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Digestive Diseases and Sciences Jun 2024Extraintestinal Manifestations (EIMs) are a common and potentially debilitating complication of Inflammatory Bowel Diseases (IBD), sometimes requiring additional...
BACKGROUND
Extraintestinal Manifestations (EIMs) are a common and potentially debilitating complication of Inflammatory Bowel Diseases (IBD), sometimes requiring additional treatment beyond those used to control intestinal disease. IBD-associated arthritis (IAA), a form of spondyloarthritis, is associated with several factors including disease location, sex, and IBD type. However, much remains unknown about other clinical factors predicting development of EIMs. Our goal was to identify additional factors associated with IAA.
METHODS
Participants in the LOCATION-IBD cohort were included in this analysis. We performed univariate and multivariate analysis of demographics, clinical data, and patient-reported outcomes data.
RESULTS
The LOCATION-IBD cohort included 182 participants with (n = 53) and without (n = 110) joint EIMs and with joint pain of unclear etiology (n = 19). In a multivariate analysis comparing those with and without joint EIMs, female sex (OR = 2.5, p = 0.014), the presence of concomitant autoimmune and inflammatory disorders (OR = 2.5, p = 0.038), and Crohn's disease (OR = 2.9, p = 0.026) were associated with the presence of joint EIMs.
CONCLUSION
This analysis reveals patients with IAA are more likely to have concomitant autoimmune disorders. Further studies are needed to confirm this association, understand the mechanisms underlying the common pathogenesis of these concurrent disorders, and evaluate their impact on the treatment of IAA.
PubMed: 38902460
DOI: 10.1007/s10620-024-08478-7 -
BMJ Case Reports Jun 2024This case report describes a man in his 20s presenting with bilateral crypto-orchidism, micropenis and underdeveloped secondary sexual characteristics. The patient also...
This case report describes a man in his 20s presenting with bilateral crypto-orchidism, micropenis and underdeveloped secondary sexual characteristics. The patient also exhibited hyposmia, eunuchoid stature and gynecomastia. Biochemical investigations revealed low levels of testosterone, luteinising hormone and follicle-stimulating hormone. Hence, he was diagnosed with Kallmann syndrome. Imaging studies showed an absent right kidney and cystic dilatation of the distal ureteric bud, seminal vesicle and absent/hypoplastic ejaculatory duct. The association of hypogonadotropic hypogonadism with Zinner syndrome, a rare condition characterised by renal agenesis, seminal vesicle cyst and ejaculatory duct obstruction, was noted.
Topics: Humans; Male; Hypogonadism; Kallmann Syndrome; Seminal Vesicles; Kidney; Ejaculatory Ducts; Adult; Penis
PubMed: 38901851
DOI: 10.1136/bcr-2023-259363 -
Behavioral and Brain Functions : BBF Jun 2024Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disorders with higher incidence in males and is characterized by atypical verbal/nonverbal communication,...
BACKGROUND
Autism Spectrum Disorder (ASD) is a group of neurodevelopmental disorders with higher incidence in males and is characterized by atypical verbal/nonverbal communication, restricted interests that can be accompanied by repetitive behavior, and disturbances in social behavior. This study investigated brain mechanisms that contribute to sociability deficits and sex differences in an ASD animal model.
METHODS
Sociability was measured in C58/J and C57BL/6J mice using the 3-chamber social choice test. Bulk RNA-Seq and snRNA-Seq identified transcriptional changes in C58/J and C57BL/6J amygdala within which DMRseq was used to measure differentially methylated regions in amygdala.
RESULTS
C58/J mice displayed divergent social strata in the 3-chamber test. Transcriptional and pathway signatures revealed immune-related biological processes differ between C58/J and C57BL/6J amygdala. Hypermethylated and hypomethylated genes were identified in C58/J versus C57BL/6J amygdala. snRNA-Seq data in C58/J amygdala identified differential transcriptional signatures within oligodendrocytes and microglia characterized by increased ASD risk gene expression and predicted impaired myelination that was dependent on sex and sociability. RNA velocity, gene regulatory network, and cell communication analysis showed diminished oligodendrocyte/microglia differentiation. Findings were verified using Bulk RNA-Seq and demonstrated oxytocin's beneficial effects on myelin gene expression.
LIMITATIONS
Our findings are significant. However, limitations can be noted. The cellular mechanisms linking reduced oligodendrocyte differentiation and reduced myelination to an ASD phenotype in C58/J mice need further investigation. Additional snRNA-Seq and spatial studies would determine if effects in oligodendrocytes/microglia are unique to amygdala or if this occurs in other brain regions. Oxytocin's effects need further examination to understand its' potential as an ASD therapeutic.
CONCLUSIONS
Our work demonstrates the C58/J mouse model's utility in evaluating the influence of sex and sociability on the transcriptome in concomitant brain regions involved in ASD. Our single-nucleus transcriptome analysis elucidates potential pathological roles of oligodendrocytes and microglia in ASD. This investigation provides details regarding regulatory features disrupted in these cell types, including transcriptional gene dysregulation, aberrant cell differentiation, altered gene regulatory networks, and changes to key pathways that promote microglia/oligodendrocyte differentiation. Our studies provide insight into interactions between genetic risk and epigenetic processes associated with divergent affiliative behavior and lack of positive sociability.
Topics: Animals; Male; Microglia; Mice; Amygdala; Female; Oligodendroglia; Autism Spectrum Disorder; Mice, Inbred C57BL; Social Behavior; Gene Expression Profiling; Phenotype; Sex Characteristics; Transcriptome; Disease Models, Animal; Oxytocin
PubMed: 38898502
DOI: 10.1186/s12993-024-00240-3 -
Psychoneuroendocrinology Jun 2024Type 2 Diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia, resulting from deficits in insulin secretion, insulin action, or both....
Type 2 Diabetes mellitus (T2DM) is a metabolic disorder characterized by chronic hyperglycemia, resulting from deficits in insulin secretion, insulin action, or both. Whilst the role of insulin in the peripheral nervous system has been ascertained in countless studies, its role in the central nervous system (CNS) is emerging only recently. Brain insulin has been lately associated with brain disorders like Alzheimer's disease, obsessive compulsive disorder, and attention deficit hyperactivity disorder. Thus, understanding the role of insulin as a common risk factor for mental and somatic comorbidities may disclose novel preventative and therapeutic approaches. We evaluated general metabolism (glucose tolerance, insulin sensitivity, energy expenditure, lipid metabolism, and polydipsia) and cognitive capabilities (attention, cognitive flexibility, and memory), in adolescent, young adult, and adult male and female TALLYHO/JngJ mice (TH, previously reported to constitute a valid experimental model of T2DM due to impaired insulin signaling). Adult TH mice have also been studied for alterations in gut microbiota diversity and composition. While TH mice exhibited profound deficits in cognitive flexibility and altered glucose metabolism, we observed that these alterations emerged either much earlier (males) or independent of (females) a comprehensive constellation of symptoms, isomorphic to an overt T2DM-like phenotype (insulin resistance, polydipsia, higher energy expenditure, and altered lipid metabolism). We also observed significant sex-dependent alterations in gut microbiota alpha diversity and taxonomy in adult TH mice. Deficits in insulin signaling may represent a common risk factor for both T2DM and CNS-related deficits, which may stem from (partly) independent mechanisms.
PubMed: 38896988
DOI: 10.1016/j.psyneuen.2024.107102 -
Journal of Developmental and Behavioral... Jun 2024To determine whether the prevalence of psychosocial risk in children and adolescents changed from before to during the COVID-19 pandemic and whether these changes...
OBJECTIVE
To determine whether the prevalence of psychosocial risk in children and adolescents changed from before to during the COVID-19 pandemic and whether these changes differed by age group, sex, and season, based on a standardized psychosocial measure completed as a routine part of primary care.
METHODS
Children and adolescents aged 5.5 to 17.9 years were screened with a parent report Pediatric Symptom Checklist-17 (PSC-17P) between November 2017 and June 2022. Changes in the prevalence of psychosocial risk (global, internalizing, externalizing, and attention scales) from before to during the pandemic were compared by age group, sex, and season.
RESULTS
In a sample of 459,767 health supervision visits, the prevalence of PSC-17P global, internalizing, and attention risk worsened significantly from before to during the pandemic, especially among female adolescents (ages 12.0-17.9). For a pediatrician seeing a hypothetical sample of 1000 adolescent girls, the expected number at risk would have increased from 103 to 131 on the global scale (26.6% increase), from 189 to 231 on the internalizing subscale (22.0% increase), and from 60 to 82 on the attention subscale (35.7% increase). Seasonality had a large effect, with significantly lower PSC-17P risk in the summer every year.
CONCLUSION
Data from a large, national sample of pediatric visits suggested that global, internalizing, and attention concerns increased slightly overall from before to during the COVID-19 pandemic, with different patterns by age group and sex. Adolescent girls showed substantially increased global, internalizing, and attention problems. These increases support the need for further research and additional individual and system-level interventions.
PubMed: 38896783
DOI: 10.1097/DBP.0000000000001273 -
Autism Research : Official Journal of... Jun 2024Younger siblings (SIBS) of children with autism exhibit a wide range of clinical and subclinical symptoms including social, cognitive, language, and adaptive functioning...
Younger siblings (SIBS) of children with autism exhibit a wide range of clinical and subclinical symptoms including social, cognitive, language, and adaptive functioning delays. Identifying factors linked with this phenotypic heterogeneity is essential for improving understanding of the underlying biology of the heterogenous outcomes and for early identification of the most vulnerable SIBS. Prevalence of neurodevelopmental (NDD) and neuropsychiatric disorders (NPD) is significantly elevated in families of children with autism. It remains unknown, however, if the family history associates with the developmental outcomes among the SIBS. We quantified history of the NDDs and NPDs commonly reported in families of children with autism using a parent interview and assessed autism symptoms, verbal, nonverbal, and adaptive skills in a sample of 229 SIBS. Multiple regression analyses were used to examine links between family history and phenotypic outcomes, whereas controlling for birth year, age, sex, demographics, and parental education. Results suggest that family history of schizophrenia, depression, anxiety, bipolar disorder, and intellectual disability associate robustly with dimensional measures of social affect, verbal and nonverbal IQ, and adaptive functioning in the SIBS. Considering family history of these disorders may improve efforts to predict long-term outcomes in younger siblings of children with autism and inform about familial factors contributing to high phenotypic heterogenetity in this cohort.
PubMed: 38896553
DOI: 10.1002/aur.3175 -
Obstetrical & Gynecological Survey Jun 2024Polycystic ovary syndrome (PCOS) is a common endocrine syndrome with multiple causes and polymorphic clinical manifestations, which is one of the important causes of... (Review)
Review
IMPORTANCE
Polycystic ovary syndrome (PCOS) is a common endocrine syndrome with multiple causes and polymorphic clinical manifestations, which is one of the important causes of menstrual disorders in women of childbearing age. It has been found that branched-chain amino acids (BCAAs), a class of essential amino acids that cannot be synthesized by the human body, play a significant role in the metabolic changes of PCOS, which may be involved in the pathogenesis of PCOS.
OBJECTIVE
The purpose of this review is to summarize the relevance between BCAAs and metabolic abnormalities in PCOS and to explore their possible mechanisms.
EVIDENCE ACQUISITION
The evidence is mainly obtained by reviewing the literature on PubMed related to PCOS, BCAAs, and related metabolic abnormalities and conducting summary analysis.
RESULTS
The metabolism of BCAAs can affect the homeostasis of glucose metabolism, possibly by disrupting the balance of gut microbiota, activating mTORC1 targets, producing mitochondrial toxic metabolites, and increasing the expression of proinflammatory genes. The correlation between obesity and BCAAs in PCOS patients may be related to the gene expression of BCAA metabolism-related enzymes in adipose tissue. The association between BCAA metabolic changes and nonalcoholic fatty liver disease in PCOS patients has not been fully clarified, which may be related to the lipid accumulation caused by BCAAs. At present, it is believed that hyperandrogenism in patients with PCOS is not related to BCAAs. However, through the study of changes in BCAA metabolism in prostate cancer caused by hyperandrogenism, we speculate that the relationship between BCAAs and hyperandrogenism may be mediated by mTORC1 and amino acid transporters.
CONCLUSIONS AND RELEVANCE
Review of prior articles reveals that BCAAs may be related to insulin resistance, obesity, nonalcoholic fatty liver, and hyperandrogenism in PCOS patients, and its mechanisms are complex, diverse, and interrelated. This review also discussed the mechanism of BCAAs and these metabolic disorders in non-PCOS patients, which may provide some help for future research.
Topics: Humans; Polycystic Ovary Syndrome; Amino Acids, Branched-Chain; Female; Hyperandrogenism; Non-alcoholic Fatty Liver Disease; Obesity; Insulin Resistance
PubMed: 38896430
DOI: 10.1097/OGX.0000000000001272 -
Frontiers in Public Health 2024Habitual substance use, i. e., alcohol, tobacco and betel nut, has been found with an increased risk of metabolic syndrome (MetS) in the general population, whereas the...
BACKGROUNDS
Habitual substance use, i. e., alcohol, tobacco and betel nut, has been found with an increased risk of metabolic syndrome (MetS) in the general population, whereas the association remains unclear in physically fit military personnel. This study aimed to investigate the combination of these substances use and their associations with new-onset MetS in the military.
METHODS
A total of 2,890 military men and women, aged 18-39 years, without MetS were obtained from the cardiorespiratory fitness and health in eastern armed forces study (CHIEF) in Taiwan and followed for incident MetS from baseline (2014) through the end of 2020. Incident MetS event was defined by the International Diabetes Federation guideline and confirmed in the annual health examinations. A self-report was used to assess the alcohol, tobacco and betel nut use status (active vs. former/never). Multivariable Cox regression model was performed to determine the association with adjustments for sex, age, body mass index and physical activity at baseline.
RESULTS
At baseline, there were 279 active betel nut chewers (9.7%), 991 active smokers (34.3%) and 1,159 active alcohol consumers (40.1%). During a mean follow-up of 6.0 years, 673 incident MetS (23.3%) were observed. As compared to no substance users, only one substance, and two and three substances users had a greater risk of incident MetS [hazard ratios (HRs) and 95% confidence intervals: 1.27 (1.06-1.54), 1.38 (1.12-1.69) and 1.78 (1.37-2.32), respectively]. In subgroup analyses, the risk of incident MetS in two and three substances users was significantly greater in those free of baseline low high-density lipoprotein [HRs: 1.54 (1.21-1.95) and 2.57 (1.92-3.46), respectively], as compared to their counterparts (both p for interactions <0.05).
CONCLUSION
A dose-response association of more substances use for new-onset MetS was noted in military personnel. This finding suggests that the combined alcohol, tobacco and betel nut use may play a role in the development of MetS. Further study is required to establish causation and to investigate the potential benefits of substance use cessation in reducing the risk of MetS.
Topics: Humans; Male; Female; Adult; Military Personnel; Metabolic Syndrome; Taiwan; Incidence; Young Adult; Adolescent; Alcohol Drinking; Substance-Related Disorders; Risk Factors; Areca; Cohort Studies
PubMed: 38894993
DOI: 10.3389/fpubh.2024.1406524 -
Nutrients May 2024During the last decades, endocrine-disrupting chemicals (EDCs) have attracted the attention of the scientific community, as a result of a deepened understanding of their... (Review)
Review
During the last decades, endocrine-disrupting chemicals (EDCs) have attracted the attention of the scientific community, as a result of a deepened understanding of their effects on human health. These compounds, which can reach populations through the food chain and a number of daily life products, are known to modify the activity of the endocrine system. Regarding vulnerable groups like pregnant mothers, the potential damage they can cause increases their importance, since it is the health of two lives that is at risk. EDCs can affect the gestation process, altering fetal development, and eventually inducing the appearance of many disorders in their childhood and/or adulthood. Because of this, several of these substances have been studied to clarify the influence of their prenatal exposure on the cognitive and psychomotor development of the newborn, together with the appearance of non-communicable diseases and other disorders. The most novel research on the subject has been gathered in this narrative review, with the aim of clarifying the current knowledge on the subject. EDCs have shown, through different studies involving both animal and human investigation, a detrimental effect on the development of children exposed to the during pregnancy, sometimes with sex-specific outcomes. However, some other studies have failed to find these associations, which highlights the need for deeper and more rigorous research, that will provide an even more solid foundation for the establishment of policies against the extended use of these chemicals.
Topics: Humans; Endocrine Disruptors; Pregnancy; Prenatal Exposure Delayed Effects; Female; Animals; Child Development; Male; Maternal Exposure; Fetal Development; Infant, Newborn
PubMed: 38892490
DOI: 10.3390/nu16111556 -
International Journal of Molecular... May 2024Fetal alcohol spectrum disorders (FASDs) are leading causes of neurodevelopmental disability but cannot be diagnosed early in utero. Because several microRNAs (miRNAs)...
Fetal alcohol spectrum disorders (FASDs) are leading causes of neurodevelopmental disability but cannot be diagnosed early in utero. Because several microRNAs (miRNAs) are implicated in other neurological and neurodevelopmental disorders, the effects of EtOH exposure on the expression of these miRNAs and their target genes and pathways were assessed. In women who drank alcohol (EtOH) during pregnancy and non-drinking controls, matched individually for fetal sex and gestational age, the levels of miRNAs in fetal brain-derived exosomes (FB-Es) isolated from the mothers' serum correlated well with the contents of the corresponding fetal brain tissues obtained after voluntary pregnancy termination. In six EtOH-exposed cases and six matched controls, the levels of fetal brain and maternal serum miRNAs were quantified on the array by qRT-PCR. In FB-Es from 10 EtOH-exposed cases and 10 controls, selected miRNAs were quantified by ddPCR. Protein levels were quantified by ELISA. There were significant EtOH-associated reductions in the expression of several miRNAs, including miR-9 and its downstream neuronal targets BDNF, REST, Synapsin, and Sonic hedgehog. In 20 paired cases, reductions in FB-E miR-9 levels correlated strongly with reductions in fetal eye diameter, a prominent feature of FASDs. Thus, FB-E miR-9 levels might serve as a biomarker to predict FASDs in at-risk fetuses.
Topics: Humans; Fetal Alcohol Spectrum Disorders; Female; Exosomes; Pregnancy; Biomarkers; MicroRNAs; Brain; Adult; Fetus; Case-Control Studies; Ethanol; Male
PubMed: 38892014
DOI: 10.3390/ijms25115826