Enhanced Interleukin 6 Trans-Signaling Modulates Disease Process in Amyotrophic Lateral Sclerosis Mouse Models.

Charcot first described ALS in 1869, but the specific mechanisms that mediate the disease pathology are still not clear. Intense research efforts have provided insight into unique neuroanatomical regions, specific neuronal populations and genetic associations for ALS and other neurodegenerative diseases; however, the experimental results also suggest a convergence of these events to common toxic pathways. We propose that common toxic pathways can be therapeutically targeted, and this intervention will be effective in slowing progression and improving patient quality of life.

A solution to the pervasive problem of response bias in self-reports.

Self-reports are used ubiquitously to probe people's thoughts, feelings, and behaviors and inform medical decisions, enterprise operations, and government policy and legislation. Despite their pervasive use, self-report measures such as Likert scales have a profound problem: Standard analytic approaches do not control for the confounding effects of idiosyncratic response biases. Here, we present a model-based solution to this problem.

Occurrence, Fate, and Removal of Per- and Polyfluoroalkyl Substances (PFAS) in Small- and Large-Scale Municipal Wastewater Treatment Facilities in the United States.

Wastewater treatment plants (WWTPs) could be conduits of polyfluoroalkyl substances (PFAS) contaminants in the environment. This study investigated the fate of 40 PFAS compounds across nine municipal WWTPs with varying treatment capacity and processes. High concentrations of perfluoroalkyl carboxylic acids (PFCAs) and perfluoroalkyl sulfonic acids (PFSAs) were detected in wastewater, with the ratio of their total concentrations (∑PFCAs/∑PFSAs) always greater than one.

How do we conduct a national transfusion related lookback program?

Background: Lookback investigations are conducted by blood services when a risk of transmission of infection from a donor to a recipient has been identified. They involve tracing transfusion recipients and offering them testing for the relevant infectious agent. Results are relayed to the recipient to provide reassurance that there has been no transmission or to ensure appropriate treatment and care if required, and blood services are able to learn lessons from the planning, delivery, and outcomes of the investigation.

Digital Divide Among Medicare Beneficiaries and the Diabetes Prevention Program.

Introduction: Successful delivery of the virtual Medicare Diabetes Prevention Program (MDPP) is influenced by a beneficiary's access to a computer and use of the Internet.

Methods: Using the 2020 nationally representative Medicare Current Beneficiary Survey Public Use File, a three-level categorical dependent variable was created: (1) has a computer AND uses Internet, (2) has a computer OR uses Internet, and (3) has no access to either (reference group). A survey-weighted multinomial logit model was performed in 2023 to examine associations between socio-demographics, comorbidities, and computer access and Internet use.

Autotrophic adaptive laboratory evolution of the acetogen Clostridium autoethanogenum delivers the gas-fermenting strain LAbrini with superior growth, products, and robustness.

Microbes able to convert gaseous one-carbon (C1) waste feedstocks are increasingly important to transition to the sustainable production of renewable chemicals and fuels. Acetogens are interesting biocatalysts since gas fermentation using Clostridium autoethanogenum has been commercialised. However, most acetogen strains need complex nutrients, display slow growth, and are not robust for bioreactor fermentations.

Assessing the effectiveness of virtual reality to promote empathy for patients through a mixed-methods study.

Objective: To describe the implementation and outcomes of EmpathyVR, an immersive experience using virtual reality (VR) to promote empathy for patients with physical limitations due to chronic diseases.

Methods: First-year student pharmacists participated in a learning experience that incorporated VR and stiff gloves to simulate physical limitations associated with color-blindness and arthritis, respectively. Students completed pre- and post-intervention surveys that included the Kiersma-Chen Empathy Scale and measures of immersion, user enjoyment, perceived usefulness for learning, and adverse effects of the experience.

Linoleic acid exhibits anti-proliferative and anti-invasive activities in endometrial cancer cells and a transgenic model of endometrial cancer.

Emerging evidence has provided considerable insights into the integral function of reprogramming fatty acid metabolism in the carcinogenesis and progression of endometrial cancer. Linoleic acid, an essential fatty acid with the highest consumption in the Western diet regimen, has shown pro-tumorigenic or anti-tumorigenic effects on tumor cell growth and invasion in multiple types of cancer. However, the biological role of linoleic acid in endometrial cancer remains unclear.

Adaptation of SARS-CoV-2 to ACE2 mice reveals new spike residues that drive mouse infection.

The Coronavirus Disease 2019 (COVID-19) pandemic continues to cause extraordinary loss of life and economic damage. Animal models of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection are needed to better understand disease pathogenesis and evaluate preventive measures and therapies. While mice are widely used to model human disease, mouse angiotensin converting enzyme 2 (ACE2) does not bind the ancestral SARS-CoV-2 spike protein to mediate viral entry.

A Whole School, Whole Community, Whole Child Approach to Support Student Physical Activity and Nutrition: Introduction/Methods.

Background: We introduce the Whole School, Whole Community, Whole Child approach to supporting student and school staff physical activity and nutrition and describe the methods used to generate the evidence synthesized across the special issue articles.

Methods: A 2-phase literature review search included a search of systematic reviews (2010-2018) for individual qualifying articles (Phase 1) and a search for individual articles on topics not addressed by a review (2010-2020) or that needed an update because they were in a review that was older (2010-2016) or showed insufficient evidence (Phase 2). Research librarians developed search strategies.

The School Environment and Physical and Social-Emotional Well-Being: Implications for Students and School Employees.

Background: The school environment, consisting of the physical environment and social-emotional climate (SEC), plays a crucial role in both student and employee health; however, there is a lack of recent literature synthesizing school environment interventions in K-12 settings. We describe updated evidence about school environment interventions to support K-12 student and employee health in the United States.

Methods: A 2-phase search included a review of reviews (2010-2018), followed by a search for individual articles (2010-2020) that targeted school physical environment and/or SEC to address physical activity (PA) and/or nutrition.

Hyperbaric oxygen therapy for late radiation tissue injury.

Background: This is the third update of the original Cochrane Review published in July 2005 and updated previously in 2012 and 2016. Cancer is a significant global health issue. Radiotherapy is a treatment modality for many malignancies, and about 50% of people having radiotherapy will be long-term survivors.

Impact of Bronchiectasis on COPD Severity and Alpha-1 Antitrypsin Deficiency as a Risk Factor in Individuals with a Heavy Smoking History.

Rationale: Bronchiectasis is common among those with heavy smoking histories, but risk factors for bronchiectasis, including alpha-1 antitrypsin deficiency, and its implications for COPD severity are uncharacterized in such individuals.

Objectives: To characterize the impact of bronchiectasis on COPD and explore alpha-1antitrypsin as a risk factor for bronchiectasis.

Methods: SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) participants (N=914; ages 40-80 years; ≥20-pack-year smoking) had high-resolution computed tomography (CT) scans interpreted visually for bronchiectasis, based on airway dilation without fibrosis or cicatrization.

Exploring the gap between refugee-background communities' needs and existing community-based physical activity programs in Australia.

Physical activity programs run by local government, public health and not-for-profit sectors are a key public health strategy for improving rates of physical activity within local communities. However, these programs are underutilized. This is especially the case among members of refugee-background communities whose participation could have far-ranging and multilevel benefits.

A novel dopamine receptor D2 antagonist (ONC206) potentiates the effects of olaparib in endometrial cancer.

Poly ADP-ribose polymerase (PARP) inhibitors are effective therapies for cancer patients with homologous recombination (HR) deficient tumors. The imipridone ONC206 is an orally bioavailable dopamine receptor D2 antagonist and mitochondrial protease ClpP agonist that has anti-tumorigenic effects in endometrial cancer via induction of apoptosis, activation of the integrated stress response and modulation of PI3K/AKT signaling. Both PARP inhibitors and imipridones are being evaluated in endometrial cancer clinical trials but have yet to be explored in combination.

Dissatisfaction of Out-of-Pocket Costs and Problems Paying Medical Bills Among Medicare Beneficiaries With Type 2 Diabetes.

Purpose: The purpose of the study was to examine the relationship between satisfaction of Medicare coverage for out-of-pocket costs and problems paying medical bills among Medicare beneficiaries with type 2 diabetes.

Methods: The 2019 Medicare Current Beneficiary Survey Public Use File, a nationally representative sample of Medicare beneficiaries aged ≥65 years with type 2 diabetes, was analyzed (n = 2178). A survey-weighted multivariable logit regression model was conducted to examine the association between satisfaction of Medicare coverage for out-of-pocket costs and problems paying medical bills, adjusted for sociodemographics and comorbidities.

A cell-free platform to measure coronavirus membrane fusion.

Here we present a protocol to measure coronavirus-mediated membrane fusion, an essential event in coronavirus cell entry. The approach uses nanoluciferase (Nluc) "HiBiT"-tagged corona virus-like particles (VLPs) and Nluc "LgBiT"-containing extracellular vesicles (EVs) as proxies for virus and cell, respectively. VLP-EV membrane fusion allows HiBiT and LgBiT to combine into measurable Nluc, which signifies virus fusion with target cell membranes.

Levels of Soluble Interleukin 6 Receptor and Asp358Ala Are Associated With Cognitive Performance and Alzheimer Disease Biomarkers.

Background And Objectives: Alzheimer disease (AD) is a neurodegenerative disease process manifesting clinically with cognitive impairment and dementia. AD pathology is complex, and in addition to plaques and tangles, neuroinflammation is a consistent feature. Interleukin (IL) 6 is a multifaceted cytokine involved in a plethora of cellular mechanisms including both anti-inflammatory and inflammatory processes.

Patient attitudes, experiences, and satisfaction with healthcare and office visit utilization among Medicare beneficiaries with type 2 diabetes.

Objectives: To examine patient attitudes, experiences, and satisfaction with healthcare associated with office visit utilization among Medicare beneficiaries with type 2 diabetes.

Methods: We analyzed the 2019 Medicare Current Beneficiary Survey Public Use File of beneficiaries aged ≥65 years with type 2 diabetes ( = 1092). The ordinal dependent variable was defined as 0, 1 to 5, and ≥6 office visits.

Jointly modeling behavioral and EEG measures of proactive control in task switching.

In this study, we implement joint modeling of behavioral and single-trial electroencephalography (EEG) data derived from a cued-trials task-switching paradigm to test the hypothesis that trial-by-trial adjustment of response criterion can be linked to changes in the event-related potentials (ERPs) elicited during the cue-target interval (CTI). Specifically, we assess whether ERP components associated with preparation to switch task and preparation of the relevant task are linked to a response criterion parameter derived from a simple diffusion decision model (DDM). Joint modeling frameworks characterize the brain-behavior link by simultaneously modeling behavioral and neural data and implementing a linking function to bind these two submodels.

3D printing-enabled uniform temperature distributions in microfluidic devices.

Many microfluidic processes rely heavily on precise temperature control. Though internally-contained heaters have been developed using traditional fabrication methods, they are limited in their ability to isothermally heat a precisely defined volume. Advances in 3D printing have led to high resolution printers capable of using bio-compatible materials and achieving geometry resolutions near 20 μm.

Genetic Mapping of Multiple Traits Identifies Novel Genes for Adiposity, Lipids, and Insulin Secretory Capacity in Outbred Rats.

Despite the successes of human genome-wide association studies, the causal genes underlying most metabolic traits remain unclear. We used outbred heterogeneous stock (HS) rats, coupled with expression data and mediation analysis, to identify quantitative trait loci (QTLs) and candidate gene mediators for adiposity, glucose tolerance, serum lipids, and other metabolic traits. Physiological traits were measured in 1,519 male HS rats, with liver and adipose transcriptomes measured in >410 rats.