Kristensenholder3364

The generation of mature, functional, thyroid follicular cells from pluripotent stem cells would potentially provide a therapeutic benefit for patients with hypothyroidism, but in vitro differentiation remains difficult. We earlier reported the in vivo generation of lung organs via blastocyst complementation in fibroblast growth factor 10 (Fgf10), compound, heterozygous mutant (Fgf10 Ex1mut/Ex3mut) mice. Fgf10 also plays an essential role in thyroid development and branching morphogenesis, but any role thereof in thyroid organogenesis remains unclear. Here, we report that the thyroids of Fgf10 Ex1mut/Ex3mut mice exhibit severe hypoplasia, and we generate thyroid tissues from mouse embryonic stem cells (ESCs) in Fgf10 Ex1mut/Ex3mut mice via blastocyst complementation. The tissues were morphologically normal and physiologically functional. The thyroid follicular cells of Fgf10 Ex1mut/Ex3mut chimeric mice were derived largely from GFP-positive mouse ESCs although the recipient cells were mixed. Thyroid generation in vivo via blastocyst complementation will aid functional thyroid regeneration.The balance of the cell redox state is a key point for the maintenance of cellular homeostasis. Increased reactive oxygen species (ROS) generation leads to oxidative damage of tissues, which is involved in the development of several diseases, including autoimmune diseases. Graves' Orbitopathy (GO) is a disfiguring autoimmune-related condition associated with Graves' Disease (GD). Patients with active, moderate-to-severe GO, are generally treated with high doses intravenous glucocorticoids (ivGCs) and/or orbital radiotherapy. On the contrary, up to recently, local ointments were the treatment most frequently offered to patients with mild GO, because the risks related to ivGCs does not justify the relatively poor benefits expected in mild GO. However, a medical treatment for these patients is heavily wanted, considering that GO can progress into more severe forms and also patients with mild GO complain with an impairment in their quality of life. Thus, based on the role of oxidative stress in the pathogenesis of GO, a therapy with antioxidant agents has been proposed and a number of studies have been performed, both in vitro and in vivo, which is reviewed here.The rising global prevalence of obesity, metabolic syndrome, and type 2 diabetes has driven a sharp increase in non-alcoholic fatty liver disease (NAFLD), characterized by excessive fat accumulation in the liver. Approximately one-sixth of the NAFLD population progresses to non-alcoholic steatohepatitis (NASH) with liver inflammation, hepatocyte injury and cell death, liver fibrosis and cirrhosis. NASH is one of the leading causes of liver transplant, and an increasingly common cause of hepatocellular carcinoma (HCC), underscoring the need for intervention. The complex pathophysiology of NASH, and a predicted prevalence of 3-5% of the adult population worldwide, has prompted drug development programs aimed at multiple targets across all stages of the disease. Currently, there are no approved therapeutics. Liver-related morbidity and mortality are highest in more advanced fibrotic NASH, which has led to an early focus on anti-fibrotic approaches to prevent progression to cirrhosis and HCC. Due to limited clinical efficacy, anti-fibrotic approaches have been superseded by mechanisms that target the underlying driver of NASH pathogenesis, namely steatosis, which drives hepatocyte injury and downstream inflammation and fibrosis. Among this wave of therapeutic mechanisms targeting the underlying pathogenesis of NASH, the hormone fibroblast growth factor 21 (FGF21) holds considerable promise; it decreases liver fat and hepatocyte injury while suppressing inflammation and fibrosis across multiple preclinical studies. In this review, we summarize preclinical and clinical data from studies with FGF21 and FGF21 analogs, in the context of the pathophysiology of NASH and underlying metabolic diseases.

Turner syndrome (TS) is characterized by complete or partial loss of one sex chromosome and is commonly associated with short stature, metabolic changes (such as central obesity, abnormal glucose tolerance and high triglycerides) and premature ovarian insufficiency (POI). Primary management of TS during childhood and adolescence comprises treatment with human growth hormone (hGH) and, in cases with early loss of ovarian function, hormone replacement therapy (HRT). Given that metabolic parameters are altered when HRT is applied during menopause, we analyzed whether metabolic changes might be positively or negatively affected within 10 years after HRT and/or hGH in girls with TS.

Observational study.

Data were collected from the medical records of 31 girls with TS attending two endocrinologic centers in Germany between 2000 and 2020. Descriptive statistics are reported as the mean ± SEM or percentages.

The mean age at first presentation was 99.06 ± 8.07 months, the mean height was 115.8 ± 3.94 cm, and tfects, and could guide treatment adjustment and duration.

Treatment with hGH and HRT is provided to most girls with TS. Metabolic effects are associated with both modalities. Monitoring of metabolic changes appears to be important to detect unfavorable effects, and could guide treatment adjustment and duration.

The prevalence of MS among children and adolescents continues to rise, which has become an escalating serious health issue worldwide. It had been reported that maternal current lifestyle had a strong independent correlation with offspring health. However, it is not clear whether comprehensive lifestyle of mother has an impact on the MS risk in offspring and the role of offspring's lifestyle in it.

We included 4,837 mother-child pairs from a multi-centered cross-sectional study conducted in China. The information of maternal lifestyle was obtained by self-reported questionnaire, and metabolic syndrome (MS) in offspring was determined by anthropometric measurements and blood tests. Logistic regression models were employed to evaluate the association between maternal lifestyle and risk of MS in offspring. We found maternal healthy lifestyle was independently associated with lower risk of offspring MS, and the risk of MS in offspring decreased with the increased number of maternal ideal lifestyle factors. Although adolescents' lifestyle did not fully explain the relationship between maternal lifestyle and risk of offspring MS, compared with those had less ideal lifestyle factors in both mothers and offspring, the risk of offspring MS was lower in those had more ideal lifestyle factors in both mothers and adolescents.

Healthy lifestyle in mothers was associated with a lower risk of MS in offspring, which was independent of offspring's lifestyle. These findings support mother-based lifestyle intervention could be an effective strategy to reduce the MS risk in adolescents.

Healthy lifestyle in mothers was associated with a lower risk of MS in offspring, which was independent of offspring's lifestyle. These findings support mother-based lifestyle intervention could be an effective strategy to reduce the MS risk in adolescents.Purpose To assess the efficacy and safety of rituximab treatment as second-line immunotherapy in pediatric cases of anti-NMDA receptor (NMDAR) encephalitis. Methods We retrospectively recruited 8 patients with anti-NMDAR encephalitis who were treated with rituximab as second-line immunotherapy. We evaluated the clinical features, laboratory examination results and treatment protocols of the Chinese children and defined good outcomes based on the modified Rankin scale (mRS) score (0-2) at the last follow-up. Results A total of eight pediatric patients (median age 6.7 years; four female) with refractory anti-NMDAR encephalitis were recruited to the study. Rituximab was given after a median duration of disease of 57 days (range 50.5-113.75 days). The use of rituximab led to a significant reduction in the mRS and CD19+ B-cells compared to before rituximab infusion (P less then 0.05). Five patients (62.5%) had a good outcome (mRS ≤ 2) including four patients (50%) who showed complete recovery (mRS = 0) at the last follow-up. Transient infusion adverse events were recorded in 2 patients (25%). Two patients (25%) had severe infectious adverse events (AEs) and two patients with grade 5 (death). None of the patients developed progressive multifocal leukoencephalopathy (PML). Conclusion Our study provides evidence that rituximab can efficiently improve the clinical symptoms of anti-NMDAR encephalitis in children. However, due to the risk of adverse infections, rituximab should be restricted in pediatric patients with high rates of mortality and disability.Although carotid artery intraplaque hemorrhage (IPH) is a known risk-factor for cerebral ischemic events in patients of advanced age, its prevalence in younger cohorts is less certain. The purpose of this study was to assess the prevalence of carotid artery IPH across the age spectrum. A retrospective review was completed of all adult patients from our institution who underwent neck MRA with high-resolution carotid plaque imaging between 2017 and 2020. The mean ages of patients with and without IPH were calculated. The prevalence of IPH was compared between patients that were categorized into age groups. Patients with and without a cerebral ischemic event (e.g., stroke, retinal ischemia) were included. Unilateral anterior circulation ischemic events in patients without atrial fibrillation were presumed to be likely related to ipsilateral carotid artery disease. Multiple regression analysis was performed to determine independent associations with IPH. 634 patients were included (1,268 carotid arteries). Increasing age (OR 1.04; 95% CI 1.02-1.06; P = 0.001) was independently associated with IPH. 211 patients had unilateral anterior circulation ischemic events. The mean age of patients with carotid IPH was 71.4 years (SD = 9.9), compared to 62.8 years (SD = 15.8) of those without (P ≤ 0.0001). The prevalence of IPH increased with age in all patients (P = 0.0002). Among patients with ipsilateral anterior circulation ischemic events, each age category above 50 years had a significantly higher prevalence of IPH when compared to patients 18-50 years (P ≤ 0.05 for all comparisons). The prevalence of carotid IPH increases with age and is rare in patients under 50 years. The approximate threshold age for IPH development is likely around 50 years.Background and Objectives Distal hereditary motor neuropathy (dHMN) is a clinically and genetically heterogeneous group of inherited neuropathies. The objectives of this study were to report the clinical and genetic features of dHMN patients in a Chinese cohort. Aims and Methods We performed clinical assessments and whole-exome sequencing in 24 dHMN families from Mainland China. We conducted a retrospective analysis of the data and investigated the frequency and clinical features of patients with a confirmed mutation. Results Two novel heterozygous mutations in GARS, c.373G>C (p.E125Q) and c.1015G>A (p.G339R), were identified and corresponded to the typical dHMN-V phenotype. Together with families with WARS, SORD, SIGMAR1, and HSPB1 mutations, 29.2% of families (7/24) acquired a definite genetic diagnosis. One novel heterozygous variant of uncertain significance, c.1834G>A (p.G612S) in LRSAM1, was identified in a patient with mild dHMN phenotype. Conclusion Our study expanded the mutation spectrum of GARS mutations and added evidence that GARS mutations are associated with both axonal Charcot-Marie-Tooth and dHMN phenotypes.