1 4101 78 MDCT AND MR UROGRAM SPECTRUM OF CONGENITAL ANOMALIES OF THE KIDNEY AND URINARY TRACT DIAGNOSED IN ADULTHOOD. OBJECTIVE: CONGENITAL ANOMALIES OF THE KIDNEYS AND URINARY TRACT (CAKUT) ENCOMPASS A SPECTRUM OF ANOMALIES THAT RESULT FROM GENETIC, EPIGENETIC, ENVIRONMENTAL, AND MOLECULAR SIGNAL ABERRATIONS AT KEY STAGES OF URINARY TRACT DEVELOPMENT. CAKUT CAN BE SEEN INCIDENTALLY ON CROSS-SECTIONAL IMAGING OF THE ABDOMEN OR CAN BE A CAUSE FOR ADULT-ONSET CHRONIC KIDNEY DISEASE, POSING NEW CHALLENGES FOR NEPHROLOGISTS, UROLOGISTS, AND RADIOLOGISTS. CONCLUSION: AWARENESS OF CAKUT AND FAMILIARITY WITH THEIR IMAGING FINDINGS PERMIT OPTIMAL PATIENT MANAGEMENT AND THOROUGH WORKUP TO PREVENT HYPERTENSION AND PROGRESSION FROM CAKUT TO RENAL FAILURE. THE PURPOSE OF THIS ARTICLE IS TO REVIEW THE CROSS-SECTIONAL IMAGING FINDINGS OF CAKUT THAT MAY PRESENT IN ADULTHOOD. 2015 2 6160 33 THE GENETICS AND PATHOGENESIS OF CAKUT. CONGENITAL ANOMALIES OF THE KIDNEY AND URINARY TRACT (CAKUT) COMPRISE A LARGE VARIETY OF MALFORMATIONS THAT ARISE FROM DEFECTIVE KIDNEY OR URINARY TRACT DEVELOPMENT AND FREQUENTLY LEAD TO KIDNEY FAILURE. THE CLINICAL SPECTRUM RANGES FROM SEVERE MALFORMATIONS, SUCH AS RENAL AGENESIS, TO POTENTIALLY MILDER MANIFESTATIONS, SUCH AS VESICOURETERAL REFLUX. ALMOST 50% OF CASES OF CHRONIC KIDNEY DISEASE THAT MANIFEST WITHIN THE FIRST THREE DECADES OF LIFE ARE CAUSED BY CAKUT. EVIDENCE SUGGESTS THAT A LARGE NUMBER OF CAKUT ARE GENETIC IN ORIGIN. TO DATE, MUTATIONS IN ~54 GENES HAVE BEEN IDENTIFIED AS MONOGENIC CAUSES OF CAKUT, CONTRIBUTING TO 12-20% OF THE AETIOLOGY OF THE DISEASE. PATHOGENIC COPY NUMBER VARIANTS HAVE ALSO BEEN SHOWN TO CAUSE CAKUT AND CAN BE DETECTED IN 4-11% OF PATIENTS. FURTHERMORE, ENVIRONMENTAL AND EPIGENETIC FACTORS CAN INCREASE THE RISK OF CAKUT. THE DISCOVERY OF NOVEL CAKUT-CAUSING GENES IS CHALLENGING OWING TO VARIABLE EXPRESSIVITY, INCOMPLETE PENETRANCE AND VARIABLE GENOTYPE-PHENOTYPE CORRELATION. HOWEVER, SUCH A DISCOVERY COULD ULTIMATELY LEAD TO IMPROVEMENTS IN THE ACCURATE MOLECULAR GENETIC DIAGNOSIS, ASSESSMENT OF PROGNOSIS AND MULTIDISCIPLINARY CLINICAL MANAGEMENT OF PATIENTS WITH CAKUT, POTENTIALLY INCLUDING PERSONALIZED THERAPEUTIC APPROACHES. 2023 3 1055 31 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 4 1145 26 CONCURRENT DIAGNOSIS OF ADENOMYOSIS AND CONGENITAL UTERINE ANOMALIES: A REVIEW. BACKGROUND: ADENOMYOSIS AND CONGENITAL UTERINE ANOMALIES (CUAS) CAN COMPROMISE REPRODUCTIVE POTENTIAL AND MAY COEXIST IN THE SAME PATIENT, ESPECIALLY IN CASES OF INFERTILITY. THIS REVIEW (CRD42022382850) AIMS TO EVALUATE THE PUBLISHED CASES OF CONCURRENT ADENOMYOSIS AND SYNDROMIC AND NONSYNDROMIC CUAS. METHODS: A LITERATURE SEARCH FOR SUITABLE ARTICLES PUBLISHED IN THE ENGLISH LANGUAGE WAS PERFORMED USING THE FOLLOWING DATABASES FROM INCEPTION TO 30 NOVEMBER 2022: MEDLINE, EMBASE, GLOBAL HEALTH, THE COCHRANE LIBRARY, HEALTH TECHNOLOGY ASSESSMENT DATABASE, AND WEB OF SCIENCE. ARTICLES INCLUDING BOTH CUAS AND ADENOMYOSIS, WITH DATA ABOUT THEIR POTENTIAL RELATIONSHIP, WERE INCLUDED. RESULTS: THE LITERATURE SEARCH RETRIEVED 14 ARTICLES THAT MET THE PURPOSE OF THIS REVIEW AND SUMMARIZED THE MOST RECENT FINDINGS REGARDING THE CONCURRENT DIAGNOSIS OF ADENOMYOSIS AND CUAS. CONCLUSIONS: ADENOMYOSIS CAN BE FOUND IN BOTH SYNDROMIC AND NONSYNDROMIC CUAS, AND MAY ARISE FROM SEVERAL ETIOLOGIES. THE HYPOTHESIS THAT OBSTRUCTIONS IN CUAS INCREASE UTERINE PRESSURE AND PROMOTE THE DEVELOPMENT OF ADENOMYOSIS REMAINS TO BE FURTHER ELUCIDATED, AND ADDITIONAL FINDINGS MAY ALSO PLAY A ROLE. THE PATIENT'S GENETIC, EPIGENETIC, AND HORMONAL PATTERNS, AS WELL AS NORMAL PHYSIOLOGICAL PROCESSES, SUCH AS PREGNANCY, MAY INFLUENCE THE GROWTH OF ADENOMYOSIS. 2023 5 6744 23 WHO CARES ABOUT OLIGOZOOSPERMIA WHEN WE HAVE ICSI. THE VALUE OF ASSESSING SUBFERTILE MALES WITH OLIGOZOOSPERMIA IS CONTROVERSIAL DUE TO PREVAILING NOTIONS THAT THERAPIES ARE LIMITED AND ICSI MAY PROVIDE THE COUPLE WITH A BABY WITHOUT THE NEED TO EXPLAIN THE NATURE OR CAUSE OF UNDERLYING MALE INFERTILITY. THIS ARTICLE HIGHLIGHTS THAT INDISCRIMINATELY OFFERING ICSI TO OLIGOZOOSPERMIC MEN IS NOT FREE OF POTENTIAL ADVERSE EFFECTS AND DOES NOT GRANT SUBFERTILE MEN THE BEST FERTILITY PATHWAY. RECENT DATA SUPPORT ASSOCIATIONS BETWEEN OLIGOZOOSPERMIA AND POOR MALE REPRODUCTIVE HEALTH, DNA AND EPIGENETIC DAMAGE IN SPERMATOZOA, AND POSSIBLE ADVERSE HEALTH CONSEQUENCES TO OFFSPRING. MANY CONDITIONS AFFECTING THE TESTICLES ARE CAPABLE OF CAUSING OLIGOZOOSPERMIA (VARICOCELE, GENITAL INFECTIONS, CONGENITAL AND GENETIC DEFECTS TESTICULAR TORSION/TRAUMA, CHRONIC DISEASES, INADEQUATE LIFESTYLE, OCCUPATIONAL/ENVIRONMENTAL EXPOSURE TO TOXICANTS, DRUGS, CANCER AND RELATED TREATMENTS, ACUTE FEBRILE ILLNESS, ENDOCRINE DISORDERS, AND IATROGENIC DAMAGE TO THE GENITOURINARY SYSTEM). IF OLIGOZOOSPERMIA IS DETECTED, THERAPEUTIC INTERVENTIONS CAN IMPROVE SPERM QUANTITY/QUALITY AND THE OVERALL MALE HEALTH, ULTIMATELY RESULTING IN BETTER PREGNANCY OUTCOMES EVEN WHEN ICSI IS USED. FERTILITY CLINICS ARE URGED TO ENGAGE MALE INFERTILITY SPECIALISTS IN DIAGNOSING AND TREATING OLIGOZOOSPERMIA AS A MATTER OF BEST CLINICAL PRACTICE. A WELL-CONDUCTED MALE INFERTILITY EVALUATION REPRESENTS A UNIQUE OPPORTUNITY TO IDENTIFY RELEVANT MEDICAL AND INFERTILITY CONDITIONS, MANY OF WHICH MAY BE TREATED OR ALLEVIATED. THE ANDROLOGICAL ASSESSMENT MAY ALSO HELP GUIDE THE OPTIMAL APPLICATION OF ICSI. THE FINAL GOALS ARE TO POSITIVELY IMPACT THE OVERALL PATIENT HEALTH, THE COUPLE'S PREGNANCY PROSPECTS, AND THE OFFSPRING'S WELL-BEING. 2022 6 746 9 CANNABIS TERATOLOGY EXPLAINS CURRENT PATTERNS OF COLORADAN CONGENITAL DEFECTS: THE CONTRIBUTION OF INCREASED CANNABINOID EXPOSURE TO RISING TERATOLOGICAL TRENDS. RISING DELTA9-TETRAHYDROCANNABINOL CONCENTRATIONS IN MODERN CANNABIS INVITES INVESTIGATION OF THE TERATOLOGICAL IMPLICATIONS OF PRENATAL CANNABIS EXPOSURE. DATA FROM COLORADO RESPONDS TO CHILDREN WITH SPECIAL NEEDS (CRCSN), NATIONAL SURVEY OF DRUG USE AND HEALTH, AND DRUG ENFORCEMENT AGENCY WAS ANALYZED. SEVEN, 40, AND 2 DEFECTS WERE RISING, FLAT, AND FALLING, RESPECTIVELY, AND 10/12 SUMMARY INDICES ROSE. ATRIAL SEPTAL DEFECT, SPINA BIFIDA, MICROCEPHALUS, DOWN'S SYNDROME, VENTRICULAR SEPTAL DEFECT, AND PATENT DUCTUS ARTERIOSUS ROSE, AND ALONG WITH CENTRAL NERVOUS SYSTEM, CARDIOVASCULAR, GENITOURINARY, RESPIRATORY, CHROMOSOMAL, AND MUSCULOSKELETAL DEFECTS ROSE 5 TO 37 TIMES FASTER THAN THE BIRTH RATE (3.3%) TO GENERATE AN EXCESS OF 11 753 (22%) MAJOR ANOMALIES. CANNABIS WAS THE ONLY DRUG WHOSE USE GREW FROM 2000 TO 2014 WHILE PAIN RELIEVERS, COCAINE, ALCOHOL, AND TOBACCO DID NOT. THE CORRELATION OF CANNABIS USE WITH MAJOR DEFECTS IN 2014 (2019 DATASET) WAS R = .77, P = .0011. MULTIPLE CANNABINOIDS WERE LINKED WITH SUMMARY MEASURES OF CONGENITAL ANOMALIES AND WERE ROBUST TO MULTIVARIATE ADJUSTMENT. 2019 7 4559 25 MUTATIONS OF THE TRANSCRIPTIONAL COREPRESSOR ZMYM2 CAUSE SYNDROMIC URINARY TRACT MALFORMATIONS. CONGENITAL ANOMALIES OF THE KIDNEY AND URINARY TRACT (CAKUT) CONSTITUTE ONE OF THE MOST FREQUENT BIRTH DEFECTS AND REPRESENT THE MOST COMMON CAUSE OF CHRONIC KIDNEY DISEASE IN THE FIRST THREE DECADES OF LIFE. DESPITE THE DISCOVERY OF DOZENS OF MONOGENIC CAUSES OF CAKUT, MOST PATHOGENIC PATHWAYS REMAIN ELUSIVE. WE PERFORMED WHOLE-EXOME SEQUENCING (WES) IN 551 INDIVIDUALS WITH CAKUT AND IDENTIFIED A HETEROZYGOUS DE NOVO STOP-GAIN VARIANT IN ZMYM2 IN TWO DIFFERENT FAMILIES WITH CAKUT. THROUGH COLLABORATION, WE IDENTIFIED IN TOTAL 14 DIFFERENT HETEROZYGOUS LOSS-OF-FUNCTION MUTATIONS IN ZMYM2 IN 15 UNRELATED FAMILIES. MOST MUTATIONS OCCURRED DE NOVO, INDICATING POSSIBLE INTERFERENCE WITH REPRODUCTIVE FUNCTION. HUMAN DISEASE FEATURES ARE REPLICATED IN X. TROPICALIS LARVAE WITH MORPHOLINO KNOCKDOWNS, IN WHICH EXPRESSION OF TRUNCATED ZMYM2 PROTEINS, BASED ON INDIVIDUAL MUTATIONS, FAILED TO RESCUE RENAL AND CRANIOFACIAL DEFECTS. MOREOVER, HETEROZYGOUS ZMYM2-DEFICIENT MICE RECAPITULATED FEATURES OF CAKUT WITH HIGH PENETRANCE. THE ZMYM2 PROTEIN IS A COMPONENT OF A TRANSCRIPTIONAL COREPRESSOR COMPLEX RECENTLY LINKED TO THE SILENCING OF DEVELOPMENTALLY REGULATED ENDOGENOUS RETROVIRUS ELEMENTS. USING PROTEIN-PROTEIN INTERACTION ASSAYS, WE SHOW THAT ZMYM2 INTERACTS WITH ADDITIONAL EPIGENETIC SILENCING COMPLEXES, AS WELL AS CONFIRMING THAT IT BINDS TO FOXP1, A TRANSCRIPTION FACTOR THAT HAS ALSO BEEN LINKED TO CAKUT. IN SUMMARY, OUR FINDINGS ESTABLISH THAT LOSS-OF-FUNCTION MUTATIONS OF ZMYM2, AND POTENTIALLY THAT OF OTHER PROTEINS IN ITS INTERACTOME, AS CAUSES OF HUMAN CAKUT, OFFERING NEW ROUTES FOR STUDYING THE PATHOGENESIS OF THE DISORDER. 2020 8 5797 23 STEM CELL-BASED THERAPY FOR HIRSCHSPRUNG DISEASE, DO WE HAVE THE GUTS TO TREAT? HIRSCHSPRUNG DISEASE (HSCR) IS A CONGENITAL ANOMALY OF THE COLON THAT RESULTS FROM FAILURE OF ENTERIC NERVOUS SYSTEM FORMATION, LEADING TO A CONSTRICTED DYSFUNCTIONAL SEGMENT OF THE COLON WITH VARIABLE LENGTHS, AND NECESSITATING SURGICAL INTERVENTION. THE UNDERLYING PATHOPHYSIOLOGY INCLUDES A DEFECT IN NEURAL CREST CELLS MIGRATION, PROLIFERATION AND DIFFERENTIATION, WHICH ARE PARTIALLY EXPLAINED BY IDENTIFIED GENETIC AND EPIGENETIC ALTERATIONS. DESPITE THE HIGH SUCCESS RATE OF THE CURATIVE SURGERIES, THEY ARE ASSOCIATED WITH SIGNIFICANT ADVERSE OUTCOMES SUCH AS ENTEROCOLITIS, FECAL SOILING, AND CHRONIC CONSTIPATION. IN ADDITION, SOME PATIENTS SUFFER FROM EXTENSIVE LETHAL VARIANTS OF THE DISEASE, ALL OF WHICH JUSTIFY THE NEED FOR AN ALTERNATIVE CURE. DURING THE LAST 5 YEARS, THERE HAS BEEN CONSIDERABLE PROGRESS IN HSCR STEM CELL-BASED THERAPY RESEARCH. HOWEVER, MANY MAJOR ISSUES REMAIN UNSOLVED. THIS REVIEW WILL PROVIDE CONCISE BACKGROUND INFORMATION ON HSCR, OUTLINE THE FUTURE APPROACHES OF STEM CELL-BASED HSCR THERAPY, REVIEW RECENT KEY PUBLICATIONS, DISCUSS TECHNICAL AND ETHICAL CHALLENGES THE FIELD FACES PRIOR TO CLINICAL TRANSLATION, AND TACKLE SUCH CHALLENGES BY PROPOSING SOLUTIONS AND EVALUATING EXISTING APPROACHES TO PROGRESS FURTHER. 2022 9 6825 20 [GENETIC AND EPIGENETIC FACTORS OF POLYCYSTIC OVARY SYNDROME]. THE DEVELOPMENT OF POLYCYSTIC OVARY SYNDROME AND ITS EXACT PATHOPHYSIOLOGICAL MECHANISM IS STILL UNCLEAR, BUT ENVIRONMENTAL AND GENETIC FACTORS LIKELY PLAY A ROLE. EXPOSITION TO TERATOGENIC EFFECTS DURING THE PRENATAL DEVELOPMENT CAN LEAD TO CHRONIC DISEASES IN THE POSTNATAL PERIOD. THIS FINDING CONFIRMS THE COMMON FAMILIAL AGGREGATION AS WELL. A LITERATURE SEARCH WAS CONDUCTED UP TO JANUARY 1, 2016 FOR ARTICLES DEALING WITH THE GENETIC OR EPIGENETIC FACTORS OF POLYCYSTIC OVARY SYNDROME. THIS REVIEW WILL DISCUSS THE CURRENT UNDERSTANDING OF THE GENETIC BASIS AND CLINICAL PRESENTATION OF THIS DISEASE. ORV. HETIL., 2016, 157(32), 1275-1281. 2016 10 5154 18 PRAKRITI-BASED MEDICINE: A STEP TOWARDS PERSONALIZED MEDICINE. THE CONCEPT OF PERSONALIZED MEDICINE HAS BEEN AROUND FOR AS LONG AS PEOPLE HAVE BEEN PRACTICING MEDICINE. FROM CHARAKA TO HIPPOCRATES, ALL HAVE PRACTICED THE PERSONALIZED APPROACH FOR TREATING A DISEASE. IN THE 21(ST) CENTURY, PERSONALIZED MEDICINE IS ALL ABOUT DNA. WHEREAS THE SINGLE NUCLEOTIDE POLYMORPHISM (SNP) AND EPIGENETIC FACTORS INFLUENCE DRUG RESPONSE AND FORM THE BASIS OF PERSONALIZED MEDICINE, THE TRIDOSHA THEORY FORMS THE BASIS OF PRAKRITI-BASED MEDICINE. IT IS WELL ESTABLISHED BY NOW THAT WESTERN ALLOPATHIC MEDICINE IS EXCELLENT IN HANDLING ACUTE MEDICAL CRISES, WHEREAS AYURVEDA HAS SUCCESSFULLY DEMONSTRATED AN ABILITY TO MANAGE CHRONIC DISORDERS THAT WESTERN MEDICINE HAS BEEN UNABLE TO CURE. WITH EFFECTIVE INTEGRATION OF 'OMICS' PRAKRITI-BASED MEDICINE CAN PLAY A VITAL ROLE IN THIS CHANGING SCENARIO OF GLOBAL HEALTH WISDOM AS AYURVEDA OFFERS ITS MODALITIES BY WAY OF AHARA (DIET), VIHARA (LIFESTYLE), AND AUSHADHI (MEDICATION), WHICH ARE THE THREE PILLARS OF PRAKRITI-BASED MEDICINE MAKING IT A HOLISTIC SCIENCE. PRAKRITI-BASED MEDICINE AND OTHER TRADITIONAL MEDICINE SYSTEMS HAVE THE POTENTIAL TO OFFER REMEDIES TO THE CHALLENGING HEALTH ISSUES LIKE ADVERSE DRUG REACTIONS, DRUG WITHDRAWALS, AND ECONOMIC DISPARITIES AMONG FEW. AN INTEGRATIVE GLOBAL APPROACH COULD DO WONDERS TO HEALTH SCIENCES BENEFITING A BROAD SPECTRUM OF PATIENTS. 2011 11 2814 24 FIBRODYSPLASIA OSSIFICANS PROGRESSIVA: MIDDLE-AGE ONSET OF HETEROTOPIC OSSIFICATION FROM A UNIQUE MISSENSE MUTATION (C.974G>C, P.G325A) IN ACVR1. FIBRODYSPLASIA OSSIFICANS PROGRESSIVA (FOP) IS THE RARE MENDELIAN DISEASE CHARACTERIZED BY CONGENITAL MALFORMATION OF THE GREAT TOES PRECEDING HETEROTOPIC OSSIFICATION (HO) AND CAUSED BY HETEROZYGOUS ACTIVATING MUTATION OF THE ACVR1 GENE, WHICH ENCODES THE ALK2 RECEPTOR FOR BONE MORPHOGENETIC PROTEINS. EARLY ADULT LIFE IS THE LATEST REPORTED PRESENTATION FOR THE HO OF FOP. THE PATIENT OF OUR REPORT FIRST DEVELOPED HO FROM FOP AT 47 YEARS OF AGE. SHE HAD CONGENITAL HALLUX VALGUS DEFORMITY BUT DESPITE VARIOUS TRAUMAS WAS PREVIOUSLY WELL. HO BEGAN SEVERAL MONTHS AFTER A BRIEF, SEEMINGLY VIRAL, ILLNESS. SUDDEN AND PROGRESSIVE PAIN, REDNESS, WARMTH, AND SWELLING APPEARED OVER A SCAPULA. COMPUTED TOMOGRAPHY WAS REMARKABLE FOR ASYMMETRICAL THICKENING OF MUSCLES AND FASCIAL PLANES. AT FIRST, THE SIGNIFICANCE OF THE GREAT TOE ABNORMALITIES WENT UNRECOGNIZED ELSEWHERE, AND BIOPSY FOR SUSPECTED INFLAMMATORY FASCIITIS REVEALED PROLIFERATING FIBROBLASTS WITH SCATTERED INFLAMMATORY CELLS. PREDNISONE IMPROVED HER SYMPTOMS BUT, WHEN TAPERED, SWELLINGS DEVELOPED ON HER CHEST, POSTERIOR THORAX, AND FLANK, AND FOP WAS DIAGNOSED. METHYLPREDNISOLONE, METHOTREXATE, AND ALENDRONATE SEEMED TO HELP HER SYMPTOMS, BUT THE LESIONS WORSENED AND HO APPEARED AND RAPIDLY PROGRESSED. MUTATION ANALYSIS OF THE ACVR1 GENE REVEALED HETEROZYGOSITY FOR A UNIQUE MISSENSE DEFECT (C.974G>C, P.G325A) THAT PREDICTED A CONSERVATIVE (MILD) AMINO ACID CHANGE WITHIN THE KINASE DOMAIN OF ALK2. HENCE, HO IN FOP CAN BE DELAYED UNTIL MIDDLE-AGE, AND PERHAPS PROVOKED BY A VIRAL ILLNESS. NEVERTHELESS, PROGRESSION OF HO CAN THEN BE RAPID DESPITE BISPHOSPHONATE AND HIGH-DOSE IMMUNOSUPPRESSIVE THERAPY. POSSIBLY, OUR PATIENT'S LATE-ONSET HO REFLECTS HER MILD ALTERATION OF ALK2 OR SOME PROTECTIVE AND THERAPEUTICALLY USEFUL GENETIC, EPIGENETIC, OR NONGENETIC FACTOR. RECOGNITION OF PRESYMPTOMATIC INDIVIDUALS OR LATE-ONSET HO IN FOP SHOULD HAVE THESE PATIENTS AVOID TRAUMAS, TREATMENTS, AND MAYBE VIRAL ILLNESSES THAT CAN INITIATE OR EXACERBATE THE HO. IF THE DIAGNOSIS OF FOP IS UNCLEAR, ACVR1 MUTATION ANALYSIS IS AVAILABLE AT CERTIFIED LABORATORIES. 2012 12 6815 17 [EVOLUTIONARY ONTOGENETIC ASPECTS OF PATHOGENETICS OF CHRONIC HUMAN DISEASES]. THIS ARTICLE IS A REVIEW OF SCIENTIFIC PUBLICATIONS, IN WHICH ISSUES OF PATHOGENETICS OF MULTIFACTORIAL DISEASES (MFDS) ARE CONSIDERED FROM THE VIEWPOINT OF EVOLUTION AND ONTOGENY. CONCEPTS EXPLAINING SIGNIFICANCE OF EVOLUTIONARY PROCESSES IN THE FORMATION OF GENETIC ARCHITECTURE OF HUMAN CHRONIC DISEASES ("THRIFTY" GENOMES AND PHENOTYPES, "DRIFTING GENES," DECANALIZATION) ARE ANALYZED. THE ROLES OF NATURAL SELECTION AND GENETIC DRIFT IN THE FORMATION OF HEREDITARY DIVERSITY OF GENES FOR SUSCEPTIBILITY TO MFDS ARE CONSIDERED. THE MODERN CONCEPT OF DISEASE ONTOGENY (SOMATIC MOSAICISM, LOSS OFHETEROZYGOSITY, PARADOMINANT INHERITANCE, EPIGENETIC VARIABILITY) IS DISCUSSED. IT IS DEMONSTRATED THAT THE EVOLUTIONARY AND ONTOGENETIC APPROACHES TO ANALYSIS OF GENIMUC AND OTHER "-OMIC" DATA ARE ESSENTIAL FOR UNDERSTANDING THE BIOLOGY OF DISEASES. 2011 13 3400 23 HOW CAN PRECISION MEDICINE BE APPLIED TO TEMPOROMANDIBULAR DISORDERS AND ITS COMORBIDITIES? THE EIGHTH SCIENTIFIC MEETING OF THE TMJ ASSOCIATION, LTD. WAS HELD IN BETHESDA, MARYLAND, SEPTEMBER 11-13, 2016. AS IN THE PAST, THE MEETING WAS COSPONSORED BY COMPONENTS OF THE NATIONAL INSTITUTES OF HEALTH WITH SPEAKERS INVITED TO REVIEW THE STATE OF TEMPOROMANDIBULAR DISORDER SCIENCE AND PROPOSE RECOMMENDATIONS TO FURTHER PROGRESS. THE THEME OF PRECISION MEDICINE, WHICH AIMS TO TAILOR DISEASE TREATMENT AND PREVENTION TO MATCH THE CHARACTERISTICS OF AN INDIVIDUAL PATIENT (GENETIC, EPIGENETIC, ENVIRONMENTAL, LIFESTYLE) UNDERSCORED THE CURRENT CONSENSUS THAT TEMPOROMANDIBULAR DISORDERS ARE NO LONGER VIEWED AS LOCAL CONDITIONS OF JAW PAIN AND DYSFUNCTION. RATHER, THEY REPRESENT A COMPLEX FAMILY OF BIOPSYCHOSOCIAL DISORDERS THAT CAN PROGRESS TO CHRONIC PAIN, MOST OFTEN ACCOMPANIED BY ONE OR MORE OTHER CHRONIC PAIN CONDITIONS. TEMPOROMANDIBULAR DISORDERS AND THESE COMORBIDITIES, CALLED CHRONIC OVERLAPPING PAIN CONDITIONS, PREDOMINANTLY OR EXCLUSIVELY AFFECT WOMEN IN THEIR CHILDBEARING YEARS AND REFLECT CENTRAL NERVOUS SYSTEM SENSITIZATION. PRESENTERS AT THE MEETING INCLUDED LEADERS IN TEMPOROMANDIBULAR DISORDER AND PAIN RESEARCH, TEMPOROMANDIBULAR DISORDER PATIENTS AND ADVOCATES, AND EXPERTS IN OTHER FIELDS OR IN THE USE OF TECHNOLOGIES THAT COULD FACILITATE THE DEVELOPMENT OF PRECISION MEDICINE APPROACHES IN TEMPOROMANDIBULAR DISORDERS. 2017 14 1892 18 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 15 1148 25 CONGENITAL HYPOTHYROIDISM AND THYROID CANCER. DIFFERENTIATED THYROID CARCINOMA (DTC) COMBINED WITH CONGENITAL HYPOTHYROIDISM (CH) IS A RARE SITUATION, AND THERE IS NO WELL-ESTABLISHED CAUSAL RELATIONSHIP. CH IS A COMMON CONGENITAL ENDOCRINE, WHILE DTC OCCURRING IN CHILDHOOD REPRESENTS 0.4-3% OF ALL MALIGNANCIES AT THIS STAGE OF LIFE. THE ASSOCIATION OF CH WITH DTC COULD BE RELATED TO DYSHORMONOGENETIC GOITER (DHG) OR DEVELOPMENTAL ABNORMALITIES. THIS REVIEW WILL EXPLORE THE CLINICAL FEATURES AND THE MOLECULAR MECHANISMS POTENTIALLY ASSOCIATED WITH THE APPEARANCE OF DTC IN CH: SPORADIC SOMATIC DRIVER MUTATIONS, CHRONIC INCREASE OF THYROID-STIMULATING HORMONE (TSH) LEVELS, HIGHER CONCENTRATIONS OF HYDROGEN PEROXIDE (H2O2), CELL DIVISION CYCLE ASSOCIATED 8 (BORELAIN/CDC8) GENE MUTATIONS, AND IN OTHERS GENES ASSOCIATED WITH CH - EITHER ALONE OR ASSOCIATED WITH THE MECHANISMS INVOLVED IN DYSHORMONOGENESIS. THERE ARE SOME PITFALLS IN THE DIAGNOSIS OF THYROID CANCER IN PATIENTS WITH CH WITH NODULAR GOITER, AS THE PROPER CYTOLOGICAL DIAGNOSIS OF NODULES OF PATIENTS WITH DYSHORMONOGENESIS MIGHT BE DEMANDING DUE TO THE SPECIFIC ARCHITECTURAL AND CYTOLOGICAL APPEARANCE, WHICH MAY LEAD TO AN ERRONEOUS INTERPRETATION OF MALIGNANCY. THE PURPOSE OF THIS ARTICLE IS TO SUGGEST AN ANALYTICAL FRAMEWORK THAT EMBRACES THE FUNDAMENTAL RELATIONSHIPS BETWEEN THE VARIOUS ASPECTS OF CH AND CDT. IN FACE OF THIS SCENARIO, THE ENTIRE GENETIC AND EPIGENETIC CONTEXT, THE COMPLEX FUNCTIONING, AND CROSS TALK OF CELL SIGNALING MAY DETERMINE CELLULAR MECHANISMS PROMOTING BOTH THE MAINTENANCE OF THE DIFFERENTIATED STATE OF THE THYROID FOLLICULAR CELL AND THE DISRUPTION OF ITS HOMEOSTASIS LEADING TO CANCER. WHEREAS, THE EXACT MECHANISMS FOR THYROID CANCER DEVELOPMENT IN CH REMAIN TO BE ELUCIDATED. 2021 16 6917 18 [WHOSE BORDERLINE IS IT? HYPOTHESIZED ETIOLOGIES OF BORDERLINE PERSONALITY]. BORDERLINE PERSONALITY IS A WELL KNOWN CONCEPT IN PSYCHIATRIC LITERATURE, HOWEVER, NOT FULLY UNDERSTOOD AS TO ITS VERY NATURE. THIS ARTICLE PRESENTS A SHORT REVIEW OF HYPOTHESIZED ETIOLOGIES OF THE BORDERLINE PERSONALITY, STARTING WITH SO CALLED TRADITIONAL THEORIES, NAMELY, BORDERLINE PERSONALITY AS A CONSOLIDATED PERSONALITY ORGANIZATION, IN WHICH THE PATIENT PATHOLOGICALLY DEALS WITH HIS OR HER INNER AGGRESSION, OR WITH AN ENDURING DEVELOPMENTAL FAILURE. MORE MODERN HYPOTHESES FOCUS ON POSSIBLE CHILDHOOD SEXUAL ABUSE AS THE ORIGIN OF THE BORDERLINE, VIEWING THE ADULT PERSONALITY AS A CHRONIC, UNRESOLVED, POST-TRAUMATIC DISORDER. ADDITIONALLY, A NEURO-EPIGENETIC VIEW HYPOTHESIZED THAT A UNIQUE CONGENITAL NEUROLOGICAL STRUCTURE INTERACTS WITH CONSEQUENTIAL EVENTS IN EARLY CHILDHOOD TO CREATE THE BORDERLINE PERSONALITY. 2008 17 6649 20 UPDATE ON ENDOMETRIOSIS PATHOGENESIS. ENDOMETRIOSIS IS A CHRONIC, INFLAMMATORY, CONDITION OF HIGH INCIDENCE AND SERIOUS REPRODUCTIVE AND GENERAL HEALTH CONSEQUENCES. UNDERSTANDING THE PATHOGENESIS OF ENDOMETRIOSIS IS CRUCIAL FOR PROPER DIAGNOSTIC AND ORDERING THE MOST EFFECTIVE TREATMENT. EVEN THOUGH THERE IS A LARGE BODY OF DATA REGARDING THIS PATHOLOGY OUR UNDERSTANDING OF THE PATHOGENESIS OF THIS DISEASE REMAINS INCOMPLETE. THE AIM OF THIS REVIEW IS TO SUMMARIZE CONTEMPORARY DATA REGARDING PATHOGENESIS OF ENDOMETRIOSIS. CURRENT DATA REGARDING ENDOMETRIAL ORIGIN, METAPLASTIC AND MULLERIAN EMBRYONIC RESTS THEORY WILL BE REVIEWED HERE. ALSO GENETIC, EPIGENETIC, ENVIRONMENTAL FACTORS AND IMMUNOLOGICAL DYSFUNCTION ROLE IN ENDOMETRIOSIS WILL BE SUMMARIZED. TO CONCLUDE, A LOT OF EFFORT MUST BE PUT TO INTEGRATE THE ABUNDANT DATA FROM GENETIC, EPIGENETIC AND IMMUNOLOGICAL STUDIES TO PROPOSE ONE COHERENT THEORY FOR THE PATHOGENESIS OF ENDOMETRIOSIS. 2017 18 6537 21 TRANSCRIPTIONAL REGULATOR PRDM12 IS ESSENTIAL FOR HUMAN PAIN PERCEPTION. PAIN PERCEPTION HAS EVOLVED AS A WARNING MECHANISM TO ALERT ORGANISMS TO TISSUE DAMAGE AND DANGEROUS ENVIRONMENTS. IN HUMANS, HOWEVER, UNDESIRABLE, EXCESSIVE OR CHRONIC PAIN IS A COMMON AND MAJOR SOCIETAL BURDEN FOR WHICH AVAILABLE MEDICAL TREATMENTS ARE CURRENTLY SUBOPTIMAL. NEW THERAPEUTIC OPTIONS HAVE RECENTLY BEEN DERIVED FROM STUDIES OF INDIVIDUALS WITH CONGENITAL INSENSITIVITY TO PAIN (CIP). HERE WE IDENTIFIED 10 DIFFERENT HOMOZYGOUS MUTATIONS IN PRDM12 (ENCODING PRDI-BF1 AND RIZ HOMOLOGY DOMAIN-CONTAINING PROTEIN 12) IN SUBJECTS WITH CIP FROM 11 FAMILIES. PRDM PROTEINS ARE A FAMILY OF EPIGENETIC REGULATORS THAT CONTROL NEURAL SPECIFICATION AND NEUROGENESIS. WE DETERMINED THAT PRDM12 IS EXPRESSED IN NOCICEPTORS AND THEIR PROGENITORS AND PARTICIPATES IN THE DEVELOPMENT OF SENSORY NEURONS IN XENOPUS EMBRYOS. MOREOVER, CIP-ASSOCIATED MUTANTS ABROGATE THE HISTONE-MODIFYING POTENTIAL ASSOCIATED WITH WILD-TYPE PRDM12. PRDM12 EMERGES AS A KEY FACTOR IN THE ORCHESTRATION OF SENSORY NEUROGENESIS AND MAY HOLD PROMISE AS A TARGET FOR NEW PAIN THERAPEUTICS. 2015 19 2865 18 FUNCTIONAL ABDOMINAL PAIN DISORDERS IN CHILDREN. CHRONIC ABDOMINAL PAIN IS A COMMON PROBLEM IN PEDIATRIC PRACTICE. THE MAJORITY OF CASES FULFILL THE ROME IV CRITERIA FOR FUNCTIONAL ABDOMINAL PAIN DISORDERS (FAPDS). AT TIMES, THESE DISORDERS MAY LEAD TO RATHER SERIOUS REPERCUSSIONS. AREA COVERED: WE HAVE ATTEMPTED TO COVER CURRENT KNOWLEDGE ON EPIDEMIOLOGY, PATHOPHYSIOLOGY, RISK FACTORS RELATED TO PATHOPHYSIOLOGY, CLINICAL EVALUATION AND MANAGEMENT OF CHILDREN WITH FAPDS. EXPERT COMMENTARY: FAPDS ARE A WORLDWIDE PROBLEM WITH A POOLED PREVALENCE OF 13.5%. THERE ARE A NUMBER OF PREDISPOSING FACTORS AND PATHOPHYSIOLOGICAL MECHANISMS INCLUDING STRESSFUL EVENTS, CHILD MALTREATMENT, VISCERAL HYPERSENSITIVITY, ALTERED GASTROINTESTINAL MOTILITY AND CHANGE IN INTESTINAL MICROBIOTA. IT IS POSSIBLE THAT THE ENVIRONMENTAL RISK FACTORS INTRICATELY INTERACT WITH GENES THROUGH EPIGENETIC MECHANISMS TO CONTRIBUTE TO THE PATHOPHYSIOLOGY. THE DIAGNOSIS MAINLY DEPENDS ON CLINICAL EVALUATION. COMMONLY USED PHARMACOLOGICAL INTERVENTIONS DO NOT PLAY A MAJOR ROLE IN RELIEVING SYMPTOMS. CENTRALLY DIRECTED, NONPHARMACOLOGICAL INTERVENTIONS SUCH AS HYPNOTHERAPY AND COGNITIVE BEHAVIORAL THERAPY HAVE SHOWN BOTH SHORT AND LONG TERM EFFICACY IN RELIEVING PAIN IN CHILDREN WITH FAPDS. HOWEVER, THESE INTERVENTIONS ARE TIME CONSUMING AND NEED SPECIALLY TRAINED STAFF AND THEREFORE, NOT CURRENTLY AVAILABLE AT GRASS ROOT LEVEL. CLINICIANS AND RESEARCHERS SHOULD JOIN HANDS IN SEARCHING FOR MORE PRAGMATIC AND EFFECTIVE THERAPEUTIC MODALITIES TO IMPROVE OVERALL CARE OF CHILDREN WITH FAPDS. 2018 20 3821 23 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