Spatial proteomic differences in chronic traumatic encephalopathy, Alzheimer's disease, and primary age-related tauopathy hippocampi.

Introduction: Alzheimer's disease (AD), primary age-related tauopathy (PART), and chronic traumatic encephalopathy (CTE) all feature hyperphosphorylated tau (p-tau)-immunoreactive neurofibrillary degeneration, but differ in neuroanatomical distribution and progression of neurofibrillary degeneration and amyloid beta (Aβ) deposition.

Methods: We used Nanostring GeoMx Digital Spatial Profiling to compare the expression of 70 proteins in neurofibrillary tangle (NFT)-bearing and non-NFT-bearing neurons in hippocampal CA1, CA2, and CA4 subregions and entorhinal cortex of cases with autopsy-confirmed AD (n = 8), PART (n = 7), and CTE (n = 5).

Results: There were numerous subregion-specific differences related to Aβ processing, autophagy/proteostasis, inflammation, gliosis, oxidative stress, neuronal/synaptic integrity, and p-tau epitopes among these different disorders.

Two-Drug Combination Antiretroviral Therapy for HIV-1: Case Series and Literature Review.

Doravirine (DOR) is a non-nucleoside reverse transcriptase inhibitor (NNRTI) approved for use in combination antiretroviral therapy (cART) for treatment of human immunodeficiency virus (HIV) in treatment-naive patients. Doravirine-based regimens are an option for patients with limited alternatives due to drug-drug interactions, toxicities, or resistance. A paucity of data exists for use of two-drug DOR-based regimens in treatment-experienced individuals.

Association between glucagon-like peptide-1 receptor agonist use and progression of monoclonal gammopathy of uncertain significance to multiple myeloma among patients with diabetes.

Background: In patients with diabetes and monoclonal gammopathy of uncertain significance (MGUS), the impact of glucagon-like peptide-1 (GLP-1) receptor agonists on the natural history of MGUS is unknown. We aimed to assess the association of GLP-1 receptor agonist use in the progression of MGUS to multiple myeloma in patients with diabetes.

Methods: This is a population-based cohort study of veterans diagnosed with MGUS from 2006 to 2021 with a prior diagnosis of diabetes.

Chimeric antigen receptor macrophages target and resorb amyloid plaques.

Substantial evidence suggests a role for immunotherapy in treating Alzheimer's disease (AD). While the precise pathophysiology of AD is incompletely understood, clinical trials of antibodies targeting aggregated forms of β amyloid (Aβ) have shown that reducing amyloid plaques can mitigate cognitive decline in patients with early-stage AD. Here, we describe what we believe to be a novel approach to target and degrade amyloid plaques by genetically engineering macrophages to express an Aβ-targeting chimeric antigen receptor (CAR-Ms).

NK3.3-Derived Extracellular Vesicles Penetrate and Selectively Kill Treatment-Resistant Tumor Cells.

Cancer treatments often become ineffective due to the development of tumor resistance, leading to metastasis and relapse. Treatments may also fail because of their inability to access cells deep within the tumor tissue. When this occurs, new therapeutic agents are needed.

Associations Between Adiponectin and the Development of Diabetes in Rheumatoid Arthritis.

Purpose: We evaluated associations between adiponectin and the risk of diabetes among patients with rheumatoid arthritis (RA), a systemic inflammatory disease associated with metabolic disturbance.

Methods: This prospective cohort study included adults with RA from the Veterans Affairs Rheumatoid Arthritis Registry. Adiponectin and inflammatory cytokines/chemokines were measured at enrollment on stored serum samples.

Mechanosensing in Metabolism.

Electrical mechanosensing is a process mediated by specialized ion channels, gated directly or indirectly by mechanical forces, which allows cells to detect and subsequently respond to mechanical stimuli. The activation of mechanosensitive (MS) ion channels, intrinsically gated by mechanical forces, or mechanoresponsive (MR) ion channels, indirectly gated by mechanical forces, results in electrical signaling across lipid bilayers, such as the plasma membrane. While the functions of mechanically gated channels within a sensory context (e.

Neuroinflammation and white matter alterations in occupational manganese exposure assessed by diffusion basis spectrum imaging.

Objective: To evaluate in-vivo neuroinflammation and white matter (WM) microstructural integrity in occupational manganese (Mn) exposure.

Methods: We assessed brain inflammation using Diffusion Basis Spectrum Imaging (DBSI) in 26 Mn-exposed welders, 17 Mn-exposed workers, and 26 non-exposed participants. Cumulative Mn exposure was estimated from work histories and the Unified Parkinson's Disease Rating Scale motor subsection 3 (UPDRS3) scores were completed by a movement specialist.

Influence of Perioperative COVID-19 Infection on Surgical Outcomes and Risk Adjustment for Quality Assessment in the American College of Surgeons NSQIP.

Background: Surgical patients with perioperative coronavirus disease 19 (COVID-19) infection experience higher rates of adverse events than those without COVID-19, which may lead to imprecision in hospital-level quality assessment. Our objectives were to quantify differences in COVID-19-associated adverse events in a large national sample and examine distortions in surgical quality benchmarking if COVID-19 status is not considered.

Study Design: Data included 793,280 patient records from the American College of Surgeons NSQIP from April 1, 2020, to March 31, 2021.

Rates and Correlates of Alcohol and Substance Use Among Women Veterans During the COVID-19 Pandemic: The Moderating Role of COVID-Specific Anxiety.

Introduction: Mental health symptoms and substance use increased during the COVID-19 pandemic, and women may be disproportionately affected. Women report substantial mental health consequences, and women veterans may experience additional risks associated with military service. However, rates and correlates of substance use and consequences among women veterans are largely unknown.

A literature review of local and systemic considerations for endodontic treatments in older adults.

Objectives: The aim of this literature review was to summarise the clinical important findings on the endodontic treatment outcome in older patients (≥60 years old) with pulpal/periapical disease considering local and systemic factors from a body of knowledge that is heterogeneous in methods or disciplines.

Background: Due to the increasing number of older patients in the endodontic practice, and the current trend for tooth preservation, the need for clinicians to have a better understanding of age-related implications that may influence the required endodontic treatment in older adults to retain their natural dentition is indispensable.

Methods: PubMed/Medline and Embase was searched by a medical librarian using specific terms based on inclusion/exclusion criteria.

Surgical Outcomes in Canada and the United States: An Analysis of the ACS-NSQIP Clinical Registry.

Background: There has been longstanding uncertainty over whether lower healthcare spending in Canada might be associated with inferior outcomes for hospital-based care. We hypothesized that mortality and surgical complication rates would be higher for patients who underwent four common surgical procedures in Canada as compared to the US.

Design, Setting, And Participants: We conducted a retrospective cohort study of all adults who underwent hip fracture repair, colectomy, pancreatectomy, or spine surgery in 96 Canadian and 585 US hospitals participating in the American College of Surgeons National Surgical Quality Improvement Project (ACS-NSQIP) between January 1, 2015 and December 31, 2019.

Biofilm Formation and Virulence of Shigella flexneri Are Modulated by pH of Gastrointestinal Tract.

infection remains a public health problem in much of the world. Classic models of pathogenesis suggest that microfold epithelial cells in the small intestine are the preferred initial site of invasion. However, recent evidence supports an alternative model in which primarily infects a much wider range of epithelial cells that reside primarily in the colon.

Extracellular Vesicles From the Human Natural Killer Cell Line NK3.3 Have Broad and Potent Anti-Tumor Activity.

Natural killer (NK) cells are critical mediators of immune function, responsible for rapid destruction of tumor cells. They kill primarily through the release of granules containing potent cytolytic molecules. NK cells also release these molecules within membrane-bound exosomes and microvesicles - collectively known as extracellular vesicles (EV).

Performance Analysis of the National Early Warning Score and Modified Early Warning Score in the Adaptive COVID-19 Treatment Trial Cohort.

Unlabelled: We sought to validate prognostic scores in coronavirus disease 2019 including National Early Warning Score, Modified Early Warning Score, and age-based modifications, and define their performance characteristics.

Design: We analyzed prospectively collected data from the Adaptive COVID-19 Treatment Trial. National Early Warning Score was collected daily during the trial, Modified Early Warning Score was calculated, and age applied to both scores.

Frailty in Older Adults With Multiple Myeloma: A Study of US Veterans.

Purpose: Age-associated cumulative decline across physiologic systems results in a diminished resistance to stressors, including cancer and its treatment, creating a vulnerable state known as frailty. Frailty is associated with increased risk of adverse outcomes in patients with cancer. Identification of frailty in administrative data can allow for assessment of prognosis and facilitate control for confounding variables.