Prescribing Trends of Antidiabetes Medications Near End-of-Life Among Adults With Type 2 Diabetes: A Cohort Study.

Objective: To assess prescribing trends of antidiabetes medications in the last year of life among older adults with type 2 diabetes (T2D) and explore whether frailty is associated with differential prescribing.

Research Design And Methods: In this observational cohort study of Medicare beneficiaries aged ≥67 years (2015-2019) with T2D, we assessed temporal trends in prescribing an antidiabetes medication, stratified by frailty. The main outcome included antidiabetes medication fills within 1 year of death.

Nomadic Nanomedicines: Medicines Enabled by the Paracrine Transfer Effect.

In nanomedicine, the cellular export of nanomaterials has been less explored than uptake. Traditionally viewed in a negative light, recent findings highlight the potential of nanomedicine export to enhance therapeutic effects. This Perspective examines key pathways for export and how nanomaterial design affects removal rates.

Rare germline structural variants increase risk for pediatric solid tumors.

Pediatric solid tumors are a leading cause of childhood disease mortality. In this work, we examined germline structural variants (SVs) as risk factors for pediatric extracranial solid tumors using germline genome sequencing of 1765 affected children, their 943 unaffected parents, and 6665 adult controls. We discovered a sex-biased association between very large (>1 megabase) germline chromosomal abnormalities and increased risk of solid tumors in male children.

Parkinson disease-associated toxic exposures selectively upregulate vesicular glutamate transporter vGlut2 in a model of human cortical neurons.

Parkinson disease (PD) is the second most common neurodegenerative disease, characterized by both motor and cognitive features. Motor symptoms primarily involve midbrain dopaminergic neurons, while cognitive dysfunction involves cortical neurons. Environmental factors are important contributors to PD risk.

The Captopril Challenge Test Predicts Cardiac Structure and Dysfunction in Primary Aldosteronism.

Context: The captopril challenge test (CCT) is a commonly used confirmation test that identifies the magnitude of renin- and angiotensin II-independent aldosterone production, and thus the presence and severity of primary aldosteronism (PA).

Objective: This study investigated the association between the post-CCT plasma aldosterone concentration (PAC) and cardiovascular remodeling and diastolic dysfunction.

Methods: A total of 540 PA patients with complete CCT and echocardiographic data were retrospectively analyzed.

Medical Reference Tools and Pharmaceutical Promotion: A History of Entanglement.

Reference tools are often uncritically accepted as balanced, objective, definitive, and evidence-based guides to medical knowledge. Yet for centuries textbooks and manuals have been entangled in various ways with industry interests. This essay shows how reference tools have served as sites of pharmaceutical promotion.

Prospective pooled analyses of ambient ultraviolet radiation levels and risk of non-Hodgkin lymphoma and multiple myeloma.

Case-control studies of sun exposure and ultraviolet radiation (UVR) have consistently reported inverse associations with non-Hodgkin lymphoma (NHL) risk, but prospective studies have yielded mixed results. Few studies have explored these exposures in relation to multiple myeloma (MM) risk. To further evaluate these associations with NHL and MM risk and identify etiologically relevant exposure timing, we pooled data on 566,693 individuals from 6 United States (U.

Systolic Blood Pressure and Pulse Pressure in Heart Failure: Pooled Participant-Level Analysis of 4 Trials.

Background: Hypertension is common in patients with heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), and current guidelines recommend treating systolic blood pressure (SBP) to a target <130 mm Hg. However, data supporting treatment to this target are limited. Additionally, pulse pressure (PP), a marker of aortic stiffness, has been associated with increased risk of cardiovascular events, but its prognostic impact in HFpEF has not been extensively studied.

Human intraepithelial mast cell differentiation and effector function are directed by TGF-β signaling.

Mast cells (MCs) expressing a distinctive protease phenotype (MCTs) selectively expand within the epithelium of human mucosal tissues during type 2 (T2) inflammation. While MCTs are phenotypically distinct from subepithelial MCs (MCTCs), signals driving human MCT differentiation and this subset's contribution to inflammation remain unexplored. Here, we have identified TGF-β as a key driver of the MCT transcriptome in nasal polyps.

Cardiac fibroblast BAG3 regulates TGFBR2 signaling and fibrosis in dilated cardiomyopathy.

Loss of Bcl2-associated athanogene 3 (BAG3) is associated with dilated cardiomyopathy (DCM). BAG3 regulates sarcomere protein turnover in cardiomyocytes; however, the function of BAG3 in other cardiac cell types is understudied. In this study, we used an isogenic pair of BAG3-knockout and wild-type human induced pluripotent stem cells (hiPSCs) to interrogate the role of BAG3 in hiPSC-derived cardiac fibroblasts (CFs).

Conceptual Frameworks in Neurology Education Research.

This article discusses conceptual frameworks in neurology education research. We provide practical case examples highlighting the conceptual framework development process for different research scenarios in neurology education. We explore the steps that shape the conceptual framework process, including defining the educational problem, exploring the scholarly conversation on the topic of study through understanding the literature and outlining its gaps, constructing research questions, selecting the theoretical frameworks that underpin the study, and choosing the appropriate methodology and methods for the research questions.

Melanoma toolkit for early detection for primary care clinicians: a 1-year follow-up on outcomes.

Introduction: Primary care providers or clinicians (PCPs) have the potential to assist dermatologists in screening patients at risk for skin cancer, but require training to appropriately identify higher-risk patients, perform skin checks, recognize and biopsy concerning lesions, interpret pathology results, document the exam, and bill for the service. Very few validated dermatology training programs exist for PCPs and those that are available focus primarily on one emphasis area, which results in variable efficacy and single-topic limited scope.

Methods: We have created a free, online, continuing education program (Melanoma Toolkit for Early Detection, MTED) that allows learners to choose from a variety of multimedia tools (image recognition, videos, written material, in-person seminars, self-tests, etc.

Long-term impact of Diabetes Prevention Program interventions on walking endurance.

Objectives: Type 2 diabetes (T2D) and prediabetes are associated with poor walking endurance, a marker of physical function. We aimed to examine the long-term effects of metformin or intensive lifestyle intervention in adults at high risk of T2D on their 6-min walk test (6MWT) performance.

Methods: Participants were randomized in the 3-year Diabetes Prevention Program (DPP) to one of the three groups: lifestyle intervention, metformin, or placebo, and were subsequently followed in the DPP Outcomes Study.

Dysregulation of mTOR signalling is a converging mechanism in lissencephaly.

Cerebral cortex development in humans is a highly complex and orchestrated process that is under tight genetic regulation. Rare mutations that alter gene expression or function can disrupt the structure of the cerebral cortex, resulting in a range of neurological conditions. Lissencephaly ('smooth brain') spectrum disorders comprise a group of rare, genetically heterogeneous congenital brain malformations commonly associated with epilepsy and intellectual disability.

Renal denervation for hypertension.

Innovative therapies for hypertension are desperately needed given the rising prevalence and falling rates of control of hypertension despite an abundance of available medical therapies. Procedural interventions lower blood pressure without depending on adherence to medications, and endovascular renal denervation (RDN) is the interventional procedure with the best evidence base for the treatment of hypertension. After nearly two decades of study, with major refinements to devices, technique and trial design, two different systems for RDN received approval from the FDA in late 2023 for the treatment of hypertension.

Mechanical Circulatory Support for Acute Myocardial Infarction Cardiogenic Shock: Review and Recent Updates.

Cardiogenic shock (CS) in acute myocardial infarction (AMI) is a life-threatening syndrome characterized by systemic hypoperfusion that can quickly progress to multiorgan failure and death. Various devices and configurations of mechanical circulatory support (MCS) exist to support patients, each with unique pathophysiological characteristics. The Intra-aortic balloon pump can improve coronary perfusion, decrease afterload, and indirectly augment cardiac output.

Associations of pesticide residue exposure from fruit and vegetable intake with ovarian reserve.

Background: We previously reported that the intake of fruits and vegetables (FV) known to have high pesticide contamination in the US food supply is related to lower sperm counts. Whether the same is true for ovarian reserve is unknown.

Methods: Participants were 633 females, 21-45 years, presenting to an academic fertility center.

Subsequent pregnancies in the IMPAACT 2010/VESTED Trial: high rate of adverse outcomes in women living with HIV.

Introduction: Women with HIV (WHIV) have higher risks of adverse pregnancy outcomes, particularly in the absence of antiretroviral treatment(ART), and timing of ART may impact risk.

Methods: In IMPAACT 2010 (VESTED), 643 pregnant WHIV in 9 countries were randomized 1:1:1 to initiate ART: dolutegravir (DTG)+emtricitabine(FTC)/tenofovir alafenamide(TAF); DTG+FTC/tenofovir disoproxil fumarate (TDF) or efavirenz (EFV)/FTC/TDF. We describe adverse pregnancy outcomes in women with a subsequent pregnancy during 50 weeks of postpartum follow-up: spontaneous abortion (<20 weeks), stillbirth (≥20 weeks), preterm delivery (<37 weeks) and small-for-gestational-age (SGA).