERY, LIFESTYLE MODIFICATIONS, AND COMBINATIONS THEREOF. FURTHER PROGRESS IN UNDERSTANDING THE PATHOMECHANISM OF COMPLEX CARDIOVASCULAR DISEASES AND IDENTIFICATION OF CAUSATIVE FACTORS AT THE INDIVIDUAL PATIENT LEVEL WILL PROVIDE OPPORTUNITIES FOR THE DEVELOPMENT OF PERSONALIZED CARDIOLOGY. APPLICATION OF PRINCIPLES OF PERSONALIZED MEDICINE WILL IMPROVE THE CARE OF THE PATIENTS WITH CVD. 2017 20 1403 32 DIETARY APPROACHES TO WOMEN'S SEXUAL AND REPRODUCTIVE HEALTH. OVER THE COURSE OF THE REPRODUCTIVE LIFE SPAN, IT IS COMMON FOR WOMEN TO EXPERIENCE ONE OR MORE OF THE MOST COMMON GYNECOLOGIC CONDITIONS, INCLUDING SEXUAL DYSFUNCTION, POLYCYSTIC OVARY SYNDROME, FIBROIDS, ENDOMETRIOSIS, AND INFERTILITY. ALTHOUGH CURRENT MANAGEMENT GUIDELINES OFTEN TURN TO THE ESTABLISHED PHARMACEUTICAL APPROACHES FOR EACH OF THESE DIAGNOSES, THE SCIENTIFIC LITERATURE ALSO SUPPORTS AN EVIDENCE-BASED APPROACH ROOTED IN THE PARADIGM OF FOOD AS MEDICINE. ACHIEVING HEALTHY DIETARY PATTERNS IS A CORE GOAL OF LIFESTYLE MEDICINE, AND A PLANT-FORWARD APPROACH AKIN TO THE MEDITERRANEAN DIET HOLDS GREAT PROMISE FOR IMPROVING MANY CHRONIC GYNECOLOGIC DISEASES. FURTHERMORE, CREATING AN OPTIMAL PRECONCEPTION ENVIRONMENT FROM A NUTRITIONAL STANDPOINT MAY FACILITATE EPIGENETIC SIGNALING, THUS IMPROVING THE HEALTH OF FUTURE GENERATIONS. THIS STATE-OF-THE-ART REVIEW EXPLORES THE LITERATURE CONNECTING DIET WITH SEXUAL AND REPRODUCTIVE HEALTH IN PREMENOPAUSAL WOMEN. 2021