The Golgi complex governs natural killer cell lytic granule positioning to promote directionality in cytotoxicity.

Cytotoxic immune cells mediate precise attacks against diseased cells to maintain organismal health. Their operational unit of killing and host defense is lytic granules (LGs), which are specialized lysosomal-related organelles. Precision in cytotoxicity is achieved by converging the many LGs to the microtubule-organizing center (MTOC) and polarizing these to the diseased cell for secretion.

Ages and Stages Questionnaires in the assessment of young children after cardiac surgery.

Aims: This study explored the prospective use of the Ages and Stages Questionnaires-3 in follow-up after cardiac surgery.

Materials And Method: For children undergoing cardiac surgery at 5 United Kingdom centres, the Ages and Stages Questionnaires-3 were administered 6 months and 2 years later, with an outcome based on pre-defined cut-points: Red = 1 or more domain scores >2 standard deviations below the normative mean, Amber = 1 or more domain scores 1-2 standard deviations below the normal range based on the manual, Green = scores within the normal range based on the manual.

Results: From a cohort of 554 children <60 months old at surgery, 306 participated in the postoperative assessment: 117 (38.

Structured tailored rehabilitation after hip fragility fracture: The 'Stratify' feasibility and pilot randomised controlled trial protocol.

Background: Rehabilitation in hospital is effective in reducing mortality after hip fracture. However, there is uncertainty over optimal in-hospital rehabilitation treatment ingredients, and the generalizability of trial findings to subgroups of patients systematically excluded from previous trials. The aim of this study is to determine the feasibility of a randomized controlled trial which aims to assess the clinical- and cost-effectiveness of adding a stratified care intervention to usual care designed to improve outcomes of acute rehabilitation for all older adults after hip fracture.

Language Preference, Surgical Wait Time, and Outcomes Among Older Adults With Hip Fracture.

Importance: Patients with a non-English language preference served within English-dominant health care settings are at increased risk of adverse events that may be associated with communication barriers and inequitable access to care.

Objective: To investigate the association of non-English language preference with surgical wait time and postoperative outcomes in older patients undergoing hip fracture repair.

Design, Setting, And Participants: This population-based, retrospective cohort study was conducted using linked databases to measure surgical wait time and postoperative outcomes among older adults (aged ≥66 years) in Ontario, Canada, who underwent hip fracture surgery between January 1, 2017, and December 31, 2022.

Antibody Aggregation: A Problem Within the Biopharmaceutical Industry and Its Role in AL Amyloidosis Disease.

Due to the large size and rapid growth of the global therapeutic antibody market, there is major interest in understanding the aggregation of protein products as it can compromise efficacy, concentration, and safety. Various production and storage conditions have been identified as capable of inducing aggregation of polyclonal and monoclonal antibody (mAb) therapies such as low pH, freezing, light exposure, lyophilisation and increased ionic strength. The addition of stabilising excipients to these therapeutics helps to combat the formation of aggregates with future aggregation inhibition mechanisms involving the introduction of point mutations and glycoengineering within aggregation prone regions (APRs).

Outcomes Associated With Stereotactic Radiosurgery After Multiple Resections of Nonfunctioning Pituitary Macroadenomas: An International, Multicenter Case Series.

Background And Objectives: Stereotactic radiosurgery (SRS) represents an effective treatment for nonfunctioning pituitary adenomas (NFPAs). However, no data have yet been published regarding results of SRS on NFPAs after multiple previous resections.

Methods: Retrospective multicentric data of patients diagnosed with NFPA and who underwent multiple resections (≥2) before SRS were reviewed and analyzed.

Epistaxis in COVID positive ICU patients, implications, and future interventions.

Purpose: Epistaxis in critically ill patients may prevent the use of non-invasive ventilation and impair nasal oxygen delivery. Since the onset of COVID-19, high-flow nasal oxygen has dramatically increased. There is a paucity of literature on characteristics of epistaxis in critically ill, COVID-19 positive patients.

Quality of life after stereotactic radiosurgery for brain metastasis: an assessment from a prospective national registry.

Purpose: Stereotactic radiosurgery (SRS) is frequently used in the management of brain metastasis patients. However, there is an urgent need to evaluate post-treatment outcomes and quality of life metrics for patients undergoing SRS for brain metastases.

Methods: The NeuroPoint Alliance (NPA) SRS Quality Registry conducted prospective enrollment of patients undergoing SRS from 2017 to 2024.

Identification of pharmacological inducers of a reversible hypometabolic state for whole organ preservation.

Drugs that induce reversible slowing of metabolic and physiological processes would have great value for organ preservation, especially for organs with high susceptibility to hypoxia-reperfusion injury, such as the heart. Using whole-organism screening of metabolism, mobility, and development in , we identified an existing drug, SNC80, that rapidly and reversibly slows biochemical and metabolic activities while preserving cell and tissue viability. Although SNC80 was developed as a delta opioid receptor activator, we discovered that its ability to slow metabolism is independent of its opioid modulating activity as a novel SNC80 analog (WB3) with almost 1000 times less delta opioid receptor binding activity is equally active.

Donepezil Nanoemulsion Induces a Torpor-like State with Reduced Toxicity in Nonhibernating Tadpoles.

Achieving a reversible decrease of metabolism and other physiological processes in the whole organism, as occurs in animals that experience torpor or hibernation, could contribute to increased survival after serious injury. Using a Bayesian network tool with transcriptomic data and chemical structure similarity assessments, we predicted that the Alzheimer's disease drug donepezil (DNP) could be a promising candidate for a small molecule drug that might induce a torpor-like state. This was confirmed in a screening study with tadpoles, a nonhibernator whole animal model.

Protocol for a feasibility randomised controlled trial of the 'Outdoor' mobility intervention for older adults after hip fracture.

Background: A high proportion of patients do not regain outdoor mobility after hip fracture. Rehabilitation explicitly targeting outdoor mobility is needed to enable these older adults to recover activities which they value most. The overarching aim of this study is to determine the feasibility of a randomised controlled trial which aims to assess the clinical- and cost-effectiveness of an intervention designed to enable recovery of outdoor mobility among older adults after hip fracture (the OUTDOOR intervention).

Legislative Advocacy in Illinois for Firearm Injury Prevention.

The leading cause of death in children in the United States is injury caused by firearm violence. States that enact stricter laws related to firearm injury prevention have lower rates of mortality in children. In Illinois, we formed a coalition with medical professionals, medical organizations, community partners, and legislators to craft legislation to reduce the burden of firearm violence on children.

Secondary Stroke Prevention in People With Schizophrenia.

Background: People with schizophrenia are less likely than those without to be treated for cardiovascular disease. We aimed to evaluate the association between schizophrenia and secondary preventive care after ischemic stroke.

Methods And Results: In this retrospective cohort study, we used linked population-based administrative data to identify adults who survived 1 year after ischemic stroke hospitalization in Ontario, Canada between 2004 and 2017.

Spinal infection: Assessing comorbidities and costs to inform patient management and resource use strategies.

Background: Spinal Infection (SI) is associated with various comorbidities. The interaction of these comorbidities and their impact on costs and complexity of care has not been fully assessed.

Methods: This is a retrospective cohort study of SI patients in an urban hospital system to characterize comorbidities and outcomes in adult patients with SI.

Neoantigen-specific cytotoxic Tr1 CD4 T cells suppress cancer immunotherapy.

CD4 T cells can either enhance or inhibit tumour immunity. Although regulatory T cells have long been known to impede antitumour responses, other CD4 T cells have recently been implicated in inhibiting this response. Yet, the nature and function of the latter remain unclear.

Rehabilitation after surgery for hip fracture - the impact of prompt, frequent and mobilisation-focused physiotherapy on discharge outcomes: an observational cohort study.

Purpose: To determine the relationship between three postoperative physiotherapy activities (time to first postoperative walk, activity on the day after surgery, and physiotherapy frequency), and the outcomes of hospital length of stay (LOS) and discharge destination after hip fracture.

Methods: A cohort study was conducted on 437 hip fracture surgery patients aged ≥ 50 years across 36 participating hospitals from the Australian and New Zealand Hip Fracture Registry Acute Rehabilitation Sprint Audit during June 2022. Study outcomes included hospital LOS and discharge destination.