To develop and examine the feasibility and preliminary effectiveness of a multicomponent diabetes prevention programme, Preventing Diabetes Via Volunteers Engaging Residence using Technology (P-Divert), in improving intentions to prevent diabetes and promoting healthy lifestyle behaviours.

Pilot quasi-experimental study with matched controls.

The P-Divert programme was developed following the UK Medical Research Council framework for developing and evaluating complex interventions. Field testing with lay participants and relevant experts informed programme refinement prior to implementation. A pilot quasi-experimental study with matched controls was conducted among adults aged 21-69 years at risk of developing diabetes in Singapore. Data were collected at baseline and 12 weeks using validated instruments. Outcomes included the Diabetes Intentions, Attitudes and Behaviour Questionnaire (DIAB-Q), Generalized Self-Efficacy Scale (GSES), Multidimensional Health Locus of Control Form C (MHLC-C), Exercise Goal Setting Scale (EGS), Weight-Related Eating Questionnaire (WREQ), and clinical outcomes.

The programme demonstrated acceptable feasibility, with an 80% retention rate and a 70% adherence rate. Compared with the control group, participants in the intervention group reported significantly higher DIAB-Q subjective norm and planning scores, exercise goal setting scores, and WREQ compensatory restraint scores, as well as significantly lower MHLC-C Chance scores.

The P-Divert programme was feasible and showed preliminary potential to improve intentions to prevent diabetes and promote the adoption of healthy lifestyle behaviours among individuals at risk of developing diabetes.

The P-Divert programme can potentially enhance at-risk individuals' intentions to adopt healthier behaviours, possibly lowering diabetes prevalence and healthcare burden in Singapore. Its integration into community nursing services could strengthen diabetes prevention efforts and may also have potential applications in the prevention of other chronic diseases, thereby reducing long-term disease management burdens.

Members of the public were recruited as participants in this study.

The core pathological feature of type 2 diabetes mellitus (T2DM) is pancreatic β-cell failure; therefore, the identification of effective circulating biomarkers and molecular targets that regulate pancreatic β-cell homeostasis is of significant practical importance. As key regulatory molecules of gene expression, miRNAs play an important role in the proliferation, apoptosis, and insulin secretion of pancreatic β-cells. The purpose of this study is to investigate the expression patterns and clinical value of miR-3619-5p in the serum of T2DM and to clarify its regulatory role in pancreatic β-cell proliferation. RT-qPCR was used to detect the expression of miR-3619-5p and MTA3. ROC curves were used to evaluate diagnostic performance. Bioinformatics and dual-luciferase assays were used to validate the target-ligand relationship. Cell proliferation was measured by CCK-8 assay, while apoptosis was examined via flow cytometry. Insulin secretion levels were measured using ELISA. The results showed that miR-3619-5p and MTA3 were downregulated in T2DM patients and pancreatic β-cells. miR-3619-5p might be a biomarker for the diagnosis of T2DM; its overexpression promotes cell proliferation, inhibits apoptosis, and enhances insulin secretion. miR-3619-5p targets and regulates MTA3, and the two are significantly positively correlated. miR-3619-5p mimic can reverse the damage caused by si-MTA3 to pancreatic β-cell function. In short, miR-3619-5p is downregulated in T2DM and has diagnostic value. miR-3619-5p may participate in the regulation of pancreatic β-cell function by targeting MTA3.

Diabetic lower extremity peripheral artery disease (PAD) is a complex and multifactorial complication of diabetes mellitus, characterized by extensive distal disease burden, accelerated progression, and a markedly elevated risk of major adverse limb events. Despite considerable advances in endovascular and surgical revascularization, limb salvage rates in this population remain suboptimal, largely due to the limited efficacy of current pharmacological options in improving microvascular perfusion, accelerating wound healing, or preventing re-occlusion. In recent years, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a transformative therapeutic class, demonstrating cardiovascular protective effects beyond glycemic control. Large-scale real-world studies have generated encouraging signals regarding their potential to reduce amputation risk and promote wound healing. However, the current evidence base remains limited, and the precise molecular mechanisms by which GLP-1 RAs may protect the diabetic lower extremity require further elucidation. This review systematically examines the epidemiology and pathophysiology of diabetic lower extremity PAD, elucidates the molecular mechanisms of GLP-1 RA-mediated vascular protection, critically evaluates clinical and real-world evidence, and discusses key challenges and future directions for optimizing therapeutic outcomes in this high risk population.

Neonatal diabetes mellitus (NDM) is a rare monogenic form of diabetes presenting before six months of age which can be permanent (PNDM) or transient (TNDM). In rare cases, NDM can be diagnosed between 6 and 12 months of age. Whilst TNDM is commonly associated with chromosome 6q24 methylation defects, the commonest causes of PNDM are KCNJ11 and ABCC8 gene mutations. This observational study's aim was to assess the clinical features and genetic aetiologies in patients with NDM diagnosed in Bangladesh. The clinical characteristics of 28 patients who presented with NDM from 2001 to 2018 in the in the department of Neonatology and Paediatrics, BIRDEM, Dhaka, Bangladesh were studied. Mutation analyses were carried out by DNA sequencing at Peninsula Molecular Genetics Laboratory, Exeter, UK. Thirteen patients were from 11 consanguineous families. Comprehensive genetic testing was performed on 24 patients. Out of the 28 patients studied, 18(64.0%) had PNDM, 7(25.0%) had TNDM and for 3 the subtype was not known. Causative mutations were detected in 22 of the 24(92.0%) who underwent genetic testing. This included 15 PNDM patients (ABCC8 31.0%, KCNJ11 25.0%, EIF2AK3 19.0%, INS 6.0%) and 7 TNDM patients (6q24 43.0%, ABCC8 29.0%, KCNJ11 14.0%, INS 14.0%). Among consanguineous families, mutations in the ABCC8 gene and E1F2AK3 were common. The median age at diabetes presentation was 80 days (3-210 days), median birth weight was 2250g (1000-3700g), mean gestational age 37.15±1.91 weeks (32-40 weeks). The mean blood glucose at presentation was 29.30±11.73mmol/L (14.0-61mmol/L) with 11 patients (39.0%) presenting with diabetic ketoacidosis. Outcome was good in majority of patents except those with Wolcott-Rallison syndrome due to homozygous EIF2AK3 mutation. All patients with KCNJ11 or ABCC8 NDM were transferred from insulin to sulphonylurea except one. Genetic testing identified mutations in 79.0% (22/28) of this study's NDM cohort. An early genetic diagnosis is essential for patients' clinical management and informing parents on recurrence risk.

Type 1 diabetes (T1D) is characterized by progressive loss of pancreatic β cell mass driven by inflammatory cytokine-induced apoptosis. Although glucagon-like peptide-1 receptor (GLP-1R) agonists improve β cell function and survival, their efficacy may be limited under hyperglycemic conditions. Growth hormone-releasing hormone receptor (GHRH-R) agonists have emerged as potential β cell-protective agents through activation of cAMP-dependent signaling pathways. Here, we investigated the effects of the GHRH-R agonist MR-409, alone or in combination with the GLP-1R agonist exendin-4 (Ex-4), on β cell survival and glucose homeostasis. In human islets, combined MR-409 and Ex-4 treatment enhanced glucose-stimulated insulin secretion and increased CREB phosphorylation. The combination also reduced cytokine-induced apoptosis, with decreased caspase 3/7 activity compared with MR-409 alone and reduced BAX protein levels compared with either individual treatment. MR-409 alone increased IRS2 protein levels, consistent with activation of pro-survival signaling pathways. In a multiple low-dose streptozotocin (STZ) mouse model, MR-409, Ex-4, and their combination improved glucose homeostasis and increased β cell mass compared with vehicle-treated mice. However, the combination did not confer additional metabolic benefit over single treatments. Notably, MR-409 treatment was associated with greater improvements in glucose tolerance and insulin levels. These findings support further investigation of GHRH receptor agonism as a strategy to preserve β-cell survival under diabetogenic stress.

Objective: To explore the clinical characteristics and treatment status in elderly patients with oral emergencies, and to provide a reference for improving emergency care level for this population. Methods: A retrospective study was performed on the patients aged 80 years and above in the Department of Oral Emergency in Peking University School and Hospital of Stomatology from January 2022 to December 2024. Gender, age, systemic conditions, disease types and treatment strategies were statistically analyzed. Results: A total of 3 470 patients were enrolled, including 1 403 males (1 403/3 470) and 2, 067 females (2 067/3 470), with a male-to-female ratio of 0.68∶1. The age range was 80 to 101 years, with median age of 84 years. Elderly patients had a wide variety of diseases involving multiple disciplines, in which acute toothache [38.3%(1 330/3 470)], maxillofacial trauma [10.14%(352/3 470)], infectious diseases [10.06%(349/3 470)], hemorrhage [9.00%(312/3 470)], and temporomandibular joint emergencies [6.43%(223/3 470)] were the most prevalent. Comorbid systemic diseases were present in 63% of patients, showing an increasing trend with advancing age. Hypertension [43.8%(1 519/3 470)], cardiovascular and cerebrovascular diseases [27.6%(958/3 470)], and diabetes mellitus [16.9%(588/3 470)] were the most common comorbidities. Emergencies were effectively managed in 69.6% (2 414/3 470) patients. 30.4% (1 056/3 470) patients had no effective resolution, mostly due to the need for scheduled treatment under electrocardiographic monitoring or surgical tooth extraction. Whether electrocardiographic monitoring was needed varied between the two groups with different age characteristics. Conclusions: Elderly patients with oral emergencies have a diverse range of diseases involving multiple disciplines, and the risk of treatment complications is relatively high due to their complex comorbid systemic conditions. Clinicians should formulate individualized treatment plans based on patients' systemic status in clinical treatment.

Suriname's ethnically diverse population lacks recent national pathology-based data on prostate cancer presentation. The aim of this study was to characterize clinicopathologic presentation patterns among histologically confirmed prostate adenocarcinoma patient cases in Suriname, with emphasis on ethnic and geographic variation in prostate-specific antigen (PSA) level and International Society of Urological Pathology (ISUP) grade group.

We retrospectively analyzed 570 histologically confirmed prostate adenocarcinoma patient cases from the National Pathology Database of Suriname (2018-2023). Data on age, ethnicity, PSA level, ISUP grade group, and district of residence (remote versus nonremote) were extracted. Unadjusted comparisons were performed using nonparametric and chi-square tests, and multivariable logistic regression was used to identify factors independently associated with high-grade disease (ISUP grade groups 4-5).

Among 570 patients (median age, 69 years; IQR, 63-75), 40.9% had high-grade disease, and the overall median PSA was 21.0 ng/mL (IQR, 12.0-47.4). Although median PSA did not differ between African- and Asian-ancestry groups (21.0 v 20.3 ng/mL; P = .72), intragroup heterogeneity was observed: Maroon patients had numerically higher PSA levels than Creole patients (32.8 v 19.3 ng/mL; adjusted P = .228). In multivariable logistic regression (n = 331), Javanese ethnicity was independently associated with high-grade disease compared with Creole ethnicity (adjusted odds ratio, 3.31 [95% CI, 1.31 to 8.39]; P = .012). Patients from remote districts showed numerically higher PSA levels and a greater proportion of high-grade disease, although these differences were not statistically significant.

This national pathology-based study found a high proportion of high-grade disease among histologically confirmed prostate cancer patients cases in Suriname and observed ethnic and geographic variation in disease presentation. These findings are hypothesis generating and support further prospective studies on diagnostic access and presentation patterns across population subgroups and geographic regions.

In South Africa, the metastatic response rate for stage 4 high-risk neuroblastoma (HR-NB) to induction chemotherapy is lower than that of similar regimens in well-resourced settings. Augmenting current induction chemotherapy regimens with molecular radiotherapy, without increasing toxicity, is an attractive systemic treatment in radioisotope-avid tumors, especially in a resource-limited setting where stem cell transplantation and immunotherapy are unavailable and costly. Clinical trials of [¹⁷⁷Lu]Lutetium DOTATATE ([¹⁷⁷Lu]Lu-DOTATATE) have primarily focused on refractory or relapsed HR-NB, with disappointing results. This study evaluates the feasibility and dose-limiting toxicity grading of adding a single dose of [¹⁷⁷Lu]Lu-DOTATATE to induction chemotherapy in achieving metastatic remission rates.

The aim of the proof-of-concept, open-label study is to evaluate the safety and efficacy of induction [¹⁷⁷Lu]Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) on postinduction response rate in children diagnosed with HR-NB. The primary objectives are to evaluate the dose-limiting toxicity profile of participants treated with induction [¹⁷⁷Lu]Lu-DOTATATE PRRT in conjunction with standard induction chemotherapy; to evaluate the dosimetry in South African patients receiving induction [¹⁷⁷Lu]Lu-DOTATATE PRRT; and to evaluate the feasibility related to resources in patients treated with induction [¹⁷⁷Lu]Lu-DOTATATE PRRT in conjunction with standard induction chemotherapy. The secondary objective is to determine the postinduction metastatic response rate in patients diagnosed with HR-NB after receiving induction [¹⁷⁷Lu]Lu-DOTATATE PRRT in conjunction with standard induction chemotherapy.

The LuDO-SA trial is a phase 1, open-label, multicenter, 2-arm, randomized controlled clinical trial. Children aged 18 months to 18 years are eligible. The experimental arm, consisting of a single dose of [¹⁷⁷Lu]Lu-DOTATATE after cycle 1 of OJEC (vincristine, carboplatin, etoposide, and cyclophosphamide) and OPEC (vincristine, cisplatin, etoposide, and cyclophosphamide) chemotherapy, will be compared to the standard arm of OJEC and OPEC chemotherapy. The postinduction metastatic response rate is based on the International Neuroblastoma Response Criteria (INRC). The statistical analysis will be descriptive. The Fisher exact test will be used to evaluate the significance of end-of-trial outcomes.

The trial received institutional ethics approval from 4 South African universities in 2022 and SAHPRA (South African Health Products Regulatory Authority) regulatory approval. The trial, funded by Kinderkankerfonds vzw and the UZA Foundation, commenced recruitment in January 2023. As of July 2026, a total of 15 patients have been enrolled across 4 academic hospital sites. Recruitment is projected to be completed by June 2027, with results expected to be published in December 2027.

In this paper, we present the protocol of the LuDO-SA trial. The rationale and design of the trial in a resource-limited setting and its use in first-line regimens are discussed, and the current status of international [¹⁷⁷Lu]Lu-DOTATATE molecular radiotherapy trials is summarized.

Maintenance of fissed mitochondria is viewed as a defining feature of Kirsten rat sarcoma viral oncogene homolog (KRAS)-mutant cancers. However, regulation of this process by accompanying comutations or environmental factors is not clearly defined. Here, by analyzing a subset of pancreatic cancer lesions driven by concurrent Kras^G12D and GNAS complex locus gene (GNAS^R201C/H) mutations, we found that despite the presence of mutant Kras, hyperactive Gnas^R201C maintains mitochondria predominantly in a fused state, which is necessary for tumor growth. Multiplex proteomics, super-resolution microscopy, loss- and gain-of-function studies, coupled with metabolite rescue experiments, revealed that Gnas^R201C-regulated branched-chain amino acid (BCAA) pathway is a previously unidentified regulator of mitochondrial morphology. Mechanistically, the BCAA pathway, the associated tricarboxylic acid cycle, and aspartate metabolism converge on nicotinamide adenine dinucleotide (NADH-NAD⁺) metabolites to promote mitochondrial elongation. NAD⁺ availability is crucial for mitochondrial fusion, as facilitating NAD⁺ generation through alternative means promotes fusion. Collectively, we unraveled a new mechanism that drives mitochondrial fusion and showed that the combination of oncogenic signaling and metabolism can maintain distinct mitochondrial morphology within genetic subsets of KRAS-mutant pancreatic cancer.

Ectopic parathyroid adenomas represent an uncommon but clinically significant cause of primary hyperparathyroidism, particularly when located in the mediastinum. Their diagnosis may be challenging, especially in the presence of concomitant thyroid pathology, which can obscure imaging interpretation and lead to misleading localization studies.

We report the case of a 63-year-old man who presented with persistent hoarseness and was found to have marked hypercalcemia and elevated parathormone levels consistent with primary hyperparathyroidism. Neck ultrasonography demonstrated multinodular goiter, while dual-tracer technetium-99m pertechnetate and technetium-99m sestamibi scintigraphy with SPECT/CT suggested a functional thyroid adenoma and raised suspicion for a possible parathyroid lesion within the thyroid gland. Fine-needle aspiration with parathormone washout did not confirm an intrathyroidal parathyroid origin. Subsequent cross-sectional imaging revealed a large cystic mass in the anterior superior mediastinum compressing adjacent structures. After medical stabilization with cinacalcet, the patient underwent surgical excision through a right axillary thoracotomy. Intraoperative and biochemical findings confirmed the lesion as the source of excessive parathormone secretion. Histopathological and immunohistochemical examination established the diagnosis of a cystic ectopic parathyroid adenoma. Postoperatively, serum calcium and parathormone levels normalized, and the patient remained free of biochemical evidence of recurrent disease during the available follow-up period.

This case highlights the diagnostic complexity of mediastinal ectopic parathyroid adenomas, particularly in patients with coexisting multinodular goiter and inconclusive scintigraphic findings. Clinicians should maintain a high index of suspicion for ectopic parathyroid tissue in cases of unexplained hyperparathyroidism with negative or discordant cervical imaging, as accurate localization is critical for definitive surgical management.