Integrating molecular and cellular components of endothelial shear stress mechanotransduction.

The lining of blood vessels is constantly exposed to mechanical forces exerted by blood flow against the endothelium. Endothelial cells detect these tangential forces (i.e.

Should Prophylactic Endotracheal Intubation Be Performed in Upper Gastrointestinal Bleeding?

No consensus exists on the standard of intraoperative airway management approach to prevent endoscopy complications in acute gastrointestinal (GI) bleeding. Eight years after our initial meta-analysis, we reassessed the effect of prophylactic endotracheal intubation in acute GI bleeding in hospitalized patients. Multiple databases were reviewed in 2024, identifying 10 studies that compared prophylactic endotracheal intubation (PEI) versus no intubation in acute upper GI bleeding in hospitalized patients.

Single Chelator-Minibody Theranostic Agents for Zr PET Imaging and Lu Radiopharmaceutical Therapy of PSMA-Expressing Prostate Cancer.

Here we describe an anti-prostate-specific membrane antigen (PSMA) minibody (IAB2MA) conjugated to an octadentate, macrocyclic chelator based on four 1-hydroxypyridin-2-one coordinating units (Lumi804 [L804]) labeled with Zr (PET imaging) and Lu (radiopharmaceutical therapy), with the goal of developing safer and more efficacious treatment options for prostate cancer. L804 was compared with the current gold standard chelators, DOTA and deferoxamine (DFO), conjugated to IAB2MA for radiolabeling with Lu and Zr in cell binding, preclinical biodistribution, imaging, dosimetry, and efficacy studies in the PSMA-positive PC3-PIP tumor-bearing mouse model of prostate cancer. Quantitative radiolabeling (>99% radiochemical yield) of L804-IAB2MA with Lu or Zr was achieved at ambient temperature in under 30 min, comparable to Zr labeling of DFO-IAB2MA.

Posttraumatic Stress Disorder and Type 2 Diabetes Outcomes in Veterans.

Importance: Posttraumatic stress disorder (PTSD) symptom reduction is linked with lower risk of incident type 2 diabetes (T2D), but little is known about the association between PTSD and comorbid T2D outcomes. Whether PTSD is a modifiable risk factor for adverse T2D outcomes is unknown.

Objective: To determine whether patients with PTSD who improved and no longer met diagnostic criteria for PTSD had a lower risk of adverse T2D outcomes compared with patients with persistent PTSD.

ADAR1 Is Essential for Smooth Muscle Homeostasis and Vascular Integrity.

Vascular smooth muscle cells (VSMCs) play a critical role in maintaining vascular integrity. VSMC dysfunction leads to numerous vascular diseases. Adenosine deaminases acting on RNA 1 (ADAR1), an RNA editing enzyme, has shown both RNA editing and non-editing functions.

Evaluation of a bimodal, matched pair theranostic agent targeting prostate-specific membrane antigen.

Background: Prostate cancer affects 1 in 6 men, and it is the second‑leading cause of cancer-related death in American men. Surgery is one of the main treatment modalities for prostate cancer, but it often results in incomplete resection margins or complete resection that leads to nerve damage and undesirable side effects. In the present work, we have developed a new bimodal tracer, NODAGA-sCy7.

Targeting AKR1B10 by Drug Repurposing with Epalrestat Overcomes Chemoresistance in Non-Small Cell Lung Cancer Patient-Derived Tumor Organoids.

Purpose: Systemic treatments given to patients with non-small cell lung cancer (NSCLC) are often ineffective due to drug resistance. In the present study, we investigated patient-derived tumor organoids (PDTO) and matched tumor tissues from surgically treated patients with NSCLC to identify drug repurposing targets to overcome resistance toward standard-of-care platinum-based doublet chemotherapy.

Experimental Design: PDTOs were established from 10 prospectively enrolled patients with non-metastatic NSCLC from resected tumors.

When to feed after percutaneous endoscopic gastrostomy: A systematic review and meta-analysis of randomized controlled trials.

Background: Initiation of feeding after percutaneous endoscopic gastrostomy (PEG) placement has been debated. Randomized controlled trials (RCTs) have been performed on early feeding compared with delayed feeding after PEG placement with varying results. Therefore, a meta-analysis was conducted examining early vs delayed feeding after placement of a PEG.

Individualized high-resolution analysis to categorize diverse learning and memory deficits in tau rTg4510 mice exposed to low-intensity blast.

Mild traumatic brain injury (mTBI) resulting from low-intensity blast (LIB) exposure in military and civilian individuals is linked to enduring behavioral and cognitive abnormalities. These injuries can serve as confounding risk factors for the development of neurodegenerative disorders, including Alzheimer's disease-related dementias (ADRD). Recent animal studies have demonstrated LIB-induced brain damage at the molecular and nanoscale levels.

PAI-1 Regulates the Cytoskeleton and Intrinsic Stiffness of Vascular Smooth Muscle Cells.

Background: Plasma concentration of PAI-1 (plasminogen activator inhibitor-1) correlates with arterial stiffness. Vascular smooth muscle cells (SMCs) express PAI-1, and the intrinsic stiffness of SMCs is a major determinant of total arterial stiffness. We hypothesized that PAI-1 promotes SMC stiffness by regulating the cytoskeleton and that pharmacological inhibition of PAI-1 decreases SMC and aortic stiffness.

Chronic intermittent hypoxia facilitates the development of angiotensin II-induced abdominal aortic aneurysm in male mice.

Obstructive sleep apnea (OSA), characterized by episodes of intermittent hypoxia (IH), is highly prevalent in patients with abdominal aortic aneurysm (AAA). However, whether IH serves as an independent risk factor for AAA development remains to be investigated. Here, we determined the effects of chronic (6 mo) IH on angiotensin (Ang II)-induced AAA development in C57BL/6J male mice and investigated the underlying mechanisms of IH in cultured vascular smooth muscle cells (SMCs).

Effect of acute intranasal insulin administration on muscle sympathetic nerve activity in healthy young adults.

Systemic insulin increases muscle sympathetic nerve activity (MSNA) via both central actions within the brainstem and peripheral activation of the arterial baroreflex. Augmented MSNA during hyperinsulinemia likely restrains peripheral vasodilation and contributes to the maintenance of blood pressure (BP). However, in the absence of insulin action within the peripheral vasculature, whether central insulin stimulation increases MSNA and influences peripheral hemodynamics in humans remains unknown.

CISD3/MiNT is required for complex I function, mitochondrial integrity, and skeletal muscle maintenance.

Mitochondria play a central role in muscle metabolism and function. A unique family of iron-sulfur proteins, termed CDGSH Iron Sulfur Domain-containing (CISD/NEET) proteins, support mitochondrial function in skeletal muscles. The abundance of these proteins declines during aging leading to muscle degeneration.

Expanding landscape of coronary microvascular disease in co-morbid conditions: Metabolic disease and beyond.

Coronary microvascular disease (CMD) and impaired coronary blood flow control are defects that occur early in the pathogenesis of heart failure in cardiometabolic conditions, prior to the onset of atherosclerosis. In fact, recent studies have shown that CMD is an independent predictor of cardiac morbidity and mortality in patients with obesity and metabolic disease. CMD is comprised of functional, structural, and mechanical impairments that synergize and ultimately reduce coronary blood flow in metabolic disease and in other co-morbid conditions, including transplant, autoimmune disorders, chemotherapy-induced cardiotoxicity, and remote injury-induced CMD.

Elevating theranostics: The emergence and promise of radiopharmaceutical cell-targeting heterodimers in human cancers.

Optimal therapeutic and diagnostic efficacy is essential for healthcare's global mission of advancing oncologic drug development. Accurate diagnosis and detection are crucial prerequisites for effective risk stratification and personalized patient care in clinical oncology. A paradigm shift is emerging with the promise of multi-receptor-targeting compounds.

Albumin-Binding Lutetium-177-Labeled LLP2A Derivatives as Theranostics for Melanoma.

Very late antigen-4 (VLA-4) is a transmembrane integrin protein that is highly expressed in aggressive forms of metastatic melanoma. A small-molecule peptidomimetic, LLP2A, was found to have a low pM affinity binding to VLA-4. Because LLP2A itself does not inhibit cancer cell proliferation and survival, it is an ideal candidate for the imaging and delivery of therapeutic payloads.

Blast injury: Impact to the cornea.

Visual disorders are common even after mild traumatic brain injury (mTBI) or blast exposure. The cost of blast-induced vision loss in civilians, military personnel, and veterans is significant. The visual consequences of blasts associated with TBI are elusive.

Targeted Therapy for Highly Desmoplastic and Immunosuppressive Tumor Microenvironment of Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a very poor prognosis. Despite advancements in treatment strategies, PDAC remains recalcitrant to therapies because patients are often diagnosed at an advanced stage. The advanced stage of PDAC is characterized by metastasis, which typically renders it unresectable by surgery or untreatable by chemotherapy.

Age and Sex in the Development of Hepatic Encephalopathy: Role of Alcohol.

Hepatic encephalopathy (HE) is a neurological condition linked to liver failure. Acute HE (Type A) occurs with acute liver failure, while chronic HE (Type C) is tied to cirrhosis and portal hypertension. HE treatments lag due to gaps in understanding its development by gender and age.

Identifying gene expression programs in single-cell RNA-seq data using linear correlation explanation.

Objective: Gene expression analysis through single-cell RNA sequencing (scRNA-seq) has revolutionized our understanding of gene regulation in diverse cell types, tissues, and organisms. While existing methods primarily focus on identifying cell type-specific gene expression programs (GEPs), the characterization of GEPs associated with biological processes and stimuli responses remains limited. In this study, we aim to infer biologically meaningful GEPs that are associated with both cellular phenotypes and activity programs directly from scRNA-seq data.

Hemoadsorption: consensus report of the 30th Acute Disease Quality Initiative workgroup.

Adsorption-based extracorporeal therapies have been subject to technical developments and clinical application for close to five decades. More recently, new technological developments in membrane and sorbent manipulation have made it possible to deliver more biocompatible extracorporeal adsorption therapies to patients with a variety of conditions. There are several key rationales based on physicochemical principles and clinical considerations that justify the application and investigation of such therapies as evidenced by multiple ex vivo, experimental and clinical observations.