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   176  41 ACCELERATED DNA METHYLATION AGE AND MEDICATION USE AMONG AFRICAN AMERICANS. DNA METHYLATION AGE ACCELERATION, THE DISCREPANCY BETWEEN EPIGENETIC AGE AND CHRONOLOGICAL AGE, IS ASSOCIATED WITH MORTALITY AND CHRONIC DISEASES, INCLUDING DIABETES, HYPERTENSION, AND HYPERLIPIDEMIA. IN THIS STUDY, WE INVESTIGATE WHETHER MEDICATIONS COMMONLY USED TO TREAT THESE DISEASES IN 15 DRUG CATEGORIES ARE ASSOCIATED WITH FOUR EPIGENETIC AGE ACCELERATION MEASURES: HORVATHAGE ACCELERATION (HORVATHAA), HANNUMAGE ACCELERATION (HANNUMAA), PHENOAGE ACCELERATION, AND GRIMAGE ACCELERATION (GRIMAA) USING CROSS-SECTIONAL (PHASE 1, N=1,100) AND LONGITUDINAL (PHASES 1 AND 2, N=266) DATA FROM AFRICAN AMERICANS IN THE GENETIC EPIDEMIOLOGY NETWORK OF ARTERIOPATHY (GENOA) STUDY. IN CROSS-SECTIONAL ANALYSES, THE USE OF CALCIUM CHANNEL BLOCKERS WAS ASSOCIATED WITH 1.27 YEARS LOWER HANNUMAA AFTER ADJUSTING FOR COVARIATES INCLUDING HYPERTENSION (P=0.001). LONGITUDINAL ANALYSES SHOWED THAT, COMPARED TO THOSE WHO NEVER USED ANTIHYPERTENSIVES, THOSE WHO STARTED TO TAKE ANTIHYPERTENSIVES AFTER PHASE 1 HAD A 0.97-YEAR DECREASE IN GRIMAA (P=0.007). IN ADDITION, COMPARED TO THOSE WHO NEVER USED NSAID ANALGESICS, THOSE WHO STARTED TO TAKE THEM AFTER PHASE 1 HAD A 2.61-YEAR INCREASE IN HORVATHAA (P=0.0005). OUR STUDY DEMONSTRATES THAT THREE COMMONLY USED MEDICATIONS ARE ASSOCIATED WITH DNAM AGE ACCELERATION IN AFRICAN AMERICANS AND SHEDS LIGHT ON THE POTENTIAL EPIGENETIC EFFECTS OF PHARMACEUTICALS ON AGING AT THE CELLULAR LEVEL.	2021	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                 
3  5172  60 PREDICTING PAIN AFTER STANDARD PAIN THERAPY FOR KNEE OSTEOARTHRITIS - THE FIRST STEPS TOWARDS PERSONALIZED MECHANISTIC-BASED PAIN MEDICINE IN OSTEOARTHRITIS. OBJECTIVES: THE PREVALENCE OF OSTEOARTHRITIS (OA) IS RISING, AND PAIN IS THE HALLMARK SYMPTOM OF OA. PAIN IN OA IS COMPLICATED AND CAN BE INFLUENCED BY MULTIPLE JOINT-RELATED FACTORS AND FACTORS RELATED TO, E.G., PHYSIOLOGICAL, EPIGENETIC, AND PAIN SENSORY PROFILES. INCREASING EVIDENCE SUGGESTS THAT A SUBSET OF PATIENTS WITH OA ARE PAIN SENSITIVE. THIS CAN BE ASSESSED USING QUANTITATIVE SENSORY TESTING (QST). COMMON TREATMENTS OF OA ARE TOTAL KNEE ARTHROPLASTY (TKA) AND ADMINISTRATION OF 3-WEEKS OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS), WHICH PROVIDE PAIN RELIEF TO MANY PATIENTS WITH OA. HOWEVER, APPROX. 20% OF PATIENTS EXPERIENCE CHRONIC POSTOPERATIVE PAIN AFTER TKA, WHEREAS NSAIDS PROVIDE AN AVERAGE PAIN RELIEF OF APPROX. 25%. THE CURRENT TOPICAL REVIEW FOCUSES ON THE EMERGING EVIDENCE LINKING PRETREATMENT QST TO THE TREATMENT RESPONSE OF TKA AND NSAID TREATMENTS. CONTENT: MEDLINE WAS SYSTEMATICALLY SEARCHED FOR ALL STUDIES FROM 2000 TO 2022 ON PRETREATMENT QST, TKA, AND NSAIDS. PRE-CLINICAL STUDIES, REVIEWS, AND META-ANALYSES WERE EXCLUDED. SUMMARY: CURRENTLY, 14 STUDIES ON TKA AND FOUR STUDIES ON NSAIDS HAVE BEEN PUBLISHED WITH THE AIM TO ATTEMPT PREDICTION OF THE TREATMENT RESPONSE. THE QST METHODOLOGIES IN THE STUDIES ARE INCONSISTENT, BUT 11/14 (79%) STUDIES ON TKA AND 4/4 (100%) STUDIES ON NSAIDS REPORT STATISTICALLY SIGNIFICANT ASSOCIATIONS BETWEEN PRETREATMENT QST AND CHRONIC POSTOPERATIVE PAIN AFTER TKA OR ANALGESIC EFFECT AFTER NSAID TREATMENT. THE STRENGTH OF THE ASSOCIATIONS REMAINS LOW-TO-MODERATE. THE MOST CONSISTENT PRETREATMENT QST PREDICTORS ARE PRESSURE PAIN THRESHOLDS, TEMPORAL SUMMATION OF PAIN, AND CONDITIONED PAIN MODULATION. OUTLOOK: THE USE OF QST AS PREDICTORS OF STANDARD OA TREATMENT IS INTERESTING, BUT THE PREDICTIVE STRENGTH REMAINS LOW-TO-MODERATE. A TRANSITION OF QST FROM A RESEARCH-BASED SETTING AND INTO THE CLINIC IS NOT ADVISED UNTIL THE PREDICTIVE STRENGTH HAS BEEN IMPROVED AND THE METHODOLOGY HAS BEEN STANDARDIZED.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
4   983  59 CHRONIC PROSTATITIS AFFECTS MALE REPRODUCTIVE HEALTH AND IS ASSOCIATED WITH SYSTEMIC AND LOCAL EPIGENETIC INACTIVATION OF C-X-C MOTIF CHEMOKINE 12 RECEPTOR C-X-C CHEMOKINE RECEPTOR TYPE 4. BACKGROUND/AIMS/OBJECTIVES: CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME (CP/CPPS) HAS DETRIMENTAL EFFECTS ON THE QUALITY OF LIFE INCLUDING THE ASPECT OF SEXUAL DYSFUNCTION. THE AIM OF THE STUDY WAS TO IDENTIFY IF THERE WAS AN ADVERSE EFFECT ON THE MALE GENITAL COMPARTMENT AND IF THERE ARE SYSTEMIC OR COMPARTMENT-SPECIFIC LOCAL SIGNALS FOR EPIGENETIC DYSREGULATION OF INFLAMMATORY FACTORS IN CP/CPPS PATIENTS. METHODS: ONE HUNDRED FIVE NIH IIIB CP/CPPS PATIENTS AND 41 HEALTHY MEN WERE RECRUITED AND UNDERWENT INVESTIGATIONS OF URINES, SEMEN AND BLOOD. PROMOTER METHYLATION AND EXPRESSION OF THE CHEMOKINE C-X-C MOTIF CHEMOKINE 12 AND ITS RECEPTOR C-X-C CHEMOKINE RECEPTOR TYPE 4 (CXCR4) (INVOLVED IN THE RECRUITMENT OF MAST CELLS) WERE ANALYZED IN PROSTATE EPITHELIAL CELL LINES AND IN HEALTHY VOLUNTEERS' AND PATIENTS' BLOOD, EJACULATE CELL PELLETS, AND SEPARATED EJACULATE FRACTIONS (SPERM AND SEMINAL SOMATIC CELLS). RESULTS: INDEPENDENTLY FROM AGE, CP/CPPS NIH IIIB WAS ASSOCIATED WITH SIGNIFICANT IMPAIRMENT OF SPERM MOTILITY, MORPHOLOGY AND SEMEN PH (P < 0.001). PATIENTS OLDER THAN 33 YEARS SHOWED SIGNIFICANTLY INCREASED SEMINAL INTERLEUKIN-8 AND SERUM PROSTATE SPECIFIC ANTIGEN VALUES. IN PATIENTS, THE CXCR4 MRNA-EXPRESSION WAS SIGNIFICANTLY DECREASED IN WHOLE BLOOD AND EJACULATE CELL PELLETS DUE TO PROMOTER HYPERMETHYLATION. ANALYSES ON SEPARATED FRACTIONS OF SPERM AND SEMINAL SOMATIC CELLS REVEALED THAT SPERM DNA WAS UNAFFECTED, WHEREAS SOMATIC CELL DNA WAS DIFFERENTIALLY METHYLATED. CONCLUSIONS: NIH IIIB CP/CPPS HAS NEGATIVE EFFECTS ON SURROGATE PARAMETERS OF MALE FERTILITY AND IS ASSOCIATED SIGNIFICANTLY WITH SYSTEMIC AND LOCAL EPIGENETIC INACTIVATION OF CXCR4.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                             
5  5786  49 SPORT AND MALE SEXUALITY. THE RELATIONSHIPS BETWEEN SPORT AND SEXUALITY IN MALES ARE OF GREAT SOCIAL AND CLINICAL INTEREST, BECAUSE OF SPORTS AND MOTOR ACTIVITIES THAT HIGHLY PROMOTE SOCIAL AND SEXUAL RELATIONSHIPS. EVEN IF FEW LITERATURE EXIST, TWO MAIN QUESTIONS SHOULD BE TAKEN INTO ACCOUNT: WHETHER AND HOW PHYSICAL EXERCISE AND SPORT POSITIVELY OR NEGATIVELY INFLUENCE SEXUAL HEALTH AND BEHAVIOR AND/OR WHETHER AND HOW SEXUAL BEHAVIOR MAY AFFECT A SUB-SEQUENT SPORT PERFORMANCE. PHYSICAL EXERCISE AND SPORT PER SE CAN INFLUENCE, POSITIVELY OR NEGATIVELY, THE HYPOTHALAMIC-PITUITARY-TESTICULAR AXIS FUNCTION AND, CONSEQUENTLY, THE INDIVIDUAL'S REPRODUCTIVE AND/OR SEXUAL HEALTH. THIS DEPENDS ON INDIVIDUAL FACTORS SUCH AS GENETIC AND EPIGENETIC ONES AND ON DIFFERENT VARIABLES INVOLVED IN THE PRACTICE OF SPORT ACTIVITIES (TYPE OF SPORT, INTENSITY AND DURATION OF TRAINING, DOPING AND DRUG USE AND ABUSE, NUTRITION, SUPPLEMENTS, PSYCHOLOGICAL STRESS, ALLOSTATIC LOAD, ETC.). IF WELL CONDUCTED, MOTOR AND SPORT ACTIVITIES COULD HAVE BENEFICIAL EFFECTS ON SEXUAL HEALTH IN MALES. AMONG DIFFERENT LIFESTYLE CHANGES, INFLUENCING SEXUAL HEALTH, REGULAR PHYSICAL ACTIVITY IS FUNDAMENTAL TO ANTAGONIZE THE ONSET OF ERECTILE DYSFUNCTION (ED). HOWEVER, COMPETITIVE SPORT CAN LEAD BOTH REPRODUCTIVE AND/OR SEXUAL TRACT DAMAGES AND DYSFUNCTIONS, TRANSIENT (GENITAL PAIN, HYPOESTHESIA OF THE GENITALIA, HYPOGONADISM, DE, ALTERED SEXUAL DRIVE, ETC.) OR PERMANENT (HYPOGONADISM, DE, ETC.), BY ACTING DIRECTLY (TRAUMAS OF THE EXTERNAL GENITALIA, SADDLE-RELATED DISORDERS IN CYCLISTS, ETC.) OR INDIRECTLY (EXERCISE-RELATED HYPOGONADISM, DRUG ABUSE, DOPING, STRESS, ETC.). SEXUAL ACTIVITIES SHORTLY PERFORMED BEFORE A SPORT COMPETITION COULD DIFFERENTLY INFLUENCE SPORT PERFORMANCE. DUE TO THE FEW EXISTING DATA, IT IS ADVISABLE TO AVOID AN ABSOLUTE PRE-COMPETITION SEXUAL ABSTINENCE.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                     
6  1780  44 EDUCATION AND LIFESTYLE FACTORS ARE ASSOCIATED WITH DNA METHYLATION CLOCKS IN OLDER AFRICAN AMERICANS. DNA METHYLATION (DNAM) CLOCKS ARE IMPORTANT BIOMARKERS OF CELLULAR AGING AND ARE ASSOCIATED WITH A VARIETY OF AGE-RELATED CHRONIC DISEASES AND ALL-CAUSE MORTALITY. EXAMINING THE RELATIONSHIP BETWEEN EDUCATION AND LIFESTYLE RISK FACTORS FOR AGE-RELATED DISEASES AND MULTIPLE DNAM CLOCKS CAN INCREASE THE UNDERSTANDING OF HOW RISK FACTORS CONTRIBUTE TO AGING AT THE CELLULAR LEVEL. THIS STUDY EXPLORED THE ASSOCIATION BETWEEN EDUCATION OR LIFESTYLE RISK FACTORS FOR AGE-RELATED DISEASES AND THE ACCELERATION OF FOUR DNAM CLOCKS, INCLUDING INTRINSIC (IEAA) AND EXTRINSIC EPIGENETIC AGE ACCELERATION (EEAA), PHENOAGE ACCELERATION (PHENOAA), AND GRIMAGE ACCELERATION (GRIMAA) IN THE AFRICAN AMERICAN PARTICIPANTS OF THE GENETIC EPIDEMIOLOGY NETWORK OF ARTERIOPATHY. WE PERFORMED BOTH CROSS-SECTIONAL AND LONGITUDINAL ANALYSES. IN CROSS-SECTIONAL ANALYSES, GENDER, EDUCATION, BMI, SMOKING, AND ALCOHOL CONSUMPTION WERE ALL INDEPENDENTLY ASSOCIATED WITH GRIMAA, WHEREAS ONLY SOME OF THEM WERE ASSOCIATED WITH OTHER CLOCKS. THE EFFECT OF SMOKING AND EDUCATION ON GRIMAA VARIED BY GENDER. LONGITUDINAL ANALYSES SUGGEST THAT AGE AND BMI CONTINUED TO INCREASE GRIMAA, AND THAT AGE AND CURRENT SMOKING CONTINUED TO INCREASE PHENOAA AFTER CONTROLLING DNAM CLOCKS AT BASELINE. IN CONCLUSION, EDUCATION AND COMMON LIFESTYLE RISK FACTORS WERE ASSOCIATED WITH MULTIPLE DNAM CLOCKS. HOWEVER, THE ASSOCIATION WITH EACH RISK FACTOR VARIED BY CLOCK, WHICH SUGGESTS THAT DIFFERENT CLOCKS MAY CAPTURE ADVERSE EFFECTS FROM DIFFERENT ENVIRONMENTAL STIMULI.	2019	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  
7  5478  39 RESULTS OF A RANDOMIZED STUDY OF 3 SCHEDULES OF LOW-DOSE DECITABINE IN HIGHER-RISK MYELODYSPLASTIC SYNDROME AND CHRONIC MYELOMONOCYTIC LEUKEMIA. EPIGENETIC THERAPY WITH HYPOMETHYLATING DRUGS IS NOW THE STANDARD OF CARE IN MYELODYSPLASTIC SYNDROME (MDS). RESPONSE RATES REMAIN LOW, AND MECHANISM-BASED DOSE OPTIMIZATION HAS NOT BEEN REPORTED. WE INVESTIGATED THE CLINICAL AND PHARMACODYNAMIC RESULTS OF DIFFERENT DOSE SCHEDULES OF DECITABINE. ADULTS WITH ADVANCED MDS OR CHRONIC MYELOMONOCYTIC LEUKEMIA (CMML) WERE RANDOMIZED TO 1 OF 3 DECITABINE SCHEDULES: (1) 20 MG/M2 INTRAVENOUSLY DAILY FOR 5 DAYS; (2) 20 MG/M2 SUBCUTANEOUSLY DAILY FOR 5 DAYS; AND (3) 10 MG/M2 INTRAVENOUSLY DAILY FOR 10 DAYS. RANDOMIZATION FOLLOWED A BAYESIAN ADAPTIVE DESIGN. NINETY-FIVE PATIENTS WERE TREATED (77 WITH MDS, AND 18 WITH CMML). OVERALL, 32 PATIENTS (34%) ACHIEVED A COMPLETE RESPONSE (CR), AND 69 (73%) HAD AN OBJECTIVE RESPONSE BY THE NEW MODIFIED INTERNATIONAL WORKING GROUP CRITERIA. THE 5-DAY INTRAVENOUS SCHEDULE, WHICH HAD THE HIGHEST DOSE-INTENSITY, WAS SELECTED AS OPTIMAL; THE CR RATE IN THAT ARM WAS 39%, COMPARED WITH 21% IN THE 5-DAY SUBCUTANEOUS ARM AND 24% IN THE 10-DAY INTRAVENOUS ARM (P < .05). THE HIGH DOSE-INTENSITY ARM WAS ALSO SUPERIOR AT INDUCING HYPOMETHYLATION AT DAY 5 AND AT ACTIVATING P15 EXPRESSION AT DAYS 12 OR 28 AFTER THERAPY. WE CONCLUDE THAT A LOW-DOSE, DOSE-INTENSITY SCHEDULE OF DECITABINE OPTIMIZES EPIGENETIC MODULATION AND CLINICAL RESPONSES IN MDS.	2007	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                               
8   518  52 ASSOCIATIONS BETWEEN ANTIBIOTIC EXPOSURE DURING PREGNANCY, BIRTH WEIGHT AND ABERRANT METHYLATION AT IMPRINTED GENES AMONG OFFSPRING. OBJECTIVES: LOW BIRTH WEIGHT (LBW) HAS BEEN ASSOCIATED WITH COMMON ADULT-ONSET CHRONIC DISEASES, INCLUDING OBESITY, CARDIOVASCULAR DISEASE, TYPE II DIABETES AND SOME CANCERS. THE ETIOLOGY OF LBW IS MULTI-FACTORIAL. HOWEVER, RECENT EVIDENCE SUGGESTS EXPOSURE TO ANTIBIOTICS MAY ALSO INCREASE THE RISK OF LBW. THE MECHANISMS UNDERLYING THIS ASSOCIATION ARE UNKNOWN, ALTHOUGH EPIGENETIC MECHANISMS ARE HYPOTHESIZED. IN THIS STUDY, WE EVALUATED THE ASSOCIATION BETWEEN MATERNAL ANTIBIOTIC USE AND LBW AND EXAMINED THE POTENTIAL ROLE OF ALTERED DNA METHYLATION THAT CONTROLS GROWTH REGULATORY IMPRINTED GENES IN THESE ASSOCIATIONS. METHODS: BETWEEN 2009-2011, 397 PREGNANT WOMEN WERE ENROLLED AND FOLLOWED UNTIL DELIVERY. PRENATAL ANTIBIOTIC USE WAS ASCERTAINED THROUGH MATERNAL SELF-REPORT. IMPRINTED GENES METHYLATION LEVELS WERE MEASURED AT DIFFERENTIALLY METHYLATED REGIONS (DMRS) USING BISULFITE PYROSEQUENCING. GENERALIZED LINEAR MODELS WERE USED TO EXAMINE ASSOCIATIONS AMONG ANTIBIOTIC USE, BIRTH WEIGHT AND DMR METHYLATION FRACTIONS. RESULTS: AFTER ADJUSTING FOR INFANT GENDER, RACE/ETHNICITY, MATERNAL BODY MASS INDEX, DELIVERY ROUTE, GESTATIONAL WEIGHT GAIN, GESTATIONAL AGE AT DELIVERY, FOLIC ACID INTAKE, PHYSICAL ACTIVITY, MATERNAL SMOKING AND PARITY, ANTIBIOTIC USE DURING PREGNANCY WAS ASSOCIATED WITH 138 G LOWER BIRTH WEIGHT COMPARED WITH NON-ANTIBIOTIC USE (BETA-COEFFICIENT=-132.99, S.E.=50.70, P=0.008). THESE ASSOCIATIONS WERE STRONGEST IN NEWBORNS OF WOMEN WHO REPORTED ANTIBIOTIC USE OTHER THAN PENICILLINS (BETA-COEFFICIENT=-135.57, S.E.=57.38, P=0.02). METHYLATION AT FIVE DMRS, IGF2 (P=0.05), H19 (P=0.15), PLAGL1 (P=0.01), MEG3 (P=0.006) AND PEG3 (P=0.08), WAS ASSOCIATED WITH MATERNAL ANTIBIOTIC USE; AMONG THESE, ONLY METHYLATION AT THE PLAGL1 DMR WAS ALSO ASSOCIATED WITH BIRTH WEIGHT. CONCLUSION: WE REPORT AN INVERSE ASSOCIATION BETWEEN IN UTERO EXPOSURE TO ANTIBIOTICS AND LOWER INFANT BIRTH WEIGHT AND PROVIDE THE FIRST EMPIRICAL EVIDENCE SUPPORTING IMPRINTED GENE PLASTICITY IN THESE ASSOCIATIONS.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
9  2150  44 EPIGENETIC MEASURES OF AGEING PREDICT THE PREVALENCE AND INCIDENCE OF LEADING CAUSES OF DEATH AND DISEASE BURDEN. BACKGROUND: INDIVIDUALS OF THE SAME CHRONOLOGICAL AGE DISPLAY DIFFERENT RATES OF BIOLOGICAL AGEING. A NUMBER OF MEASURES OF BIOLOGICAL AGE HAVE BEEN PROPOSED WHICH HARNESS AGE-RELATED CHANGES IN DNA METHYLATION PROFILES. THESE MEASURES INCLUDE FIVE 'EPIGENETIC CLOCKS' WHICH PROVIDE AN INDEX OF HOW MUCH AN INDIVIDUAL'S BIOLOGICAL AGE DIFFERS FROM THEIR CHRONOLOGICAL AGE AT THE TIME OF MEASUREMENT. THE FIVE CLOCKS ENCOMPASS METHYLATION-BASED PREDICTORS OF CHRONOLOGICAL AGE (HORVATHAGE, HANNUMAGE), ALL-CAUSE MORTALITY (DNAM PHENOAGE, DNAM GRIMAGE) AND TELOMERE LENGTH (DNAM TELOMERE LENGTH). A SIXTH EPIGENETIC MEASURE OF AGEING DIFFERS FROM THESE CLOCKS IN THAT IT ACTS AS A SPEEDOMETER PROVIDING A SINGLE TIME-POINT MEASUREMENT OF THE PACE OF AN INDIVIDUAL'S BIOLOGICAL AGEING. THIS MEASURE OF AGEING IS TERMED DUNEDINPOAM. IN THIS STUDY, WE TEST THE ASSOCIATION BETWEEN THESE SIX EPIGENETIC MEASURES OF AGEING AND THE PREVALENCE AND INCIDENCE OF THE LEADING CAUSES OF DISEASE BURDEN AND MORTALITY IN HIGH-INCOME COUNTRIES (N </= 9537, GENERATION SCOTLAND: SCOTTISH FAMILY HEALTH STUDY). RESULTS: DNAM GRIMAGE PREDICTED INCIDENCE OF CLINICALLY DIAGNOSED CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD), TYPE 2 DIABETES AND ISCHEMIC HEART DISEASE AFTER 13 YEARS OF FOLLOW-UP (HAZARD RATIOS = 2.22, 1.52 AND 1.41, RESPECTIVELY). DUNEDINPOAM PREDICTED THE INCIDENCE OF COPD AND LUNG CANCER (HAZARD RATIOS = 2.02 AND 1.45, RESPECTIVELY). DNAM PHENOAGE PREDICTED INCIDENCE OF TYPE 2 DIABETES (HAZARD RATIO = 1.54). DNAM TELOMERE LENGTH ASSOCIATED WITH THE INCIDENCE OF ISCHEMIC HEART DISEASE (HAZARD RATIO = 0.80). DNAM GRIMAGE ASSOCIATED WITH ALL-CAUSE MORTALITY, THE PREVALENCE OF COPD AND SPIROMETRY MEASURES AT THE STUDY BASELINE. THESE ASSOCIATIONS WERE PRESENT AFTER ADJUSTING FOR POSSIBLE CONFOUNDING RISK FACTORS INCLUDING ALCOHOL CONSUMPTION, BODY MASS INDEX, DEPRIVATION, EDUCATION AND TOBACCO SMOKING AND SURPASSED STRINGENT BONFERRONI-CORRECTED SIGNIFICANCE THRESHOLDS. CONCLUSIONS: OUR DATA SUGGEST THAT EPIGENETIC MEASURES OF AGEING MAY HAVE UTILITY IN CLINICAL SETTINGS TO COMPLEMENT GOLD-STANDARD METHODS FOR DISEASE ASSESSMENT AND MANAGEMENT.	2020	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
10  1854  61 ELEVATED SEMINAL PLASMA ESTRADIOL AND EPIGENETIC INACTIVATION OF ESR1 AND ESR2 IS ASSOCIATED WITH CP/CPPS. CHRONIC PROSTATITIS/CHRONIC PELVIC PAIN SYNDROME (CP/CPPS) IS ASSOCIATED WITH URINARY TRACT SYMPTOMS AND HORMONAL IMBALANCES AMONGST OTHERS. THE HETEROGENEOUS CLINICAL PRESENTATION, UNEXPLORED MOLECULAR BACKGROUND AND LACK OF PROSTATE BIOPSIES COMPLICATE THERAPY. HERE, USING LIQUID BIOPSIES, WE PERFORMED A COMPREHENSIVE TRANSLATIONAL STUDY ON MEN DIAGNOSED WITH CP/CPPS TYPE III (N= 50; MEDIAN AGE 39.8, RANGE 23-65) AND AGE-MATCHED CONTROLS (N= 61; MEDIAN AGE 36.8, RANGE 20-69), CONSIDERING BIOCHEMICAL PARAMETERS OF BLOOD AND EJACULATES, AND EPIGENETIC REGULATION OF THE ESTROGEN RECEPTOR GENES (ESR1 AND ESR2) IN LEUKOCYTES ISOLATED FROM BLOOD (SYSTEMIC REGULATION) AND IN SOMATIC CELLS ISOLATED FROM EJACULATES (LOCAL REGULATION). WE FOUND ELEVATED 17BETA-ESTRADIOL (E(2)) LEVELS IN SEMINAL PLASMA, BUT NOT IN BLOOD PLASMA, THAT WAS SIGNIFICANTLY ASSOCIATED WITH CP/CPPS AND IMPAIRED URINARY TRACT SYMPTOMS. IN EJACULATED SOMATIC CELLS OF CP/CPPS PATIENTS WE FOUND THAT ESR1 AND ESR2 WERE BOTH SIGNIFICANTLY HIGHER METHYLATED IN CPG-PROMOTERS AND EXPRESSIONALLY DOWN-REGULATED IN COMPARISON TO CONTROLS. MAST CELLS ARE REPORTED TO CONTRIBUTE TO CP/CPPS AND ARE ESTROGEN RESPONSIVE. CONSISTENT WITH THIS, WE FOUND THAT E(2) -TREATMENT OF HUMAN MAST CELL LINES (HMC-1 AND LAD2) RESULTED IN ALTERED CYTOKINE AND CHEMOKINE EXPRESSION. INTERESTINGLY, IN HMC-1 CELLS, POSSESSING EPIGENETICALLY INACTIVATED ESR1 AND ESR2, E(2) -TREATMENT LED TO A REDUCED TRANSCRIPTION OF A NUMBER OF INFLAMMATORY GENES. OVERALL, THESE DATA SUGGEST THAT ELEVATED LOCAL E(2) LEVELS ASSOCIATE WITH AN EPIGENETIC DOWN-REGULATION OF THE ESTROGEN RECEPTORS AND HAVE A PROMINENT ROLE IN CP/CPPS. INVESTIGATING E(2) LEVELS IN SEMEN COULD THEREFORE SERVE AS A PROMISING BIOMARKER TO SELECT PATIENTS FOR ESTROGEN TARGETED THERAPY.	2018	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
11  2734  48 EXPLORING THE RELATIONSHIP BETWEEN DNA METHYLATION AGE MEASURES AND PSYCHONEUROLOGICAL SYMPTOMS IN WOMEN WITH EARLY-STAGE BREAST CANCER. PURPOSE: THE EPIGENETIC CLOCK HAS BEEN ACKNOWLEDGED AS AN INDICATOR FOR MOLECULAR AGING, BUT FEW STUDIES HAVE EXAMINED POSSIBLE ASSOCIATIONS OF DNA METHYLATION (DNAM) AGE OR AGE ACCELERATION (AA) WITH SYMPTOM BURDEN IN INDIVIDUALS WHO ARE TREATED FOR CANCER. THIS STUDY EXPLORED THE ASSOCIATION OF DNAM AGE OR AA WITH PSYCHONEUROLOGICAL (PN) SYMPTOMS, INCLUDING COGNITIVE IMPAIRMENT, FATIGUE, SLEEP DISTURBANCES, PAIN, AND DEPRESSIVE SYMPTOMS, IN BREAST CANCER SURVIVORS OVER A 2-YEAR PERIOD. METHODS: WE MEASURED PN SYMPTOMS USING RELIABLE INSTRUMENTS AND DNAM LEVELS BY INFINIUM HUMANMETHYLATION450K BEADCHIP (N = 72). DNAM AGE WAS CALCULATED BY THE HORVATH, GRIM, AND HANNUM-BASED INTRINSIC AND EXTRINSIC AGE ESTIMATIONS. AA WAS DEFINED BY THE RESIDUAL REGRESSING ESTIMATED EPIGENETIC AGE ON CHRONOLOGICAL AGE. MIXED REGRESSION MODELS WERE FITTED FOR AA AND CHANGES IN AA TO STUDY THE ASSOCIATION OVER TIME. SEPARATE LINEAR REGRESSION MODELS AND A MIXED-EFFECTS MODEL WERE FITTED FOR AA AT EACH TIME POINT. RESULTS: HORVATH-AA, GRIM-AA, AND EXTRINSIC EPIGENETIC AA WERE SIGNIFICANTLY CHANGED OVER TIME, WHILE INTRINSIC EPIGENETIC AA DID NOT EXHIBIT ANY TEMPORAL CHANGES. INCREASED AA WAS ASSOCIATED WITH GREATER ANXIETY AND FATIGUE, AS WELL AS WORSE COGNITIVE MEMORY, ADJUSTING FOR RACE, BMI, INCOME, CHEMOTHERAPY, RADIATION THERAPY, AND CHRONOLOGICAL AGE. INCREASED DNAM AGE WAS ASSOCIATED WITH GREATER ANXIETY OVER 2 YEARS. CONCLUSION: OUR FINDINGS SUGGEST DNAM AGE AND AA MAY BE ASSOCIATED WITH PN SYMPTOMS OVER THE COURSE OF CANCER TREATMENT AND SURVIVORSHIP. SOME PN SYMPTOMS MAY BE AMENABLE TO PREVENTIVE INTERVENTIONS TARGETED TO EPIGENETIC CLOCKS THAT INFLUENCE AGING-ASSOCIATED PROCESSES.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                      
12   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	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
13  5395  47 REDUCED EPIGENETIC AGE IN OLDER ADULTS WITH HIGH SENSE OF PURPOSE IN LIFE. PSYCHOSOCIAL RISK FACTORS HAVE BEEN LINKED WITH ACCELERATED EPIGENETIC AGING, BUT LITTLE IS KNOWN ABOUT WHETHER PSYCHOSOCIAL RESILIENCE FACTORS (EG, SENSE OF PURPOSE IN LIFE) MIGHT REDUCE EPIGENETIC AGE ACCELERATION. IN THIS STUDY, WE TESTED IF OLDER ADULTS WHO EXPERIENCE HIGH LEVELS OF PURPOSE MIGHT SHOW REDUCED EPIGENETIC AGE ACCELERATION. WE EVALUATED THE RELATIONSHIP BETWEEN PURPOSE AND EPIGENETIC AGE ACCELERATION AS MEASURED BY 13 DNA METHYLATION (DNAM) "EPIGENETIC CLOCKS" ASSESSED IN 1 572 OLDER ADULTS FROM THE HEALTH AND RETIREMENT STUDY (MEAN AGE 70 YEARS). WE QUANTIFIED THE TOTAL ASSOCIATION BETWEEN PURPOSE AND DNAM AGE ACCELERATION AS WELL AS THE EXTENT TO WHICH THAT TOTAL ASSOCIATION MIGHT BE ATTRIBUTABLE TO DEMOGRAPHIC FACTORS, CHRONIC DISEASE, OTHER PSYCHOSOCIAL VARIABLES (EG, POSITIVE AFFECT), AND HEALTH-RELATED BEHAVIORS (HEAVY DRINKING, SMOKING, PHYSICAL ACTIVITY, AND BODY MASS INDEX [BMI]). PURPOSE IN LIFE WAS ASSOCIATED WITH REDUCED EPIGENETIC AGE ACCELERATION ACROSS 4 "SECOND-GENERATION" DNAM CLOCKS OPTIMIZED FOR PREDICTING HEALTH AND LONGEVITY (FALSE DISCOVERY RATE [FDR] Q < 0.0001: PHENOAGE, GRIMAGE, ZHANG EPIGENETIC MORTALITY INDEX; FDR Q < 0.05: DUNEDINPOAM). THESE ASSOCIATIONS WERE INDEPENDENT OF DEMOGRAPHIC AND PSYCHOSOCIAL FACTORS, BUT SUBSTANTIALLY ATTENUATED AFTER ADJUSTING FOR HEALTH-RELATED BEHAVIORS (DRINKING, SMOKING, PHYSICAL ACTIVITY, AND BMI). PURPOSE SHOWED NO SIGNIFICANT ASSOCIATION WITH 9 "FIRST-GENERATION" DNAM EPIGENETIC CLOCKS TRAINED ON CHRONOLOGICAL AGE. OLDER ADULTS WITH GREATER PURPOSE IN LIFE SHOW "YOUNGER" DNAM EPIGENETIC AGE ACCELERATION. THESE RESULTS MAY BE DUE IN PART TO ASSOCIATED DIFFERENCES IN HEALTH-RELATED BEHAVIORS. RESULTS SUGGEST NEW OPPORTUNITIES TO REDUCE BIOLOGICAL AGE ACCELERATION BY ENHANCING PURPOSE AND ITS BEHAVIORAL SEQUELAE IN LATE ADULTHOOD.	2023	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                        
14  6743  76 WHITHER THE ETIOPATHOGENESIS (AND SCOLIOGENY) OF ADOLESCENT IDIOPATHIC SCOLIOSIS? INCORPORATING PRESENTATIONS ON SCOLIOGENY AT THE 2012 IRSSD AND SRS MEETINGS. THIS PAPER AIMS TO INTEGRATE INTO CURRENT UNDERSTANDING OF AIS CAUSATION, ETIOPATHOGENETIC INFORMATION PRESENTED AT TWO MEETINGS DURING 2012 NAMELY, THE INTERNATIONAL RESEARCH SOCIETY OF SPINAL DEFORMITIES (IRSSD) AND THE SCOLIOSIS RESEARCH SOCIETY (SRS). THE ULTIMATE HOPE IS TO PREVENT THE OCCURRENCE OR PROGRESSION OF THE SPINAL DEFORMITY OF AIS WITH NON-INVASIVE TREATMENT, POSSIBLY MEDICAL. THIS MIGHT BE ATTAINED BY PERSONALISED POLYMECHANISTIC PREVENTIVE THERAPY TARGETING THE APPROPRIATE ETIOLOGY AND/OR ETIOPATHOGENETIC PATHWAYS, TO AVOID FUSION AND MAINTAIN SPINAL MOBILITY. ALTHOUGH CONSIDERABLE PROGRESS HAD BEEN MADE IN THE PAST TWO DECADES IN UNDERSTANDING THE ETIOPATHOGENESIS OF ADOLESCENT IDIOPATHIC SCOLIOSIS (AIS), IT STILL LACKS AN AGREED THEORY OF ETIOPATHOGENESIS. ONE PROBLEM MAY BE THAT AIS RESULTS NOT FROM ONE CAUSE, BUT SEVERAL THAT INTERACT WITH VARIOUS GENETIC PREDISPOSING FACTORS. THERE IS A VIEW THERE ARE TWO OTHER PATHOGENIC PROCESSES FOR IDIOPATHIC SCOLIOSIS NAMELY, INITIATING (OR INDUCING), AND THOSE THAT CAUSE CURVE PROGRESSION. TWIN STUDIES AND OBSERVATIONS OF FAMILY AGGREGATION HAVE REVEALED SIGNIFICANT GENETIC CONTRIBUTIONS TO IDIOPATHIC SCOLIOSIS, THAT PLACE AIS AMONG OTHER COMMON DISEASE OR COMPLEX TRAITS WITH A HIGH HERITABILITY INTERPRETED BY THE GENETIC VARIANT HYPOTHESIS OF DISEASE. WE SUMMARIZE ETIOPATHOGENETIC KNOWLEDGE OF AIS AS THEORIES OF PATHOGENESIS INCLUDING RECENT MULTIPLE CONCEPTS, AND BLOOD TESTS FOR AIS BASED ON PREDICTIVE BIOMARKERS AND GENETIC VARIANTS THAT SIGNIFY DISEASE RISK. THERE IS INCREASING EVIDENCE FOR THE POSSIBILITY OF AN UNDERLYING NEUROLOGICAL DISORDER FOR AIS, RESEARCH WHICH HOLDS PROMISE. LIKE BRAIN RESEARCH, MOST AIS WORKERS FOCUS ON THEIR OWN CORNER AND THERE IS A NEED FOR GREATER INTEGRATION OF RESEARCH EFFORT. EPIGENETICS, A RELATIVELY RECENT FIELD, EVALUATES FACTORS CONCERNED WITH GENE EXPRESSION IN RELATION TO ENVIRONMENT, DISEASE, NORMAL DEVELOPMENT AND AGING, WITH A COMPLEX REGULATION ACROSS THE GENOME DURING THE FIRST DECADE OF LIFE. RESEARCH ON THE ROLE OF ENVIRONMENTAL FACTORS, EPIGENETICS AND CHRONIC NON-COMMUNICABLE DISEASES (NCDS) INCLUDING ADIPOSITY, AFTER A SLOW START, HAS EXPLODED IN THE LAST DECADE. NOT SO FOR AIS RESEARCH AND THE ENVIRONMENT WHERE, EXCEPT FOR MONOZYGOTIC TWIN STUDIES, THERE ARE ONLY SPORADIC REPORTS TO SUGGEST THAT ENVIRONMENTAL FACTORS ARE AT WORK IN ETIOLOGY. HERE, WE EXAMINE EPIGENETIC CONCEPTS AS THEY MAY RELATE TO HUMAN DEVELOPMENT, NORMAL LIFE HISTORY PHASES AND AIS PATHOGENESIS. ALTHOUGH AIS IS NOT REGARDED AS AN NCD, LIKE THEM, IT IS ASSOCIATED WITH WHOLE ORGANISM METABOLIC PHENOMENA, INCLUDING LOWER BODY MASS INDEX, LOWER CIRCULATING LEPTIN LEVELS AND OTHER SYSTEMIC DISORDERS. SOME EPIGENETIC RESEARCH APPLIED TO SILVER-RUSSELL SYNDROME AND ADIPOSITY IS EXAMINED, FROM WHICH SUGGESTIONS ARE MADE FOR CONSIDERATION OF AIS EPIGENETIC RESEARCH, CROSS-SECTIONAL AND LONGITUDINAL. THE WORD SCOLIOGENY IS SUGGESTED TO INCLUDE ETIOLOGY, PATHOGENESIS AND PATHOMECHANISM.	2013	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            
15  6742  67 WHITHER THE ETIOPATHOGENESIS (AND SCOLIOGENY) OF ADOLESCENT IDIOPATHIC SCOLIOSIS? ALTHOUGH CONSIDERABLE PROGRESS HAD BEEN MADE IN THE PAST TWO DECADES IN UNDERSTANDING THE ETIOPATHOGENESIS OF ADOLESCENT IDIOPATHIC SCOLIOSIS (AIS), IT STILL LACKS AN AGREED THEORY OF ETIOPATHOGENESIS. ONE PROBLEM MAY BE THAT AIS RESULTS NOT FROM ONE CAUSE, BUT SEVERAL THAT INTERACT WITH VARIOUS GENETIC PREDISPOSING FACTORS. THERE IS A VIEW THERE ARE TWO OTHER PATHOGENIC PROCESSES FOR IDIOPATHIC SCOLIOSIS NAMELY, INITIATING (OR INDUCING), AND THOSE THAT CAUSE CURVE PROGRESSION. TWIN STUDIES AND OBSERVATIONS OF FAMILY AGGREGATION HAVE REVEALED SIGNIFICANT GENETIC CONTRIBUTIONS TO IDIOPATHIC SCOLIOSIS, THAT PLACE AIS AMONG OTHER COMMON DISEASE OR COMPLEX TRAITS WITH A HIGH HERITABILITY INTERPRETED BY THE GENETIC VARIANT HYPOTHESIS OF DISEASE. WE SUMMARIZE ETIOPATHOGENETIC KNOWLEDGE OF AIS AS THEORIES OF PATHOGENESIS INCLUDING RECENT MULTIPLE CONCEPTS, AND BLOOD TESTS FOR AIS BASED ON PREDICTIVE BIOMARKERS AND GENETIC VARIANTS THAT SIGNIFY DISEASE RISK. THERE IS INCREASING EVIDENCE FOR THE POSSIBILITY OF AN UNDERLYING NEUROLOGICAL DISORDER FOR AIS, RESEARCH WHICH HOLDS PROMISE. LIKE BRAIN RESEARCH, MOST AIS WORKERS FOCUS ON THEIR OWN CORNER AND THERE IS A NEED FOR GREATER INTEGRATION OF RESEARCH EFFORT. EPIGENETICS, A RELATIVELY RECENT FIELD, EVALUATES FACTORS CONCERNED WITH GENE EXPRESSION IN RELATION TO ENVIRONMENT, DISEASE, NORMAL DEVELOPMENT AND AGING, WITH A COMPLEX REGULATION ACROSS THE GENOME DURING THE FIRST DECADE OF LIFE. RESEARCH ON THE ROLE OF ENVIRONMENTAL FACTORS, EPIGENETICS AND CHRONIC NON-COMMUNICABLE DISEASES (NCDS) INCLUDING ADIPOSITY, AFTER A SLOW START, HAS EXPLODED IN THE LAST DECADE. NOT SO FOR AIS RESEARCH AND THE ENVIRONMENT WHERE, EXCEPT FOR MONOZYGOTIC TWIN STUDIES, THERE ARE ONLY SPORADIC REPORTS TO SUGGEST THAT ENVIRONMENTAL FACTORS ARE AT WORK IN ETIOLOGY. HERE, WE EXAMINE EPIGENETIC CONCEPTS AS THEY MAY RELATE TO HUMAN DEVELOPMENT, NORMAL LIFE HISTORY PHASES AND AIS PATHOGENESIS. ALTHOUGH AIS IS NOT REGARDED AS AN NCD, LIKE THEM, IT IS ASSOCIATED WITH WHOLE ORGANISM METABOLIC PHENOMENA, INCLUDING LOWER BODY MASS INDEX, LOWER CIRCULATING LEPTIN LEVELS AND OTHER SYSTEMIC DISORDERS. SOME EPIGENETIC RESEARCH APPLIED TO SILVER-RUSSELL SYNDROME AND ADIPOSITY IS EXAMINED, FROM WHICH SUGGESTIONS ARE MADE FOR CONSIDERATION OF AIS EPIGENETIC RESEARCH, CROSS-SECTIONAL AND LONGITUDINAL. THE WORD SCOLIOGENY IS SUGGESTED TO INCLUDE ETIOLOGY, PATHOGENESIS AND PATHOMECHANISM.	2012	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
16  3850  48 IS GENDER A FACTOR AFFECTING LONG-TERM HETEROTOPIC OSSIFICATION INCIDENCE AFTER SINGLE-LEVEL CERVICAL DISC ARTHROPLASTY? BACKGROUND: CERVICAL DISC DISEASES HAVE BEEN TREATED BY CERVICAL DISC ARTHROPLASTY (CDA). NEVERTHELESS, SOME PATIENTS WILL EXPERIENCE A MOBILITY FAILURE IN THEIR CERVICAL PROSTHESES OVER TIME BECAUSE OF HETEROTOPIC OSSIFICATION. THE AIM OF THIS STUDY WAS TO INVESTIGATE THE ROLE OF GENDER IN LONG-TERM OUTCOMES AFTER CDA. METHODS: A RETROSPECTIVE, SINGLE-CENTER STUDY OF PATIENTS WHO UNDERWENT SINGLE-LEVEL CDA WITH A BRYAN CERVICAL DISC PROSTHESIS WAS PERFORMED, INCLUDING A NARRATIVE REVIEW ABOUT GENDER DIFFERENCES IN BOTH STRUCTURAL AND BIOMECHANICAL FEATURES OF THE CERVICAL SPINE. RESULTS: STUDY PATIENTS (14 MEN, 30 WOMEN) HAD AN AVERAGE FOLLOW-UP OF 9.8 +/- 3.2 YEARS. SIGNIFICANT DIFFERENCES EMERGED BETWEEN GENDERS FOR SPECIFIC ITEMS IN NECK DISABILITY INDEX PREOPERATIVE EVALUATION, WITH WOMEN REPORTING WORSE PAIN SCORES (P = 0.05). AFTER STRATIFICATION BY AGE, WE FOUND A HIGHER PREOPERATIVE OVERALL NECK DISABILITY INDEX SCORE FOR FEMALE PATIENTS <36 YEARS OF AGE (P = 0.03). IN AN INTERGENDER, BODY MASS INDEX-SPECIFIC COMPARISON, WE ALSO FOUND A SIGNIFICANT DIFFERENCE IN NECK DISABILITY INDEX PREOPERATIVE SCORE WITH NORMAL-WEIGHT MALE PATIENTS FARING WORSE THAN OVERWEIGHT MALE PATIENTS (P = 0.05). AT A RADIOLOGICAL LEVEL, WE FOUND A TENDENCY TOWARD A HIGHER HETEROTOPIC OSSIFICATION INCIDENCE IN MALE PATIENTS (62% IN MEN, 17% IN WOMEN, P = 0.06). THE FEMALE CERVICAL SPINE HAS DISTINCTIVE FEATURES, INCLUDING BONE STRUCTURE, MUSCULAR ACTION, SOFT TISSUE RESPONSE, AND GENETIC AND EPIGENETIC RESPONSE TO OSTEOARTHRITIS. CONCLUSIONS: THE INCIDENCE OF MOBILITY FAILURE IN OUR SERIES OF SINGLE-LEVEL CDA WAS LOWER IN FEMALE PATIENTS. SEVERAL GENDER-SPECIFIC FACTORS BOTH IN STATIC AND IN DYNAMIC FEATURES MAY PLAY A SIGNIFICANT ROLE IN SPINAL PATHOLOGY AND CDA LONG-TERM RADIOLOGICAL OUTCOME.	2022	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                         
17  5612  72 SAFETY AND ACTIVITY OF RRX-001 IN PATIENTS WITH ADVANCED CANCER: A FIRST-IN-HUMAN, OPEN-LABEL, DOSE-ESCALATION PHASE 1 STUDY. BACKGROUND: EPIGENETIC ALTERATIONS HAVE BEEN STRONGLY ASSOCIATED WITH TUMOUR FORMATION AND RESISTANCE TO CHEMOTHERAPEUTIC DRUGS, AND EPIGENETIC MODIFICATIONS ARE AN ATTRACTIVE TARGET IN CANCER RESEARCH. RRX-001 IS ACTIVATED BY HYPOXIA AND INDUCES THE GENERATION OF REACTIVE OXYGEN AND NITROGEN SPECIES THAT CAN EPIGENETICALLY MODULATE DNA METHYLATION, HISTONE DEACETYLATION, AND LYSINE DEMETHYLATION. THE AIM OF THIS PHASE 1 STUDY WAS TO ASSESS THE SAFETY, TOLERABILITY, AND PHARMACOKINETICS OF RRX-001. METHODS: IN THIS OPEN-LABEL, DOSE-ESCALATION, PHASE 1 STUDY, WE RECRUITED ADULT PATIENTS (AGED >18 YEARS) WITH HISTOLOGICALLY OR CYTOLOGICALLY CONFIRMED DIAGNOSIS OF ADVANCED, MALIGNANT, INCURABLE SOLID TUMOURS FROM UNIVERSITY OF CALIFORNIA AT SAN DIEGO, CA, USA, AND SARAH CANNON RESEARCH INSTITUTE, NASHVILLE, TN, USA. KEY ELIGIBILITY CRITERIA INCLUDED EVALUABLE DISEASE, EASTERN COOPERATIVE GROUP PERFORMANCE STATUS OF 2 OR LESS, AN ESTIMATED LIFE EXPECTANCY OF AT LEAST 12 WEEKS, ADEQUATE LABORATORY PARAMETERS, DISCONTINUATION OF ALL PREVIOUS ANTINEOPLASTIC THERAPIES AT LEAST 6 WEEKS BEFORE INTERVENTION, AND NO RESIDUAL SIDE-EFFECTS FROM PREVIOUS THERAPIES. PATIENTS WERE ASSIGNED TO RECEIVE INTRAVENOUS INFUSIONS OF RRX-001 AT INCREASING DOSES (10 MG/M(2), 16.7 MG/M(2), 24.6 MG/M(2), 33 MG/M(2), 55 MG/M(2), AND 83 MG/M(2)) EITHER ONCE OR TWICE-WEEKLY FOR AT LEAST 4 WEEKS, WITH AT LEAST THREE PATIENTS PER DOSE COHORT AND ALLOWING A 2-WEEK OBSERVATION PERIOD BEFORE DOSE ESCALATION. SAMPLES FOR SAFETY AND PHARMACOKINETICS ANALYSIS, INCLUDING STANDARD CHEMISTRY AND HAEMATOLOGICAL PANELS, WERE TAKEN ON EACH TREATMENT DAY. THE PRIMARY OBJECTIVE WAS TO ASSESS SAFETY, TOLERABILITY, AND DOSE-LIMITING TOXIC EFFECTS OF RRX-001, TO DETERMINE SINGLE-DOSE PHARMACOKINETICS, AND TO IDENTIFY A RECOMMENDED DOSE FOR PHASE 2 TRIALS. ALL ANALYSES WERE DONE PER PROTOCOL. ACCRUAL IS COMPLETE AND FOLLOW-UP IS STILL ON-GOING. THIS TRIAL IS REGISTERED WITH CLINICALTRIALS.GOV, NUMBER NCT01359982. FINDINGS: BETWEEN OCT 10, 2011, AND MARCH 18, 2013, WE ENROLLED 25 PATIENTS AND TREATED SIX PATIENTS IN THE 10 MG/M(2) COHORT, THREE PATIENTS IN THE 16.7 MG/M(2) COHORT, THREE PATIENTS IN THE 24.6 MG/M(2) COHORT, FOUR PATIENTS IN THE 33 MG/M(2) COHORT, THREE PATIENTS IN THE 55 MG/M(2), AND SIX PATIENTS IN THE 83 MG/M(2) COHORT. PAIN AT THE INJECTION SITE, MOSTLY GRADE 1 AND GRADE 2, WAS THE MOST COMMON ADVERSE EVENT RELATED TO TREATMENT, EXPERIENCED BY 21 (84%) PATIENTS. OTHER COMMON DRUG-RELATED ADVERSE EVENTS INCLUDED ARM SWELLING OR OEDEMA (EIGHT [32%] PATIENTS), AND VEIN HARDENING (SEVEN [28%] PATIENTS). NO DOSE-LIMITING TOXICITIES WERE OBSERVED. TIME CONSTRAINTS RELATED TO MANAGEMENT OF INFUSION PAIN FROM RRX-001 RESULTED IN A MAXIMALLY FEASIBLE DOSE OF 83 MG/M(2). OF THE 21 EVALUABLE PATIENTS, ONE (5%) PATIENT HAD A PARTIAL RESPONSE, 14 (67%) PATIENTS HAD STABLE DISEASE, AND SIX (29%) PATIENTS HAD PROGRESSIVE DISEASE; ALL RESPONSES WERE ACROSS A VARIETY OF TUMOUR TYPES. FOUR PATIENTS WHO HAD RECEIVED RRX-001 WERE SUBSEQUENTLY RECHALLENGED WITH A TREATMENT THAT THEY HAD BECOME REFRACTORY TO; ALL FOUR RESPONDED TO THE RECHALLENGE. INTERPRETATION: RRX-001 IS A WELL-TOLERATED NOVEL COMPOUND WITHOUT CLINICALLY SIGNIFICANT TOXIC EFFECTS AT THE TESTED DOSES. PRELIMINARY EVIDENCE OF ACTIVITY IS PROMISING AND, ON THE BASIS OF ALL FINDINGS, A DOSE OF 16.7 MG/M(2) WAS RECOMMENDED AS THE TARGETED DOSE FOR PHASE 2 TRIALS. FUNDING: EPICENTRX (FORMERLY RADIORX).	2015	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
18   108  41 A REVIEW OF THE PROTECTIVE EFFECT OF MELATONIN IN PESTICIDE-INDUCED TOXICITY. PESTICIDES ARE AMONG THE MOST IMPORTANT CHEMICALS USED IN AGRICULTURE SECTOR. HOWEVER, THEIR EXTENSIVE USE HAS POLLUTED THE ENVIRONMENT AND INCREASED HUMAN VULNERABILITY TO VARIOUS CHRONIC DISEASES. PESTICIDE EXPOSURE CAUSES GENETIC AND EPIGENETIC MODIFICATIONS, ENDOCRINE DISRUPTION, MITOCHONDRIAL DYSFUNCTION AND OXIDATIVE STRESS. AREAS COVERED: THIS REVIEW IS BASED ON THE LITERATURE STUDIES CURRENTLY REPORTED ON PESTICIDE-INDUCED TOXICITY AND THE PROTECTIVE ROLE OF MELATONIN. SCIENTIFIC DATABASES SUCH AS PUBMED, SCOPUS AND WEB OF SCIENCE WERE SEARCHED USING KEYWORDS 'PESTICIDE' AND 'MELATONIN' UP TO JANUARY 2016. FULL LENGTH ARTICLES RELATED TO ANIMAL AND HUMAN EXPOSURE WERE RETRIEVED. A TOTAL NUMBER OF 181 RECORDS WERE OBTAINED, AND AFTER EXCLUDING THE DUPLICATES, 97 PAPERS WERE FURTHER SCREENED ON THE BASIS OF RELEVANCE TO THE TOPIC. EXPERT OPINION: MELATONIN AS A BROAD-SPECTRUM ANTIOXIDANT IS ABLE TO PENETRATE CELLULAR COMPARTMENTS SPECIFICALLY THE MITOCHONDRIA. IT IS A POTENT FREE RADICAL SCAVENGER WITH LOW TOXICITY AND DESIRABLE SOLUBILITY IN ORGANIC AND AQUEOUS PHASES. WE ARE OF THE OPINION THAT MELATONIN IS A PROMISING AGENT IN MINIMIZING ORGAN INJURIES INDUCED BY PESTICIDES.	2017	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
19  3179  57 HAIR CORTISOL AS A HYPOTHALAMIC-PITUITARY-ADRENAL AXIS BIOMARKER IN PREGNANT WOMEN WITH ASTHMA: A RETROSPECTIVE OBSERVATIONAL STUDY. BACKGROUND: CORTISOL IS A HORMONE INVOLVED IN MANY PHYSIOLOGICAL FUNCTIONS INCLUDING FETAL MATURATION AND EPIGENETIC PROGRAMMING DURING PREGNANCY. THIS STUDY AIMED TO USE HAIR CORTISOL AS A BIOMARKER OF CHRONIC INHALED CORTICOSTEROID (ICS) EXPOSURE AND ASSESS THE POTENTIAL EFFECTS OF ASTHMA ON THE HYPOTHALAMIC-PITUITARY-ADRENAL (HPA) AXIS IN PREGNANT WOMEN. WE HYPOTHESIZED THAT PREGNANT WOMEN WITH ASTHMA TREATED WITH ICS WOULD EXHIBIT LOWER HAIR CORTISOL CONCENTRATIONS, INDICATIVE OF ADRENAL SUPPRESSION, COMPARED TO WOMEN WITH ASTHMA NOT USING ICS AND WOMEN WHO DO NOT HAVE ASTHMA. METHODS: WE PERFORMED AN OBSERVATIONAL RETROSPECTIVE COHORT STUDY. HAIR SAMPLES WERE ANALYZED FROM PREGNANT WOMEN WITH ASTHMA, WITH (N = 56) AND WITHOUT (N = 31) ICS TREATMENT, AND PREGNANT WOMEN WITHOUT ASTHMA (N = 31). HAIR SAMPLES WERE SEGMENTED BASED ON THE GROWTH RATE OF 1 CM/MONTH AND ANALYZED BY ENZYME IMMUNOASSAY TO PROVIDE CORTISOL CONCENTRATIONS CORRESPONDING TO PRECONCEPTION, TRIMESTERS 1-3, AND POSTPARTUM. HAIR CORTISOL CONCENTRATIONS WERE COMPARED WITHIN AND AMONG THE GROUPS USING NON-PARAMETRIC STATISTICAL TESTS. RESULTS: HAIR CORTISOL CONCENTRATIONS INCREASED ACROSS TRIMESTERS FOR ALL THREE GROUPS, BUT THIS INCREASE WAS DAMPENED IN WOMEN WITH ASTHMA (P = 0.03 FOR CONTROLS VS. ICS TREATED AND CONTROLS VS. NO ICS). ICS TREATED WOMEN TAKING MORE THAN FIVE DOSES PER WEEK HAD HAIR CORTISOL CONCENTRATIONS 47 % LOWER IN THIRD TRIMESTER THAN CONTROLS. LINEAR REGRESSION OF THE THIRD TRIMESTER HAIR CORTISOL RESULTS IDENTIFIED ASTHMA AS A SIGNIFICANT FACTOR WHEN COMPARING CONSISTENT ICS USE OR ASTHMA AS THE PREDICTOR (F(1, 25) = 9.7, P = 0.005, R(2) ADJ = 0.257). CONCLUSIONS: HAIR CORTISOL SUCCESSFULLY SHOWED THE EXPECTED CHANGE IN CORTISOL OVER THE COURSE OF PREGNANCY AND MAY BE A USEFUL BIOMARKER OF HPA AXIS FUNCTION IN PREGNANT WOMEN WITH ASTHMA. THE POTENTIAL IMPACT OF DECREASED MATERNAL CORTISOL IN WOMEN WITH ASTHMA ON PERINATAL OUTCOMES REMAINS TO BE DETERMINED.	2016	
                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                
20   190  46 ACETYL-L-CARNITINE IN PAINFUL PERIPHERAL NEUROPATHY: A SYSTEMATIC REVIEW. ACETYL-L-CARNITINE (ALC) HAS SHOWN A NEUROPROTECTIVE EFFECT IN PATIENTS WITH PERIPHERAL NEUROPATHIES OF DIFFERENT ETIOLOGIES. PRECLINICAL STUDIES DEMONSTRATED A CENTRAL ANTI-NOCICEPTIVE ACTION, BOTH IN NEUROPATHIC AND NOCICEPTIVE PAIN MODELS. THE PRESENT REVIEW AIMS TO PROVIDE THE KNOWLEDGE ON THE EFFICACY OF ALC IN PATIENTS WITH PAINFUL PERIPHERAL NEUROPATHY, BASED ON THE EVIDENCE. CONSISTENT WITH THE PRISMA STATEMENT, AUTHORS SEARCHED PUBMED, EMBASE AND THE COCHRANE DATABASE OF SYSTEMATIC REVIEWS FOR RELEVANT PAPERS, INCLUDING THOSE ISSUED BEFORE APRIL 2018. TWO AUTHORS INDEPENDENTLY SELECTED STUDIES FOR INCLUSION AND DATA EXTRACTION: ONLY TRIALS INCLUDING PATIENTS WITH A DIAGNOSIS OF PERIPHERAL NEUROPATHY AND INVOLVING AT LEAST 10 PATIENTS WERE CONSIDERED FOR THE PURPOSES OF THIS REVIEW. FOURTEEN CLINICAL TRIALS WERE REVISED, TO PROVIDE THE LEVEL OF EVIDENCE FOR NEUROPATHY. TO ASSESS THE GLOBAL EFFICACY OF ALC IN PAINFUL PERIPHERAL NEUROPATHY, A META-ANALYSIS OF FOUR RANDOMIZED CONTROLLED TRIALS WAS PERFORMED. MEAN DIFFERENCE IN PAIN REDUCTION AS MEASURED ON A 10-CM VAS, AND 95% CIS WERE USED FOR POOLING CONTINUOUS DATA FROM EACH TRIAL. FOUR RANDOMIZED CONTROLLED TRIALS TESTED ALC IN PATIENTS WITH NEUROPATHY SECONDARY TO DIABETES AND TO ANTIRETROVIRAL THERAPY FOR HIV. COMPARED TO PLACEBO, ALC PRODUCED A SIGNIFICANT PAIN REDUCTION EQUAL TO 20.2% (95% CI: 8.3%-32.1%, P<0.0001) WITH RESPECT TO BASELINE. CLINICAL TRIALS ALSO SHOWED BENEFICIAL EFFECTS ON NERVE CONDUCTION PARAMETERS AND NERVE FIBER REGENERATION, WITH A GOOD SAFETY PROFILE. THESE DATA INDICATE THAT ALC PROVIDES AN EFFECTIVE AND SAFE TREATMENT IN PATIENTS WITH PAINFUL PERIPHERAL NEUROPATHY. WE RECOMMEND FURTHER STUDIES TO ASSESS THE OPTIMAL DOSE AND DURATION OF THE THERAPEUTIC EFFECT (ALSO AFTER TREATMENT WITHDRAWAL).	2019