Nicotinamide Riboside and CD38: Covalent Inhibition and Live-Cell Labeling.

Nicotinamide adenine dinucleotide (NAD) is required for a myriad of metabolic, signaling, and post-translational events in cells. Its levels in tissues and organs are closely associated with health conditions. The homeostasis of NAD is regulated by biosynthetic pathways and consuming enzymes.

Neuroinflammation modifies the relationship between stress and perivascular spaces in an elderly population with different levels of cognitive impairment.

Background: Perivascular spaces (PVS) are fluid-filled spaces surrounding the brain parenchymal vasculature. Literature suggests that PVS may play a significant role in aging and neurological disorders, including Alzheimer's disease (AD). The aim of this study is to investigate whether the relationship between MRI-visible PVS and stress is influenced by neuroinflammation in an elderly population with different levels of cognitive impairment.

Real-world diagnostic, referral, and treatment patterns in early Alzheimer's disease among community-based practices in the United States.

Background: Over 90% of individuals with mild cognitive impairment (MCI) may not receive a timely diagnosis. Understanding community-based practice patterns, where most individuals are seen, is critical to improving patient care.

Objective: To understand how patients with MCI and mild dementia due to Alzheimer's disease (AD) are diagnosed and managed in community-based settings, including the use of clinical and cognitive assessments, referrals to dementia-related specialties, and receipt of treatment.

Medicare's comprehensive care for joint replacement model increased public hospitals' inpatient length of stay.

Background: The Comprehensive Care for Joint Replacement (CJR) model is an alternative Medicare payment model for joint replacement that mandated participation by hospitals in randomly selected Metropolitan Statistical Areas (MSAs). On average, the program decreased inpatient length of stay and increased home discharge rates. It is unclear if these effects differed based on hospital ownership type, even though ownership may impact care redesign opportunities.

Integrative multi-omics profiling of colorectal cancer from a Hispanic/Latino cohort of patients.

Colorectal cancer contributes to cancer-related deaths and health disparities in the Hispanic and Latino community. To probe both the biological and genetic bases of the disparities, we characterized features of colorectal cancer in terms of somatic alterations and genetic similarity. Specifically, we conducted a comprehensive genome-scale analysis of 67 Hispanic and Latino samples.

Biomechanical predictors of primary ACL injury: A scoping review of prospective studies.

Background: ACL injuries commonly occur in non-contact situations, particularly in sports involving jumping, landing, and cutting. Numerous biomechanical predictors for non-contact ACL injury have been proposed, yet existing reviews on biomechanical predictors vary in scope and findings.

Research Question: This review aims to identify biomechanical predictors of primary ACL injury using a scoping review.

The BRAIN Initiative data-sharing ecosystem: Characteristics, challenges, benefits, and opportunities.

In this paper, we provide an overview and analysis of the BRAIN Initiative data-sharing ecosystem. First, we compare and contrast the characteristics of the seven BRAIN Initiative data archives germane to data sharing and reuse, namely data submission and access procedures and aspects of interoperability. Second, we discuss challenges, benefits, and future opportunities, focusing on issues largely specific to sharing human data and drawing on = 34 interviews with diverse stakeholders.

Multi-Omic Characterization of Single Cells and Cell-Free Components Detected in the Cerebrospinal Fluid of Patients with Leptomeningeal Disease.

Background/objectives: Up to 30% of patients with breast cancers will develop brain or leptomeningeal metastases, and this risk is especially high with HER2-positive cancers. For patients with central nervous system metastases, cerebrospinal fluid (CSF) liquid biopsies are a promising opportunity to monitor disease, inform treatment, and predict prognosis. This pilot study investigated CSF liquid biopsy analytes from three patients diagnosed with central nervous system metastases based on imaging but not confirmed via clinical cytology.

Developmental hematopoietic stem cell variation explains clonal hematopoiesis later in life.

Clonal hematopoiesis becomes increasingly common with age, but its cause is enigmatic because driver mutations are often absent. Serial observations infer weak selection indicating variants are acquired much earlier in life with unexplained initial growth spurts. Here we use fluctuating CpG methylation as a lineage marker to track stem cell clonal dynamics of hematopoiesis.

Epitope tagging with genome editing in mice reveals that the proton channel OTOP1 is apically localized and not restricted to Type III "sour" taste receptor cells.

The gustatory system allows animals to assess the nutritive value and safety of foods prior to ingestion. The first step in gustation is the interaction of taste stimuli with one or more specific sensory receptors, that are generally believed to be present on the apical surface of the taste receptor cells. However, this assertion is rarely tested.

Long-term Outcomes of a Modified Straight-line Palate Repair Technique: Low Speech Correcting Surgery and Fistula Rates.

Background: The goal of cleft palate (CP) repair is to restore normal speech, however, rates of velopharyngeal insufficiency (VPI) after palatoplasty remain high. We present a modified straight-line palate repair (SLR) technique that facilitates velum length to alleviate VPI. The technique releases nasal mucosa with the levator muscle off the hard palate.

Wnt/β-catenin maintains epithelial IL-33 in the colonic stem and progenitor cell niche and drives its induction in colitis.

Interleukin (IL)-33 is a key responder to intestinal injury and inflammation. In the colon, it is expressed by several cell populations, with the specific cellular source likely determining its role. The colonic epithelium expresses IL-33; however, the factors controlling its production and the specific epithelial lineage(s) expressing IL-33 are poorly understood.

VprBP regulates osteoclast differentiation via an epigenetic mechanism involving histone H2A phosphorylation.

Background: Bone remodeling is a continuous and balanced process which relies on the dynamic equilibrium between osteoclastic bone resorption and osteoblastic bone formation. During osteoclast differentiation, pro-osteoclastogenic and anti-osteoclastogenic genes are selectively targeted by positive and negative transcription regulators, respectively. VprBP, also known as DCAF1, is a recently identified kinase and plays an important role in driving epigenetic gene silencing and oncogenic transformation.

Early COVID-19 Vaccine Initiation and Completion Among Cancer Survivors and Barriers to Vaccine Completion: Implications for Future COVID-19 Vaccination Uptake Rates.

Purpose: Cancer survivors are considered by public health officials as a high-risk group in the United States for severe complications from COVID-19. We aimed to characterize patterns of early uptake of the COVID-19 vaccine among cancer survivors and to determine modifiable barriers to vaccine completion that can be addressed to ensure future booster adherence.

Methods: Cross-sectional data of vaccine uptake by summer 2021 was extracted from adult cancer survivors enrolled in the "All of Us" research program.

Design and In Vivo Testing of an Anatomic 3D-Printed Peripheral Nerve Conduit in a Rat Sciatic Nerve Model.

Three-dimensional (3D) printer technology has seen a surge in use in medicine, particularly in orthopedics. A recent area of research is its use in peripheral nerve repair, which often requires a graft or conduit to bridge segmental defects. Currently, nerve gaps are bridged using autografts, allografts, or synthetic conduits.

Discovery of penicillic acid as a chemical probe against tau aggregation in Alzheimer's disease.

Alzheimer's Disease (AD) is a neurodegenerative disorder proven to be caused by the aggregation of protein tau into fibrils, resulting in neuronal death. The irreparable neuronal damage leads to irreversible symptoms with no cure; therefore, disaggregation of these tau fibrils could be targeted as a therapeutic approach to AD. Here we have developed a fungal natural product library to screen for secondary metabolites that have bioactive potential towards AD tau.

Pharmacokinetics of Omadacycline in Adults with Cystic Fibrosis.

Background: Omadacycline offers a potential advancement in the management of infections in people with cystic fibrosis (CF) because of its spectrum of activity, intrapulmonary penetration, and oral bioavailability. A prospective single-dose, single-arm study was conducted to characterize the pharmacokinetic (PK) profile of omadacycline in people with CF, considering the known alterations in PK observed in this population (NCT04460586, 2020-07-01).

Methods: Plasma samples were obtained from nine adults with CF who received a single dose of intravenous omadacycline 100 mg over 0.

Development of Calcium-Dependent Phospholipase A2 Inhibitors to Target Cellular Senescence and Oxidative Stress in Neurodegenerative Diseases.

Cellular senescence is a critical process underlying aging and is associated with age-related diseases such as Alzheimer's disease. Lipids are implicated in cellular senescence. Fatty acids, particularly eicosanoids, have been associated with various forms of senescence and inflammation, and the associated reactive oxygen species production has been proposed as a therapeutic target for mitigating senescence.

Cryptic phosphoribosylase activity of NAMPT restricts the virion incorporation of viral proteins.

As obligate intracellular pathogens, viruses activate host metabolic enzymes to supply intermediates that support progeny production. Nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme of salvage nicotinamide adenine dinucleotide (NAD) synthesis, is an interferon-inducible protein that inhibits the replication of several RNA and DNA viruses through unknown mechanisms. Here, we show that NAMPT restricts herpes simplex virus type 1 (HSV-1) replication by impeding the virion incorporation of viral proteins owing to its phosphoribosyl-hydrolase (phosphoribosylase) activity, which is independent of the role of NAMPT in NAD synthesis.

Endogenous mitochondrial NAD(P)H fluorescence can predict lifespan.

Many aging clocks have recently been developed to predict health outcomes and deconvolve heterogeneity in aging. However, existing clocks are limited by technical constraints, such as low spatial resolution, long processing time, sample destruction, and a bias towards specific aging phenotypes. Therefore, here we present a non-destructive, label-free and subcellular resolution approach for quantifying aging through optically resolving age-dependent changes to the biophysical properties of NAD(P)H in mitochondria through fluorescence lifetime imaging (FLIM) of endogenous NAD(P)H fluorescence.