1 30 180 A BRIEF LOOK AT HASHIMOTO'S DISEASE, ADRENAL INCIDENTALOMAS, OBESITY AND INSULIN RESISTANCE-COULD ENDOCRINE DISRUPTORS BE THE OTHER SIDE OF THE SAME COIN? HASHIMOTO'S DISEASE (HD) IS THE MOST COMMON CAUSE OF HYPOTHYROIDISM IN DEVELOPED COUNTRIES. THE EXACT PATHOMECHANISM BEHIND IT HAS NOT BEEN CLEARLY ESTABLISHED; HOWEVER, AN INTERPLAY OF GENETIC SUSCEPTIBILITY, ENVIRONMENTAL TRIGGERS (INCLUDING DIET) AND EPIGENETIC FACTORS SEEMS TO BE INVOLVED. AMONG THE LATTER, INCREASINGLY MORE ATTENTION HAS BEEN PAID TO SOME HORMONALLY ACTIVE SUBSTANCES, KNOWN AS ENDOCRINE DISRUPTORS, WHICH ARE COMMONLY USED WORLDWIDE. HD HAS BECOME A CONDITION WIDELY REPORTED IN THE MEDIA, ACTING AS A CULPRIT FOR INEXPLICABLE WEIGHT GAIN, CHRONIC FATIGUE OR WEAKNESS. NEVERTHELESS, THE RECOGNITION OF HD IS UNDENIABLY INCREASING AND REPRESENTS A MAJOR PUBLIC HEALTH BURDEN. AT THE SAME TIME, IMPROVING ACCESS TO IMAGING TESTS HAS INCREASED THE NUMBER OF INCIDENTALLY DIAGNOSED ADRENAL TUMORS. ABOVE ALL, THE WIDESPREAD USE OF CHEST COMPUTED TOMOGRAPHY (CT) DUE TO THE COVID-19 PANDEMIC HAS CONTRIBUTED TO FREQUENT INCIDENTAL DETECTION OF ADRENAL LESIONS. FORTUNATELY, A VAST MAJORITY OF THESE FINDINGS ARE ASYMPTOMATIC BENIGN TUMORS WITH NO EXCESSIVE HORMONAL ACTIVITY, AND THEREFORE, THEY ARE DEFINED AS ADRENAL INCIDENTALOMAS (AIS). INTERESTINGLY, RECENT STUDIES HAVE INDICATED THAT PATIENTS WITH AIS ARE MORE PRONE TO OBESITY AND INSULIN RESISTANCE. ALTHOUGH MUTUAL RELATIONSHIPS BETWEEN THE THYROID AND THE ADRENAL GLANDS HAVE BEEN STUDIED WIDELY, STILL, LITTLE IS KNOWN ABOUT THE POSSIBLE PATHOPHYSIOLOGICAL ASSOCIATIONS BETWEEN THYROID AUTOIMMUNITY AND THE OCCURRENCE OF ADRENAL INCIDENTALOMAS. THIS ARTICLE PRESENTS A BRIEF REVIEW OF THE COMMON ENDOCRINE DISORDERS WITH A SPECIAL FOCUS ON THE FREQUENTLY COEXISTING INSULIN RESISTANCE AND/OR OBESITY. FURTHERMORE, IN RESPONSE TO THE RECENT GROWING INTEREST IN ENDOCRINE DISRUPTORS, WITH THEIR TRANSGENERATIONAL EPIGENETIC EFFECTS THAT INFLUENCE HORMONAL SYSTEM FUNCTION, A CONCISE OVERVIEW OF THE TOPIC HAS ALSO BEEN INCLUDED. 2023 2 6406 39 THE SEARCH FOR RELIABLE BIOMARKERS OF DISEASE IN MULTIPLE CHEMICAL SENSITIVITY AND OTHER ENVIRONMENTAL INTOLERANCES. WHILST FACING A WORLDWIDE FAST INCREASE OF FOOD AND ENVIRONMENTAL ALLERGIES, THE MEDICAL COMMUNITY IS ALSO CONFRONTED WITH ANOTHER INHOMOGENEOUS GROUP OF ENVIRONMENT-ASSOCIATED DISABLING CONDITIONS, INCLUDING MULTIPLE CHEMICAL SENSITIVITY (MCS), FIBROMYALGIA, CHRONIC FATIGUE SYNDROME, ELECTRIC HYPERSENSITIVITY, AMALGAM DISEASE AND OTHERS. THESE SHARE THE FEATURES OF POLY-SYMPTOMATIC MULTI-ORGAN CUTANEOUS AND SYSTEMIC MANIFESTATIONS, WITH POSTULATED INHERITED/ACQUIRED IMPAIRED METABOLISM OF CHEMICAL/PHYSICAL/NUTRITIONAL XENOBIOTICS, TRIGGERING ADVERSE REACTIONS AT EXPOSURE LEVELS FAR BELOW TOXICOLOGICALLY-RELEVANT VALUES, OFTEN IN THE ABSENCE OF CLEAR-CUT ALLERGOLOGIC AND/OR IMMUNOLOGIC INVOLVEMENT. DUE TO THE LACK OF PROVEN PATHOGENIC MECHANISMS GENERATING MEASURABLE DISEASE BIOMARKERS, THESE ENVIRONMENTAL HYPERSENSITIVITIES ARE GENERALLY IGNORED BY SANITARY AND SOCIAL SYSTEMS, AS PSYCHOGENIC OR "MEDICALLY UNEXPLAINED SYMPTOMS". THE UNCONTROLLED APPLICATION OF DIAGNOSTIC AND TREATMENT PROTOCOLS NOT CORRESPONDING TO ACCEPTABLE LEVELS OF VALIDATION, SAFETY, AND CLINICAL EFFICACY, TO A STEADILY INCREASING NUMBER OF PATIENTS DEMANDING ASSISTANCE, OCCURS IN MANY COUNTRIES IN THE ABSENCE OF EVIDENCE-BASED GUIDELINES. HERE WE REVISE AVAILABLE INFORMATION SUPPORTING THE ORGANIC NATURE OF THESE CLINICAL CONDITIONS. FOLLOWING INTENSE RESEARCH ON GENE POLYMORPHISMS OF PHASE I/II DETOXIFICATION ENZYME GENES, SO FAR STATISTICALLY INCONCLUSIVE, EPIGENETIC AND METABOLIC FACTORS ARE UNDER INVESTIGATION, IN PARTICULAR FREE RADICAL/ANTIOXIDANT HOMEOSTASIS DISTURBANCES. THE FINDING OF RELEVANT ALTERATIONS OF CATALASE, GLUTATHIONE-TRANSFERASE AND PEROXIDASE DETOXIFYING ACTIVITIES SIGNIFICANTLY CORRELATING WITH CLINICAL MANIFESTATIONS OF MCS, HAS RECENTLY REGISTERED SOME PROGRESS TOWARDS THE IDENTIFICATION OF RELIABLE BIOMARKERS OF DISEASE ONSET, PROGRESSION, AND TREATMENT OUTCOMES. 2011 3 6142 41 THE EVALUATION OF CYTOKINES TO HELP ESTABLISH DIAGNOSIS AND GUIDE TREATMENT OF AUTOINFLAMMATORY AND AUTOIMMUNE DISEASES. OUR KNOWLEDGE OF THE ROLE OF CYTOKINES IN PATHOLOGIC CONDITIONS HAS INCREASED CONSIDERABLY WITH THE EMERGENCE OF MOLECULAR AND GENETIC STUDIES, PARTICULARLY IN THE CASE OF AUTOINFLAMMATORY MONOGENIC DISEASES. MANY RARE DISORDERS, CONSIDERED ORPHAN UNTIL RECENTLY, ARE DIRECTLY RELATED TO ABNORMAL GENE REGULATION, AND THE TREATMENT WITH BIOLOGIC AGENTS (BIOLOGICS) TARGETING CYTOKINE RECEPTORS, INTRACELLULAR SIGNALING OR SPECIFIC CYTOKINES IMPROVE THE SYMPTOMS OF AN INCREASING NUMBER OF CHRONIC INFLAMMATORY DISEASES. AS IT IS CURRENTLY IMPOSSIBLE TO SYSTEMATICALLY CONDUCT GENETIC STUDIES FOR ALL PATIENTS WITH AUTOINFLAMMATORY AND AUTOIMMUNE DISEASES, THE EVALUATION OF CYTOKINES CAN BE SEEN AS A SIMPLE, LESS TIME CONSUMING, AND LESS EXPENSIVE ALTERNATIVE. THIS APPROACH COULD BE ESPECIALLY USEFUL WHEN THE DIAGNOSIS OF SYNDROMES OF DISEASES OF UNKNOWN ETIOLOGY REMAINS PROBLEMATIC. THE EVALUATION OF CYTOKINES COULD ALSO HELP AVOID THE CURRENT TRIAL-AND-ERROR APPROACH, WHICH HAS THE DISADVANTAGES OF EXPOSING PATIENTS TO INEFFECTIVE DRUGS WITH POSSIBLE UNNECESSARY SIDE EFFECTS AND PERMANENT ORGAN DAMAGES. IN THIS REVIEW, WE DISCUSS THE VARIOUS POSSIBILITIES, AS WELL AS THE LIMITATIONS OF EVALUATING THE CYTOKINE PROFILES OF PATIENTS SUFFERING FROM AUTOINFLAMMATORY AND AUTOIMMUNE DISEASES, WITH METHODS SUCH AS DIRECT DETECTION OF CYTOKINES IN THE PLASMA/SERUM OR FOLLOWING EX VIVO STIMULATION OF PBMCS LEADING TO THE PRODUCTION OF THEIR CYTOKINE SECRETOME. THE PATIENTS' SECRETOME, COMBINED WITH BIOMARKERS RANGING FROM GENETIC AND EPIGENETIC ANALYSES TO IMMUNOLOGIC BIOMARKERS, MAY HELP NOT ONLY THE DIAGNOSIS BUT ALSO GUIDE THE CHOICE OF BIOLOGICS FOR MORE EFFICIENT AND RAPID TREATMENTS. 2020 4 6252 39 THE MICROBIOME AND CANCER: IMPLICATIONS FOR ONCOLOGY NURSING SCIENCE. BACKGROUND: APPROXIMATELY 1.6 MILLION AMERICANS WERE DIAGNOSED WITH CANCER IN 2014. TO COMBAT THEIR DISEASE, MANY INDIVIDUALS RECEIVED EITHER CURATIVE OR PALLIATIVE TREATMENTS THAT PRODUCED UNDESIRED SYMPTOMS. THESE SYMPTOMS, WHICH OFTEN CAUSE SIGNIFICANT DISTRESS FOR INDIVIDUALS COPING WITH CANCER, MAY SHARE BIOLOGIC UNDERPINNINGS SUCH AS EPIGENETIC CHANGES AND IMMUNE DYSREGULATION. ALTERATIONS IN THE NORMAL FLORA OF THE GUT MAY ALSO INFLUENCE CANCER SYMPTOMS. OBJECTIVE: THE AIM OF THIS REVIEW IS TO DESCRIBE THE EMERGING ROLE FOR THE GUT MICROBIOME IN CANCER RESEARCH, ESPECIALLY THE POTENTIAL RELATIONSHIP BETWEEN THE GUT MICROBIOME AND CANCER SYMPTOMS. METHODS: EXTANT LITERATURE WAS REVIEWED AND SYNTHESIZED. RESULTS: THE MAJORITY OF STUDIES LINKING THE GUT MICROBIOTA AND CANCER ARE ANIMAL MODELS AND FOCUS ON THE RELATIONSHIP BETWEEN DYSBIOSIS AND COLORECTAL CANCER. EMERGING EVIDENCE SUPPORTS THAT THE "GUT-BRAIN" CONNECTION IS A PLAUSIBLE MECHANISM FOR "PSYCHONEUROLOGICAL" CANCER SYMPTOMS SUCH AS DEPRESSION, PAIN, AND FATIGUE. CONCLUSIONS: THERE IS COMPELLING EVIDENCE THAT THE GUT MICROBIOTA AFFECTS CANCER VIA SEVERAL MECHANISMS, INCLUDING MICROBIAL DIVERSITY AND NUMBER, METABOLISM, AND/OR IMMUNE INITIATION. HOWEVER, MORE RESEARCH IS NECESSARY TO ELUCIDATE THESE MECHANISMS, PARTICULARLY AMONG A VARIETY OF CANCERS AND CANCER-RELATED SYMPTOMS. IMPLICATIONS FOR PRACTICE: A BETTER UNDERSTANDING OF THE ROLE OF THE GUT MICROBIOTA IN CANCER SYMPTOMS MAY LEAD TO THE DEVELOPMENT OF TARGETED INDIVIDUALIZED INTERVENTIONS AFFECTING THE GUT MICROBIOTA THAT PREVENT OR AMELIORATE DYSBIOSIS, THEREBY REDUCING SYMPTOMS. THESE INTERVENTIONS MAY EMPHASIZE SELF-CARE MANAGEMENT STRATEGIES ESSENTIAL FOR WELLNESS, SUCH AS DIET, NUTRITION, AND STRESS REDUCTION. 2016 5 727 35 CAN VITAMINS, AS EPIGENETIC MODIFIERS, ENHANCE IMMUNITY IN COVID-19 PATIENTS WITH NON-COMMUNICABLE DISEASE? PURPOSE OF REVIEW: THE HIGHLY INFECTIOUS TRANSMISSIBLE DISEASE, THE NOVEL SARS-COV-2, CAUSING THE CORONAVIRUS DISEASE (COVID-19), HAS A MEDIAN INCUBATION TIME OF 5 TO 15 DAYS. THE SYMPTOMS VARY FROM PERSON TO PERSON AND MANY ARE "HIDDEN CARRIERS." FEW PEOPLE EXPERIENCE IMMEDIATE REACTION AND EVEN DEATH WITHIN 48 H OF INFECTION. HOWEVER, MANY SHOW MILD TO CHRONIC SYMPTOMS AND RECOVER. NEVERTHELESS, THE DEATH RATE DUE TO COVID-19 TRANSMISSION IS HIGH ESPECIALLY AMONG PATIENTS WITH NON-COMMUNICABLE DISEASES. THE PURPOSE OF THIS REVIEW IS TO PROVIDE EVIDENCE TO CONSIDER VITAMINS AS EPIGENETIC MODIFIERS TO ENHANCE IMMUNITY AND REDUCE INFLAMMATORY RESPONSE IN COVID-19 PATIENTS WITH NON-COMMUNICABLE DISEASES. RECENT FINDINGS: CLINICAL EVIDENCE HAS SUGGESTED THE RISK OF GETTING INFECTED IS HIGH AMONG INDIVIDUALS WITH NON-COMMUNICABLE DISEASES SUCH AS CARDIOVASCULAR DISEASE, TYPE-2 DIABETES, CANCER, ACUTE RESPIRATORY DISTRESS SYNDROME, AND RENAL DISEASE, AS WELL AS THE ELDERLY WITH HIGH MORTALITY RATE AMONG THE COHORT. THE IMPACT IS DUE TO AN ALREADY COMPROMISED IMMUNE SYSTEM OF PATIENTS. EVERY PATIENT HAS A DIFFERENT RESPONSE TO COVID-19, WHICH SHOWS THAT THE ABILITY TO COMBAT THE DEADLY VIRUS VARIES INDIVIDUALLY. THUS, TREATMENT CAN BE PERSONALIZED AND ADJUSTED TO HELP PROTECT AND COMBAT COVID-19 INFECTIONS, ESPECIALLY IN INDIVIDUALS WITH NON-COMMUNICABLE DISEASES. BASED ON CURRENT PUBLISHED SCIENTIFIC AND MEDICAL EVIDENCE, THE SUGGESTIONS MADE IN THIS ARTICLE FOR COMBINATION OF VITAMIN THERAPY AS EPIGENETIC MODIFIERS TO CONTROL THE UNREGULATED INFLAMMATORY AND CYTOKINE MARKER EXPRESSIONS, FURTHER NEEDS TO BE CLINICALLY PROVEN. FUTURE RESEARCH AND CLINICAL TRIALS CAN APPLY THE SUGGESTIONS GIVEN IN THIS ARTICLE TO SUPPORT METABOLIC ACTIVITIES IN PATIENTS AND ENHANCE THE IMMUNE RESPONSE. 2020 6 3035 36 GENETICS/GENOMICS IN CHRONIC KIDNEY DISEASE--TOWARDS PERSONALIZED MEDICINE? THE PROGRESSION RATE OF CHRONIC KIDNEY DISEASE (CKD) TO ITS TERMINAL STAGE, END-STAGE RENAL DISEASE (ESRD), AND THE DEVELOPMENT AND SEVERITY OF VARIOUS COMPLICATIONS, ARE AT LEAST INDIRECTLY INFLUENCED BY GENETIC--AND EPIGENETIC--FACTORS. FOR YEARS, SCIENTISTS HAVE HELD OUT HOPE THAT THE RAPIDLY EVOLVING FIELD OF GENETICS COULD TRANSFORM MEDICAL DIAGNOSIS AND TREATMENT, MOVING BEYOND A TRIAL-AND-ERROR APPROACH TOWARDS "PERSONALIZED MEDICINE." INDEED, THERE ARE NOW SIGNS THAT THE ROLE OF GENETICS AND THE PURSUIT OF "PERSONALIZED MEDICINE" IN MEDICAL CARE WILL BE A PRIORITY FOR GOVERNMENTS DURING YEARS TO COME. BUT THE VISION OF INDIVIDUALIZED TREATMENT BASED ON A PATIENT'S GENETIC MAKEUP AND OTHER BIOLOGICAL MARKERS HAS YET TO MATERIALIZE IN THE FIELD OF CKD AND ESRD. AS THE TOXIC UREMIC ENVIRONMENT MAY RENDER CKD PATIENTS MORE SENSITIVE TO THE EFFECTS OF GENETIC VARIANTS, IT IS LIKELY THAT GENETIC FACTORS COULD BE OF SPECIAL IMPORTANCE IN THIS HIGH-RISK POPULATION. THEREFORE, OUTCOME IN THE CKD POPULATION MAY BE IMPROVED BY ESTABLISHING INDIVIDUAL GENETIC/EPIGENETIC PROFILES, THUS ENABLING PHYSICIANS TO DESIGN AN INDIVIDUALIZED THERAPEUTIC STRATEGY. PERSONALIZED MEDICINE BASED ON A MORE INDIVIDUALIZED THERAPY COULD BE APPLIED IN, FOR EXAMPLE, PHARMACOTHERAPY (CYP GENES), DIALYSIS THERAPY, AND NUTRITIONAL AND LIFESTYLE MODIFICATIONS. 2009 7 3395 37 HOST GENETIC FACTORS PREDISPOSING TO HIV-ASSOCIATED NEUROCOGNITIVE DISORDER. THE SUCCESS OF COMBINATION ANTIRETROVIRAL THERAPY (CART) IN TRANSFORMING THE LIVES OF HIV-INFECTED INDIVIDUALS WITH ACCESS TO THESE DRUGS IS TEMPERED BY THE INCREASING THREAT OF HIV-ASSOCIATED NEUROCOGNITIVE DISORDERS (HAND) TO THEIR OVERALL HEALTH AND QUALITY OF LIFE. INTENSIVE INVESTIGATIONS OVER THE PAST TWO DECADES HAVE UNDERSCORED THE ROLE OF HOST IMMUNE RESPONSES, INFLAMMATION, AND MONOCYTE-DERIVED MACROPHAGES IN HAND, BUT THE PRECISE PATHOGENIC MECHANISMS UNDERLYING HAND REMAIN ONLY PARTIALLY DELINEATED. COMPLICATING RESEARCH EFFORTS AND THERAPEUTIC DRUG DEVELOPMENT ARE THE SHEER COMPLEXITY OF HAND PHENOTYPES, DIAGNOSTIC IMPRECISION, AND THE GROWING INTERSECTION OF CHRONIC IMMUNE ACTIVATION WITH AGING-RELATED COMORBIDITIES. YET, GENETIC STUDIES STILL OFFER A POWERFUL MEANS OF ADVANCING INDIVIDUALIZED CARE FOR HIV-INFECTED INDIVIDUALS AT RISK. THERE IS AN URGENT NEED FOR 1) LONGITUDINAL STUDIES USING CONSISTENT PHENOTYPIC DEFINITIONS OF HAND IN HIV-INFECTED SUBPOPULATIONS AT VERY HIGH RISK OF BEING ADVERSELY IMPACTED, SUCH AS CHILDREN, 2) TISSUE STUDIES THAT CORRELATE NEUROPATHOLOGICAL CHANGES IN MULTIPLE BRAIN REGIONS WITH GENOMIC MARKERS IN AFFECTED INDIVIDUALS AND WITH CHANGES AT THE RNA, EPIGENOMIC, AND/OR PROTEIN LEVELS, AND 3) GENETIC ASSOCIATION STUDIES USING MORE SENSITIVE SUBPHENOTYPES OF HAND. THE NIH BRAIN INITIATIVE AND HUMAN CONNECTOME PROJECT, COUPLED WITH RAPIDLY EVOLVING SYSTEMS BIOLOGY AND MACHINE LEARNING APPROACHES FOR ANALYZING HIGH-THROUGHPUT GENETIC, TRANSCRIPTOMIC AND EPIGENETIC DATA, HOLD PROMISE FOR IDENTIFYING ACTIONABLE BIOLOGICAL PROCESSES AND GENE NETWORKS THAT UNDERLIE HAND. THIS REVIEW SUMMARIZES THE CURRENT STATE OF UNDERSTANDING OF HOST GENETIC FACTORS PREDISPOSING TO HAND IN LIGHT OF PAST CHALLENGES AND SUGGESTS SOME PRIORITIES FOR FUTURE RESEARCH TO ADVANCE THE UNDERSTANDING AND CLINICAL MANAGEMENT OF HAND IN THE CART ERA. 2014 8 4805 35 OBESITY AND METABOLIC COMORBIDITIES: ENVIRONMENTAL DISEASES? OBESITY AND METABOLIC COMORBIDITIES REPRESENT INCREASING HEALTH PROBLEMS. ENDOCRINE DISRUPTING COMPOUNDS (EDCS) ARE EXOGENOUS AGENTS THAT CHANGE ENDOCRINE FUNCTION AND CAUSE ADVERSE HEALTH EFFECTS. MOST EDCS ARE SYNTHETIC CHEMICALS; SOME ARE NATURAL FOOD COMPONENTS AS PHYTOESTROGENS. PEOPLE ARE EXPOSED TO COMPLEX MIXTURES OF CHEMICALS THROUGHOUT THEIR LIVES. EDCS IMPACT HORMONE-DEPENDENT METABOLIC SYSTEMS AND BRAIN FUNCTION. LABORATORY AND HUMAN STUDIES PROVIDE COMPELLING EVIDENCE THAT HUMAN CHEMICAL CONTAMINATION CAN PLAY A ROLE IN OBESITY EPIDEMIC. CHEMICAL EXPOSURES MAY INCREASE THE RISK OF OBESITY BY ALTERING THE DIFFERENTIATION OF ADIPOCYTES. EDCS CAN ALTER METHYLATION PATTERNS AND NORMAL EPIGENETIC PROGRAMMING IN CELLS. OXIDATIVE STRESS MAY BE INDUCED BY MANY OF THESE CHEMICALS, AND ACCUMULATING EVIDENCE INDICATES THAT IT PLAYS IMPORTANT ROLES IN THE ETIOLOGY OF CHRONIC DISEASES. THE INDIVIDUAL SENSITIVITY TO CHEMICALS IS VARIABLE, DEPENDING ON ENVIRONMENT AND ABILITY TO METABOLIZE HAZARDOUS CHEMICALS. A NUMBER OF GENES, ESPECIALLY THOSE REPRESENTING ANTIOXIDANT AND DETOXIFICATION PATHWAYS, HAVE POTENTIAL APPLICATION AS BIOMARKERS OF RISK ASSESSMENT. THE POTENTIAL HEALTH EFFECTS OF COMBINED EXPOSURES MAKE THE RISK ASSESSMENT PROCESS MORE COMPLEX COMPARED TO THE ASSESSMENT OF SINGLE CHEMICALS. TECHNIQUES AND METHODS NEED TO BE FURTHER DEVELOPED TO FILL DATA GAPS AND INCREASE THE KNOWLEDGE ON HARMFUL EXPOSURE COMBINATIONS. 2013 9 6165 35 THE GLOBAL DIABETES EPIDEMIC AS A CONSEQUENCE OF LIFESTYLE-INDUCED LOW-GRADE INFLAMMATION. THE RECENT MAJOR INCREASE IN THE GLOBAL INCIDENCE OF TYPE 2 DIABETES SUGGESTS THAT MOST CASES OF THIS DISEASE ARE CAUSED BY CHANGES IN ENVIRONMENT AND LIFESTYLE. ALL MAJOR RISK FACTORS FOR TYPE 2 DIABETES (OVERNUTRITION, LOW DIETARY FIBRE, SEDENTARY LIFESTYLE, SLEEP DEPRIVATION AND DEPRESSION) HAVE BEEN FOUND TO INDUCE LOCAL OR SYSTEMIC LOW-GRADE INFLAMMATION THAT IS USUALLY TRANSIENT OR MILDER IN INDIVIDUALS NOT AT RISK FOR TYPE 2 DIABETES. BY CONTRAST, INFLAMMATORY RESPONSES TO LIFESTYLE FACTORS ARE MORE PRONOUNCED AND PROLONGED IN INDIVIDUALS AT RISK OF TYPE 2 DIABETES AND APPEAR TO OCCUR ALSO IN THE PANCREATIC ISLETS. CHRONIC LOW-GRADE INFLAMMATION WILL EVENTUALLY LEAD TO OVERT DIABETES IF COUNTER-REGULATORY CIRCUITS TO INFLAMMATION AND METABOLIC STRESS ARE COMPROMISED BECAUSE OF A GENETIC AND/OR EPIGENETIC PREDISPOSITION. HENCE, IT IS NOT THE LIFESTYLE CHANGE PER SE BUT A DEFICIENT COUNTER-REGULATORY RESPONSE IN PREDISPOSED INDIVIDUALS WHICH IS CRUCIAL TO DISEASE PATHOGENESIS. NOVEL APPROACHES OF INTERVENTION MAY TARGET THESE DEFICIENT DEFENCE MECHANISMS. 2010 10 2816 51 FIBROMYALGIA: PATHOGENESIS, MECHANISMS, DIAGNOSIS AND TREATMENT OPTIONS UPDATE. FIBROMYALGIA IS A SYNDROME CHARACTERIZED BY CHRONIC AND WIDESPREAD MUSCULOSKELETAL PAIN, OFTEN ACCOMPANIED BY OTHER SYMPTOMS, SUCH AS FATIGUE, INTESTINAL DISORDERS AND ALTERATIONS IN SLEEP AND MOOD. IT IS ESTIMATED THAT TWO TO EIGHT PERCENT OF THE WORLD POPULATION IS AFFECTED BY FIBROMYALGIA. FROM A MEDICAL POINT OF VIEW, THIS PATHOLOGY STILL PRESENTS INEXPLICABLE ASPECTS. IT IS KNOWN THAT FIBROMYALGIA IS CAUSED BY A CENTRAL SENSITIZATION PHENOMENON CHARACTERIZED BY THE DYSFUNCTION OF NEURO-CIRCUITS, WHICH INVOLVES THE PERCEPTION, TRANSMISSION AND PROCESSING OF AFFERENT NOCICEPTIVE STIMULI, WITH THE PREVALENT MANIFESTATION OF PAIN AT THE LEVEL OF THE LOCOMOTOR SYSTEM. IN RECENT YEARS, THE PATHOGENESIS OF FIBROMYALGIA HAS ALSO BEEN LINKED TO OTHER FACTORS, SUCH AS INFLAMMATORY, IMMUNE, ENDOCRINE, GENETIC AND PSYCHOSOCIAL FACTORS. A RHEUMATOLOGIST TYPICALLY MAKES A DIAGNOSIS OF FIBROMYALGIA WHEN THE PATIENT DESCRIBES A HISTORY OF PAIN SPREADING IN ALL QUADRANTS OF THE BODY FOR AT LEAST THREE MONTHS AND WHEN PAIN IS CAUSED BY DIGITAL PRESSURE IN AT LEAST 11 OUT OF 18 ALLOGENIC POINTS, CALLED TENDER POINTS. FIBROMYALGIA DOES NOT INVOLVE ORGANIC DAMAGE, AND SEVERAL DIAGNOSTIC APPROACHES HAVE BEEN DEVELOPED IN RECENT YEARS, INCLUDING THE ANALYSIS OF GENETIC, EPIGENETIC AND SEROLOGICAL BIOMARKERS. SYMPTOMS OFTEN BEGIN AFTER PHYSICAL OR EMOTIONAL TRAUMA, BUT IN MANY CASES, THERE APPEARS TO BE NO OBVIOUS TRIGGER. WOMEN ARE MORE PRONE TO DEVELOPING THE DISEASE THAN MEN. UNFORTUNATELY, THE CONVENTIONAL MEDICAL THERAPIES THAT TARGET THIS PATHOLOGY PRODUCE LIMITED BENEFITS. THEY REMAIN LARGELY PHARMACOLOGICAL IN NATURE AND TEND TO TREAT THE SYMPTOMATIC ASPECTS OF VARIOUS DISORDERS REPORTED BY THE PATIENT. THE STATISTICS, HOWEVER, HIGHLIGHT THE FACT THAT 90% OF PEOPLE WITH FIBROMYALGIA ALSO TURN TO COMPLEMENTARY MEDICINE TO MANAGE THEIR SYMPTOMS. 2021 11 1932 41 ENVIRONMENTAL EXPOSURES: AN UNDERRECOGNIZED CONTRIBUTION TO NONCOMMUNICABLE DISEASES. PREVIOUS ATTEMPTS TO DETERMINE THE DEGREE TO WHICH EXPOSURE TO ENVIRONMENTAL FACTORS CONTRIBUTE TO NONCOMMUNICABLE DISEASES (NCDS) HAVE BEEN VERY CONSERVATIVE AND HAVE SIGNIFICANTLY UNDERESTIMATED THE ACTUAL CONTRIBUTION OF THE ENVIRONMENT FOR AT LEAST TWO REASONS. FIRSTLY, MOST PREVIOUS REPORTS HAVE EXCLUDED THE CONTRIBUTION OF LIFESTYLE BEHAVIORAL RISK FACTORS, BUT THESE USUALLY INVOLVE SIGNIFICANT EXPOSURE TO ENVIRONMENTAL CHEMICALS THAT INCREASE RISK OF DISEASE. SECONDLY, EARLY LIFE EXPOSURE TO CHEMICAL CONTAMINANTS IS NOW CLEARLY ASSOCIATED WITH AN ELEVATED RISK OF SEVERAL DISEASES LATER IN LIFE, BUT THESE CONNECTIONS ARE OFTEN DIFFICULT TO DISCERN. THIS IS ESPECIALLY TRUE FOR ASTHMA AND NEURODEVELOPMENTAL CONDITIONS, BUT THERE IS ALSO A MAJOR CONTRIBUTION TO THE DEVELOPMENT OF OBESITY AND CHRONIC DISEASES. MOST CANCERS ARE CAUSED BY ENVIRONMENTAL EXPOSURES IN GENETICALLY SUSCEPTIBLE INDIVIDUALS. IN ADDITION, NEW INFORMATION SHOWS SIGNIFICANT ASSOCIATIONS BETWEEN CARDIOVASCULAR DISEASES AND DIABETES AND EXPOSURE TO ENVIRONMENTAL CHEMICALS PRESENT IN AIR, FOOD, AND WATER. THESE RELATIONSHIPS LIKELY REFLECT THE COMBINATION OF EPIGENETIC EFFECTS AND GENE INDUCTION. ENVIRONMENTAL FACTORS CONTRIBUTE SIGNIFICANTLY MORE TO NCDS THAN PREVIOUS REPORTS HAVE SUGGESTED. PREVENTION NEEDS TO SHIFT FOCUS FROM INDIVIDUAL RESPONSIBILITY TO SOCIETAL RESPONSIBILITY AND AN UNDERSTANDING THAT EFFECTIVE PREVENTION OF NCDS ULTIMATELY RELIES ON IMPROVED ENVIRONMENTAL MANAGEMENT TO REDUCE EXPOSURE TO MODIFIABLE RISKS. 2013 12 5025 35 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 13 380 42 AN EPIGENETIC PERSPECTIVE ON LIFESTYLE MEDICINE FOR DEPRESSION: IMPLICATIONS FOR PRIMARY CARE PRACTICE. DEPRESSION IS THE MOST COMMON PRESENTING MENTAL HEALTH DISORDER IN PRIMARY CARE. IT IS ALSO A MAJOR CONTRIBUTOR TO SOMATIC COMPLAINTS, WORSENING OF CHRONIC MEDICAL CONDITIONS, POOR QUALITY OF LIFE, AND SUICIDE. CURRENT PHARMACOLOGIC AND PSYCHOTHERAPEUTIC APPROACHES AVERT LESS THAN HALF OF DEPRESSION'S CUMULATIVE BURDEN ON SOCIETY. HOWEVER, THERE IS A GROWING BODY OF RESEARCH DESCRIBING BOTH HOW MALADAPTIVE LIFESTYLE CHOICES CONTRIBUTE TO THE DEVELOPMENT AND WORSENING OF DEPRESSION AND HOW LIFESTYLE-ORIENTED MEDICAL INTERVENTIONS CAN REDUCE THE INCIDENCE AND SEVERITY OF DEPRESSION. THIS RESEARCH, LARGELY DERIVED FROM AN EMERGING FIELD CALLED EPIGENETICS, ELUCIDATES THE INTERACTIONS BETWEEN OUR LIFESTYLE CHOICES AND THOSE EPIGENETIC FACTORS WHICH MEDIATE OUR TENDENCIES TOWARD EITHER HEALTH, OR THE ONSET, IF NOT WORSENING OF DISEASE. THE PRESENT REVIEW HIGHLIGHTS HOW LIFESTYLE CHOICES INVOLVING DIET, PHYSICAL ACTIVITY, SLEEP, SOCIAL RELATIONSHIPS, AND STRESS INFLUENCE EPIGENETIC PROCESSES POSITIVELY OR NEGATIVELY, AND THEREBY PLAY A SIGNIFICANT ROLE IN DETERMINING WHETHER ONE DOES OR DOES NOT SUFFER FROM DEPRESSION. THE AUTHORS PROPOSE THAT MEDICAL TRAINING PROGRAMS CONSIDER AND ADOPT LIFESTYLE MEDICINE ORIENTED INSTRUCTIONAL INITIATIVES THAT WILL ENABLE TOMORROW'S PRIMARY CARE PROVIDERS TO MORE EFFECTIVELY IDENTIFY AND THERAPEUTICALLY INTERVENE IN THE MALADAPTIVE CHOICES CONTRIBUTING TO THEIR PATIENTS' DEPRESSION. 2022 14 5290 19 PROSTATE CANCER PREVENTION: AGENT DEVELOPMENT STRATEGIES. DESPITE ADVANCES IN SURGERY, RADIATION, AND MEDICAL THERAPY OVER THE PAST DECADE AND THE WIDESPREAD ADOPTION OF PSA SCREENING, PROSTATE CANCER CONTINUES TO BE THE SECOND LEADING CAUSE OF CANCER DEATH IN MEN IN THE UNITED STATES. INVASIVE CANCER IS THE END RESULT OF CARCINOGENESIS, A CHRONIC PROCESS OCCURRING OVER MANY YEARS DRIVEN BY GENETIC AND EPIGENETIC ALTERATIONS. THE PROTRACTED NATURE OF THIS TRANSFORMATION TO THE MALIGNANT PHENOTYPE PROVIDES AN OPPORTUNITY TO INTERVENE PHARMACOLOGICALLY TO PREVENT, REVERSE, OR DELAY CARCINOGENESIS, I.E. CHEMOPREVENTION. HEREIN, WE DESCRIBE THE UNIQUE FEATURES OF CANCER PREVENTION, AS OPPOSED TO CANCER TREATMENT, AGENT DEVELOPMENT CLINICAL TRIALS, AND PROVIDE A SUMMARY OF THE ONGOING RESEARCH IN THIS FIELD BEING SUPPORTED BY THE NATIONAL CANCER INSTITUTE. 2014 15 4422 42 MOLECULAR AND GENETIC INFLAMMATION NETWORKS IN MAJOR HUMAN DISEASES. IT HAS BEEN WELL-RECOGNIZED THAT INFLAMMATION ALONGSIDE TISSUE REPAIR AND DAMAGE MAINTAINING TISSUE HOMEOSTASIS DETERMINES THE INITIATION AND PROGRESSION OF COMPLEX DISEASES. ALBEIT WITH THE ACCOMPLISHMENT OF HAVING CAPTURED THE MOST CRITICAL INFLAMMATION-INVOLVED MOLECULES, GENETIC SUSCEPTIBILITIES, EPIGENETIC FACTORS, AND ENVIRONMENTAL FACTORS, OUR SCHEMATA ON THE ROLE OF INFLAMMATION IN COMPLEX DISEASES REMAIN LARGELY PATCHY, IN PART DUE TO THE SUCCESS OF REDUCTIONISM IN TERMS OF RESEARCH METHODOLOGY PER SE. OMICS DATA ALONGSIDE THE ADVANCES IN DATA INTEGRATION TECHNOLOGIES HAVE ENABLED RECONSTRUCTION OF MOLECULAR AND GENETIC INFLAMMATION NETWORKS WHICH SHED LIGHT ON THE UNDERLYING PATHOPHYSIOLOGY OF COMPLEX DISEASES OR CLINICAL CONDITIONS. GIVEN THE PROVEN BENEFICIAL ROLE OF ANTI-INFLAMMATION IN CORONARY HEART DISEASE AS WELL AS OTHER COMPLEX DISEASES AND IMMUNOTHERAPY AS A REVOLUTIONARY TRANSITION IN ONCOLOGY, IT BECOMES TIMELY TO REVIEW OUR CURRENT UNDERSTANDING OF THE MOLECULAR AND GENETIC INFLAMMATION NETWORKS UNDERLYING MAJOR HUMAN DISEASES. IN THIS REVIEW, WE FIRST BRIEFLY DISCUSS THE COMPLEXITY OF INFECTIOUS DISEASES AND THEN HIGHLIGHT RECENTLY UNCOVERED MOLECULAR AND GENETIC INFLAMMATION NETWORKS IN OTHER MAJOR HUMAN DISEASES INCLUDING OBESITY, TYPE II DIABETES, CORONARY HEART DISEASE, LATE ONSET ALZHEIMER'S DISEASE, PARKINSON'S DISEASE, AND SPORADIC CANCER. THE COMMONALITY AND SPECIFICITY OF THESE MOLECULAR NETWORKS ARE ADDRESSED IN THE CONTEXT OF GENETICS BASED ON GENOME-WIDE ASSOCIATION STUDY (GWAS). THE DOUBLE-SWORD ROLE OF INFLAMMATION, SUCH AS HOW THE ABERRANT TYPE 1 AND/OR TYPE 2 IMMUNITY LEADS TO CHRONIC AND SEVERE CLINICAL CONDITIONS, REMAINS OPEN IN TERMS OF THE INFLAMMASOME AND THE CORE INFLAMMATOME NETWORK FEATURES. INCREASINGLY AVAILABLE LARGE OMICS AND CLINICAL DATA IN TANDEM WITH SYSTEMS BIOLOGY APPROACHES HAVE OFFERED AN EXCITING YET CHALLENGING OPPORTUNITY TOWARD RECONSTRUCTION OF MORE COMPREHENSIVE AND DYNAMIC MOLECULAR AND GENETIC INFLAMMATION NETWORKS, WHICH HOLD GREAT PROMISE IN TRANSITING NETWORK SNAPSHOTS TO VIDEO-STYLE MULTI-SCALE INTERPLAYS OF DISEASE MECHANISMS, IN TURN LEADING TO EFFECTIVE CLINICAL INTERVENTION. 2016 16 2881 44 FUTURE PERSPECTIVES OF PERSONALIZED WEIGHT LOSS INTERVENTIONS BASED ON NUTRIGENETIC, EPIGENETIC, AND METAGENOMIC DATA. AS OBESITY HAS BECOME A MAJOR GLOBAL PUBLIC HEALTH CHALLENGE, A LARGE NUMBER OF STUDIES HAVE ANALYZED DIFFERENT STRATEGIES AIMED AT INDUCING A NEGATIVE ENERGY BALANCE AND, CONSEQUENTLY, BODY WEIGHT LOSS. HOWEVER, MOST EXISTING WEIGHT LOSS PROGRAMS ARE GENERALLY UNSUCCESSFUL, SO SEVERAL INTERVENTIONS HAVE BEEN CARRIED OUT TO IDENTIFY PHYSIOLOGIC AND BEHAVIORAL FACTORS CONCERNING THIS VARIABILITY IN ORDER TO IMPLEMENT MORE PERSONALIZED TREATMENT. NOWADAYS, AN INDIVIDUALIZED APPROACH IS BEING PROPOSED THROUGH SO-CALLED PERSONALIZED NUTRITION, WHEREBY NOT ONLY THE PHENOTYPE BUT ALSO THE GENOTYPE IS USED FOR CUSTOMIZED NUTRITION TREATMENT. REGARDING BODY WEIGHT REGULATION, APPROXIMATELY 70 POLYMORPHISMS HAVE BEEN IDENTIFIED IN OR NEAR GENES RELATED TO ENERGY EXPENDITURE, APPETITE, ADIPOGENESIS, INSULIN RESISTANCE, AND LIPID METABOLISM. ALTHOUGH PERSONALIZED NUTRITION REFERS MAINLY TO GENETIC MAKEUP, RECENT ADVANCES IN THE INVESTIGATION OF THE EPIGENOME AND THE MICROBIOME OPEN THE DOOR TO IMPLEMENT MORE PERSONALIZED RECOMMENDATIONS FOR BODY WEIGHT MANAGEMENT. IN THIS CONTEXT, RECENT STUDIES HAVE DEMONSTRATED THE EXISTENCE OF SEVERAL EPIGENETIC MARKERS THAT MAY MODIFY GENE EXPRESSION AND COULD BE INVOLVED IN THE OUTCOME OF WEIGHT LOSS INTERVENTIONS. MOREOVER, DIFFERENT STUDIES HAVE SHOWN THAT DIETARY INTERVENTIONS COULD AFFECT THE COMPOSITION OF GUT MICROBIOTA AND HAVE AN IMPACT ON BODY WEIGHT. THE INTEGRATION OF NUTRIGENETIC, EPIGENETIC, AND METAGENOMIC DATA MAY LEAD TO THE DESIGN OF MORE PERSONALIZED DIETARY TREATMENTS TO PREVENT CHRONIC DISEASES AND TO OPTIMIZE THE INDIVIDUAL'S RESPONSE TO DIETARY INTERVENTIONS. 2015 17 3773 26 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 18 1415 35 DIETARY POLYPHENOLS AND THEIR RELATIONSHIP TO THE MODULATION OF NON-COMMUNICABLE CHRONIC DISEASES AND EPIGENETIC MECHANISMS: A MINI-REVIEW. CHRONIC NON-COMMUNICABLE DISEASES (NCDS) HAVE BEEN CONSIDERED A GLOBAL HEALTH PROBLEM, CHARACTERIZED AS DISEASES OF MULTIPLE FACTORS, WHICH ARE DEVELOPED THROUGHOUT LIFE, AND REGARDLESS OF GENETICS AS A RISK FACTOR OF IMPORTANT RELEVANCE, THE INCREASE IN MORTALITY ATTRIBUTED TO THE DISEASE TO ENVIRONMENTAL FACTORS AND THE LIFESTYLE ONE LEADS. ALTHOUGH THE REACTIVE SPECIES (ROS/RNS) ARE NECESSARY FOR SEVERAL PHYSIOLOGICAL PROCESSES, THEIR OVERPRODUCTION IS DIRECTLY RELATED TO THE PATHOGENESIS AND AGGRAVATION OF NCDS. IN CONTRAST, DIETARY POLYPHENOLS HAVE BEEN WIDELY ASSOCIATED WITH MINIMIZING OXIDATIVE STRESS AND INFLAMMATION. IN ADDITION TO THEIR ANTIOXIDANT POWER, POLYPHENOLS HAVE ALSO DRAWN ATTENTION FOR BEING ABLE TO MODULATE BOTH GENE EXPRESSION AND MODIFY EPIGENETIC ALTERATIONS, SUGGESTING AN ESSENTIAL INVOLVEMENT IN THE PREVENTION AND/OR DEVELOPMENT OF SOME PATHOLOGIES. THEREFORE, THIS REVIEW BRIEFLY EXPLAINED THE MECHANISMS IN THE DEVELOPMENT OF SOME NCDS, FOLLOWED BY A SUMMARY OF SOME EVIDENCE RELATED TO THE INTERACTION OF POLYPHENOLS IN OXIDATIVE STRESS, AS WELL AS THE MODULATION OF EPIGENETIC MECHANISMS INVOLVED IN THE MANAGEMENT OF NCDS. 2023 19 1673 32 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 20 367 36 AMPLIFIED PAIN SYNDROMES IN CHILDREN: TREATMENT AND NEW INSIGHTS INTO DISEASE PATHOGENESIS. PURPOSE OF REVIEW: ALTHOUGH MANY DIAGNOSTIC TERMS ARE USED FOR PEDIATRIC CHRONIC PAIN, EVIDENCE SUGGESTS A COMMON THREAD OF SIGNAL AMPLIFICATION, LEADING TO THE UNIFYING TERM 'AMPLIFIED PAIN SYNDROMES'. ONGOING RESEARCH PROVIDES NEW INSIGHTS INTO BIOPSYCHOSOCIAL CONTRIBUTORS AND TREATMENTS FOR PEDIATRIC AMPLIFIED PAIN SYNDROMES. RECENT FINDINGS: BASIC SCIENCE INDICATES A COMPLEX INTERPLAY OF GENETIC, EPIGENETIC, NEUROCHEMICAL, ENDOCRINE, AND INFLAMMATORY CONTRIBUTORS, ALONG WITH ENVIRONMENTAL AND PSYCHOLOGICAL FACTORS. ALTHOUGH MEDICATIONS AND INTERVENTIONS REMAIN COMMON APPROACHES TO CHILDREN WITH CHRONIC PAIN, THEIR EVIDENCE IS LIMITED. PRELIMINARY EVIDENCE EXISTS FOR MINDFULNESS-BASED THERAPIES, YOGA, AND OTHER COMPLEMENTARY/ALTERNATIVE MEDICINE APPROACHES. THE STRONGEST EVIDENCE IS FOR EXERCISE-BASED AND COGNITIVE-BEHAVIORAL TREATMENTS, IN PARTICULAR, WHEN COMBINED IN A MULTIDISCIPLINARY FORMAT. INTENSIVE APPROACHES (PAIN REHABILITATION) HAVE THE POTENTIAL TO EFFECTIVELY AND EFFICIENTLY TREAT THOSE MOST DISABLED BY AMPLIFIED PAIN SYNDROMES, AND LEAD TO SUSTAINED IMPROVEMENT IN PAIN, FUNCTIONING, AND MEDICAL UTILIZATION. SUMMARY: ALTHOUGH UNDERSTANDING OF THE MECHANISMS UNDERLYING PEDIATRIC AMPLIFIED PAIN SYNDROMES EVOLVES, STANDARD OF CARE IS MULTIDISCIPLINARY EMPHASIZING EXERCISE THERAPY, COGNITIVE-BEHAVIORAL TREATMENT, AND SELF-REGULATION. TREATMENT SHOULD TARGET FULL RETURN TO PHYSICAL FUNCTION, WHICH LEADS TO SUBSEQUENT IMPROVEMENT OR RESOLUTION OF PAIN. MULTIDISCIPLINARY CARE CAN BE COORDINATED BY A RHEUMATOLOGIST OR OTHER PHYSICIAN WITH APPROPRIATE REFERRALS, OR THROUGH A MULTIDISCIPLINARY TEAM. 2014