1 3851 182 IS IRRITABLE BOWEL SYNDROME OUT OF DATE AND MISLEADING AS A DIAGNOSIS? AIM: THIS STUDY AIMED AT ASSESSING THE EFFICACY OF TARGETED INTERVENTIONS ADDRESSING COMMON FOOD SENSITIVITIES AND LIFESTYLE FACTORS THAT COMMONLY CONTRIBUTE TO THE PRESENTATION OF GASTROINTESTINAL PROBLEMS IDENTIFIED AS IRRITABLE BOWEL SYNDROME (IBS). BACKGROUND: IBS HAS SERVED TO COVER THE EXPRESSION OF MULTIFACTORIAL DISORDERS WITH VARIABLE AETIOLOGY AND PATHOPHYSIOLOGY. FOOD ANTIGENS IMPLICATED IN THE MODERN LIFESTYLE, ACTING AS STRONG EPIGENETIC FACTORS IS STRONGLY IMPLICATED IN PATHOPHYSIOLOGY OF CONDITIONS UNDER IBS. IDENTIFYING AND ADDRESSING FOOD SENSITIVITIES IN PATIENTS PRESENTING WITH IBS LIKE SYMPTOMS ARE CURRENTLY UNDEREMPHASISED IN CLINICAL GUIDELINES YET HAVE THE POTENTIAL TO PROVIDE MAJOR BENEFITS FOR PATIENTS. METHODS: INFORMATION WAS COLLECTED FROM THE MEDICAL RECORDS OF PATIENTS THAT WERE REFERRED TO THE GASTROENTEROLOGY UNIT OF PALMERSTON NORTH DHB WITH UNEXPLAINED GASTROINTESTINAL (GI) SYMPTOMS WITH OR WITHOUT OTHER GI COMORBIDITIES BETWEEN SEPTEMBER 2018 AND NOVEMBER 2021. RESULTS: THE MAIN MANAGEMENT OPTION OFFERED TO THE 121 PATIENTS INCLUDED IN THIS STUDY, WAS LIFESTYLE ADJUSTMENT AND/OR A TRIAL OF 6 WEEKS, ELIMINATING GLUTEN AND LACTOSE FROM THE DIET. THE MOST PREVALENT SYMPTOMS WERE ABDOMINAL PAIN 96/121 (79%), DIARRHOEA 83/121 (69%), FOLLOWED BY BLOATING AND CONSTIPATION. SEVENTY-EIGHT PATIENTS HAD THE OUTCOMES OF THEIR IMPROVEMENT AVAILABLE. A TOTAL OF 42 OUT OF 78 PATIENTS (54%) WERE TREATED EXCLUSIVELY WITH GLUTEN AND LACTOSE-FREE DIET, IN THIS GROUP OF PATIENTS 86% (36/42) REPORTED A SIGNIFICANT IMPROVEMENT IN THEIR SYMPTOMS WITH A SCORE IN THE RANGE OF 40-100%. CONCLUSION: OUR STUDY ILLUSTRATES THE IMPORTANCE OF FOCUSING ON TRIGGERING FACTORS WHEN ASSESSING PATIENTS WITH IBS. WE SUGGEST THAT CAREFUL IDENTIFYING AND ELIMINATING THE TRIGGERING FOOD ANTIGENS AS MONOTHERAPY OR IN ADDITION TO THE LIFESTYLE ADJUSTMENT WHERE APPROPRIATE SHOULD BE THE MAIN OBJECTIVE IN SYMPTOMATIC PATIENTS FULFILLING THE IBS DIAGNOSTIC CRITERIA. THESE COMBINATIONS AND HOLISTIC APPROACH IN TREATING IBS' PATIENTS' SYMPTOMS ARE LESS EXPENSIVE, NON-TOXIC, AND HIGHLY EFFECTIVE IN ACHIEVING OPTIMAL OUTCOMES AND IMPROVING THESE PATIENT'S QUALITY OF LIFE. 2023 2 4673 51 NEW INSIGHTS INTO THE PATHOGENESIS AND TREATMENT OF IRRITABLE BOWEL SYNDROME. IRRITABLE BOWEL SYNDROME (IBS) IS ONE OF THE MOST COMMON FUNCTIONAL GASTROINTESTINAL DISORDERS (FGID), CHARACTERIZED BY ABDOMINAL PAIN AND A CHANGE IN STOOL FORM THAT CANNOT BE EXPLAINED BY STRUCTURAL ABNORMALITIES. ITS PREVALENCE RANGES FROM 9 TO 23% OF THE WORLDWIDE POPULATION. THE PATHOPHYSIOLOGY OF IBS IS DIVERSE AND NOT WELL UNDERSTOOD. BIOPSYCHOSOCIAL CONCEPT ASSUMES THAT THE DISEASE IS A PRODUCT OF PSYCHOSOCIAL FACTORS AND ALTERED AT MULTIPLE LEVELS OF GUT PHYSIOLOGY INTERACTIONS. SOME AETIOLOGICAL FACTORS HAVE BEEN IDENTIFIED, YET. ONE OF THE MOST IMPORTANT IS THE DISRUPTION OF BRAIN-GUT MUTUAL COMMUNICATION THAT LEADS TO VISCERAL HYPERSENSITIVITY. ALSO GENETIC AND EPIGENETIC FACTORS ARE INVOLVED. CHRONIC STRESS MAY PREDISPOSE TO IBS AS WELL AS EXACERBATE ITS SYMPTOMS. BOTH QUANTITATIVE AND QUALITATIVE DISORDERS OF THE GUT MICROBIOTA ARE OBSERVED. THERE IS ALSO A RELATIONSHIP BETWEEN THE IBS SYMPTOMS AND THE INTAKE OF A SPECIFIC TYPE OF FOOD PRODUCTS. IN THE DIARRHOEA TYPE OF IBS THE ROLE OF PREVIOUS GASTROINTESTINAL INFECTION IS DEMONSTRATED. RECENT STUDIES HAVE SUGGESTED THAT VISCERAL HYPERSENSITIVITY IN PATIENTS WITH IBS MAY BE SECONDARY TO THE ACTIVATION OF THE IMMUNE CELLS AND LOW-GRADE INFLAMMATION. CLINICAL SYMPTOMS OF IBS INCLUDE ABDOMINAL PAIN AND CHANGE IN BOWEL HABITS AS WELL AS SOMATIC AND PSYCHIATRIC COMORBIDITIES. IBS IS DIAGNOSED ON THE BASIS OF ROME DIAGNOSTIC CRITERIA. RECENTLY, THEIR NEWEST VERSION (ROME IV) HAS BEEN PRESENTED. THE AIM OF THIS REVIEW IS TO SUMMARIZE THE PAST DECADE PROGRESS IN IBS DIAGNOSIS, MAIN PATHOPHYSIOLOGICAL ASPECTS AND THERAPEUTIC MANAGEMENT STRATEGY. 2017 3 4174 36 MELATONIN MEDIATED INHIBITION OF EZH2-NOS2 CROSSTALK ATTENUATES INFLAMMATORY BOWEL DISEASE IN PRECLINICAL IN VITRO AND IN VIVO MODELS. AIMS: INFLAMMATORY BOWEL DISEASE IS CHARACTERISED BY ABDOMINAL PAIN, DIARRHOEA, RECTAL BLEEDING AND WEIGHT LOSS. SOMETIMES IT MAY LEADS TO SEVERE HEALTH COMPLICATIONS RESULTING IN DEATH OF AN INDIVIDUAL. CURRENT RESEARCH EFFORTS TO HIGHLIGHT THE ROLE OF MELATONIN IN REGULATING EZH2, A MASTER EPIGENETIC REGULATOR AND ITS BENEFICIARY EFFECT IN CASE OF IBD MANAGEMENT. MATERIAL METHODS: MURINE MACROPHAGES (RAW 264.7) WERE TREATED WITH LIPOPOLYSACCHARIDES (LPS) TO ACTIVATE THEM FOR GENERATING INFLAMMATORY RESPONSE TO INVESTIGATE EFFICACY OF MELATONIN IN-VITRO MODELS. SIMILARLY, FOR DEVELOPING IN VIVO MODELS, DEXTRAN SODIUM SULPHATE (36-50 KDA) WAS USED. EVALUATIONS OF ANTI-INFLAMMATORY ACTIVITIES WERE CARRIED OUT BY NITRITE ASSAY, WESTERN BLOTTING, Q-PCR, IMMUNOFLUORESCENCE, AND HISTOLOGICAL STUDIES. KEY FINDINGS: REDUCTION OF EPIGENETIC TARGET, EZH2 BY MELATONIN SIGNIFICANTLY IMPROVES THE CLINICAL SYMPTOMS OF DEXTRAN SODIUM SULPHATE INDUCED COLITIS AND MAY BE IMPLICATED AS A POTENTIAL THERAPEUTIC TARGET IN IBD MANAGEMENT. THE PRESENT STUDY EVALUATES THE EFFICACY OF MELATONIN BY EPIGENETIC REGULATION IN IBD MODELS. DOWN REGULATION OF EZH2 BY MELATONIN REDUCED THE CHEMICAL INDUCED INFLAMMATORY INSULTS IN IN VITRO AND IN VIVO MODELS. EXPLORATION OF MOLECULAR PATHWAYS HAS REVEALED INTERLINK OF EZH2 AND NOS2, A HALLMARK OF INFLAMMATION. MOLECULAR MECHANISTIC ACTION OF MELATONIN IS ATTRIBUTED TO INHIBITION OF THE EXPRESSION AND PHYSICAL INTERACTION OF EZH2 AND NOS2. SIGNIFICANCE: OUR STUDY HIGHLIGHTS MELATONIN THERAPEUTIC EFFECT VIA ATTENUATING INTERACTION BETWEEN EZH2 AND NOS2 WHICH IS BENEFICIAL IN MANAGING IBD TREATMENT. 2022 4 4428 29 MOLECULAR BASIS OF THE IRRITABLE BOWEL SYNDROME. IRRITABLE BOWEL SYNDROME (IBS) IS A FUNCTIONAL DISORDER CHARACTERIZED BY ABDOMINAL PAIN, DISCOMFORT AND BLOATING. THE PATHOPHYSIOLOGY OF IBS IS POORLY UNDERSTOOD, BUT THE PRESENCE OF PSYCHOSOCIAL BASIS IS NOW KNOWN. THERE IS AN INCREASING NUMBER OF PUBLICATIONS SUPPORTING THE ROLE OF GENETICS IN IBS. MOST OF THE VARIATIONS ARE FOUND IN GENES ASSOCIATED WITH THE BRAIN-GUT AXIS, REVEALING THE STRONG CORRELATION OF BRAIN-GUT AXIS AND IBS. MIRNAS, WHICH PLAY CRITICAL ROLES IN PHYSIOLOGICAL PROCESSES, ARE NOT WELL STUDIED IN IBS. HOWEVER, SO FAR THERE IS FOUND AN INVOLVEMENT OF ALTERATIONS IN MIRNA EXPRESSION OR SEQUENCE, IN IBS SYMPTOMS. IBS PHENOTYPE IS AFFECTED BY EPIGENETIC ALTERATION AND ENVIRONMENT. CHANGES IN DNA AND HISTONE METHYLATION ARE OBSERVED IN PATIENTS WHO SUFFERED CHILDHOOD TRAUMA OR ABUSE, RESULTING IN ALTERED GENE EXPRESSION, SUCH AS THE GLUCOCORTICOID RECEPTOR GENE. FINALLY, DIET IS ANOTHER FACTOR ASSOCIATED WITH IBS, WHICH MAY CONTRIBUTE TO SYMPTOM ONSET. CERTAIN FOODS MAY AFFECT ON BACTERIAL METABOLISM AND EPIGENETIC MODIFICATIONS, PREDISPOSING TO IBS. 2014 5 4518 36 MULTI-OMICS FOR BIOMARKER APPROACHES IN THE DIAGNOSTIC EVALUATION AND MANAGEMENT OF ABDOMINAL PAIN AND IRRITABLE BOWEL SYNDROME: WHAT LIES AHEAD. RELIABLE BIOMARKERS FOR COMMON DISORDERS OF GUT-BRAIN INTERACTION CHARACTERIZED BY ABDOMINAL PAIN, INCLUDING IRRITABLE BOWEL SYNDROME (IBS), ARE CRITICALLY NEEDED TO ENHANCE CARE AND DEVELOP INDIVIDUALIZED THERAPIES. THE DYNAMIC AND HETEROGENEOUS NATURE OF THE PATHOPHYSIOLOGICAL MECHANISMS THAT UNDERLIE VISCERAL HYPERSENSITIVITY HAVE CHALLENGED SUCCESSFUL BIOMARKER DEVELOPMENT. CONSEQUENTLY, EFFECTIVE THERAPIES FOR PAIN IN IBS ARE LACKING. HOWEVER, RECENT ADVANCES IN MODERN OMICS TECHNOLOGIES OFFER NEW OPPORTUNITIES TO ACQUIRE DEEP BIOLOGICAL INSIGHTS INTO MECHANISMS OF PAIN AND NOCICEPTION. NEWER METHODS FOR LARGE-SCALE DATA INTEGRATION OF COMPLEMENTARY OMICS APPROACHES HAVE FURTHER EXPANDED OUR ABILITY TO BUILD A HOLISTIC UNDERSTANDING OF COMPLEX BIOLOGICAL NETWORKS AND THEIR CO-CONTRIBUTIONS TO ABDOMINAL PAIN. HERE, WE REVIEW THE MECHANISMS OF VISCERAL HYPERSENSITIVITY, FOCUSING ON IBS. WE DISCUSS CANDIDATE BIOMARKERS FOR PAIN IN IBS IDENTIFIED THROUGH SINGLE OMICS STUDIES AND SUMMARIZE EMERGING MULTI-OMICS APPROACHES FOR DEVELOPING NOVEL BIOMARKERS THAT MAY TRANSFORM CLINICAL CARE FOR PATIENTS WITH IBS AND ABDOMINAL PAIN. 2023 6 105 37 A REVIEW OF MICROBIOTA AND IRRITABLE BOWEL SYNDROME: FUTURE IN THERAPIES. IRRITABLE BOWEL SYNDROME (IBS), ONE OF THE MOST FREQUENT DIGESTIVE DISORDERS, IS CHARACTERIZED BY CHRONIC AND RECURRENT ABDOMINAL PAIN AND ALTERED BOWEL HABIT. THE ORIGIN SEEMS TO BE MULTIFACTORIAL AND IS STILL NOT WELL DEFINED FOR THE DIFFERENT SUBTYPES. GENETIC, EPIGENETIC AND SEX-RELATED MODIFICATIONS OF THE FUNCTIONING OF THE NERVOUS AND IMMUNE-ENDOCRINE SUPERSYSTEMS AND REGULATION OF BRAIN-GUT PHYSIOLOGY AND BILE ACID PRODUCTION AND ABSORPTION ARE CERTAINLY INVOLVED. ACQUIRED PREDISPOSITION MAY ACT IN CONJUNCTION WITH INFECTIOUS, TOXIC, DIETARY AND LIFE EVENT-RELATED FACTORS TO ENHANCE EPITHELIAL PERMEABILITY AND ELICIT MUCOSAL MICROINFLAMMATION, IMMUNE ACTIVATION AND DYSBIOSIS. NOTABLY, STRONG EVIDENCE SUPPORTS THE ROLE OF BACTERIAL, VIRAL AND PARASITIC INFECTIONS IN TRIGGERING IBS, AND TARGETING MICROBIOTA SEEMS PROMISING IN VIEW OF THE POSITIVE RESPONSE TO MICROBIOTA-RELATED THERAPIES IN SOME PATIENTS. HOWEVER, THE LACK OF HIGHLY PREDICTIVE DIAGNOSTIC BIOMARKERS AND THE COMPLEXITY AND HETEROGENEITY OF IBS PATIENTS MAKE MANAGEMENT DIFFICULT AND UNSATISFACTORY IN MANY CASES, REDUCING PATIENT HEALTH-RELATED QUALITY OF LIFE AND INCREASING THE SANITARY BURDEN. THIS ARTICLE REVIEWS SPECIFIC ALTERATIONS AND INTERVENTIONS TARGETING THE GUT MICROBIOTA IN IBS, INCLUDING PREBIOTICS, PROBIOTICS, SYNBIOTICS, NON-ABSORBABLE ANTIBIOTICS, DIETS, FECAL TRANSPLANTATION AND OTHER POTENTIAL FUTURE APPROACHES USEFUL FOR THE DIAGNOSIS, PREVENTION AND TREATMENT OF IBS. 2018 7 6254 31 THE MICROBIOME AND IRRITABLE BOWEL SYNDROME - A REVIEW ON THE PATHOPHYSIOLOGY, CURRENT RESEARCH AND FUTURE THERAPY. IRRITABLE BOWEL SYNDROME (IBS) IS A FUNCTIONAL DISORDER WHICH AFFECTS A LARGE PROPORTION OF THE POPULATION GLOBALLY. THE PRECISE ETIOLOGY OF IBS IS STILL UNKNOWN, ALTHOUGH CONSENSUS UNDERSTANDING PROPOSES IBS TO BE OF MULTIFACTORIAL ORIGIN WITH YET UNDEFINED SUBTYPES. GENETIC AND EPIGENETIC FACTORS, STRESS-RELATED NERVOUS AND ENDOCRINE SYSTEMS, IMMUNE DYSREGULATION AND THE BRAIN-GUT AXIS SEEM TO BE CONTRIBUTING FACTORS THAT PREDISPOSE INDIVIDUALS TO IBS. IN ADDITION TO FOOD HYPERSENSITIVITY, TOXINS AND ADVERSE LIFE EVENTS, CHRONIC INFECTIONS AND DYSBIOTIC GUT MICROBIOTA HAVE BEEN SUGGESTED TO TRIGGER IBS SYMPTOMS IN TANDEM WITH THE PREDISPOSING FACTORS. THIS REVIEW WILL SUMMARIZE THE PATHOPHYSIOLOGY OF IBS AND THE ROLE OF GUT MICROBIOTA IN RELATION TO IBS. CURRENT METHODOLOGIES FOR MICROBIOME STUDIES IN IBS SUCH AS GENOME SEQUENCING, METAGENOMICS, CULTUROMICS AND ANIMAL MODELS WILL BE DISCUSSED. THE MYRIAD OF THERAPY OPTIONS SUCH AS IMMUNOGLOBULINS (IMMUNE-BASED THERAPY), PROBIOTICS AND PREBIOTICS, DIETARY MODIFICATIONS INCLUDING FODMAP RESTRICTION DIET AND GLUTEN-FREE DIET, AS WELL AS FECAL TRANSPLANTATION WILL BE REVIEWED. FINALLY THIS REVIEW WILL HIGHLIGHT FUTURE DIRECTIONS IN IBS THERAPY RESEARCH, INCLUDING IDENTIFICATION OF NEW MOLECULAR TARGETS, APPLICATION OF 3-D GUT MODEL, GUT-ON-A-CHIP AND PERSONALIZED THERAPY. 2019 8 2167 41 EPIGENETIC MECHANISMS IN IRRITABLE BOWEL SYNDROME. IRRITABLE BOWEL SYNDROME (IBS) IS A BRAIN-GUT AXIS DISORDER CHARACTERIZED BY ABDOMINAL PAIN AND ALTERED BOWEL HABITS. IBS IS A MULTIFACTORIAL, STRESS-SENSITIVE DISORDER WITH EVIDENCE FOR FAMILIAL CLUSTERING ATTRIBUTED TO GENETIC OR SHARED ENVIRONMENTAL FACTORS. HOWEVER, THERE ARE WEAK GENETIC ASSOCIATIONS REPORTED WITH IBS AND A LACK OF EVIDENCE TO SUGGEST THAT MAJOR GENETIC FACTOR(S) CONTRIBUTE TO IBS PATHOPHYSIOLOGY. STUDIES ON ANIMAL MODELS OF STRESS, INCLUDING EARLY LIFE STRESS, SUGGEST A ROLE FOR ENVIRONMENTAL FACTORS, SPECIFICALLY, STRESS ASSOCIATED WITH DYSREGULATION OF CORTICOTROPIN RELEASING FACTOR AND HYPOTHALAMUS-PITUITARY-ADRENAL (HPA) AXIS PATHWAYS IN THE PATHOPHYSIOLOGY OF IBS. RECENT EVIDENCE SUGGESTS THAT EPIGENETIC MECHANISMS, WHICH CONSTITUTE MOLECULAR CHANGES NOT DRIVEN BY A CHANGE IN GENE SEQUENCE, CAN MEDIATE ENVIRONMENTAL EFFECTS ON CENTRAL AND PERIPHERAL FUNCTION. EPIGENETIC ALTERATIONS INCLUDING DNA METHYLATION CHANGES, HISTONE MODIFICATIONS, AND DIFFERENTIAL EXPRESSION OF NON-CODING RNAS (MICRORNA [MIRNA] AND LONG NON-CODING RNA) HAVE BEEN ASSOCIATED WITH SEVERAL DISEASES. THE OBJECTIVE OF THIS REVIEW IS TO ELUCIDATE THE MOLECULAR FACTORS IN THE PATHOPHYSIOLOGY OF IBS WITH AN EMPHASIS ON EPIGENETIC MECHANISMS. EMERGING EVIDENCE FOR EPIGENETIC CHANGES IN IBS INCLUDES CHANGES IN DNA METHYLATION IN ANIMAL MODELS OF IBS AND PATIENTS WITH IBS, AND VARIOUS MIRNAS THAT HAVE BEEN ASSOCIATED WITH IBS AND ENDOPHENOTYPES, SUCH AS INCREASED VISCERAL SENSITIVITY AND INTESTINAL PERMEABILITY. DNA METHYLATION, IN PARTICULAR, IS AN EMERGING FIELD IN THE REALM OF COMPLEX DISEASES AND A PROMISING MECHANISM WHICH CAN PROVIDE IMPORTANT INSIGHTS INTO IBS PATHOGENESIS AND IDENTIFY POTENTIAL TARGETS FOR TREATMENT. 2020 9 5835 36 STRESS-INDUCED VISCERAL PAIN: TOWARD ANIMAL MODELS OF IRRITABLE-BOWEL SYNDROME AND ASSOCIATED COMORBIDITIES. VISCERAL PAIN IS A GLOBAL TERM USED TO DESCRIBE PAIN ORIGINATING FROM THE INTERNAL ORGANS, WHICH IS DISTINCT FROM SOMATIC PAIN. IT IS A HALLMARK OF FUNCTIONAL GASTROINTESTINAL DISORDERS SUCH AS IRRITABLE-BOWEL SYNDROME (IBS). CURRENTLY, THE TREATMENT STRATEGIES TARGETING VISCERAL PAIN ARE UNSATISFACTORY, WITH DEVELOPMENT OF NOVEL THERAPEUTICS HINDERED BY A LACK OF DETAILED KNOWLEDGE OF THE UNDERLYING MECHANISMS. STRESS HAS LONG BEEN IMPLICATED IN THE PATHOPHYSIOLOGY OF VISCERAL PAIN IN BOTH PRECLINICAL AND CLINICAL STUDIES. HERE, WE DISCUSS THE COMPLEX ETIOLOGY OF VISCERAL PAIN REVIEWING OUR CURRENT UNDERSTANDING IN THE CONTEXT OF THE ROLE OF STRESS, GENDER, GUT MICROBIOTA ALTERATIONS, AND IMMUNE FUNCTIONING. FURTHERMORE, WE REVIEW THE ROLE OF GLUTAMATE, GABA, AND EPIGENETIC MECHANISMS AS POSSIBLE THERAPEUTIC STRATEGIES FOR THE TREATMENT OF VISCERAL PAIN FOR WHICH THERE IS AN UNMET MEDICAL NEED. MOREOVER, WE DISCUSS THE MOST WIDELY DESCRIBED RODENT MODELS USED TO MODEL VISCERAL PAIN IN THE PRECLINICAL SETTING. THE THEORY BEHIND, AND APPLICATION OF, ANIMAL MODELS IS KEY FOR BOTH THE UNDERSTANDING OF UNDERLYING MECHANISMS AND DESIGN OF FUTURE THERAPEUTIC INTERVENTIONS. TAKEN TOGETHER, IT IS APPARENT THAT STRESS-INDUCED VISCERAL PAIN AND ITS PSYCHIATRIC COMORBIDITIES, AS TYPIFIED BY IBS, HAS A MULTIFACETED ETIOLOGY. MOREOVER, TREATMENT STRATEGIES STILL LAG FAR BEHIND WHEN COMPARED TO OTHER PAIN MODALITIES. THE DEVELOPMENT OF NOVEL, EFFECTIVE, AND SPECIFIC THERAPEUTICS FOR THE TREATMENT OF VISCERAL PAIN HAS NEVER BEEN MORE PERTINENT. 2015 10 367 33 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 11 537 29 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 12 6827 26 [GILLES DE LA TOURETTE'S DISEASE. SYMPTOMS, ETIOPATHOGENESIS AND THERAPEUTIC APPROACHES]. THE GILLES DE LA TOURETTE SYNDROME IS A USUALLY CHRONIC NEUROPSYCHIATRIC DISORDER WITH AN EARLY CHILDHOOD ONSET FEATURING MAINLY MOTOR AND VOCAL TICS. IT SEEMS THAT STRONG GENETIC FACTORS MAKE A MAJOR CONTRIBUTION TO THE ETIOLOGY OF THIS DISORDER, BUT THERE ARE ALSO CLUES THAT EPIGENETIC FACTORS ARE INVOLVED IN THE PATHOGENESIS OF TOURETTE'S SYNDROME, SUCH AS MATERNAL STRESS DURING PREGNANCY, BIRTH COMPLICATIONS AND HORMONAL INFLUENCES. FIRST IN LINE FOR ADEQUATE TREATMENT ARE NEUROLEPTIC COMPOUNDS OF HIGH POTENCY, BESIDES, SEVERAL OTHER PSYCHOACTIVE DRUGS HAVE SHOWN SOME THERAPEUTIC EFFECTS. LESS EVIDENT IS THE EFFICACY OF NEUROSURGICAL AND PSYCHOTHERAPEUTIC INTERVENTIONS. 1997 13 5637 38 SEROTONIN TRANSPORTER GENE POLYMORPHISMS IN SOUTHWESTERN IRANIAN PATIENTS WITH IRRITABLE BOWEL SYNDROME. BACKGROUND AND STUDY AIMS: IRRITABLE BOWEL SYNDROME IS A COMMON CHRONIC FUNCTIONAL GASTROINTESTINAL DISORDER OF UNKNOWN ETIOLOGY. SEROTONIN IS AN IMPORTANT FACTOR IN SENSORY SIGNALING IN THE BRAIN-GUT AXIS, WHICH PLAYS A KEY ROLE IN INTESTINAL MOTILITY AND SECRETION. SEROTONIN CLEARANCE IS MEDIATED BY A SPECIFIC PROTEIN CALLED THE SEROTONIN REUPTAKE TRANSPORTER. TRANSCRIPTION ACTIVITY OF THE SEROTONIN TRANSPORTER GENE IS AFFECTED BY SOME POLYMORPHISMS IN THIS GENE. THE AIM OF THIS STUDY WAS TO INVESTIGATE THE RELATIONSHIP BETWEEN SEROTONIN TRANSPORTER GENE POLYMORPHISMS AND IRRITABLE BOWEL SYNDROME. PATIENTS/MATERIAL AND METHODS: THE 5-HTTLPR, RS25531 AND STIN2VNTR POLYMORPHISMS OF THE SEROTONIN TRANSPORTER GENE WERE ANALYZED BY PCR-BASED METHODS IN 50 PATIENTS WITH IRRITABLE BOWEL SYNDROME AND 100 HEALTHY CONTROLS. RESULTS: SEROTONIN TRANSPORTER POLYMORPHISMS WERE SIMILAR IN PATIENTS AND HEALTHY CONTROLS. THERE WERE NO SIGNIFICANT DIFFERENCES IN ALLELE OR GENOTYPE FREQUENCIES BETWEEN THE TWO GROUPS. CONCLUSION: OUR FINDINGS SUGGEST THAT POLYMORPHISMS IN THE GENE ENCODING FOR THE SEROTONIN TRANSPORTER ARE NOT ASSOCIATED WITH IRRITABLE BOWEL SYNDROME. INTERACTIONS BETWEEN ENVIRONMENTAL FACTORS AND PREDISPOSING GENETIC FACTORS ARE IMPORTANT IN THE PATHOPHYSIOLOGY OF IRRITABLE BOWEL SYNDROME, AND FURTHER GENETIC AND EPIGENETIC RESEARCH MAY PROVIDE NOVEL INSIGHTS INTO THE MECHANISMS CONTRIBUTING TO THIS DISEASE. 2013 14 5039 39 PHARMACOGENETICS OF CHRONIC PAIN MANAGEMENT. OBJECTIVE: THE EXPERIENCE OF CHRONIC PAIN IS ONE OF THE COMMONEST REASONS INDIVIDUALS SEEK MEDICAL ATTENTION, MAKING THE MANAGEMENT OF CHRONIC PAIN A MAJOR ISSUE IN CLINICAL PRACTICE. DRUG METABOLISM AND RESPONSES ARE AFFECTED BY MANY FACTORS, WITH GENETIC VARIATIONS OFFERING ONLY A PARTIAL EXPLANATION OF AN INDIVIDUAL'S RESPONSE. THERE IS A PAUCITY OF EVIDENCE FOR THE BENEFITS OF PHARMACOGENETIC TESTING IN THE CONTEXT OF PAIN MANAGEMENT. DESIGN AND METHODS: WE REVIEWED THE LITERATURE BETWEEN 2000 AND 2013, AND REFERENCES CITED THEREIN, USING VARIOUS KEYWORDS RELATED TO PAIN MANAGEMENT, PHARMACOLOGY AND PHARMACOGENETICS. RESULTS: OPIOIDS CONTINUE TO BE THE MAINSTAY OF CHRONIC PAIN MANAGEMENT. SEVERAL NON-OPIOID BASED THERAPIES, SUCH AS TREATMENT WITH CANNABINOIDS, GENE THERAPY AND EPIGENETIC-BASED APPROACHES ARE NOW AVAILABLE FOR THESE PATIENTS. ADJUVANT THERAPIES WITH ANTIDEPRESSANTS, BENZODIAZEPINES OR ANTICONVULSANTS CAN ALSO BE USEFUL IN MANAGING PAIN. CURRENTLY, LABORATORY MONITORING OF PAIN MANAGEMENT PATIENTS, IF PERFORMED, IS LARGELY THROUGH URINE DRUG MEASUREMENTS. CONCLUSIONS: DRUG HALF-LIFE CALCULATIONS CAN BE USED AS FUNCTIONAL MARKERS OF THE CUMULATIVE EFFECT OF PHARMACOGENETICS AND DRUG-DRUG INTERACTIONS. ASSESSMENT OF HALF-LIFE AND THERAPEUTIC EFFECTS MAY BE MORE USEFUL THAN GENETIC TESTING IN PREVENTING ADVERSE DRUG REACTIONS TO PAIN MEDICATIONS, WHILE ENSURING EFFECTIVE ANALGESIA. DEFINITIVE, MASS SPECTROMETRY-BASED METHODS, CAPABLE OF MEASURING PARENT DRUG AND METABOLITE LEVELS, ARE THE MOST USEFUL ASSAYS FOR THIS PURPOSE. URINE DRUG MEASUREMENTS DO NOT NECESSARILY CORRELATE WITH SERUM DRUG CONCENTRATIONS OR THERAPEUTIC EFFECTS. THEREFORE, THEY ARE LIMITED IN THEIR USE IN MONITORING EFFICACY AND TOXICITY. 2014 15 5331 46 PUTTING THE PIECES TOGETHER IN GILLES DE LA TOURETTE SYNDROME: EXPLORING THE LINK BETWEEN CLINICAL OBSERVATIONS AND THE BIOLOGICAL BASIS OF DYSFUNCTION. GILLES DE LA TOURETTE SYNDROME IS A COMPLEX, IDIOPATHIC NEUROPSYCHIATRIC DISORDER WHOSE PATHOPHYSIOLOGICAL MECHANISMS HAVE YET TO BE ELUCIDATED. IT IS PHENOTYPICALLY HETEROGENEOUS AND MANIFESTS MORE OFTEN THAN NOT WITH BOTH MOTOR AND BEHAVIORAL IMPAIRMENT, ALTHOUGH TICS ARE ITS CLINICAL HALLMARK. TICS THEMSELVES PRESENT WITH A COMPLEX PROFILE AS THEY CHARACTERISTICALLY WAX AND WANE AND ARE OFTEN PRECEDED BY PREMONITORY SOMATOSENSORY SENSATIONS TO WHICH IT IS SAID A TIC IS THE RESPONSE. HIGHLY COMORBID WITH OBSESSIVE-COMPULSIVE DISORDER AND ATTENTION DEFICIT-HYPERACTIVITY DISORDER, IT IS PURPORTED TO BE AN EPIGENETIC, NEURODEVELOPMENTAL SPECTRUM DISORDER WITH A COMPLEX GENETIC PROFILE. IT HAS A CHILDHOOD ONSET, OCCURS DISPROPORTIONATELY IN MALES, AND SHOWS SPONTANEOUS SYMPTOMATIC ATTENUATION BY ADULTHOOD IN THE MAJORITY OF THOSE AFFLICTED. ALTHOUGH NOT FULLY UNDERSTOOD, ITS NEUROBIOLOGICAL BASIS IS LINKED TO DYSFUNCTION IN THE CORTICO-BASAL GANGLIA-THALAMO-CORTICAL NETWORK. TREATMENT MODALITIES FOR TOURETTE SYNDROME INCLUDE BEHAVIORAL, PHARMACOLOGICAL AND SURGICAL INTERVENTIONS, BUT THERE IS PRESENTLY NO CURE FOR THE DISORDER. FOR THOSE SEVERELY AFFECTED, DEEP BRAIN STIMULATION (DBS) HAS RECENTLY BECOME A VIABLE THERAPEUTIC OPTION. A KEY FACTOR TO ATTAINING OPTIMAL RESULTS FROM THIS SURGERY IS TARGET SELECTION, A TOPIC STILL UNDER DEBATE DUE TO THE COMPLEX CLINICAL PROFILE PRESENTED BY GTS PATIENTS. DEPENDING ON ITS PHENOTYPIC EXPRESSION AND THE MOST PROBLEMATIC ASPECT OF THE DISORDER FOR THE INDIVIDUAL, ONE OF THREE BRAIN REGIONS IS MOST COMMONLY CHOSEN FOR STIMULATION: THE THALAMUS, GLOBUS PALLIDUS, OR NUCLEUS ACCUMBENS. NEUROPHYSIOLOGICAL ANALYSES OF INTRA- AND POST-OPERATIVE HUMAN ELECTROPHYSIOLOGICAL RECORDINGS FROM CLINICAL DBS STUDIES SUGGEST A LINK BETWEEN TIC BEHAVIOR AND ACTIVITY IN BOTH THE THALAMUS AND GLOBUS PALLIDUS. IN PARTICULAR, CHRONIC RECORDINGS FROM THE THALAMUS HAVE SHOWN A CORRELATION BETWEEN SYMPTOMATOLOGY AND (1) SPECTRAL ACTIVITY IN GAMMA BAND POWER AND (2) THETA/GAMMA CROSS FREQUENCY COHERENCE. THESE RESULTS SUGGEST GAMMA OSCILLATIONS AND THETA/GAMMA CROSS CORRELATION DYNAMICS MAY SERVE AS BIOMARKERS FOR DYSFUNCTION. WHILE ACUTE AND CHRONIC RECORDINGS FROM HUMAN SUBJECTS UNDERGOING DBS HAVE PROVIDED BETTER INSIGHT INTO TIC GENESIS AND THE NEUROPATHOPHYSIOLOGICAL MECHANISMS UNDERLYING TOURETTE SYNDROME, THESE STUDIES ARE STILL SPARSE AND THE FIELD WOULD GREATLY BENEFIT FROM FURTHER INVESTIGATIONS. THIS REVIEW REPORTS DATA AND DISCOVERIES OF SCIENTIFIC AND CLINICAL RELEVANCE FROM A WIDE VARIETY OF METHODS AND PROVIDES UP-TO-DATE INFORMATION ABOUT OUR CURRENT UNDERSTANDING OF THE PATHOMECHANISMS UNDERLYING TOURETTE SYNDROME. IT GIVES A COMPREHENSIVE OVERVIEW OF THE CURRENT STATE OF KNOWLEDGE AND ADDRESSES OPEN QUESTIONS IN THE FIELD. 2017 16 4274 30 MICROBIOTA IN INFLAMMATORY BOWEL DISEASE PATHOGENESIS AND THERAPY: IS IT ALL ABOUT DIET? INFLAMMATORY BOWEL DISEASE (IBD), INCLUDING ULCERATIVE COLITIS, CROHN'S DISEASE, AND UNCLASSIFIED IBD, CONTINUES TO CAUSE SIGNIFICANT MORBIDITY. WHILE ITS INCIDENCE IS INCREASING, NO CLEAR ETIOLOGY AND NO CURE HAVE YET BEEN DISCOVERED. RECENT FINDINGS SUGGEST THAT IBD MAY HAVE A MULTIFACTORIAL ETIOLOGY, WHERE COMPLEX INTERACTIONS BETWEEN GENETICS, EPIGENETICS, ENVIRONMENTAL FACTORS (INCLUDING DIET BUT ALSO INFECTIONS, ANTIBIOTICS, AND SANITATION), AND HOST IMMUNE SYSTEM LEAD TO ABNORMAL IMMUNE RESPONSES AND CHRONIC INFLAMMATION. OVER THE PAST YEARS, THE ROLE OF ALTERED GUT MICROBIOTA (IN BOTH COMPOSITION AND FUNCTION) IN IBD PATHOGENESIS HAS EMERGED AS AN OUTSTANDING AREA OF INTEREST. ACCORDING TO NEW FINDINGS, GUT DYSBIOSIS MAY APPEAR AS A KEY ELEMENT IN INITIATION OF INFLAMMATION IN IBD AND ITS COMPLICATIONS. MOREOVER, COMPLEX METAGENOMIC STUDIES PROVIDE POSSIBILITIES TO DISTINGUISH BETWEEN IBD TYPES AND APPRECIATE SEVERITY AND PROGNOSIS OF THE DISEASE, AS WELL AS RESPONSE TO THERAPY. THIS REVIEW PROVIDES AN UPDATED KNOWLEDGE OF RECENT FINDINGS LINKING ALTERED BACTERIAL COMPOSITION AND FUNCTIONS, VIRUSES, AND FUNGI TO IBD PATHOGENESIS. IT ALSO HIGHLIGHTS THE COMPLEX GENETIC, EPIGENETIC, IMMUNE, AND MICROBIAL INTERACTIONS IN RELATION TO ENVIRONMENTAL FACTORS (INCLUDING DIET). WE OVERVIEW THE ACTUAL OPTIONS TO MANIPULATE THE ALTERED MICROBIOTA, SUCH AS MODIFIED DIET, PROBIOTICS, PREBIOTICS, SYNBIOTICS, ANTIBIOTICS, AND FECAL TRANSPLANTATION. FUTURE POSSIBLE THERAPIES ARE ALSO INCLUDED. TARGETING ALTERED MICROBIOTA COULD BE THE NEXT THERAPEUTIC PERSONALIZED APPROACH, BUT MORE RESEARCH AND WELL-DESIGNED COMPARATIVE PROSPECTIVE STUDIES ARE REQUIRED TO FORMULATE ADEQUATE DIRECTIONS FOR PREVENTION AND THERAPY. 2015 17 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 18 6375 45 THE ROLE OF NEURO-IMMUNE INTERACTION IN CHRONIC PAIN CONDITIONS; FUNCTIONAL SOMATIC SYNDROME, NEUROGENIC INFLAMMATION, AND PERIPHERAL NEUROPATHY. FUNCTIONAL SOMATIC SYNDROMES ARE INCREASINGLY DIAGNOSED IN CHRONICALLY ILL PATIENTS PRESENTING WITH AN ARRAY OF SYMPTOMS NOT ATTRIBUTED TO PHYSICAL AILMENTS. CONDITIONS SUCH AS CHRONIC FATIGUE SYNDROME, FIBROMYALGIA SYNDROME, OR IRRITABLE BOWEL SYNDROME ARE COMMON DISORDERS THAT BELONG IN THIS BROAD CATEGORY. SUCH SYNDROMES ARE CHARACTERISED BY THE PRESENCE OF ONE OR MULTIPLE CHRONIC SYMPTOMS INCLUDING WIDESPREAD MUSCULOSKELETAL PAIN, FATIGUE, SLEEP DISORDERS, AND ABDOMINAL PAIN, AMONGST OTHER ISSUES. SYMPTOMS ARE BELIEVED TO RELATE TO A COMPLEX INTERACTION OF BIOLOGICAL AND PSYCHOSOCIAL FACTORS, WHERE A DEFINITE AETIOLOGY HAS NOT BEEN ESTABLISHED. THEORIES SUGGEST CAUSATIVE PATHWAYS BETWEEN THE IMMUNE AND NERVOUS SYSTEMS OF AFFECTED INDIVIDUALS WITH SEVERAL RISK FACTORS IDENTIFIED IN PATIENTS PRESENTING WITH ONE OR MORE FUNCTIONAL SYNDROMES. RISK FACTORS INCLUDING STRESS AND CHILDHOOD TRAUMA ARE NOW RECOGNISED AS IMPORTANT CONTRIBUTORS TO CHRONIC PAIN CONDITIONS. EMOTIONAL, PHYSICAL, AND SEXUAL ABUSE DURING CHILDHOOD IS CONSIDERED A SEVERE STRESSOR HAVING A HIGH PREVALENCE IN FUNCTIONAL SOMATIC SYNDROME SUFFERS. SUCH TRAUMA PERMANENTLY ALTERS THE BIOLOGICAL STRESS RESPONSE OF THE SUFFERS LEADING TO NEUROEXCITATORY AND OTHER NERVE ISSUES ASSOCIATED WITH CHRONIC PAIN IN ADULTS. TRAUMATIC AND CHRONIC STRESS RESULTS IN EPIGENETIC CHANGES IN STRESS RESPONSE GENES, WHICH ULTIMATELY LEADS TO DYSREGULATION OF THE HYPOTHALAMIC-PITUITARY AXIS, THE AUTONOMIC NERVOUS SYSTEM, AND THE IMMUNE SYSTEM MANIFESTING IN A BROAD ARRAY OF SYMPTOMS. IMPORTANTLY, THESE SYSTEMS ARE KNOWN TO BE DYSREGULATED IN PATIENTS SUFFERING FROM FUNCTIONAL SOMATIC SYNDROME. FUNCTIONAL SOMATIC SYNDROMES ARE ALSO HIGHLY PREVALENT CO-MORBIDITIES OF PSYCHIATRIC CONDITIONS, MOOD DISORDERS, AND ANXIETY. CONSEQUENTLY, THIS REVIEW AIMS TO PROVIDE INSIGHT INTO THE ROLE OF THE NERVOUS SYSTEM AND IMMUNE SYSTEM IN CHRONIC PAIN DISORDERS ASSOCIATED WITH THE MUSCULOSKELETAL SYSTEM, AND CENTRAL AND PERIPHERAL NERVOUS SYSTEMS. 2022 19 2900 30 GENDER BIAS IN THERAPEUTIC EFFORT: FROM RESEARCH TO HEALTH CARE. THERE ARE RELEVANT DIMENSIONS FROM A GENDER PERSPECTIVE RELATED TO THERAPEUTIC EFFORT. TO ILLUSTRATE AND DISCUSS POSSIBLE GENDER BIAS RELATED TO MEDICINES, THROUGH THE CONSUMPTION ANALYSIS IN WOMEN, THE PRESCRIPTION OF BIOLOGICAL DRUGS ACCORDING TO SEX, THE POTENTIAL GENDER INEQUALITY IN ADVERSE DRUG REACTIONS, AND RESEARCH WITH CLINICAL TRIALS, AS WELL AS THE DECISIONS OF INTERNATIONAL INSTITUTIONS IN THE MARKETING OF MEDICINAL PRODUCTS. THERE IS GREATER TENDENCY TO PRESCRIBE PAIN RELIEVERS, REGARDLESS OF PAIN, AND DRUGS FOR LOW INTENSITY DEPRESSIVE SYMPTOMS IN WOMEN THAN IN MEN. THE OPPOSITE OCCURS IN THE PRESCRIPTION OF STATINS AND ADEQUATE DOSES, AND WITH THE GREATER PROBABILITY OF PRESCRIBING ANTI-TUMOR NECROSIS FACTOR IN MEN THAN IN WOMEN WITH ANKYLOSING SPONDYLITIS, DESPITE A SIMILAR DISEASE BURDEN. ADVERSE DRUG REACTIONS ARE OBSERVED MORE FREQUENTLY IN WOMEN THAN IN MEN, WHERE DETERMINANTS SUCH AS BODY WEIGHT ARE HAVING LITTLE INFLUENCE ON THE DOSAGE. IT IS CURRENTLY SCARCELY CONSIDERED IN THE PRESCRIPTION THAT WOMEN HAVE DIFFERENCES IN THE ACTIVITY OF CYTOCHROME CYPP450 ENZYMES, WHICH CAN AFFECT THE LIVER'S METABOLISM RATE. THERE ARE EVEN IMMUNOLOGICAL, GENETIC AND EPIGENETIC EFFECTS (DUE TO HEREDITY AND UNEVEN GENE DOSING LOCATED IN THE X AND Y CHROMOSOMES) THAT CAN INFLUENCE THESE DIFFERENCES BY SEX. FINALLY, THROUGH CASES OF HORMONAL THERAPY CLINICAL TRIALS, A DRUG FOR WOMEN'S INHIBITED SEXUAL DESIRE AND A CONTRACEPTIVE FOR MEN, GENDER BIAS AND STEREOTYPES ARE SHOWN TO INFLUENCE A POTENTIAL GENERATION OF INEQUALITIES, ESPECIALLY IN ADVERSE DRUG REACTIONS TO THE DETRIMENT OF WOMEN. IN CONCLUSION, HEALTH PROFESSIONALS FREQUENTLY ATTRIBUTE PHYSICAL SYMPTOMS TO WOMEN'S EMOTIONALITY, INFLUENCING THEIR GREATER PRESCRIPTION OF SYMPTOMATIC DRUGS. WHETHER THE SAME REASON INFLUENCES THE LOWER PRESCRIPTION OF THERAPEUTIC DRUGS IN WOMEN THAN IN MEN SHOULD BE ANALYZED. THERE ARE BIOLOGICAL DETERMINANTS TO CONSIDER DUE TO THEIR INFLUENCE ON A GREATER PHARMACOLOGICAL TOXICITY IN WOMEN. CLINICAL TRIALS SHOULD IMPROVE ACCORDING TO THE GENDER RECOMMENDATIONS BY THE FOOD AND DRUGS ADMINISTRATION. 2020 20 455 48 APPLICATIONS OF YOGA IN ORAL ONCOLOGY: A SYSTEMATIC SCOPING REVIEW. BACKGROUND AND AIMS: YOGA IS WELL-THOUGHT-OUT AS AN ALL-INCLUSIVE APPROACH GLOBALLY AND CAN BE ADMINISTERED IN CLINICAL CARE AS AN INTEGRATIVE OR ALTERNATE APPROACH TO REGULAR TREATMENT. YOGA EXERCISE HAS BEEN DISCLOSED TO INFLUENCE REMISSION FROM CANCER CELLS OVER A LONG PERIOD OF TIME AND ALSO REVERSES EPIGENETIC ALTERATIONS. APPLICATIONS OF YOGA IN THE MANAGEMENT OF ORAL ONCOLOGY PATIENTS ARE SCARCE, HENCE THE NEED FOR A SCOPING REVIEW OF THE LITERATURE. HENCE, THIS STUDY AIMED TO CONDUCT A SCOPING REVIEW OF THE EXISTING EMPIRICAL EVIDENCE ON THE APPLICATIONS OF YOGA IN ORAL ONCOLOGY. METHODS: THE REVIEW METHODOLOGY WAS INFORMED BY JOANNA BRIGG'S INSTITUTE GUIDELINES FOR SYSTEMATIC SCOPING REVIEWS, AND THE REVIEW WAS REPORTED IN ACCORDANCE WITH THE PREFERRED REPORTING ITEMS FOR SYSTEMATIC REVIEWS AND META-ANALYSES EXTENSION FOR SCOPING REVIEWS. TEN DATABASES WERE SEARCHED. THE RECORDS OF ALL THE LITERATURE RETRIEVED FROM THE SEARCH WERE IMPORTED INTO THE RAYYAN SOFTWARE FOR DEDUPLICATION. AFTER THE FULL-TEXT SCREENING, ONLY TWO WERE FOUND ELIGIBLE FOR INCLUSION IN THE SCOPING REVIEW. DATA OBTAINED IN THE INCLUDED LITERATURE WERE EXTRACTED AND SYNTHESIZED. RESULTS: THIS REVIEW FOUND THAT YOGA WAS NOT SIGNIFICANTLY EFFECTIVE IN THE MANAGEMENT OF STRESS AMONG ORAL CANCER PATIENTS (P-VALUES > 0.04). HOWEVER, IT WAS FOUND THAT YOGA SIGNIFICANTLY REDUCED ANXIETY, SALIVA STICKINESS, AND EPISODES OF FALLING ILL (P-VALUES < 0.05) WHILE IT IMPROVED MENTAL WELL-BEING, COGNITIVE FUNCTIONING, EMOTIONAL FUNCTIONING, AND HEAD AND NECK PAIN OF THOSE ORAL CANCER PATIENTS THAT RECEIVED IT (P-VALUES < 0.05). CONCLUSION: AN INTEGRATIVE CARE APPROACH THAT CONSIDERS NONPHARMACEUTICAL TECHNIQUES SUCH AS YOGA COULD HELP TO REDUCE CARE COST WHILE IMPROVING CARE OUTCOMES AND QUALITY OF LIFE OF ORAL CANCER PATIENTS. HENCE, IT IS IMPERATIVE TO CONSIDER YOGA ALONG WITH ITS POTENTIAL BENEFITS, AND WE RECOMMEND GRADUAL INCORPORATION OF YOGA INTO ORAL CANCER CARE. 2023