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Modifications on histone tails in psychiatric disorders.1 week agoThe present study provides a comprehensive introduction to the features of histone tails, including their length, subtypes, nomenclature, biological functions, and regulation, and systematically reviews their roles in psychiatric disorders. A literature search was conducted, covering over 200 common histone modifications and the top 20 common psychiatric disorders. The results indicate that 26 histone tail modifications are positively associated with ten psychiatric disorders, with most located at H3 and H4 tails, and only one at the H2AX tail. All modifications occur at lysines (K), except for two at arginine (R) or serine (S). The top five modifications associated with psychiatric disorders are H3K9ac, H3K4me3, H3K27ac, H3K9me2, and γH2AX. The majority of the studies (92%) report substance use disorders, Alzheimer's disease, major depressive disorder, schizophrenia, and autism spectrum disorders as the top five psychiatric disorders associated with histone tail modifications. In conclusion, histone tail modifications play crucial roles in various psychiatric disorders, and targeting them and associated epigenetic regulators may offer potential therapeutic strategies for treating psychiatric disorders by providing new insights into the molecular mechanisms underlying abnormal gene expression.Mental HealthCare/ManagementPolicy
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Effectiveness of Multi-Level Implementation Strategies on Caregiver-Identified "Top Problems:" Secondary Outcomes of a Hybrid Trial of Two Autism Interventions.1 week agoMeeting the needs of autistic children requires the effective implementation of evidence-based interventions (EBIs). The TEAMS project tested the effectiveness of leader-level and provider-level implementation strategies to support the implementation of two autism-focused EBIs. The leader-level strategy was found effective in improving observed provider fidelity and standardized caregiver-reported child outcomes. This study extends the primary trial findings by assessing individualized child outcomes.
The current study examines the individual and combined effects of the TEAMS implementation strategies - TEAMS Leadership Institute (TLI) and TEAMS Individualized Provider Strategy (TIPS) - on caregiver-identified Top Problems.
Data were extracted from the TEAMS project, a hybrid type 3 implementation-effectiveness trial testing the effects of implementation strategies when paired with AIM HI (An Individualized Mental Health Intervention for Autism) in mental health programs (Study 1) and CPRT (Classroom Pivotal Response Teaching) in classrooms (Study 2). Programs/districts were randomized to TLI and/or TIPS. Data from 353 caregivers of autistic children (M age = 7.89 years, SD = 2.92, 80.1% male, 44.2% Latinx) were analyzed. Clinical outcomes were measured using the Top Problems Assessment at intake and after 6 months.
Controlling for study intervention (AIM HI or CPRT), a significant TLI x Time interaction (B = -0.95, p = .021) indicated greater reductions in Top Problem intensity in the TLI (vs. no-TLI) condition. No significant effects were found for TIPS or TIPSxTLI.
Findings support the effectiveness of leader-focused implementation strategies in improving the outcomes valued most by families.Mental HealthCare/Management -
Depression.1 week agoDepression is a common illness that affects people within every society around the world. It afflicts the young and the old and everyone in between, and as such poses an immense global burden. New interventions and a deeper understanding of this illness are emerging, but improving the use of existing treatments is equally important and might be a more efficient and effective strategy to addressing depression. Therefore, it is imperative that we improve the diagnosis of depression and its clinical management.Mental HealthCare/Management
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Diagnostic Utility of a Cost-Effective Four-Gene Next Generation Sequencing Panel for Predicting Papillary Thyroid Carcinoma in Indeterminate Thyroid Cytology: A Multicenter Study in China.1 week agoMolecular testing has emerged as a pivotal tool for the preoperative assessment of cytologically indeterminate thyroid nodules. In this cross-sectional study, we evaluated the diagnostic utility of a targeted next-generation sequencing (NGS) 4-gene panel, including BRAFV600E, TERT promoter mutations, RET fusions, and NTRK3 fusion, for enhancing the cytological diagnosis of thyroid nodules prior to surgical intervention. A total of 827 thyroid nodules subjected to fine-needle aspiration and subsequent histopathological confirmation were analyzed, among which 773 (93.5%) were classified as malignant or noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). The observed prevalence of molecular alterations was: BRAFV600E, 68.3% (526/770); TERT promoter mutations, 10.3% (79/770); RET fusions, 10.3% (79/770); and NTRK3 fusion, 3.9% (30/770). Notably, the 4-gene NGS panel demonstrated brilliant diagnostic performance for indeterminate cytological nodules (Bethesda categories III-V), achieving a sensitivity of 87.9%, specificity of 96.3%, positive predictive value (PPV) of 99.7%, negative predictive value (NPV) of 35.9%, and overall accuracy of 88.2%. These findings indicate that the targeted NGS 4-gene panel provides high diagnostic precision in distinguishing benign from malignant nodules. Its implementation offers a cost-effective, efficient molecular diagnostic strategy that may reduce unnecessary diagnostic procedures and facilitate optimized clinical management.Non-Communicable DiseasesCancerAccessCare/ManagementAdvocacy
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Late and Durable Minimal Residual Disease Response Predicts Favorable Outcomes in Newly Diagnosed Multiple Myeloma.1 week agoMinimal residual disease (MRD) negativity is a well-established prognostic marker in multiple myeloma (MM), yet the clinical relevance of MRD response timing and duration remains unclear, particularly in real-world settings. We retrospectively analyzed 1048 newly diagnosed MM patients from the National Longitudinal Cohort of Hematological Diseases in China (NICHE) between 2012 and 2023, with a total of 5406 MRD assessments. A longer time to best MRD response (> 6 months) was significantly associated with improved progression-free and overall survival, especially among those with persistent MRD positivity but stable low-level disease burden. Early responders were more likely to exhibit high tumor burden and high-risk cytogenetic abnormalities. Notably, a prolonged MRD duration (≥ 36 months) predicted favorable outcomes regardless of MRD negativity status. Integrating response timing and duration identified a "Late + Durable" MRD pattern consistently associated with the best prognosis, even in patients with persistent MRD positivity, high-risk cytogenetics, or without ASCT. These findings highlight the prognostic significance of longitudinal MRD monitoring beyond single-timepoint assessments. A slow but durable MRD response may overcome adverse biological features and support individualized risk stratification, therapeutic decisions, and long-term disease monitoring in MM.Non-Communicable DiseasesCare/Management
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Plant proteins for human health: the current status and future needs.1 week agoPlant based protein consumption is increasingly recognized for its therapeutic potential in managing metabolic health and preventing chronic diseases. This review provides a comprehensive analysis of the physiological impact of plant proteins, including their roles in satiety regulation and weight management via the modulation of appetite regulating hormones. We examine how plant proteins optimize lipid metabolism and reinforce gut homeostasis by promoting diverse microbiota and increasing the production of short chain fatty acids. Furthermore, we dissect the mechanisms through which plant proteins and their digestion derived peptides attenuate the pathogenesis of cardiovascular disease, type 2 diabetes, and chronic kidney disease. Specific attention is given to the modulation of intracellular signaling pathways such as PI3K-Akt and the regulation of the renin angiotensin system. The review also highlights that the health efficacy of plant proteins is highly dependent on the food matrix, where synergistic interactions between proteins, fiber, and phytochemicals are critical. Finally, the impact of food processing on peptide bioaccessibility is examined, and a process-matrix function paradigm is proposed for future research. In conclusion, these insights underscore the role of plant proteins as functional components that are essential for developing sustainable and precise nutritional strategies to mitigate the global burden of non-communicable diseases.Non-Communicable DiseasesCardiovascular diseasesPolicy
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Multi-variant genotyping identifies association of TRPC6 rs36111323 with diabetic kidney disease in a South Indian population.1 week agoDiabetic kidney disease (DKD) is a leading cause of chronic kidney disease and end-stage kidney failure worldwide. Genetic factors contribute to inter-individual and population-specific susceptibility to DKD. Data from South Indian populations are limited, highlighting the need for region-specific genetic association studies in DKD.
This case-control study included 125 South Indian individuals: 60 patients with diabetes and proteinuria (DKD), 34 patients with diabetes without kidney disease, and 31 healthy controls. Genomic DNA was isolated and nine variants were genotyped using amplification refractory mutation system polymerase chain reaction (ARMS-PCR). Variant frequencies were compared among groups. In-silico pathogenicity prediction tools and Odds ratio (OR) with 95% confidence intervals (CIs) were estimated using multivariable logistic regression analyses were used to assess the association between genetic variants and DKD risk. Data visualization was performed using R statistical software. Among the nine variants analyzed, the TRPC6 rs36111323 (G > A; p.A404V) was independently associated with DKD (OR = 2.76; 95% CI = 1.04-7.34; p = 0.0418). This variant was more frequent in patients with DKD compared with diabetic patients without nephropathy and healthy controls. Pathogenicity prediction analyses supported a potentially deleterious effect of the variant.
The TRPC6 rs36111323 variant appears to be associated with increased susceptibility to diabetic kidney disease in a South Indian population, suggesting a population-specific genetic risk factor. Validation in larger cohorts and functional studies is warranted to clarify its role and potential application in precision nephrology.DiabetesAccessAdvocacy -
Blood Glucose Monitoring Expert Group and Best Practice Recommendation-FITTER BiG.1 week agoDiabetes mellitus presents a growing public health challenge across geographies including Asia, particularly in countries where blood glucose monitoring (BGM)-referring to capillary finger-prick self-monitoring of blood glucose (SMBG) using a meter and test strips-is underutilized. Having evolved and improved over recent decades, glucose monitoring (GM)-including SMBG and continuous glucose monitoring (CGM)-has become an essential tool for effective diabetes management, yet remains underutilized because of systemic, economic, and educational barriers. This work synthesizes expert insights and published evidence to develop best practice recommendations for BGM.
A targeted literature review (TLR) was conducted across five thematic domains: monitoring practices, clinical decision-making, patient engagement and adherence, technology and innovation, and policy and reimbursement. Insights were complemented by a structured expert forum involving clinicians from seven Asian countries, underscoring larger implications in geographies where SMBG remains underutilized within the diabetes care continuum. The forum highlighted disparities in device access, affordability, and insurance coverage, and emphasized the need for structured diabetes self-management education (DSME) and digital integration.
Findings support the use of structured SMBG for non-insulin-treated type 2 diabetes and CGM for insulin-treated individuals and those at risk of hypoglycemia. Evidence from the literature review also highlighted the importance of proper SMBG technique, with common errors such as inadequate handwashing, repeated lancet use, and excessive finger squeezing contributing to inaccurate readings and finger-site injuries. Hybrid models combining CGM and SMBG for calibration or confirmation are pragmatic solutions balancing clinical utility and affordability. Digital platforms, AI-driven analytics, and mobile apps enhance patient engagement and glycemic control but face challenges of scalability and regulation.
Policy reforms, including inclusion of BGM in national health benefit packages, expanded insurance coverage, and public-private partnerships, are critical to improving access. The recommendations advocate for personalized, context-specific monitoring strategies that balance clinical efficacy with affordability and infrastructure realities. This consensus-based framework aims to guide healthcare professionals in optimizing BGM practices and improving long-term outcomes for people living with diabetes. FITTER BiG is a new extension of the long-standing FITTER initiative, which has provided insulin injection technique recommendations for more than two decades. FITTER BiG complements this work by focusing specifically on best practice recommendations for blood glucose monitoring. FITTER BiG will provide BGM-specific recommendations designed to complement the injection technique guidance outlined in the FITTER Forward consensus statement (Klonoff et al. Mayo Clin Proc 100:682-699, 2025 [1]).DiabetesAccessCare/ManagementPolicy -
Assessing the Impact of Glucagon-like Peptide-1 and Glucagon-like Peptide-1/glucose-dependent Insulinotropic Polypeptide Receptor Agonist Shortages on Glycemic Control: A Single Center Study.1 week agoBackground: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and dual GLP-1/glucose-dependent insulinotropic polypeptide receptor agonists (GLP-1/GIP RAs) effectively manage type 2 diabetes mellitus (T2DM). Recent medication shortages have impacted patient access to treatment. The objectives of this study were to evaluate the effect of incretin therapy shortages on glycemic control and adverse patient outcomes. This retrospective cohort study evaluated the impact of interruptions in therapy on patients receiving maintenance doses of incretin therapy for at least three months. Patients were excluded if they were not on adequate maintenance doses, had missing hemoglobin A1c (HbA1c) levels, discontinued therapy due to side effects or cost, or had a history of chronic glucocorticoid use or organ transplant. The primary outcome was HbA1c levels before and after therapy interruption. Secondary outcomes were the incidence of gastrointestinal issues, hyperglycemia, and hypoglycemia-related hospital/clinic visits. A total of 71 patients were included. The median therapy duration was 9 months. Patients had a baseline HbA1c of 6.9%. Following interruption, 25.4% of patients had glucose-lowering therapy additions to their regimen, 35.2% dosage adjustments, and 39.4% no changes. HbA1c increased significantly to 7.2% at 12 months (P < 0.001). No significant differences were observed in adverse events or clinic/hospital visits (P = 0.571 and P = 1.00). Shortages of incretin therapy significantly increased patients' HbA1c levels up to 12 months post interruption. Long-term shortages or restrictions of these agents are likely to lead to adverse clinical outcomes. Further studies are needed to assess the outcomes of prolonged shortages or restrictions of these therapies.DiabetesDiabetes type 2AccessCare/Management
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Laparoscopic Pancreaticoduodenectomy - Initial Experience in a Hepatopancreatobiliary High-Volume Center.1 week agoIntroduction: Pancreaticoduodenectomy is a complex surgical procedure involving meticulous resection and reconstruction steps. Materials and Methods: We analyzed the first 15 laparoscopic pancreaticoduodenectomies performed for ampullary, periampullary, and cephalic pancreatic tumors at the Fundeni Clinical Institute, Bucharest, a high-volume center with extensive expertise in hepatopancreatobiliary surgery. Patient demographics, medical history, intraoperative parameters, early postoperative outcomes, and oncological results regarding radical resection were evaluated. Results: The mean patient age was 59.4 years, with 53.33% males. Cardiovascular comorbidities were present in 60% of patients, while 26.66% had controlled type 2 diabetes mellitus. Previous cholecystectomy was noted in 46.66% of cases, and 60% presented with jaundice at diagnosis. The mean operative time was 360 minutes. Pancreaticogastrostomy was performed in 66.66% of cases and pancreaticojejunostomy in 33.33%, with 26.66% of procedures being fully laparoscopic. Biochemical leakage occurred in 13.33% of cases, while grade B pancreatic fistula developed in 6.67% of cases and was managed conservatively. Moderate biliary fistula occurred in 13.3% of the patients, with remission under conservative treatment. All resections achieved negative margins (R0). The mean number of retrieved lymph nodes was 15.6, and the average hospital stay was 18.7 days. Discussions: Laparoscopic pancreaticoduodenectomy provides oncological outcomes comparable to the open approach and may improve postoperative recovery in experienced centers. Conclusions: Our results are encouraging, with potential for further improvement through careful patient selection and refinement of surgical technique.DiabetesCancerDiabetes type 2AccessCare/ManagementAdvocacy