Impact of Anti-CD4 Autoantibodies on Immune Reconstitution in People With Advanced Human Immunodeficiency Virus.

Background: Despite suppressive antiretroviral therapy (ART), 15%-30% of people with human immunodeficiency virus (HIV) experience a limited recovery of CD4 T cells. Although autoantibodies against the CD4 receptor have previously been identified in people with HIV (PWH), little is known about their longitudinal impact on CD4 T-cell reconstitution.

Methods: Anti-CD4 autoantibodies were evaluated by the fluid-phase luciferase immunoprecipitation systems immunoassay in ART-naive people with advanced HIV (CD4 count ≤100 cells/µL), PWH with CD4 count >200 cells/µL, long-term nonprogressors, people with idiopathic CD4 lymphopenia, people with autoimmune lymphoproliferative syndrome, and healthy volunteers without HIV.

Aspirin modulates generation of procoagulant phospholipids in cardiovascular disease, by regulating LPCAT3.

Enzymatically oxygenated phospholipids (eoxPL) from lipoxygenases (LOX) or cyclooxygenase (COX) are prothrombotic. Their generation in arterial disease, and their modulation by cardiovascular therapies is unknown. Furthermore, the Lands cycle acyl-transferases that catalyze their formation are unidentified.

Characteristics and outcomes of adults with acute brain injuries admitted to intensive care units in Australia and New Zealand from 2013 to 2022.

Background: The characteristics and outcomes of patients with acute brain injuries admitted to the intensive care unit (ICU) in Australia and New Zealand (ANZ) are insufficiently described.

Objective: This study aimed to describe the epidemiology of acute brain injury in ICU patients in ANZ.

Methods: A binational retrospective cohort study was conducted using the ANZ Intensive Care Society Adult Patient Database.

Perplexing paradoxical reactions: navigating the complexity of protracted tuberculosis meningitis-a case report.

Tuberculous meningitis (TBM) has considerable mortality and morbidity, and it often presents therapeutic challenges when complicated by paradoxical reactions (PRs). Here, the clinical course of four cases of TBM patients complicated by PRs in a longitudinal TB cohort is described while also providing insights from the larger clinical cohort. Research flow cytometry, biomarker analysis, and drug concentrations were performed on available samples.

Prophylactic Antibiotics in Adults With Acute Brain Injury Who Are Invasively Ventilated in the ICU: A Systematic Review and Meta-Analysis.

Background: Lower respiratory tract infections are common in patients receiving invasive mechanical ventilation in an ICU after an acute brain injury and may have deleterious consequences.

Research Question: In adults with acute brain injury receiving invasive mechanical ventilation in an ICU, is the administration of prophylactic parenteral antibiotics, compared with placebo or usual care, associated with reduced mortality?

Study Design And Methods: We conducted a systematic review and meta-analysis. We searched for randomized clinical trials (RCTs) in electronic databases, as well as unpublished trials.

Critical role for platelet Ral GTPases in regulating venous thrombosis in mice.

Background: Deep vein thrombosis is a major cause of morbidity and mortality globally. While its pathophysiology is complex, increasing evidence suggests a more prominent role for platelets than previously suspected. Genetic deletion of Ral GTPases, RalA and RalB, conditionally in mouse platelets (RalAB double knockout [DKO]), results in a near complete defect in P-selectin externalization upon activation, while other platelet activation responses and arterial thrombosis are preserved.

Platelet generation in vivo and in vitro.

Platelets play crucial roles in hemostasis, thrombosis, and immunity, but our understanding of their complex biogenesis (thrombopoiesis) is currently incomplete. Deeper insight into the mechanisms of platelet biogenesis inside and outside the body is fundamental for managing hematological disorders and for the development of novel cell-based therapies. In this article, we address the current understanding of in vivo thrombopoiesis, including mechanisms of platelet generation from megakaryocytes (proplatelet formation, cytoplasmic fragmentation, and membrane budding) and their physiological location.

Feasibility of a Multidomain Resiliency Assessment in Patients With Advanced Heart Failure Requiring Surgery: A Pilot Study.

Objective: The resiliency of patients who have advanced heart failure (HF) and undergo a physical stressor such as heart transplantation or left ventricular assist device implantation has yet to be studied in the physical, cognitive, and psychosocial domains. The primary aim of this pilot study was to assess the feasibility of a multidomain resiliency assessment in patients who have advanced HF and require surgery.

Methods: A battery of assessments in each of the domains was completed at baseline before surgical intervention, after intensive care discharge, and 3 and 6 months after surgery.

Mitochondrial complex I promotes kidney cancer metastasis.

Most kidney cancers are metabolically dysfunctional, but how this dysfunction affects cancer progression in humans is unknown. We infused C-labelled nutrients in over 80 patients with kidney cancer during surgical tumour resection. Labelling from [U-C]glucose varies across subtypes, indicating that the kidney environment alone cannot account for all tumour metabolic reprogramming.

CryoET reveals actin filaments within platelet microtubules.

Crosstalk between the actin and microtubule cytoskeletons is important for many cellular processes. Recent studies have shown that microtubules and F-actin can assemble to form a composite structure where F-actin occupies the microtubule lumen. Whether these cytoskeletal hybrids exist in physiological settings and how they are formed is unclear.

Gut microbial features and dietary fiber intake predict gut microbiota response to resistant starch supplementation.

Resistant starch (RS) consumption can have beneficial effects on metabolic health, but the response, in terms of effects on the gut microbiota and host physiology, varies between individuals. Factors predicting the response to RS are not yet established and would be useful for developing precision nutrition approaches that maximize the benefits of dietary fiber intake. We sought to identify predictors of gut microbiota response to RS supplementation.

Specific Mitotic Events Drive Cytoskeletal Remodeling Required for Left-Right Organizer Development.

Cellular proliferation is vital for tissue development, including the Left-Right Organizer (LRO), a transient organ critical for establishing the vertebrate LR body plan. This study investigates cell redistribution and the role of specific progenitor cells in LRO formation, focusing on cell lineage and behavior. Using zebrafish as a model, we mapped all mitotic events in Kupffer's Vesicle (KV), revealing an FGF-dependent, anteriorly enriched mitotic pattern.

Impact of High-Dose Early Mobilization on Outcomes for Patients with Diabetes: A Secondary Analysis of the TEAM Trial.

Patients with diabetes represent almost 20% of all ICU admissions and might respond differently to high-dose early active mobilization. To assess whether diabetes modified the relationship between the dose of early mobilization on clinical outcomes in the TEAM trial. All TEAM trial patients were included.

An Exploration of Doctor of Physical Therapy Students' Belongingness in Clinical Education: A Validation Study.

Introduction: The aim of this study was to adapt and validate the Belongingness Scale-Clinical Placement Experience (BES-CPE) for Doctor of Physical Therapy (DPT) students in the United States.

Review Of Literature: Belongingness is vital to one's mental, emotional, and physical health. Research has shown that belongingness is positively correlated with students' academic performance and achievement.

Colon cancer survival in the elderly without curative surgery.

Introduction: The aim of this study was to chart the natural history of elderly patients with colon cancer who are managed nonoperatively, with the primary outcome being life expectancy from diagnosis to death.

Methods: This was a retrospective analysis of patients aged 80 years and above diagnosed with colon cancer in a tertiary care referral hospital in England between 1 January 2012 and 31 December 2017.

Results: Thirty-two patients were diagnosed with non-metastatic colon cancer and managed non-operatively.

The Constructive Black Queen hypothesis: new functions can evolve under conditions favouring gene loss.

Duplication is a major route for the emergence of new gene functions. However, the emergence of new gene functions via this route may be reduced in prokaryotes, as redundant genes are often rapidly purged. In lineages with compact, streamlined genomes, it thus appears challenging for novel function to emerge via duplication and divergence.

REVISE: re-evaluating the inhibition of stress erosions in the ICU-statistical analysis plan for a randomized trial.

Background: The REVISE (Re-Evaluating the Inhibition of Stress Erosions in the ICU) trial will evaluate the impact of the proton pump inhibitor pantoprazole compared to placebo in invasively ventilated critically ill patients.

Objective: To outline the statistical analysis plan for the REVISE trial.

Methods: REVISE is a randomized clinical trial ongoing in intensive care units (ICUs) internationally.

Structome: a tool for the rapid assembly of datasets for structural phylogenetics.

Summary: Protein structures carry signal of common ancestry and can therefore aid in reconstructing their evolutionary histories. To expedite the structure-informed inference process, a web server, Structome, has been developed that allows users to rapidly identify protein structures similar to a query protein and to assemble datasets useful for structure-based phylogenetics. Structome was created by clustering of the structures in RCSB PDB using 90% sequence identity and representing each cluster by a centroid structure.