Efficacy, safety and tolerability of GSK3858279, an anti-CCL17 monoclonal antibody and analgesic, in healthy volunteers and patients with knee osteoarthritis pain: a phase I, randomised, double-blind, placebo-controlled, proof-of-mechanism and proof-of-concept study.

Objectives: The objective of this study was to evaluate efficacy, safety and tolerability of the first-in-class, anti-CCL17 monoclonal antibody, GSK3858279, in treating knee osteoarthritis (OA) pain.

Methods: This was a phase I, randomised, placebo-controlled, two-part, proof-of-mechanism and proof-of-concept study. In part A, healthy participants were randomised 3:1 to receive GSK3858279 as either single intravenous (0.

3D printed feathers with embedded aerodynamic sensing.

Bird flight is often characterized by outstanding aerodynamic efficiency, agility and adaptivity in dynamic conditions. Feathers play an integral role in facilitating these aspects of performance, and the benefits feathers provide largely derive from their intricate and hierarchical structures. Although research has been attempted on developing membrane-type artificial feathers for bio-inspired aircraft and micro air vehicles (MAVs), fabricating anatomically accurate artificial feathers to fully exploit the advantages of feathers has not been achieved.

Ocular Inflammation and Oxidative Stress as a Result of Chronic Intermittent Hypoxia: A Rat Model of Sleep Apnea.

Obstructive sleep apnea (OSA) is a sleep disorder characterized by intermittent complete or partial occlusion of the airway. Despite a recognized association between OSA and glaucoma, the nature of the underlying link remains unclear. In this study, we investigated whether mild OSA induces morphological, inflammatory, and metabolic changes in the retina resembling those seen in glaucoma using a rat model of OSA known as chronic intermittent hypoxia (CIH).

The ketogenic diet and hypoxia promote mitophagy in the context of glaucoma.

Mitochondrial homeostasis includes balancing organelle biogenesis with recycling (mitophagy). The ketogenic diet protects retinal ganglion cells (RGCs) from glaucoma-associated neurodegeneration, with a concomitant increase in mitochondrial biogenesis. This study aimed to determine if the ketogenic diet also promoted mitophagy.

The burden of periprosthetic femoral fractures in England and Wales: Insights from the first two years of data collection in the National Hip Fracture Database and regional variation in care.

Introduction: Periprosthetic femoral fractures (PPFFs) represent an important healthcare problem, with a rising incidence noted due to an increase in the number of arthroplasty surgeries being performed. There is a current lack of national consensus as to how these complex, often frail patients are managed.

Aims: Our primary aim was to present the epidemiology of PPFFs in England and Wales over the first two years of data collection by the National Hip Fracture Database (NHFD).

The coupling between healthspan and lifespan in depends on complex interactions between compound intervention and genetic background.

Aging is characterized by declining health that results in decreased cellular resilience and neuromuscular function. The relationship between lifespan and health, and the influence of genetic background on that relationship, has important implications in the development of pharmacological anti-aging interventions. Here we assessed swimming performance as well as survival under thermal and oxidative stress across a nematode genetic diversity test panel to evaluate health effects for three compounds previously studied in the Intervention Testing Program and thought to promote longevity in different ways - NP1 (nitrophenyl piperazine-containing compound 1), propyl gallate, and resveratrol.

Multi-variate coding for possession: methodology and preliminary results.

In this work we are presenting a database structure to encode the phenomenon of differential possession across languages, considering noun possession classes and possessive constructions as independent but linked. We show how this structure can be used to study different dimensions of possession: semantics, noun valence, and possessive constructions. We present preliminary survey results from a global sample of 120 languages and show that there is a universal semantic core in both inalienable and non-possessible noun classes.

Long-term HIF-1α stabilization reduces respiration, promotes mitophagy, and results in retinal cell death.

Ocular hypertension during glaucoma can lead to hypoxia, activation of the HIF transcription factors, and a metabolic shift toward glycolysis. This study aims to test whether chronic HIF activation and the attendant metabolic reprogramming can initiate glaucoma-associated pathology independently of ocular hypertension. HIF-1α stabilization was induced in mice for 2 and 4 weeks by inhibiting prolyl hydroxylases using the small molecule Roxadustat.

Addressing the Mental Health of Nursing Students During the Pandemic: The Evaluation of a Needs Assessment by a College of Nursing Mental Health Task Force.

Background: A Mental Health Task Force (MHTF) was developed in a large public college of nursing in the Southeastern United States to address the urgent mental health needs expressed by growing numbers of nursing students related to the coronavirus disease 2019 (COVID-19).

Aims: The purpose of this study was to report on a needs assessment conducted by the MHTF.

Methods: The needs assessment study design was a 16-item cross-sectional online survey and four "Town Hall" focus groups with nursing students, faculty, and staff ( = 1-8 participants per group).

Antioxidants green tea extract and nordihydroguaiaretic acid confer species and strain-specific lifespan and health effects in Caenorhabditis nematodes.

The Caenorhabditis Intervention Testing Program (CITP) is an NIH-funded research consortium of investigators who conduct analyses at three independent sites to identify chemical interventions that reproducibly promote health and lifespan in a robust manner. The founding principle of the CITP is that compounds with positive effects across a genetically diverse panel of Caenorhabditis species and strains are likely engaging conserved biochemical pathways to exert their effects. As such, interventions that are broadly efficacious might be considered prominent compounds for translation for pre-clinical research and human clinical applications.

Longitudinal wave scattering in thin plates with symmetric damage considering oblique incidence.

The interactions between ultrasonic waves and damage provide crucial information for developing effective damage detection techniques in various fields, including non-destructive testing and structural health monitoring, and they can be investigated through wave propagation. Then, this article presents an approach to investigate the longitudinal wave in thin plates with symmetric damage considering oblique incidence. The approach includes a strategy to determine the plate thickness reduction due to the damage presence by considering an oblique incidence of waves generated by the actuator.

Intramuscular vs Intravenous SARS-CoV-2 Neutralizing Antibody Sotrovimab for Treatment of COVID-19 (COMET-TAIL): A Randomized Noninferiority Clinical Trial.

Background: Convenient administration of coronavirus disease 2019 (COVID-19) treatment in community settings is desirable. Sotrovimab is a pan-sarbecovirus dual-action monoclonal antibody formulated for intravenous (IV) or intramuscular (IM) administration for early treatment of mild/moderate COVID-19.

Method: This multicenter phase 3 study based on a randomized open-label design tested the noninferiority of IM to IV administration according to an absolute noninferiority margin of 3.

Life Cycle Assessment of Closed-Loop Pumped Storage Hydropower in the United States.

The United States has begun unprecedented efforts to decarbonize all sectors of the economy by 2050, requiring rapid deployment of variable renewable energy technologies and grid-scale energy storage. Pumped storage hydropower (PSH) is an established technology capable of providing grid-scale energy storage and grid resilience. There is limited information about the life cycle of greenhouse gas emissions associated with state-of-the-industry PSH technologies.

Long-term implant survival following hemiarthroplasty for fractured neck of femur.

Aims: Several different designs of hemiarthroplasty are used to treat intracapsular fractures of the proximal femur, with large variations in costs. No clinical benefit of modular over monoblock designs has been reported in the literature. Long-term data are lacking.

Hydrogel-Encapsulated Biofilm Inhibitors Abrogate the Cariogenic Activity of .

We designed and synthesized analogues of a previously identified biofilm inhibitor to improve solubility, retain inhibitory activities, and to facilitate encapsulation into pH-responsive hydrogel microparticles. The optimized lead compound showed improved solubility of 120.09 μg/mL, inhibited biofilm with an IC value of 6.

Caring for patients with periprosthetic femoral fractures across England and Wales in 2021.

Aims: The aim of this study was to describe services available to patients with periprosthetic femoral fracture (PPFF) in England and Wales, with focus on variation between centres and areas for care improvement.

Methods: This work used data freely available from the National Hip Fracture Database (NHFD) facilities survey in 2021, which asked 21 questions about the care of patients with PPFFs, and nine relating to clinical decision-making around a hypothetical case.

Results: Of 174 centres contributing data to the NHFD, 161 provided full responses and 139 submitted data on PPFF.

Energy considerations and flow fields over whiffling-inspired wings.

Some bird species fly inverted, or whiffle, to lose altitude. Inverted flight twists the primary flight feathers, creating gaps along the wing's trailing edge and decreasing lift. It is speculated that feather rotation-inspired gaps could be used as control surfaces on uncrewed aerial vehicles (UAVs).

Store-operated Ca entry inhibition ameliorates high glucose and ANG II-induced podocyte apoptosis and mitochondrial damage.

Hyperglycemia and increased activity of the renal angiotensin II (ANG II) system are two primary pathogenic stimuli for the onset and progression of podocyte injury in diabetic nephropathy. However, the underlying mechanisms are not fully understood. Store-operated Ca entry (SOCE) is an important mechanism that helps maintain cell Ca homeostasis in both excitable and nonexcitable cells.

Risk Factors and 120-Day Functional Outcomes of Delirium After Hip Fracture Surgery: A Prospective Cohort Study Using the UK National Hip Fracture Database (NHFD).

Objectives: To identify risk factors of postoperative delirium among hip fracture patients with normal preoperative cognition, and examine associations with returning home or recovery of mobility.

Design: Prospective cohort study.

Setting And Participants: We used the National Hip Fracture Database (NHFD) to identify patients presenting with hip fracture in England (2018-2019), but excluded those with abnormal cognition [abbreviated mental test score (AMTS) < 8] on presentation.

Destabilizing COXIV in Müller Glia Increases Retinal Glycolysis and Alters Scotopic Electroretinogram.

Müller glia (MG), the principal glial cell of the retina, have a metabolism that defies categorization into glycolytic versus oxidative. We showed that MG mount a strong hypoxia response to ocular hypertension, raising the question of their relative reliance on mitochondria for function. To explore the role of oxidative phosphorylation (OXPHOS) in MG energy production in vivo, we generated and characterized adult mice in which MG have impaired cytochrome c oxidase (COXIV) activity through knockout of the COXIV constituent COX10.

Neuroprotective Effects of Transferrin in Experimental Glaucoma Models.

Iron is essential for retinal metabolism, but an excess of ferrous iron causes oxidative stress. In glaucomatous eyes, retinal ganglion cell (RGC) death has been associated with dysregulation of iron homeostasis. Transferrin (TF) is an endogenous iron transporter that controls ocular iron levels.

A randomised trial of anti-GM-CSF otilimab in severe COVID-19 pneumonia (OSCAR).

Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) and dysregulated myeloid cell responses are implicated in the pathophysiology and severity of COVID-19.

Methods: In this randomised, sequential, multicentre, placebo-controlled, double-blind study, adults aged 18-79 years (Part 1) or ≥70 years (Part 2) with severe COVID-19, respiratory failure and systemic inflammation (elevated C-reactive protein/ferritin) received a single intravenous infusion of otilimab 90 mg (human anti-GM-CSF monoclonal antibody) plus standard care (NCT04376684). The primary outcome was the proportion of patients alive and free of respiratory failure at Day 28.