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Urothelial carcinomas (UCs), also known as transitional cell carcinomas, are the most common canine urinary tract neoplasms. Tyrosine kinases (TKs) are enzymes that tightly regulate cell growth and differentiation through phosphorylation. Receptor TK (RTK) inhibitors are currently used to treat UCs. Toceranib phosphate (Palladia; Pfizer) is an RTK inhibitor that blocks the activity of vascular endothelial growth factor receptor 2 (VEGFR2), platelet-derived growth factor receptor-alpha and -beta (PDGFR-α, -β), FMS-like tyrosine kinase 3, stem cell factor receptor (KIT, kinase inhibitor targeting), and colony stimulating factor receptor. To better understand UCs and validate treatment targets, we performed immunohistochemical staining for RTKs, as well as a novel target, cyclin-dependent kinase 4 (CDK4, a central regulator of the mammalian cell cycle), on formalin-fixed, paraffin-embedded tissues from bladder biopsies from 17 dogs with UCs, 17 dogs with cystitis (diseased controls), and 8 normal dogs (negative controls). Although immunohistochemical scores could not be extrapolated to prognostic value, response to treatment, and outcome of patients with UC, we demonstrated expression of PDGFR-β and VEGFR2 in UCs; all UC samples staining positively for VEGFR2. Minimal positive staining for KIT was noted in the tumor samples. CDK4 staining intensity was significantly weaker in UCs compared with normal and cystitis bladder samples. The intense staining of VEGFR2 in UC cells suggested that VEGFR2 may be of prognostic and/or therapeutic value in dogs with UC. Overexpression of VEGFR2 in UC cells validates this receptor as a treatment target in UC.

Inherited forms of ichthyosis, or generalized scaling of the skin, have been reported in many animal species, including cattle, and are characterized by an autosomal recessive mode of inheritance. We investigated 2 calves affected with ichthyosis fetalis, a Polled Hereford and a Shorthorn. Both cases had hard white plaques on the skin consistent with excessive keratinization. This was confirmed by histopathology, which showed severe diffuse epidermal and follicular orthokeratotic hyperkeratosis. The known mutation (H1935R) in gene ABCA12, responsible for ichthyosis fetalis in Chianina cattle, was shown to be absent in both affected calves and their obligate heterozygous parents. These molecular findings indicate that allelic heterogeneity exists for this condition in cattle.

Background: Individuals who have a transgender or gender nonconforming (TGGNC) experience belong to a marginalized segment of the U.S. population, and healthcare can be difficult for them to navigate. Although emergency departments (EDs) traditionally serve as healthcare "safety nets" for vulnerable populations, quantitative studies outside the United States have found that TGGNC-experienced persons tend to avoid EDs and/or have negative experiences. This qualitative study primarily describes the ED experiences of people with a TGGNC history; furthermore, the study explores reasons why this population avoids U.S. EDs and their recommendations for improvements to ED care. Methods: This qualitative study used data about TGGNC-historied persons' experiences in U.S. EDs from retrospective, anonymous, written surveys (paper or web based). National data collection took place from June 2012 through December 2014. Participant responses ( n =240) were examined using thematic analysis. Results: Using a framework that recognized positive and negative responses, the themes of Self-Efficacy and Power Inequity surfaced. These themes exposed the tension between patients with TGGNC experiences and clinicians who were perceived to lack training in this area, resulting in negative patient experiences. When practitioners had specific training about this population, participants reported positive care experiences. Conclusions: This study indicates that many TGGNC-historied persons who use U.S. EDs have negative experiences, largely due to lack of provider sensitivity toward and training about this patient population. Data from this investigation suggest that training of U.S. ED providers and institutional support would help improve care for this marginalized group., Competing Interests: No competing financial interests exist.

For more than 25 years, emergency medicine researchers have examined 72-hour return visits as a marker for high-risk patient visits and as a surrogate measure for quality of care. Individual emergency departments frequently use 72-hour returns as a screening tool to identify deficits in care, although comprehensive departmental reviews of this nature may consume considerable resources. We discuss the lack of published data supporting the use of 72-hour return frequency as an overall performance measure and examine why this is not a valid use, describe a conceptual framework for reviewing 72-hour return cases as a screening tool, and call for future studies to test various models for conducting such quality assurance reviews of patients who return to the emergency department within 72 hours., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Evaluating the quality of care as part of a quality improvement process is required in many clinical environments by accrediting bodies. It produces metrics used to evaluate department and individual provider performance, provides outcomes-based feedback to clinicians, and identifies ways to reduce error., Discussion: To improve patient safety and train our residents to perform peer review, we expanded our quality assurance program from a narrow, administrative process carried out by a small number of attendings to an educationally focused activity of much greater scope incorporating all residents on a monthly basis. We developed an explicit system by which residents analyze sets of high-risk cases and record their impressions onto structured databases, which are reviewed by faculty. At monthly meetings, results from the month's case reviews are presented, learning points discussed, and corrective actions are proposed., Conclusion: By integrating Clinical Quality Review (CQR) as a core, continuous component of the residency curriculum, we increased the number of cases reviewed more than 10-fold and implemented a variety of clinical process improvements. An anonymous survey conducted after 2 years of resident-led CQR indicated that residents value their exposure to the peer review process and feel it benefits them as clinicians, but also that the program requires a significant investment of time that can be burdensome., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Alopecia areata (AA) causes hair loss due to inflammatory changes within and around hair bulbs and lower portions of the hair follicles. Documentation of AA in horses is limited to a few case reports., Hypothesis/objectives: The aim of this retrospective study was to characterize equine AA by describing patterns in age, sex, breed and lesion distribution in a series of cases. An attempt was made to characterize the long-term course of the disease by surveying owners of affected horses., Animals: Computerized records from 1 January 1980 to 1 July 2011 yielded 15 horses., Methods: Descriptive statistics were calculated for age at presentation, breed, sex, dermatological signs, season when diagnosed and any recurrence of AA. The breed and sex distribution of horses with AA was compared with the equine hospital population during the study period., Results: The prevalence of AA was 0.017%. Appaloosas and quarter horses were the most commonly recorded breeds. The median age was 9 years, with an age range from 3 to 15 years. Alopecia was the primary dermatological abnormality in all horses and commonly affected the mane, tail and face. More than half of the horses presented for other medical conditions. Five of seven (71.4%) owners who returned completed surveys reported a seasonal pattern to the disease, which usually worsened in spring and summer., Conclusions and Clinical Importance: Alopecia areata is a rare disease in horses, and is typically cosmetic in nature. To the authors' knowledge, this is the first study investigating the epidemiology of equine AA., (© 2013 The Authors. Veterinary Dermatology © 2013 ESVD and ACVD.)

Acute aortic dissection (AAD) is a rare and lethal disease with presenting signs and symptoms that can often be seen with other high risk conditions; diagnosis is therefore often delayed or missed. Pain is present in up to 90% of cases and is typically severe at onset. Many patients present with acute on chronic hypertension, but hypotension is an ominous sign, often reflecting hemorrhage or cardiac tamponade. The chest x-ray can be normal in 10-20% of patients with AAD, and though transthoracic echocardiography is useful if suggestive findings are seen, and should be used to identify pericardial effusion, TTE cannot be used to exclude AAD. Transesophageal echocardiography, however, reliably confirms or excludes the diagnosis, where such equipment and expertise is available. CT scan with IV contrast is the most common imaging modality used to diagnose and classify AAD, and MRI can be used in patients in whom the use of CT or IV contrast is undesirable. Recent specialty guidelines have helped define high-risk features and a diagnostic pathway that can be used the emergency department setting. Initial management of diagnosed or highly suspected acute aortic dissection focuses on pain control, heart rate and then blood pressure management, and immediate surgical consultation.

The present study was designed to assess the value of the presenting symptom of "typical" anginal pain, "atypical/nonanginal" pain, or the lack of chest pain in predicting the presence of inducible myocardial ischemia using cardiac stress testing in emergency department patients being evaluated for possible acute coronary syndrome. We performed a retrospective observational study of adult patients who were evaluated for acute coronary syndrome in an emergency department chest pain unit. The presenting symptoms were obtained from a structured questionnaire administered before stress testing. Patient chest pain was categorized according to the presence of substernal chest pain or discomfort that was provoked by exertion or emotional stress and was relieved by rest and/or nitroglycerin. Chest pain was classified as "typical" angina if all 3 descriptors were present and "atypical" or "nonanginal" if <3 descriptors were present. All patients underwent serial biomarker and cardiac stress testing before discharge. A total of 2,525 patients met the eligibility criteria. Inducible ischemia on stress testing was found in 33 (14%, 95% confidence interval 10% to 19%) of the 231 patients who had typical anginal pain, 238 (11%, 95% confidence interval 10% to 13%) of the 2,140 patients presenting with atypical/nonanginal chest pain, and 25 (16%, 95% confidence interval 11% to 22%) of the 153 patients who had no complaint of chest pain on presentation. Compared to patients with atypical or no chest pain, patients with typical chest pain were not significantly more likely to have inducible ischemia on stress testing (likelihood ratio +1.25, 95% confidence interval 0.89 to 1.78). In conclusion, in our study, the patients who presented with "typical" angina were no more likely to have inducible myocardial ischemia on stress testing than patients with other presenting symptoms., (Copyright 2010 Elsevier Inc. All rights reserved.)

PCR-based assays for the detection of BFDV DNA are in widespread use throughout the world. Quantitative real-time PCR assays are extremely sensitive and have the advantages over standard PCR assays that they do not require post-reaction processing to visualise PCR products and can quantify the amount of DNA present in a sample. This study describes a quantitative real-time PCR assay for the detection of BFDV DNA, using primers designed to amplify a conserved 81 bp fragment of ORFV1 and SYTO9, a fluorescent intercalating dye. A synthetic oligonucleotide was used to make standard curves for the quantitation of viral load in blood and feather preparations. The assay was very sensitive, with a detection limit of 50 copies/microL. The assay was developed using DNA extracts from the feathers of 10 different species of birds which had tested BFDV-positive previously and was validated with blood and feather samples from corellas vaccinated with an experimental BFDV vaccine, then challenged with live virus. Viral DNA was detected consistently in the blood of all control (non-vaccinated) birds and in some vaccinated birds. Contamination of the environment with feather dander from BFDV-infected birds meant that feather preparations used for the haemagglutination assay were unreliable for the detection and quantitation of viral excretion. Nonetheless, the assay should prove to be a useful and sensitive test for the detection of viral DNA in a range of samples.

Currently, the only diagnostic test available routinely for the sero-diagnosis of BFDV is the haemagglutination-inhibition (HI) assay. This test, whilst useful and applicable to samples from a wide range of psittacine birds, is not an ideal assay; it requires erythrocytes from live animals, virus purified from the feathers of infected birds and polyclonal antibody preparations in order to perform the assay. Variations in these reagents make consistency between tests difficult to achieve, underscoring the need for a new test with standardised reagents for the sero-diagnosis of BFDV infection which has led to the development of an antibody response. The methods used to develop a novel "blocking" (or "competitive") ELISA (bELISA) for the detection of anti-BFDV antibodies in psittacine sera are presented in this paper. The assay was developed using a baculovirus-expressed recombinant BFDV capsid protein and a newly developed monoclonal antibody raised against this protein. The assay was then validated with 160 samples from eastern long-billed corellas (Cacatua tenuiostris) vaccinated with the recombinant capsid protein and challenged with live virus and samples from 82 cockatiels known to be HI negative. The bELISA described in this study is a sensitive and specific diagnostic test and should have wide application for the sero-diagnosis of BFDV.

Psittacine beak and feather disease is known to occur in a wide range of psittacine species; however, there are no scientific or credible anecdotal reports of psittacine beak and feather disease occurring in the cockatiel (Nymphicus hollandicus) despite it being one of the world's most commonly kept companion bird species. Consequently, this has resulted in speculation that the species may have some innate resistance to beak and feather disease virus (BFDV) infection. To investigate this hypothesis we conducted a survey of cockatiels (n=88) at commercial aviaries to investigate whether BFDV infection occurs in cockatiels, and found that all birds were virus-free by polymerase chain reaction and haemagglutination assay and had no detectable antibody titre by haemagglutination-inhibition assay. In addition to this, we sequenced the genome of two BFDV isolates obtained from diseased cockatiel feathers and performed cross-reactivity assays using virus eluted from these feathers and sera from naturally immune psittacine birds. Serological cross-reactivity results and phylogenetic analysis of the nucleotide sequences indicated that the cockatiel virus isolates were serologically and genetically different to other BFDV isolates. This is the first paper to report evidence of an antigenically distinct BFDV in psittacine birds.

The development of diagnostic assays for detecting beak and feather disease virus (BFDV) has traditionally been hampered by the difficulty associated with producing suitable reagents, namely purified virus and polyclonal antibodies. In an effort to develop a consistent and standardised source of antibody, a monoclonal antibody to a recombinant BFDV capsid protein has been developed and its use in western blotting, immunohistochemistry (IHC), ELISA and haemagglutination-inhibition (HI) assays characterised. The antibody was specific for both the recombinant BFDV capsid protein and the whole virus and had similar optimal titres when used in western blotting and IHC. The antibody also had HI activity and detected BFDV virus from three genera of psittacine birds, including the recently described cockatiel BFDV isolate. The monoclonal antibody should have widespread application in both research and the development of diagnostic assays for BFDV.