A CADASIL NOTCH3 mutation leads to clonal hematopoiesis and expansion of Dnmt3a-R878H hematopoietic clones.

Clonal hematopoiesis (CH) is nearly universal in the elderly. The molecular and cellular mechanisms driving CH and the clinical consequences of carrying clonally derived mutant mature blood cells are poorly understood. We recently identified a C223Y mutation in the extracellular domain (ECD) of NOTCH3 as a putative CH driver in mice.

Morphometric Analysis of the Thymic Epithelial Cell (TEC) Network Using Integrated and Orthogonal Digital Pathology Approaches.

The thymus, a central primary lymphoid organ of the immune system, plays a key role in T cell development. Surprisingly, the thymus is quite neglected with regards to standardized pathology approaches and practices for assessing structure and function. Most studies use multispectral flow cytometry to define the dynamic composition of the thymus at the cell population level, but they are limited by lack of contextual insight.

Phenotyping the virulence of SARS-CoV-2 variants in hamsters by digital pathology and machine learning.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has continued to evolve throughout the coronavirus disease-19 (COVID-19) pandemic, giving rise to multiple variants of concern (VOCs) with different biological properties. As the pandemic progresses, it will be essential to test in near real time the potential of any new emerging variant to cause severe disease. BA.

Spatial analyses of immune cell infiltration in cancer: current methods and future directions: A report of the International Immuno-Oncology Biomarker Working Group on Breast Cancer.

Modern histologic imaging platforms coupled with machine learning methods have provided new opportunities to map the spatial distribution of immune cells in the tumor microenvironment. However, there exists no standardized method for describing or analyzing spatial immune cell data, and most reported spatial analyses are rudimentary. In this review, we provide an overview of two approaches for reporting and analyzing spatial data (raster versus vector-based).

Urinary bladder hemangiosarcoma in a cat treated with partial cystectomy and adjuvant metronomic cyclophosphamide and thalidomide.

Visceral hemangiosarcomas (HSA) are rare in cats and typically associated with aggressive biologic behavior and poor prognosis. A 4-year-old male neutered domestic shorthair cat was presented with a 3-month history of hematuria and stranguria; ultrasonography identified a large bladder mass. Complete excision was achieved by partial cystectomy.

Uterus Masculinus with a Patent Urethral Communication Documented with Positive Contrast Computed Tomography.

A 9 mo old male Labrador retriever presented for investigation into persistent urinary incontinence. Abdominal ultrasound and retrograde urethrocystogram with computed tomography documented a uterus masculinus (UM), which was confirmed on histopathology after surgical removal. A connection between the UM and the urethra was present, documented by positive contrast retrograde urethrocystography and confirmed with surgery.

Comparative Evaluation of Tumor-Infiltrating Lymphocytes in Companion Animals: Immuno-Oncology as a Relevant Translational Model for Cancer Therapy.

Despite the important role of preclinical experiments to characterize tumor biology and molecular pathways, there are ongoing challenges to model the tumor microenvironment, specifically the dynamic interactions between tumor cells and immune infiltrates. Comprehensive models of host-tumor immune interactions will enhance the development of emerging treatment strategies, such as immunotherapies. Although in vitro and murine models are important for the early modelling of cancer and treatment-response mechanisms, comparative research studies involving veterinary oncology may bridge the translational pathway to human studies.

Canine Gastric Carcinomas: A Histopathological and Immunohistochemical Study and Similarities with the Human Counterpart.

Canine gastric carcinoma (CGC) affects both sexes in relatively equal proportions, with a mean age of nine years, and the highest frequency in Staffordshire bull terriers. The most common histological subtype in 149 CGC cases was the undifferentiated carcinoma. CGCs were associated with increased chronic inflammation parameters and a greater chronic inflammatory score when spp.

Waterhouse-Friderichsen syndrome in a cat with Klebsiella spp. infection.

Objective: To describe a case of Waterhouse-Friderichsen syndrome of adrenocortical failure in a cat with Klebsiella spp. infection.

Case Summary: A 12-year-old male neutered domestic short-haired cat was referred for respiratory failure requiring mechanical ventilation.

Efficacy of montelukast in preventing seasonal recurrence of vernal keratoconjunctivitis in children.

Background: Vernal keratoconjunctivitis is a chronic, seasonally exacerbated, allergic inflammation of the eye. The study aims to evaluate the efficacy and safety of oral montelukast in treating vernal keratoconjunctivitis in pediatric patients.

Methods: This is a 26-week, prospective, randomized, open-label study.

The Tumor Suppressor CYLD Inhibits Mammary Epithelial to Mesenchymal Transition by the Coordinated Inhibition of YAP/TAZ and TGF Signaling.

Downregulation of the cylindromatosis (CYLD) tumor suppressor has been associated with breast cancer development and progression. Here, we report a critical role for CYLD in maintaining the phenotype of mammary epithelial cells in vitro and in vivo. CYLD downregulation or inactivation induced an epithelial to mesenchymal transition of mammary epithelial cells that was dependent on the concomitant activation of the transcription factors Yes-associated protein (YAP)/transcriptional coactivator with PDZ-binding motif (TAZ) and transforming growth factor beta (TGF)signaling.

HDAC1/2 Inhibitor Romidepsin Suppresses DEN-Induced Hepatocellular Carcinogenesis in Mice.

Background: Hepatocellular carcinoma (HCC) is a frequently diagnosed cancer and a leading cause of cancer-related death worldwide. Its rapid progression, combined with the limited treatment options at late stages, imposes the need for early detection and aggressive intervention. Based on the knowledge that hepatocarcinogenesis is significantly influenced by histone acetylation, we directed our search for novel HCC therapeutics among histone deacetylation inhibitors (HDACi).

Histiocytic sarcoma in miniature schnauzers: 30 cases.

Objectives: To summarise the clinical presentation and outcomes in a series of miniature schnauzers diagnosed with histiocytic sarcoma.

Materials And Methods: Retrospective review of medical records of miniature schnauzers diagnosed with histiocytic sarcoma between 2008 and 2019 at two referral centres in the UK. Signalment, clinical signs at initial presentation, imaging results and clinico- and histopathological findings, treatment type and outcome were recorded.

Consuming cholera toxin counteracts age-associated obesity.

During the past forty years there has been an inexplicable increase in chronic inflammatory disorders, including obesity. One theory, the 'hygiene hypothesis', involves dysregulated immunity arising after too few beneficial early life microbe exposures. Indeed, earlier studies have shown that gut microbe-immune interactions contribute to smoldering inflammation, adiposity, and weight gain.

Targeting hepatocarcinogenesis model in C56BL6 mice with pan-aurora kinase inhibitor Danusertib.

: To elucidate the expression of Aurora kinases (AURK) and the anticancer effects of pan-aurora kinase inhibitor Danusertib in hepatocarcinogenesis model in C56Bl6 mice. : Thirty mice C56Bl6 were randomly divided into Group A or control, Group B animals who underwent experimental hepatocarcinogenesis with diethylnitrosamine (DEN), and Group C animals with DEN-induced hepatocarcinogenenesis that treated with pan-aurora kinase inhibitor Danusertib. Primary antibodies for immunochistochemistry (IHC) included rabbit antibodies against Ki-67, DKK1, INCENP, cleaved caspase-3, NF-κB p65, c-Jun, β-catenin.

Effects of Wnt-1 blockade in DEN-induced hepatocellular adenomas of mice.

Recent evidence has suggested that downregulation of the Wnt/β-catenin signaling pathway may contribute to the development and growth of HCC. Consequently, elements of this pathway have begun to emerge as potential targets for improving outcomes of anti-HCC. Thus, the present study sought to examine the effects of Wnt-1 blockade using the classical diethylnitrosamine (DEN)-induced chemical carcinogenesis mouse model of HCC.

Effects of lysolecithin supplementation in low-energy diets on growth performance, nutrient digestibility, viscosity and intestinal morphology of broilers.

1. The study aimed to investigate the effect of lysolecithin supplementation in low-energy diets on growth, nutrient digestibility and intestinal mucosa characteristics of broilers. 2.

Inflammation-driven colon neoplasmatogenesis in uPA-deficient mice is associated with an increased expression of Runx transcriptional regulators.

Deregulation of the bone morphogenetic protein (BMP) pathway has been documented in colorectal cancer (CRC). Previously, we investigated possible associations between urokinase-type plasminogen activator (uPA) deficiency and expression of extracellular constituents of BMP signaling in a newly developed mouse model of inflammation-driven intestinal neoplasmatogenesis, in which chronic colitis and CRC are induced using dextran sodium sulfate (DSS). In this report, we explored the contribution of intracellular components of Smad-mediated BMP signal transduction using the same model.

Dietary supplementation of encapsulated organic acids enhances performance and modulates immune regulation and morphology of jejunal mucosa in piglets.

The aim of the study was to test two encapsulated regimens containing organic acids and/or zinc oxide (ZnO) on weaned piglet performance and jejunal mucosa morphology and immunity. For that, weaned piglets were allocated to treatments including control, supplemented with encapsulated organic acids (ACID group), and supplemented with organic acids and ZnO, both encapsulated (ACIDplus group). Antibiotics were used at similar concentrations in all groups during the first two weeks, but withdrawn from the ACIDplus group during the last three weeks of the experiment.

Canalicular lacerations: Factors predicting outcome at a tertiary eye care centre.

To determine the factors predictive of outcome in canalicular laceration repair at a tertiary eye care centre. A retrospective review of the medical records of all primary canalicular laceration repairs managed at a tertiary eye care centre between the years 2006 and 2014 was done. Thirty-nine patients were included and majority were male (79.

Microbial lysate upregulates host oxytocin.

Neuropeptide hormone oxytocin has roles in social bonding, energy metabolism, and wound healing contributing to good physical, mental and social health. It was previously shown that feeding of a human commensal microbe Lactobacillus reuteri (L. reuteri) is sufficient to up-regulate endogenous oxytocin levels and improve wound healing capacity in mice.