1 81 100 A NEW TYPE OF DENTAL ANOMALY: MOLAR-INCISOR MALFORMATION (MIM). A MOLAR-INCISOR MALFORMATION (MIM) IS A NEWLY DISCOVERED TYPE OF DENTAL ANOMALY OF THE PERMANENT FIRST MOLARS, DECIDUOUS SECOND MOLARS, AND PERMANENT MAXILLARY CENTRAL INCISORS. MIM ANOMALIES OF THE PERMANENT FIRST MOLARS AND DECIDUOUS SECOND MOLARS MAY INCLUDE NORMAL CROWNS WITH A CONSTRICTED CERVICAL REGION AND THIN, NARROW, AND SHORT ROOTS, WHEREAS THE AFFECTED MAXILLARY CENTRAL INCISORS MAY EXHIBIT A HYPOPLASTIC ENAMEL NOTCH NEAR THE CERVICAL THIRD OF THE CLINICAL CROWN. ALTHOUGH THE ETIOLOGY OF MIM REMAINS TO BE DETERMINED, IT IS THOUGHT TO BE ATTRIBUTABLE TO AN EPIGENETIC FACTOR LINKED TO BRAIN- AND CENTRAL NERVOUS SYSTEM-RELATED SYSTEMIC DISEASES AT AROUND AGE 1 TO 2 YEARS. MIM TEETH ARE ASSOCIATED WITH CLINICAL PROBLEMS SUCH AS IMPACTION, EARLY EXFOLIATION, SPACE LOSS, SPONTANEOUS PAIN, PERIAPICAL ABSCESS, AND POOR INCISOR ESTHETICS. CHILDREN WITH MIM TEETH SHOULD BE OBSERVED CLOSELY WITH RESPECT TO THEIR MEDICAL HISTORY, AND DENTISTS SHOULD FORMULATE A WIDER-RANGING TREATMENT PLAN. 2014 2 5697 19 SIMILARITIES IN PATHOGENETIC MECHANISMS UNDERLYING THE BIDIRECTIONAL RELATIONSHIP BETWEEN ENDOMETRIOSIS AND PELVIC INFLAMMATORY DISEASE. BACKGROUND: ENDOMETRIOSIS IS A COMMON INFLAMMATORY DISEASE CHARACTERIZED BY THE PRESENCE OF ENDOMETRIAL CELLS OUTSIDE OF THE UTERINE CAVITY. ENDOMETRIOSIS AFFECTS 10% OF WOMEN OF REPRODUCTIVE AGE AND SIGNIFICANTLY REDUCES THEIR QUALITY OF LIFE AS A RESULT OF CHRONIC PELVIC PAIN AND INFERTILITY. BIOLOGIC MECHANISMS, INCLUDING PERSISTENT INFLAMMATION, IMMUNE DYSFUNCTION, AND EPIGENETIC MODIFICATIONS, HAVE BEEN PROPOSED AS THE PATHOGENESIS OF ENDOMETRIOSIS. IN ADDITION, ENDOMETRIOSIS CAN POTENTIALLY BE ASSOCIATED WITH AN INCREASED RISK OF PELVIC INFLAMMATORY DISEASE (PID). CHANGES IN THE VAGINAL MICROBIOTA ASSOCIATED WITH BACTERIAL VAGINOSIS (BV) RESULT IN PID OR A SEVERE FORM OF ABSCESS FORMATION, TUBO-OVARIAN ABSCESS (TOA). THIS REVIEW AIMS TO SUMMARIZE THE PATHOPHYSIOLOGY OF ENDOMETRIOSIS AND PID AND TO DISCUSS WHETHER ENDOMETRIOSIS MAY PREDISPOSE TO PID AND VICE VERSA. METHODS: PAPERS PUBLISHED BETWEEN 2000 AND 2022 IN THE PUBMED AND GOOGLE SCHOLAR DATABASES WERE INCLUDED. RESULTS: AVAILABLE EVIDENCE SUPPORTS THAT WOMEN WITH ENDOMETRIOSIS ARE AT INCREASED RISK OF COMORBID PID AND VICE VERSA, SUPPORTING THAT ENDOMETRIOSIS AND PID ARE LIKELY TO COEXIST. THERE IS A BIDIRECTIONAL RELATIONSHIP BETWEEN ENDOMETRIOSIS AND PID THAT SHARES A SIMILAR PATHOPHYSIOLOGY, WHICH INCLUDES THE DISTORTED ANATOMY FAVORABLE TO BACTERIA PROLIFERATION, HEMORRHAGE FROM ENDOMETRIOTIC LESIONS, ALTERATIONS TO THE REPRODUCTIVE TRACT MICROBIOME, AND IMPAIRED IMMUNE RESPONSE MODULATED BY ABERRANT EPIGENETIC PROCESSES. HOWEVER, WHETHER ENDOMETRIOSIS PREDISPOSES TO PID OR VICE VERSA HAS NOT BEEN IDENTIFIED. CONCLUSIONS: THIS REVIEW SUMMARIZES OUR CURRENT UNDERSTANDING OF THE PATHOGENESIS OF ENDOMETRIOSIS AND PID AND DISCUSSES THE SIMILARITIES BETWEEN THEM. 2023 3 4594 23 NATURAL HISTORY AND LONG-TERM CLINICAL COURSE OF CROHN'S DISEASE. CROHN'S DISEASE IS A CHRONIC INFLAMMATORY DISEASE PROCESS INVOLVING DIFFERENT SITES IN THE GASTROINTESTINAL TRACT. OCCASIONALLY, SO-CALLED METASTATIC DISEASE OCCURS IN EXTRA-INTESTINAL SITES. GRANULOMATOUS INFLAMMATION MAY BE DETECTED IN ENDOSCOPIC BIOPSIES OR RESECTED TISSUES. GENETIC, EPIGENETIC AND ENVIRONMENTAL FACTORS APPEAR TO PLAY A ROLE. MULTIPLE SUSCEPTIBILITY GENES HAVE BEEN DESCRIBED IN BOTH FAMILIAL AND NON-FAMILIAL FORMS WHILE THE DISEASE IS PHENOTYPICALLY HETEROGENEOUS WITH A FEMALE PREDOMINANCE. THE DISORDER OCCURS OVER A BROAD AGE SPECTRUM, FROM EARLY CHILDHOOD TO LATE ADULTHOOD. MORE THAN 80% ARE DIAGNOSED BEFORE AGE 40 YEARS USUALLY WITH TERMINAL ILEAL AND COLONIC INVOLVEMENT. PEDIATRIC-ONSET DISEASE IS MORE SEVERE AND MORE EXTENSIVE, USUALLY WITH A HIGHER CHANCE OF UPPER GASTROINTESTINAL TRACT DISEASE, COMPARED TO ADULT-ONSET DISEASE. LONG-TERM STUDIES HAVE SHOWN THAT THE DISORDER MAY EVOLVE WITH TIME INTO MORE COMPLEX DISEASE WITH STRICTURE FORMATION AND PENETRATING DISEASE COMPLICATIONS (I.E., FISTULA, ABSCESS). ALTHOUGH PROLONGED REMISSION MAY OCCUR, DISCRETE PERIODS OF SYMPTOMATIC DISEASE MAY RE-APPEAR OVER MANY DECADES SUGGESTING RECURRENCE OR RE-ACTIVATION OF THIS INFLAMMATORY PROCESS. EVENTUAL DEVELOPMENT OF A CURE WILL LIKELY DEPEND ON IDENTIFICATION OF AN ETIOLOGIC CAUSE AND A FUNDAMENTAL UNDERSTANDING OF ITS PATHOGENESIS. UNTIL NOW, TREATMENT HAS FOCUSED ON REMOVING RISK FACTORS, PARTICULARLY CIGARETTE SMOKING, AND IMPROVING SYMPTOMS. IN CLINICAL TRIALS, CLINICAL REMISSION IS LARGELY DEFINED AS IMPROVED NUMERICAL AND ENDOSCOPIC INDICES FOR "MUCOSAL HEALING". "DEEP REMISSION" IS A CONCEPTUAL, MORE "EXTENDED" GOAL THAT MAY OR MAY NOT ALTER THE LONG-TERM NATURAL HISTORY OF THE DISEASE IN SELECTED PATIENTS, ALBEIT AT A SIGNIFICANT RISK FOR TREATMENT COMPLICATIONS, INCLUDING SERIOUS AND UNUSUAL OPPORTUNISTIC INFECTIONS. 2014 4 1892 14 ENDOMETRIOSIS: EPIDEMIOLOGY, CLASSIFICATION, PATHOGENESIS, TREATMENT AND GENETICS (REVIEW OF LITERATURE). ENDOMETRIOSIS IS A "MYSTERIOUS" DISEASE AND ITS EXACT CAUSE HAS NOT YET BEEN ESTABLISHED. AMONG THE ETIOLOGICAL FACTORS, CONGENITAL, ENVIRONMENTAL, EPIGENETIC, AUTOIMMUNE AND ALLERGIC FACTORS ARE LISTED. IT IS BELIEVED THAT THE PRIMARY MECHANISM OF THE FORMATION OF ENDOMETRIOSIS FOCI IS RETROGRADE MENSTRUATION, I.E., THE PASSAGE OF MENSTRUAL BLOOD THROUGH THE FALLOPIAN TUBES INTO THE PERITONEAL CAVITY AND IMPLANTATION OF EXFOLIATED ENDOMETRIAL CELLS. HOWEVER, SINCE THIS MECHANISM IS ALSO OBSERVED IN HEALTHY WOMEN, OTHER FACTORS MUST ALSO BE INVOLVED IN THE FORMATION OF ENDOMETRIOSIS FOCI. ENDOMETRIOSIS IS IN MANY WOMEN THE CAUSE OF INFERTILITY, CHRONIC PAIN AND THE DETERIORATION OF THE QUALITY OF LIFE. IT ALSO REPRESENTS A SIGNIFICANT FINANCIAL BURDEN ON HEALTH SYSTEMS. THE ARTICLE PRESENTS A REVIEW OF THE LITERATURE ON ENDOMETRIOSIS-A DISEASE AFFECTING WOMEN THROUGHOUT THE WORLD. 2021 5 4950 15 PATHOGENESIS OF ADENOMYOSIS: AN UPDATE ON MOLECULAR MECHANISMS. ADENOMYOSIS IS A UTERINE DISORDER BECOMING MORE COMMONLY DIAGNOSED IN WOMEN OF REPRODUCTIVE AGE BECAUSE OF DIAGNOSTIC IMAGING ADVANCEMENTS. THE NEW EPIDEMIOLOGICAL SCENARIO AND THE CLINICAL EVIDENCE OF PELVIC PAIN, ABNORMAL UTERINE BLEEDING AND INFERTILITY ARE CHANGING THE CLASSIC PERSPECTIVE OF ADENOMYOSIS AS A PREMENOPAUSAL DISEASE. IN THE LAST DECADE, THE EVALUATION OF MULTIPLE MOLECULAR MEDIATORS HAS IMPROVED OUR KNOWLEDGE OF PATHOGENIC MECHANISMS OF ADENOMYOSIS, SUPPORTING THAT THIS IS AN INDEPENDENT DISEASE FROM ENDOMETRIOSIS. ALTHOUGH THEY SHARE COMMON GENETIC MUTATIONS AND EPIGENETIC CHANGES IN SEX STEROID HORMONE RECEPTORS AND SIMILAR INFLAMMATORY MEDIATORS, AN INCREASING NUMBER OF RECENT STUDIES HAVE SHOWN PATHOGENIC PATHWAYS SPECIFIC FOR ADENOMYOSIS. A PUBMED SEARCH UP TO OCTOBER 2016 SUMMARIZES THE KEY MEDIATORS OF PAIN, ABNORMAL UTERINE BLEEDING AND INFERTILITY IN ADENOMYOSIS, INCLUDING SEX STEROID HORMONE RECEPTORS, INFLAMMATORY MOLECULES, EXTRACELLULAR MATRIX ENZYMES, GROWTH FACTORS AND NEUROANGIOGENIC FACTORS. 2017 6 1114 17 COMMONALITIES AND DISPARITIES BETWEEN ENDOMETRIOSIS AND CHRONIC ENDOMETRITIS: THERAPEUTIC POTENTIAL OF NOVEL ANTIBIOTIC TREATMENT STRATEGY AGAINST ECTOPIC ENDOMETRIUM. CHRONIC ENDOMETRITIS (CE) IS A LOCAL MUCOSAL INFLAMMATORY DISORDER OF THE UTERINE LINING, WHICH IS HISTOPATHOLOGICALLY RECOGNIZED AS THE UNUSUAL INFILTRATION OF CD138(+) PLASMACYTES INTO THE ENDOMETRIAL STROMAL COMPARTMENT. ACCUMULATING BODY OF RESEARCH DOCUMENTED THAT CE IS ASSOCIATED WITH FEMALE INFERTILITY AND SEVERAL OBSTETRIC/NEONATAL COMPLICATIONS. THE MAJOR CAUSE OF CE IS THOUGHT TO BE INTRAUTERINE INFECTION REPRESENTED BY COMMON BACTERIA (ESCHERICHIA COLI, ENTEROCOCCUS FAECALIS, STREPTOCOCCUS, AND STAPHYLOCOCCUS), MYCOPLASMA/UREAPLASMA, AND MYCOBACTERIUM. ADDITIONALLY, LOCAL DYSBIOSIS IN THE FEMALE REPRODUCTIVE TRACT MAY BE INVOLVED IN THE ONSET AND DEVELOPMENT OF CE. ANTIBIOTIC TREATMENTS AGAINST THESE MICROORGANISMS ARE EFFECTIVE IN THE ELIMINATION OF ENDOMETRIAL STROMAL PLASMACYTES IN THE AFFECTED PATIENTS. MEANWHILE, ENDOMETRIOSIS IS A COMMON FEMALE REPRODUCTIVE TRACT DISEASE CHARACTERIZED BY ENDOMETRIOTIC TISSUES (ECTOPIC ENDOMETRIUM) GROWING OUTSIDE THE UTERUS AND POTENTIALLY CAUSES CHRONIC PELVIC SYMPTOMS (DYSMENORRHEA, DYSPAREUNIA, DYSCHEZIA, AND DYSURIA), INFERTILITY, AND OVARIAN CANCERS. ENDOMETRIOSIS INVOLVES ENDOCRINOLOGICAL, GENETIC, AND EPIGENETIC FACTORS IN ITS ETIOLOGY AND PATHOGENESIS. RECENT STUDIES FOCUS ON IMMUNOLOGICAL, INFLAMMATORY, AND INFECTIOUS ASPECTS OF ENDOMETRIOSIS AND DEMONSTRATE SEVERAL COMMON CHARACTERISTICS BETWEEN ENDOMETRIOSIS AND CE. THIS REVIEW AIMED TO BETTER UNDERSTAND THE IMMUNOLOGICAL AND MICROBIAL BACKGROUNDS UNDERLYING ENDOMETRIOSIS AND CE AND LOOK INTO THE THERAPEUTIC POTENTIAL OF THE NOVEL ANTIBIOTIC TREATMENT STRATEGY AGAINST ENDOMETRIOSIS IN LIGHT OF ENDOMETRIAL INFECTIOUS DISEASE. 2023 7 4724 17 NONINVASIVE MULTIMODAL METHODS TO DIFFERENTIATE INFLAMED VS FIBROTIC STRICTURES IN PATIENTS WITH CROHN'S DISEASE. FIBROTIC STRICTURES OCCUR IN 30% OF PATIENTS WITH CROHN'S DISEASE (CD). HOWEVER, THERE ARE NO THERAPEUTIC AGENTS THAT PREVENT OR REVERSE FIBROTIC STRICTURES. STRICTURES ARE TREATED BY ENDOSCOPIC DILATATION PROCEDURES AND SURGICAL PROCEDURES, BUT THERE ARE HIGH RATES OF RECURRENCE. TWO ANTIFIBROTIC AGENTS (NINTEDANIB AND PIRFENIDONE) RECENTLY WERE APPROVED FOR THE TREATMENT OF IDIOPATHIC PULMONARY FIBROSIS AND INHIBITORS OF RHO-ASSOCIATED PROTEIN KINASES 1 AND 2 REVERSED FIBROSIS IN MICE WITH CHRONIC INTESTINAL INFLAMMATION. CROSS-SECTIONAL IMAGING TECHNIQUES, SUCH AS MAGNETIC RESONANCE (MR) ENTEROGRAPHY, COMPUTED TOMOGRAPHY ENTEROGRAPHY, AND BOWEL ULTRASOUND, ARE USED TO ASSESS SMALL-BOWEL AND CD-RELATED COMPLICATIONS, INCLUDING STRICTURES. IT IS IMPORTANT TO BE ABLE TO DETERMINE THE DEGREE OF INFLAMMATION AND FIBROSIS IN STRICTURES TO SELECT THE BEST THERAPY; THIS CAN BE A CHALLENGE BECAUSE INFLAMMATION AND FIBROSIS CO-EXIST TO VARYING DEGREES IN A DAMAGED BOWEL SEGMENT. DELAYED GADOLINIUM ENHANCEMENT, MAGNETIZATION TRANSFER MR IMAGING, AND ULTRASOUND ELASTOGRAPHY SEEM TO BE PROMISING TOOLS FOR ASSESSING FIBROSIS IN PATIENTS WITH CD. WE REVIEW NONINVASIVE TECHNIQUES FOR FIBROSIS ASSESSMENT, INCLUDING ANALYSES OF GENETIC, EPIGENETIC, AND PROTEIN MARKERS. WE DISCUSS THE POTENTIAL OF IMAGING TECHNIQUES SUCH AS DIFFUSION-WEIGHTED AND MAGNETIZATION TRANSFER MR IMAGING, STRAIN ELASTOGRAPHY, SHEAR-WAVE IMAGING, AND POSITRON EMISSION TOMOGRAPHY TO GUIDE THERAPEUTIC DECISIONS FOR PATIENTS WITH STRICTURING CD. 2019 8 3820 16 INTRODUCTION TO PRECLINICAL EVIDENCE FROM ANIMAL MODELS OF ENDOMETRIOSIS. ENDOMETRIOSIS, THE PRESENCE AND GROWTH OF UTERINE ENDOMETRIAL GLANDULAR EPITHELIAL AND STROMA CELLS OUTSIDE THE UTERINE CAVITY, CAUSES PAIN AND INFERTILITY IN WOMEN AND GIRLS OF REPRODUCTIVE AGE. AS RANDOMIZED, DOUBLE-BLINDED, CONTROLLED STUDIES OF ENDOMETRIOSIS IN WOMEN ARE IMPRACTICAL AND AT TIMES ETHICALLY PROHIBITIVE, ANIMAL MODELS FOR ENDOMETRIOSIS AROSE AS AN IMPORTANT ADJUNCT TO GAIN MECHANISTIC INSIGHTS INTO THE ETIOLOGY AND PATHOPHYSIOLOGICAL MECHANISMS OF THIS PERPLEXING DISORDER. A MORE THOROUGH UNDERSTANDING OF ENDOMETRIOSIS IN WOMEN MAY HELP DEVELOP NOVEL NONINVASIVE DIAGNOSTICS, CLASSIFICATION SYSTEMS, THERAPEUTIC REGIMES, AND EVEN PREVENTATIVE METHODS FOR THE MANAGEMENT OF ENDOMETRIOSIS. THIS CHAPTER IS INTENDED TO INTRODUCE A BRIEF HISTORICAL BACKGROUND, BIOLOGICAL AND EPIDEMIOLOGICAL ASPECTS, THE MAJOR SYMPTOMS, THE EFFECTS OF ENDOCRINE-DISRUPTING CHEMICALS, AND AN EXAMPLE OF AN EPIGENETIC FACTOR OF ENDOMETRIOSIS IN WOMEN. 2020 9 3665 13 INFECTION AS A POTENTIAL COFACTOR IN THE GENETIC-EPIGENETIC PATHOPHYSIOLOGY OF ENDOMETRIOSIS: A SYSTEMATIC REVIEW. BACKGROUND: THE GENETIC-EPIGENETIC THEORY POSTULATES THAT ENDOMETRIOSIS IS TRIGGERED BY A CUMULATIVE SET OF GENETIC-EPIGENETIC (GE) INCIDENTS. PELVIC AND UPPER GENITAL TRACT INFECTION MIGHT INDUCE GE INCIDENTS AND THUS PLAY A ROLE IN THE PATHOGENESIS OF ENDOMETRIOSIS. THUS, THIS ARTICLE AIMS TO REVIEW THE ASSOCIATION OF ENDOMETRIOSIS WITH UPPER GENITAL TRACT AND PELVIC INFECTIONS. METHODS: PUBMED, SCOPUS AND GOOGLE SCHOLAR WERE SEARCHED FOR 'ENDOMETRIOSIS AND (INFECTION OR PID OR BACTERIA OR VIRUSES OR MICROBIOME OR MICROBIOTA)', FOR 'REPRODUCTIVE MICROBIOME' AND FOR 'REPRODUCTIVE MICROBIOME AND ENDOMETRIOSIS', RESPECTIVELY. ALL 384 ARTICLES, THE FIRST 120 'BEST MATCH' ARTICLES IN PUBMED FOR 'REPRODUCTIVE MICROBIOME' AND THE FIRST 160 HITS IN GOOGLE SCHOLAR FOR 'REPRODUCTIVE MICROBIOME AND ENDOMYTRIOSIS' WERE HAND SEARCHED FOR DATA DESCRIBING AN ASSOCIATION BETWEEN ENDOMETRIOSIS AND BACTERIAL, VIRAL OR OTHER INFECTIONS. ALL 31 ARTICLES FOUND WERE INCLUDED IN THIS MANUSCRIPT. RESULTS: WOMEN WITH ENDOMETRIOSIS HAVE A SIGNIFICANTLY INCREASED RISK OF LOWER GENITAL TRACT INFECTION, CHRONIC ENDOMETRITIS, SEVERE PID AND SURGICAL SITE INFECTIONS AFTER HYSTERECTOMY. THEY HAVE MORE COLONY FORMING UNITS OF GARDNERELLA, STREPTOCOCCUS, ENTEROCOCCI AND ESCHERICHIA COLI IN THE ENDOMETRIUM. IN THE CERVIX ATOPOBIUM IS ABSENT, BUT GARDNERELLA, STREPTOCOCCUS, ESCHERICHIA, SHIGELLA, AND UREOPLASMA ARE INCREASED. THEY HAVE HIGHER CONCENTRATIONS OF ESCHERICHIA COLI AND HIGHER CONCENTRATIONS OF BACTERIAL ENDOTOXINS IN MENSTRUAL BLOOD. A SHIGELLA/ESCHERICHIA DOMINANT STOOL MICROBIOME IS MORE FREQUENT. THE PERITONEAL FLUID OF WOMEN WITH ENDOMETRIOSIS CONTAINS HIGHER CONCENTRATIONS OF BACTERIAL ENDOTOXINS AND AN INCREASED INCIDENCE OF MOLLICUTES AND OF HPV VIRUSES. ENDOMETRIOSIS LESIONS HAVE A SPECIFIC BACTERIAL COLONISATION WITH MORE FREQUENTLY MOLLICUTES (54%) AND BOTH HIGH AND MEDIUM-RISK HPV INFECTIONS (11%). THEY CONTAIN DNA WITH 96% HOMOLOGY WITH SHIGELLA. IN MICE TRANSPLANTED ENDOMETRIUM CHANGES THE GUT MICROBIOME WHILE THE GUT MICROBIOME INFLUENCES THE GROWTH OF THESE ENDOMETRIOSIS LESIONS. CONCLUSIONS: ENDOMETRIOSIS IS ASSOCIATED WITH MORE UPPER GENITAL TRACT AND PERITONEAL INFECTIONS. THESE INFECTIONS MIGHT BE CO-FACTORS CAUSING GE INCIDENTS AND INFLUENCING ENDOMETRIOSIS GROWTH. 2019 10 3821 17 INTRODUCTION: FROM PATHOGENESIS TO THERAPY, DEEP ENDOMETRIOSIS REMAINS A SOURCE OF CONTROVERSY. DEEP ENDOMETRIOSIS REMAINS A SOURCE OF CONTROVERSY. A NUMBER OF THEORIES MAY EXPLAIN ITS PATHOGENESIS AND MANY ARGUMENTS SUPPORT THE HYPOTHESIS THAT GENETIC OR EPIGENETIC CHANGES ARE A PREREQUISITE FOR DEVELOPMENT OF LESIONS INTO DEEP ENDOMETRIOSIS. DEEP ENDOMETRIOSIS IS FREQUENTLY RESPONSIBLE FOR PELVIC PAIN, DYSMENORRHEA, AND/OR DEEP DYSPAREUNIA, BUT CAN ALSO CAUSE OBSTETRICAL COMPLICATIONS. DIAGNOSIS MAY BE IMPROVED BY HIGH-QUALITY IMAGING. THERAPEUTIC APPROACHES ARE A SOURCE OF CONTENTION AS WELL. IN THIS ISSUE'S VIEWS AND REVIEWS, MEDICAL AND SURGICAL STRATEGIES ARE DISCUSSED, AND IT IS EMPHASIZED THAT TREATMENT SHOULD BE DESIGNED ACCORDING TO A PATIENT'S SYMPTOMS AND INDIVIDUAL NEEDS. IT IS ALSO VITAL THAT REFERRAL CENTERS HAVE THE KNOWLEDGE AND EXPERIENCE TO TREAT DEEP ENDOMETRIOSIS MEDICALLY AND/OR SURGICALLY. THE DEBATE MUST CONTINUE BECAUSE EMERGING TRENDS IN THERAPY NEED TO BE FOLLOWED AND INVESTIGATED FOR OPTIMAL MANAGEMENT. 2017 11 6237 12 THE MAIN THEORIES ON THE PATHOGENESIS OF ENDOMETRIOSIS. ENDOMETRIOSIS IS A COMPLEX DISEASE, WHICH IS DEFINED BY ABNORMAL GROWTH OF ENDOMETRIAL TISSUE OUTSIDE THE UTERUS. IT AFFECTS ABOUT 10% OF WOMEN OF REPRODUCTIVE AGE ALL OVER THE WORLD. ENDOMETRIOSIS CAUSES SYMPTOMS THAT NOTABLY WORSEN PATIENT'S WELL-BEING-SUCH AS SEVERE PELVIC PAIN, DYSFUNCTION OF THE ORGANS OF PELVIC CAVITY, INFERTILITY AND SECONDARY MENTAL ISSUES. THE DIAGNOSIS OF ENDOMETRIOSIS IS QUITE OFTEN DELAYED BECAUSE OF NONSPECIFIC MANIFESTATIONS. SINCE THE DISEASE WAS DEFINED, SEVERAL DIFFERENT PATHOGENETIC PATHWAYS HAVE BEEN CONSIDERED, INCLUDING RETROGRADE MENSTRUATION, BENIGN METASTASIS, IMMUNE DYSREGULATION, COELOMIC METAPLASIA, HORMONAL DISBALANCE, INVOLVEMENT OF STEM CELLS AND ALTERATIONS IN EPIGENETIC REGULATION, BUT THE TRUE PATHOGENESIS OF ENDOMETRIOSIS REMAINS POORLY UNDERSTOOD. THE KNOWLEDGE OF THE EXACT MECHANISM OF THE ORIGIN AND PROGRESSION OF THIS DISEASE IS SIGNIFICANT FOR THE APPROPRIATE TREATMENT. THEREFORE, THIS REVIEW REPORTS THE MAIN PATHOGENETIC THEORIES OF ENDOMETRIOSIS BASED ON CURRENT STUDIES. 2023 12 6577 18 TREATMENT STRATEGIES FOR COMPLEX BEHAVIORAL INSOMNIA IN CHILDREN WITH NEURODEVELOPMENTAL DISORDERS. PURPOSE OF REVIEW: THIS REVIEW DESCRIBES RECENT RESEARCH IN PEDIATRIC BEHAVIORAL INSOMNIAS IN NEURODEVELOPMENTAL DISORDERS AND THEIR TREATMENT. RECENT FINDINGS: INSOMNIA IN CHILDREN WITH AUTISM SPECTRUM DISORDER (ASD) AND OTHER NEURODEVELOPMENTAL DISORDERS (NDDS) IS TYPICALLY COMPLEX, CHRONIC, AND DIFFICULT TO ADEQUATELY CONTROL. ABNORMALITIES IN GENETIC AND/OR EPIGENETIC REGULATION OF SLEEP/WAKEFULNESS AND ITS TIMING PREDISPOSE PATIENTS WITH NDD TO INSOMNIA, ALTHOUGH POOR SLEEP HYGIENE, MALADAPTIVE ASSOCIATIONS, AND LIMIT-SETTING ARE LIKELY TO CONTRIBUTE. PARENTS ARE AGENTS FOR CHANGE IN PROBLEMATIC SLEEP BEHAVIORS IN PATIENTS WITH NDD. WE REVIEW THE BENEFITS OF BEHAVIORAL THERAPIES AND MELATONIN TO TREAT SLEEP PROBLEMS IN CHILDREN WITH NDD. PROBLEMATIC SLEEP IS SO PREVALENT IN SOME NEURODEVELOPMENTAL SYNDROMES (RETT, ANGELMAN, WILLIAMS, AND SMITH-MAGENIS) THAT IT IS PART OF THEIR DIAGNOSTIC CRITERIA. SUMMARY: CHILDREN AND ADOLESCENTS WITH NEUROLOGICAL DISORDERS FREQUENTLY HAVE COMPLEX SLEEP DISORDERS THAT REQUIRE TREATMENT. UNDERSTANDING THE BASIC PATHOLOGY AND TREATMENT STRATEGIES PROVIDES AN OPPORTUNITY TO IMPROVE WELL BEING AND QUALITY OF LIFE IN THOSE AFFECTED BY NDD AND THEIR FAMILIES. 2013 13 236 17 ADENOMYOSIS: MECHANISMS AND PATHOGENESIS. ADENOMYOSIS IS A COMMON DISORDER OF THE UTERUS, AND IS ASSOCIATED WITH AN ENLARGED UTERUS, HEAVY MENSTRUAL BLEEDING (HMB), PELVIC PAIN, AND INFERTILITY. IT IS CHARACTERIZED BY ENDOMETRIAL EPITHELIAL CELLS AND STROMAL FIBROBLASTS ABNORMALLY FOUND IN THE MYOMETRIUM WHERE THEY ELICIT HYPERPLASIA AND HYPERTROPHY OF SURROUNDING SMOOTH MUSCLE CELLS. WHILE BOTH THE MECHANISTIC PROCESSES AND THE PATHOGENESIS OF ADENOMYOSIS ARE UNCERTAIN, SEVERAL THEORIES HAVE BEEN PUT FORWARD ADDRESSING HOW THIS DISEASE DEVELOPS. THESE INCLUDE INTRINSIC OR INDUCED (1) MICROTRAUMA OF THE ENDOMETRIAL-MYOMETRIAL INTERFACE; (2) ENHANCED INVASION OF ENDOMETRIUM INTO MYOMETRIUM; (3) METAPLASIA OF STEM CELLS IN MYOMETRIUM; (4) INFILTRATION OF ENDOMETRIAL CELLS IN RETROGRADE MENSTRUAL EFFLUENT INTO THE UTERINE WALL FROM THE SEROSAL SIDE; (5) INDUCTION OF ADENOMYOTIC LESIONS BY ABERRANT LOCAL STEROID AND PITUITARY HORMONES; AND (6) ABNORMAL UTERINE DEVELOPMENT IN RESPONSE TO GENETIC AND EPIGENETIC MODIFICATIONS. DYSMENORRHEA, HMB, AND INFERTILITY ARE LIKELY RESULTS OF INFLAMMATION, NEUROGENESIS, ANGIOGENESIS, AND CONTRACTILE ABNORMALITIES IN THE ENDOMETRIAL AND MYOMETRIAL COMPONENTS. ELUCIDATING MECHANISMS UNDERLYING THE PATHOGENESIS OF ADENOMYOSIS RAISE POSSIBILITIES TO DEVELOP TARGETED THERAPIES TO AMELIORATE SYMPTOMS BEYOND THE CURRENT AGENTS THAT ARE LARGELY INEFFECTIVE. HEREIN, WE ADDRESS THESE POSSIBLE ETIOLOGIES AND DATA THAT SUPPORT UNDERLYING MECHANISMS. 2020 14 4956 15 PATHOGENESIS OF ENDOMETRIOSIS: FOCUS ON ADENOGENESIS-RELATED FACTORS. ENDOMETRIOSIS CAN BE DEFINED AS THE PRESENCE OF THE ENDOMETRIUM OUTSIDE THE UTERINE CAVITY. IT AFFECTS APPROXIMATELY 10% OF WOMEN OF REPRODUCTIVE AGE AND CAUSES INFERTILITY, CHRONIC PAIN, AND DETERIORATION OF THE QUALITY OF LIFE. SINCE THE IDENTIFICATION OF THE DISEASE, VARIOUS PATHOGENETIC MECHANISMS HAVE BEEN PROPOSED, SUCH AS RETROGRADE MENSTRUATION, COELOMIC METAPLASIA, HORMONAL IMBALANCE, STEM CELL INVOLVEMENT, AND ALTERATIONS IN EPIGENETIC REGULATION. HOWEVER, THE UNDERLYING PATHOGENESIS OF ENDOMETRIOSIS REMAINS INADEQUATELY UNDERSTOOD. ELUCIDATION OF THE PRECISE MECHANISM OF THE DEVELOPMENT AND PROGRESSION OF ENDOMETRIOSIS IS CRUCIAL FOR EFFECTIVE TREATMENT. THIS REVIEW PRESENTS THE MAJOR PATHOGENETIC THEORIES OF ENDOMETRIOSIS BASED ON CURRENT RESEARCH STUDIES WITH A MAJOR FOCUS ON THE POTENTIAL ROLE OF UTERINE FACTORS. 2023 15 1403 14 DIETARY APPROACHES TO WOMEN'S SEXUAL AND REPRODUCTIVE HEALTH. OVER THE COURSE OF THE REPRODUCTIVE LIFE SPAN, IT IS COMMON FOR WOMEN TO EXPERIENCE ONE OR MORE OF THE MOST COMMON GYNECOLOGIC CONDITIONS, INCLUDING SEXUAL DYSFUNCTION, POLYCYSTIC OVARY SYNDROME, FIBROIDS, ENDOMETRIOSIS, AND INFERTILITY. ALTHOUGH CURRENT MANAGEMENT GUIDELINES OFTEN TURN TO THE ESTABLISHED PHARMACEUTICAL APPROACHES FOR EACH OF THESE DIAGNOSES, THE SCIENTIFIC LITERATURE ALSO SUPPORTS AN EVIDENCE-BASED APPROACH ROOTED IN THE PARADIGM OF FOOD AS MEDICINE. ACHIEVING HEALTHY DIETARY PATTERNS IS A CORE GOAL OF LIFESTYLE MEDICINE, AND A PLANT-FORWARD APPROACH AKIN TO THE MEDITERRANEAN DIET HOLDS GREAT PROMISE FOR IMPROVING MANY CHRONIC GYNECOLOGIC DISEASES. FURTHERMORE, CREATING AN OPTIMAL PRECONCEPTION ENVIRONMENT FROM A NUTRITIONAL STANDPOINT MAY FACILITATE EPIGENETIC SIGNALING, THUS IMPROVING THE HEALTH OF FUTURE GENERATIONS. THIS STATE-OF-THE-ART REVIEW EXPLORES THE LITERATURE CONNECTING DIET WITH SEXUAL AND REPRODUCTIVE HEALTH IN PREMENOPAUSAL WOMEN. 2021 16 4166 23 MEDICAL, ETHICAL, AND LEGAL ASPECTS OF HEMATOPOIETIC STEM CELL TRANSPLANTATION FOR CROHN'S DISEASE IN BRAZIL. CROHN'S DISEASE (CD) IS A CHRONIC INFLAMMATORY BOWEL DISEASE THAT CAN AFFECT ANY PART OF THE GASTROINTESTINAL TRACT. THE ETIOLOGY OF CD IS UNKNOWN; HOWEVER, GENETIC, EPIGENETIC, ENVIRONMENTAL, AND LIFESTYLE FACTORS COULD PLAY AN ESSENTIAL ROLE IN THE ONSET AND ESTABLISHMENT OF THE DISEASE. CD RESULTS FROM IMMUNE DYSREGULATION DUE TO LOSS OF THE HEALTHY SYMBIOTIC RELATIONSHIP BETWEEN HOST AND INTESTINAL FLORA AND OR ITS ANTIGENS. IT AFFECTS BOTH SEXES EQUALLY WITH A MALE TO FEMALE RATIO OF 1.0, AND ITS ONSET CAN OCCUR AT ANY AGE, BUT THE DIAGNOSIS IS MOST COMMONLY OBSERVED IN THE RANGE OF 20 TO 40 YEARS OF AGE. CD DIMINISHES QUALITY OF LIFE, INTERFERES WITH SOCIAL ACTIVITIES, TRAUMATIZES DUE TO THE STIGMA OF INCONTINENCE, FISTULAE, STRICTURES, AND COLOSTOMIES, AND IN SEVERE CASES, AFFECTS SURVIVAL WHEN COMPARED TO THE GENERAL POPULATION. SYMPTOMS FLUCTUATE BETWEEN PERIODS OF REMISSION AND ACTIVITY IN WHICH COMPLICATIONS SUCH AS FISTULAS, STRICTURES, AND THE NEED FOR BOWEL RESECTION, SURGERY, AND COLOSTOMY IMPLANTATION MAKE UP THE MOST SEVERE ASPECTS OF THE DISEASE. CD CAN BE PROGRESSIVE AND THE COMPLICATIONS RECURRENT DESPITE TREATMENT WITH ANTI-INFLAMMATORY DRUGS, CORTICOSTEROIDS, IMMUNOSUPPRESSANTS, AND BIOLOGICAL AGENTS. HOWEVER, OVER TIME MANY PATIENTS BECOME REFRACTORY WITHOUT TREATMENT ALTERNATIVES, AND IN THIS SCENARIO, HEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT) HAS EMERGED AS A POTENTIAL TREATMENT OPTION. THE RATIONALE FOR THE USE OF HSCT FOR CD IS ANCHORED IN ANIMAL STUDIES AND HUMAN CLINICAL TRIALS WHERE HSCT COULD RESET A PATIENT'S IMMUNE SYSTEM BY ELIMINATING DISEASE-CAUSING EFFECTOR CELLS AND UPON IMMUNE RECOVERY INCREASE REGULATORY AND SUPPRESSIVE IMMUNE CELLS. AUTOLOGOUS HSCT USING A NON-MYELOABLATIVE REGIMEN OF CYCLOPHOSPHAMIDE AND ANTI-THYMOCYTE GLOBULIN WITHOUT CD34+ SELECTION HAS BEEN TO DATE THE MOST COMMON TRANSPLANT CONDITIONING REGIMEN ADOPTED. IN THIS REVIEW WE WILL ADDRESS THE CURRENT SITUATION REGARDING CD TREATMENT WITH HSCT AND EMPHASIZE THE MEDICAL, ETHICAL, AND LEGAL ASPECTS THAT PERMEATE THE PROCEDURE IN BRAZIL. 2020 17 1249 12 CURRENT KNOWLEDGE ON ENDOMETRIOSIS ETIOLOGY: A SYSTEMATIC REVIEW OF LITERATURE. OBJECTIVE: TO REVIEW THE MECHANISMS OF ENDOMETRIOSIS DEVELOPMENT, INCLUDING THOSE RELATED TO EPIGENETIC MUTATIONS, CELLULAR DYSREGULATION, INFLAMMATORY PROCESSES, AND OXIDATIVE STRESS. METHODS: A SYSTEMATIC LITERATURE REVIEW REGARDING CURRENT ASPECTS OF ENDOMETRIOSIS ETIOLOGY, GENESIS AND DEVELOPMENT WAS PERFORMED USING THE PUBMED, GOOGLE SCHOLAR, AND ELIBRARY DATABASES. KEYWORDS INCLUDED ENDOMETRIOSIS, ETIOLOGY, DEVELOPMENT, GENESIS, ASSOCIATIONS AND MECHANISMS. A MULTILINGUAL SEARCH WAS PERFORMED. RESULTS: SEVERAL MECHANISMS UNDERLINE THE PATHOPHYSIOLOGICAL PATHWAYS FOR ENDOMETRIOSIS DEVELOPMENT. EPIGENETIC MUTATIONS, EXTERNAL AND INTERNAL INFLUENCES, AND CHRONIC CONDITIONS HAVE A SIGNIFICANT IMPACT ON ENDOMETRIOSIS DEVELOPMENT, SURVIVAL AND REGULATION. SEVERAL HISTORICALLY VALID THEORIES ON ENDOMETRIOSIS DEVELOPMENT WERE DISCUSSED, AS WELL AS UPDATED FINDINGS. CONCLUSION: DESPITE RECENT ADVANCES, FUNDAMENTAL PROBLEMS IN UNDERSTANDING ENDOMETRIOSIS REMAIN UNRESOLVED. THE IDENTIFICATION OF UNKNOWN CIRCULATING EPITHELIAL PROGENITORS OR STEM CELLS THAT ARE RESPONSIBLE FOR EPITHELIAL GROWTH IN BOTH THE ENDOMETRIUM AND ENDOMETRIOTIC FOCI SEEMS TO BE THE NEXT STEP IN SOLVING THESE QUESTIONS. 2021 18 4080 13 MATERNAL LIFESTYLE INTERVENTIONS: TARGETING PRECONCEPTION HEALTH. ABOUT ONE-THIRD OF WOMEN OF REPRODUCTIVE AGE ARE OBESE, PREDISPOSING BOTH MOTHER AND BABY TO UNFAVOURABLE PREGNANCY OUTCOMES AND INITIATING AN INTERGENERATIONAL CYCLE OF CHRONIC METABOLIC DISORDERS. HERE WE SUMMARISE RECENT RESEARCH ON THE INFLUENCE OF MATERNAL METABOLIC HEALTH ON OFFSPRING SUSCEPTIBILITY TO FUTURE CARDIOMETABOLIC DISEASES. CURRENT PRIMARY LIFESTYLE APPROACHES (I.E., DIET AND EXERCISE INTERVENTIONS) TO HALT THE SUCCESSION OF INHERITED AND EPIGENETIC METABOLIC ABNORMALITIES HAVE MET WITH LIMITED SUCCESS DUE TO LATE IMPLEMENTATION, POOR ADHERENCE, AND/OR GENERIC GUIDELINES. IN OUR OPINION, SUCH INTERVENTIONS MUST COMMENCE PRIOR TO CONCEPTION TO IMPROVE BOTH MATERNAL AND CHILD HEALTH OUTCOMES, WITH NEW APPROACHES URGENTLY NEEDED TO INCREASE ADHERENCE TO PRIMARY LIFESTYLE CHANGES AMONG REPRODUCTIVE-AGE WOMEN. 2020 19 1055 16 CLINICAL INTEGRATION OF GENOME DIAGNOSTICS FOR CONGENITAL ANOMALIES OF THE KIDNEY AND URINARY TRACT. REVOLUTIONS IN GENETICS, EPIGENETICS, AND BIOINFORMATICS ARE CURRENTLY CHANGING THE OUTLINE OF DIAGNOSTICS AND CLINICAL MEDICINE. FROM A NEPHROLOGIST'S PERSPECTIVE, INDIVIDUALS WITH CONGENITAL ANOMALIES OF THE KIDNEY AND URINARY TRACT (CAKUT) ARE AN IMPORTANT PATIENT CATEGORY: NOT ONLY IS CAKUT THE PREDOMINANT CAUSE OF KIDNEY FAILURE IN CHILDREN AND YOUNG ADULTS, BUT THE STRONG PHENOTYPIC AND GENOTYPIC HETEROGENEITY OF KIDNEY AND URINARY TRACT MALFORMATIONS HAS HAMPERED STANDARDIZATION OF CLINICAL DECISION MAKING UNTIL NOW. HOWEVER, PATIENTS WITH CAKUT MAY BENEFIT FROM PRECISION MEDICINE, INCLUDING AN INTEGRATED DIAGNOSTICS TRAJECTORY, GENETIC COUNSELING, AND PERSONALIZED MANAGEMENT TO IMPROVE CLINICAL OUTCOMES OF DEVELOPMENTAL KIDNEY AND URINARY TRACT DEFECTS. IN THIS REVIEW, WE DISCUSS THE PRESENT UNDERSTANDING OF THE MOLECULAR ETIOLOGY OF CAKUT AND THE CURRENTLY AVAILABLE GENOME DIAGNOSTIC MODALITIES IN THE CLINICAL CARE OF PATIENTS WITH CAKUT. FINALLY, WE DISCUSS HOW CLINICAL INTEGRATION OF FINDINGS FROM LARGE-SCALE GENETIC, EPIGENETIC, AND GENE-ENVIRONMENT INTERACTION STUDIES MAY IMPROVE THE PROGNOSIS OF ALL INDIVIDUALS WITH CAKUT. 2020 20 4957 20 PATHOGENESIS OF ENDOMETRIOSIS: THE GENETIC/EPIGENETIC THEORY. OBJECTIVE: TO STUDY THE PATHOPHYSIOLOGY OF ENDOMETRIOSIS. DESIGN: OVERVIEW OF OBSERVATIONS ON ENDOMETRIOSIS. SETTING: NOT APPLICABLE. PATIENT(S): NONE. INTERVENTIONS(S): NONE. MAIN OUTCOME MEASURE(S): THE HYPOTHESIS IS COMPATIBLE WITH ALL OBSERVATIONS. RESULT(S): ENDOMETRIOSIS, ENDOMETRIUM-LIKE TISSUE OUTSIDE THE UTERUS, HAS A VARIABLE MACROSCOPIC APPEARANCE AND A POORLY UNDERSTOOD NATURAL HISTORY. IT IS A HEREDITARY AND HETEROGENEOUS DISEASE WITH MANY BIOCHEMICAL CHANGES IN THE LESIONS, WHICH ARE CLONAL IN ORIGIN. IT IS ASSOCIATED WITH PAIN, INFERTILITY, ADENOMYOSIS, AND CHANGES IN THE JUNCTIONAL ZONE, PLACENTATION, IMMUNOLOGY, PLASMA, PERITONEAL FLUID, AND CHRONIC INFLAMMATION OF THE PERITONEAL CAVITY. THE SAMPSON HYPOTHESIS OF IMPLANTED ENDOMETRIAL CELLS FOLLOWING RETROGRADE MENSTRUATION, ANGIOGENIC SPREAD, LYMPHOGENIC SPREAD, OR THE METAPLASIA THEORY CANNOT EXPLAIN ALL OBSERVATIONS IF METAPLASIA IS DEFINED AS CELLS WITH REVERSIBLE CHANGES AND AN ABNORMAL BEHAVIOR/MORPHOLOGY DUE TO THE ABNORMAL ENVIRONMENT. WE PROPOSE A POLYGENETIC/POLYEPIGENETIC MECHANISM. THE SET OF GENETIC AND EPIGENETIC INCIDENTS TRANSMITTED AT BIRTH COULD EXPLAIN THE HEREDITARY ASPECTS, THE PREDISPOSITION, AND THE ENDOMETRIOSIS-ASSOCIATED CHANGES IN THE ENDOMETRIUM, IMMUNOLOGY, AND PLACENTATION. TO DEVELOP TYPICAL, CYSTIC OVARIAN OR DEEP ENDOMETRIOSIS LESIONS, A VARIABLE SERIES OF ADDITIONAL TRANSMISSIBLE GENETIC AND EPIGENETIC INCIDENTS ARE REQUIRED TO OCCUR IN A CELL WHICH MAY VARY FROM ENDOMETRIAL TO STEM CELLS. SUBTLE LESIONS ARE VIEWED AS ENDOMETRIUM IN A DIFFERENT ENVIRONMENT UNTIL ADDITIONAL INCIDENTS OCCUR. TYPICAL CYSTIC OVARIAN OR DEEP ENDOMETRIOSIS LESIONS ARE HETEROGENEOUS AND REPRESENT THREE DIFFERENT DISEASES. CONCLUSION(S): THE GENETIC EPIGENETIC THEORY IS COMPATIBLE WITH ALL OBSERVATIONS ON ENDOMETRIOSIS. IMPLICATIONS FOR TREATMENT AND PREVENTION ARE DISCUSSED. 2019