International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Nonproliferative and Proliferative Lesions of Nonrodent Ocular Tissues.

The INHAND (International Harmonization of Nomenclature and Diagnostic Criteria for Lesions) Project (www.toxpath.org/ inhand.

Microbial intestinal dysbiosis drives long-term allergic susceptibility by sculpting an ILC2-B1 cell-innate IgE axis.

Background: The abundance and diversity of intestinal commensal bacteria influence systemic immunity with impact on disease susceptibility and severity. For example, loss of short chain fatty acid (SCFA)-fermenting bacteria in early life (humans and mice) is associated with enhanced type 2 immune responses in peripheral tissues including the lung.

Objective: Our goal was to reveal the microbiome-dependent cellular and molecular mechanisms driving enhanced susceptibility to type 2 allergic lung disease.

Hunting for a viral proxy in bioaerosols of swine buildings using molecular detection and metagenomics.

There are limited biosecurity measures directed at preventing airborne transmission of viruses in swine. The effectiveness of dust mitigation strategies such as oil sprinkling, to decrease risk of airborne virus transmission are unknown. Metagenomics and qPCR for common fecal viruses were used to hunt for a ubiquitous virus to serve as a proxy when evaluating the efficiency of mitigation strategies against airborne viral infectious agents.

A tumor-restricted glycoform of podocalyxin is a highly selective marker of immunologically cold high-grade serous ovarian carcinoma.

Introduction: Targeted-immunotherapies such as antibody-drug conjugates (ADC), chimeric antigen receptor (CAR) T cells or bispecific T-cell engagers (eg, BiTE) all aim to improve cancer treatment by directly targeting cancer cells while sparing healthy tissues. Success of these therapies requires tumor antigens that are abundantly expressed and, ideally, tumor specific. The CD34-related stem cell sialomucin, podocalyxin (PODXL), is a promising target as it is overexpressed on a variety of tumor types and its expression is consistently linked to poor prognosis.

Spatiotemporal signaling underlies progressive vascular rarefaction in myocardial infarction.

Therapeutic angiogenesis represents a promising avenue to revascularize the ischemic heart. Its limited success is partly due to our poor understanding of the cardiac stroma, specifically mural cells, and their response to ischemic injury. Here, we combine single-cell and positional transcriptomics to assess the behavior of mural cells within the healing heart.

Beneficial Effects of Two Marine Oxygen Carriers, M101 and M201, on Human Islet Quality in Hypoxic Culture Conditions.

High pancreatic islet sensitivity to hypoxia is an important issue in the field of pancreatic islet transplantation. A promising strategy to improve islet oxygenation in hypoxic conditions is to leverage the properties of hemoglobin as a natural carrier of oxygen. Studies using human or bovine hemoglobin have failed to demonstrate efficacy, probably due to the molecule being unstable in the absence of protective erythrocytes.

Antibody-Drug Conjugates Targeting Tumor-Specific Mucin Glycoepitopes.

Finding the ideal epitope to target is a key element for the development of an antibody-drug conjugate (ADC). To maximize drug delivery to tumor cells and reduce side effects, this epitope should be specific to cancer cells and spare all normal tissue. During cancer progression, glycosylation pathways are frequently altered leading to the generation of new glycosylation patterns selective to cancer cells.

Microbiota Transplantation in Day-Old Broiler Chickens Ameliorates Necrotic Enteritis via Modulation of the Intestinal Microbiota and Host Immune Responses.

A microbiota transplant (MT) originating from mature adult chicken ceca and propagated in bioreactors was administered to day-old broiler chicks to ascertain the degree to which, and how, the MT affects ()-incited necrotic enteritis (NE). Using a stress predisposition model of NE, birds administered the MT and challenged with showed fewer necrotic lesions, and exhibited a substantially higher α- and β-diversity of bacteria in their jejunum and ceca. Birds challenged with and not administered the MT showed decreased and increased 1 in the jejunum.

Interactions Between Infectious Foodborne Viruses and Bacterial Biofilms Formed on Different Food Contact Surfaces.

Bacterial biofilms contribute to contamination, spoilage, persistence, and hygiene failure in the food industry, but relatively little is known about the behavior of foodborne viruses evolving in the complex communities that make up biofilm. The aim of this study was to evaluate the association between enteric viruses and biofilms on food contact surfaces. Formed biofilms of mono- and multispecies cultures were prepared on glass, stainless steel, and polystyrene coupons and 10 pfu/ml of murine norovirus, rotavirus, and hepatitis A virus were added and incubated for 15 min, 90 min, and 24 h.

Effect of probiotic bacteria on porcine rotavirus OSU infection of porcine intestinal epithelial IPEC-J2 cells.

Rotavirus infections in nursing or post-weaning piglets are known to cause diarrhea, which can lead to commercial losses. Probiotic supplementation is used as a prophylactic or therapeutic approach to dealing with microbial infections in humans and animals. To evaluate the effect of probiotic bacteria on porcine rotavirus infections, non-transformed porcine intestinal epithelial IPEC-J2 cells were used as an in vitro model, and three different procedures were tested.

Targeting a Tumor-Specific Epitope on Podocalyxin Increases Survival in Human Tumor Preclinical Models.

Podocalyxin (Podxl) is a CD34-related cell surface sialomucin that is normally highly expressed by adult vascular endothelia and kidney podocytes where it plays a key role in blocking adhesion. Importantly, it is also frequently upregulated on a wide array of human tumors and its expression often correlates with poor prognosis. We previously showed that, in xenograft studies, Podxl plays a key role in metastatic disease by making tumor initiating cells more mobile and invasive.

Real-world serological responses to extended-interval and heterologous COVID-19 mRNA vaccination in frail, older people (UNCoVER): an interim report from a prospective observational cohort study.

Background: The use of COVID-19 vaccines has been prioritised to protect the most vulnerable-notably, older people. Because of fluctuations in vaccine availability, strategies such as delayed second dose and heterologous prime-boost have been used. However, the effectiveness of these strategies in frail, older people are unknown.

The swine enteric virome in a commercial production system and its association with neonatal diarrhea.

Swine are an important food source worldwide and producers may not always be aware of the variety of the pathogens infecting their herds, particularly viruses. In this study, 12 enteric viruses were monitored in a total of 181 diarrheic and healthy piglets; namely porcine astrovirus groups 1-5 (poAstV1-5), rotavirus A and C (RVA-RVC), caliciviruses (CaVs), porcine kobuvirus (PoK), hepatitis E virus (HEV), and torque teno sus virus 1 and k2 (TTsuV1-k2). All animals were sampled before 3 weeks of age, and then at 5, 12 and 20 weeks of age.

Human and Mouse Eosinophils Differ in Their Ability to Biosynthesize Eicosanoids, Docosanoids, the Endocannabinoid 2-Arachidonoyl-glycerol and Its Congeners.

High eosinophil (EOS) counts are a key feature of eosinophilic asthma. EOS notably affect asthmatic response by generating several lipid mediators. Mice have been utilized in hopes of defining new pharmacological targets to treat asthma.

Countering the advert effects of lung cancer on the anticancer potential of dendritic cell populations reinstates sensitivity to anti-PD-1 therapy.

Lung cancer is the leading cause of cancer-related deaths. While the recent use of immune checkpoint inhibitors significantly improves patient outcomes, responsiveness remains restricted to a small proportion of patients. Conventional dendritic cells (DCs) play a major role in anticancer immunity.

Scientific and Regulatory Policy Committee Points to Consider: Fixation, Trimming, and Sectioning of Nonrodent Eyes and Ocular Tissues for Examination in Ocular and General Toxicity Studies.

A Working Group of the Society of Toxicologic Pathology's Scientific and Regulatory Policy Committee conducted a technical and scientific review of current practices relating to the fixation, trimming, and sectioning of the nonrodent eye to identify key points and species-specific anatomical landmarks to consider when preparing and evaluating eyes of rabbits, dogs, minipigs, and nonhuman primates from ocular and general toxicity studies. The topics addressed in this article include determination of situations when more comprehensive evaluation of the globe and/or associated extraocular tissues should be implemented (expanded ocular sampling), and what constitutes expanded ocular sampling. In addition, this manuscript highlights the practical aspects of fixing, trimming, and sectioning the eye to ensure adequate histopathological evaluation of all major ocular structures, including the cone-dense areas (visual streak/macula/fovea) of the retina for rabbits, dogs, minipigs, and nonhuman primates, which is a current regulatory expectation for ocular toxicity studies.

Comprehensive Risk Pathway of the Qualitative Likelihood of Human Exposure to Severe Acute Respiratory Syndrome Coronavirus 2 from the Food Chain.

Abstract: A group of experts from all Canadian federal food safety partners was formed to monitor the potential issues relating to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) food contamination, to gather and consider all of the relevant evidence and to determine the impact for Canadian food safety. A comprehensive risk pathway was generated to consider the likelihood of a SARS-CoV-2 contamination event at any of the relevant steps of the food processing and handling chain and the potential for exposure and transmission of the virus to the consumer. The scientific evidence was reviewed and assessed for each event in the pathway, taking into consideration relevant elements that could increase or mitigate the risk of contamination.

Mutant Mice and Animal Models of Airway Allergic Disease.

Eosinophilia is a hallmark of allergic airway inflammation, and eosinophils represent an integral effector leukocyte through their release of various granule-stored cytokines and proteins. Numerous mouse models have been developed to mimic clinical disease and they have been instrumental in furthering our understanding of the role of eosinophils in disease. Most of these models consist of intranasal (i.

Immunology and Pathology in Ocular Drug Development.

Clear vision is dependent on features that protect the anatomical integrity of the eye (cornea and sclera) and those that contribute to internal ocular homeostasis by conferring hemangiogenic (avascular tissues and antiangiogenic factors), lymphangiogenic (lack of draining lymphatics), and immunologic (tight junctions that form blood-ocular barriers, immunosuppressive cells, and modulators) privileges. The later examples are necessary components that enable the eye to maintain an immunosuppressive environment that responds to foreign invaders in a deviated manner, minimizing destructive inflammation that would impair vision. These conditions allowed for the observations made by Medawar, in 1948, of delayed rejection of allogenic tissue grafts in the anterior chamber of mouse eye and permit the sequestration of foreign invaders (eg, Toxoplasma gondii) within the retina of healthy individuals.

Treatments of porcine fecal samples affect high-throughput virome sequencing results.

The porcine enteric microbiota is currently extensively studied, taking advantage of developments in high-throughput sequencing technologies. However, the viral part of the microbiota, the virome, is being lightly explored, and the impact of the pretreatments used before sequencing the viruses is barely considered. In this study, the impacts of filtration, RNase and DNase treatments on virus reads recovery and diversity after sequencing on a MiSeq platform were assessed on fecal samples individually taken at <3, 5, 12 and 20 weeks from two piglets.

Recapitulating macro-scale tissue self-organization through organoid bioprinting.

Bioprinting promises enormous control over the spatial deposition of cells in three dimensions, but current approaches have had limited success at reproducing the intricate micro-architecture, cell-type diversity and function of native tissues formed through cellular self-organization. We introduce a three-dimensional bioprinting concept that uses organoid-forming stem cells as building blocks that can be deposited directly into extracellular matrices conducive to spontaneous self-organization. By controlling the geometry and cellular density, we generated centimetre-scale tissues that comprise self-organized features such as lumens, branched vasculature and tubular intestinal epithelia with in vivo-like crypts and villus domains.