Evaluation of Choroidal Structures in Children with Newly Diagnosed Type-1 Diabetes Mellitus.

Objectives: The objective of this study was to evaluate the subfoveal choroidal thickness (SFCT) and choroidal vascularity index (CVI) in children with newly diagnosed type 1 diabetes mellitus (T1DM). Methods: A total of 80 children (40 with T1DM and 40 healthy controls) were included in this cross-sectional study. Enhanced depth imaging optical coherence tomography (EDI-OCT) images of all participants were analyzed. The SFCT, total choroidal area (TCA), luminal area (LA), stromal area (SA), and CVI measurements were obtained from EDI-OCT images and compared between groups. The effects of HbA1c, fasting plasma glucose, and axial length measurements on choroidal measurements were investigated. Results: There was no significant difference between the groups according to TCA (0.84 [0.57-1.26] vs. 0.88 [0.65-1.16] mm2, p=0.745), LA (0.55 [0.41-0.79] vs. 0.59 [0.43-0.74] mm2, p=0.745), SA (0.27 [0.15-0.47] vs. 0.28 [0.15-0.47] mm2, p=0.935), and CVI (68.03 [66.5-70.5] vs. 67.75 [66.2-69.5] %, p=0.794), respectively. However, T1DM patients had thinner SFCT compared to control subjects (309.0 [327-489] and 398.5 [219-491], p<0.044). No correlation was found between HbA1c, fasting plasma glucose, axial length measurements, and SFCT, TCA, LA, SA, or CVI. Conclusion: Children with newly diagnosed T1DM have thinner SCFT in comparison to healthy children, however, no significant difference in CVI was observed between the groups. Long-term follow-up should be used to confirm the impact of the DM duration on CVI.

Effect of Everolimus on Prognosis of Neurofibromatosis Type 1 Lesions: A Systematic Review and Meta Analysis.

PURPOSE: This study addresses the effectiveness of oral everolimus in treating various malignancies associated with Neurofibromatosis Type 1 (NF1). The purpose is to determine whether everolimus reduces lesion size in NF1 patients, considering the controversial findings from previous clinical trials. The scientific hypotheses and questions involve evaluating the impact of everolimus on NF1-associated lesions and understanding the variability in treatment outcomes. METHODS: A systematic review and meta-analysis were conducted following PRISMA and Cochrane Collaboration guidelines. The study included four-phase II, single-arm, nonrandomized trials investigating the effect of oral everolimus on NF1-associated lesion size. The search covered multiple databases, and data extraction involved evaluating studies for inclusion criteria and assessing quality using the Cochrane Collaboration's Risk of Bias in Nonrandomized Studies tool. Statistical analysis utilized Open Meta(Analyst). FINDINGS: The search yielded 388 studies, with 10 selected for full-text review and four included in the final analysis. The quality of the studies ranged from low to moderate. The meta-analysis indicated no observed heterogeneity (I^2 = 0%), and the overall estimate suggested no significant reduction in NF1-associated lesion size with everolimus (P = 0.069). IMPLICATIONS: The findings reveal a varied and inconsistent picture of everolimus efficacy in NF1 treatment. The study highlights the need for personalized approaches, considering individual genetic and clinical differences. The limitations, including small sample sizes and nonrandomized trials, call for larger, more standardized research efforts. The study emphasizes ongoing trials and the importance of future research in understanding predictors of everolimus response and optimizing treatment strategies for NF1 patients. CONCLUSION: While everolimus shows promise in reducing lesion size in a subset of NF1 patients, the study cannot draw conclusive results due to limitations in the included studies. Ongoing, adequately powered trials are crucial for advancing the evidence base and informing the potential role of everolimus in NF1 treatment. OTHERS: There was no funding for this review and no conflicts of interest.

Clinical Features and HLA Genetics Differ in Children at Type 1 Diabetes Onset by Hispanic Ethnicity.

CONTEXT: Type 1 diabetes incidence continues to increase in children, especially among Hispanic Whites (HW). OBJECTIVE: We investigated the clinical, immunologic, and genetic characteristics of HW and Non-Hispanic White (NHW) children that presented at type 1 diabetes diagnosis. METHODS: In this single-center, observational study, children who were diagnosed with type 1 diabetes (<20 years old) and tested for islet autoantibodies within 1 year of diagnosis were included in the study and divided into two groups by Hispanic ethnicity. RESULTS: Of 1297 children, 398 HW children presented with a younger age at diabetes onset (10.2 ± 3.9 vs. 11.1 ± 4.1 years, p<0.001) and more diabetic ketoacidosis (62.4% vs. 51.9%, p<0.001) compared to NHW children (n=899). There was no difference in sex, A1c levels, or the number and prevalence of islet autoantibodies between the two cohorts. A subset of our cohort was HLA typed as specific alleles confer strong genetic risk for type 1 diabetes (e.g., HLA-DR4 and DQ8). Among 637 HLA-typed children, HW children had a significantly higher prevalence of the DR4-DQ8 haplotype compared to NHW children (79.1% vs. 60.1%, p<0.001), and this frequency was much higher than a reference Hispanic population (OR = 6.5, 95% CI 4.6-9.3). CONCLUSIONS: Hispanic White children developing type 1 diabetes have a high prevalence of HLA DR4-DQ8, which can be utilized to select individuals for immune monitoring with islet autoantibodies to lessen diabetic ketoacidosis and potentially prevent diabetes onset.

Twelve-month results from a randomized controlled trial comparing differential target multiplexed spinal cord stimulation and conventional spinal cord stimulation in subjects with chronic refractory axial low back pain not eligible for spine surgery.

Background: Successful treatments for intractable chronic low back pain (CLBP) in patients who are not eligible for surgical interventions are scarce. The superior efficacy of differential target multiplexed spinal cord stimulation (DTM SCS) to conventional SCS (Conv-SCS) on the treatment of CLBP in patients with persistent spinal pain syndrome (PSPS) who have failed surgical interventions (PSPS-T2) motivated the evaluation of DTM SCS versus Conv-SCS on PSPS patients who are non-surgical candidates (PSPS-T1). Methods: This is a prospective, open label, crossover, post-market randomized controlled trial in 20 centers across the United States. Eligible patients were randomized to either DTM SCS or Conv-SCS in a 1:1 ratio. Primary endpoint was CLBP responder rate (percentage of subjects with ≥50% CLBP relief) at 3-month in randomized subjects who completed trialing (modified intention-to-treat population). Patients were followed up to 12 months. Secondary endpoints included change of CLBP and leg pain, responder rates, changes in disability, quality of life, patient satisfaction and global impression of change, and safety profile. An optional crossover was available at 6-month to all patients. Results: About 121 PSPS-T1 subjects with CLBP and leg pain mostly associated with degenerative disc disease and radiculopathy and who were not eligible for spine surgery were randomized. CLBP responder rate with DTM SCS (93.5%) was superior to Conv-SCS (36.4%) at the primary endpoint. Superior CLBP responder rates (88.1%-90.5%) were obtained with DTM SCS at all other timepoints. Mean CLBP reduction with DTM SCS (6.52 cm) was superior to that with Conv-SCS (3.01 cm) at the primary endpoint. Similar CLBP reductions (6.23-6.43 cm) were obtained with DTM SCS at other timepoints. DTM SCS provided significantly better leg pain reduction and responder rate, improvement of disability and quality of life, and better patient satisfaction and global impression of change. 90.9% of Conv-SCS subjects who crossed over were CLBP responders at completion of the study. Similar safety profiles were observed between the two groups. Conclusion: DTM SCS for chronic CLBP in nonsurgical candidates is superior to Conv-SCS. Improvements were sustained and provided significant benefits on the management of these patients.

Predictors of stigma perception by people with type 1 diabetes: A cross-sectional analysis of the BETTER registry.

AIMS: This study investigates stigma predictors across ages and genders, addressing a critical gap in understanding diverse populations to reduce related suboptimal clinical and psychosocial outcomes. METHODS: Cross-sectional analysis of self-reported data from BETTER, a Canadian registry of people with type 1 diabetes. Participants (n = 709) completed the 19-item-Diabetes-Stigma Assessment-Scale (DSAS-1) categorized into treated differently, blame and judgment, and identity concerns sub-scales. Associations with diabetes distress (DDS-17-score/102), depression (PHQ-9-score/27), social-support (ESSI-score/34), fear of hypoglycemia (HFS-II-score/132), and hyperglycemia-avoidance-behaviours (HAS-score/88) were computed. RESULTS: Perceived stigma was highest in youth aged 14-24 years (46·0 ± 15·6, p < 0·001) and women (41·2 ± 15·7, p = 0·009), compared to other age groups and men. Blame and Judgment contributed to most of stigma perception. Youth perceived significantly more blame and judgment (p < 0·001) and identity concerns (p = 0·001) compared to middle-aged adults and seniors. Women perceive significantly more blame and judgment compared to men (p < 0·001). The perception of being treated differently was not reported to be an issue across ages and genders. Participants with higher scores of depression, diabetes-distress, fear of hypoglycemia, hyperglycemia-avoidance behaviours, and lesser social-support, reported increased stigma. CONCLUSIONS: Stigma varies by age and gender, underscoring the need for targeted interventions to reduce it. Challenging stereotypes and reducing stigma-related stressors are essential for better outcomes.

Women's and Partners' Experiences with a Closed-Loop Insulin Delivery System to Manage Type 1 Diabetes in the Postpartum Period.

BACKGROUND: Closed-loop insulin delivery has the potential to offer women with type 1 diabetes a break from intense diabetes self-care efforts during postpartum. AIMS: To explore the views and opinions of hybrid closed-loop users and their partners in the first 24 weeks postpartum. METHODS: This qualitative study was embedded in a controlled study of women with type 1 diabetes randomized to (MiniMed™ 670G/770G) closed-loop insulin delivery or sensor augmented pump use 1-11 weeks 6 days postpartum, with all on closed-loop from 12 to 24 weeks postpartum. Semi-structured interviews were conducted with 16 study participants and their partners at 12 and 24 weeks postpartum. Thematic analyses were used to examine participants' and partners' experiences. RESULTS: Participants' positive perceptions of the closed-loop use related to reduced hypoglycemia, in contrast to previous experiences with nonautomated insulin delivery. These were balanced against frustrations with the system allowing blood glucose levels to be above what they desired. Closed-loop use did not influence infant feeding choice. Yet, infant feeding and care impacted participants' diabetes management. Partners expressed uncertainty about the closed-loop taking away control from participants who were highly skilled with diabetes self-management. CONCLUSIONS: Participants reported that the closed-loop resulted in less time spent in hypoglycemia; compared to previously used nonautomated insulin delivery. Yet, participants desired greater understanding into the workings of the closed-loop algorithm. This study provides potential users with realistic expectations about the user experience with the MiniMed™ 670G/770G closed-loop in the postpartum period.

Association between partial remission phase in type 1 diabetes and vitamin D receptor Fok1 rs2228570 polymorphism.

OBJECTIVES: The aim of the current study was to assess the natural course of partial remission (PR) phase of type 1 diabetes (T1D) and to highlight the putative association between vitamin D receptor (VDR) (Fok1) gene polymorphism and PR phase. METHODS: Ninety participants with newly diagnosed T1D were followed up for a total of 12 months. The VDR (Fok1) rs2228570 gene polymorphism was genotyped using allelic discrimination (AD) assay. RESULTS: Fifty-four patients (60 %) reached PR with an average duration of 5.63 ± 2.9 months. Among remitters, the frequency of CC "FF" genotype and allelic frequency of C "F" were significantly higher (p<0.001). Furthermore, participants expressing "CC" genotype had earlier onset of PR and spent a significantly longer duration in remission (p<0.001). Younger age (p<0.001; OR 41.6; CI 12.12-142.99), absence of DKA (p<0.001; OR 16, CI 4.36-50.74), higher C-peptide levels (p<0.001; OR 19.55; CI 6.52-58.63), and presence of CC "FF" genotype of VDR (p<0.001; OR 6.74; CI 2.41-18.86) best predicted the overall occurrence of PR. CONCLUSIONS: Younger age, less extent of metabolic derangements, and expression of a CC "FF" genotype were found to influence the occurrence of PR. Data from the current study showed that the "C" allele could have a protective role on preserving residual ß-cell mass and could predict both onset and duration of PR among newly diagnosed T1D. These findings support the growing concept of future tailored precision medicine.

Comparison of patients with familial chylomicronemia syndrome and multifactorial chylomicronemia syndrome.

CONTEXT: Patients with rare familial chylomicronemia syndrome (FCS) and relatively common multifactorial chylomicronemia syndrome (MCS) both express severe hypertriglyceridemia, defined as plasma triglyceride concentration ≥10 mmol/L (≥885 mg/dL). Clinically there can be confusion between the two conditions. OBJECTIVE: To compare clinical and biochemical phenotypes in patients with genotypically characterized FCS and MCS. METHODS: We performed targeted sequencing of DNA from 193 patients with severe hypertriglyceridemia, classified them as having either FCS or MCS and compared clinical and biochemical characteristics. RESULTS: FCS compared to MCS patients were significantly younger (31.4 ± 16.7 vs. 51.0 ± 11.3 years; P =0.003), with earlier age at symptom onset (15.0 ± 15.8 vs. 37.8 ± 8.8 years; P =0.00066), lower body mass index (23.3 ± 3.1 vs. 30.7 ± 5.0 kg/m2; P =0.000016), and higher prevalence of pancreatitis events (81.8% vs. 35.2%; P=0.003). Furthermore, FCS compared to MCS patients had a higher ratio of triglyceride to total cholesterol, i.e. 4.18 ± 0.92 vs 1.08 ± 0.51 (P <0.0001) and lower plasma apolipoprotein B, i.e. 0.56 ± 0.15 vs 1.02 ± 0.43 g/L (P <0.0001). MCS patients with heterozygous pathogenic variants had a relatively more severe clinical presentation than other MCS genetic subgroups. CONCLUSIONS: FCS patients have notable phenotypic differences from MCS patients, although there is overlap. While genetic analysis of patients with persistent severe hypertriglyceridemia can definitively diagnose FCS, 8.2% of MCS patients with sustained refractory hypertriglyceridemia behave functionally as if they have FCS, which should influence their eligibility for novel therapies for severe hypertriglyceridemia.

Charting a path to health: The empowering influence of self-efficacy for the self-management of type 1 diabetes in children and adolescents.

Type 1 diabetes (T1D) in children and adolescents requires a lifelong commitment to disease control, which involves insulin treatment and constant blood glucose monitoring. Framed by Albert Bandura's self-efficacy theory, we focused on analysing the impact of domain-specific self-efficacy for T1D control in children and adolescents and its relationship with different indicators of glycaemic control over time. The study included 205 participants (56.1% male), including 51.7% children and 48.3% adolescents aged 6-18 (M = 13.27, SD = 3.66) years in four longitudinal phases (6 months between phases). The results revealed that higher self-efficacy predicted better health outcomes, with more time spent actively monitoring glucose and more time in the target range. The positive effect of self-efficacy was observed to be maintained over time. This study underscores the importance of taking into account the developmental timing in the onset of T1D. There was a significant relationship between self-efficacy and glucose indicators in adolescents. Although their glucose indicators were worse, self-efficacy became more relevant as they moved from parental management to the self-management of T1D. Implications of the results show the positive effect of self-efficacy on health per glucose indicators, thus suggesting interventions that promote self-efficacy in this population.

Angiotensin II type-1 receptor autoantibody positively correlates with the rate of metaphase I oocytes in infertility with ovulatory disorder.

The renin-angiotensin system (RAS) plays an important role in reproductive function. Our previous study identified that angiotensin II type-1 receptor autoantibody (AT1-AA), an autoantibody that activates RAS, was closely associated with infertility. However, its distribution in different types of infertility remained unclear. This study was designed to explore the distribution of AT1-AA in infertile patients and the connections between AT1-AA and oocyte development and pregnancy outcome. A total of 184 infertile women participated, with samples collected from peripheral venous blood. ELISA was used to detect AT1-AA levels in their sera. It was observed that the proportion of ovulation-disorder factors in AT1-AA-positive group was significantly higher than that in negative group (P=0.001). In 59 infertile women with ovulatory disorders, compared with negative group, AT1-AA-positive group had lower rate of retrieval (P=0.032) and metaphase II (MII) oocytes (P=0.011) but higher proportion of metaphase I (MI) oocytes (P=0.019). A negative correlation was found between the levels of AT1-AA and rate of retrieval and MII oocytes (P=0.027; P=0.043), whereas a positive correlation was observed with the proportion of MI oocytes (P=0.002). Moreover, a specific predictive value for proportion of reaching MII and MI oocytes was exhibited by AT1-AA (P < 0.01; P < 0.05). But no significant difference in embryonic parameters or pregnancy outcomes between two groups was observed (P > 0.05). This study revealed that serum AT1-AA levels were significantly increased in infertile women with ovulatory disorders and positively correlated with proportion of MI oocytes, but not associated with outcomes of assisted reproduction.

A capsule-based scaffold incorporating decellularized extracellular matrix and curcumin for islet beta cell therapy in type 1 diabetes mellitus.

The transplantation of islet beta cells offers an alternative to heterotopic islet transplantation for treating type 1 diabetes mellitus (T1DM). However, the use of systemic immunosuppressive drugs in islet transplantation poses significant risks to the body. To address this issue, we constructed an encapsulated hybrid scaffold loaded with islet beta cells. This article focuses on the preparation of the encapsulated structure using 3D printing, which incorporates porcine pancreas decellularized extracellular matrix (dECM) to the core scaffold. The improved decellularization method successfully preserved a substantial proportion of protein (such as Collagen I and Laminins) architecture and glycosaminoglycans in the dECM hydrogel, while effectively removing most of the DNA. The inclusion of dECM enhanced the physical and chemical properties of the scaffold, resulting in a porosity of 83.62±1.09% and a tensile stress of 1.85±0.16 MPa. In teams of biological activity, dECM demonstrated enhanced proliferation, differentiation, and expression of transcription factors such as Ki67, PDX1, and NKX6.1, leading to improved insulin secretion function in MIN-6 pancreatic beta cells. In the glucose-stimulated insulin secretion (GSIS) experiment on day 21, the maximum insulin secretion from the encapsulated structure reached 1.96±0.08 mIU/mL, representing a 44% increase compared to the control group. Furthermore, conventional capsule scaffolds leaverage the compatibility of natural biomaterials with macrophages to mitigate immune rejection. Here, incorporating curcumin into the capsule scaffold significantly reduced the secretion of pro-inflammatory cytokine (IL-1ß, IL-6, TNF-α, IFN-γ) secretion by RAW264.7 macrophages and T cells in T1DM mice. This approach protected pancreatic islet cells against immune cell infiltration mediated by inflammatory factors and prevented insulitis. Overall, the encapsulated scaffold developed in this study shows promise as a natural platform for clinical treatment of T1DM.

Connections matter: Exploring the relationship between belonging and psychosocial well-being in type 1 diabetes in Iran.

AIM: Identify the relationship between a sense of belonging and psychosocial well-being in individuals with type 1 diabetes (T1D) in Iran. BACKGROUND: Understanding this relationship is vital for tailored nursing interventions to enhance individual's sense of belonging and improve diabetes outcomes. METHODS: This cross-sectional study included 205 participants selected via multi-stage cluster and simple random sampling from health centers in Iranian. Electronic surveys designed on Google Forms, using valid and reliable scales and compliant with HIPAA, assessed sense of belonging, distress, and burnout. Data were analyzed using SPSS (version 25). RESULTS: Participants reported high sense of belonging with varying levels of diabetes distress and burnout. Multiple regression analysis of 205 participants showed that sense of belonging index (SOBI) scores significantly predicted diabetes distress (F(2,203) = 39.71, p < 0.001) and burnout (F(2, 203) = 42.319, p < 0.001). Sense of Belonging Instrument-Psychological (SOBI-P) scores were negatively correlated with both distress (r = -0.52, p < 0.001) and burnout (r = -0.53, p < 0.001), indicating higher belonging is linked to lower distress and burnout. Sense of Belonging Instrument-Antecedents (SOBI-A) scores had positive but non-significant correlations (distress: r = 0.07, p = 0.27; burnout: r = 0.10, p = 0.13). SOBI-P accounted for ∼30 % of the variance in distress (R2 = 0.275) and burnout (R2 = 0.288), with significant contributions to both models (t = -8.8, p < 0.001; t = -9.02, p < 0.001). Anticipated belonging showed no significant correlations with distress or burnout. CONCLUSION: The negative correlations between personal belonging, self-reported distress, and burnout suggest that enhancing the psychological sense of belonging may be an effective strategy to mitigate diabetes-related distress and burnout Stigmatization and financial strain in Iran may exacerbate emotional burden, regimen related distress, and burnout. The lack of association between anticipated belonging and psychosocial well-being underscores differences in present and future perceptions of support, emphasizing the need for culturally sensitive nursing interventions.

26th Meryon Lecture St Anne's College, Oxford, 5th July 2024: FSHD: The long road to DUX4.

This Meryon lecture aims to document the history of the discovery of the gene for Facioscapulohumeral Disease.

Familial renal glycosuria identified in an Indian family.

Glycosuria can be isolated or it can be associated with other tubulopathies like proximal renal tubular acidosis, Fanconi syndrome and endocrine conditions like diabetes mellitus. The SLC5A2 gene codes for the SGLT2 transporter, which is responsible for glucose reabsorption in the proximal tubule. Previously reported cases show that mutation in this gene is associated with intellectual disability, seizure disorder and renin and angiotensin system dysfunction. In his early childhood, a male child displayed persistently high urine glucose levels. We ruled out diabetes mellitus and other tubulopathies before diagnosing the child with familial renal glycosuria, with a novel mutation in the SLC5A2 gene, and screened family members for the same condition. Child's father was found to have isolated renal glycosuria and tested positive for mutation in the SLC5A2 gene.

Recalcitrant extensive dermatophytosis in twin brothers with APECED syndrome.

Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent infections with Candida spp., often linked to primary immunodeficiencies. We report a case of two 8-year-old monozygotic twin brothers presenting with extensive dermatophytosis, later diagnosed with autoimmune polyendocrinopathy, candidiasis, and ectodermal dystrophy (APECED) syndrome due to a homozygous p.M1V mutation in the AIRE gene. The twins exhibited widespread skin and nail infection, along with malabsorption, dental caries, and other autoimmune manifestations. This case highlights the novel presentation of extensive dermatophytosis in APECED, underscoring the variability in clinical expression even within a single family.

Low-carbohydrate diet in children and young people with type 1 diabetes: A randomized controlled trial with cross-over design.

AIMS: We investigated whether a short period of tightly controlled low-carbohydrate diet (LCD) leads to higher time in range without increasing the associated risks in children and young people with diabetes (CYPwD). METHODS: Thirty-five (CYPwD) were recruited into this randomized controlled cross-over study (20 female; 20 CSII; age 14.5 ± 2.9 years; HbA1c 48.9 ± 9.4 mmol/mol). The interventions were five and five weeks of ready-made food box deliveries of isocaloric diets in random order: either LCD (94.5 ± 4.7 g/day) or recommended carbohydrate diet (RCD) (191 ± 19.2 g/day). The outcomes were continuous glucose monitoring parameters, anthropometric, laboratory and quality of life (QoL) data. RESULTS: Time in range was significantly higher in the LCD than in the RCD period (77.1 % vs. 73.8 %, P=0.008). Times in hyperglycemia and average glycaemia were significantly lower in the LCD. There was no difference between the diets in time in hypoglycemia or glycemic variability. The subjects' body weight and BMI were significantly lower during the LCD. There was no significant difference in the LDL-cholesterol levels. No significant differences were observed in the self-assessed QoL. CONCLUSIONS: Short-term LCD led to an improvement of glycemic parameters without increasing time in hypoglycemia, disturbing the lipid profile or negatively affecting the quality of life of CYPwD.

Two cases of type 1 jejunoileal atresia with multiple webs: A case report.

INTRODUCTION AND IMPORTANCE: Type 1 jejunoileal atresia with multiple webs is a rare congenital condition that poses significant surgical challenges in neonates. Understanding the unique presentation and management strategies in such cases is crucial for improving patient outcomes. CASE PRESENTATION: We report two cases involving full-term neonates presenting with severe abdominal distension and bilious vomiting. Radiologic studies confirmed intestinal obstruction due to multiple jejunoileal webs. The first case was managed with jejunoileal resection and anastomosis, while the second case underwent web excision with jejunoileoplasty. Despite successful surgeries, both patients faced significant postoperative complications, leading to fatal outcomes. CLINICAL DISCUSSION: These cases illustrate the complexity of managing type 1 jejunoileal atresia with multiple webs, emphasizing the importance of early diagnosis, meticulous surgical intervention, and comprehensive postoperative care. The condition, while rare, requires a tailored approach to optimize surgical outcomes and patient survival. CONCLUSION: The cases highlight the critical need for standardized treatment protocols and vigilant postoperative monitoring in managing neonatal intestinal obstructions, particularly in rare conditions such as type 1 jejunoileal atresia with multiple webs. This report contributes to the surgical literature by providing insights into the challenges and potential strategies for managing such complex cases.

Knowledge of and attitude toward diabetes care as predictors of school nurses' partnership with parents: A cross-sectional study.

BACKGROUND: Collaboration between parents and school nurses is important for effective healthcare in schools. This study focuses on the competency of school nurses, which encompasses their knowledge and self-efficacy in diabetes care, and investigates how these factors, along with workload, influence healthcare partnerships in schools. However, it is unknown whether school nurses' knowledge and self-efficacy about diabetes care, as well as their workload, affect school healthcare partnerships concerning children with type 1 diabetes. AIM: This study aimed to investigate the impact of school nurses' self-efficacy, knowledge, attitude, and role overload on healthcare partnerships with parents of children with type 1 diabetes in schools. DESIGN: A cross-sectional, descriptive design. SETTING AND PARTICIPANTS: Between December 2023 and January 2024 in South Korea, 142 elementary- and middle-school nurses participated in this study. METHODS: School healthcare partnership, self-efficacy in diabetes education, knowledge of and attitude toward school healthcare for type 1 diabetes, and the role-overload scale were utilized in the analysis. Data were analyzed using multiple regression. RESULTS: Knowledge of school healthcare (ß = 0.34, p < .001) and attitude toward it (ß = 0.29 p = .001) for type 1 diabetes, as well as the grade level of the current employing school (ß = -0.15, p = .039) were predictors of school healthcare partnerships. These three variables explained 30.3 % of the total variance in school healthcare partnerships (F = 21.44, p < .001). CONCLUSIONS: Knowledge of school healthcare and attitudes toward it for type 1 diabetes were identified as factors in school nurses' school healthcare partnerships. Therefore, interventions to strengthen school nurses' competencies should be developed to improve school healthcare partnerships.

Recent insights into the pathophysiology of narcolepsy type 1.

Narcolepsy type 1 (NT1) is a sleep-wake disorder in which people typically experience excessive daytime sleepiness, cataplexy and other sleep-wake disturbances impairing daily life activities. NT1 symptoms are due to hypocretin deficiency. The cause for the observed hypocretin deficiency remains unclear, even though the most likely hypothesis is that this is due to an auto-immune process. The search for autoantibodies and autoreactive T-cells has not yet produced conclusive evidence for or against the auto-immune hypothesis. Other mechanisms, such as reduced corticotrophin-releasing hormone production in the paraventricular nucleus have recently been suggested. There is no reversive treatment, and the therapeutic approach is symptomatic. Early diagnosis and appropriate NT1 treatment is essential, especially in children to prevent impaired cognitive, emotional and social development. Hypocretin receptor agonists have been designed to replace the attenuated hypocretin signalling. Pre-clinical and clinical trials have shown encouraging initial results. A better understanding of NT1 pathophysiology may contribute to faster diagnosis or treatments, which may cure or prevent it.

Valsartan Rescues Suppressed Mitochondrial Metabolism during Insulin Resistance in C2C12 Myotubes.

Elevated circulating branched-chain amino acids (BCAA) have been linked with the severity of insulin resistance across numerous populations, implicating heightened BCAA metabolism as a potential therapy for insulin resistance. Recently, the angiotensin II type 1 receptor (AT1R) inhibitor Valsartan (VAL) was identified as a potent inhibitor of branched-chain alpha-keto acid dehydrogenase kinase (BCKDK), a negative regulator of BCAA metabolism. This work investigated the effect of VAL on myotube metabolism and insulin sensitivity under both insulin sensitive and insulin resistant conditions. C2C12 myotubes were treated with or without VAL at 8 µM for 24 h, both with and without hyperinsulinemic-induced insulin resistance. Oxygen consumption and extracellular acidification were used to measure mitochondrial and glycolytic metabolism, respectively. Gene expression was assessed via qRT-PCR, and insulin sensitivity was assessed via Western blot. Insulin resistance significantly reduced both basal and peak mitochondrial function which were rescued to control levels by concurrent VAL. Changes in mitochondrial function occurred without substantial changes in mitochondrial content or related gene expression. Insulin sensitivity and glycolytic metabolism were unaffected by VAL, as was lipogenic signaling and lipid content. Additionally, both VAL and insulin resistance depressed Bckdha expression. Interestingly, an interaction effect was observed for extracellular isoleucine, valine, and total BCAA (but not leucine), suggesting VAL may alter BCAA utilization in an insulin sensitivity-dependent manner. Insulin resistance appears to suppress mitochondrial function in a myotube model which can be rescued by VAL. Further research will be required to explore the implications of these findings in more complex models.