Renal Tubule-Specific Angiotensinogen Deletion Attenuates SGLT2 Expression and Ameliorates Diabetic Kidney Disease in Murine Models of Type 1 Diabetes.

The role of the intrarenal renin-angiotensin system (iRAS) in diabetic kidney disease (DKD) progression remains unclear. In this study, we generated mice with renal tubule-specific deletion of angiotensinogen (Agt; RT-Agt-/-) in both Akita and streptozotocin (STZ)-induced mouse model of diabetes. Both Akita RT-Agt-/- and STZ-RT-Agt-/- mice exhibited significant attenuation of glomerular hyperfiltration, urinary albumin/creatinine ratio, glomerulomegaly and tubular injury.

Global niche partitioning of purine and pyrimidine cross-feeding among ocean microbes.

Cross-feeding involves microbes consuming exudates of other surrounding microbes, mediating elemental cycling. Characterizing the diversity of cross-feeding pathways in ocean microbes illuminates evolutionary forces driving self-organization of ocean ecosystems. Here, we uncover a purine and pyrimidine cross-feeding network in globally abundant groups.

Quality of Life in Patients With Acquired Anophthalmia Using an Ocular Prosthesis.

Purpose: To employ a validated survey for evaluation of quality of life (QoL) outcomes and associated factors in a US cohort of adult patients with acquired anophthalmia wearing a prosthesis.

Methods: A retrospective cohort study was performed at a single, US academic institution of patients cared for between 2012 and 2021. The electronic medical record database was queried for adult patients with a history of evisceration or enucleation surgery and placement of an orbital implant.

Lung Cancer Screening in the Incarcerated Population Through a Community Imaging Partnership.

Limited data exist on cancer screening in carceral facilities. This study evaluates the feasibility and outcomes of a population-based lung cancer screening initiative in a carceral setting. This is a retrospective review of a lung cancer screening event at the Rhode Island Department of Corrections.

Factors in Initial Anticoagulation Choice in Hospitalized Patients With Pulmonary Embolism.

Importance: Despite guideline recommendations to use low-molecular-weight heparins (LMWHs) or direct oral anticoagulants in the treatment of most patients with acute pulmonary embolism (PE), US-based studies have found increasing use of unfractionated heparin (UFH) in hospitalized patients.

Objective: To identify barriers and facilitators of guideline-concordant anticoagulation in patients hospitalized with acute PE.

Design, Setting, And Participants: This qualitative study conducted semistructured interviews from February 1 to June 3, 2024, that were recorded, transcribed, and analyzed in an iterative process using reflexive thematic analysis.

The Age-Old Question in Nipple-Sparing Mastectomy: Is Older Age a Contraindication?

Background: Nipple-sparing mastectomy (NSM) is infrequently performed in older women, at least in part owing to concerns regarding age-related complications. We describe postoperative outcomes of NSM in older women and risk factors for complications, with the goal of informing patient selection and decision-making.

Patients And Methods: Cases of NSM with immediate implant-based reconstruction were identified from an institutional database (2009-2019).

Thermogelation of nanoemulsions stabilized by a commercial pea protein isolate: high-pressure homogenization defines gel strength.

The impact of animal-based food production on climate change drives the development of plant-based alternatives. We demonstrate the use of colloidal thermogelation on a real nanoemulsion system to create structured gels that could be of interest for thermo-mechanical processing of next-generation plant-based food applications. We use a commercial pea protein isolate (PPI) without further purification to stabilize a 20 vol% peanut oil-in-water nanoemulsion at pH = 7 by high-pressure homogenization (HPH) and demonstrate the temperature induced gelation behavior of the nanoemulsion as a function of the HPH processing parameters.

Basic Science and Pathogenesis.

Background: Genome-wide association studies (GWAS) in Alzheimer's disease (AD) leveraging endophenotypes beyond case/control diagnosis, such as brain amyloid β pathology, have shown promise in identifying novel variants and understanding their potential functional impact. In this study, we leverage two brain amyloid β pathology measurement modalities, PET imaging and neuropathology, to address sample size limitations and to discover novel genetic drivers of disease.

Method: We conducted a meta-analysis on an amyloid PET imaging GWAS (N = 7,036, 35% amyloid positive, 53.

Basic Science and Pathogenesis.

Background: We aim to investigate efficacies of Ras homolog (Rho)-associated kinases (ROCK) inhibitors on Alzheimer's disease (AD) pathological proteins in human induced pluripotent stem cell (iPSC)-differentiated human neurons and the P301S tau transgenic mouse model (PS19).

Method: Quantitative liquid chromatography-mass spectrometry (LC-MS/MS) and targeted ELISA were implemented to investigate the effect of treatment with fasudil or its derivatives on the human neurons and brains from PS19 mice. We explored the efficacy of these ROCK inhibitors in reducing tau phosphorylation, and the brain proteomic profiles after their administration in mice.

Basic Science and Pathogenesis.

Background: In tauopathies, the protein tau misfolds into a b-sheet conformation that self-templates and spreads throughout the brain causing progressive degeneration. Biological and structural data have shown that the shape, or strain, that tau adopts when it misfolds determines which disease a patient will develop. We previously used HEK293T cells expressing TauRD-YFP to show that tau strain formation is isoform-specific.

Basic Science and Pathogenesis.

Background: Women are disproportionately affected by Alzheimer's disease (AD) and exhibit greater AD neuropathology than men. Women possess two X chromosomes, with one randomly silenced across each cell for dosage compensation. X chromosome inactivation (XCI) is not complete, and XCI-escaping genes provide a promising avenue of discovery for biological pathways driving sex-specific AD risk.

Basic Science and Pathogenesis.

Background: A significant proportion of individuals preserve cognitive function despite meeting neuropathological criteria for Alzheimer's disease (AD) at autopsy, known as cognitive resilience. We aimed to define the molecular and cellular signatures of cognitive resilience against AD.

Method: We integrated multi-modal data from the Religious Order Study and Memory and Aging Project (ROSMAP), including bulk (n = 631) and multi-regional single nucleus (n = 48) RNA sequencing.

Basic Science and Pathogenesis.

Background: Some individuals can tolerate the presence of Alzheimer disease neuropathologic changes (ADNC) (e.g., plaques and tangles) without developing dementia.

Basic Science and Pathogenesis.

Background: Cerebral small vessel disease (CSVD), which includes cerebral amyloid angiopathy (CAA) and arteriolosclerosis, often co-occurs with Alzheimer's disease (AD) pathology. The medial temporal lobe (MTL) is susceptible to hosting multiple AD pathologies, such as neurofibrillary tangles (NFTs), amyloid-β plaques, phospho-Tar-DNA-Binding-Protein-43 (pTDP-43), as well as CSVD. Whether a causal relationship between these pathologies exists remains largely unknown, but one potential linking mechanism is the dysfunction of perivascular clearance.

Basic Science and Pathogenesis.

Background: In cerebral amyloid angiopathy, amyloid beta accumulates within the walls of blood vessels and contributes to impaired vascular integrity and function. In this work, we observe that tau protein similarly builds up along blood vessels in Alzheimer's disease brain.

Method: We obtained frozen inferior temporal cortex from the Massachusetts Alzheimer's Disease Research Center from n = 7 neuropathological confirmed Alzheimer's disease donors and n = 6 normal aging controls.

Basic Science and Pathogenesis.

Background: Angiotensin-converting enzyme (ACE) is a validated risk locus for developing late-onset Alzheimer's disease (LOAD). ACE1 controls blood pressure through the renin-angiotensin system (RAS), but it is also present and acts locally in the brain. Hypertension is associated with an increased risk for developing AD, and people taking select RAS-targeting therapeutics have reduced incidence of AD.