Widespread occurrence of benzimidazole resistance single nucleotide polymorphisms in the canine hookworm, Ancylostoma caninum, in Australia.

Canine hookworm (Ancylostoma caninum), a gastrointestinal nematode of domestic dogs, principally infects the small intestine of dogs and has the potential to cause zoonotic disease. In greyhounds and pet dogs in the USA, A. caninum has been shown to be resistant to multiple anthelmintics.

Prevalence of feline upper respiratory tract pathogens and risk factors for clinical disease and final outcomes in an RSPCA shelter in Queensland, Australia.

Introduction: Feline respiratory tract infection poses a serious challenge in animal shelters. Potential risk factors include pathogens introduced through animals entering the shelter. We aimed to determine the proportion of animals shedding feline upper respiratory tract (URT) pathogens at the time of entry and to assess how this contributed to the burden of clinical disease and final outcomes.

Low concentration cell painting images enable the identification of highly potent compounds.

Image-based models that use features extracted from cell microscopy images can estimate the activity of small molecules in various biological assays. Typically, models are trained on images stained by an optimized protocol (e.g.

Impact of regression modeling on the assessment and harmonization of a point-of-care analyzer and commercial laboratory analyzer for feline plasma biochemistry testing.

Background: Regression describes the relationship of results from two analyzers, and the generated equation can be used to harmonize results. Point-of-care (POC) analyzers cannot be calibrated by the end user, so regression offers an opportunity for calculated harmonization. Harmonization (uniformity) of laboratory results facilitates the use of common reference intervals and medical decision thresholds.

Adenotonsillectomy for Obstructive Sleep Apnea in Children.

Obstructed breathing is the most common indication for tonsillectomy in children. Although tonsillectomy is performed frequently worldwide, the surgery is associated with a number of significant complications such as bleeding and respiratory failure. Complication risk depends on a number of complex factors, including indications for surgery, demographics, patient comorbidities, and variations in perioperative techniques.

Analytical performance of feline plasma on current Heska and IDEXX point-of-care biochemistry analyzers compared with a commercial laboratory analyzer.

Background: Point-of-care (POC) biochemistry analyzers are widely used in small animal clinical practice but infrequently independently assessed for performance.

Objective: To assess the performance of two current model point-of-care biochemistry analyzers (Heska Element DC and IDEXX Catalyst) compared with a commercial laboratory analyzer (Cobas 8000).

Methods: One hundred twenty-one cats from a feline hospital population were sampled with plasma results from a single lithium heparin tube assessed on all three analyzers.

A flexible, image-based, high-throughput platform encompassing in-depth cell profiling to identify broad-spectrum coronavirus antivirals with limited off-target effects.

The recent pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) posed a major threat to global health. Although the World Health Organization ended the public health emergency status, antiviral drugs are needed to address new variants of SARS-CoV-2 and future pandemics. To identify novel broad-spectrum coronavirus drugs, we developed a high-content imaging platform compatible with high-throughput screening.

Leveraging Cell Painting Images to Expand the Applicability Domain and Actively Improve Deep Learning Quantitative Structure-Activity Relationship Models.

The search for chemical hit material is a lengthy and increasingly expensive drug discovery process. To improve it, ligand-based quantitative structure-activity relationship models have been broadly applied to optimize primary and secondary compound properties. Although these models can be deployed as early as the stage of molecule design, they have a limited applicability domain─if the structures of interest differ substantially from the chemical space on which the model was trained, a reliable prediction will not be possible.

Angie-LAMP for diagnosis of human eosinophilic meningitis using dog as proxy: A LAMP assay for Angiostrongylus cantonensis DNA in cerebrospinal fluid.

Background: Angiostrongylus cantonensis (rat lungworm) is recognised as the leading cause of human eosinophilic meningitis, a serious condition observed when nematode larvae migrate through the CNS. Canine Neural Angiostrongyliasis (CNA) is the analogous disease in dogs. Both humans and dogs are accidental hosts, and a rapid diagnosis is warranted.

Identification of Z-Tyr-Ala-CHN, a Cathepsin L Inhibitor with Broad-Spectrum Cell-Specific Activity against Coronaviruses, including SARS-CoV-2.

The ongoing COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is partly under control by vaccination. However, highly potent and safe antiviral drugs for SARS-CoV-2 are still needed to avoid development of severe COVID-19. We report the discovery of a small molecule, Z-Tyr-Ala-CHN, which was identified in a cell-based antiviral screen.

Remodeling oncogenic transcriptomes by small molecules targeting NONO.

Much of the human proteome is involved in mRNA homeostasis, but most RNA-binding proteins lack chemical probes. Here we identify electrophilic small molecules that rapidly and stereoselectively decrease the expression of transcripts encoding the androgen receptor and its splice variants in prostate cancer cells. We show by chemical proteomics that the compounds engage C145 of the RNA-binding protein NONO.

Clinicopathologic and immunophenotypic features in dogs with presumptive large granular lymphocyte leukaemia.

Large granular lymphocytic leukaemia (LGLL) has been described in a range of species but has been most commonly reported in humans and dogs. In both species, this neoplasia exhibits diversity in both phenotype and biological behaviour with phenotype only partially predicting behaviour. There is currently little knowledge of concurrent haematological and serum biochemistry features or concurrent occurrence of distinct neoplasia in canine LGLL cases.

Establishment of reference intervals for plasma protein electrophoresis and comparison of biochemical and protein electrophoresis evaluation of albumin in central bearded dragons (Pogona vitticeps).

The aim of this study is to develop a reference interval for plasma protein electrophoresis for wild free-roaming central bearded dragons (Pogona vitticeps). This will assist the veterinarian in diagnosing and monitoring diseases in wild and captive animals. The study group consisted of 29 wild central bearded dragons of which 22 were males and 7 were females.

Development of a cellular high-content, immunofluorescent HBV core assay to identify novel capsid assembly modulators that induce the formation of aberrant HBV core structures.

Hepatitis B Virus (HBV) core protein has multiple functions in the viral life cycle and is an attractive target for new anti-viral therapies. Capsid assembly modulators (CAMs) target the core protein and induce the formation of either morphologically normal (CAM-N) or aberrant structures (CAM-A), both devoid of genomic material. To date a diverse family of CAM-N chemotypes has been identified, but in contrast, described CAM-As are based on the heteroaryldihydropyrimidine (HAP) scaffold.

Discovery of JNJ-63576253, a Next-Generation Androgen Receptor Antagonist Active Against Wild-Type and Clinically Relevant Ligand Binding Domain Mutations in Metastatic Castration-Resistant Prostate Cancer.

Numerous mechanisms of resistance arise in response to treatment with second-generation androgen receptor (AR) pathway inhibitors in metastatic castration-resistant prostate cancer (mCRPC). Among these, point mutations in the ligand binding domain can transform antagonists into agonists, driving the disease through activation of AR signaling. To address this unmet need, we report the discovery of JNJ-63576253, a next-generation AR pathway inhibitor that potently abrogates AR signaling in models of human prostate adenocarcinoma.

Haematology and plasma biochemistry reference intervals in wild bearded dragons (Pogona vitticeps).

The aim of the study is to provide haematology and plasma biochemistry reference intervals for wild free-roaming central bearded dragons (Pogona vitticeps). These data will aid the veterinarian in determining the health and husbandry status of the pet bearded dragon. The study group consisted of 130 wild central bearded dragons.

Further studies of neuroangiostrongyliasis (rat lungworm disease) in Australian dogs: 92 new cases (2010-2020) and results for a novel, highly sensitive qPCR assay.

The principal aim of this study was to optimize the diagnosis of canine neuroangiostrongyliasis (NA). In total, 92 cases were seen between 2010 and 2020. Dogs were aged from 7 weeks to 14 years (median 5 months), with 73/90 (81%) less than 6 months and 1.

Tales of 1,008 small molecules: phenomic profiling through live-cell imaging in a panel of reporter cell lines.

Phenomic profiles are high-dimensional sets of readouts that can comprehensively capture the biological impact of chemical and genetic perturbations in cellular assay systems. Phenomic profiling of compound libraries can be used for compound target identification or mechanism of action (MoA) prediction and other applications in drug discovery. To devise an economical set of phenomic profiling assays, we assembled a library of 1,008 approved drugs and well-characterized tool compounds manually annotated to 218 unique MoAs, and we profiled each compound at four concentrations in live-cell, high-content imaging screens against a panel of 15 reporter cell lines, which expressed a diverse set of fluorescent organelle and pathway markers in three distinct cell lineages.

Systemic mastocytosis and probable mast cell leukaemia in a koala (Phascolarctos cinereus).

Background: To the authors' knowledge, this is the first report of mast cell neoplasia in a koala (Phascolarctos cinereus).

Case Report: An adult female koala was presented for rapidly deteriorating health and death of a pouch young. Significant weight loss was apparent despite supplemental feeding; the abdomen was distended; and the koala was weak and mentally depressed.

Spontaneous Pneumomediastinum and Subcutaneous Emphysema following Cocaine Inhalation and Ecstasy Ingestion.

Spontaneous pneumomediastinum (SPM) and subcutaneous emphysema are rare complications of illicit drug abuse. Thorough history, examination, and investigations are required to rule out fatal complications such as oesophageal perforation. We present a case of a 21-year-old male presenting with pleuritic chest pain one day after cocaine inhalation and ingesting ecstasy.

Genetically Engineered iPSC-Derived FTDP-17 MAPT Neurons Display Mutation-Specific Neurodegenerative and Neurodevelopmental Phenotypes.

Tauopathies such as frontotemporal dementia (FTD) remain incurable to date, partially due to the lack of translational in vitro disease models. The MAPT gene, encoding the microtubule-associated protein tau, has been shown to play an important role in FTD pathogenesis. Therefore, we used zinc finger nucleases to introduce two MAPT mutations into healthy donor induced pluripotent stem cells (iPSCs).

Therapeutic efficacy of a respiratory syncytial virus fusion inhibitor.

Respiratory syncytial virus is a major cause of acute lower respiratory tract infection in young children, immunocompromised adults, and the elderly. Intervention with small-molecule antivirals specific for respiratory syncytial virus presents an important therapeutic opportunity, but no such compounds are approved today. Here we report the structure of JNJ-53718678 bound to respiratory syncytial virus fusion (F) protein in its prefusion conformation, and we show that the potent nanomolar activity of JNJ-53718678, as well as the preliminary structure-activity relationship and the pharmaceutical optimization strategy of the series, are consistent with the binding mode of JNJ-53718678 and other respiratory syncytial virus fusion inhibitors.

Prevalence of clinicopathological changes in healthy middle-aged dogs and cats presenting to veterinary practices for routine procedures.

Objective: The objective of the present study was to investigate the frequency of abnormal clinicopathological parameters in a population of client-owned clinically healthy middle-aged dogs and cats.

Materials And Methods: Biochemical and haematological profiles, urinalysis and total T4 were measured in clinically healthy middle-aged dogs (age, 5-8 years) and cats (age, 6-9 years) presenting to veterinary practices for routine procedures.

Results: Of the 406 dogs, only 55 had no abnormalities identified in the testing panel.