1 4523 443 MULTIDISCIPLINARY APPROACH TO PROSTATITIS. THE MODERN CLINICAL RESEARCH ON PROSTATITIS STARTED WITH THE WORK OF STAMEY AND COWORKERS WHO DEVELOPED THE BASIC PRINCIPLES WE ARE STILL USING. THEY ESTABLISHED THE SEGMENTED CULTURE TECHNIQUE FOR LOCALIZING THE INFECTIONS IN THE MALES TO THE URETHRA, THE BLADDER, OR THE PROSTATE AND TO DIFFERENTIATE THE MAIN CATEGORIES OF PROSTATITIS. SUCH CATEGORIES WITH SLIGHT MODIFICATIONS ARE STILL USED ACCORDING TO THE NIH CLASSIFICATION: ACUTE BACTERIAL PROSTATITIS, CHRONIC BACTERIAL PROSTATITIS, CHRONIC PELVIC PAIN SYNDROME (CPPS) AND ASYMPTOMATIC PROSTATITIS. PROSTATIC INFLAMMATION IS CONSIDERED AN IMPORTANT FACTOR IN INFLUENCING BOTH PROSTATIC GROWTH AND PROGRESSION OF SYMPTOMS OF BENIGN PROSTATIC HYPERPLASIA AND PROSTATITIS. CHRONIC INFLAMMATION/NEUROINFLAMMATION IS A RESULT OF A DEREGULATED ACUTE PHASE RESPONSE OF THE INNATE IMMUNE SYSTEM AFFECTING SURROUNDING NEURAL TISSUE AT MOLECULAR, STRUCTURAL AND FUNCTIONAL LEVELS. CLINICAL OBSERVATIONS SUGGEST THAT CHRONIC INFLAMMATION CORRELATES WITH CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME (CP/CPPS) AND BENIGN PROSTATIC HYPERPLASIA (BPH) AND AN HISTORY OF CLINICAL CHRONIC PROSTATITIS SIGNIFICANTLY INCREASES THE ODDS FOR PROSTATE CANCER. THE NIHNIDDK CLASSIFICATION BASED ON THE USE OF THE MICROBIOLOGICAL 4- GLASSES LOCALIZATION TEST OR SIMPLIFIED 2-GLASSES TEST, IS CURRENTLY ACCEPTED WORLDWIDE. THE UPOINT SYSTEM IDENTIFIES GROUPS OF CLINICIANS WITH HOMOGENEOUS CLINICAL PRESENTATION AND IS USED TO RECOGNIZE PHENOTYPES TO BE SUBMITTED TO SPECIFIC TREATMENTS. THE UPOINTS ALGORITHM IMPLEMENTED THE ORIGINAL UPOINT ADDING TO THE URINARY DOMAINS (U), PSYCHO-SOCIAL (P), ORGANSPECIFIC (O), INFECTION (I), NEUROLOGICAL (N), MUSCLE TENSION AND TENDERNESS (T) A FURTHER DOMAIN RELATED TO SEXUALITY (S). IN FACT SEXUAL DYSFUNCTION (ERECTILE, EJACULATORY, LIBIDO LOSS) HAS BEEN DESCRIBED IN 46-92% OF CASES WITH A HIGH IMPACT ON THE QUALITY OF LIFE OF PATIENTS WITH CP/CPPS. PROSTATIC ULTRASOUND REPRESENTS THE MOST POPULAR IMAGING TEST IN THE WORK-UP OF EITHER ACUTE AND CHRONIC PROSTATITIS ALTHOUGH NO SPECIFIC HYPO-HYPERECHOIC PATTERN HAS BEEN CLEARLY ASSOCIATED WITH CHRONIC BACTERIAL PROSTATITIS AND CPPS. USE OF A DIGITAL-PROCESSING SOFTWARE TO CALCULATE THE EXTENSION OF PROSTATIC CALCIFICATION AREA AT ULTRASOUND DEMONSTRATED A HIGHER PERCENTAGE OF PROSTATIC CALCIFICATION IN PATIENTS WITH CHRONIC BACTERIAL PROSTATITIS. MULTIPARAMETRIC MAGNETIC RESONANCE IMAGING (MPMRI) IS THE CURRENT STATE-OF-THE ART IMAGING MODALITY IN THE ASSESSMENT OF PATIENTS WITH PROSTATE CANCER ALTHOUGH A VARIETY OF BENIGN CONDITIONS, INCLUDING INFLAMMATION, MAY MIMIC PROSTATE CANCER AND ACT AS CONFOUNDING FACTORS IN THE DISCRIMINATION BETWEEN NEOPLASTIC AND NON-NEOPLASTIC LESIONS. BACTERIA CAN INFECT PROSTATE GLAND BY: ASCENDING THE URETHRA, REFLUX OF URINE INTO THE PROSTATIC DUCTS, DIRECT INOCULATION OF BACTERIA THROUGH INSERTED BIOPSY NEEDLES OR HEMATOGENOUS SEEDING. ENTEROBACTERIACEAE ARE THE PREDOMINANT PATHOGENS IN ACUTE AND CHRONIC BACTERIAL PROSTATITIS, BUT AN INCREASING ROLE OF ENTEROCOCCI HAS BEEN REPORTED. MANY STRAINS OF THESE UROPATHOGENS EXHIBIT THE ABILITY TO FORM BIOFILM AND MULTIDRUG- RESISTANCE. SEXUALLY TRANSMITTED INFECTIONS (STI) AGENTS, IN PARTICULAR CHLAMYDIA TRACHOMATIS AND MYCOPLASMA GENITALIUM, HAVE BEEN ALSO CONSIDERED AS CAUSATIVE PATHOGENS OF CHRONIC BACTERIAL PROSTATITIS. ON THE CONTRARY THE EFFECTIVE ROLE IN GENITAL DISEASES OF OTHER "GENITAL MYCOPLASMAS" IS STILL A MUCH DEBATED ISSUE. SEXUALLY TRANSMITTED INFECTIONS AGENTS SHOULD BE INVESTIGATED BY MOLECULAR METHODS IN BOTH PATIENT AND SEXUAL PARTNER. "NEXT GENERATION" INVESTIGATIONS, SUCH AS CYTOKINE ANALYSIS, CYTOLOGICAL TYPING OF IMMUNE CELLS COULD HELP STRATIFYING THE IMMUNE RESPONSE. EPIGENETIC DYSREGULATION OF INFLAMMATORY FACTORS SHOULD BE INVESTIGATED ACCORDING TO SYSTEMIC AND COMPARTMENT-SPECIFIC SIGNALS. THE SEARCH FOR BIOMARKERS SHOULD ALSO INCLUDE EVALUATION OF HORMONAL PATHWAYS, AS MEASUREMENT OF ESTROGEN LEVELS IN SEMEN. ANTIMICROBIALS ARE THE FIRST LINE AGENTS FOR THE TREATMENT OF BACTERIAL PROSTATITIS. THE SUCCESS OF ANTIMICROBIAL TREATMENT DEPENDS ON THE ANTIBACTERIAL ACTIVITY AND THE PHARMACOKINETIC CHARACTERISTICS OF THE DRUG WHICH MUST REACH HIGH CONCENTRATIONS IN PROSTATE SECRETION AND PROSTATE TISSUE. ACUTE BACTERIAL PROSTATITIS CAN BE A SERIOUS INFECTION WITH A POTENTIAL RISK FOR UROSEPSIS FOR IINITIAL TREATMENT OF SEVERELY ILL PATIENTS, INTRAVENOUS ADMINISTRATION OF HIGH DOSES OF BACTERICIDAL ANTIMICROBIALS, SUCH AS BROAD-SPECTRUM PENICILLINS, THIRD-GENERATION CEPHALOSPORINS OR FLUOROQUINOLONES, IS RECOMMENDED IN COMBINATION WITH AN AMINOGLYCOSIDE. USE OF PIPERACILLIN-TAZOBACTAM AND MEROPENEM IS JUSTIFIED IN PRESENCE OF MULTIRESISTANT GRAMNEGATIVE PATHOGENS. THE ANTIBIOTIC TREATMENT OF CHRONIC PROSTATITIS IS CURRENTLY BASED ON THE USE OF FLUOROQUINOLONES THAT, GIVEN FOR 2 TO 4 WEEKS, CURED ABOUT 70% OF MEN WITH CHRONIC BACTERIAL PROSTATITIS. FOR THE TREATMENT OF CHLAMYDIAL PROSTATITIS MACROLIDES WERE SHOWN TO BE MORE EFFECTIVE THAN FLUOROQUINOLONES, WHEREAS NO DIFFERENCES WERE OBSERVED IN MICROBIOLOGICAL AND CLINICAL EFFICACY BETWEEN MACROLIDES AND TETRACYCLINES FOR THE TREATMENT OF INFECTIONS CAUSED BY INTRACELLULAR PATHOGENS. AMINOGLYCOSIDES AND FOSFOMYCIN COULD BE CONSIDERED AS A THERAPEUTIC ALTERNATIVE FOR THE TREATMENT OF QUINOLONE RESISTANT PROSTATITIS. USE OF ALPHA-BLOCKERS IN CP/CPPS PATIENTS WITH URINARY SYMPTOMS AND ANALGESICS +/- NON STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAID), IN PRESENCE OF PAIN DEMONSTRATED A REDUCTION OF SYMPTOMS REDUCTION AND AN IMPROVEMENT OF QUALITY OF LIFE, ALTHOUGH LONG TERM USE OF NSAID IS LIMITED BY SIDE EFFECT PROFILE. HOWEVER, THE MULTIMODAL THERAPEUTIC REGIMEN BY CONTEMPORARY USE OF ALPHABLOCKERS, ANTIBIOTICS AND ANTI-INFLAMMATORY SHOWED A BETTER CONTROL OF PROSTATITIS SYMPTOMS THAN SINGLE DRUG TREATMENT. NOVEL THERAPEUTIC SUBSTANCES FOR THE TREATMENT OF PAIN, SUCH AS THE CANNABINOID ANANDAMIDE WOULD BE HIGHLY INTERESTING TO TEST. AN ALTERNATIVE FOR THE TREATMENT OF CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME IS PHYTOTHERAPY, AS PRIMARY THERAPY OR IN ASSOCIATION WITH OTHER DRUGS. QUERCETIN, POLLEN EXTRACT, EXTRACT OF SERENOA REPENS AND OTHER MIXTURES OF HERBAL EXTRACTS SHOWED A POSITIVE EFFECT ON SYMPTOMS AND QUALITY OF LIFE WITHOUT SIDE EFFECTS. THE ASSOCIATION OF CP/CPPS WITH ALTERATIONS OF INTESTINAL FUNCTION HAS BEEN DESCRIBED. DIET HAS ITS EFFECTS ON INFLAMMATION BY REGULATION OF THE COMPOSITION OF INTESTINAL FLORA AND DIRECT ACTION ON THE INTESTINAL CELLS (STERILE INFLAMMATION). INTESTINAL BACTERIA (MICROBIOTA) INTERACTS WITH FOOD INFLUENCING THE METABOLIC, IMMUNE AND INFLAMMATORY RESPONSE OF THE ORGANISM. THE INTESTINAL MICROBIOTA HAS PROTECTIVE FUNCTION AGAINST PATHOGENIC BACTERIA, METABOLIC FUNCTION BY SYNTHESIS OF VITAMINS, DECOMPOSITION OF BILE ACIDS AND PRODUCTION OF TROPHIC FACTORS (BUTYRATE), AND MODULATION OF THE INTESTINAL IMMUNE SYSTEM. THE ALTERATION OF THE MICROBIOTA IS CALLED "DYSBIOSIS" CAUSING INVASIVE INTESTINAL DISEASES PATHOLOGIES (LEAKY GUT SYNDROME AND FOOD INTOLERANCES, IRRITABLE BOWEL SYNDROME OR CHRONIC INFLAMMATORY BOWEL DISEASES) AND CORRELATING WITH NUMEROUS SYSTEMIC DISEASES INCLUDING ACUTE AND CHRONIC PROSTATITIS. ADMINISTRATION OF LIVE PROBIOTICS BACTERIA CAN BE USED TO REGULATE THE BALANCE IF INTESTINAL FLORA. SESSIONS OF HYDROCOLONTHERAPY CAN REPRESENT AN INTEGRATION TO THIS THERAPEUTIC APPROACH. FINALLY, MICROBIOLOGICAL EXAMINATION OF SEXUAL PARTNERS CAN OFFER SUPPLEMENTARY INFORMATION FOR TREATMENT. 2019 2 2518 49 EPIGENETICS AND THE EMBODIMENT OF RACE: DEVELOPMENTAL ORIGINS OF US RACIAL DISPARITIES IN CARDIOVASCULAR HEALTH. THE RELATIVE CONTRIBUTION OF GENETIC AND ENVIRONMENTAL INFLUENCES TO THE US BLACK-WHITE DISPARITY IN CARDIOVASCULAR DISEASE (CVD) IS HOTLY DEBATED WITHIN THE PUBLIC HEALTH, ANTHROPOLOGY, AND MEDICAL COMMUNITIES. IN THIS ARTICLE, WE REVIEW EVIDENCE FOR DEVELOPMENTAL AND EPIGENETIC PATHWAYS LINKING EARLY LIFE ENVIRONMENTS WITH CVD, AND CRITICALLY EVALUATE THEIR POSSIBLE ROLE IN THE ORIGINS OF THESE RACIAL HEALTH DISPARITIES. AFRICAN AMERICANS NOT ONLY SUFFER FROM A DISPROPORTIONATE BURDEN OF CVD RELATIVE TO WHITES, BUT ALSO HAVE HIGHER RATES OF THE PERINATAL HEALTH DISPARITIES NOW KNOWN TO BE THE ANTECEDENTS OF THESE CONDITIONS. THERE IS EXTENSIVE EVIDENCE FOR A SOCIAL ORIGIN TO PREMATURITY AND LOW BIRTH WEIGHT IN AFRICAN AMERICANS, REFLECTING PATHWAYS SUCH AS THE EFFECTS OF DISCRIMINATION ON MATERNAL STRESS PHYSIOLOGY. IN LIGHT OF THE INVERSE RELATIONSHIP BETWEEN BIRTH WEIGHT AND ADULT CVD, THERE IS NOW A STRONG RATIONALE TO CONSIDER DEVELOPMENTAL AND EPIGENETIC MECHANISMS AS LINKS BETWEEN EARLY LIFE ENVIRONMENTAL FACTORS LIKE MATERNAL STRESS DURING PREGNANCY AND ADULT RACE-BASED HEALTH DISPARITIES IN DISEASES LIKE HYPERTENSION, DIABETES, STROKE, AND CORONARY HEART DISEASE. THE MODEL OUTLINED HERE BUILDS UPON SOCIAL CONSTRUCTIVIST PERSPECTIVES TO HIGHLIGHT AN IMPORTANT SET OF MECHANISMS BY WHICH SOCIAL INFLUENCES CAN BECOME EMBODIED, HAVING DURABLE AND EVEN TRANSGENERATIONAL INFLUENCES ON THE MOST PRESSING US HEALTH DISPARITIES. WE CONCLUDE THAT ENVIRONMENTALLY RESPONSIVE PHENOTYPIC PLASTICITY, IN COMBINATION WITH THE BETTER-STUDIED ACUTE AND CHRONIC EFFECTS OF SOCIAL-ENVIRONMENTAL EXPOSURES, PROVIDES A MORE PARSIMONIOUS EXPLANATION THAN GENETICS FOR THE PERSISTENCE OF CVD DISPARITIES BETWEEN MEMBERS OF SOCIALLY IMPOSED RACIAL CATEGORIES. 2009 3 6908 23 [THYROID AND HEPATITIS C]. AUTOIMMUNE THYROID DISEASES ARE COMPLEX DISEASES THAT DEVELOP AS A RESULT OF INTERACTIONS BETWEEN GENETIC, EPIGENETIC AND ENVIRONMENTAL FACTORS. IFNA THERAPY OF CHRONIC HCV INFECTION IS ASSOCIATED WITH SUBCLINICAL OR CLINICAL THYROIDITIS, WHILE THE RELATIONSHIP BETWEEN THYROIDITIS AND VIRUS C INFECTION IS STILL DEBATED. 2012 4 5387 54 REDOX MECHANISMS IN MIGRAINE: NOVEL THERAPEUTICS AND DIETARY INTERVENTIONS. SIGNIFICANCE: MIGRAINE REPRESENTS THE THIRD MOST PREVALENT AND THE SEVENTH MOST DISABLING HUMAN DISORDER. APPROXIMATELY 30% OF MIGRAINE PATIENTS EXPERIENCE TRANSIENT, FULLY REVERSIBLE, FOCAL NEUROLOGICAL SYMPTOMS (AURA) PRECEDING THE ATTACK. RECENT ADVANCES: AWARENESS OF THE HYPOTHESIS THAT MIGRAINE ACTUALLY EMBODIES A SPECTRUM OF ILLNESSES-RANGING FROM EPISODIC TO CHRONIC FORMS-IS PROGRESSIVELY INCREASING AND POSES NOVEL CHALLENGES FOR CLARIFYING THE UNDERLYING PATHOPHYSIOLOGICAL MECHANISMS OF MIGRAINE AS WELL AS FOR THE DEVELOPMENT OF NOVEL THERAPEUTIC INTERVENTIONS. SEVERAL THEORIES HAVE EVOLVED TO THE CURRENT CONCEPT THAT A COMBINATION OF GENETIC, EPIGENETIC, AND ENVIRONMENTAL FACTORS MAY PLAY A ROLE IN MIGRAINE PATHOGENESIS, ALTHOUGH THEIR RELATIVE IMPORTANCE IS STILL BEING DEBATED. CRITICAL ISSUES: ONE CRITICAL ISSUE THAT DESERVES A PARTICULAR ATTENTION IS THE ROLE OF OXIDATIVE STRESS IN MIGRAINE. INDEED, POTENTIALLY HARMFUL OXIDATIVE EVENTS OCCUR DURING THE MIGRAINE ATTACK AND LONG-LASTING OR FREQUENT MIGRAINE EPISODES MAY INCREASE BRAIN EXPOSURE TO OXIDATIVE EVENTS THAT CAN LEAD TO CHRONIC TRANSFORMATION. MOREOVER, A WIDE VARIETY OF DIETARY, ENVIRONMENTAL, PHYSIOLOGICAL, BEHAVIORAL, AND PHARMACOLOGICAL MIGRAINE TRIGGERS MAY ACT THROUGH OXIDATIVE STRESS, WITH CLEAR IMPLICATIONS FOR MIGRAINE TREATMENT AND PROPHYLAXIS. INTERESTINGLY, ALMOST ALL CURRENT PROPHYLACTIC MIGRAINE AGENTS EXERT ANTIOXIDANT EFFECTS. FUTURE DIRECTIONS: INCREASING AWARENESS OF THE ROLE OF OXIDATIVE STRESS AND/OR DECREASED ANTIOXIDANT DEFENSES IN MIGRAINE PATHOGENESIS AND PROGRESSION TO A CHRONIC CONDITION LAYS THE FOUNDATIONS FOR THE DESIGN OF NOVEL PROPHYLACTIC APPROACHES, WHICH, BY REDUCING BRAIN OXIDATIVE PHENOMENA, COULD FAVORABLY MODIFY THE CLINICAL COURSE OF MIGRAINE. ANTIOXID. REDOX SIGNAL. 28, 1144-1183. 2018 5 537 47 ASYMPTOMATIC HYPERURICEMIA: IS IT REALLY ASYMPTOMATIC? PURPOSE OF REVIEW: HYPERURICEMIA IS HIGHLY PREVALENT, AFFECTING APPROXIMATELY 38 MILLION INDIVIDUALS IN THE UNITED STATES. HOWEVER, THE SIGNIFICANCE OF ASYMPTOMATIC HYPERURICEMIA - HYPERURICEMIA IN THE ABSENCE OF GOUT - CONTINUES TO BE DEBATED. RECENT FINDINGS: ASYMPTOMATIC HYPERURICEMIA RESULTS IN MONOSODIUM URATE CRYSTAL DEPOSITION IN TISSUES, WHICH MAY PROMOTE CHRONIC INFLAMMATION. INTRACELLULARLY, HYPERURICEMIA INHIBITS THE MASTER REGULATOR ADENOSINE MONOPHOSPHATE (AMP)-ASSOCIATED PROTEIN KINASE AND MAY CONDITION INNATE IMMUNE RESPONSES THROUGH DURABLE EPIGENETIC MODIFICATIONS. AT THE POPULATION LEVEL, ASYMPTOMATIC HYPERURICEMIA IS ASSOCIATED WITH MULTIPLE COMORBIDITIES, INCLUDING HYPERTENSION, CHRONIC KIDNEY DISEASE, CORONARY ARTERY DISEASE, AND DIABETES; LIMITATIONS OF THESE STUDIES INCLUDE THAT MOST ARE RETROSPECTIVE AND SOME DO NOT RIGOROUSLY DISTINGUISH BETWEEN ASYMPTOMATIC HYPERURICEMIA AND GOUT. TREATMENT STUDIES SUGGEST THAT URATE LOWERING MAY REDUCE THE RISK OF INCIDENCE OR PROGRESSION OF SOME OF THESE COMORBIDITIES; UNFORTUNATELY, MANY OF THESE TREATMENT STUDIES ARE SMALL OR FLAWED, AND NOT ALL STUDY RESULTS ARE CONSISTENT. SUMMARY: ACCUMULATING EVIDENCE SUGGESTS THAT ASYMPTOMATIC HYPERURICEMIA CONTRIBUTES TO THE COMORBIDITIES WITH WHICH IT ASSOCIATES AND THAT PROPER ASYMPTOMATIC HYPERURICEMIA TREATMENT MAY REDUCE FUTURE RISK. ADDITIONAL PROSPECTIVE TRIALS ARE NEEDED TO DEFINITELY ESTABLISH CAUSALITY AND SUPPORT DECISION-MAKING AS TO WHETHER, AND WHICH PATIENTS WITH ASYMPTOMATIC HYPERURICEMIA WOULD WARRANT URATE-LOWERING TREATMENT. 2020 6 244 62 ADOLESCENT IDIOPATHIC SCOLIOSIS (AIS), ENVIRONMENT, EXPOSOME AND EPIGENETICS: A MOLECULAR PERSPECTIVE OF POSTNATAL NORMAL SPINAL GROWTH AND THE ETIOPATHOGENESIS OF AIS WITH CONSIDERATION OF A NETWORK APPROACH AND POSSIBLE IMPLICATIONS FOR MEDICAL THERAPY. GENETIC FACTORS ARE BELIEVED TO PLAY AN IMPORTANT ROLE IN THE ETIOLOGY OF ADOLESCENT IDIOPATHIC SCOLIOSIS (AIS). DISCORDANT FINDINGS FOR MONOZYGOTIC (MZ) TWINS WITH AIS SHOW THAT ENVIRONMENTAL FACTORS INCLUDING DIFFERENT INTRAUTERINE ENVIRONMENTS ARE IMPORTANT IN ETIOLOGY, BUT WHAT THESE ENVIRONMENTAL FACTORS MAY BE IS UNKNOWN. RECENT EVIDENCE FOR COMMON CHRONIC NON-COMMUNICABLE DISEASES SUGGESTS EPIGENETIC DIFFERENCES MAY UNDERLIE MZ TWIN DISCORDANCE, AND BE THE LINK BETWEEN ENVIRONMENTAL FACTORS AND PHENOTYPIC DIFFERENCES. DNA METHYLATION IS ONE IMPORTANT EPIGENETIC MECHANISM OPERATING AT THE INTERFACE BETWEEN GENOME AND ENVIRONMENT TO REGULATE PHENOTYPIC PLASTICITY WITH A COMPLEX REGULATION ACROSS THE GENOME DURING THE FIRST DECADE OF LIFE. THE WORD EXPOSOME REFERS TO THE TOTALITY OF ENVIRONMENTAL EXPOSURES FROM CONCEPTION ONWARDS, COMPRISING FACTORS IN EXTERNAL AND INTERNAL ENVIRONMENTS. THE WORD EXPOSOME IS USED HERE ALSO IN RELATION TO PHYSIOLOGIC AND ETIOPATHOGENETIC FACTORS THAT AFFECT NORMAL SPINAL GROWTH AND MAY INDUCE THE DEFORMITY OF AIS. IN NORMAL POSTNATAL SPINAL GROWTH WE PROPOSE A NEW TERM AND CONCEPT, PHYSIOLOGIC GROWTH-PLATE EXPOSOME FOR THE NORMAL PROCESSES PARTICULARLY OF THE INTERNAL ENVIRONMENTS THAT MAY HAVE EPIGENETIC EFFECTS ON GROWTH PLATES OF VERTEBRAE. IN AIS, WE PROPOSE A NEW TERM AND CONCEPT PATHOPHYSIOLOGIC SCOLIOGENIC EXPOSOME FOR THE ABNORMAL PROCESSES IN MOLECULAR PATHWAYS PARTICULARLY OF THE INTERNAL ENVIRONMENT CURRENTLY EXPRESSED AS ETIOPATHOGENETIC HYPOTHESES; THESE ARE SUGGESTED TO HAVE DEFORMING EFFECTS ON THE GROWTH PLATES OF VERTEBRAE AT CELL, TISSUE, STRUCTURE AND/OR ORGAN LEVELS THAT ARE CONSIDERED TO BE EPIGENETIC. NEW RESEARCH IS REQUIRED FOR CHROMATIN MODIFICATIONS INCLUDING DNA METHYLATION IN AIS SUBJECTS AND VERTEBRAL GROWTH PLATES EXCISED AT SURGERY. IN ADDITION, CONSIDERATION IS NEEDED FOR A POSSIBLE NETWORK APPROACH TO ETIOPATHOGENESIS BY CONSTRUCTING AIS DISEASOMES. THESE APPROACHES MAY LEAD THROUGH SCREENING, GENETIC, EPIGENETIC, BIOCHEMICAL, METABOLIC PHENOTYPES AND PHARMACOGENOMIC RESEARCH TO IDENTIFY SUSCEPTIBLE INDIVIDUALS AT RISK AND MODULATE ABNORMAL MOLECULAR PATHWAYS OF AIS. THE POTENTIAL OF EPIGENETIC-BASED MEDICAL THERAPY FOR AIS CANNOT BE ASSESSED AT PRESENT, AND MUST AWAIT NEW RESEARCH DERIVED FROM THE EVALUATION OF EPIGENETIC CONCEPTS OF SPINAL GROWTH IN HEALTH AND DEFORMITY. THE TENETS OUTLINED HERE FOR AIS ARE APPLICABLE TO OTHER MUSCULOSKELETAL GROWTH DISORDERS INCLUDING INFANTILE AND JUVENILE IDIOPATHIC SCOLIOSIS. 2011 7 5151 54 PPARS IN LIVER DISEASES AND CANCER: EPIGENETIC REGULATION BY MICRORNAS. PEROXISOME-PROLIFERATOR-ACTIVATED RECEPTORS (PPARS) ARE LIGAND-ACTIVATED NUCLEAR RECEPTORS THAT EXERT IN THE LIVER A TRANSCRIPTIONAL ACTIVITY REGULATING A WHOLE SPECTRUM OF PHYSIOLOGICAL FUNCTIONS, INCLUDING CHOLESTEROL AND BILE ACID HOMEOSTASIS, LIPID/GLUCOSE METABOLISM, INFLAMMATORY RESPONSES, REGENERATIVE MECHANISMS, AND CELL DIFFERENTIATION/PROLIFERATION. DYSREGULATIONS OF THE EXPRESSION, OR ACTIVITY, OF SPECIFIC PPAR ISOFORMS IN THE LIVER ARE THEREFORE BELIEVED TO REPRESENT CRITICAL MECHANISMS CONTRIBUTING TO THE DEVELOPMENT OF HEPATIC METABOLIC DISEASES, DISORDERS INDUCED BY HEPATIC VIRAL INFECTIONS, AND HEPATOCELLULAR ADENOMA AND CARCINOMA. IN THIS REGARD, SPECIFIC PPAR AGONISTS HAVE PROVEN TO BE USEFUL TO TREAT THESE METABOLIC DISEASES, BUT FOR CANCER THERAPIES, THE USE OF PPAR AGONISTS IS STILL DEBATED. INTERESTINGLY, IN ADDITION TO PREVIOUSLY DESCRIBED MECHANISMS REGULATING PPARS EXPRESSION AND ACTIVITY, MICRORNAS ARE EMERGING AS NEW IMPORTANT REGULATORS OF PPAR EXPRESSION AND ACTIVITY IN PATHOPHYSIOLOGICAL CONDITIONS AND THEREFORE MAY REPRESENT FUTURE THERAPEUTIC TARGETS TO TREAT HEPATIC METABOLIC DISORDERS AND CANCERS. HERE, WE REVIEWED THE CURRENT KNOWLEDGE ABOUT THE GENERAL ROLES OF THE DIFFERENT PPAR ISOFORMS IN COMMON CHRONIC METABOLIC AND INFECTIOUS LIVER DISEASES, AS WELL AS IN THE DEVELOPMENT OF HEPATIC CANCERS. RECENT WORKS HIGHLIGHTING THE REGULATION OF PPARS BY MICRORNAS IN BOTH PHYSIOLOGICAL AND PATHOLOGICAL SITUATIONS WITH A FOCUS ON THE LIVER ARE ALSO DISCUSSED. 2012 8 4062 57 MATERNAL AND CHILD HEALTH SERVICES AND AN INTEGRATED, LIFE-CYCLE APPROACH TO THE PREVENTION OF NON-COMMUNICABLE DISEASES. DESCRIBED AS THE 'INVISIBLE EPIDEMIC', NON-COMMUNICABLE DISEASES (NCDS) ARE THE WORLD'S LEADING CAUSE OF DEATH. MOST ARE CAUSED BY PREVENTABLE FACTORS, INCLUDING POOR DIET, TOBACCO USE, HARMFUL USE OF ALCOHOL AND PHYSICAL INACTIVITY. DIABETES, CANCER AND CARDIOVASCULAR AND CHRONIC LUNG DISEASES WERE RESPONSIBLE FOR 38 MILLION (68%) OF GLOBAL DEATHS IN 2012. SINCE 1990, PROPORTIONATE NCD MORTALITY HAS INCREASED SUBSTANTIALLY AS POPULATIONS HAVE AGED AND COMMUNICABLE DISEASES DECLINE. THE MAJORITY OF NCD DEATHS, ESPECIALLY PREMATURE NCD DEATHS (<70 YEARS, 82%), OCCUR IN LOW-INCOME AND MIDDLE-INCOME COUNTRIES, AND AMONG POOR COMMUNITIES WITHIN THEM. ADDRESSING NCDS IS RECOGNISED AS CENTRAL TO THE POST-2015 AGENDA; ACCORDINGLY, NCDS HAVE A SPECIFIC OBJECTIVE AND TARGET IN THE SUSTAINABLE DEVELOPMENT GOALS. WHILE DEATHS FROM NCDS OCCUR MAINLY IN ADULTHOOD, MANY HAVE THEIR ORIGINS IN EARLY LIFE, INCLUDING THROUGH EPIGENETIC MECHANISMS OPERATING BEFORE CONCEPTION. GOOD NUTRITION BEFORE CONCEPTION AND INTERVENTIONS AIMED AT PREVENTING NCDS DURING THE FIRST 1000 DAYS (FROM CONCEPTION TO AGE 2 YEARS), CHILDHOOD AND ADOLESCENCE MAY BE MORE COST-EFFECTIVE THAN MANAGING ESTABLISHED NCDS IN LATER LIFE WITH COSTLY TESTS AND DRUGS. FOLLOWING A LIFE-COURSE APPROACH, MATERNAL AND CHILD HEALTH INTERVENTIONS, BEFORE DELIVERY AND DURING CHILDHOOD AND ADOLESCENCE, CAN PREVENT NCDS AND SHOULD INFLUENCE GLOBAL HEALTH AND SOCIOECONOMIC DEVELOPMENT. THIS PAPER DESCRIBES HOW SUCH AN APPROACH MAY BE PURSUED, INCLUDING THROUGH THE ENGAGEMENT OF NON-HEALTH SECTORS. IT ALSO EMPHASISES EVALUATING AND DOCUMENTING RELATED INITIATIVES TO UNDERWRITE SYSTEMATIC AND EVIDENCE-BASED CROSS-SECTORAL ENGAGEMENT ON NCD PREVENTION IN THE FUTURE. 2017 9 29 53 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 10 1931 41 ENVIRONMENTAL EXPOSURES, THE EPIGENOME, AND AFRICAN AMERICAN WOMEN'S HEALTH. STRESS IS A COMMON FEATURE OF MODERN LIFE, BUT BOTH THE EXTENT OF EXPOSURE TO STRESSORS AND THE DOWNSTREAM EFFECTS OF THESE STRESS EXPOSURES CAN VARY CONSIDERABLY AMONG INDIVIDUALS, COMMUNITIES, AND POPULATIONS. WHEN INDIVIDUALS ARE EXPOSED TO REPEATED OR CHRONIC STRESS, WEAR AND TEAR ON THE BODY CAN ACCUMULATE AND MANIFEST IN MANY WAYS. THE TERM "ALLOSTATIC LOAD" REPRESENTS THE PHYSIOLOGICAL CONSEQUENCES OF REPEATED OR CHRONIC EXPOSURE TO ENVIRONMENTAL STRESSORS AND IS LINKED TO FLUCTUATING AND/OR HEIGHTENED NEURAL OR NEUROENDOCRINE RESPONSES. AFRICAN AMERICAN WOMEN ARE ONE POPULATION SUBGROUP THAT HAS BEEN IDENTIFIED AS POTENTIALLY HAVING BOTH AN ELEVATED ALLOSTATIC LOAD AND AN ENHANCED RESILIENCE TO EXTERNAL FACTORS. ONE MECHANISM BY WHICH ENVIRONMENTAL STRESSORS MAY IMPACT HUMAN HEALTH IS VIA EPIGENETIC REMODELING OF THE GENOME. THIS REVIEW WILL FOCUS ON WHAT IS KNOWN ABOUT HOW DIFFERENT TYPES OF ENVIRONMENTAL STRESSORS MAY AFFECT THE EPIGENOME AND EXPLORE LINKS BETWEEN EPIGENETIC REPROGRAMMING AND ALTERED ALLOSTATIC LOAD AND RESILIENCE AS IT PERTAINS TO AFRICAN AMERICAN WOMEN'S HEALTH. 2019 11 380 49 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 12 6894 32 [SOCIAL INEQUALITY AND MENTAL HEALTH]. SOCIAL INEQUALITY REFERS TO THE INEQUITABLE DISTRIBUTION OF SOCIAL PROSPERITY INCLUDING THE RESOURCE OF HEALTH. THE RELATIONSHIP BETWEEN SOCIAL INEQUALITY AND MENTAL HEALTH CAN BE ESTABLISHED BY MEANS OF INDICATORS OF SOCIAL INEQUALITY THROUGHOUT ALL AGE GROUPS IN GERMANY. THERE ARE SOCIAL GRADIENTS OF MENTAL HEALTH ON THE POPULATION LEVEL, I.E. THE LINEAR RELATIONSHIP BETWEEN SOCIAL CLASSES OR STATUS AND STATE OF HEALTH. FUNDAMENTAL DETERMINANTS OF HEALTH DISPARITY ARE CULTURAL, SOCIAL, POLITICAL, AND GEOGRAPHICAL CONDITIONS, WHICH INTERACT WITH THE GENETIC MAKE-UP AND EPIGENETIC PROCESSES. THESE DETERMINANTS ALSO INFLUENCE THE MANAGEMENT OF DEVELOPMENTAL TASKS DURING THE LIFE COURSE AND ARE OF UTMOST IMPORTANCE FOR THE DEVELOPMENT OF MENTAL DISORDERS. THE MALADAPTATION TO CHRONIC STRESS IS AT THE CORE OF HEALTH DISPARITY. INTERVENTIONS AT THE INDIVIDUAL BEHAVIORAL LEVEL SHOULD COMPRISE THE DEVELOPMENT OF STRESS MANAGEMENT AND COPING STRATEGIES. 2019 13 30 69 A BRIEF LOOK AT HASHIMOTO'S DISEASE, ADRENAL INCIDENTALOMAS, OBESITY AND INSULIN RESISTANCE-COULD ENDOCRINE DISRUPTORS BE THE OTHER SIDE OF THE SAME COIN? HASHIMOTO'S DISEASE (HD) IS THE MOST COMMON CAUSE OF HYPOTHYROIDISM IN DEVELOPED COUNTRIES. THE EXACT PATHOMECHANISM BEHIND IT HAS NOT BEEN CLEARLY ESTABLISHED; HOWEVER, AN INTERPLAY OF GENETIC SUSCEPTIBILITY, ENVIRONMENTAL TRIGGERS (INCLUDING DIET) AND EPIGENETIC FACTORS SEEMS TO BE INVOLVED. AMONG THE LATTER, INCREASINGLY MORE ATTENTION HAS BEEN PAID TO SOME HORMONALLY ACTIVE SUBSTANCES, KNOWN AS ENDOCRINE DISRUPTORS, WHICH ARE COMMONLY USED WORLDWIDE. HD HAS BECOME A CONDITION WIDELY REPORTED IN THE MEDIA, ACTING AS A CULPRIT FOR INEXPLICABLE WEIGHT GAIN, CHRONIC FATIGUE OR WEAKNESS. NEVERTHELESS, THE RECOGNITION OF HD IS UNDENIABLY INCREASING AND REPRESENTS A MAJOR PUBLIC HEALTH BURDEN. AT THE SAME TIME, IMPROVING ACCESS TO IMAGING TESTS HAS INCREASED THE NUMBER OF INCIDENTALLY DIAGNOSED ADRENAL TUMORS. ABOVE ALL, THE WIDESPREAD USE OF CHEST COMPUTED TOMOGRAPHY (CT) DUE TO THE COVID-19 PANDEMIC HAS CONTRIBUTED TO FREQUENT INCIDENTAL DETECTION OF ADRENAL LESIONS. FORTUNATELY, A VAST MAJORITY OF THESE FINDINGS ARE ASYMPTOMATIC BENIGN TUMORS WITH NO EXCESSIVE HORMONAL ACTIVITY, AND THEREFORE, THEY ARE DEFINED AS ADRENAL INCIDENTALOMAS (AIS). INTERESTINGLY, RECENT STUDIES HAVE INDICATED THAT PATIENTS WITH AIS ARE MORE PRONE TO OBESITY AND INSULIN RESISTANCE. ALTHOUGH MUTUAL RELATIONSHIPS BETWEEN THE THYROID AND THE ADRENAL GLANDS HAVE BEEN STUDIED WIDELY, STILL, LITTLE IS KNOWN ABOUT THE POSSIBLE PATHOPHYSIOLOGICAL ASSOCIATIONS BETWEEN THYROID AUTOIMMUNITY AND THE OCCURRENCE OF ADRENAL INCIDENTALOMAS. THIS ARTICLE PRESENTS A BRIEF REVIEW OF THE COMMON ENDOCRINE DISORDERS WITH A SPECIAL FOCUS ON THE FREQUENTLY COEXISTING INSULIN RESISTANCE AND/OR OBESITY. FURTHERMORE, IN RESPONSE TO THE RECENT GROWING INTEREST IN ENDOCRINE DISRUPTORS, WITH THEIR TRANSGENERATIONAL EPIGENETIC EFFECTS THAT INFLUENCE HORMONAL SYSTEM FUNCTION, A CONCISE OVERVIEW OF THE TOPIC HAS ALSO BEEN INCLUDED. 2023 14 1932 45 ENVIRONMENTAL EXPOSURES: AN UNDERRECOGNIZED CONTRIBUTION TO NONCOMMUNICABLE DISEASES. PREVIOUS ATTEMPTS TO DETERMINE THE DEGREE TO WHICH EXPOSURE TO ENVIRONMENTAL FACTORS CONTRIBUTE TO NONCOMMUNICABLE DISEASES (NCDS) HAVE BEEN VERY CONSERVATIVE AND HAVE SIGNIFICANTLY UNDERESTIMATED THE ACTUAL CONTRIBUTION OF THE ENVIRONMENT FOR AT LEAST TWO REASONS. FIRSTLY, MOST PREVIOUS REPORTS HAVE EXCLUDED THE CONTRIBUTION OF LIFESTYLE BEHAVIORAL RISK FACTORS, BUT THESE USUALLY INVOLVE SIGNIFICANT EXPOSURE TO ENVIRONMENTAL CHEMICALS THAT INCREASE RISK OF DISEASE. SECONDLY, EARLY LIFE EXPOSURE TO CHEMICAL CONTAMINANTS IS NOW CLEARLY ASSOCIATED WITH AN ELEVATED RISK OF SEVERAL DISEASES LATER IN LIFE, BUT THESE CONNECTIONS ARE OFTEN DIFFICULT TO DISCERN. THIS IS ESPECIALLY TRUE FOR ASTHMA AND NEURODEVELOPMENTAL CONDITIONS, BUT THERE IS ALSO A MAJOR CONTRIBUTION TO THE DEVELOPMENT OF OBESITY AND CHRONIC DISEASES. MOST CANCERS ARE CAUSED BY ENVIRONMENTAL EXPOSURES IN GENETICALLY SUSCEPTIBLE INDIVIDUALS. IN ADDITION, NEW INFORMATION SHOWS SIGNIFICANT ASSOCIATIONS BETWEEN CARDIOVASCULAR DISEASES AND DIABETES AND EXPOSURE TO ENVIRONMENTAL CHEMICALS PRESENT IN AIR, FOOD, AND WATER. THESE RELATIONSHIPS LIKELY REFLECT THE COMBINATION OF EPIGENETIC EFFECTS AND GENE INDUCTION. ENVIRONMENTAL FACTORS CONTRIBUTE SIGNIFICANTLY MORE TO NCDS THAN PREVIOUS REPORTS HAVE SUGGESTED. PREVENTION NEEDS TO SHIFT FOCUS FROM INDIVIDUAL RESPONSIBILITY TO SOCIETAL RESPONSIBILITY AND AN UNDERSTANDING THAT EFFECTIVE PREVENTION OF NCDS ULTIMATELY RELIES ON IMPROVED ENVIRONMENTAL MANAGEMENT TO REDUCE EXPOSURE TO MODIFIABLE RISKS. 2013 15 5169 53 PRECONCEPTIONAL STRESS AND RACIAL DISPARITIES IN PRETERM BIRTH: AN OVERVIEW. OBJECTIVE: WE REVIEWED THE EVIDENCE FOR THREE THEORIES OF HOW PRECONCEPTIONAL PSYCHOSOCIAL STRESS COULD ACT AS A CONTRIBUTING DETERMINANT OF EXCESS PRETERM BIRTH RISK AMONG AFRICAN AMERICAN WOMEN: EARLY LIFE DEVELOPMENTAL PLASTICITY AND EPIGENETIC PROGRAMMING OF ADULT NEUROENDOCRINE SYSTEMS; BLUNTING, WEATHERING, OR DYSFUNCTION OF NEUROENDOCRINE AND IMMUNE FUNCTION IN RESPONSE TO CHRONIC STRESS ACTIVATION THROUGH THE LIFE COURSE; INDIVIDUALS' ADOPTION OF RISKY BEHAVIORS SUCH AS SMOKING AS A RESPONSE TO STRESSFUL STIMULI. METHODS: BASIC SCIENCE, CLINICAL, AND EPIDEMIOLOGIC STUDIES INDEXED IN MEDLINE AND WEB OF SCIENCE DATABASES ON PRECONCEPTIONAL PSYCHOSOCIAL STRESS, PRETERM BIRTH AND RACE WERE REVIEWED. RESULTS: MIXED EVIDENCE LEANS TOWARDS MODEST ASSOCIATIONS BETWEEN PRECONCEPTIONAL CHRONIC STRESS AND PRETERM BIRTH (FOR EXAMPLE COMMON ODDS RATIOS OF 1.2-1.4), PARTICULARLY IN AFRICAN AMERICAN WOMEN, BUT IT IS UNCLEAR WHETHER THIS ASSOCIATION IS CAUSAL OR EXPLAINS A SUBSTANTIAL PORTION OF THE BLACK-WHITE RACIAL DISPARITY IN PRETERM BIRTH. THE STRESS-PRETERM BIRTH ASSOCIATION MAY BE MEDIATED BY HYPOTHALAMIC-PITUITARY-ADRENAL AXIS DYSFUNCTION AND SUSCEPTIBILITY TO BACTERIAL VAGINOSIS, ALTHOUGH THESE MECHANISMS ARE INCOMPLETELY UNDERSTOOD. EVIDENCE FOR THE ROLE OF EPIGENETIC OR EARLY LIFE PROGRAMMING AS A DETERMINANT OF RACIAL DISPARITIES IN PRETERM BIRTH RISK IS MORE CIRCUMSTANTIAL. CONCLUSIONS: PRECONCEPTIONAL STRESS, DIRECTLY OR IN INTERACTION WITH HOST GENETIC SUSCEPTIBILITY OR INFECTION, REMAINS AN IMPORTANT HYPOTHESIZED RISK FACTOR FOR UNDERSTANDING AND REDUCING RACIAL DISPARITIES IN PRETERM BIRTH. FUTURE STUDIES THAT INTEGRATE ADEQUATELY SIZED EPIDEMIOLOGIC SAMPLES WITH MEASURES OF STRESS, INFECTION, AND GENE EXPRESSION, WILL ADVANCE OUR KNOWLEDGE AND ALLOW DEVELOPMENT OF TARGETED INTERVENTIONS. 2011 16 1911 41 ENVIRONMENT IN CHILDREN'S HEALTH: A NEW CHALLENGE FOR RISK ASSESSMENT. IN THE LAST FEW YEARS, MANY STUDIES HAVE FOCUSED ON THE EFFECTS OF ENVIRONMENTAL CONTAMINANT EXPOSURE DURING THE PRENATAL PERIOD OR INFANCY AS PREDICTORS OF HEALTH OUTCOMES IN THE FUTURE. IN THESE TIME WINDOWS, DUE TO THEIR RAPID GROWTH, AND PHYSIOLOGIC AND METABOLIC DEVELOPMENT, WE CAN OBSERVE A HIGHER VULNERABILITY TO THE EFFECTS OF ENVIRONMENT, WITH RESPECT TO ADULTHOOD. THE EVIDENCE OF POSSIBLE INFLUENCES, PARTLY MEDIATED BY EPIGENETIC MECHANISMS, INVOLVE NEUROBEHAVIORAL RESPONSES AND IMMUNE, ENDOCRINE, AND RESPIRATORY SYSTEMS, ACTING DIRECTLY ON THE CHILD OR INDIRECTLY WHEN MEDIATED BY PLACENTAL TRANSFER OR BREAST FEEDING. IN PARTICULAR, DUE TO A GREATER INTAKE OF AIR, FOOD, AND FLUIDS RELATIVE TO BODY WEIGHT, CRAWLING BEHAVIORS AND SHORT STATURE, THE RISK OF EXCESSIVE EXPOSURE IS GREATER IN CHILDREN. HOWEVER, DATA ON THE LONG-TERM IMPLICATIONS OF EARLY EXPOSURES ARE SCARCE. ADDITIONALLY, SO THAT PHYSICIANS AND INSTITUTIONS FOR CHILD CARE AND ASSISTANCE OF PREGNANT WOMEN CAN TAKE ACTIONS TO COUNTERACT THE EFFECTS OF CHEMICAL POLLUTION (I.E., BY EDUCATIONAL OPPORTUNITIES), A RISK ASSESSMENT PERSPECTIVE THAT RESPONDS TO THE BIOCOMPLEXITY OF THE HUMAN BEING IS NEEDED. THE PRESENT PAPER PROVIDES AN OVERVIEW OF PHYSIOLOGIC AND BEHAVIORAL CHARACTERISTICS DURING THE PERINATAL PERIOD AND IN CHILDHOOD, SUGGESTING IN A MORE INTEGRATED WAY, THE NEED OF A NEW RISK-ASSESSMENT APPROACH TO MANAGING CHRONIC DISEASE IN PEDIATRIC PATIENTS. 2021 17 5179 55 PREGNANCY: AN UNDERUTILIZED WINDOW OF OPPORTUNITY TO IMPROVE LONG-TERM MATERNAL AND INFANT HEALTH-AN APPEAL FOR CONTINUOUS FAMILY CARE AND INTERDISCIPLINARY COMMUNICATION. PHYSIOLOGIC ADAPTATIONS DURING PREGNANCY UNMASK A WOMAN'S PREDISPOSITION TO DISEASES. COMPLICATIONS ARE INCREASINGLY PREDICTED BY FIRST-TRIMESTER ALGORITHMS, AMPLIFY A PRE-EXISTING MATERNAL PHENOTYPE AND ACCELERATE RISKS FOR CHRONIC DISEASES IN THE OFFSPRING UP TO ADULTHOOD (BARKER HYPOTHESIS). RECENT EVIDENCE SUGGESTS THAT VICE VERSA, PREGNANCY DISEASES ALSO INDICATE MATERNAL AND EVEN GRANDPARENT'S RISKS FOR CHRONIC DISEASES (REVERSE BARKER HYPOTHESIS). PUB-MED AND EMBASE WERE REVIEWED FOR MESH TERMS "FETAL PROGRAMMING" AND "PREGNANCY COMPLICATIONS COMBINED WITH MATERNAL DISEASE" UNTIL JANUARY 2017. STUDIES LINKING PREGNANCY COMPLICATIONS TO FUTURE CARDIOVASCULAR, METABOLIC, AND THROMBOTIC RISKS FOR MOTHER AND OFFSPRING WERE REVIEWED. WOMEN WITH A HISTORY OF MISCARRIAGE, FETAL GROWTH RESTRICTION, PREECLAMPSIA, PRETERM DELIVERY, OBESITY, EXCESSIVE GESTATIONAL WEIGHT GAIN, GESTATIONAL DIABETES, SUBFERTILITY, AND THROMBOPHILIA MORE FREQUENTLY DEMONSTRATE WITH ECHOCARDIOGRAPHIC ABNORMALITIES, HIGHER FASTING INSULIN, DEVIATING LIPIDS OR CLOTTING FACTORS AND SHOW DEFECTIVE ENDOTHELIAL FUNCTION. THROMBOPHILIA HINTS TO THROMBOTIC RISKS IN LATER LIFE. PREGNANCY ABNORMALITIES CORRELATE WITH FUTURE CARDIOVASCULAR AND METABOLIC COMPLICATIONS AND EARLIER MORTALITY. CONVERSELY, WOMEN WITH A NORMAL PREGNANCY HAVE LOWER RATES OF SUBSEQUENT DISEASES THAN THE GENERAL FEMALE POPULATION CREATING THE TERM: "PREGNANCY AS A WINDOW FOR FUTURE HEALTH." ALTHOUGH THE PLACENTA WORKS AS A GATEKEEPER, MANY PREGNANCY COMPLICATIONS MAY LEAD TO SICKNESS AND EARLIER DEATH IN LATER LIFE WHEN THE CHILD BECOMES AN ADULT. THE EPIGENETIC MECHANISMS AND THE MISMATCH BETWEEN PRE- AND POSTNATAL LIFE HAVE CREATED THE TERM "FETAL ORIGIN OF ADULT DISEASE." UP TO NOW, THE IMPACT OF CARDIOVASCULAR, METABOLIC, OR THROMBOTIC RISK PROFILES HAS BEEN INVESTIGATED SEPARATELY FOR MOTHER AND CHILD. IN THIS MANUSCRIPT, WE STRIVE TO ILLUSTRATE THE CONSEQUENCES FOR BOTH, FETUS AND MOTHER WITHIN A COHESIVE PERSPECTIVE AND THUS TRY TO DEMONSTRATE THE COMPLEX INTERRELATIONSHIP OF GENETICS AND EPIGENETICS FOR LONG-TERM HEALTH OF SOCIETIES AND FUTURE GENERATIONS. MATERNAL-FETAL MEDICINE SPECIALISTS SHOULD HAVE A KEY ROLE IN THE PREVENTION OF NON-COMMUNICABLE DISEASES BY IMPLEMENTING A FRAMEWORK FOR PATIENT CONSULTATION AND INTERDISCIPLINARY NETWORKS. HEALTH-CARE PROVIDERS AND POLICY MAKERS SHOULD INCREASINGLY INVEST IN A STRATIFIED PRIMARY PREVENTION AND FOLLOW-UP TO REDUCE THE INCREASING NUMBER OF MANIFEST CARDIOVASCULAR AND METABOLIC DISEASES AND TO PREVENT WASTE OF HEALTH-CARE RESOURCES. 2017 18 3975 63 LONG-TERM CONSEQUENCES OF PLACENTAL VASCULAR PATHOLOGY ON THE MATERNAL AND OFFSPRING CARDIOVASCULAR SYSTEMS. OVER THE LAST THIRTY YEARS, EVIDENCE HAS BEEN ACCUMULATING THAT HYPERTENSIVE DISORDERS OF PREGNANCY (HDP) AND, SPECIFICALLY, PREECLAMPSIA (PE) PRODUCE NOT ONLY LONG-TERM EFFECTS ON THE PREGNANT WOMAN, BUT HAVE ALSO LASTING CONSEQUENCES FOR THE FETUS. AT THE CORE OF THESE CONSEQUENCES IS THE PHENOMENON KNOWN AS DEFECTIVE DEEP PLACENTATION, BEING PRESENT IN VIRTUALLY EVERY MAJOR OBSTETRICAL SYNDROME. THE PROFOUND PLACENTAL VASCULAR LESIONS CHARACTERISTIC OF THIS PATHOLOGY CAN INDUCE LONG-TERM ADVERSE CONSEQUENCES FOR THE PREGNANT WOMAN'S ENTIRE ARTERIAL SYSTEM. IN ADDITION, PLACENTAL GROWTH RESTRICTION AND FUNCTION CAN, IN TURN, CAUSE A DECREASED BLOOD SUPPLY TO THE FETUS, WITH LONG-LASTING EFFECTS. WOMEN WITH A HISTORY OF HDP HAVE AN INCREASED RISK OF CARDIOVASCULAR DISEASES (CVD) COMPARED WITH WOMEN WITH NORMAL PREGNANCIES. SPECIFICALLY, THESE SUBJECTS ARE AT A FUTURE HIGHER RISK OF: HYPERTENSION; CORONARY ARTERY DISEASE; HEART FAILURE; PERIPHERAL VASCULAR DISEASE; CEREBROVASCULAR ACCIDENTS (STROKE); CVD-RELATED MORTALITY. VASCULAR PATHOLOGY IN PREGNANCY AND CVD MAY SHARE A COMMON ETIOLOGY AND MAY HAVE COMMON RISK FACTORS, WHICH ARE UNMASKED BY THE "STRESS" OF PREGNANCY. IT IS ALSO POSSIBLE THAT THE FUTURE OCCURRENCE OF A CVD MAY BE THE CONSEQUENCE OF ENDOTHELIAL DYSFUNCTION GENERATED BY PREGNANCY-INDUCED HYPERTENSION THAT PERSISTS AFTER DELIVERY. ALTHOUGH BIOCHEMICAL AND BIOPHYSICAL MARKERS OF PE ABOUND, INFORMATION ON MARKERS FOR A COMPARATIVE EVALUATION IN THE VARIOUS GROUPS IS STILL LACKING. LONG-TERM CONSEQUENCES FOR THE FETUS ARE AN INTEGRAL PART OF THE THEORY OF A FETAL ORIGIN OF A NUMBER OF ADULT DISEASES, KNOWN AS THE BARKER HYPOTHESIS. INDEED, INTRAUTERINE MALNUTRITION AND FETAL GROWTH RESTRICTION REPRESENT SIGNIFICANT RISK FACTORS FOR THE DEVELOPMENT OF CHRONIC HYPERTENSION, DIABETES, STROKE AND DEATH FROM CORONARY ARTERY DISEASE IN ADULTS. OTHER FACTORS WILL ALSO INFLUENCE THE DEVELOPMENT LATER IN LIFE OF HYPERTENSION, CORONARY AND MYOCARDIAL DISEASE; THEY INCLUDE PARENTAL GENETIC DISPOSITION, EPIGENETIC MODIFICATIONS, ENDOTHELIAL DYSFUNCTION, CONCURRENT INTRAUTERINE EXPOSURES, AND THE LIFESTYLE OF THE AFFECTED INDIVIDUAL. 2021 19 3934 97 LIVER TUMOR INDUCTION. THE SIGNIFICANCE OF THE DEVELOPMENT OF NODULAR LIVER LESIONS IN RODENTS FOLLOWING THE ADMINISTRATION OF TEST AGENTS RAISES SEVERAL QUESTIONS WHICH COULD BE PLACED IN ONE OF TWO GENERAL CATEGORIES: DIAGNOSTIC AND INTERPRETATIONAL. FROM A DIAGNOSTIC POINT OF VIEW, THE PROPER CLASSIFICATION OF LIVER TUMORS INTO A BENIGN AND MALIGNANT CATEGORY HAS TO BE BASED ON THE DIRECT CORRELATION BETWEEN THE MORPHOLOGY AND THE BIOLOGIC BEHAVIOR OF THE LESIONS. THEREFORE, EXTREME CARE SHOULD BE TAKEN TO SEPARATE THE MALIGNANT TUMORS FROM THE BENIGN AND THE BENIGN NEOPLASIA FROM THE HYPERPLASIA. THE SUBSTITUTION OF THE TERM "NEOPLASTIC NODULE" FOR HYPERPLASTIC NODULE IN RATS IS MISLEADING. MOST OF THESE NODULES, WHEN INDUCED UNDER SPECIAL EXPERIMENTAL CONDITIONS, MAY REGRESS OR REMODEL AND THUS THEY ARE NOT NEOPLASTIC IN NATURE. CHRONIC CARCINOGENICITY BIOASSAYS SHOULD INCLUDE "STOP" TYPE OF TREATMENT LEAVING ENOUGH OF THE OBSERVATIONAL TIME TO ESTABLISH THE FATE OF INDUCED NODULAR LESIONS. THE INDUCTION OF HISTOCHEMICALLY CHANGED FOCI CAN SERVE ONLY AS AN INDICATION OF POTENTIAL HEPATOCARCINOGENICITY AND SHOULD NOT BE EQUATED WITH THE INDUCTION OF BONA FIDE CANCER. THE BIOLOGIC INTERPRETATION OF NODULAR LIVER LESIONS, ESPECIALLY IN MICE, NEEDS FURTHER SCRUTINY BECAUSE THESE LESIONS HAVE A TENDENCY TO DEVELOP SPONTANEOUSLY WITH HIGH INCIDENCE IN SOME STRAINS. THIS CHARACTERISTIC THEN RAISES THE QUESTION AS TO THE MECHANISM BY WHICH VARIOUS AGENTS AUGMENT AND/OR ACCELERATE THE DEVELOPMENT OF SUCH TUMORS. IS THIS ACTION PRIMARILY PROMOTING OR INITIATING IN NATURE OR DOES IT REPRESENT THE INDUCTION OF TUMORS DE NOVO? THE ANSWER TO THIS DILEMMA MAY HAVE A DECISIVE BEARING ON CARCINOGENIC RISK ASSESSMENT AND THE TYPE OF REGULATORY ACTION, SINCE THE PROMOTING AGENTS POSSESS A THRESHOLD EFFECT AND THE PROMOTED CHANGES MAY REGRESS FOLLOWING WITHDRAWAL OF TREATMENT. THE INTERPRETATION OF HEPATOCARCINOGENESIS IS FURTHER COMPLICATED BY THE FACT THAT SEVERAL FACTORS, SUCH AS SEX HORMONAL ENVIRONMENT, INCREASED MITOTIC ACTIVITY FOLLOWING AN EXCESSIVE LOSS OF PARENCHYMAL CELLS, DEGREE OF CALORIC INTAKE, ENZYMATIC COMPLEMENT, AND ANIMALS' AGE AT THE TIME OF THE EXPOSURE TO A TEST AGENT, MAY INFLUENCE THE OUTCOME OF LIVER TUMOR DEVELOPMENT BY MODULATING "INITIATION" AND/OR "PROMOTION" OF CARCINOGENESIS. BROAD FLUCTUATION IN THE HISTORIC INCIDENCE OF LIVER TUMORS FURTHER COMPOUNDS THE COMPLEXITY OF THE PROPER BIOASSAY INTERPRETATION. THE SPECIFICALLY DESIGNED EXPERIMENTS MAY HAVE THE OBJECTIVE TO EXPLORE PREDOMINANTLY THE INITIATING OR PROMOTING EFFECTS OF THE AGENT. SUCH PROTOCOLS SHOULD BE USED WHENEVER NECESSARY TO DIFFERENTIATE BETWEEN THESE TWO MECHANISMS OF ACTION. IN THE CAUCASIANS, THE "SPONTANEOUS" DEVELOPMENT OF THE PRIMARY HEPATOCELLULAR TUMORS IS RARE. THE MAJORITY OF THESE TUMORS ARE MALIGNANT AND RAPIDLY FATAL. ACCORDING TO SOME HUMAN PATHOLOGISTS, THE BENIGN VARIETY OF LIVER TUMORS IS RARE AND IT DOES NOT REPRESENT NECESSARILY A PREMALIGNANT STAGE IN TUMOR DEVELOPMENT. CARCINOMA OF THE LIVER MAY OCCUR IN INFANCY, ESPECIALLY IN MALES BEFORE THE AGE OF 2 YEARS. THIS SUGGESTS A GENETIC CAUSATION OR CARCINOGENIC EXPOSURE IN UTERO. ONE OF THE GEOGRAPHIC FACTORS WHICH SIGNIFICANTLY ENHANCES THE INCIDENCE OF HEPATOCELLULAR CARCINOMA IN HUMANS IS EXPOSURE TO AFLATOXIN B(1) WHICH IS APPARENTLY POTENTIATED BY CONCURRENT LIVER CIRRHOSIS. BECAUSE MANY MORE AGENTS HAVE BEEN FOUND TO BE HEPATOCARCINOGENIC IN MICE AND RATS THAN IN MEN, A QUESTION ARISES AS TO THE DIRECT RELEVANCE OF RODENT STUDIES TO HUMANS. A BALANCED ASSESSMENT OF THE CARCINOGENICITY OF THE AGENT COULD ONLY BE REACHED IN CONSIDERING BOTH THE PHARMACOKINETICS AND THE DEVELOPMENT OF MALIGNANT NEOPLASIA IN OTHER ORGANS. IN THE CASE OF POSITIVE CARCINOGENICITY ASSESSMENT, THE OUTCOME OF THE MUTAGENICITY BIOASSAYS CAN SUGGEST GENIC (GENOTOXIC) OR PARAGENIC (EPIGENETIC) MODE OF ACTION IN MAMMALIAN SYSTEMS. 1982 20 6489 47 TRACHOMA AND OCULAR CHLAMYDIAL INFECTION IN THE ERA OF GENOMICS. TRACHOMA IS A BLINDING DISEASE USUALLY CAUSED BY INFECTION WITH CHLAMYDIA TRACHOMATIS (CT) SEROVARS A, B, AND C IN THE UPPER TARSAL CONJUNCTIVA. INDIVIDUALS IN ENDEMIC REGIONS ARE REPEATEDLY INFECTED WITH CT THROUGHOUT CHILDHOOD. A PROPORTION OF INDIVIDUALS EXPERIENCE PROLONGED OR SEVERE INFLAMMATORY EPISODES THAT ARE KNOWN TO BE SIGNIFICANT RISK FACTORS FOR OCULAR SCARRING IN LATER LIFE. CONTINUED SCARRING OFTEN LEADS TO TRICHIASIS AND IN-TURNING OF THE EYELASHES, WHICH CAUSES PAIN AND CAN EVENTUALLY CAUSE BLINDNESS. THE MECHANISMS DRIVING THE CHRONIC IMMUNOPATHOLOGY IN THE CONJUNCTIVA, WHICH LARGELY PROGRESSES IN THE ABSENCE OF DETECTABLE CT INFECTION IN ADULTS, ARE LIKELY TO BE MULTIFACTORIAL. SOCIOECONOMIC STATUS, EDUCATION, AND BEHAVIOR HAVE BEEN IDENTIFIED AS CONTRIBUTING TO THE RISK OF SCARRING AND INFLAMMATION. WE FOCUS ON THE CONTRIBUTION OF HOST AND PATHOGEN GENETIC VARIATION, BACTERIAL ECOLOGY OF THE CONJUNCTIVA, AND HOST EPIGENETIC IMPRINTING INCLUDING SMALL RNA REGULATION BY BOTH HOST AND PATHOGEN IN THE DEVELOPMENT OF OCULAR PATHOLOGY. EACH OF THESE FACTORS OR PROCESSES CONTRIBUTES TO PATHOGENIC OUTCOMES IN OTHER INFLAMMATORY DISEASES AND WE OUTLINE THEIR POTENTIAL ROLE IN TRACHOMA. 2015