Using NIRS-Based Spectroscopy for the Comparison of Cerebral Net-Water Uptake and Microcirculation in Posttraumatic Penumbra in Severe Traumatic Brain Injury Patients.

Purpose: The aim of our study was to compare net-water uptake (NWU), which serves as a quantitative imaging marker of cerebral edema, with brain oxygen status and cerebral microcirculation changes in posttraumatic peri-ischemic foci (PIF) in severe traumatic brain injury (sTBI) patients.

Materials And Methods: 89 sTBI patients (women 35; men 54, age 37 years [25;47]) with unilateral frontal/frontotemporal lesions were included in this retrospective, non-randomized, single-center study. Cerebral blood flow (CBF), cerebral blood volume (CBV), delay time (DT), time to maximum contrast concentration (Tmax), and mean transit time (MTT) were measured in PIF and determined using dynamic perfusion computed tomography (PCT) in the first 2 days after trauma and admission.

CRISPR-based therapeutic genome editing for inherited blood disorders.

Therapeutic genome editing promises to transform medicine. Pivotal discoveries have provided a diverse and versatile set of tools to correct pathogenic mutations or produce protective alleles using CRISPR-based technologies. These innovative therapies are especially adaptable for blood and immune disorders, where clinical methods allow haematopoietic stem cells (HSCs) to be mobilized, harvested, engineered ex vivo and transplanted back into a patient to permanently replace their blood system.

AI-driven predictive biomarker discovery with contrastive learning to improve clinical trial outcomes.

Modern clinical trials can capture tens of thousands of clinicogenomic measurements per individual. Discovering predictive biomarkers, as opposed to prognostic markers, remains challenging. To address this, we present a neural network framework based on contrastive learning-the Predictive Biomarker Modeling Framework (PBMF)-that explores potential predictive biomarkers in an automated, systematic, and unbiased manner.

Predicting 1p/19q Codeletion Status in Glioma Using MRI-Derived Radiomics: A Systematic Review and Meta-Analysis of Diagnostic Accuracy.

Background: The 1p/19q codeletion is a key genetic marker in gliomas and plays a crucial role in prognosis and treatment decisions. Traditional methods for detecting this genetic alteration rely on invasive tissue biopsies.

Purpose: This systematic review and meta-analysis aimed to evaluate the performance of MRI-derived radiomics-based models to predict glioma 1p/19q codeletion status.

Adherence to Pharmacological Treatment in Chronic Venous Disease: Results of a Real-World, Prospective, Observational Cohort Study.

Chronic venous disease (CVeD) affects millions of patients globally, being a multifactorial progressive condition that significantly impacts the quality of life of individuals. Micronized Purified Flavonoid Fraction (MPFF) is the most utilized and studied venoactive drug because of its safety and effectiveness. This study is a real-world, prospective, observational, multicenter cohort study including patients diagnosed with CVeD who were receiving one tablet of MPFF 1000 mg/day for at least one month and who visited medical facilities in Romania in June-July 2022.

Biotechnology research security: challenges in Latin America.

Biotechnology research presents significant security challenges in Latin America. Protecting intellectual property, managing risk associated with dual-use technologies, and upholding research integrity and ethics are particularly challenging in emerging countries due to resource constraints, political instability, and regulatory shortcomings. Regional efforts are needed to foster secure research environments.

Preparing Surrogates for Decision-Making: Development and Pilot Testing of Prepare for Their Care.

Context: Surrogate decision-makers have expressed the need for better preparation around communication and medical decision-making.

Objectives: This mixed-methods feasibility study aimed to assess the feasibility and usability of an online program to prepare surrogates for their role.

Methods: We developed a 2-part program for surrogates called PREPARE For THEIR Care with a diverse group of Community Advisory Board members and caregivers recruited from the National Patient Advocacy Foundation.

Gene editing without ex vivo culture evades genotoxicity in human hematopoietic stem cells.

Gene editing the BCL11A erythroid enhancer is a validated approach to fetal hemoglobin (HbF) induction for β-hemoglobinopathy therapy, though heterogeneity in edit allele distribution and HbF response may impact its safety and efficacy. Here, we compare combined CRISPR-Cas9 editing of the BCL11A +58 and +55 enhancers with leading gene modification approaches under clinical investigation. Dual targeting of the BCL11A +58 and +55 enhancers with 3xNLS-SpCas9 and two single guide RNAs (sgRNAs) resulted in superior HbF induction, including in sickle cell disease (SCD) patient xenografts, attributable to simultaneous disruption of core half E-box/GATA motifs at both enhancers.

UBR1 Promotes Sex-Dependent ACE2 Ubiquitination in Hypertension.

Background: Ang-II (angiotensin II) impairs the function of the antihypertensive enzyme ACE2 (angiotensin-converting enzyme 2) by promoting its internalization, ubiquitination, and degradation, thus contributing to hypertension. However, few ACE2 ubiquitination partners have been identified, and their role in hypertension remains unknown.

Methods: Proteomics and bioinformatic analyses were used to identify ACE2 ubiquitination partners in the brain, heart, and kidney of hypertensive C57BL6/J mice of both sexes.

Global trends in antibiotic consumption during 2016-2023 and future projections through 2030.

Antibiotic resistance is a global public health threat. Many factors contribute to this issue, with human antibiotic consumption being significant among them. Analyzing trends and patterns in consumption can aid in developing policies to mitigate the burden of antimicrobial resistance and global disparities in access to antibiotics.

Detecting context dependence in the expression of life history trade-offs.

Life history trade-offs are one of the central tenets of evolutionary demography. Trade-offs, depicting negative covariances between individuals' life history traits, can arise from genetic constraints, or from a finite amount of resources that each individual has to allocate in a zero-sum game between somatic and reproductive functions. While theory predicts that trade-offs are ubiquitous, empirical studies have often failed to detect such negative covariances in wild populations.

Sustained Cognitive Improvement in Alzheimer's Disease Patients Following a Precision Medicine Protocol: Case Series.

Arguably, the most important parameter in treating cognitive decline associated with Alzheimer's disease is the length of time in which improvement, if achieved at all, is sustained. However, monotherapies such as donepezil and memantine are associated with a more rapid decline than no treatment in patients over multi-year follow-ups. Furthermore, anti-amyloid antibody treatment, which at best simply slows decline, is associated with accelerated cerebral atrophy, resulting in earlier dementia-associated brain volumes for those treated at the MCI stage than untreated patients.

KLS-13019, a Novel Structural Analogue of Cannabidiol and GPR55 Receptor Antagonist, Prevents and Reverses Chemotherapy-Induced Peripheral Neuropathy in Rats.

Neuropathic pain is a form of chronic pain that develops because of damage to the nervous system. Treatment of neuropathic pain is often incompletely effective, and most available therapeutics have only moderate efficacy and present side effects that limit their use. Opioids are commonly prescribed for the management of neuropathic pain despite equivocal results in clinical studies and significant abuse potential.

The economic case for scaling up health research and development: Lessons from the COVID-19 pandemic.

In response to the COVID-19 pandemic, governments directly funded vaccine research and development (R&D), quickly leading to multiple effective vaccines and resulting in enormous health and economic benefits to society. We develop a simple economic model showing this feat could potentially be repeated for other health challenges. Based on inputs from the economic and medical literatures, the model yields estimates of optimal R&D spending on treatments and vaccines for known diseases.

TRIM35 Monoubiquitinates H2B in Cardiac Cells, Implications for Heart Failure.

Background: The tumor suppressor and proapoptotic transcription factor P53 is induced (and activated) in several forms of heart failure, including cardiotoxicity and dilated cardiomyopathy; however, the precise mechanism that coordinates its induction with accessibility to its transcriptional promoter sites remains unresolved, especially in the setting of mature terminally differentiated (nonreplicative) cardiomyocytes.

Methods: Male and female control or TRIM35 (tripartite motif containing 35) overexpression adolescent (aged 1-3 months) and adult (aged 4-6 months) transgenic mice were used for all in vivo experiments. Primary adolescent or adult mouse cardiomyocytes were isolated from control or TRIM35 overexpression transgenic mice for all in vitro experiments.

Enhancing prime editing in hematopoietic stem and progenitor cells by modulating nucleotide metabolism.

Therapeutic prime editing of hematopoietic stem and progenitor cells (HSPCs) holds great potential to remedy blood disorders. Quiescent cells have low nucleotide levels and resist retroviral infection, and it is possible that nucleotide metabolism could limit reverse transcription-mediated prime editing in HSPCs. We demonstrate that deoxynucleoside supplementation and Vpx-mediated degradation of SAMHD1 improve prime editing efficiency in HSPCs, especially when coupled with editing approaches that evade mismatch repair.

Near-Infrared II Photobiomodulation Preconditioning Ameliorates Stroke Injury via Phosphorylation of eNOS.

Background: The current management of patients with stroke with intravenous thrombolysis and endovascular thrombectomy is effective only when it is timely performed on an appropriately selected but minor fraction of patients. The development of novel adjunctive therapy is highly desired to reduce morbidity and mortality with stroke. Since endothelial dysfunction is implicated in the pathogenesis of stroke and is featured with suppressed endothelial nitric oxide synthase (eNOS) with concomitant nitric oxide deficiency, restoring endothelial nitric oxide represents a promising approach to treating stroke injury.

Circadian Regulation of Cardiac Arrhythmias and Electrophysiology.

Circadian rhythms in physiology and behavior are ≈24-hour biological cycles regulated by internal biological clocks (ie, circadian clocks) that optimize organismal homeostasis in response to predictable environmental changes. These clocks are present in virtually all cells in the body, including cardiomyocytes. Many decades ago, clinicians and researchers became interested in studying daily patterns of triggers for sudden cardiac death, the incidence of sudden cardiac death, and cardiac arrhythmias.

Cost of care for Alzheimer's disease and related dementias in the United States: 2016 to 2060.

Medical and long-term care for Alzheimer's disease and related dementias (ADRDs) can impose a large economic burden on individuals and societies. We estimated the per capita cost of ADRDs care in the in the United States in 2016 and projected future aggregate care costs during 2020-2060. Based on a previously published methodology, we used U.

Internal mammary artery injury complicating a Surfacer inside-out central venous catheterization.

We report the case of a near fatal arterial injury in a patient undergoing an inside-out catheter placement through an occluded central venous system using the Surfacer device (Bluegrass Vascular). The right internal mammary artery was inadvertently lacerated during the procedure, leading to cardiovascular collapse. The patient was rescued by transfusion, placement of a chest tube, and coil embolization of the right internal mammary artery.

Partnering to cope with pain: A pilot study of a caregiver-assisted pain coping skills intervention for patients with cognitive impairment and dementia.

Objective: To develop a new caregiver-assisted pain coping skills training protocol specifically tailored for community-dwelling persons with cognitive impairment and pain, and assess its feasibility and acceptability.

Method: In Phase I, we conducted interviews with 10 patient-caregiver dyads to gather feedback about intervention content and delivery. Phase II was a single-arm pilot test to evaluate the intervention's feasibility and acceptability.