Diffusion-weighted arterial spin labeling MRI to investigate mannitol-induced blood brain barrier disruption.

Purpose: Diffusion-weighted arterial spin labeling (DW-ASL) MRI has been proposed to determine the rate of water exchange (K) across the blood brain barrier (BBB). This study aims to further evaluate K MRI by comparing it with standard dynamic contrast-enhanced (DCE) MRI and histology in association with mannitol-induced disruption of the BBB.

Methods: DW-ASL was measured using a multiple b-value MRI protocol in normal rats at three post-labeling delays (N = 19), before and after intra-carotid injection of mannitol to disrupt BBB in one hemisphere (N = 13).

Ultra-processed food consumption and risk of dementia and Alzheimer's disease: The Framingham Heart Study.

Background: Ultra-processed food consumption is emerging as a risk factor for various cardiometabolic diseases, however its association with dementia and Alzheimer's disease has rarely been explored.

Objectives: We sought to examine whether ultra-processed food consumption is associated with risk of all-cause dementia and Alzheimer's disease among middle-age and older adults.

Design: A prospective cohort study.

Immunology of Biliary Atresia.

Biliary atresia is a progressive neonatal cholangiopathy that leads to liver failure. Characterized by inflammation-mediated liver injury, the immune system plays a critical role in the pathogenesis of this disease. Though several types of immune cells and mediators have been implicated in animal models of biliary atresia, emerging literature reflects the complex interplay of components of the immune response that contributes to disease progression in humans.

Conjugation of Short-Chain Fatty Acids to Bicyclic-Amines for Analysis by Liquid Chromatography Tandem Mass Spectroscopy.

Conjugation of short-chain fatty acids (SDFAs) to amines containing ring structures allows for better measurement by liquid chromatography tandem mass spectroscopy (LC-MS/MS). However, collision-induced dissociation (CID) results in breaking the conjugate back to the original SCFA and amine. We therefore set out to find an amine that would remain on the SCFA after CID and create a unique daughter for selectivity of measurement.

A Senescent Cluster in Aged Human Hematopoietic Stem Cell Compartment as Target for Senotherapy.

To identify the differences between aged and young human hematopoiesis, we performed a direct comparison of aged and young human hematopoietic stem and progenitor cells (HSPCs). Alterations in transcriptome profiles upon aging between humans and mice were then compared. Human specimens consist of CD34+ cells from bone marrow, and mouse specimens of hematopoietic stem cells (HSCs; Lin- Kit+ Sca1+ CD150+).

Targeting Metabolic and Epigenetic Vulnerabilities in Glioblastoma with SN-38 and Rabusertib Combination Therapy.

Glioblastoma (GBM), the most prevalent primary malignant brain tumor, remains challenging to treat due to extensive inter- and intra-tumor heterogeneity. This variability demands combination treatments to improve therapeutic outcomes. A significant obstacle in treating GBM is the expression of O-methylguanine-DNA methyltransferase, a DNA repair enzyme that reduces the efficacy of the standard alkylating agent, temozolomide, in about 50% of patients.

Surgical Outcomes and Associated Morbidity of Active and Expectant Management of Second-Trimester Placenta Accreta Spectrum (PAS).

Management of second-trimester placenta accreta spectrum (PAS) is currently center-dependent with minimal evidence-based practices. This study aims to analyze outcomes of hysterectomy as second-trimester active management (AM) versus cesarean hysterectomy as expectant management (EM) in cases of PAS with intraoperative and postoperative outcomes. This study is a retrospective case-control study of patients with a pathology-confirmed diagnosis of PAS managed at a single center over 16 years (2005-2020).

Circulating Isthmin-1 Levels and Their Relationship with Diabetes and Metabolic Diseases in Kuwaiti Adults.

Obesity and type 2 diabetes (T2D) are associated with significant alterations in various metabolic biomarkers. Isthmin-1 (Ism1) has recently emerged as a potential marker of metabolic health and was shown in animal studies to associate with metabolic-associated fatty liver disease (MAFLD). In this study, we aimed to investigate the circulatory levels of Ism1 in individuals with obesity compared to non-obese individuals and evaluate their association with insulin resistance, MAFLD, and T2D.

Design, Synthesis, and Biological Evaluation of Thieno[3,2-]pyrimidine Derivatives as the First Bifunctional PI3Kδ Isoform Selective/Bromodomain and Extra-Terminal Inhibitors.

The concomitant inhibition of PI3Kδ and bromodomain and extra-terminal (BET) that exerts a synergistic effect on the B-cell receptor signaling pathway provides a new strategy for the treatment of aggressive diffuse large B-cell lymphoma (DLBCL). Herein, a merged pharmacophore strategy was utilized to discover a series of thieno[3,2-]pyrimidine derivatives as the first-in-class bifunctional PI3Kδ-BET inhibitors. Through optimization, a highly potent compound () was identified to possess excellent and balanced activities against PI3Kδ [inhibitory concentration (IC) = 112 ± 8 nM] and BRD4-BD1 (IC = 19 ± 1 nM) and exhibited strong antiproliferative activities in DLBCL cells.

Bone Marrow Stromal Cells Generate a Pro-Healing Inflammasome When Cultured on Titanium-Aluminum-Vanadium Surfaces with Microscale/Nanoscale Structural Features.

The surface topography and chemistry of titanium-aluminum-vanadium (Ti6Al4V) implants play critical roles in the osteoblast differentiation of human bone marrow stromal cells (MSCs) and the creation of an osteogenic microenvironment. To assess the effects of a microscale/nanoscale (MN) topography, this study compared the effects of MN-modified, anodized, and smooth Ti6Al4V surfaces on MSC response, and for the first time, directly contrasted MN-induced osteoblast differentiation with culture on tissue culture polystyrene (TCPS) in osteogenic medium (OM). Surface characterization revealed distinct differences in microroughness, composition, and topography among the Ti6Al4V substrates.

Development, Validation, and Application of the Paya Hamsan Technologies Underivatized Newborn Screening Assay (PHUNSA) for Inborn Metabolic Disorders in Dried Blood Spot Samples from Iranian Infants.

Screening for inborn metabolic disorders (IMDs) in newborns is an important way to prevent serious metabolic and developmental difficulties that can result in lasting disabilities or even death. Electrospray ionization tandem mass spectrometry (MS/MS) provides an efficacious newborn blood spot screening (NBS) mechanism for analyzing dried blood spot specimens (DBSs) for biochemical markers for these conditions. Where possible, the elimination of derivatization in specimen preparation can simplify and streamline analysis.

Consolidated Newborn Bloodspot Screening Efforts in Developing Countries in the Asia Pacific-2024.

Approximately half of all births globally occur in the Asia Pacific Region. Concerted efforts to support local activities aimed at developing national newborn screening (NBS) have been ongoing for almost 30 years, first by the International Atomic Energy Agency (IAEA) and then through volunteer efforts. Sustainable newborn bloodspot screening (NBS) continues to be initiated and develop in many of the countries with developing economies in the region.

Management of Chronic Post-Endodontic Pain with a Standardized Gabapentin Pyramid Protocol: A Case Series and Clinical Guidelines.

Introduction: Persistent post-endodontic pain following endodontic therapy is a rare but substantial clinical challenge. Mechanisms that mediate peripheral neuropathy and/or central sensitization likely play a pivotal role in its development and chronification. The objective of this case series is to describe a management plan for persistent post-endodontic pain and provide prescription guidelines using a standardized "Gabapentin Pyramid Protocol" for clinical practice.

Circulating Endocannabinoids and Cognitive Function in Older Adults.

The role of endogenous cannabinoids (endocannabinoids; eCBs) in cognitive-related processes has been demonstrated in preclinical studies. However, observational studies are lacking. We examined the associations of multiple circulating eCBs and eCB-like molecules with cognitive function in a sample of dementia-free older adults.

Metabolic Signaling in the Tumor Microenvironment.

Cancer cells must reprogram their metabolism to sustain rapid growth. This is accomplished in part by switching to aerobic glycolysis, uncoupling glucose from mitochondrial metabolism, and performing anaplerosis via alternative carbon sources to replenish intermediates of the tricarboxylic acid (TCA) cycle and sustain oxidative phosphorylation (OXPHOS). While this metabolic program produces adequate biosynthetic intermediates, reducing agents, ATP, and epigenetic remodeling cofactors necessary to sustain growth, it also produces large amounts of byproducts that can generate a hostile tumor microenvironment (TME) characterized by low pH, redox stress, and poor oxygenation.

Impacts of Diabetes Self-Management Education and Support Programs in Hispanic Church Settings: A Cluster-Randomized Trial Comparing Faith-Based and Faith-Placed Approaches.

This study aimed to adapt evidence-based diabetes self-management education and support (DSMES) into a faith-based (FB) context for Hispanic communities and compare its effectiveness to a faith-placed (FP) approach using the church as a venue for DSMES delivery. A cluster-randomized trial was conducted among adults with type 2 diabetes from predominantly Hispanic churches. The churches were assigned to either the FB Group (nine churches, n = 146) or the FP Group (seven churches, n = 125).

Head-to-Head Comparison of Aptamer- and Antibody-Based Proteomic Platforms in Human Cerebrospinal Fluid Samples from a Real-World Memory Clinic Cohort.

High-throughput proteomic platforms are crucial to identify novel Alzheimer's disease (AD) biomarkers and pathways. In this study, we evaluated the reproducibility and reliability of aptamer-based (SomaScan 7k) and antibody-based (Olink Explore 3k) proteomic platforms in cerebrospinal fluid (CSF) samples from the Ace Alzheimer Center Barcelona real-world cohort. Intra- and inter-platform reproducibility were evaluated through correlations between two independent SomaScan assays analyzing the same samples, and between SomaScan and Olink results.

Molecular Basis of Interchain Disulfide Bond Formation in BMP-9 and BMP-10.

BMP-9 and BMP-10 are TGF-β family signaling ligands naturally secreted into blood. They act on endothelial cells and are required for proper development and maintenance of the vasculature. In hereditary hemorrhagic telangiectasia, regulation is disrupted due to mutations in the BMP-9/10 pathway, namely in the type I receptor ALK1 or the co-receptor endoglin.

The adiponectin-PPARγ axis in hepatic stellate cells regulates liver fibrosis.

Hepatic stellate cells (HSCs) are key drivers of local fibrosis. Adiponectin, conventionally thought of as an adipokine, is also expressed in quiescent HSCs. However, the impact of its local expression on the progression of liver fibrosis remains unclear.

Targeting N-Myc in neuroblastoma with selective Aurora kinase A degraders.

The N-Myc transcription factor, encoded by MYCN, is a mechanistically validated, yet challenging, target for neuroblastoma (NB) therapy development. In normal neuronal progenitors, N-Myc undergoes rapid degradation, while, in MYCN-amplified NB cells, Aurora kinase A (Aurora-A) binds to and stabilizes N-Myc, resulting in elevated protein levels. Here, we demonstrate that targeted protein degradation of Aurora-A decreases N-Myc levels.

Oral cavity and oropharyngeal cancers in Texas: examining incidence rates in dental health professional shortage areas.

Purpose: Oral cavity (OC) and oropharyngeal (OP) cancer rates have increased annually rising in the U.S. and Texas.

Conventional Cytogenetic Analysis of Solid Tumor Abnormalities: A 25-Year Review of Proficiency Test Results from the College of American Pathologists/American College of Medical Genetics and Genomics Cytogenetics Committee.

The joint College of American Pathologists/American College of Medical Genetics and Genomics Cytogenetics Committee works to ensure the competency and proficiency of clinical cytogenetic testing laboratories through proficiency testing (PT) programs for various clinical tests offered by such laboratories, including the evaluation of cytogenetic abnormalities in solid tumors. Review and analyze 25 years (1999-2023) of solid tumor chromosome analysis PT results, utilizing G-banded karyograms. A retrospective review of results from 1999 to 2023 was performed, identifying the challenges addressing solid tumors.

A Novel Triplet of Alisertib Plus Ibrutinib Plus Rituximab Is Active in Mantle Cell Lymphoma.

: Aurora (AK) A/B are oncogenic mitotic kinases that when over-expressed are poor prognostic markers in mantle cell lymphoma (MCL). : Alisertib, an AK-A inhibitor, has anti-tumor activity in relapsed/refractory (r/r) MCL patients. We evaluated alisertib plus ibrutinib in MCL to abrogate ibrutinib resistance.

Prevalence, patterns, and predictors of prescribing medications for opioid use disorder (MOUD) in the Inpatient setting.

Background: There are many barriers to prescribing medications for opioid use disorder (MOUD). This study evaluates the prevalence, patterns, and predictors of inpatient MOUD prescribing at discharge to patients with a diagnosis of opioid use/opioid use disorder (OUD) that developed opioid withdrawal during their hospital stay.

Methods: This multicenter, retrospective cross-sectional study occurred at three hospitals in Arizona.

Mammalian ZAP and KHNYN independently restrict CpG-enriched avian viruses.

Zoonotic viruses are an omnipresent threat to global health. Influenza A virus (IAV) transmits between birds, livestock, and humans. Proviral host factors involved in the cross-species interface are well known.