The University of Medicine and Health Sciences (also known as UMHS) is a private, for-profit medical school located in Basseterre, Saint Kitts in the Caribbean. UMHS confers upon its graduates the Doctor of Medicine (MD) degree. The university also has a 5th semester campus in Portland, Maine and an administrative office in New York, New York.
BACKGROUND:Cardiovascular disease has historically been the most common cause of death (COD) among people with and without diabetes. However, substantial progress has been made in the management of cardiovascular disease. We conducted a multinational analysis to establish whether this trend is still the case. METHODS:In this multinational, population-based study, we assembled aggregated annual mortality data collected during routine clinical care from nationally or regionally representative administrative datasets in high-income jurisdictions between 2000 and 2023. For inclusion, datasets must have ongoing enrolment of new patients with diabetes, cause-specific death counts in people with and without diabetes, and sex-specific and age-specific data. We collected population size, counts of prevalent diabetes (type 1 and type 2), death counts, and person-years of follow-up in people with and without diagnosed diabetes by sex and 10-year age group. We estimated cause-specific trends in mortality rates, proportional mortality, and mortality rate ratios (MRR) for people with versus those without diabetes (type 1 and type 2) using Poisson models standardised for age and sex. FINDINGS:Using data from 11 jurisdictions, we identified 2·7 million deaths in people with diabetes and 11·0 million deaths in people without diabetes during a total of 1·7 billion person-years of follow-up. Cardiovascular disease mortality decreased in all jurisdictions in populations with and without diabetes. Mean 5-year declines in cardiovascular disease mortality among people with diabetes ranged from 8·3% (95% CI 5·9 to 10·7) to 25·4% (22·8 to 28·0). Mortality due to diabetes declined in most jurisdictions. Dementia mortality increased in people with and without diabetes in six (86%) of seven jurisdictions. Cancer mortality declined in people with diabetes in three (33%) of nine jurisdictions and in people without diabetes in six (67%). At the end of the observation period, cancer was the leading COD in people with diabetes in four (36%) of 11 jurisdictions. MRRs were generally stable for all CODs. Exceptions include Lithuania, where the mean 5-year change in MRR for cardiovascular disease was -7·6% (-10·1 to -5·1), indicating a more rapid fall in cardiovascular disease mortality in people with diabetes than in people without. For dementia, the MRR increased in Denmark (5-year change 8·0% [5·0 to 11·1]) and Scotland (11·4% [8·5 to 14·3]). INTERPRETATION:Mortality from cardiovascular disease and diabetes has declined among people with diabetes in most jurisdictions, whereas mortality from dementia has increased markedly, independent of age. Cardiovascular disease is no longer universally the most common COD among people with diabetes in high-income countries. FUNDING:US Centers for Disease Control and Prevention, Diabetes Australia Research Program, and Victoria State Government Operational Infrastructure Support Program.
INTRODUCTION:Aldose reductase-2 (ALR2) is a key enzyme in the polyol pathway whose overexpression is implicated in several diabetic complications, including neuropathy, nephropathy, retinopathy, and atherosclerotic plaque formation. Under hyperglycemic conditions, the intracellular accumulation of sorbitol and the depletion of NADPH lead to osmotic imbalance and oxidative stress, driven by the formation of reactive oxygen species and advanced glycation end products. Although various ALR2 inhibitors have been developed, their clinical application has been hampered by nonselective inhibition of both ALR2 and the homologous enzyme ALR1. METHODS:In this study, we employed a comprehensive iin silicoi approach to evaluate the inhibitory potential of natural compounds from iCynomorium songaricumi against ALR2. Our workflow integrated with ADMET, molecular docking with scoring function and glide XP, molecular dynamics (MD) simulations, PCA, FEL, and MM/GBSA. Through this analysis, four natural compounds of C. songaricum (Compound Name: p-Coumaric acid, Vanillic acid, 4-Oxoniobenzoate, and Phloroglucinol) displayed significant bonds formation including hydrogen and hydrophobic bonds with the target protein. RESULTS:These bonds exhibited the ligand stability. Further, the MD simulation analysis, followed by postsimulation analysis, verified the dynamic stability of these four natural compounds and compared them with the native ligand of the target protein. These natural compounds exhibit particularly stable binding within the ALR2 selectivity pocket, demonstrating an inhibitory effect over ALR1 when compared with the reference inhibitor, Epalrestat. CONCLUSION:These promising iin silicoi findings suggest that CID: 8468 and CID: 135 merit further evaluation through iin vitro, in vivoi, and clinical studies as potential selective inhibitors for the treatment of diabetic complications.
Introduction:Menstrual disorders-including premenstrual syndrome (PMS), premenstrual dysphoric disorder (PMDD), and dysmenorrhea-are highly prevalent among women of reproductive age and are associated with impaired academic performance, psychological distress, and reduced social functioning. Nursing students are particularly vulnerable due to the combined demands of intensive academic schedules and clinical training, yet prevalence estimates and institutional responses remain inconsistent. Methods:A systematic review and meta-analysis were conducted in accordance with PRISMA 2020 guidelines and registered in PROSPERO (CRD420251109363). PubMed, Scopus, Web of Science, CINAHL Ultimate, and APA PsycINFO were searched for studies published between 2016 and 2025. Eligible studies reported prevalence or impact of PMS, PMDD, or dysmenorrhea exclusively in nursing students. The Joanna Briggs Institute checklist for prevalence studies was used for quality appraisal. Random-effects meta-analysis was applied to calculate pooled prevalence estimates, and thematic synthesis was used to evaluate academic, social, and psychosocial impacts, coping strategies, and interventions. Results:Twenty studies involving 5,131 nursing students were included. The pooled prevalence was 62% for PMS, 21% for PMDD (including severe PMS), and 72% for dysmenorrhea, with substantial heterogeneity (I 2 > 80%). Reported impacts included absenteeism, reduced concentration, diminished clinical performance, and impaired quality of life. Coping strategies were largely self-directed, including analgesics, rest, and dietary modifications, while few students accessed formal healthcare or institutional support. Only a limited number of studies evaluated structured interventions such as exercise, yoga, or nutritional supplementation. Conclusion:Menstrual disorders are highly prevalent among nursing students and carry significant academic, social, and psychological consequences. Nursing education programs should integrate routine screening, structured wellness initiatives, and evidence-based interventions to improve student wellbeing, reduce academic disruption, and strengthen workforce preparedness. Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/view/CRD420251109363, PROSPERO CRD420251109363.
Background Cyclin-dependent kinase 12 (CDK12) regulates general gene transcription elongation and plays multiple roles in RNA splicing, DNA damage-response, cell cycle, and genomic stability. However, transcriptional partners that guide CDK12-specific gene programs have not been identified. Genomic alterations in CDK12 have been observed in multiple cancers, exhibiting both pro-tumorigenic and tumor-suppressive functions, suggesting a context-dependent mechanism of action.Methods CDK12 copy number alterations and gene expression levels were analyzed in matched primary and brain metastatic patient tumors. Clinical significance was assessed by immunohistochemistry in a large cohort of primary breast cancer patient tumors. RNA sequencing, ChIP sequencing, and molecular studies were conducted to explore CDK12's mechanism of action, and pharmacological studies were performed both in vitro and in vivo using models of advanced (endocrine-resistant and metastatic) estrogen receptor positive (ER+) disease.Results CDK12 amplifications and gene overexpression were observed in brain metastatic tumors. In ER+ primary patient tumors, high CDK12 protein expression was significantly associated with poor overall survival, particularly within the ER+/HER2-negative group. In ER+ endocrine resistant models, CDK12 regulated estrogen signaling pathways, with ER/MED1 identified as the master transcriptional complex directing CDK12-specific pro-tumorigenic gene programs. Pharmacological inhibition of CDK12 significantly reduced viability in endocrine resistant and metastatic cell and organoid models in vitro, and decreased metastatic spread in vivo.Conclusion This work describes a novel mechanism for CDK12, suggesting a potential vulnerability in ER+ breast cancer. These findings provide a basis for further investigation into the role of CDK12 inhibition as a therapeutic approach, particularly in advanced disease settings.
Background:Stage III colorectal cancer poses a significant threat of metastasis development, as tumour resection and adjuvant chemotherapy do not guarantee prolonged disease-free survival. Objective:The spatial, quantitative, and qualitative characteristics of various cell types within tumour tissues could be key to developing accurate prognostic AI models. Design:Tissue microarrays created from primary tumour tissues collected during surgical resection from a cohort of 493 stage III colorectal cancer (CRC) patients were analysed for 61 protein markers at the single-cell level using multiplexed immunofluorescence imaging via the Cell DIVE™ platform. Subsequent cell-type classification enabled quantitative cell-type analyses, co-localisation neighbourhood assessments, and cell-type-specific protein signature discoveries that distinguish between early and late/non-recurring patient samples. Results:This study identifies a stem cell protein profile that drives tumour relapse. A deep neural network (DNN) model, based on a stem cell protein signature composed of BAX, MLKL, FLIP, GLUT1, and CDX2, provided accurate prognosis for stage III CRC patients in both discovery and validation cohorts and in an independent validation cohort. Nodal count-based metric further increased prognosis accuracy. Our study also revealed distinct spatial arrangements of immune, endothelial, and stem cells that were linked to early tumour recurrence. Conclusion:Our findings propose a clinically promising prognostic tool based on a five-protein stem cell signature. These markers not only predict chemotherapy resistance in cancer stem cells but also suggest potential therapeutic strategies such as combinatorial treatments incorporating small molecule inhibitors targeting FLIP and GLUT1.
