Endovascular Thrombectomy for Extracranial Internal Carotid Artery Occlusions With Large Ischemic Strokes: Insights From the SELECT2 Trial.

Background And Objectives: Although previous trials have established the efficacy and safety of endovascular thrombectomy (EVT) in large ischemic core strokes, most of them excluded patients with extracranial internal carotid artery (e-ICA) occlusion. We aimed to compare outcomes in patients with e-ICA occlusion and large ischemic core infarcts treated with EVT vs medical management (MM).

Methods: This was a secondary analysis of the SELECT2 trial, a randomized controlled trial conducted at 31 international sites.

Ciliary Body Medulloepithelioma: Clinical and Pathologic Challenges with a Focus on Molecular Genetics.

Objective: Ciliary body medulloepithelioma (CBME), a pediatric intraocular tumor with potential for locally aggressive behavior and metastasis, may present with a diverse spectrum of clinical and histopathologic features leading to diagnostic and management challenges. Examination of unusual CBME cases highlights challenges and modern diagnostic techniques which facilitate accurate diagnosis and guide management.

Methods: A retrospective clinicopathologic analysis of 6 patients with unusual clinical or pathologic features of CBME was performed.

CaML: Chemistry-informed machine learning explains mutual changes between protein conformations and calcium ions in calcium-binding proteins using structural and topological features.

Proteins' flexibility is a feature in communicating changes in cell signaling instigated by binding with secondary messengers, such as calcium ions, associated with the coordination of muscle contraction, neurotransmitter release, and gene expression. When binding with the disordered parts of a protein, calcium ions must balance their charge states with the shape of calcium-binding proteins and their versatile pool of partners depending on the circumstances they transmit. Accurately determining the ionic charges of those ions is essential for understanding their role in such processes.

The hypercapnic environment on the International Space Station (ISS): A potential contributing factor to ocular surface symptoms in astronauts.

With increasing advancements and efforts towards space exploration, there is a pressing need to understand the impacts of spaceflight on astronauts' health. Astronauts have reported signs and symptoms of dry eye disease upon traveling to the International Space Station (ISS), thus necessitating an evaluation of the factors that contribute to the onset of spaceflight associated dry eye disease. Prior literature describes the hypercapnic environment of the ISS; however, the link between the high CO levels and astronauts' symptoms of dry eye disease remains unexplored.

Effects of exercise and transient estradiol exposure in middle-aged female rats.

The benefits of estrogen treatment on cognition in middle-aged and older women are dependent on many factors, including the timing of treatment. Moreover, the potential interactive effects with other lifestyle factors, such as exercise, are poorly understood. In this study, we tested for lasting benefits of independent and combined treatment with estrogen and voluntary exercise initiated in midlife, using a rat model of menopause.

Enhancing Radiation Therapy Response in Prostate Cancer Through Metabolic Modulation by Mito-Lonidamine: A H and P Magnetic Resonance Spectroscopy Study.

Radiation therapy (RT) is the cornerstone treatment for prostate cancer; however, it frequently induces gastrointestinal and genitourinary toxicities that substantially diminish the patients' quality of life. While many individuals experience transient side effects, a subset endures persistent, long-term complications. A promising strategy to mitigate these toxicities involves enhancing tumor radiosensitivity, potentially allowing for lower radiation doses.

Mechanical thrombectomy in elderly stroke patients with low ASPECTS: insights from STAR.

Background: The elderly population (≥80 years) were underrepresented in recent trials of endovascular thrombectomy (EVT) for anterior circulation large vessel occlusion acute ischemic stroke (LVO-AIS) with low Alberta Stroke Program Early CT Score (ASPECTS) (≤5).

Methods: This study analyzed data from a prospectively maintained database of 37 thrombectomy centers. The primary cohort of the study comprised patients with LVO-AIS aged ≥80 who underwent EVT with ASPECTS≤5 from 2013 to 2023.

The association between county-level social determinants of health and cardio-kidney-metabolic disease attributed all-cause mortality in the US: A cross sectional analysis.

Background: The American Heart Association recently defined cardio-kidney-metabolic (CKM) syndrome as the intersection between metabolic, renal, and cardiovascular disease. Understanding the contemporary estimates of CKM related mortality in the US is essential for developing targeted public interventions.

Methods: We analyzed state-level and county-level CKM-associated all-cause mortality data (2010-2019) from the CDC Wide-ranging Online Data for Epidemiologic Research (WONDER).

Long-Term Management of Sleep Apnea-Hypopnea Syndrome: Efficacy and Challenges of Continuous Positive Airway Pressure Therapy-A Narrative Review.

Sleep apnea-hypopnea syndrome (SAHS) is a respiratory disorder characterized by cessation of breathing during sleep, resulting in daytime somnolence and various comorbidities. SAHS encompasses obstructive sleep apnea (OSA), caused by upper airway obstruction, and central sleep apnea (CSA), resulting from lack of brainstem signaling for respiration. Continuous positive airway pressure (CPAP) therapy is the gold standard treatment for SAHS, reducing apnea and hypopnea episodes by providing continuous airflow.

Harnessing the Potential of Human Breast Milk to Boost Intestinal Permeability for Nanoparticles and Macromolecules.

The intricate interplay between human breast milk, nanoparticles, and macromolecules holds promise for innovative nutritional delivery strategies. Compared to bovine milk and infant formula, this study explores human breast milk's role in modulating intestinal permeability and its impact on nanoparticle and macromolecule transport. Comparative analysis with bovine milk and infant formula reveals significant elevations in permeability with human breast milk, accompanied by a decrease in transepithelial electrical resistance, suggesting enhanced paracellular transport.

Exposomic Determinants of Atherosclerosis: Recent Evidence.

Purpose Of Review: The exposome refers to the total environmental exposures a person encounters throughout life, and its relationship with human health is increasingly studied. This non-systematic review focuses on recent research investigating the effects of environmental factors-such as air pollution, noise, greenspace, neighborhood walkability, and metallic pollutants-on atherosclerosis, a major cause of cardiovascular disease.

Recent Findings: Studies show that long-term exposure to airborne particulate matter can impair endothelial function and elevate adhesion molecule levels, leading to vascular damage.

Perceived Discrimination in the Healthcare Setting and Medical Mistrust: Findings from the Health Information National Trends Survey, 2022.

Background: Perceived discrimination and medical mistrust are barriers to care that impact both individual and population health.

Objective: This study aims to characterize the prevalence of perceived racial or ethnic discrimination in healthcare as well as mistrust in the medical system and explore their associations with race and ethnicity.

Design: Cross-sectional study of nationally representative data from the Health Information National Trends Survey (fielded March-November 2022).

MnSOD non-acetylation mimic knock-in mice exhibit dilated cardiomyopathy.

Manganese superoxide dismutase (MnSOD/SOD2) is an essential mitochondrial enzyme that detoxifies superoxide radicals generated during oxidative respiration. MnSOD/SOD2 lysine 68 acetylation (K68-Ac) is an important post-translational modification (PTM) that regulates enzymatic activity, responding to nutrient status or oxidative stress, and elevated levels have been associated with human illness. To determine the in vivo role of MnSOD-K68 in the heart, we used a whole-body non-acetylation mimic mutant (MnSOD) knock-in mouse.

The effect of the foreign body response on drug elution from subdermal delivery systems.

Contrasting findings are presented in the literature regarding the influence of foreign body response (FBR) on drug release from implantable drug delivery systems. To this end, here we sought direct evidence of the effect of the fibrotic tissue on subcutaneous drug release from long-acting drug delivery implants. Specifically, we investigated the pharmacokinetic impact of fibrotic encapsulation on a small molecule drug, islatravir (293 Da), and a large protein, IgG (150 kDa), administered via biocompatible implants.

Longitudinal host transcriptional responses to SARS-CoV-2 infection in adults with extremely high viral load.

Current understanding of viral dynamics of SARS-CoV-2 and host responses driving the pathogenic mechanisms in COVID-19 is rapidly evolving. Here, we conducted a longitudinal study to investigate gene expression patterns during acute SARS-CoV-2 illness. Cases included SARS-CoV-2 infected individuals with extremely high viral loads early in their illness, individuals having low SARS-CoV-2 viral loads early in their infection, and individuals testing negative for SARS-CoV-2.

ATXN10 Gene Expansions in Mexican Patients with Ataxia Without Epilepsy.

Spinocerebellar ataxia type 10 (SCA10) is an autosomal dominant (AD) neurodegenerative disorder prevalent in the Americas, particularly in Mexico. Clinical manifestations include progressive ataxia and epilepsy. However, it can exhibit wide phenotypic variability and even reduced penetrance.

Loss of Sirtuin 7 impairs cell motility and proliferation and enhances S-phase cell arrest after 5-fluorouracil treatment in head and neck cancer.

Sirtuin 7 (SIRT7), a member of the sirtuin family of NAD+-dependent deacetylases, plays a vital role in cancer, exhibiting context-dependent functions across various malignancies. Our study investigates the role of SIRT7 depletion in head and neck squamous cell carcinoma (HNSCC) progression. In vitro and 3D organotypic models demonstrated that SIRT7 knock-out attenuates cancer cell viability, proliferation, and motility as well as induces downregulation of migration- and epithelial-mesenchymal transition (EMT)-related gene expression.

The association between physician sex and patient outcomes: a systematic review and meta-analysis.

Background: Some prior studies have found that patients treated by female physicians may experience better outcomes, as well as lower healthcare costs than those treated by male physicians. Physician-patient sex concordance may also contribute to better patient outcomes. However, other studies have not identified a significant difference.

Reevaluating Anti-Inflammatory Therapy: Targeting Senescence to Balance Anti-Cancer Efficacy and Vascular Disease.

Modulating immune function is a critical strategy in cancer and atherosclerosis treatments. For cancer, boosting or maintaining the immune system is crucial to prevent tumor growth. However, in vascular disease, mitigating immune responses can decrease inflammation and slow atherosclerosis progression.

Cardiovascular Disease Risk in South Asians in the Baylor Scott and White Health DILWALE Registry.

Background: Despite implementation of preventive interventions targeting cardiovascular disease (CVD), atherosclerotic CVD (ASCVD) remains a major public health concern in the South Asian (SA) population.

Objectives: The purpose of this study was to assess the risk factor prevalence and ASCVD outcomes in SA population in the United States.

Methods: The DIL Wellness and Arterial health Longitudinal Evaluation registry collected data retrospectively on SA adult patients receiving care in the Baylor Scott & White Healthcare system.

Brain aging rejuvenation factors in adults with genetic and sporadic neurodegenerative disease.

The largest risk factor for dementia is age. Heterochronic blood exchange studies have uncovered age-related blood factors that demonstrate 'pro-aging' or 'pro-youthful' effects on the mouse brain. The clinical relevance and combined effects of these factors for humans is unclear.

Initiation and sequencing of guideline-directed medical therapy for heart failure across the ejection fraction spectrum.

Strong evidence supports the importance of rapid sequence or simultaneous initiation of quadruple guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) for substantially reducing risk of mortality and hospitalization. Barring absolute contraindications for each individual medication, employing the strategy of rapid sequence, simultaneous, and/or in-hospital initiation at the time of HF diagnosis best ensures patients with HFrEF have the opportunity to benefit from proven medications and achieve large absolute risk reductions for adverse clinical outcomes. However, despite guideline recommendations supporting this approach, implementation in clinical practice remains persistently low, with less than one-fifth of eligible patients being prescribed the quadruple GDMT regimen.

Content Validity of the Friedreich Ataxia Rating Scale in Patients with Spinocerebellar Ataxia.

Introduction: The Friedreich Ataxia Rating Scale-Activities of Daily Living (FARS-ADL) is a validated and highly utilized measure for evaluating patients with Friedreich Ataxia. While construct validity of FARS-ADL has been shown for spinocerebellar ataxia (SCA), content validity has not been established.

Methods: Individuals with SCA1 or SCA3 (n = 7) and healthcare professionals (HCPs) with SCA expertise (n = 8) participated in qualitative interviews evaluating the relevance, clarity, and clinical meaningfulness of FARS-ADL for assessment of individuals with SCA.