Drug therapy versus placebo or usual care for comatose survivors of cardiac arrest; a systematic review with meta-analysis.

Background: In Europe, approximately 291,000 cardiac arrests occur annually. Despite critical care therapy, hospital mortality remains high. This systematic review assessed whether, in comatose survivors of cardiac arrest, any drug therapy, compared to placebo or usual care, improves outcomes.

A randomized control trial evaluating the advice of a physiological-model/digital twin-based decision support system on mechanical ventilation in patients with acute respiratory distress syndrome.

Background: Acute respiratory distress syndrome (ARDS) is highly heterogeneous, both in its clinical presentation and in the patient's physiological responses to changes in mechanical ventilator settings, such as PEEP. This study investigates the clinical efficacy of a physiological model-based ventilatory decision support system (DSS) to personalize ventilator therapy in ARDS patients.

Methods: This international, multicenter, randomized, open-label study enrolled patients with ARDS during the COVID-19 pandemic.

Small volume fluid resuscitation and supplementation with 20% albumin versus buffered crystalloids in adults with septic shock: A protocol for a randomised feasibility trial.

Background: Fluid therapy is universally administered in the management of patients with sepsis, however excessive cumulative fluid balance has been shown to result in worse outcomes. Hyperoncotic albumin results in both lower fluid volumes and early cumulative fluid balance, and may reduce short-term mortality in patients with septic shock.

Methods: In this single centre, open label, feasibility trial; patients with early septic shock will be randomly allocated either 20% albumin for resuscitation and daily supplementation, versus buffered crystalloids alone for all fluid therapy.

Astrocyte aquaporin mediates a tonic water efflux maintaining brain homeostasis.

Brain water homeostasis not only provides a physical protection, but also determines the diffusion of chemical molecules key for information processing and metabolic stability. As a major type of glia in brain parenchyma, astrocytes are the dominant cell type expressing aquaporin water channel. How astrocyte aquaporin contributes to brain water homeostasis in basal physiology remains to be understood.

Massively parallel sequencing of mitochondrial genome in primary open angle glaucoma identifies somatically acquired mitochondrial mutations in ocular tissue.

Glaucoma is a sight threatening neurodegenerative condition of the optic nerve head associated with ageing and marked by the loss of retinal ganglion cells. Mitochondrial dysfunction plays a crucial role in the pathogenesis of neurodegeneration in the most prevalent type of glaucoma: primary open angle glaucoma (POAG). All previous mitochondrial genome sequencing studies in POAG analyzed mitochondrial DNA (mtDNA) isolated from peripheral blood leukocytes and have not evaluated cells derived from ocular tissue, which better represent the glaucomatous disease context.

PROTECTION OF MICE AGAINST CECAL LIGATION AND PUNCTURE-INDUCED POLYMICROBIAL SEPSIS BY A FASCIOLA HEPATICA HELMINTH DEFENSE MOLECULE.

Sepsis results from a dysregulated host immune response to infection and is responsible for ~11 million deaths each year. In the laboratory, many aspects of sepsis can be replicated using a cecal ligation and puncture model, which is considered the most clinically relevant rodent model of sepsis. In the present study, histological and biomarker multiplex analyses revealed that the cecal ligation and puncture model initiated a large-scale inflammatory response in mice by 24 h, with evidence of acute organ damage by 48-72 h.

Comparative Analysis of Extracellular Vesicles from Cytotoxic CD8 αβ T Cells and γδ T Cells.

Background: Although belonging to different branches of the immune system, cytotoxic CD8 αβ T cells and γδ T cells utilize common cytolytic effectors including FasL, granzymes, perforin and granulysin. The effector proteins are stored in different subsets of lysosome-related effector vesicles (LREVs) and released to the immunological synapse upon target cell encounter. Notably, in activated cells, LREVs and potentially other vesicles are continuously produced and released as extracellular vesicles (EVs).

Future Directions in Therapies for Acute Respiratory Distress Syndrome.

Acute respiratory distress syndrome (ARDS) is caused by a complex interplay among hyperinflammation, endothelial dysfunction, and alveolar epithelial injury. Targeted treatments toward the underlying pathways have been unsuccessful in unselected patient populations. The first reliable biological subphenotypes reflective of these biological disease states have been identified in the past decade.

Influence of different sample preparation approaches on proteoform identification by top-down proteomics.

Top-down proteomics using mass spectrometry facilitates the identification of intact proteoforms, that is, all molecular forms of proteins. Multiple past advances have lead to the development of numerous sample preparation workflows. Here we systematically investigated the influence of different sample preparation steps on proteoform and protein identifications, including cell lysis, reduction and alkylation, proteoform enrichment, purification and fractionation.

Update to: Study Pre-protocol for "BronchStart - The Impact of the COVID-19 Pandemic on the Timing, Age and Severity of Respiratory Syncytial Virus (RSV) Emergency Presentations; a Multi-Centre Prospective Observational Cohort Study".

Background: In 2021 we launched the BronchStart study, which collected information on 17,899 presentations in children with serious respiratory tract infections following the release of lockdown restrictions. Our study informed the Joint Committee on Vaccination and Immunisation's decision to recommend the introduction maternal respiratory syncytial virus (RSV) vaccination, which was introduced in the United Kingdom in August/September 2024.

Study Question: We modified our original protocol to conduct a United Kingdom-wide assessment of maternal vaccination against RSV.

An array of Zymoseptoria tritici effectors suppress plant immune responses.

Zymoseptoria tritici is the most economically significant fungal pathogen of wheat in Europe. However, despite the importance of this pathogen, the molecular interactions between pathogen and host during infection are not well understood. Herein, we describe the use of two libraries of cloned Z.

Induction of drug metabolizing enzyme and drug transporter expression by antifungal triazole pesticides in human HepaSH hepatocytes.

Triazole pesticides are widely used fungicides, to which humans are rather highly exposed. They are known to activate drug-sensing receptors regulating expression of hepatic drug metabolizing enzymes and drug transporters, thus suggesting that the hepatic drug detoxification system is modified by these agrochemicals. To investigate this hypothesis, the effects of 9 triazole fungicides towards expression of drug metabolizing enzymes and transporters were characterized in cultured human HepaSH cells, that are human hepatocytes deriving from chimeric humanized liver TK-NOG mice.

Utility of respiratory viral testing in the risk stratification of young febrile infants presenting to emergency care settings: a protocol for systematic review and meta-analysis.

Introduction: Febrile infants under 3 months of age are at risk of invasive bacterial infection (IBI). It is currently unclear if testing for respiratory viruses may have a role in IBI risk stratification. If found to be associated with the likelihood of IBI, respiratory viral point-of-care testing may improve patient and caregiver experience, reduce costs and enhance antimicrobial stewardship.

Clemastine enhances exercise-induced motor improvement in hypoxic ischemic rats.

Neonatal hypoxic ischemia (HI) occurs owing to reduced cerebral oxygen levels and perfusion during the perinatal period. Brain injury after HI triggers neurological manifestations such as motor impairment, and the improvement of impaired brain function remains challenging. Recent studies suggest that cortical myelination plays a role in motor learning, but its involvement in motor improvement after HI injury is not well understood.