A Phenotypic High-Throughput Screen Identifies Small Molecule Modulators of Endogenous RGS10 in BV-2 Cells.

Chronic dysregulation of microglial phenotypic balance contributes to prolonged neuroinflammation and neurotoxicity, which is a hallmark of neurodegenerative diseases. Thus, targeting microglial inflammatory signaling represents a promising therapeutic strategy for neurodegenerative diseases. Regulator of G protein Signaling 10 (RGS10) is highly expressed in microglia, where it suppresses pro-inflammatory signaling.

Maximizing the reach of universal child sexual abuse prevention: Protocol for an equivalence trial.

Background: Child sexual abuse (CSA) affects 1 in 5 girls and 1 in 12 boys before age 18. Universal school-based prevention programs are an effective and cost-efficient method of teaching students an array of personal safety skills. However, the programmatic reach of universal school-based programs is limited by the inherent reliance on the school infrastructure and a dearth of available alternative delivery modalities.

Americans' willingness to give to global immunization programs: Political heterogeneity in preferences for program management and response to priming communications.

To develop effective private donation campaigns that support vaccine distribution in low- and middle-income countries (LMICs), one must understand donors' willingness to give, response to stimuli, and preferences for program management. We use a contingent valuation method to estimate United States citizens' willingness to give to nongovernmental COVID-19 immunization programs in LMICs during the emergency phase of the pandemic. Using split-sample treatments, we evaluate the impact of the immunization program administrator (generic NGO or COVAX) and the role of priming communications on inequality in income and vaccination rates between the US and recipient countries.

Compartmentalized mitochondrial ferroptosis converges with optineurin-mediated mitophagy to impact airway epithelial cell phenotypes and asthma outcomes.

A stable mitochondrial pool is crucial for healthy cell function and survival. Altered redox biology can adversely affect mitochondria through induction of a variety of cell death and survival pathways, yet the understanding of mitochondria and their dysfunction in primary human cells and in specific disease states, including asthma, is modest. Ferroptosis is traditionally considered an iron dependent, hydroperoxy-phospholipid executed process, which induces cytosolic and mitochondrial damage to drive programmed cell death.

Effects of alcohol consumption and tobacco smoking on the composition of the ensemble of drug metabolizing enzymes and transporters in human liver.

We examined the effect of alcohol consumption and smoking on the abundance of drug-metabolizing enzymes and transporters (DMET) in human liver microsomes (HLM) isolated from liver tissues of 94 donors. Global proteomics analysis was performed and DMET protein levels were analyzed in relation to alcohol consumption levels, smoking history, and sex using non-parametric tests (p-value ≤ 0.05; cutoff of 1.

CanVasc consensus recommendations for the use of avacopan in antineutrophil cytoplasm antibody-associated vasculitis: 2022 addendum.

Objective: In 2020, the Canadian Vasculitis Research Network (CanVasc) published their updated recommendations for the management of ANCA-associated vasculitides (AAV). The current addendum provides further recommendations regarding the use of avacopan in AAV based on a review of newly available evidence.

Methods: An updated systematic literature review on avacopan (formerly, CCX168) using Medline, Embase, and the Cochrane Library was performed for publications up to September 2022.

Potential for prolongation of fibrinogen concentrates post-reconstitution.

Background And Objectives: Reconstituted fibrinogen concentrate is considered stable for 8-24 h based on product monographs. Given the long half-life of fibrinogen in vivo (3-4 days), we hypothesized that reconstituted sterile fibrinogen protein would remain stable longer than 8-24 h. Extending the expiry date for reconstituted fibrinogen concentrate could decrease wastage and facilitate reconstitution in advance to minimize turnaround times.

Health-related quality of life in patients given ciltacabtagene autoleucel for relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b-2, open-label study.

Background: CARTITUDE-1 is a phase 1b-2 study evaluating ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor T cell therapy with two B-cell maturation antigen-targeting single-domain antibodies, in patients with relapsed or refractory multiple myeloma. Primary efficacy outcomes have previously been reported. Here, we report health-related quality of life (HRQOL) secondary outcomes evaluated using patient-reported outcomes.

Prediction of massive transfusion with the Revised Assessment of Bleeding and Transfusion (RABT) score at Canadian level I trauma centers.

Background: Early damage control resuscitation and massive transfusion (MT) protocol activations improve outcomes in trauma patients with hemorrhagic shock, where scores to guide MT prediction are used including: the Assessment of Blood Consumption (ABC), Shock Index (SI), and Revised Assessment of Bleeding and Transfusion (RABT) scores. Our aim was to validate the RABT score in patients from two level I trauma centers in Canada.

Methods: A retrospective review of adult patients meeting trauma team activation criteria receiving >1 unit of red blood cells (RBCs) within 24 h of admission, from 2015 to 2020, was conducted.

Health-related quality of life and treatment satisfaction in Chronic Lymphocytic Leukemia (CLL) patients on ibrutinib compared to other CLL treatments in a real-world US cross sectional study.

The objective of this study was to describe real-world health-related quality of life (HRQoL) and treatment satisfaction of ibrutinib-treated patients with CLL compared to a reference group. This study was completed in two parts. The first portion (Norming Study) was a US online survey conducted to serve as a reference population.

Measuring the impact of an educational intervention in rheumatoid arthritis: An open-label, randomized trial.

Objectives: This study aims to determine whether patients with active rheumatoid arthritis (RA), either starting on or changing biological or targeted synthetic disease-modifying antirheumatic drugs (DMARDs), demonstrate better self-management safety skills three months after receiving a multidisciplinary educational intervention compared to patients receiving usual care.

Patients And Methods: Between October 2015 and October 2018 , this open-label, randomized-controlled trial included a total of 107 RA patients (27 males, 80 females; mean age: 60.2±10.

Virtual Delivery of A School-Based Child Sexual Abuse Prevention Program: A Pilot Study.

Universal child sexual abuse (CSA) prevention is a public health priority. The prevailing prevention strategy is school-based CSA prevention programming. School closures during the COVID-19 pandemic highlighted the need for flexible modes of delivery, including virtual programs.

Disrupted Lessons in Engineering Robotics: Pivoting Knowledge Transfer From Physical to Virtual Learning Environments.

This study examined the effects of an Arduino microrobot activity on college students' interest in robotics through three specific objectives: (1) determining how students' conceptual understanding regarding the basics of microcomputing and computer programming changes after engaging in an engineering robotics learning module, (2) assessing the impact of these changes on students' sense of competence in engineering robotics, and (3) explaining the role of students' perceived knowledge transferability in the relationship between their sense of competence and changes in their interest for pursuing engineering robotics. Participants (n = 58) were recruited from two Engineering Physics courses and surveyed before (Time 1) and after (Time 2) an Arduino microcomputing learning activity. First, significant increases were reported post-activity for interest in robotics, as well as conceptual understanding of microelectronics and computer programming.

Characteristics of Inpatients With Blood Cancers Who Experience a Fall: A Retrospective Study.

Background: Inpatients with cancer are at the greatest risk for falling. Although studies have identified the characteristics of patients with cancer who fall, few studies have focused on the characteristics of patients with blood cancers who fall.

Objectives: The objectives of this study are to identify characteristics of inpatients with blood cancers who fall and implement fall-mitigation efforts through an enhanced assessment of chemotherapy-induced peripheral neuropathy.

Ultra-light photosensor collars to monitor Arctic lemming activity.

Background: Studying the anti-predatory behavior of mammals represents an important challenge, especially for fossorial small mammals that hide in burrows. In the Arctic, such behaviors are critical to the survival of lemmings considering that predation risks are high every summer. Because detailed information about how lemmings use burrows as hideouts is still lacking, we developed a 1.

15LO1 dictates glutathione redox changes in asthmatic airway epithelium to worsen type 2 inflammation.

Altered redox biology challenges all cells, with compensatory responses often determining a cell's fate. When 15 lipoxygenase 1 (15LO1), a lipid-peroxidizing enzyme abundant in asthmatic human airway epithelial cells (HAECs), binds phosphatidylethanolamine-binding protein 1 (PEBP1), hydroperoxy-phospholipids, which drive ferroptotic cell death, are generated. Peroxidases, including glutathione peroxidase 4 (GPX4), metabolize hydroperoxy-phospholipids to hydroxy derivatives to prevent ferroptotic death, but consume reduced glutathione (GSH).

Will Americans Get Vaccinated? Predicting COVID-19 Vaccine Uptake Rates Under Contingent Scenarios.

Objectives: Amid a pandemic, vaccines represent a promising solution for mitigating public health and economic crises, and an improved understanding of individuals' vaccination intentions is crucial to design optimal immunization campaigns. This study predicts uptake rates for different COVID-19 vaccine specifications and identifies personal characteristics that moderate an individual's responsiveness to vaccine attributes.

Methods: We developed an online survey with contingent specifications of a COVID-19 vaccine, varying in effectiveness, risks of side effects, duration of immunity, and out-of-pocket cost.

Immediate and informative feedback during a pandemic: Using stated preference analysis to predict vaccine uptake rates.

In response to an emerging pandemic, there is urgent need for information regarding individual evaluation of risk and preferences toward mitigation strategies such as vaccinations. However, with social distancing policies and financial stress during an outbreak, traditional robust survey methodologies of face-to-face, probabilistic sampling, may not be feasible to deploy quickly, especially in developing countries. We recommend a protocol that calls for a sensitive survey design, acceptance of a web-based approach and adjustments for uncertainty of respondents, to deliver urgently needed information to policymakers as the public health crisis unfolds, rather than in its aftermath.

Health-related Quality of Life at the SPARTAN Final Analysis of Apalutamide for Nonmetastatic Castration-resistant Prostate Cancer Patients Receiving Androgen Deprivation Therapy.

Background: In SPARTAN, apalutamide improved metastasis-free and overall survival for patients with nonmetastatic castration-resistant prostate cancer (nmCRPC) with a prostate-specific antigen doubling time of ≤10 mo.

Objective: We evaluated health-related quality of life (HRQoL) at the final analysis of the SPARTAN study.

Intervention: Patients received apalutamide (240 mg/d) or placebo in 28-d cycles.

Impacts of COVID-19 and elective surgery cancellations on platelet supply and utilization in the Canadian Province of British Columbia.

Background And Objectives: The coronavirus disease 2019 (COVID-19) pandemic raised concerns about the vulnerability of platelet supply and the uncertain impact of the resumption of elective surgery on utilization. We report the impact of COVID-19 on platelet supply and utilization across a large, integrated healthcare system in the Canadian province of British Columbia (BC).

Materials And Methods: Historical platelet use in BC by indication was compiled for fiscal year 2010/2011-2019/2020.

Willingness to give amid pandemics: a contingent valuation of anticipated nongovernmental immunization programs.

Given that altruism is crucial in assisting impoverished households to cope with health and economic crises, it is important to improve our understanding of how preferences and motives for giving differ during a pandemic. We implemented a web-based, contingent valuation survey to estimate Americans' willingness to give for nongovernmental immunization programs in the context of the COVID-19 pandemic. Our results indicate that the median person is willing to give a one-time donation of $26, or at least $13 when willingness-to-give estimates are corrected for uncertainty regarding future donations.