1 2273 169 EPIGENETIC REGULATION ALTERS BIOFILM ARCHITECTURE AND COMPOSITION IN MULTIPLE CLINICAL ISOLATES OF NONTYPEABLE HAEMOPHILUS INFLUENZAE. BIOFILMS PLAY A CRITICAL ROLE IN THE COLONIZATION, PERSISTENCE, AND PATHOGENESIS OF MANY HUMAN PATHOGENS. MULTIPLE MUCOSA-ASSOCIATED PATHOGENS HAVE EVOLVED A MECHANISM OF RAPID ADAPTATION, TERMED THE PHASEVARION, WHICH FACILITATES A COORDINATED REGULATION OF NUMEROUS GENES THROUGHOUT THE BACTERIAL GENOME. THIS EPIGENETIC REGULATION OCCURS VIA PHASE VARIATION OF A DNA METHYLTRANSFERASE, MOD. THE PHASEVARION OF NONTYPEABLE HAEMOPHILUS INFLUENZAE (NTHI) SIGNIFICANTLY AFFECTS THE SEVERITY OF EXPERIMENTAL OTITIS MEDIA AND REGULATES SEVERAL DISEASE-RELATED PROCESSES. HOWEVER, THE ROLE OF THE NTHI PHASEVARION IN BIOFILM FORMATION IS UNCLEAR. THE PRESENT STUDY SHOWS THAT THE PHASEVARIONS OF MULTIPLE NTHI CLINICAL ISOLATES REGULATE IN VITRO BIOFILM FORMATION UNDER DISEASE-SPECIFIC MICROENVIRONMENTAL CONDITIONS. THE IMPACT OF PHASEVARION REGULATION WAS GREATEST UNDER ALKALINE CONDITIONS THAT MIMIC THOSE KNOWN TO OCCUR IN THE MIDDLE EAR DURING DISEASE. UNDER ALKALINE CONDITIONS, NTHI STRAINS THAT EXPRESS THE MODA2 METHYLTRANSFERASE FORMED BIOFILMS WITH SIGNIFICANTLY GREATER BIOMASS AND LESS DISTINCT ARCHITECTURE THAN THOSE FORMED BY A MODA2-DEFICIENT POPULATION. THE BIOFILMS FORMED BY NTHI STRAINS THAT EXPRESS MODA2 ALSO CONTAINED LESS EXTRACELLULAR DNA (EDNA) AND SIGNIFICANTLY LESS EXTRACELLULAR HU, A DNABII DNA-BINDING PROTEIN CRITICAL FOR BIOFILM STRUCTURAL STABILITY. STABLE BIOFILM STRUCTURE IS CRITICAL FOR BACTERIAL PATHOGENESIS AND PERSISTENCE IN MULTIPLE EXPERIMENTAL MODELS OF DISEASE. THESE RESULTS IDENTIFY A ROLE FOR THE PHASEVARION IN REGULATION OF BIOFILM FORMATION, A PROCESS INTEGRAL TO THE CHRONIC NATURE OF MANY INFECTIONS. UNDERSTANDING THE ROLE OF THE PHASEVARION IN BIOFILM FORMATION IS CRITICAL TO THE DEVELOPMENT OF PREVENTION AND TREATMENT STRATEGIES FOR THESE CHRONIC DISEASES.IMPORTANCE UPPER RESPIRATORY TRACT INFECTIONS ARE THE NUMBER ONE REASON FOR A CHILD TO VISIT THE EMERGENCY DEPARTMENT, AND OTITIS MEDIA (MIDDLE EAR INFECTION) RANKS THIRD OVERALL. BIOFILMS CONTRIBUTE SIGNIFICANTLY TO THE CHRONIC NATURE OF BACTERIAL RESPIRATORY TRACT INFECTIONS, INCLUDING OTITIS MEDIA, AND MAKE THESE DISEASES PARTICULARLY DIFFICULT TO TREAT. SEVERAL MUCOSA-ASSOCIATED HUMAN PATHOGENS UTILIZE A MECHANISM OF RAPID ADAPTATION TERMED THE PHASEVARION, OR PHASEVARIABLE REGULON, TO RESIST ENVIRONMENTAL AND HOST IMMUNE PRESSURES. IN THIS STUDY, WE ASSESSED THE ROLE OF THE PHASEVARION IN REGULATION OF BIOFILM FORMATION BY NONTYPEABLE HAEMOPHILUS INFLUENZAE (NTHI), WHICH CAUSES NUMEROUS RESPIRATORY TRACT DISEASES. WE FOUND THAT THE NTHI PHASEVARION REGULATES BIOFILM STRUCTURE AND CRITICAL BIOFILM MATRIX COMPONENTS UNDER DISEASE-SPECIFIC CONDITIONS. THE FINDINGS OF THIS WORK COULD BE SIGNIFICANT IN THE DESIGN OF IMPROVED STRATEGIES AGAINST NTHI INFECTIONS, AS WELL AS DISEASES DUE TO OTHER PATHOGENS THAT UTILIZE A PHASEVARION. 2018 2 5016 40 PERSISTENT BACTERIAL COINFECTION OF A COVID-19 PATIENT CAUSED BY A GENETICALLY ADAPTED PSEUDOMONAS AERUGINOSA CHRONIC COLONIZER. PSEUDOMONAS AERUGINOSA IS A BIOFILM-FORMING OPPORTUNISTIC PATHOGEN WHICH CAUSES CHRONIC INFECTIONS IN IMMUNOCOMPROMISED PATIENTS AND LEADS TO HIGH MORTALITY RATE. IT IS IDENTIFIED AS A COMMON COINFECTING PATHOGEN IN COVID-19 PATIENTS CAUSING EXACERBATION OF ILLNESS. IN OUR HOSPITAL, P. AERUGINOSA IS ONE OF THE TOP COINFECTING BACTERIA IDENTIFIED AMONG COVID-19 PATIENTS. WE COLLECTED A STRONG BIOFILM-FORMING P. AERUGINOSA STRAIN DISPLAYING SMALL COLONY VARIANT MORPHOLOGY FROM A SEVERE COVID-19 PATIENT. GENOMIC AND TRANSCRIPTOMIC SEQUENCING ANALYSES WERE PERFORMED WITH PHENOTYPIC VALIDATION TO INVESTIGATE ITS ADAPTATION IN SARS-COV-2 INFECTED ENVIRONMENT. GENOMIC CHARACTERIZATION PREDICTED SPECIFIC GENOMIC ISLANDS HIGHLY ASSOCIATED WITH VIRULENCE, TRANSCRIPTIONAL REGULATION, AND DNA RESTRICTION-MODIFICATION SYSTEMS. EPIGENETIC ANALYSIS REVEALED A SPECIFIC N(6)-METHYL ADENINE (M(6)A) METHYLATING PATTERN INCLUDING METHYLATION OF ALGINATE, FLAGELLAR AND QUORUM SENSING ASSOCIATED GENES. DIFFERENTIAL GENE EXPRESSION ANALYSIS INDICATED THAT THIS ISOLATE FORMED EXCESSIVE BIOFILM BY REDUCING FLAGELLAR FORMATION (7.4 TO 1,624.1 FOLDS) AND OVERPRODUCING EXTRACELLULAR MATRIX COMPONENTS INCLUDING CDRA (4.4 FOLDS), ALGINATE (5.2 TO 29.1 FOLDS) AND PEL (4.8-5.5 FOLDS). IN SUMMARY, WE DEMONSTRATED THAT P. AEUGINOSA CLINICAL ISOLATES WITH NOVEL EPIGENETIC MARKERS COULD FORM EXCESSIVE BIOFILM, WHICH MIGHT ENHANCE ITS ANTIBIOTIC RESISTANCE AND IN VIVO COLONIZATION IN COVID-19 PATIENTS. 2021 3 4523 56 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 4 4395 43 MODM DNA METHYLTRANSFERASE METHYLOME ANALYSIS REVEALS A POTENTIAL ROLE FOR MORAXELLA CATARRHALIS PHASEVARIONS IN OTITIS MEDIA. MORAXELLA CATARRHALIS IS A SIGNIFICANT CAUSE OF OTITIS MEDIA AND EXACERBATIONS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE. HERE, WE CHARACTERIZE A PHASE-VARIABLE DNA METHYLTRANSFERASE (MODM), WHICH CONTAINS 5'-CAAC-3' REPEATS IN ITS OPEN READING FRAME THAT MEDIATE HIGH-FREQUENCY MUTATION RESULTING IN REVERSIBLE ON/OFF SWITCHING OF MODM EXPRESSION. THREE MODM ALLELES HAVE BEEN IDENTIFIED (MODM1-3), WITH MODM2 BEING THE MOST COMMONLY FOUND ALLELE. USING SINGLE-MOLECULE, REAL-TIME (SMRT) GENOME SEQUENCING AND METHYLOME ANALYSIS, WE HAVE DETERMINED THAT THE MODM2 METHYLATION TARGET IS 5'-GAR(M6)AC-3', AND 100% OF THESE SITES ARE METHYLATED IN THE GENOME OF THE M. CATARRHALIS 25239 MODM2 ON STRAIN. PROTEOMIC ANALYSIS OF MODM2 ON AND OFF VARIANTS REVEALED THAT MODM2 REGULATES EXPRESSION OF MULTIPLE GENES THAT HAVE POTENTIAL ROLES IN COLONIZATION, INFECTION, AND PROTECTION AGAINST HOST DEFENSES. INVESTIGATION OF THE DISTRIBUTION OF MODM ALLELES IN A PANEL OF M. CATARRHALIS STRAINS, ISOLATED FROM THE NASOPHARYNX OF HEALTHY CHILDREN OR MIDDLE EAR EFFUSIONS FROM PATIENTS WITH OTITIS MEDIA, REVEALED A STATISTICALLY SIGNIFICANT ASSOCIATION OF MODM3 WITH OTITIS MEDIA ISOLATES. THE MODULATION OF GENE EXPRESSION VIA THE MODM PHASE-VARIABLE REGULON (PHASEVARION), AND THE SIGNIFICANT ASSOCIATION OF THE MODM3 ALLELE WITH OTITIS MEDIA, SUGGESTS A KEY ROLE FOR MODM PHASEVARIONS IN THE PATHOGENESIS OF THIS ORGANISM. 2014 5 1673 30 DRIVER GENE MUTATIONS AND EPIGENETICS IN COLORECTAL CANCER. OBJECTIVE: THE MAJORITY OF PATIENTS WITH COLORECTAL CANCER ARE DIAGNOSED WITH LOCALLY ADVANCED AND/OR DISSEMINATED DISEASE, AND TREATMENT OPTIONS INCLUDE SURGERY IN COMBINATION WITH CYTOTOXIC CHEMOTHERAPY REGIMENS, BIOLOGICS, AND/OR RADIOTHERAPY. THUS, COLORECTAL CANCER REMAINS A HEAVY BURDEN ON SOCIETY AND HEALTH CARE SYSTEMS.MOUNTING EVIDENCE SHOW THAT DRIVER GENE MUTATIONS PLAY ONLY PART OF THE ROLE IN CARCINOGENESIS. EPIGENETICS ARE STRONGLY IMPLICATED IN INITIATION AND PROGRESSION OF COLORECTAL CANCER ALONG WITH MAJOR PLAYERS SUCH AS INTESTINAL MICROBIOTIC DYSBIOSIS AND CHRONIC MUCOSAL INFLAMMATION.TO ASSESS PHENOTYPIC CHANGES IN PROTEINS AND GENE EXPRESSION, MULTIGENE EXPRESSION SIGNATURES BASED ON SEQUENCING TECHNIQUES HAVE BEEN DEVELOPED TO HOPEFULLY IMPROVE PREDICTORS OF THE TUMOR PROFILE, IMMUNE RESPONSE, AND THERAPEUTIC OUTCOMES. OUR OBJECTIVE WAS TO REVIEW CURRENT ADVANCES IN THE FIELD AND TO UPDATE SURGEONS AND ACADEMICS ON DRIVER GENE MUTATIONS AND EPIGENETICS IN COLORECTAL CANCER. BACKGROUND AND METHODS: THIS IS A NARRATIVE REVIEW STUDYING RELEVANT RESEARCH PUBLISHED IN THE PUBMED DATABASE FROM 2012-2018. RESULTS AND CONCLUSION: INCREASED UNDERSTANDING OF THE MOLECULAR BIOLOGY WILL IMPROVE OPTIONS TO CHARACTERIZE COLORECTAL CANCER WITH REGARD TO MUTATIONS AND MOLECULAR PATHWAYS, INCLUDING MICROSATELLITE INSTABILITY, EPIGENETICS, MICROBIOTA, AND MICROENVIRONMENT. RESEARCH WILL INEVITABLY IMPROVE RISK GROUP STRATIFICATION AND TARGETED TREATMENT APPROACHES.EPIGENETIC PROFILING AND EPIGENETIC MODULATING DRUGS WILL INCREASE RISK STRATIFICATION, INCREASE ACCESSIBILITY FOR DNA TARGETING CHEMOTHERAPEUTICS AND REDUCE CYTOTOXIC DRUG RESISTANCE.NEW GENERATION ANTIBIOTICS SUCH AS BIOFILM INHIBITORS AND QUORUM SENSING INHIBITORS ARE BEING DEVELOPED TO TARGET THE CARCINOGENETIC IMPACT OF COLONIC DYSBIOSIS AND INFLAMMATION. 2020 6 1124 21 COMPLETE GENOME SEQUENCE OF MORAXELLA CATARRHALIS STRAIN CCRI-195ME, ISOLATED FROM THE MIDDLE EAR. MORAXELLA CATARRHALIS IS AN IMPORTANT BACTERIAL PATHOGEN THAT CAUSES OTITIS MEDIA AND EXACERBATIONS OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE. HERE, WE REPORT THE COMPLETE GENOME SEQUENCE OF M. CATARRHALIS STRAIN CCRI-195ME, WHICH CONTAINS THE PHASE-VARIABLE EPIGENETIC REGULATOR MODM3. 2017 7 5286 29 PRORESOLVING LIPID MEDIATORS: POTENTIAL FOR PREVENTION AND TREATMENT OF PERIODONTITIS. AIM: PERIODONTITIS IS AN INFLAMMATORY DISEASE INITIATED BY MICROBIAL BIOFILM. THE HOST RESPONSE TO THE BIOFILM DESTROYS THE PERIODONTIUM MEDIATED BY AN OVERLY ROBUST INFLAMMATORY RESPONSE IN SUSCEPTIBLE INDIVIDUALS. WHETHER THE EXCESSIVE HOST RESPONSE IS GENETIC, EPIGENETIC OR MEDIATED BY ENVIRONMENT IS UNKNOWN. NEW PATHWAYS OF RESOLUTION OF INFLAMMATION HAVE BEEN DISCOVERED. RESOLUTION OF INFLAMMATION IS AN ACTIVE, AGONIST-MEDIATED, PROGRAMMED RETURN TO TISSUE HOMEOSTASIS. MATERIALS AND METHODS: VARIOUS COMPUTER-BASED SEARCH ENGINES WERE EMPLOYED TO IDENTIFY PAPERS RELEVANT TO RESOLUTION OF INFLAMMATION. RESULTS: RECENT DATA SUGGEST THAT CHRONIC INFLAMMATORY PERIODONTAL DISEASE MAY BE A FAILURE OF RESOLUTION PATHWAYS AS WELL AS OVEREXPRESSION OF PROINFLAMMATORY PATHWAYS. IN THIS REVIEW, THE BIOLOGY OF RESOLUTION OF INFLAMMATION WILL BE EXAMINED IN NORMAL TISSUES AND PERIODONTAL DISEASE. ANTI-INFLAMMATORY PHARMACOLOGIC AGENTS [NON-STEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS)] HAVE BEEN SHOWN TO PREVENT AND SLOW THE PROGRESSION OF PERIODONTITIS IN ANIMALS AND HUMANS. HOWEVER, THE SIDE EFFECT PROFILE OF NSAIDS OR OTHER INHIBITORS OR RECEPTOR ANTAGONISTS PRECLUDE THEIR USE IN PERIODONTAL THERAPY. CONCLUSION: THE ISOLATION AND CHARACTERIZATION OF PRORESOLVING LIPID MEDIATORS THAT ARE RECEPTOR AGONISTS HAS OPENED A NEW AREA OF RESEARCH FOR POTENTIAL THERAPEUTIC AGENTS FOR THE MANAGEMENT OF INFLAMMATORY PERIODONTITIS. 2011 8 6261 49 THE MORAXELLA CATARRHALIS PHASE-VARIABLE DNA METHYLTRANSFERASE MODM3 IS AN EPIGENETIC REGULATOR THAT AFFECTS BACTERIAL SURVIVAL IN AN IN VIVO MODEL OF OTITIS MEDIA. BACKGROUND: MORAXELLA CATARRHALIS IS A LEADING CAUSE OF OTITIS MEDIA (OM) AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE (COPD). M. CATARRHALIS CONTAINS A TYPE III DNA ADENINE METHYLTRANSFERASE (MODM) THAT IS PHASE-VARIABLY EXPRESSED (I.E., ITS EXPRESSION IS SUBJECT TO RANDOM, REVERSIBLE ON/OFF SWITCHING). MODM HAS SIX TARGET RECOGNITION DOMAIN ALLELES (MODM1-6), AND WE HAVE PREVIOUSLY SHOWN THAT MODM2 IS THE PREDOMINANT ALLELE, WHILE MODM3 IS ASSOCIATED WITH OM. PHASE-VARIABLE DNA METHYLTRANSFERASES MEDIATE EPIGENETIC REGULATION AND MODULATE PATHOGENESIS IN SEVERAL BACTERIA. MODM2 OF M. CATARRHALIS REGULATES THE EXPRESSION OF A PHASEVARION CONTAINING GENES IMPORTANT FOR COLONIZATION AND INFECTION. HERE WE DESCRIBE THE PHASE-VARIABLE EXPRESSION OF MODM3, THE MODM3 METHYLATION SITE AND THE SUITE OF GENES REGULATED WITHIN THE MODM3 PHASEVARION. RESULTS: PHASE-VARIABLE EXPRESSION OF MODM3, MEDIATED BY VARIATION IN LENGTH OF A 5'-(CAAC)(N)-3' TETRANUCLEOTIDE REPEAT TRACT IN THE OPEN READING FRAME WAS DEMONSTRATED IN M. CATARRHALIS STRAIN CCRI-195ME WITH GENESCAN FRAGMENT LENGTH ANALYSIS AND WESTERN IMMUNOBLOT. WE DETERMINED THAT MODM3 IS AN ACTIVE N6-ADENINE METHYLTRANSFERASE THAT METHYLATES THE SEQUENCE 5'-AC(M6)ATC-3'. METHYLATION WAS DETECTED AT ALL 4446 5'-ACATC-3' SITES IN THE GENOME WHEN MODM3 IS EXPRESSED. RNASEQ ANALYSIS IDENTIFIED 31 GENES THAT ARE DIFFERENTIALLY EXPRESSED BETWEEN MODM3 ON AND OFF VARIANTS, INCLUDING FIVE GENES THAT ARE INVOLVED IN THE RESPONSE TO OXIDATIVE AND NITROSATIVE STRESS, WITH POTENTIAL ROLES IN BIOFILM FORMATION AND SURVIVAL IN ANAEROBIC ENVIRONMENTS. AN IN VIVO CHINCHILLA (CHINCHILLA LANIGERA) MODEL OF OTITIS MEDIA DEMONSTRATED THAT TRANSBULLAR CHALLENGE WITH THE MODM3 OFF VARIANT RESULTED IN AN INCREASED MIDDLE EAR BACTERIAL LOAD COMPARED TO A MODM3 ON VARIANT. IN ADDITION, CO-INFECTION EXPERIMENTS WITH NTHI AND M. CATARRHALIS MODM3 ON OR MODM3 OFF VARIANTS REVEALED THAT PHASE VARIATION OF MODM3 ALTERED SURVIVAL OF NTHI IN THE MIDDLE EAR DURING EARLY AND LATE STAGE INFECTION. CONCLUSIONS: PHASE VARIATION OF MODM3 EPIGENETICALLY REGULATES THE EXPRESSION OF A PHASEVARION CONTAINING MULTIPLE GENES THAT ARE POTENTIALLY IMPORTANT IN THE PROGRESSION OF OTITIS MEDIA. 2019 9 107 42 A REVIEW OF PRE-CLINICAL MODELS FOR GULF WAR ILLNESS. GULF WAR ILLNESS (GWI) IS A CHRONIC MULTISYMPTOMATIC DISORDER THAT AFFLICTS OVER 1/3RD OF THE 1991 GW VETERANS. IT SPANS MULTIPLE BODILY SYSTEMS AND PRESENTS ITSELF AS A SYNDROME EXHIBITING DIVERSE SYMPTOMS INCLUDING FATIGUE, DEPRESSION, MOOD, AND MEMORY AND CONCENTRATION DEFICITS, MUSCULOSKELETAL PAIN AND GASTROINTESTINAL DISTRESS IN GW VETERANS. THE ETIOLOGY OF GWI IS COMPLEX AND MANY FACTORS, INCLUDING CHEMICAL, PHYSIOLOGICAL, AND ENVIRONMENTAL STRESSORS PRESENT IN THE GW ARENA, HAVE BEEN IMPLICATED FOR ITS DEVELOPMENT. IT HAS BEEN OVER 30 YEARS SINCE THE END OF THE GW BUT, GWI HAS BEEN PERSISTENT IN SUFFERING VETERANS WHO ARE ALSO DEALING WITH PAUCITY OF EFFECTIVE TREATMENTS. THE MULTIFACTORIAL ASPECT OF GWI ALONG WITH GENETIC HETEROGENEITY AND LACK OF AVAILABLE DATA SURROUNDING WAR-TIME EXPOSURES HAVE PROVED TO BE CHALLENGING IN DEVELOPING PRE-CLINICAL MODELS OF GWI. DESPITE THIS, OVER A DOZEN GWI ANIMAL MODELS EXIST IN THE LITERATURE. IN THIS ARTICLE, FOLLOWING A BRIEF DISCUSSION OF GW HISTORY, GWI DEFINITIONS, AND PROBABLE CAUSES FOR ITS PATHOGENESIS, WE WILL EXPAND UPON VARIOUS EXPERIMENTAL MODELS USED IN GWI LABORATORY RESEARCH. THESE ANIMAL MODELS WILL BE DISCUSSED IN THE CONTEXT OF THEIR ATTEMPTS AT MIMICKING GW-RELATED EXPOSURES WITH REGARDS TO THE VARIATIONS IN CHEMICAL COMBINATIONS, DOSES, AND FREQUENCY OF EXPOSURES. WE WILL DISCUSS THEIR ADVANTAGES AND LIMITATIONS IN MODELING GWI FOLLOWED BY A DISCUSSION OF BEHAVIORAL AND MOLECULAR FINDINGS IN THESE MODELS. THE MECHANISTIC DATA OBTAINED FROM THESE PRECLINICAL STUDIES HAVE OFFERED MULTIPLE MOLECULAR PATHWAYS INCLUDING CHRONIC INFLAMMATION, MITOCHONDRIAL DYSFUNCTION, OXIDATIVE STRESS, LIPID DISTURBANCES, CALCIUM HOMEOSTATIC ALTERATIONS, CHANGES IN GUT MICROBIOTA, AND EPIGENETIC MODIFICATIONS, AMONGST OTHERS FOR EXPLAINING GWI DEVELOPMENT AND ITS PERSISTENCE. FINALLY, THESE FINDINGS HAVE ALSO INFORMED US ON NOVEL DRUGGABLE TARGETS IN GWI. WHILE, IT HAS BEEN DIFFICULT TO CONCEIVE A SINGLE PRE-CLINICAL MODEL THAT COULD EXPRESS ALL THE GWI SIGNS AND EXHIBIT BIOLOGICAL COMPLEXITY REFLECTIVE OF THE CLINICAL PRESENTATION IN GWI, ANIMAL MODELS HAVE BEEN CRITICAL FOR IDENTIFYING MOLECULAR UNDERPINNINGS OF GWI AND EVALUATING TREATMENT STRATEGIES FOR GWI. 2021 10 1948 44 EPIGENETIC ACQUISITION OF INDUCIBILITY OF TYPE III CYTOTOXICITY IN P. AERUGINOSA. BACKGROUND: PSEUDOMONAS AERUGINOSA, AN OPPORTUNISTIC PATHOGEN, IS OFTEN ENCOUNTERED IN CHRONIC LUNG DISEASES SUCH AS CYSTIC FIBROSIS OR CHRONIC OBSTRUCTIVE PNEUMONIA, AS WELL AS ACUTE SETTINGS LIKE MECHANICAL VENTILATION ACQUIRED PNEUMONIA OR NEUTROPENIC PATIENTS. IT IS A MAJOR CAUSE OF MORTALITY AND MORBIDITY IN THESE DISEASES. IN LUNGS, P. AERUGINOSA SETTLES IN A BIOFILM MODE OF GROWTH WITH THE SECRETION OF EXOPOLYSACCHARIDES IN WHICH IT IS ENCAPSULATED, ENHANCING ITS ANTIBIOTIC RESISTANCE AND CONTRIBUTING TO THE RESPIRATORY DEFICIENCY OF PATIENTS. HOWEVER, BACTERIA MUST FIRST MULTIPLY TO A HIGH DENSITY AND DISPLAY A CYTOTOXIC PHENOTYPE TO AVOID THE HOST'S DEFENCES. A VIRULENCE DETERMINANT IMPLICATED IN THIS STEP OF INFECTION IS THE TYPE III SECRETION SYSTEM (TTSS), ALLOWING TOXIN INJECTION DIRECTLY INTO HOST CELLS. AT THE BEGINNING OF THE INFECTION, MOST STRAINS ISOLATED FROM PATIENTS' LUNGS POSSESS AN INDUCIBLE TTSS ALLOWING TOXINS INJECTION OR SECRETION UPON IN VIVO OR IN VITRO ACTIVATION SIGNALS. AS THE INFECTION PERSISTS MOST OF THE BACTERIA PERMANENTLY LOOSE THIS CAPACITY, ALTHOUGH NO MUTATIONS HAVE BEEN EVIDENCED. WE NAME "NON INDUCIBLE" THIS PHENOTYPE. AS SUGGESTED BY THE PRESENCE OF A POSITIVE FEEDBACK CIRCUIT IN THE REGULATORY NETWORK CONTROLLING TTSS EXPRESSION, IT MAY BE DUE TO AN EPIGENETIC SWITCH ALLOWING HERITABLE PHENOTYPIC MODIFICATIONS WITHOUT GENOTYPE'S MUTATIONS. RESULTS: USING THE GENERALISED LOGICAL METHOD, WE DESIGNED A MINIMAL MODEL OF THE TTSS REGULATORY NETWORK THAT COULD SUPPORT THE EPIGENETIC HYPOTHESIS, AND STUDIED ITS DYNAMICS WHICH HELPED TO DEFINE A DISCRIMINATING EXPERIMENTAL SCENARIO SUFFICIENT TO VALIDATE THE EPIGENETIC HYPOTHESIS. A MATHEMATICAL FRAMEWORK BASED ON FORMAL METHODS FROM COMPUTER SCIENCE ALLOWED A RIGOROUS VALIDATION AND CERTIFICATION OF PARAMETERS OF THIS MODEL LEADING TO EPIGENETIC BEHAVIOUR. THEN, WE DEMONSTRATED THAT A NON INDUCIBLE STRAIN OF P. AERUGINOSA CAN STABLY ACQUIRE THE CAPACITY TO BE INDUCED BY CALCIUM DEPLETION FOR THE TTSS AFTER A SHORT PULSE OF A REGULATORY PROTEIN. FINALLY, THE INCREASED CYTOTOXICITY OF A STRAIN AFTER THIS EPIGENETIC SWITCH WAS DEMONSTRATED IN VIVO IN AN ACUTE PULMONARY INFECTION MODEL. CONCLUSION: THESE RESULTS MAY OFFER NEW PERSPECTIVES FOR THERAPEUTIC STRATEGIES TO PREVENT LETHAL INFECTIONS BY P. AERUGINOSA BY REVERTING THE EPIGENETIC INDUCIBILITY OF TYPE III CYTOTOXICITY. 2006 11 4858 31 ORAL ANTIBIOTIC USE AND CHRONIC DISEASE: LONG-TERM HEALTH IMPACT BEYOND ANTIMICROBIAL RESISTANCE AND CLOSTRIDIOIDES DIFFICILE. WE RECENTLY REPORTED AN INCREASED COLON CANCER RISK ASSOCIATED WITH ORAL ANTIBIOTIC USE IN A LARGE UNITED KINGDOM POPULATION. THIS ASSOCIATION BETWEEN ANTIBIOTIC EXPOSURE AND CANCER RISK ADDS TO A GROWING BODY OF EVIDENCE THAT ANTIBIOTIC USE HAS UNINTENDED OFF-TARGET LONG-TERM HEALTH CONSEQUENCES. THIS ADDENDUM HIGHLIGHTS MAJOR STUDIES LINKING ANTIBIOTIC USE AND CHRONIC DISEASE IN PEDIATRIC AND ADULT POPULATIONS. MICROBIOTA DYSBIOSIS IS THE KEY PROPOSED MECHANISM UNDERLYING ANTIBIOTIC:DISEASE ASSOCIATIONS, RESULTING IN ALTERATIONS IN GENE EXPRESSION, EPIGENETIC MODIFICATION, COLONIZATION BY PATHOGENIC BACTERIA, INSTIGATION OF BIOFILMS, AND IMMUNE REGULATION AND INFLAMMATION. THESE ADVERSE OUTCOMES OF ANTIBIOTIC EXPOSURE UNDERSCORE THE NEED FOR DIAGNOSTIC AND ANTIBIOTIC STEWARDSHIP, AS WELL AS THE URGENCY FOR FURTHER DEVELOPMENT OF NON-ANTIBIOTIC THERAPIES FOR BACTERIAL INFECTIONS. 2020 12 6742 44 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 13 6743 47 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 14 734 38 CANCER HEALTHCARE DISPARITIES AMONG AFRICAN AMERICANS IN THE UNITED STATES. A NEED EXISTS TO EXAMINE RACIAL DISPARITIES IN THE HEALTHCARE ARENA AND THE IMPACT ON PATIENTS WITH CANCER. DESPITE ONGOING EFFORTS TO INCREASE EQUITY IN PRIMARY HEALTHCARE ACCESS, RACIAL AND SOCIOECONOMIC DISPARITIES PERSIST, THUS CONTRIBUTING TO DISPROPORTIONATE TREATMENT OUTCOMES AND SURVIVORSHIP AMONG MINORITY AND LOW-INCOME PATIENTS. SUCH DISPARITIES HAVE BEEN REVEALED IN TREATMENT COHORTS OF PATIENTS WITH MULTIPLE FORMS OF CANCER, INCLUDING BREAST, CERVICAL, OVARIAN, ENDOMETRIAL, PROSTATE, LUNG, COLORECTAL, GASTROINTESTINAL, AND HEPATOCELLULAR, AND HAVE BEEN ATTRIBUTED TO A RANGE OF CO-OCCURRING BEHAVIORAL, SOCIAL DETERMINANTS OF HEALTH, UNDERLYING GENETIC FACTORS, AS WELL AS ACCESS TO EDUCATIONAL OPPORTUNITIES THAT LIMIT THE QUALITY OF INFORMED HEALTHCARE. THESE VARIOUS INTERRELATED FACTORS WIDEN CANCER HEALTHCARE DISPARITIES SYNERGISTICALLY THROUGHOUT UNDERSERVED COMMUNITIES, AND THEIR INFLUENCE HAS BEEN AMPLIFIED BY THE CORONAVIRUS DISEASE 2019 (COVID-19) PANDEMIC. FUNDAMENTALLY, A LACK OF BASIC AND CLINICAL RESEARCH EXISTS THAT FAILS TO ADEQUATELY REFLECT DIVERSITY AND MINORITY INVOLVEMENT IN DRUG DEVELOPMENT. ALTHOUGH OVERCOMING THE OBSTACLES RESPONSIBLE FOR CHRONIC TREATMENT DISPARITIES IS A FORMIDABLE TASK, PROMISING MEANS OF ACHIEVING MORE UNIFORM QUALITY HEALTHCARE ARE BECOMING MORE CLEARLY ELUCIDATED. TO REDUCE DISEASE PROGRESSION, INCREASE OVERALL SURVIVAL, AND IMPROVE THE HEALTH OF VULNERABLE POPULATIONS, IT IS NECESSARY TO IDENTIFY AND FULLY DISCLOSE ENVIRONMENTAL, BIOLOGICAL, AND ANCESTRAL FACTORS THAT IMPACT THE RISK FOR CANCER; HEAL HISTORICAL FRACTURES WITHIN COMMUNITIES; AND INCREASE PARTICIPATION OF RACIAL AND ETHNIC MINORITIES IN SCREENING EFFORTS AND RESEARCH STUDIES. THIS REQUIRES DEVELOPING A SYSTEM OF JUSTICE AND TRUST BASED ON SPECIFIC, SOLUTION-ORIENTED GRASSROOTS COMMUNITY EFFORTS WORKING IN TANDEM WITH MEDICAL AND PHARMACEUTICAL LEADERS. BY FULLY EXPLORING AND PINPOINTING THE UNDERLYING CAUSES OF HEALTHCARE DISPARITIES, IT SHOULD BE POSSIBLE TO DEFINE STRATEGIES AND INTERVENTIONS MOST LIKELY TO TRANSFORM CANCER CARE. THE ULTIMATE GOAL IS UNDERSTANDING INDIVIDUAL, CULTURAL, AND BIOLOGICAL VULNERABILITIES, INCLUDING ENVIRONMENTAL AND EPIGENETIC LIABILITIES, TO OPTIMIZE CANCER PREVENTION, DIAGNOSIS, AND TREATMENT. 2022 15 5025 31 PERSONALIZED MANAGEMENT OF CARDIOVASCULAR DISORDERS. PERSONALIZED MANAGEMENT OF CARDIOVASCULAR DISORDERS (CVD), ALSO REFERRED TO AS PERSONALIZED OR PRECISION CARDIOLOGY IN ACCORDANCE WITH GENERAL PRINCIPLES OF PERSONALIZED MEDICINE, IS SELECTION OF THE BEST TREATMENT FOR AN INDIVIDUAL PATIENT. IT INVOLVES THE INTEGRATION OF VARIOUS "OMICS" TECHNOLOGIES SUCH AS GENOMICS AND PROTEOMICS AS WELL AS OTHER NEW TECHNOLOGIES SUCH AS NANOBIOTECHNOLOGY. MOLECULAR DIAGNOSTICS AND BIOMARKERS ARE IMPORTANT FOR LINKING DIAGNOSIS WITH THERAPY AND MONITORING THERAPY. BECAUSE CVD INVOLVE PERTURBATIONS OF LARGE COMPLEX BIOLOGICAL NETWORKS, A SYSTEMS BIOLOGY APPROACH TO CVD RISK STRATIFICATION MAY BE USED FOR IMPROVING RISK-ESTIMATING ALGORITHMS, AND MODELING OF PERSONALIZED BENEFIT OF TREATMENT MAY BE HELPFUL FOR GUIDING THE CHOICE OF INTERVENTION. BIOINFORMATICS TOOLS ARE HELPFUL IN ANALYZING AND INTEGRATING LARGE AMOUNTS OF DATA FROM VARIOUS SOURCES. PERSONALIZED THERAPY IS CONSIDERED DURING DRUG DEVELOPMENT, INCLUDING METHODS OF TARGETED DRUG DELIVERY AND CLINICAL TRIALS. INDIVIDUALIZED RECOMMENDATIONS CONSIDER MULTIPLE FACTORS - GENETIC AS WELL AS EPIGENETIC - FOR PATIENTS' RISK OF HEART DISEASE. EXAMPLES OF PERSONALIZED TREATMENT ARE THOSE OF CHRONIC MYOCARDIAL ISCHEMIA, HEART FAILURE, AND HYPERTENSION. SIMILAR APPROACHES CAN BE USED FOR THE MANAGEMENT OF ATRIAL FIBRILLATION AND HYPERCHOLESTEROLEMIA, AS WELL AS THE USE OF ANTICOAGULANTS. PERSONALIZED MANAGEMENT INCLUDES PHARMACOTHERAPY, SURGERY, LIFESTYLE MODIFICATIONS, AND COMBINATIONS THEREOF. FURTHER PROGRESS IN UNDERSTANDING THE PATHOMECHANISM OF COMPLEX CARDIOVASCULAR DISEASES AND IDENTIFICATION OF CAUSATIVE FACTORS AT THE INDIVIDUAL PATIENT LEVEL WILL PROVIDE OPPORTUNITIES FOR THE DEVELOPMENT OF PERSONALIZED CARDIOLOGY. APPLICATION OF PRINCIPLES OF PERSONALIZED MEDICINE WILL IMPROVE THE CARE OF THE PATIENTS WITH CVD. 2017 16 537 32 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 17 1888 29 ENDOMETRIOSIS AND IN VITRO FERTILISATION. THE AIM OF THE PRESENT REVIEW WAS TO DISCUSS A MATTER OF CONCERN IN THE CLINICAL FIELD OF OBSTETRICS/GYNECOLOGY, NAMELY THE POTENCY OF IN VITRO FERTILIZATION (IVF) IN THE MANAGEMENT OF ENDOMETRIOSIS-ASSOCIATED INFERTILITY. ENDOMETRIOSIS IS A MEDICAL CONDITION AFFECTING ONE TENTH OF WOMEN IN THEIR FERTILE YEARS, AND ACCOUNTS FOR UP TO 50% OF INFERTILE WOMEN. THUS, SUCH HIGH PREVALENCE HAS ESTABLISHED THE NECESSITY FOR INVESTIGATING THE EFFECTIVENESS OF AVAILABLE TECHNIQUES IN ERADICATING THE DISEASE AND CONSTRAINING INFERTILITY AS WELL AS THE ACCOMPANYING PAIN SYMPTOMS OF ENDOMETRIOSIS. THE UNDERLYING MECHANISMS CONNECTING ENDOMETRIOSIS WITH LOW FECUNDITY HAVE BEEN EXTENSIVELY STUDIED, BOTH IN TERMS OF GENETIC ALTERATIONS AND EPIGENETIC EVENTS THAT CONTRIBUTE TO THE MANIFESTATION OF AN INFERTILITY PHENOTYPE IN WOMEN WITH THE DISEASE. SEVERAL STUDIES HAVE DEALT WITH THE IMPACT OF IVF IN PREGNANCY RATES (PRS) ON PATIENTS WITH ENDOMETRIOSIS, PARTICULARLY REGARDING WOMEN WHO WISH TO CONCEIVE. RESULTS RETRIEVED FROM STUDIES AND META-ANALYSES DEPICT A DIVERSE PATTERN OF IVF SUCCESS, UNDERLINING THE INVOLVEMENT OF INDIVIDUAL PARAMETERS IN THE CONFIGURATION OF THE FINAL OUTCOME. THE ULTIMATE DECISION ON UNDERGOING IVF TREATMENT SHOULD BE BASED ON OBJECTIVE CRITERIA AND CLINICIANS' EXPERIENCE, CUSTOMIZED ACCORDING TO PATIENTS' INDIVIDUAL NEEDS. 2018 18 3773 27 INTERACTION OF CERVICAL MICROBIOME WITH EPIGENOME OF EPITHELIAL CELLS: SIGNIFICANCE OF INFLAMMATION TO PRIMARY HEALTHCARE. ONE PILLAR OF THE PREDICTIVE, PREVENTIVE, AND PERSONALIZED MEDICINE FRAMEWORK STRATEGIES IS THE FEMALE HEALTH. THE EVALUATION OF WOMEN'S LIFESTYLE AND DIETARY HABITS IN CONTEXT WITH GENETIC AND MODIFIABLE RISK FACTORS MAY REFLECT THE PREVENTION OF CERVICAL CANCER BEFORE THE OCCURRENCE OF CLINICAL SYMPTOMS AND PREDICTION OF CERVICAL LESION BEHAVIOR. THE MAIN AIM OF THIS REVIEW IS TO ANALYZE PUBLICATIONS IN THE FIELD OF PRECISION MEDICINE THAT ALLOW THE USE OF RESEARCH KNOWLEDGE OF CERVICAL MICROBIOME, EPIGENETIC MODIFICATIONS, AND INFLAMMATION IN POTENTIAL APPLICATION IN CLINICAL PRACTICE. PERSONALIZED APPROACH IN EVALUATING PATIENT'S RISK OF FUTURE DEVELOPMENT OF CERVICAL ABNORMALITY SHOULD CONSIDER THE BIOMARKERS OF THE LOCAL MICROENVIRONMENT CHARACTERIZED BY THE MICROBIAL COMPOSITION, EPIGENETIC PATTERN OF CERVICAL EPITHELIUM, AND PRESENCE OF CHRONIC INFLAMMATION. NOVEL SEQUENCING TECHNIQUES ENABLE A MORE DETAILED CHARACTERIZATION OF ACTUAL STATE IN CERVICAL EPITHELIUM. BETTER UNDERSTANDING OF ALL CHANGES IN MULTIOMICS LEVEL ENABLES A BETTER ASSESSMENT OF DISEASE PROGNOSIS AND SELECTS THE ELIGIBLE TARGETED THERAPY IN PERSONALIZED MEDICINE. RESTORING OF HEALTHY VAGINAL MICROFLORA AND REVERSING THE OUTBREAK OF CERVICAL ABNORMALITY CAN BE ALSO ACHIEVED BY DIETARY HABITS AS WELL AS UPTAKE OF PREBIOTICS, PROBIOTICS, SYNBIOTICS, MICROBIAL TRANSPLANTATION, AND OTHERS. 2022 19 1887 43 ENDOMETRIAL RECEPTIVITY IN WOMEN OF ADVANCED AGE: AN UNDERRATED FACTOR IN INFERTILITY. BACKGROUND: MODERN LIFESTYLE HAS LED TO AN INCREASE IN THE AGE AT CONCEPTION. ADVANCED AGE IS ONE OF THE CRITICAL RISK FACTORS FOR FEMALE-RELATED INFERTILITY. IT IS WELL KNOWN THAT MATERNAL AGE POSITIVELY CORRELATES WITH THE DETERIORATION OF OOCYTE QUALITY AND CHROMOSOMAL ABNORMALITIES IN OOCYTES AND EMBRYOS. THE EFFECT OF AGE ON ENDOMETRIAL FUNCTION MAY BE AN EQUALLY IMPORTANT FACTOR INFLUENCING IMPLANTATION RATE, PREGNANCY RATE, AND OVERALL FEMALE FERTILITY. HOWEVER, THERE ARE ONLY A FEW PUBLISHED STUDIES ON THIS TOPIC, SUGGESTING THAT THIS AREA HAS BEEN UNDER-EXPLORED. IMPROVING OUR KNOWLEDGE OF ENDOMETRIAL AGING FROM THE BIOLOGICAL (CELLULAR, MOLECULAR, HISTOLOGICAL) AND CLINICAL PERSPECTIVES WOULD BROADEN OUR UNDERSTANDING OF THE RISKS OF AGE-RELATED FEMALE INFERTILITY. OBJECTIVE AND RATIONALE: THE OBJECTIVE OF THIS NARRATIVE REVIEW IS TO CRITICALLY EVALUATE THE EXISTING LITERATURE ON ENDOMETRIAL AGING WITH A FOCUS ON SYNTHESIZING THE EVIDENCE FOR THE IMPACT OF ENDOMETRIAL AGING ON CONCEPTION AND PREGNANCY SUCCESS. THIS WOULD PROVIDE INSIGHTS INTO EXISTING GAPS IN THE CLINICAL APPLICATION OF RESEARCH FINDINGS AND PROMOTE THE DEVELOPMENT OF TREATMENT OPTIONS IN THIS FIELD. SEARCH METHODS: THE REVIEW WAS PREPARED USING PUBMED (MEDLINE) UNTIL FEBRUARY 2023 WITH THE KEYWORDS SUCH AS 'ENDOMETRIAL AGING', 'RECEPTIVITY', 'DECIDUALIZATION', 'HORMONE', 'SENESCENCE', 'CELLULAR', 'MOLECULAR', 'METHYLATION', 'BIOLOGICAL AGE', 'EPIGENETIC', 'OOCYTE RECIPIENT', 'OOCYTE DONATION', 'EMBRYO TRANSFER', AND 'PREGNANCY RATE'. ARTICLES IN A LANGUAGE OTHER THAN ENGLISH WERE EXCLUDED. OUTCOMES: IN THE AGING ENDOMETRIUM, ALTERATIONS OCCUR AT THE MOLECULAR, CELLULAR, AND HISTOLOGICAL LEVELS SUGGESTING THAT AGING HAS A NEGATIVE EFFECT ON ENDOMETRIAL BIOLOGY AND MAY IMPAIR ENDOMETRIAL RECEPTIVITY. ADDITIONALLY, ADVANCED AGE INFLUENCES CELLULAR SENESCENCE, WHICH PLAYS AN IMPORTANT ROLE DURING THE INITIAL PHASE OF IMPLANTATION AND IS A MAJOR OBSTACLE IN THE DEVELOPMENT OF SUITABLE SENOLYTIC AGENTS FOR ENDOMETRIAL AGING. AGING IS ALSO ACCOUNTABLE FOR CHRONIC CONDITIONS ASSOCIATED WITH INFLAMMAGING, WHICH EVENTUALLY CAN LEAD TO INCREASED PRO-INFLAMMATION AND TISSUE FIBROSIS. FURTHERMORE, ADVANCED AGE INFLUENCES EPIGENETIC REGULATION IN THE ENDOMETRIUM, THUS ALTERING THE RELATION BETWEEN ITS EPIGENETIC AND CHRONOLOGICAL AGE. THE STUDIES IN OOCYTE DONATION CYCLES TO DETERMINE THE EFFECT OF AGE ON ENDOMETRIAL RECEPTIVITY WITH RESPECT TO THE RATES OF IMPLANTATION, CLINICAL PREGNANCY, MISCARRIAGE, AND LIVE BIRTH HAVE REVEALED CONTRADICTORY INFERENCES INDICATING THE NEED FOR FUTURE RESEARCH ON THE MECHANISMS AND CORRESPONDING CAUSAL EFFECTS OF WOMEN'S AGE ON ENDOMETRIAL RECEPTIVITY. WIDER IMPLICATIONS: INCREASING AGE CAN BE ACCOUNTABLE FOR FEMALE INFERTILITY AND IVF FAILURES. BASED ON THE COMPLIED OBSERVATIONS AND SYNTHESIZED CONCLUSIONS IN THIS REVIEW, ADVANCED AGE HAS BEEN SHOWN TO HAVE A NEGATIVE IMPACT ON ENDOMETRIAL FUNCTIONING. THIS INFORMATION CAN PROVIDE RECOMMENDATIONS FOR FUTURE RESEARCH FOCUSING ON MOLECULAR MECHANISMS OF AGE-RELATED CELLULAR SENESCENCE, CELLULAR COMPOSITION, AND TRANSCRIPTOMIC CHANGES IN RELATION TO ENDOMETRIAL AGING. ADDITIONALLY, FURTHER PROSPECTIVE RESEARCH IS NEEDED TO EXPLORE NEWLY EMERGING THERAPEUTIC OPTIONS, SUCH AS THE SENOLYTIC AGENTS THAT CAN TARGET ENDOMETRIAL AGING WITHOUT AFFECTING DECIDUALIZATION. MOREOVER, CLINICAL TRIAL PROTOCOLS, FOCUSING ON OOCYTE DONATION CYCLES, WOULD BE BENEFICIAL IN UNDERSTANDING THE DIRECT CLINICAL IMPLICATIONS OF ENDOMETRIAL AGING ON PREGNANCY OUTCOMES. 2023 20 103 37 A REHABILOMICS FRAMEWORK FOR PERSONALIZED AND TRANSLATIONAL REHABILITATION RESEARCH AND CARE FOR INDIVIDUALS WITH DISABILITIES: PERSPECTIVES AND CONSIDERATIONS FOR SPINAL CORD INJURY. DESPITE MANY PEOPLE HAVING SIMILAR CLINICAL PRESENTATION, DEMOGRAPHIC FACTORS, AND CLINICAL CARE, OUTCOME CAN DIFFER FOR THOSE SUSTAINING SIGNIFICANT INJURY SUCH AS SPINAL CORD INJURY (SCI) AND TRAUMATIC BRAIN INJURY (TBI). IN ADDITION TO TRADITIONAL DEMOGRAPHIC, SOCIAL, AND CLINICAL FACTORS, VARIABILITY ALSO MAY BE ATTRIBUTABLE TO INNATE (INCLUDING GENETIC, TRANSCRIPTOMIC PROTEOMIC, EPIGENETIC) BIOLOGICAL VARIATION THAT INDIVIDUALS BRING TO RECOVERY AND THEIR UNIQUE RESPONSE TO THEIR CARE AND ENVIRONMENT. TECHNOLOGIES COLLECTIVELY CALLED "-OMICS" ENABLE SIMULTANEOUS MEASUREMENT OF AN ENORMOUS NUMBER OF BIOMOLECULES THAT CAN CAPTURE MANY POTENTIAL BIOLOGICAL CONTRIBUTORS TO HETEROGENEITY OF INJURY/DISEASE COURSE AND OUTCOME. DUE TO THE NATURE OF INJURY AND COMPLEX DISEASE, AND ITS ASSOCIATIONS WITH IMPAIRMENT, DISABILITY, AND RECOVERY, REHABILITATION DOES NOT LEND ITSELF TO A SINGULAR "PROTOCOLIZED" PLAN OF THERAPY. YET, BY NATURE AND BY NECESSITY, REHABILITATION MEDICINE OPERATES AS A FUNCTIONAL MODEL OF "PERSONALIZED CARE". THUS, THE CHALLENGE FOR SUCCESSFUL PROGRAMS OF TRANSLATIONAL REHABILITATION CARE AND RESEARCH IS TO IDENTIFY VIABLE APPROACHES TO EXAMINE BROAD POPULATIONS, WITH VARIED IMPAIRMENTS AND FUNCTIONAL LIMITATIONS, AND TO IDENTIFY EFFECTIVE TREATMENT RESPONSES THAT INCORPORATE PERSONALIZED PROTOCOLS TO OPTIMIZE FUNCTIONAL RECOVERY. THE REHABILOMICS FRAMEWORK IS A TRANSLATIONAL MODEL THAT PROVIDES AN "-OMICS" OVERLAY TO THE SCIENTIFIC STUDY OF REHABILITATION PROCESSES AND MULTIDIMENSIONAL OUTCOMES. REHABILOMICS RESEARCH PROVIDES NOVEL OPPORTUNITIES TO EVALUATE THE NEUROBIOLOGY OF COMPLEX INJURY OR CHRONIC DISEASE AND CAN BE USED TO EXAMINE METHODS AND TREATMENTS FOR PERSON-CENTERED CARE AMONG POPULATIONS WITH DISABILITIES. EXEMPLARS FOR APPLICATION IN SCI AND OTHER NEUROREHABILITATION POPULATIONS ARE DISCUSSED. 2014