Engaging dystonia networks with subthalamic stimulation.

Deep brain stimulation is an efficacious treatment for dystonia. While the internal pallidum serves as the primary target, recently, stimulation of the subthalamic nucleus (STN) has been investigated. However, optimal targeting within this structure and its surroundings have not been studied in depth.

Medication adherence in rheumatoid arthritis: implications for cardiovascular disease risk and strategies to address in U.S. Veterans.

Introduction: Rheumatoid arthritis (RA) is a systemic inflammatory disease associated with an increased risk of cardiovascular disease (CVD) and premature mortality. The risk of CVD is closely associated with RA disease activity, and achieving RA remission using disease-modifying anti-rheumatic drugs (DMARDs) can significantly mitigate this risk. However, despite the availability of highly effective DMARDs, many veterans fail to achieve sustained RA remission.

Left Ventricular Assist Device Therapy in Cold and Dry Patients.

Background: Patients with end-stage heart failure and low pulmonary capillary wedge pressure are referred to as cold and dry and represent an understudied minority in whom the benefit of left ventricular assist device (LVAD) therapy is unclear.

Methods: Adults receiving LVADs between 2006 and 2017 in the Interagency Registry for Mechanically Assisted Circulatory Support database were classified as cold and wet (pulmonary capillary wedge pressure >15 mm Hg) and cold and dry (pulmonary capillary wedge pressure ≤15 mm Hg) based on pre-LVAD hemodynamics obtained via right heart catheterization. The primary outcome was 1-year survival.

Lung Endothelial Cell Heterogeneity in Health and Pulmonary Vascular Disease.

Lung endothelial cells (ECs) are essential for maintaining organ function and homeostasis. Despite sharing some common features with ECs from organ systems, lung ECs exhibit significant heterogeneity in morphology, function, and gene expression. This heterogeneity is increasingly recognized as a key contributor to the development of pulmonary diseases like pulmonary hypertension (PH).

Brentuximab Vedotin Combination for Relapsed Diffuse Large B-Cell Lymphoma.

Purpose: In patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL), brentuximab vedotin (BV) as monotherapy or combined with either lenalidomide (Len) or rituximab (R) has demonstrated efficacy with acceptable safety. We evaluated the efficacy and safety of BV + Len + R versus placebo + Len + R in patients with R/R DLBCL.

Methods: ECHELON-3 is a randomized, double-blind, placebo-controlled, multicenter, phase 3 trial comparing BV + Len + R with placebo + Len + R in patients with R/R DLBCL.

Single-Cell Analysis in Cerebrovascular Research: Primed for Breakthroughs and Clinical Impact.

Data generated using single-cell RNA-sequencing has the potential to transform understanding of the cerebral circulation and advance clinical care. However, the high volume of data, sometimes generated and presented without proper pathophysiological context, can be difficult to interpret and integrate into current understanding of the cerebral circulation and its disorders. Furthermore, heterogeneity in the representation of brain regions and vascular segments makes it difficult to compare results across studies.

Whole-Body MRI in Children: Concepts and Controversies- Expert Panel Narrative Review.

The use of whole-body MRI (WBMRI) in children, from infancy to adolescence, has expanded rapidly over the past decade, with increasing uptake and a broadening range of clinical indications. Current indications include screening for presymptomatic lesions in cancer predisposition syndromes; tumor staging in known malignancies; investigating fevers of unknown origin; as well as diagnosing and monitoring rheumatologic diseases, vascular anomalies and neuromuscular disorders. This AJR Expert Panel Narrative Review aims to offer a comprehensive discussion of WBMRI in pediatric patients, exploring protocols and other technical considerations, clinical indications, implementation challenges and troubleshooting, as well as controversies in widespread adoption, while considering emerging trends and directions.

The 'Oma's of the Gammas-Cancerogenesis by γ-Herpesviruses.

Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), which are the only members of the gamma(γ) herpesviruses, are oncogenic viruses that significantly contribute to the development of various human cancers, such as Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's lymphoma, Kaposi's sarcoma, and primary effusion lymphoma. Oncogenesis triggered by γ-herpesviruses involves complex interactions between viral genetics, host cellular mechanisms, and immune evasion strategies. At the genetic level, crucial viral oncogenes participate in the disruption of cell signaling, leading to uncontrolled proliferation and inhibition of apoptosis.

Seroprevalence of Antibodies to Filoviruses with Outbreak Potential in Sub-Saharan Africa: A Systematic Review to Inform Vaccine Development and Deployment.

: Orthoebolaviruses and orthomarburgviruses are filoviruses that can cause viral hemorrhagic fever and significant morbidity and mortality in humans. The evaluation and deployment of vaccines to prevent and control Ebola and Marburg outbreaks must be informed by an understanding of the transmission and natural history of the causative infections, but little is known about the burden of asymptomatic infection or undiagnosed disease. This systematic review of the published literature examined the seroprevalence of antibodies to orthoebolaviruses and orthomarburgviruses in sub-Saharan Africa.

The Association of Dietary Polyamines with Mortality and the Risk of Cardiovascular Disease: A Prospective Study in UK Biobank.

Background: Polyamines, including spermidine (SPD), spermine (SPM) and putrescine (PUT), are essential for cellular physiology and various cellular processes. This study aimed to examine the associations of dietary polyamines intake and all-cause mortality and incident cardiovascular disease (CVD).

Methods: This prospective cohort study included 184,732 participants without CVD at baseline from the UK Biobank who had completed at least one dietary questionnaire.

The Potential Application of Resveratrol and Its Derivatives in Central Nervous System Tumors.

Resveratrol, a naturally occurring polyphenolic compound found in various plants, has been extensively studied for its broad spectrum of beneficial biological effects. These encompass its potent antioxidant properties, anti-inflammatory activities, anti-aging capabilities, cardioprotective functions, and neuroprotective potential. The diverse biological actions of resveratrol extend beyond these well-established properties.

Catheter Ablation in Atrial Fibrillation: Recent Advances.

Atrial fibrillation (AF) is the leading cause of arrhythmia-related morbidity and mortality. Recurrent symptoms, hospitalizations, and cost burden to patients have necessitated treatments beyond antiarrhythmic drugs (AADs) for patients with AF. Catheter ablation has proven to be effective over medical therapy alone; however the recurrence rates for atrial tachyarrhythmias post-ablation remain significant, particularly in patients with persistent and long-standing persistent AF.

A Practical Clinical Approach to Navigate Pulmonary Embolism Management: A Primer and Narrative Review of the Evolving Landscape.

Advances in imaging, pharmacological, and procedural technologies have rapidly expanded the care of pulmonary embolism. Earlier, more accurate identification and quantification has enhanced risk stratification across the spectrum of the disease process, with a number of clinical tools available to prognosticate outcomes and guide treatment. Direct oral anticoagulants have enabled a consistent and more convenient long-term therapeutic option, with a greater shift toward outpatient treatment for a select group of low-risk patients.

The Biomechanics of Fibrillin Microfibrils: Lessons from the Ciliary Zonule.

Marfan syndrome is an inherited connective tissue disorder that affects the cardiovascular, musculoskeletal, and ocular systems. It is caused by pathogenic variants in the fibrillin-1 gene (). Fibrillin is a primary component of microfibrils, which are found throughout the extracellular matrix (ECM) and provide elasticity and resilience to connective tissue.

Experimental Pain Sensitivity and Parental Pain Catastrophizing.

Background/objectives: Variability in biopsychosocial factors can explain the interindividual variability in pain. One factor that can impact pain is the pain catastrophizing level. Interestingly, parental pain catastrophizing is related to the severity of the clinical pain of their children.

Bile Acids in Inflammatory Bowel Disease: From Pathophysiology to Treatment.

Inflammatory bowel disease (IBD) is a chronic condition that affects about 7 million people worldwide, and new therapies are needed. Understanding the complex roles that bile acids (BAs) play in IBD may lead to the development of novel IBD treatments independent of direct immunosuppression. This review discusses the latest discoveries in the roles BAs play in IBD pathogenesis and explores how these discoveries offer promising new therapeutic targets to treat IBD and improve patient outcomes.

Gut Microbial Dysbiosis and Implications in Solid Organ Transplantation.

The gut microbiome has been shown to play a significant role in solid organ transplantation, potentially influencing graft function and patient outcomes. Dysbiosis, characterized by reduced microbial diversity and an increase in pathogenic taxa, has been linked to higher incidences of allograft rejection, graft dysfunction, and post-transplant mortality. Several studies suggest that the gut microbiome might be able to serve as both a biomarker and a therapeutic target, potentially guiding personalized immunosuppressive therapies and other interventions to improve outcomes after solid organ transplantation.

Conventional Cytogenetic Analysis of Solid Tumor Abnormalities: A 25-Year Review of Proficiency Test Results from the College of American Pathologists/American College of Medical Genetics and Genomics Cytogenetics Committee.

The joint College of American Pathologists/American College of Medical Genetics and Genomics Cytogenetics Committee works to ensure the competency and proficiency of clinical cytogenetic testing laboratories through proficiency testing (PT) programs for various clinical tests offered by such laboratories, including the evaluation of cytogenetic abnormalities in solid tumors. Review and analyze 25 years (1999-2023) of solid tumor chromosome analysis PT results, utilizing G-banded karyograms. A retrospective review of results from 1999 to 2023 was performed, identifying the challenges addressing solid tumors.

Rapid Detection of Fusions in Acute Promyelocytic Leukemia: CRISPR/Cas9 Nanopore Sequencing with Adaptive Sampling.

Acute promyelocytic leukemia (APL) accounts for approximately 10-15% of newly diagnosed acute myeloid leukemia cases and presents with coagulopathy and bleeding. Prompt diagnosis and treatment are required to minimize early mortality in APL as initiation of all-trans retinoic acid therapy rapidly reverses coagulopathy. The fusion is a hallmark of APL and its rapid identification is essential for rapid initiation of specific treatment to prevent early deaths from coagulopathy and bleeding and optimize patient outcomes.

The Effects of Aldosterone on Hypertension-Associated Kidney Injury in a Tg-hAS Mouse Model.

Hypertension remains a global health challenge due to its high prevalence and association with premature morbidity and mortality. Aldosterone, a mineralocorticoid hormone, and its receptor, the mineralocorticoid receptor (MR), are highly implicated in hypertension pathogenesis. Aldosterone synthase is the sole enzyme responsible for producing aldosterone in humans.

Senescent brain cell types in Alzheimer's disease: Pathological mechanisms and therapeutic opportunities.

Cellular senescence is a cell state triggered by programmed physiological processes or cellular stress responses. Stress-induced senescent cells often acquire pathogenic traits, including a toxic secretome and resistance to apoptosis. When pathogenic senescent cells form faster than they are cleared by the immune system, they accumulate in tissues throughout the body and contribute to age-related diseases, including neurodegeneration.

Plasma brain-related biomarkers and potential therapeutic targets in pediatric ECMO.

Extracorporeal membrane oxygenation (ECMO) is a technique used to support severe cardiopulmonary failure. Its potential life-saving benefits are tempered by the significant risk for acute brain injury (ABI), from both primary pathophysiologic factors and ECMO-related complications through central nervous system cellular injury, blood-brain barrier dysfunction (BBB), systemic inflammation and neuroinflammation, and coagulopathy. Plasma biomarkers are an emerging tool used to stratify risk for and diagnose ABI, and prognosticate neurofunctional outcomes.

The Ability of Healthcare Professionals to Predict Patient Outcomes Following Bariatric Surgery.

Introduction: Patients with obesity seeking bariatric surgery undergo an extensive evaluation by a multidisciplinary team of healthcare professionals' (HCPs) to assess patient compliance among other factors and determine their eligibility for surgery. However, the HCPs' assessments are not devoid of bias that may affect eligibility and preoperative decisions. This study aimed to investigate team members' ability to predict patient outcomes following bariatric surgery.

Prognostic significance of serum complement activation, neutrophil extracellular traps and extracellular DNA in newly diagnosed epithelial ovarian cancer.

Purpose: We observed that the tumor microenvironment (TME) in metastatic epithelial ovarian cancer (EOC) and in other solid tumors can reprogram normal neutrophils to acquire a complement-dependent suppressor phenotype characterized by inhibition of stimulated T cell activation. This study aims to evaluate whether serum markers of neutrophil activation and complement at diagnosis of EOC would be associated with clinical outcomes.

Experimental Design: We conducted a two-center prospective study of patients with newly diagnosed EOC (N = 188).