Serum metabolome analysis in hyperthyroid cats before and after radioactive iodine therapy.

Hyperthyroidism is the most common feline endocrinopathy. In hyperthyroid humans, untargeted metabolomic analysis identified persistent metabolic derangements despite achieving a euthyroid state. Therefore, we sought to define the metabolome of hyperthyroid cats and identify ongoing metabolic changes after treatment. We prospectively compared privately-owned hyperthyroid cats (n = 7) admitted for radioactive iodine (I-131) treatment and euthyroid privately-owned control (CON) cats (n = 12). Serum samples were collected before (T0), 1-month (T1), and three months after (T3) I-131 therapy for untargeted metabolomic analysis by MS/MS. Hyperthyroid cats (T0) had a distinct metabolic signature with 277 significantly different metabolites than controls (70 increased, 207 decreased). After treatment, 66 (T1 vs. CON) and 64 (T3 vs. CON) metabolite differences persisted. Clustering and data reduction analysis revealed separate clustering of hyperthyroid (T0) and CON cats with intermediate phenotypes after treatment (T1 & T3). Mevalonate/mevalonolactone and creatine phosphate were candidate biomarkers with excellent discrimination between hyperthyroid and healthy cats. We found several metabolic derangements (e.g., decreased carnitine and α-tocopherol) do not entirely resolve after achieving a euthyroid state after treating hyperthyroid cats with I-131. Further investigation is warranted to determine diagnostic and therapeutic implications for candidate biomarkers and persistent metabolic abnormalities.

Randomized controlled trial of hydrolyzed fish diets in dogs with chronic enteropathy.

BACKGROUND: The role of diet in the pathogenesis and treatment of chronic enteropathies (CE) in dogs is unresolved. OBJECTIVES: To compare the ability of diets composed of hydrolyzed fish, rice starch, and fish oil without (HF) or with prebiotics, turmeric, and high cobalamin (HF+) against a limited ingredient diet containing mixed nonhydrolyzed antigens and oils (control) to resolve clinical signs and maintain serum cobalamin and folate concentrations in dogs with nonprotein losing CE (non-PLE). To determine the ability of hydrolyzed fish diets to support recovery and remission in dogs with PLE. ANIMALS: Thirty-one client-owned dogs with CE: 23 non-PLE, 8 PLE. METHODS: Randomized, blinded, controlled trial. Diets were fed for 2 weeks; responders continued for 12 weeks. Nonresponders were crossed over to another diet for 12 weeks. Response was determined by standardized clinical evaluation with long-term follow-up at 26 weeks. Concurrent medications were allowed in PLE. RESULTS: Nineteen of 23 (83%; 95% confidence interval [CI], 60%-94%) non-PLE CE responded clinically to their initial diet, with no difference between diets (P > .05). Four nonresponders responded to another diet, with sustained remission of 18/18 (100%; 95%CI, 78%-100%) at 26 weeks. Serum cobalamin concentration was increased (P < .05) and maintained by diet. Serum folate concentration decreased posttreatment (P < .05) but was restored by dietary supplementation. Hydrolyzed fish diets supported weight gain, serum albumin concentration, and recovery (P < .05) in dogs with PLE. CONCLUSIONS AND CLINICAL IMPORTANCE: Changing diet, independent of antigen restriction or supplemental ingredients, induced long-term remission in dogs with non-PLE CE. Serum cobalamin and folate concentrations were maintained by diet. Hydrolyzed fish diets supported clinical recovery and remission in PLE.

Biological variation of serum thyrotropin and thyroid hormones concentrations determined at 8-week intervals for 1 year in clinically healthy cats.

BACKGROUND: Cats commonly develop thyroid disease but little is known about the long-term biological variability of serum thyroid hormone and thyrotropin (thyroid-stimulating hormone; TSH) concentrations. OBJECTIVES: We aimed to determine the long-term biological variation of thyroid hormones and TSH in clinically healthy cats. METHODS: A prospective, observational study was carried out. Serum samples for analysis of total thyroxine (T4, by radioimmunoassay [RIA] and homogenous enzyme immunoassay [EIA]), triiodothyronine (T3 ), free T4 (by dialysis), and TSH were obtained every 8 weeks for 1 year from 15 healthy cats, then frozen until single-batch analysis. Coefficients of variation (CV) within individual cats ( CV I ) and among individual cats ( CV G ), as well as the variation between duplicates (ie, analytical variation [ CV A ]) were determined with restricted maximum likelihood estimation. The indices of individuality (IoI) and reference change values (RCVs) for each hormone were calculated. RESULTS: Some thyroid hormones showed similar (total T4 by EIA) or greater (TSH) interindividual relative to intraindividual variation resulting in intermediate to high IoI, consistent with previous studies evaluating the biological variation of these hormones weekly for 5-6 weeks. By contrast, total T4 (by RIA) and free T4 had a low IoI. Total T3 had a high ratio of CV A to CV I ; therefore, interindividual variation could not be distinguished from analytical variation. No seasonal variability in the hormones could be demonstrated. CONCLUSIONS: Clinicians might improve the diagnosis of feline thyroid disease by establishing baseline concentrations for analytes with intermediate-high IoI (total T4, TSH) for individual cats and applying RCVs to subsequent measurements.

Analytical validation of a multi-cancer early detection test with cancer signal origin using a cell-free DNA-based targeted methylation assay.

The analytical validation is reported for a targeted methylation-based cell-free DNA multi-cancer early detection test designed to detect cancer and predict the cancer signal origin (tissue of origin). A machine-learning classifier was used to analyze the methylation patterns of >105 genomic targets covering >1 million methylation sites. Analytical sensitivity (limit of detection [95% probability]) was characterized with respect to tumor content by expected variant allele frequency and was determined to be 0.07%-0.17% across five tumor cases and 0.51% for the lymphoid neoplasm case. Test specificity was 99.3% (95% confidence interval, 98.6-99.7%). In the reproducibility and repeatability study, results were consistent in 31/34 (91.2%) pairs with cancer and 17/17 (100%) pairs without cancer; between runs, results were concordant for 129/133 (97.0%) cancer and 37/37 (100%) non-cancer sample pairs. Across 3- to 100-ng input levels of cell-free DNA, cancer was detected in 157/182 (86.3%) cancer samples but not in any of the 62 non-cancer samples. In input titration tests, cancer signal origin was correctly predicted in all tumor samples detected as cancer. No cross-contamination events were observed. No potential interferent (hemoglobin, bilirubin, triglycerides, genomic DNA) affected performance. The results of this analytical validation study support continued clinical development of a targeted methylation cell-free DNA multi-cancer early detection test.

Biological variation of biochemical analytes determined at 8-week intervals for 1 year in clinically healthy cats.

BACKGROUND: Biological variation helps determine whether population-based or subject-based reference intervals are more appropriate to assess changes in serial analytical values. Previous studies have investigated the biological variation of biochemical analytes weekly or with variable frequency over 5-14 weeks in cats, but none have considered biological variation at less frequent intervals over 1 year. OBJECTIVES: We aimed to evaluate the long-term biological variation of 19 biochemical analytes in clinically healthy cats. METHODS: A prospective, observational study in which 15 clinically healthy, client-owned cats were sampled for serum biochemical analyses every 8 weeks for 1 year. Frozen serum samples were single-batch analyzed. Restricted maximum likelihood estimation was used to determine the coefficients of variation (CV), describing variation within each cat, between cats, and the analytical variation. These CVs were used to determine the indices of individuality and reference change values (RCVs). RESULTS: Albumin, alkaline phosphatase, creatine kinase, and globulin had high indices of individuality, indicating that they are best evaluated by RCVs. Phosphorus, potassium, chloride, sodium, symmetric dimethylarginine, and total CO2 had low indices of individuality, indicating that population-based reference intervals are appropriate. Alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, calcium, cholesterol, creatinine, glucose, total bilirubin, and total protein had intermediate indices of individuality, indicating that RCVs may provide additional insight into the interpretation of analyte measurements beyond the population-based reference intervals. CONCLUSIONS: For many analytes, the biological variation detected was similar to that reported in prior studies. Clinicians should consider the biological variation of analytes to best interpret clinically relevant changes in serial analyte measurements.

Enhancing DNA barcode reference libraries by harvesting terrestrial arthropods at the Smithsonian's National Museum of Natural History.

The use of DNA barcoding has revolutionised biodiversity science, but its application depends on the existence of comprehensive and reliable reference libraries. For many poorly known taxa, such reference sequences are missing even at higher-level taxonomic scales. We harvested the collections of the Smithsonian's National Museum of Natural History (USNM) to generate DNA barcoding sequences for genera of terrestrial arthropods previously not recorded in one or more major public sequence databases. Our workflow used a mix of Sanger and Next-Generation Sequencing (NGS) approaches to maximise sequence recovery while ensuring affordable cost. In total, COI sequences were obtained for 5,686 specimens belonging to 3,737 determined species in 3,886 genera and 205 families distributed in 137 countries. Success rates varied widely according to collection data and focal taxon. NGS helped recover sequences of specimens that failed a previous run of Sanger sequencing. Success rates and the optimal balance between Sanger and NGS are the most important drivers to maximise output and minimise cost in future projects. The corresponding sequence and taxonomic data can be accessed through the Barcode of Life Data System, GenBank, the Global Biodiversity Information Facility, the Global Genome Biodiversity Network Data Portal and the NMNH data portal.

A workflow for expanding DNA barcode reference libraries through 'museum harvesting' of natural history collections.

Natural history collections are the physical repositories of our knowledge on species, the entities of biodiversity. Making this knowledge accessible to society - through, for example, digitisation or the construction of a validated, global DNA barcode library - is of crucial importance. To this end, we developed and streamlined a workflow for 'museum harvesting' of authoritatively identified Diptera specimens from the Smithsonian Institution's National Museum of Natural History. Our detailed workflow includes both on-site and off-site processing through specimen selection, labelling, imaging, tissue sampling, databasing and DNA barcoding. This approach was tested by harvesting and DNA barcoding 941 voucher specimens, representing 32 families, 819 genera and 695 identified species collected from 100 countries. We recovered 867 sequences (> 0 base pairs) with a sequencing success of 88.8% (727 of 819 sequenced genera gained a barcode > 300 base pairs). While Sanger-based methods were more effective for recently-collected specimens, the methods employing next-generation sequencing recovered barcodes for specimens over a century old. The utility of the newly-generated reference barcodes is demonstrated by the subsequent taxonomic assignment of nearly 5000 specimen records in the Barcode of Life Data Systems.

Accuracy and reliability of forensic handwriting comparisons.

Forensic handwriting examination involves the comparison of writing samples by forensic document examiners (FDEs) to determine whether or not they were written by the same person. Here we report the results of a large-scale study conducted to assess the accuracy and reliability of handwriting comparison conclusions. Eighty-six practicing FDEs each conducted up to 100 handwriting comparisons, resulting in 7,196 conclusions on 180 distinct comparison sets, using a five-level conclusion scale. Erroneous "written by" conclusions (false positives) were reached in 3.1% of the nonmated comparisons, while 1.1% of the mated comparisons yielded erroneous "not written by" conclusions (false negatives). False positive rates were markedly higher for nonmated samples written by twins (8.7%) compared to nontwins (2.5%). Notable associations between training and performance were observed: FDEs with less than 2 y of formal training generally had higher error rates, but they also had higher true positive and true negative rates because they tended to provide more definitive conclusions; FDEs with at least 2 y of formal training were less likely to make definitive conclusions, but those definitive conclusions they made were more likely to be correct (higher positive predictive and negative predictive values). We did not observe any association between writing style (cursive vs. printing) and rates of errors or incorrect conclusions. This report also provides details on the repeatability and reproducibility of conclusions, and reports how conclusions are affected by the quantity of writing and the similarity of content.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.

A molecular-based identification resource for the arthropods of Finland.

To associate specimens identified by molecular characters to other biological knowledge, we need reference sequences annotated by Linnaean taxonomy. In this study, we (1) report the creation of a comprehensive reference library of DNA barcodes for the arthropods of an entire country (Finland), (2) publish this library, and (3) deliver a new identification tool for insects and spiders, as based on this resource. The reference library contains mtDNA COI barcodes for 11,275 (43%) of 26,437 arthropod species known from Finland, including 10,811 (45%) of 23,956 insect species. To quantify the improvement in identification accuracy enabled by the current reference library, we ran 1000 Finnish insect and spider species through the Barcode of Life Data system (BOLD) identification engine. Of these, 91% were correctly assigned to a unique species when compared to the new reference library alone, 85% were correctly identified when compared to BOLD with the new material included, and 75% with the new material excluded. To capitalize on this resource, we used the new reference material to train a probabilistic taxonomic assignment tool, FinPROTAX, scoring high success. For the full-length barcode region, the accuracy of taxonomic assignments at the level of classes, orders, families, subfamilies, tribes, genera, and species reached 99.9%, 99.9%, 99.8%, 99.7%, 99.4%, 96.8%, and 88.5%, respectively. The FinBOL arthropod reference library and FinPROTAX are available through the Finnish Biodiversity Information Facility (www.laji.fi) at https://laji.fi/en/theme/protax. Overall, the FinBOL investment represents a massive capacity-transfer from the taxonomic community of Finland to all sectors of society.

Relationships between congenital peritoneopericardial diaphragmatic hernia or congenital central diaphragmatic hernia and ductal plate malformations in dogs and cats.

OBJECTIVE: To characterize the association between peritoneopericardial diaphragmatic hernia (PPDH) or congenital central diaphragmatic hernia (CCDH) and ductal plate malformations (DPMs) in dogs and cats. ANIMALS: 18 dogs and 18 cats with PPDH or CCDH and 19 dogs and 18 cats without PPDH or CCDH. PROCEDURES: Evaluation of clinical details verified PPDH or CCDH and survival times. Histologic features of nonherniated liver samples were used to categorize DPM. Immunohistochemical staining for cytokeratin-19 distinguished bile duct profiles per portal tract and for Ki-67-assessed cholangiocyte proliferation. Histologic features of herniated liver samples from PPDH or CCDH were compared with those of pathological controls (traumatic diaphragmatic hernia, n = 6; liver lobe torsion, 6; ischemic hepatopathy, 2). RESULTS: DPM occurred in 13 of 18 dogs with the proliferative-like phenotype predominating and in 15 of 18 cats with evenly distributed proliferative-like and Caroli phenotypes. Congenital hepatic fibrosis DPM was noted in 3 dogs and 2 cats and renal DPM in 3 dogs and 3 cats. No signalment, clinical signs, or clinicopathologic features discriminated DPM. Kaplan Meier survival curves were similar in dogs and cats. Bile duct profiles per portal tract in dogs (median, 5.0; range, 1.4 to 100.8) and cats (6.6; 1.9 to 11.0) with congenital diaphragmatic hernias significantly exceeded those in healthy dogs (1.4; 1.2 to 1.6) and cats (2.3; 1.7 to 2.6). Animals with DPM lacked active cholangiocyte proliferation. Histologic features characterizing malformative bile duct profiles yet without biliary proliferation were preserved in herniated liver lobes in animals with DPM. CONCLUSIONS AND CLINICAL RELEVANCE: DPM was strongly associated with PPDH and CCDH. Because DPM can impact health, awareness of its coexistence with PPDH or CCDH should prompt biopsy of nonherniated liver tissue during surgical correction of PPDH and CCDH.

Fatal Complications of Nasogastric Tube Misplacement in Two Dogs.

Provision of enteral nutrition via the use of nasoenteric feeding tubes is a commonly used method in both veterinary and human medicine. Although case reports in human medicine have identified fatalities due to misplacement of nasogastric (NG) tubes into the tracheobronchial tree and subsequent pneumothorax, there are no case reports, to our knowledge, of fatalities in veterinary patients. This case report describes two fatalities caused by misplaced NG tubes in intubated patients (one intraoperative, one postoperative). This report highlights risk factors for feeding tube complications and methods to prevent future fatalities such as two-view radiography, two-step insertion, capnography, laryngoscopic-assisted placement, and palpation of the NG tube in the stomach. The recent fatalities discussed within this case series demonstrate that deaths as a result of NG tubes misplaced into the tracheobronchial tree occur in veterinary patients, and measures should be taken to prevent this complication.

PRMT1-dependent regulation of RNA metabolism and DNA damage response sustains pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer that has remained clinically challenging to manage. Here we employ an RNAi-based in vivo functional genomics platform to determine epigenetic vulnerabilities across a panel of patient-derived PDAC models. Through this, we identify protein arginine methyltransferase 1 (PRMT1) as a critical dependency required for PDAC maintenance. Genetic and pharmacological studies validate the role of PRMT1 in maintaining PDAC growth. Mechanistically, using proteomic and transcriptomic analyses, we demonstrate that global inhibition of asymmetric arginine methylation impairs RNA metabolism, which includes RNA splicing, alternative polyadenylation, and transcription termination. This triggers a robust downregulation of multiple pathways involved in the DNA damage response, thereby promoting genomic instability and inhibiting tumor growth. Taken together, our data support PRMT1 as a compelling target in PDAC and informs a mechanism-based translational strategy for future therapeutic development.Statement of significancePDAC is a highly lethal cancer with limited therapeutic options. This study identified and characterized PRMT1-dependent regulation of RNA metabolism and coordination of key cellular processes required for PDAC tumor growth, defining a mechanism-based translational hypothesis for PRMT1 inhibitors.

Lyophilized platelets versus cryopreserved platelets for management of bleeding in thrombocytopenic dogs: A multicenter randomized clinical trial.

BACKGROUND: Thrombocytopenia in dogs is common in critical care medicine, but availability of fresh platelet concentrates in veterinary medicine can be limiting. Lyophilized platelets have long shelf-lives and can be easily transported, stored, and administered in various settings. OBJECTIVE: To evaluate the efficacy and safety of a novel trehalose-stabilized canine lyophilized platelet product in thrombocytopenic dogs with clinically-evident bleeding. ANIMALS: Eighty-eight dogs with platelet counts <50 × 103 /µL and a standardized bleeding assessment tool (DOGiBAT) score ≥2. METHODS: Multicenter, randomized, non-blinded, non-inferiority clinical trial comparing dimethyl sulfoxide (DMSO)-stabilized cryopreserved platelet concentrates (CPP) with trehalose-stabilized lyophilized platelets (LP) for control of bleeding in thrombocytopenic dogs. Dogs were randomized to receive 3 × 109 platelets/kg of LP or CPP. Primary outcome measures were change in DOGiBAT score, platelet count, need for additional red cell transfusion and all-cause mortality. RESULTS: Fifty dogs received LP and 38 received CPP. Baseline demographics and clinical characteristics of both groups were comparable. At 1-hour post-transfusion, LP were superior for change in DOGiBAT score, and non-inferior at 24-hours post-transfusion. The LP were non-inferior to CPP for change in platelet count, need for additional red blood cell units, and survival to discharge. The LP were superior for change in hematocrit at 1-hour post-transfusion, and non-inferior at 24-hours. No adverse effects were noted in either group. CONCLUSIONS AND CLINICAL IMPORTANCE: A novel trehalose-stabilized canine LP product appears to be logistically superior and is clinically non-inferior to DMSO-stabilized canine CPP for management of bleeding in thrombocytopenic dogs.

Discovery of IPN60090, a Clinical Stage Selective Glutaminase-1 (GLS-1) Inhibitor with Excellent Pharmacokinetic and Physicochemical Properties.

Inhibition of glutaminase-1 (GLS-1) hampers the proliferation of tumor cells reliant on glutamine. Known glutaminase inhibitors have potential limitations, and in vivo exposures are potentially limited due to poor physicochemical properties. We initiated a GLS-1 inhibitor discovery program focused on optimizing physicochemical and pharmacokinetic properties, and have developed a new selective inhibitor, compound 27 (IPN60090), which is currently in phase 1 clinical trials. Compound 27 attains high oral exposures in preclinical species, with strong in vivo target engagement, and should robustly inhibit glutaminase in humans.

Allosteric SHP2 Inhibitor, IACS-13909, Overcomes EGFR-Dependent and EGFR-Independent Resistance Mechanisms toward Osimertinib.

Src homology 2 domain-containing phosphatase (SHP2) is a phosphatase that mediates signaling downstream of multiple receptor tyrosine kinases (RTK) and is required for full activation of the MAPK pathway. SHP2 inhibition has demonstrated tumor growth inhibition in RTK-activated cancers in preclinical studies. The long-term effectiveness of tyrosine kinase inhibitors such as the EGFR inhibitor (EGFRi), osimertinib, in non-small cell lung cancer (NSCLC) is limited by acquired resistance. Multiple clinically identified mechanisms underlie resistance to osimertinib, including mutations in EGFR that preclude drug binding as well as EGFR-independent activation of the MAPK pathway through alternate RTK (RTK-bypass). It has also been noted that frequently a tumor from a single patient harbors more than one resistance mechanism, and the plasticity between multiple resistance mechanisms could restrict the effectiveness of therapies targeting a single node of the oncogenic signaling network. Here, we report the discovery of IACS-13909, a specific and potent allosteric inhibitor of SHP2, that suppresses signaling through the MAPK pathway. IACS-13909 potently impeded proliferation of tumors harboring a broad spectrum of activated RTKs as the oncogenic driver. In EGFR-mutant osimertinib-resistant NSCLC models with EGFR-dependent and EGFR-independent resistance mechanisms, IACS-13909, administered as a single agent or in combination with osimertinib, potently suppressed tumor cell proliferation in vitro and caused tumor regression in vivo. Together, our findings provide preclinical evidence for using a SHP2 inhibitor as a therapeutic strategy in acquired EGFRi-resistant NSCLC. SIGNIFICANCE: These findings highlight the discovery of IACS-13909 as a potent, selective inhibitor of SHP2 with drug-like properties, and targeting SHP2 may serve as a therapeutic strategy to overcome tumor resistance to osimertinib.

Biologic variation of symmetric dimethylarginine and creatinine in clinically healthy cats.

BACKGROUND: Biologic variation of biochemical analytes, both within individuals and between individuals, determines whether population-based reference intervals (RIs) are appropriate when interpreting if a particular change is clinically relevant for a specific individual. OBJECTIVES: We aimed to evaluate the biologic variation of symmetric dimethylarginine (SDMA) in clinically healthy cats. METHODS: A prospective, observational study was performed in which 10 clinically healthy, client-owned cats were sampled for serum biochemical analyses once weekly for 6 weeks. Serum samples were frozen, and then single batches were analyzed for SDMA, using both liquid chromatography-mass spectroscopy (LC-MS), and an enzyme multiplied immunoassay technique (EMIT), and creatinine by modified Jaffe method. Restricted maximum likelihood estimations were used to determine the coefficients of variation (CVs) describing variation within each cat, between cats, and the analytical variation. These CVs were used to determine the indices of individuality and reference change values (RCVs). RESULTS: SDMA had an intermediate index of individuality that could be evaluated by both RCV and population-based RIs. In contrast, creatinine had a high index of individuality best evaluated with RCVs. Serum SDMA concentrations evaluated with either the reference standard, LC-MS, or the clinically used EMIT yielded similar results. CONCLUSIONS: Clinicians should consider biologic variation when selecting the best method for interpreting changes in biochemical analytes. Specifically, establishing each cat's baseline serum creatinine and SDMA concentrations during health, and applying RCVs to subsequent measurements could improve the recognition of meaningful biologic changes.

Investigation of burnout syndrome and job-related risk factors in veterinary technicians in specialty teaching hospitals: a multicenter cross-sectional study.

OBJECTIVES: To investigate veterinary technician burnout and associations with frequency of self-reported medical error, resilience, and depression and job-related risk factors. DESIGN: Cross-sectional observational study using an anonymous survey conducted between November 2017 and June 2018. SETTING: Four referral teaching hospitals in the United States and Canada. SUBJECTS: A total of 344 veterinary technicians were invited to participate. Response rate was 95%. Overall 256 surveys were ultimately analyzed. INTERVENTIONS: Burnout, depression, and resilience were measured using validated instruments. Respondents reported perceptions of workload, working environment, and medical error frequency. Associations between burnout and factors related to physical work environment, workload and schedule, compensation package, interpersonal relationships, intellectual enrichment, and exposure to ethical conflicts were analyzed. MEASUREMENTS AND MAIN RESULTS: Burnout, characterized by high emotional exhaustion, depersonalization, and low sense of personal accomplishment was common, and was positively associated with perceived medical errors, desire to change career, and depression. Burnout levels on all 3 burnout subscales were higher in this population than previously reported for a contemporaneous group of trauma nurses working with human patients (P < 0.05). Burnout was negatively associated with resilience. Respondents' feelings of fear or anxiety around supervisor communications, perception that patient load was too high to allow for excellent patient care, and perceived lack of available assistance during sudden workload increases were all associated with burnout. CONCLUSIONS: Burnout in veterinary technicians is common and is associated with numerous undesirable outcomes. Work-related interventions to reduce burnout should focus on improving supervisor relationships and maintaining an appropriate patient:caregiver ratio.

A Small-Molecule Pan-Id Antagonist Inhibits Pathologic Ocular Neovascularization.

Id helix-loop-helix (HLH) proteins (Id1-4) bind E protein bHLH transcription factors, preventing them from forming active transcription complexes that drive changes in cell states. Id proteins are primarily expressed during development to inhibit differentiation, but they become re-expressed in adult tissues in diseases of the vasculature and cancer. We show that the genetic loss of Id1/Id3 reduces ocular neovascularization in mouse models of wet age-related macular degeneration (AMD) and retinopathy of prematurity (ROP). An in silico screen identifies AGX51, a small-molecule Id antagonist. AGX51 inhibits the Id1-E47 interaction, leading to ubiquitin-mediated degradation of Ids, cell growth arrest, and reduced viability. AGX51 is well-tolerated in mice and phenocopies the genetic loss of Id expression in AMD and ROP models by inhibiting retinal neovascularization. Thus, AGX51 is a first-in-class compound that antagonizes an interaction formerly considered undruggable and that may have utility in the management of multiple diseases.

Sex-hormone producing adrenal tumors causing behavioral changes as the sole clinical sign in 3 cats.

Three neutered cats with adrenocortical tumors that were presented with behavioral changes but no evidence of hyperaldosteronism or hypercortisolism are described. All 3 cats had resolution of their clinical signs following adrenalectomy. For neutered cats presenting with behavior changes, a sex-hormone secreting adrenal tumor should be considered as a differential diagnosis.

Tumeurs surrénaliennes produisant des hormones sexuelles causant des changements de comportement comme seul signe clinique chez 3 chats. Les cas de trois chats stérilisés ayant des tumeurs surrénaliennes qui ont été présentés avec des changements comportementaux mais aucun signe d'hyperaldostéronisme ou hypercortisolisme sont décrits. Les trois chats ont eu une résorption de leurs signes cliniques après une surrénalectomie. Pour les chats stérilisés présentant des changements comportementaux, une tumeur surrénalienne sécrétant des hormones sexuelles devrait être considérée comme un diagnostic différentiel.(Traduit par Isabelle Vallières).