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Background: Modest inverse associations have been found between dairy intake, particularly yogurt, and type 2 diabetes risk. Investigating associations of dairy intake with early onset of type 2 diabetes offers opportunities for effective prevention of this condition., Objectives: This study aims to investigate the relationships between the intake of different dairy types, prediabetes risk, and continuous glycemic outcomes., Methods: Systematic literature searches across multiple databases were performed of studies published up to September 2023. Included were prospective cohort studies in healthy adults that examined the association between dairy intake and prediabetes risk according to diagnostic criteria, or continuous glycemic markers. A dose-response random-effects meta-analysis was used to derive incremental relative risks (RRs) for associations of total dairy, fermented dairy, milk, yogurt, cheese (all total, high-fat, and low-fat), cream, and ice cream with prediabetes risk adjusted for sociodemographic, health and cardiometabolic risk factors, and dietary characteristics., Results: The meta-analyses encompassed 6653 prediabetes cases among 95,844 individuals (age range 45.5-65.5 y) including 6 articles describing 9 cohorts. A quadratic inverse association was observed for total dairy intake and prediabetes risk, with the lowest risk at 3.4 servings/d (RR: 0.75; 95% confidence interval: 0.60, 0.93; I 2 = 18%). Similarly, total, and high-fat cheese exhibited nonlinear inverse associations with prediabetes risk, showing the lowest risk at 2.1 servings/d (0.86; 0.78, 0.94; I 2 = 0%, and 0.90; 0.81, 0.99; I 2 = 12%), but a higher risk at intakes exceeding 4 servings/d. Ice cream intake was linearly associated with prediabetes risk (0.85; 0.73, 0.99; I 2 = 0% at the highest median intake of 0.23 servings/d). Other dairy types showed no statistically significant associations. The systematic review on dairy intake and glycemic outcomes showed considerable variabilities in design and results., Conclusions: The findings suggest an inverse association between moderate dairy and cheese intake in preventing prediabetes. The potential for reverse causation and residual confounding highlights the need for studies with comprehensive repeated measurements., Trial Registration Number: PROSPERO 2023 CRD42023431251., (© 2024 The Authors.)

The prevalence of an unhealthy lifestyle among patients with gynecological cancer is high and associated with increased risk of all-cause mortality. Although lifestyle changes have the potential to improve outcomes, lifestyle counseling is not routinely integrated into standard care. This review explores research on the barriers to and facilitators of both the promotion of healthy lifestyles by healthcare providers (HCPs) and healthy lifestyle changes by patients with gynecological cancer. The Theoretical Domains Framework (TDF) was used to deductively code the identified factors for a comprehensive understanding of the barriers and facilitators. A search across five databases yielded a total of 12,687 unique studies, of which 43 were included in the review. Of these 43, 39 included gynecological cancer patients and only 6 included HCPs. Among the barriers identified for HCPs, most studies evaluated barriers regarding weight loss counseling. Limited knowledge, reluctance to address weight loss, skepticism about the benefits, and workload concerns were commonly reported barriers for HCPs. HCPs will benefit from education and training in lifestyle counseling, including effective communication skills like motivational interviewing. Gynecological cancer patients lacked tools, support, knowledge, and faced mental health issues, environmental constraints, and physical limitations. The review emphasizes the importance of addressing these barriers and utilizing identified facilitators, such as social support, to promote and support healthy lifestyle behaviors on the part of patients and their promotion by HCPs. Future research should focus not only on patients but also on supporting HCPs and implementing necessary changes in current practices., Competing Interests: Declaration of competing interest The authors declare that they have no competing interest., (Copyright © 2023. Published by Elsevier B.V.)

Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs. Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel. Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1-25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0-88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%-subcutaneous; 29%-intravenous; 1%-unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy. Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.

Death receptor 5 (DR5) is an apoptosis-inducing member of the tumor necrosis factor receptor superfamily, whose activity has been linked to membrane cholesterol content. Upon ligand binding, DR5 forms large clusters within the plasma membrane that have often been assumed to be manifestations of receptor co-localization in cholesterol-rich membrane domains. However, we have recently shown that DR5 clusters are more than just randomly aggregated receptors. Instead, these are highly structured networks held together by receptor dimers. These dimers are stabilized by specific transmembrane helix-helix interactions, including a disulfide bond in the long isoform of the receptor. The complex relationships among DR5 network formation, transmembrane helix dimerization, membrane cholesterol, and receptor activity has not been established. It is unknown whether the membrane itself plays an active role in driving DR5 transmembrane helix interactions or in the formation of the networks. We show that cholesterol depletion in cells does not inhibit the formation of DR5 networks. However, the networks that form in cholesterol-depleted cells fail to induce caspase cleavage. These results suggest a potential structural difference between active and inactive networks. As evidence, we show that cholesterol is necessary for the covalent dimerization of DR5 transmembrane domains. Molecular simulations and experiments in synthetic vesicles on the DR5 transmembrane dimer suggest that dimerization is facilitated by increased helicity in a thicker bilayer., (Copyright © 2016. Published by Elsevier Ltd.)

Objective: To analyse ovarian Sertoli-Leydig cell tumours (SLCTs) for potential prognostic markers and their use for treatment stratification., Patients: Forty-four patients were included. Patients were prospectively reported to the German MAKEI (Maligne Keimzelltumoren) studies (n=23), French TGM protocols (n=10), Italian Rare Tumour Project (TREP) registry (n=6), and the Polish Pediatric Rare Tumour Study group (n=5). Tumours were classified according to World Health Organisation (WHO) and staged according to International Federation of Gynecological Oncology (FIGO)., Results: Median age was 13.9 (0.5-17.4) years. All patients underwent resection by tumour enucleation (n=8), ovariectomy (n=17), adenectomy isolated (n=18) or with hysterectomy (n=1). FIGO-stage: Ia 24pts., Ic 17pts., II/III 3pts. One patient had bilateral tumours. Four patients (stage Ia: 3, stage Ic: 1) developed a metachronous contralateral tumour. Otherwise, all stage Ia patients remained in complete remission. Among 20 patients with incomplete resection or tumour spread (stage Ic-III), eight relapsed, and five patients died. Eleven patients were initially treated with two to sixcycles of cisplatin-based chemotherapy. Of these, seven patients are in continuous remission. Poor histological differentiation was associated with higher relapse rate (5/13) compared to intermediate (3/18) and high differentiation (0/4). Tumours with retiform pattern or heterologous elements showed a high relapse rate, too (5/11). After a median follow-up of 62 months, event-free survival is 0.70±0.07, relapse-free survival 0.81±0.06 and overall survival 0.87±0.05., Conclusions: Prognosis of SLCTs is determined by stage and histopathologic differentiation. Complete resection with careful avoidance of spillage is a prerequisite of cure. The impact of chemotherapy in incompletely resected and advanced stage tumours remains to be evaluated., (Copyright © 2014 Elsevier Ltd. All rights reserved.)