Transmucosal glucagon rapidly increases blood glucose concentration in healthy cats.

Objectives: To evaluate the effect of transmucosal glucagon powder (Baqsimi; Amphastar Pharmaceuticals) on blood glucose (BG) concentrations in healthy cats and describe adverse reactions to its administration.

Methods: A randomized, controlled, crossover study was conducted on six healthy cats with a 7-day washout period between treatments. Transmucosal glucagon powder was administered intranasally and rectally and compared with intranasal placebo.

Next steps for targeted protein degradation.

Targeted protein degradation (TPD) has greatly advanced as a therapeutic strategy in the past two decades, and we are on the cusp of rationally designed protein degraders reaching clinical approval. Offering pharmacological advantages relative to occupancy-driven protein inhibition, chemical methods for regulating biomolecular proximity have provided opportunities to tackle disease-related targets that were undruggable. Despite the pre-clinical success of designed degraders and existence of clinical therapies that serendipitously utilize TPD, expansion of the TPD toolbox is necessary to identify and characterize the next generation of molecular degraders.

An atypical E3 ligase safeguards the ribosome during nutrient stress.

Metabolic stress must be effectively mitigated for the survival of cells and organisms. Ribosomes have emerged as signaling hubs that sense metabolic perturbations and coordinate responses that either restore homeostasis or trigger cell death. As yet, the mechanisms governing these cell fate decisions are not well understood.

Development of Ligands and Degraders Targeting MAGE-A3.

Type I melanoma antigen (MAGE) family members are detected in numerous tumor types, and expression is correlated with poor prognosis, high tumor grade, and increased metastasis. Type I MAGE proteins are typically restricted to reproductive tissues, but expression can recur during tumorigenesis. Several biochemical functions have been elucidated for them, and notably, MAGEs regulate proteostasis by serving as substrate recognition modules for E3 ligase complexes.

Assessing ventilation through ambient carbon dioxide concentrations across multiple healthcare levels in Ghana.

Infection prevention and control (IPC) measures safeguard primary healthcare systems, especially as the infectious disease landscape evolves due to climate and environmental change, increased global mobility, and vaccine hesitancy and inequity, which can introduce unexpected pathogens. This study explores the importance of an "always-on," low-cost IPC approach, focusing on the role of natural ventilation in health facilities, particularly in low-resource settings. Ambient carbon dioxide (CO2) levels are increasingly used as a measure of ventilation effectiveness allowing for spot checks and targeted ventilation improvements.

Isolation of feline islets of Langerhans by selective osmotic shock produces glucose responsive islets.

Introduction: Pancreatic islet isolation is essential for studying islet physiology, pathology, and transplantation, and feline islets could be an important model for human type II diabetes mellitus (T2D). Traditional isolation methods utilizing collagenases inflict damage and, in cats, may contribute to the difficulty in generating functional islets, as demonstrated by glucose-stimulated insulin secretion (GSIS). GLUT2 expression in β cells may allow for adaptation to hyperosmolar glucose solutions while exocrine tissue is selectively disrupted.

Interferon-γ/IL-2 ELISpot and mRNA Responses to the SARS-CoV2, Feline Coronavirus Serotypes 1 (FCoV1), and FCoV2 Receptor Binding Domains by the T Cells from COVID-19-Vaccinated Humans and FCoV1-Infected Cats.

The receptor binding domain (RBD) of SARS-CoV-2 (SCoV2) has been used recently to identify the RBD sequences of feline coronavirus serotypes 1 (FCoV1) and 2 (FCoV2). Cats naturally infected with FCoV1 have been shown to possess serum reactivities with FCoV1 and SCoV2 RBDs but not with FCoV2 RBD. In the current study, COVID-19-vaccinated humans and FCoV1-infected laboratory cats were evaluated for interferon-gamma (IFNγ) and interleukin-2 (IL-2 ELISpot responses by their peripheral blood mononuclear cells (PBMC) to SCoV2, FCoV1, and FCoV2 RBDs.

Development of a Small Molecule Downmodulator for the Transcription Factor Brachyury.

Brachyury is an oncogenic transcription factor whose overexpression drives chordoma growth. The downmodulation of brachyury in chordoma cells has demonstrated therapeutic potential, however, as a transcription factor it is classically deemed "undruggable". Given that direct pharmacological intervention against brachyury has proven difficult, attempts at intervention have instead targeted upstream kinases.

Effect of Coal Mining on Health Outcomes Between Male and Female Miners in Southern West Virginia: A Brief Report.

Purpose: There is evidence of an association between coal mining and an increased prevalence of respiratory and cardiovascular disease (CVD). Mining is significantly associated with elevated chronic CVD mortality rates. Research is limited and looks at the differences between specific health outcomes between male and female coal miners.

The impact of anthropogenic climate change on pediatric viral diseases.

The adverse effects of climate change on human health are unfolding in real time. Environmental fragmentation is amplifying spillover of viruses from wildlife to humans. Increasing temperatures are expanding mosquito and tick habitats, introducing vector-borne viruses into immunologically susceptible populations.

Assessment of the FreeStyle Libre 2 interstitial glucose monitor in hypo- and euglycemic cats.

Background: Continuous glucose monitoring systems have been validated for eu- and hyperglycemic cats. The FreeStyle Libre 2 (FSL2) is sufficiently accurate in people during hypoglycemia to guide critical treatment decisions without confirmation of blood glucose concentration (BG).

Objectives: Assess FSL2 accuracy in cats with hypoglycemia.

Geometric, landmark-guided technique reduces tissue trauma, surgery time, and subjective difficulty for canine peripheral lymphadenectomies: an educational crossover study.

Objective: To compare the effect of a geometric, landmark-guided lymphadenectomy (LL) approach to peripheral lymph nodes (LNs) on successful LN identification, surgical time, tissue trauma, and ease of LN identification compared to standard lymphadenectomy (SL) and methylene blue-guided lymphadenectomy (MBL).

Sample: 18 adult, mixed-breed canine cadavers operated on by 7 veterinarians and 5 fourth-year veterinary students between July 23 and October 12, 2022.

Methods: Participants were provided standardized, publicly available materials regarding the anatomy and surgical techniques for SL of 3 peripheral lymphocentrums: superficial cervical, axillary (ALN), and superficial inguinal (SILN).

Both Feline Coronavirus Serotypes 1 and 2 Infected Domestic Cats Develop Cross-Reactive Antibodies to SARS-CoV-2 Receptor Binding Domain: Its Implication to Pan-CoV Vaccine Development.

The current study was initiated when our specific-pathogen-free laboratory toms developed unexpectedly high levels of cross-reactive antibodies to human SARS-CoV-2 (SCoV2) receptor binding domain (RBD) upon mating with feline coronavirus (FCoV)-positive queens. Multi-sequence alignment analyses of SCoV2 Wuhan RBD and four strains each from FCoV serotypes 1 and 2 (FCoV1 and FCoV2) demonstrated an amino acid sequence identity of 11.5% and a similarity of 31.

Emerging Issues on Tropane Alkaloid Contamination of Food in Europe.

The occurrence of tropane alkaloids (TAs), toxic plant metabolites, in food in Europe was studied to identify those TAs in food most relevant for human health. Information was extracted from the literature and the 2016 study from the European Food Safety Authority. Calystegines were identified as being inherent TAs in foods common in Europe, such as (potato), (eggplant, aubergine), (bell pepper) and (broccoli, Brussels sprouts).

Protein degraders enter the clinic - a new approach to cancer therapy.

Heterobifunctional protein degraders, such as PROteolysis TArgeting Chimera (PROTAC) protein degraders, constitute a novel therapeutic modality that harnesses the cell's natural protein-degradation machinery - that is, the ubiquitin-proteasome system - to selectively target proteins involved in disease pathogenesis for elimination. Protein degraders have several potential advantages over small-molecule inhibitors that have traditionally been used for cancer treatment, including their event-driven (rather than occupancy-driven) pharmacology, which permits sub-stoichiometric drug concentrations for activity, their capacity to act iteratively and target multiple copies of a protein of interest, and their potential to target nonenzymatic proteins that were previously considered 'undruggable'. Following numerous innovations in protein degrader design and rigorous evaluation in preclinical models, protein degraders entered clinical testing in 2019.

Targeted Dephosphorylation of Tau by Phosphorylation Targeting Chimeras (PhosTACs) as a Therapeutic Modality.

Microtubule-associated protein tau is essential for microtubule assembly and stabilization. Hyperphosphorylation of the microtubule-associated protein tau plays an important pathological role in the development of Alzheimer's disease and other tauopathies. studies using kinase inhibitors suggest that reducing tau phosphorylation levels has therapeutic potential; however, such approaches showed limited benefits.

Regulated Induced Proximity Targeting Chimeras (RIPTACs): a Novel Heterobifunctional Small Molecule Therapeutic Strategy for Killing Cancer Cells Selectively.

While specific cell signaling pathway inhibitors have yielded great success in oncology, directly triggering cancer cell death is one of the great drug discovery challenges facing biomedical research in the era of precision oncology. Attempts to eradicate cancer cells expressing unique target proteins, such as antibody-drug conjugates (ADCs), T-cell engaging therapies, and radiopharmaceuticals have been successful in the clinic, but they are limited by the number of targets given the inability to target intracellular proteins. More recently, heterobifunctional small molecules such as Proteolysis Targeting Chimera (PROTACs) have paved the way for protein proximity inducing therapeutic modalities.

OligoTRAFTACs: A generalizable method for transcription factor degradation.

Dysregulated transcription factors (TFs) that rewire gene expression circuitry are frequently identified as key players in disease. Although several TFs have been drugged with small molecules, the majority of oncogenic TFs are not currently pharmaceutically tractable due to their paucity of ligandable pockets. The first generation of transcription factor targeting chimeras (TRAFTACs) was developed to target TFs for proteasomal degradation by exploiting their DNA binding ability.

Acceptability of Active Shooter Prevention Strategies on College and University Campuses.

Colleges and universities are challenged with making their campuses safe from many threats of violence such as active shooters by using strategies that are effective and acceptable to their campus communities. Implementing strategies that are ineffective can waste resources and implementing strategies that are unacceptable may result in students, faculty, and staff that protest or leave the campus. The current study evaluated the acceptability of 11 different strategies to prevent active shooters on college/university campuses.

Targeted Degradation of mRNA Decapping Enzyme DcpS by a VHL-Recruiting PROTAC.

The RNA decapping scavenger protein, DcpS, has recently been identified as a dependency in acute myeloid leukemia (AML). The potent DcpS inhibitor RG3039 attenuates AML cell viability, and shRNA knockdown of DcpS is also antiproliferative. Importantly, DcpS was found to be non-essential in normal human hematopoietic cells, which opens a therapeutic window for AML treatment by DcpS modulation.