TY - MGZN TI - Summer body condition at farrowing influences litter size T2 - National Hog Farmer DA - 2022/9/1/ PY - 2022/9/1/ UR - https://www.nationalhogfarmer.com/livestock/summer-body-condition-farrowing-influences-litter-size ER - TY - MGZN TI - Prefarrow fat supplementation impact on piglet survival, reproduction T2 - National Hog Farmer DA - 2022/5/5/ PY - 2022/5/5/ UR - https://www.nationalhogfarmer.com/nutrition/prefarrow-fat-supplementation-impact-piglet-survival-reproduction ER - TY - JOUR TI - Gastrointestinal obstruction secondary to seminal vesicle cystic hyperplasia in an African pygmy hedgehog (Atelerix albiventris) AU - Wooten, McCaide T. AU - Snider, Timothy A. T2 - Veterinary Record Case Reports AB - Abstract A 3‐year‐old, male, entire African pygmy hedgehog ( Atelerix albiventris ) was presented for a 10‐day history of hyporexia, mucoid green faeces and lethargy. Survey radiographs revealed a left caudal abdominal mass effect with cranial displacement and gas distension of the intestinal loops. During exploratory laparotomy, the cause of the mass effect was revealed to be grossly enlarged seminal vesicles, which were excised. Histopathology revealed uniform polycystic glandular architecture, consistent with benign cystic hyperplasia. The patient recovered and was clinically healthy at the last follow‐up examination. This is the first detailed report describing the antemortem diagnosis of benign seminal vesicular cystic hyperplasia resulting in presumptive clinical gastrointestinal disease in an African pygmy hedgehog. DA - 2022/6/28/ PY - 2022/6/28/ DO - 10.1002/vrc2.446 VL - 10 IS - 4 J2 - Vet Record Case Reports LA - en OP - SN - 2052-6121 2052-6121 UR - http://dx.doi.org/10.1002/vrc2.446 DB - Crossref ER - TY - JOUR TI - Long-term effects of ciclosporin and oclacitinib on mediators of tolerance, regulatory T-cells, IL-10 and TGF-beta, in dogs with atopic dermatitis AU - Herrmann, Ina AU - Mamo, Lisa B. AU - Holmes, Jenny AU - Mohammed, Javid P. AU - Murphy, K. Marcia AU - Bizikova, Petra T2 - VETERINARY DERMATOLOGY AB - Atopic dogs often are managed with allergen-specific immunotherapy (AIT) and concurrent dosages of ciclosporin (CSA) or oclacitinib to alleviate their clinical signs. Both drugs might affect proper tolerance induction by inhibiting regulatory T-cell (Treg) induction.We evaluated Treg cell numbers and serum interleukin (IL)-10 and transforming growth factor-beta (TGF-β)1 levels in dogs diagnosed with atopic dermatitis (AD) and successfully treated with either CSA or oclacitinib for nine or more months.We included 15 dogs receiving oclacitinib, 14 dogs treated with CSA, 15 healthy dogs, 13 dogs with untreated moderate-to-severe AD and 15 atopic dogs controlled with AIT.Peripheral blood CD4+CD25+FOXP3+ T-cell percentages were determined using flow cytometry. Serum concentrations of IL-10 and TGF-β1 were measured by enzyme-linked immunosorbent assay.The percentage of Treg cells in the CSA group was significantly lower in comparison with the healthy group (p = 0.0003), the nontreated AD group (p = 0.0056) or the AIT group (p = 0.0186). There was no significant difference in Treg cell percentages between the CSA and oclacitinib groups, nor between the oclacitinib and the healthy, nontreated AD or AIT-treated dogs. No significant differences were detected in IL-10 and TGF-β1 serum concentrations between the five groups.Lower Treg cell percentages in the CSA-treated dogs suggest an impact of this drug on this cell population; however, it does not necessarily mean that it diminishes tolerance. Functionality and cytokine production may be more important than the number of Treg cells. Further studies evaluating the treatment outcome of dogs receiving AIT and concurrent drugs are needed to show clinical relevance.Les chiens atopiques sont souvent traités avec une immunothérapie spécifique d'allergène (AIT) et des doses concomitantes de ciclosporine ou d'oclacitinib pour atténuer leurs signes cliniques. Les deux médicaments pourraient affecter l'induction de la tolérance appropriée en inhibant l'induction des lymphocytes T régulateurs (Treg). HYPOTHÈSE/OBJECTIFS: Nous avons évalué le nombre de cellules Treg et les taux sériques d'interleukine (IL)-10 et de TGF-β-1 chez des chiens diagnostiqués avec une dermatite atopique (DA) et traités avec succès par la ciclosporine ou l'oclacitinib pendant neuf mois ou plus.Nous avons inclus 15 chiens recevant de l'oclacitinib, 14 chiens traités par ciclosporine, 15 chiens sains, 13 chiens atteints de DA modérée à sévère non traitée et 15 chiens atopiques contrôlés par AIT. MATÉRIELS ET MÉTHODES: Les pourcentages de lymphocytes T CD4+CD25+FOXP3+ du sang périphérique ont été déterminés par cytométrie de flux. Les concentrations sériques d'IL-10 et de TGF-β1 ont été mesurées par dosage immuno-enzymatique. RÉSULTATS: Le pourcentage de cellules Treg dans le groupe ciclosporine était significativement plus faible par rapport au groupe sain (p = 0,0003), au groupe AD non traité (p = 0,0056) ou au groupe AIT (p = 0,0186). Il n'y avait pas de différence significative dans les pourcentages de cellules Treg entre le groupe ciclosporine et oclacitinib, ni entre l'oclacitinib et les chiens sains non traités AD ou traités AIT. Aucune différence significative n'a été détectée dans les concentrations sériques d'IL-10 et de TGF-β1 entre les cinq groupes.Des pourcentages de cellules Treg plus faibles chez les chiens traités à la ciclosporine suggèrent un impact de ce médicament sur cette population cellulaire ; cependant, cela ne signifie pas nécessairement qu'il diminue la tolérance. La fonctionnalité et la production de cytokines peuvent être plus importantes que le nombre de cellules Treg. D'autres études évaluant les résultats du traitement des chiens recevant l'AIT et des médicaments concomitants sont nécessaires pour montrer la pertinence clinique.INTRODUCCIÓN: los perros atópicos a menudo se tratan con inmunoterapia específica para alérgenos (AIT) y dosis simultáneas de ciclosporina u oclacitinib para aliviar sus signos clínicos. Ambos fármacos podrían afectar la inducción de tolerancia adecuada al inhibir la inducción de células T reguladoras (Treg). HIPÓTESIS/OBJETIVOS: Evaluamos el número de células Treg y los niveles séricos de interleuquina (IL)-10 y factor de crecimiento transformante-beta (TGF-β)1 en perros diagnosticados con dermatitis atópica (AD) y tratados con éxito con ciclosporina u oclacitinib durante nueve o mas meses ANIMALES: Incluimos 15 perros que recibieron oclacitinib, 14 perros tratados con ciclosporina, 15 perros sanos, 13 perros con AD de moderada a grave no tratada y 15 perros atópicos controlados con AIT. MATERIALES Y MÉTODOS: Los porcentajes de células T CD4+CD25+FOXP3+ en sangre periférica se determinaron mediante citometría de flujo. Las concentraciones séricas de IL-10 y TGF-β1 se midieron mediante ensayo inmunoabsorbente ligado a enzimas. RESULTADOS: El porcentaje de células Treg en el grupo de ciclosporina fue significativamente menor en comparación con el grupo sano (p = 0,0003), el grupo AD no tratado (p = 0,0056) o el grupo AIT (p = 0,0186). No hubo diferencias significativas en los porcentajes de células Treg entre el grupo de ciclosporina y oclacitinib, ni entre el oclacitinib y los perros sanos, no tratados con AD o tratados con AIT. No se detectaron diferencias significativas en las concentraciones séricas de IL-10 y TGF-β1 entre los cinco grupos. CONCLUSIONES Y RELEVANCIA CLÍNICA: Los porcentajes más bajos de células Treg en los perros tratados con ciclosporina sugieren un impacto de este fármaco en esta población celular; sin embargo, no significa necesariamente que disminuya la tolerancia. La funcionalidad y la producción de citoquinas pueden ser más importantes que el número de células Treg. Se necesitan más estudios que evalúen el resultado del tratamiento de perros que reciben AIT y medicamentos concurrentes para mostrar relevancia clínica.Atopische Hunde werden oft mit Allergen-spezifischer Immuntherapie (AIT) gemanagt, wobei gleichzeitig Ciclosporin oder Oclacitinib verabreicht werden, um ihre klinischen Zeichen zu lindern. Beide Medikamente können die Toleranzinduktion durch eine Inhibition der regulatorischen T Zellen (Treg) Induktion beeinflussen.Wir evaluierten die Treg Zellzahlen und Serum Interleukin (IL)-10 und Transforming Growth Factor-beta (TGF-β) Werte bei Hunden, die mit einer atopischen Dermatitis (AD) diagnostiziert worden waren und entweder mit Ciclosporin oder mit Oclacitinib für neun Monate oder länger erfolgreich behandelt worden waren.Wir inkludierten 15 Hunde, die Oclacitinib erhielten, 14 Hunde, die mit Ciclosporin behandelt worden waren, 15 gesunde Hunde, 13 Hunde mit unbehandelter moderater-bis-hochgradiger AD und 15 atopische Hunde, die mit AIT kontrolliert waren.Periphere Blut CD4+CD25+FOXP3+ T-Zell Prozentanteile wurden mittels Flowzytometrie bestimmt. Serumkonzentrationen von IL-10 und TGF-β wurden mittels Enzym-linked Immunosorbent Assay gemessen.Der Prozentanteil der Treg Zellen in der Ciclosporingruppe war signifikant niedriger im Vergleich zur gesunden Gruppe (p = 0,0003), zur nichtbehandelten AD-Gruppe (p = 0,0056), oder der AIT-Gruppe (p = 0,0186). Es bestand kein signifikanter Unterschied zwischen den prozentualen Anteilen der Treg Zellen zwischen Ciclosporin und der Oclacitinib Gruppe, und auch nicht zwischen der Oclacitinib und der gesunden, nichtbehandelten AD-Gruppe, oder den AIT-behandelten Hunden. Es wurden keine signifikanten Unterschiede zwischen IL-10 und TGF-β1 Serumkonzentrationen zwischen den fünf Gruppen gefunden.Niedrigere Prozentanteile der Treg Zellen bei den Ciclosporin-behandelten Hunden weisen darauf hin, dass dieses Medikament auf diese Zellpopulation einen Einfluss hat; es bedeutet jedoch nicht unbedingt, dass es die Toleranz vermindert. Die Funktionalität und die Ciclosporin Produktion könnte wichtiger sein als die Anzahl der Treg Zellen. Weitere Studien sind nötig, die den Behandlungserfolg bei Hunden, die AIT und gleichzeitig Medikamente erhalten, evaluieren, um die klinische Relevanz zu zeigen.背景: アトピー犬は、しばしばアレルゲン特異的免疫療法(AIT)を行い、同時にシクロスポリンやオクラシチニブを投与して臨床症状を軽減している。両薬剤は、制御性T細胞(Treg)の誘導を阻害することにより、適切な寛容誘導に影響を与える可能性がある。 仮説/目的: 本研究の目的は、 アトピー性皮膚炎(AD)と診断され、シクロスポリンまたはオクラシチニブによる9ヶ月以上の治療に成功した犬において、Treg細胞数、血清インターロイキン(IL)-10およびトランスフォーミング増殖因子-β(TGF-β)1レベルを評価することであった。 供試動物: オクラシチニブ投与犬15頭、シクロスポリン投与犬14頭、健常犬15頭、未治療の中等度から重度のAD犬13頭、AITでコントロールしたアトピー犬15頭を対象とした。 材料と方法: 末梢血CD4+CD25+FOXP3+ T細胞の割合をフローサイトメトリーで測定した。血清中のIL-10およびTGF-β1濃度は、酵素結合免疫吸着法で測定した。 結果: シクロスポリン投与群では、健常群(p=0.0003)、AD未治療群(p=0.0056)、AIT群(p=0.0186)と比較して、Treg細胞の割合が有意に低下した。シクロスポリン群とオクラシチニブ群、オクラシチニブ群と健常群、AD未治療群、AIT治療群との間でもTreg細胞の割合に有意差はなかった。IL-10およびTGF-β1血清濃度には5群間で有意差は検出されなかった。 結論と臨床的関連性: シクロスポリン投与犬におけるTreg細胞の割合の低下は、シクロスポリンがこの細胞集団に影響を与えることを示唆していた。しかし、それは必ずしも耐性を低下させることを意味するものではない。機能性やサイトカイン産生は、Treg細胞数よりも重要である可能性がある。臨床的な関連性を示すためには、AITと併用薬を投与された犬の治療成績を評価する更なる研究が必要である。.背景: 特应性犬通常通过过敏原特异性免疫治疗 (AIT) 和同时给予环孢素或奥拉替尼缓解其临床症状。两种药物均可能通过抑制调节性 T 细胞 (Treg) 诱导影响适当的耐受诱导。 假设/目的: 我们在诊断为特应性皮炎 (AD) 并成功接受环孢素或奥拉替尼治疗9个月或以上的犬中评价了 Treg 细胞数量以及血清白细胞介素 (IL)-10 和转化生长因子-β (TGF-β)1水平。 动物: 我们纳入了15只接受奥拉替尼的犬、14只接受环孢素治疗的犬、15只健康犬、13只未治疗的中度至重度 AD 犬和15只接受 AIT 控制的特应性犬。 材料和方法: 使用流式细胞术测定外周血CD4 + CD25 + FOXP3 + T细胞百分比。采用酶联免疫吸附法检测血清 IL-10 和TGF-β1的浓度。 结果: 环孢素组的 Treg 细胞百分比显著低于健康组 (p = 0.0003)、未治疗 AD 组 (p = 0.0056) 或 AIT 组 (p = 0.0186)。环孢素和奥拉替尼组、奥拉替尼和健康、未治疗 AD 或 AIT 治疗犬之间的 Treg 细胞百分比无显著差异。5组间 IL-10 和TGF-β1血清浓度未检测到明显差异。 结论和临床相关性: 环孢素给药犬中较低的 Treg 细胞百分比表明该药物对该细胞群有影响;然而,这并不一定意味着其会降低耐受性。功能和细胞因子的产生可能比 Treg 细胞的数量更重要。需要进一步研究评价接受 AIT 和伴随药物的犬的治疗结果,以显示临床相关性。.Cães atópicos geralmente são tratados com imunoterapia alérgeno-específica (AIT) e dosagens concomitantes de ciclosporina ou oclacitinib para aliviar seus sinais clínicos. Ambas as drogas podem afetar a indução de tolerância adequada ao inibir a indução de células T reguladoras (Treg). HIPÓTESE/OBJETIVOS: Avaliamos o número de células Treg e os níveis séricos de interleucina (IL)-10 e fator transformador de crescimento beta (TGF-β)1 em cães diagnosticados com dermatite atópica (DA) e tratados com sucesso com ciclosporina ou oclacitinib por nove ou mais meses.Foram incluídos 15 cães recebendo oclacitinib, 14 cães tratados com ciclosporina, 15 cães saudáveis, 13 cães com DA moderada a grave não tratada e 15 cães atópicos controlados com AIT. MATERIAIS E MÉTODOS: As porcentagens de células T CD4+CD25+FOXP3+ do sangue periférico foram determinadas por citometria de fluxo. As concentrações séricas de IL-10 e TGF-β1 foram medidas por ensaio imunoenzimático.A porcentagem de células Treg no grupo ciclosporina foi significativamente menor em comparação ao grupo saudável (p = 0,0003), ao grupo DA não tratado (p = 0,0056) ou ao grupo AIT (p = 0,0186). Não houve diferença significativa nas porcentagens de células Treg entre o grupo ciclosporina e oclacitinib, nem o oclacitinib e os cães saudáveis, ou oclacitinib e os cães com DA não tratados ou tratados com AIT. Não foram detectadas diferenças significativas nas concentrações séricas de IL-10 e TGF-β1 entre os cinco grupos. CONCLUSÕES E RELEVÂNCIA CLÍNICA: Percentagens mais baixas de células Treg nos cães tratados com ciclosporina sugerem um impacto deste fármaco nesta população de células; no entanto, isso não significa necessariamente que diminui a tolerância. A funcionalidade e a produção de citocinas podem ser mais importantes do que o número de células Treg. Mais estudos avaliando o resultado do tratamento de cães recebendo AIT e drogas concomitantes são necessários para mostrar a relevância clínica. DA - 2022/12/8/ PY - 2022/12/8/ DO - 10.1111/vde.13140 SP - SN - 1365-3164 KW - canine atopic dermatitis KW - ciclosporin KW - oclacitinib KW - T regulatory cell ER - TY - JOUR TI - Vandetanib Blocks the Cytokine Storm in SARS-CoV-2-Infected Mice AU - Puhl, Ana C. AU - Gomes, Giovanni F. AU - Damasceno, Samara AU - Fritch, Ethan J. AU - Levi, James A. AU - Johnson, Nicole J. AU - Scholle, Frank AU - Premkumar, Lakshmanane AU - Hurst, Brett L. AU - Lee-Montiel, Felipe AU - Veras, Flavio P. AU - Batah, Sabrina S. AU - Fabro, Alexandre T. AU - Moorman, Nathaniel J. AU - Yount, Boyd L. AU - Dickmander, Rebekah J. AU - Baric, Ralph S. AU - Pearce, Kenneth H. AU - Cunha, Fernando Q. AU - Alves-Filho, Jose C. AU - Cunha, Thiago M. AU - Ekins, Sean T2 - ACS OMEGA AB - The portfolio of SARS-CoV-2 small molecule drugs is currently limited to a handful that are either approved (remdesivir), emergency approved (dexamethasone, baricitinib, paxlovid, and molnupiravir), or in advanced clinical trials. Vandetanib is a kinase inhibitor which targets the vascular endothelial growth factor receptor (VEGFR), the epidermal growth factor receptor (EGFR), as well as the RET-tyrosine kinase. In the current study, it was tested in different cell lines and showed promising results on inhibition versus the toxic effect on A549-hACE2 cells (IC50 0.79 μM) while also showing a reduction of >3 log TCID50/mL for HCoV-229E. The in vivo efficacy of vandetanib was assessed in a mouse model of SARS-CoV-2 infection and statistically significantly reduced the levels of IL-6, IL-10, and TNF-α and mitigated inflammatory cell infiltrates in the lungs of infected animals but did not reduce viral load. Vandetanib also decreased CCL2, CCL3, and CCL4 compared to the infected animals. Vandetanib additionally rescued the decreased IFN-1β caused by SARS-CoV-2 infection in mice to levels similar to that in uninfected animals. Our results indicate that the FDA-approved anticancer drug vandetanib is worthy of further assessment as a potential therapeutic candidate to block the COVID-19 cytokine storm. DA - 2022/9/13/ PY - 2022/9/13/ DO - 10.1021/acsomega.2c02794 VL - 7 IS - 36 SP - 31935-31944 SN - 2470-1343 ER - TY - JOUR TI - Identification of redundancy between human Fc epsilon RI beta and MS4A6A proteins points toward additional complex mechanisms for Fc epsilon RI trafficking and signaling AU - Bitting, Katie AU - Hedgespeth, Barry AU - Ehrhardt-Humbert, Lauren C. AU - Arthur, Greer K. AU - Schubert, Alicia G. AU - Bradding, Peter AU - Tilley, Stephen L. AU - Cruse, Glenn T2 - ALLERGY AB - Allergic diseases are triggered by signaling through the high-affinity IgE receptor, FcεRI. In both mast cells (MCs) and basophils, FcεRI is a tetrameric receptor complex comprising a ligand-binding α subunit (FcεRIα), a tetraspan β subunit (FcεRIβ, MS4A2) responsible for trafficking and signal amplification, and a signal transducing dimer of single transmembrane γ subunits (FcεRIγ). However, FcεRI also exists as presumed trimeric complexes that lack FcεRIβ and are expressed on several cell types outside the MC and basophil lineages. Despite known differences between humans and mice in the presence of the trimeric FcεRI complex, questions remain as to how it traffics and whether it signals in the absence of FcεRIβ. We have previously reported that targeting FcεRIβ with exon-skipping oligonucleotides eliminates IgE-mediated degranulation in mouse MCs, but equivalent targeting in human MCs was not effective at reducing degranulation.Here, we report that the FcεRIβ-like protein MS4A6A exists in human MCs and compensates for FcεRIβ in FcεRI trafficking and signaling. Human MS4A6A promotes surface expression of FcεRI complexes and facilitates degranulation. MS4A6A and FcεRIβ are encoded by highly related genes within the MS4A gene family that cluster within the human gene loci 11q12-q13, a region linked to allergy and asthma susceptibility.Our data suggest the presence of either FcεRIβ or MS4A6A is sufficient for degranulation, indicating that MS4A6A could be an elusive FcεRIβ-like protein in human MCs that performs compensatory functions in allergic disease. DA - 2022/12/7/ PY - 2022/12/7/ DO - 10.1111/all.15595 SP - SN - 1398-9995 KW - asthma KW - IgE KW - mast cells ER - TY - JOUR TI - Point-of-care viscoelastic coagulation assessment in healthy dogs during the perianesthetic period AU - Wang, Wen H. AU - Lynch, Alex M. AU - Balko, Julie A. AU - Duffy, Daniel J. AU - Robertson, James B. AU - Posner, Lysa P. T2 - BMC VETERINARY RESEARCH AB - The viscoelastic coagulation monitor (VCM Vet) is a novel, portable device that provides a global assessment of hemostasis. The study aims were to evaluate serial viscoelastic analysis during the perianesthetic period in healthy dogs and to compare the agreement between two VCM Vet devices. Twenty healthy dogs undergoing orthopedic surgery were enrolled. Whole blood samples were collected from an intravenous catheter at four time points: baseline, 15 min after premedication, 60 min after inhalant initiation, and 60 min after inhalant termination. Viscoelastic tests were performed in duplicate on different devices, providing: clot time (CT; seconds), clot formation time (CFT; seconds), alpha angle (α; degrees), amplitude (units) at 10 (A10) and 20 (A20) minutes post clot time, maximum clot firmness (MCF; units), and lysis index (%) at 30 (Li30) and 45 (Li45) minutes post maximum clot formation.One hundred sixty samples were analyzed. The speed of CT and CFT significantly decreased an average of 25.5 s (95% confidence interval [CI]15.9-35.0) and 6.9 s (95% CI 3.1-10.7) per time point, respectively. There were no significant changes in clot strength or lysis variables. The Bland-Altman style plot shows an acceptable rate of agreement for all variables with intra-class correlation ranging from 0.64-0.94.The rate of clot formation (CT and CFT) decreased over the perianesthetic period in healthy dogs undergoing surgery. These changes were small and occurred without changes in clot strength or fibrinolysis rate, thus were not clinically relevant. There was clinically acceptable consistency between devices. DA - 2022/9/14/ PY - 2022/9/14/ DO - 10.1186/s12917-022-03442-x VL - 18 IS - 1 SP - SN - 1746-6148 KW - Coagulation KW - Viscoelastic testing KW - VCM Vet KW - Perianesthetic period ER - TY - JOUR TI - Tracking the Transmission of Antimicrobial-Resistant Non-O157 Escherichia coli and Salmonella Isolates at the Interface of Food Animals and Fresh Produce from Agriculture Operations Using Whole-Genome Sequencing AU - Glaize, Ayanna AU - Hull, Dawn AU - Raymond, Luke AU - Vliet, Arnoud H. M. AU - Gutierrez-Rodriguez, Eduardo AU - Thakur, Siddhartha T2 - FOODBORNE PATHOGENS AND DISEASE AB - An increasing number of outbreaks are caused by foodborne pathogens such as Escherichia coli and Salmonella, which often harbor antimicrobial resistance (AMR) genes. We previously demonstrated the transmission of pathogens from animal operations to produce fields on sustainable farms, which illustrated an urgent need to develop and implement novel prevention methods and remediation practices such as the vegetative buffer zone (VBZ) to prevent this movement. The focus of this study was to use whole-genome sequencing (WGS) to characterize the AMR, virulence, and single-nucleotide polymorphism profile of 15 Salmonella and 128 E. coli isolates collected from small-scale dairy and poultry farms on a research station in North Carolina. Phenotypically, seven E. coli and three Salmonella isolates displayed resistance to antibiotics such as tetracycline (n = 4), ampicillin (n = 4), nalidixic acid (n = 3), chloramphenicol (n = 2), sulfisoxazole (n = 1), and streptomycin (n = 1). A single E. coli isolate was found to be resistant to five different antibiotic class types and possessed the blaTEM-150 resistance gene. Virulence genes that facilitate toxin production and cell invasion were identified. Mauve analysis of the E. coli isolates identified seven clusters (dairy-six and poultry-one) indicating that transmission is occurring from animal operations to fresh produce fields and the surrounding environment when the VBZ is denudated. This suggests that the VBZ is a useful barrier to reducing the transmission of enteric pathogens in agricultural systems. Our study demonstrates the prevalence of AMR and virulence genes on small-scale sustainable farms and highlights the advantage of using WGS to assess the impact of the VBZ to reduce the transmission of E. coli and Salmonella. DA - 2022/8/4/ PY - 2022/8/4/ DO - 10.1089/fpd.2022.0016 VL - 8 SP - SN - 1556-7125 KW - extended-spectrum beta-lactamase KW - phylogroups KW - antimicrobial resistance KW - enteropathogenic Escherichia coli KW - dairy KW - poultry ER - TY - JOUR TI - Metabolic and antioxidant status during transition is associated with changes in the granulosa cell transcriptome in the preovulatory follicle in high-producing dairy cows at the time of breeding AU - Marei, Waleed F. A. AU - De Bie, Jessie AU - Xhonneux, Inne AU - Andries, Silke AU - Britt, Jack H. AU - Leroy, Jo L. M. R. T2 - JOURNAL OF DAIRY SCIENCE AB - In this study, we hypothesized that early postpartum (pp) metabolic and oxidative stress conditions in dairy cows (particularly those with severe negative energy balance, NEB) are associated with long-term changes in granulosa cell (GC) functions in the preovulatory follicle at the time of breeding. Blood samples were collected at wk 2 and wk 8 pp from 47 healthy multiparous cows. Follicular fluid (FF) and GC were collected from the preovulatory follicle after estrous synchronization at wk 8. Several metabolic and antioxidant parameters were measured in blood and FF, and their correlations were studied. Subsequently, 27 representative GC samples were selected for RNA sequencing analysis. The GC gene expression data of LH-responsive genes and the estradiol:progesterone ratio in FF were used to identify pre- and post-LH surge cohorts. We compared the transcriptomic profile of subgroups of cows within the highest and lowest quartiles (Q4 vs. Q1) of each parameter, focusing on the pre-LH surge cohort (n = 16, at least 3 in each subgroup). Differentially expressed genes (DEG: adjusted P-value < 0.05, 5% false discovery rate) were determined using DESeq2 analysis and were functionally annotated. Blood and FF β-carotene and vitamin E concentrations at wk 2, but not at wk 8, were associated with the most pronounced transcriptomic differences in the GC, with up to 341 DEG indicative for lower catabolism, increased oxidoreductase activity and signaling cascades that are known to enhance oocyte developmental competence, increased responsiveness to LH, and a higher steroidogenic activity. In contrast, elevated blood NEFA concentrations at wk 2 (and not at wk 8) were associated with a long-term carryover effect detectable in the GC transcriptome at wk 8 (64 DEG). These genes are related to response to lipids and ketones, oxidative stress, and immune responses, which suggests persistent cellular stress and oxidative damage. This effect was more pronounced in cows with antioxidant deficiencies at wk 8 (up to 148 DEG), with more genes involved in oxidative stress-dependent responses, apoptosis, autophagy and catabolic processes, and mitochondrial damage. Interestingly, within the severe NEB cows (high blood NEFA at wk 2), blood antioxidant concentrations (high vs. low) at wk 8 were associated with up to 194 DEG involved in activation of meiosis and other signaling pathways, indicating a better oocyte supportive capacity. This suggests that the cow antioxidant profile at the time of breeding might alleviate, at least in part, the effect of NEB on GC functions. In conclusion, these results provide further evidence that the metabolic and oxidative stress in dairy cows early postpartum can have long-term effects on GC functions in preovulatory follicles at the time of breeding. The interplay between the effects of antioxidants and NEFA illustrated here might be useful to develop intervention strategies to minimize the effect of severe NEB on fertility. DA - 2022/8// PY - 2022/8// DO - 10.3168/jds.2022-21928 VL - 105 IS - 8 SP - 6956-6972 SN - 1525-3198 UR - https://doi.org/10.3168/jds.2022-21928 KW - high-yielding dairy cow KW - beta-carotene KW - nonesterified fatty acids KW - metabolic stress KW - folliculogenesis ER - TY - JOUR TI - Characterization of vaccine-induced immune responses against coccidiosis in broiler chickens AU - Gaghan, Carissa AU - Adams, Daniel AU - Mohammed, Javid AU - Crespo, Rocio AU - Livingston, Kimberly AU - Kulkarni, Raveendra R. T2 - VACCINE AB - Coccidiosis, caused by Eimeria protozoan species, is an economically important enteric disease of poultry. Although commercial live vaccines are widely used for disease control, the vaccine-induced protective immune mechanisms are poorly characterized. The present study used a commercial broiler vaccine containing a mixture of E. acervulina, E. maxima, and E. tenella. One-day-old chicks were vaccinated by spray followed by a challenge at 21 days of age with a mixture of wild type Eimeria species via oral gavage. Oocyst shedding, immune gene expression and cellular responses in the spleen and cecal tonsils were measured at pre- (days 14 and 21) and post-challenge (days 24, 28 and 35) time points. Results showed that the oocyst counts were significantly reduced in the vaccinated chickens at post-challenge compared to unvaccinated control group. While the vaccinated birds had a significantly increased toll-like receptor (TLR) 21 gene expression at pre-challenge, the transcription of interferon (IFN)γ, Interleukin (IL)-12 and CD40 genes in spleen and cecal tonsils of these birds was significantly higher at post-challenge compared to unvaccinated chickens. Cellular immunophenotyping analysis found that vaccination led to increased frequency of macrophages and activated T cells (CD8+CD44+ and CD4+CD44+) in the spleen and cecal tonsils at post-challenge. Furthermore, in vitro stimulation of chicken macrophages (MQ-NCSU cells) with purified individual species of E. acervulina, E. maxima, and E. tenella showed a significantly increased expression of TLR21, TLR2 and IFNγ genes as well as nitric oxide production. Collectively, these findings suggest that TLR21 and TLR2 may be involved in the immune cell recognition of Eimeria parasites and that the vaccine can induce a robust macrophage activation leading to a T helper-1 dominated protective response at both local and systemic lymphoid tissues. DA - 2022/6/23/ PY - 2022/6/23/ DO - 10.1016/j.vaccine.2022.05.043 VL - 40 IS - 29 SP - 3893-3902 SN - 1873-2518 KW - Coccidiosis KW - Eimeria KW - Vaccine KW - Immunity KW - Immune response ER - TY - JOUR TI - Veterinary house officer perceptions of dimensions of well-being during postgraduate training AU - McPhetridge, Jourdan B. AU - Scharf, Valery F. AU - Dickson, Rachel AU - Thieman, Kelley M. AU - Oblak, Michelle L. AU - Regier, Penny J. AU - Skinner, Owen T. AU - Tinga, Selena AU - Townsend, Katy L. AU - Wallace, Mandy L. AU - Walton, Rebecca AU - Marks, Steven L. AU - Nelson, Laura T2 - JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION AB - Abstract OBJECTIVE To describe veterinary house officers’ perceptions of dimensions of well-being during postgraduate training and to identify potential areas for targeted intervention. SAMPLE 303 house officers. PROCEDURES A 62-item questionnaire was generated by use of an online platform and sent to house officers at participating institutions in October 2020. Responses were analyzed for trends and associations between selected variables. RESULTS 239 residents, 45 rotating interns, and 19 specialty interns responded to the survey. The majority of house officers felt that their training program negatively interfered with their exercise habits, diet, and social engagement. House officers reported engaging in exercise significantly less during times of clinical responsibility, averaging 1.6 exercise sessions/wk (SD ± 0.8) on clinical duty and 2.4 exercise sessions/wk (SD ± 0.9) when not on clinical duty ( P < 0.001). Ninety-four percent of respondents reported experiencing some degree of anxiety regarding their physical health, and 95% of house officers reported feeling some degree of anxiety regarding their current financial situation. Overall, 47% reported that their work-life balance was unsustainable for > 1 year; there was no association between specialty and sustainability of work-life balance. Most house officers were satisfied with their current training program, level of clinical responsibility, and mentorship. CLINICAL RELEVANCE Veterinary house officers demonstrated a poor balance between the demands of postgraduate training and maintenance of personal health. Thoughtful interventions are needed to support the well-being of veterinary house officers. DA - 2022/8/1/ PY - 2022/8/1/ DO - 10.2460/javma.21.05.0233 VL - 260 IS - 11 SP - 1369-1376 SN - 1943-569X ER - TY - JOUR TI - Enumeration and speciation of coccidia affecting turkeys using flow cytometry method AU - Boyett, Taylor AU - Crespo, Rocio AU - Vinueza, Valeria C. AU - Gaghan, Carissa AU - Mohammed, Javid P. AU - Kulkarni, Raveendra R. T2 - JOURNAL OF APPLIED POULTRY RESEARCH AB - Enumeration of Eimeria oocysts is a common practice in monitoring coccidiosis in turkeys; however, the conventional method of manual microscopic examination of Eimeria oocysts is time-consuming. Previously, we used flow cytometry (FCM) to enumerate and speciate coccidia affecting chickens and here, we extended those findings to turkey coccidia species, E. adenoides and E. meleagrimitis. Using FCM, a commercial vaccine containing these species was used to optimize the scatter-plot parameters, including Forward-(size) and Side-(shape/granularity) scatter Area, Height, and Width patterns for Eimeria. The two Eimeria species populations in the vaccine were accurately phenotyped and the gated populations were then sorted using a Cell sorter instrument to obtain pure oocyst suspensions. The individual Eimeria species identity of sorted oocysts was confirmed by PCR using species-specific primers. A significant (P = 0.0466) correlation (R = 0.9893) in the total oocyst count between FCM and manual methods were observed. Furthermore, when FCM was employed to analyze farm fecal samples, the close similarities in the oocyst morphologies coupled with organic debris particulate interference prevented a precise separation of these 2 species resulting in a lack of oocyst count (OPG) correlation between the 2 methods. The OPG counts by FCM were much lower than the manual method; however, a partial OPG trend between the two methods was observed only at the early timepoint collections during a period of 35 d. Collectively, our findings showed that FCM can be used in the enumeration of turkey Eimeria oocysts with a potential scope for a more precise enumeration and speciation in field samples. DA - 2022/9// PY - 2022/9// DO - 10.1016/j.japr.2022.100270 VL - 31 IS - 3 SP - SN - 1537-0437 KW - Eimeria KW - coccidiosis KW - turkey KW - flow cytometry KW - diagnosis ER - TY - JOUR TI - Googling for a veterinary diagnosis: A replication study using Google as a diagnostic aid AU - Allen, E. Carley AU - Alpi, Kristine M. AU - Schaaf, George W. AU - Marks, Steven L. T2 - JOURNAL OF VETERINARY INTERNAL MEDICINE AB - The purpose of this study was to replicate in the veterinary context a BMJ study using Google to assist in diagnosis of complex cases.To assess percentage of diagnoses identified using Google as a diagnostic aid in veterinary medicine.None; 13 cases in cats and 17 in dogs published in JAVMA.Cross-sectional survey of Google results from searches using keywords generated independently by a generalist and a specialist veterinarian who reviewed the published case history and diagnostic components while blind to the diagnosis. They offered diagnoses and generated up to 5 search strategies for each case. The top 30 Google results for each search were reviewed by the generalist to inform a final Google-aided diagnosis. Both veterinarians' initial diagnoses and the Google-aided diagnoses were compared with the published diagnoses.Google searching led to 52 diagnoses out of 60 possible. Twenty-two (42%, 95% confidence interval [95% CI] 29%-55%) Google-aided diagnoses matched the JAVMA diagnosis. This accuracy rate does not differ significantly from 58% (n = 15/26, 95% CI 38%-77%) identified in the BMJ study. Google-aided results were not statistically different from those achieved unaided by each veterinarian (33%, 95% CI 16%-50%).Published information found searching Google using keywords related to complicated or unusual cases could assist veterinarians to reinforce their initial diagnosis or consider other differential diagnoses. Search strategies using words representing either signs or the preliminary diagnoses can yield results useful to confirming a correct diagnosis. DA - 2022/7/11/ PY - 2022/7/11/ DO - 10.1111/jvim.16484 SP - SN - 1939-1676 KW - differential diagnoses KW - information resources KW - open access KW - problem lists ER - TY - JOUR TI - Hands-on learning: from at-risk wolves to teeming Galapagos AU - Meurs, Kathryn T2 - JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION DA - 2022/7/1/ PY - 2022/7/1/ DO - 10.2460/javma.22.05.0216 VL - 260 IS - 10 SP - 1140-1140 SN - 1943-569X ER - TY - JOUR TI - A novel mutation of the CLCN1 gene in a cat with myotonia congenita: Diagnosis and treatment AU - Woelfel, Christian AU - Meurs, Kathryn AU - Friedenberg, Steven AU - DeBruyne, Nicole AU - Olby, Natasha J. T2 - JOURNAL OF VETERINARY INTERNAL MEDICINE AB - Abstract Case Description A 10‐month‐old castrated male domestic longhair cat was evaluated for increasing frequency of episodic limb rigidity. Clinical Findings The cat presented for falling over and lying recumbent with its limbs in extension for several seconds when startled or excited. Upon examination, the cat had hypertrophied musculature, episodes of facial spasm, and a short‐strided, stiff gait. Diagnostics Electromyography (EMG) identified spontaneous discharges that waxed and waned in amplitude and frequency, consistent with myotonic discharges. A high impact 8‐base pair (bp) deletion across the end of exon 3 and intron 3 of the chloride voltage‐gated channel 1 ( CLCN1 ) gene was identified using whole genome sequencing. Treatment and Outcome Phenytoin treatment was initiated at 3 mg/kg po q24 h and resulted in long‐term improvement. Clinical Relevance This novel mutation within the CLCN1 gene is a cause of myotonia congenita in cats and we report for the first time its successful treatment. DA - 2022/7/11/ PY - 2022/7/11/ DO - 10.1111/jvim.16471 VL - 7 SP - SN - 1939-1676 KW - chloride channel KW - electromyography KW - nondystrophic myotonia KW - phenytoin ER - TY - JOUR TI - A Pilot, Open-Label Study to Evaluate the Efficacy of Intra-Articular Administration of a Caninized TNF Receptor Fc Fusion Protein as a Treatment for Osteoarthritis-Associated Joint Pain AU - Nakanishi, Aoi AU - Lascelles, B. Duncan X. AU - Allen, Julie AU - Case, Beth AU - Gearing, David AU - Enomoto, Masataka T2 - FRONTIERS IN VETERINARY SCIENCE AB - Tumor necrosis factor-α (TNF-α) is a potential target for osteoarthritis (OA) treatment. In several recent clinical studies in human OA, anti-TNF-α therapy showed promising results; however, these were open-label and based on patient-reported outcome measures. In this study, we developed a caninized TNF-α receptor-Fc (caTNFR-Fc) fusion protein and conducted a non-randomized, open-label, pilot study in dogs with OA using objectively measured ground reaction forces and activity. The aims of the study were to assess the efficacy of the intra-articular (IA) injection of the caTNFR-Fc fusion protein as a treatment for OA pain, and additionally to evaluate TNF concentrations in synovial fluid (SF) between joints with/without OA in dogs. Dogs ( n = 12) with single-limb lameness due to single joint appendicular OA were recruited. All dogs received caTNFR-Fc fusion protein injection into the affected joint under sedation. Objective kinetic gait analysis using force plate was performed prior to (baseline), and at 14- and 28-days following treatment. Additionally, SF samples were collected from OA joints ( n = 69) and non-OA joints ( n = 79) in a different cohort of dogs and TNF-α were measured using enzyme-linked immunosorbent assay. No significant treatment effects on the limb use, activity, and the questionnaire were found. The concentration of TNF-α was significantly higher in OA joints than in healthy joints ( p = 0.0019), but TNF-α was detected in only 10/69 OA samples. The IA injection of caTNFR-Fc fusion protein provided no benefit in terms of objective limb use and activity data in dogs with OA in this pilot study. Although the SF concentration of TNF-α was significantly higher in OA joints, few OA joints had measurable TNF-α. Collectively, the data indicate TNF-α may not be a good therapeutic target in canine OA. DA - 2022/6/2/ PY - 2022/6/2/ DO - 10.3389/fvets.2022.836709 VL - 9 SP - SN - 2297-1769 KW - osteoarthritis KW - joint pain KW - TNF-alpha KW - force plate KW - limb use asymmetry test ER - TY - JOUR TI - Perianesthetic mortality in English Bulldogs: a retrospective analysis in 2010-2017 AU - Oda, Ayako AU - Wang, Wen Hui AU - Hampton, Amanda K. AU - Robertson, James B. AU - Posner, Lysa P. T2 - BMC VETERINARY RESEARCH AB - Many veterinarians consider English Bulldogs to have a greater perianesthetic mortality risk. The aims of this study were to 1) determine total and anesthesia-related, perianesthetic mortality (PAM) rates in English Bulldogs (EB), 2) identify potential risk factors associated with mortality in EB, and 3) determine the difference in the perianesthetic mortality rates between EB, other-brachycephalic breeds (OB), and non-brachycephalic breeds (NB). Records from EB that were anesthetized between 2010 and 2017, were investigated. OB and NB were enrolled to match with each EB based on a procedure and age from the study period. Data collected in EB included: age, ASA status, weight, procedure types, anesthetic and analgesic management, anesthetic duration, anesthetic recovery location, and cause of death. Age and cause of death were determined from OB and NB. Fisher's exact test was used to compare PAM rate and age in EB, OB, and NB. Mann-Whitney U test was used to compare EB survivor and EB non-survivor. Logistic regression models were used to identify factors and odds ratio (OR) associated with PAM in EB.Two hundred twenty nine EB, 218 OB, and 229 NB were identified. The total and anesthesia-related PAM rates in EB were 6.6 and 3.9%, respectively. EB had a greater total PAM rate compared with OB (p = 0.007). ASA status was different between survivors and non-survivors in EB (p < 0.01). Risk factors identified regardless of the cause of death were premedication with full μ opioids (OR = 0.333, p = 0.114), continuous infusion of ketamine post-operatively (OR = 13.775, p = 0.013), and acepromazine administration post-operatively (OR = 7.274, p = 0.004). The most common cause of death in EB was postoperative respiratory dysfunction (87.5%).Total and anesthesia-related mortality in EB is considerable. Most deaths in EB occurred during the postoperative period secondary to respiratory complications. DA - 2022/5/25/ PY - 2022/5/25/ DO - 10.1186/s12917-022-03301-9 VL - 18 IS - 1 SP - SN - 1746-6148 KW - English Bulldog KW - Brachycephalic KW - Peri-anesthetic mortality KW - Respiratory KW - Obstructive airway KW - Veterinary anesthesia ER - TY - JOUR TI - Association of diet with clinical outcomes in dogs with dilated cardiomyopathy and congestive heart failure* AU - Walker, A. L. AU - DeFrancesco, T. C. AU - Bonagura, J. D. AU - Keene, B. W. AU - Meurs, K. M. AU - Tou, S. P. AU - Kurtz, K. AU - Aona, B. AU - Barron, L. AU - McManamey, A. AU - Robertson, J. AU - Adin, D. B. T2 - JOURNAL OF VETERINARY CARDIOLOGY AB - Dilated cardiomyopathy (DCM) in dogs has been associated with feeding of grain-free (GF), legume-rich diets. Some dogs with presumed diet-associated DCM have shown improved myocardial function and clinical outcomes following a change in diet and standard medical therapy. Prior GF (pGF) diet influences reverse cardiac remodeling and clinical outcomes in dogs with DCM and congestive heart failure (CHF). A retrospective study was performed with 67 dogs with DCM and CHF for which diet history was known. Dogs were grouped by diet into pGF and grain-inclusive (GI) groups. Dogs in the pGF group were included if diet change was a component of therapy. Survival was analyzed using Kaplan–Meier curves and the Cox proportional-hazards model. The median survival time was 344 days for pGF dogs vs. 253 days for GI dogs (P = 0.074). Statistically significant differences in median survival were identified when the analysis was limited to dogs surviving longer than one week (P = 0.033). Prior GF dogs had a significantly worse outcome the longer a GF diet was fed prior to diagnosis (P = 0.004) or if they were diagnosed at a younger age (P = 0.017). Prior GF dogs showed significantly greater improvement in normalized left ventricular internal diastolic diameter (P = 0.038) and E-point septal separation (P = 0.031) measurements and significant decreases in their furosemide (P = 0.009) and pimobendan (P < 0.005) dosages over time compared to GI dogs. Prior GF dogs that survived at least one week after diagnosis of DCM, treatment of CHF, and diet change had better clinical outcomes and showed reverse ventricular remodeling compared to GI dogs. DA - 2022/4// PY - 2022/4// DO - 10.1016/j.jvc.2021.02.001 VL - 40 SP - 99-109 SN - 1875-0834 KW - Canine KW - Survival KW - Grain-free KW - Echocardiography KW - Nutritional ER - TY - JOUR TI - A review of the underlying genetics and emerging therapies for canine cardiomyopathies AU - Shen, L. AU - Estrada, A. H. AU - Meurs, K. M. AU - Sleeper, M. AU - Vulpe, C. AU - Martyniuk, C. J. AU - Pacak, C. A. T2 - JOURNAL OF VETERINARY CARDIOLOGY AB - Cardiomyopathies such as dilated cardiomyopathy and arrhythmogenic right ventricular cardiomyopathy are common in large breed dogs and carry an overall poor prognosis. Research shows that these diseases have strong breed predilections, and selective breeding has historically been recommended to reduce the disease prevalence in affected breeds. Treatment of these diseases is typically palliative and aimed at slowing disease progression and managing clinical signs of heart failure as they develop. The discovery of specific genetic mutations underlying cardiomyopathies, such as the striatin mutation in Boxer arrhythmogenic right ventricular cardiomyopathy and the pyruvate dehydrogenase kinase 4 and titin mutations in Doberman Pinschers, has strengthened our ability to screen and selectively breed individuals in an attempt to produce unaffected offspring. The discovery of these disease-linked mutations has also opened avenues for the development of gene therapies, including gene transfer and genome-editing approaches. This review article discusses the known genetics of cardiomyopathies in dogs, reviews existing gene therapy strategies and the status of their development in canines, and discusses ongoing challenges in the clinical translation of these technologies for treating heart disease. While challenges remain in using these emerging technologies, the exponential growth of the gene therapy field holds great promise for future clinical applications. DA - 2022/4// PY - 2022/4// DO - 10.1016/j.jvc.2021.05.003 VL - 40 SP - 2-14 SN - 1875-0834 KW - Dilated cardiomyopathy KW - Arrhythmogenic right ventricular cardiomyo-pathy KW - Gene therapy KW - Gene editing KW - Clustered regularly in-terspaced short palin-dromic repeats ER - TY - JOUR TI - Clinical features and posttreatment monitoring of dogs administered rivaroxaban (2018-2020): 19 cases AU - Tracy, Alyxandra L. AU - Goggs, Robert AU - Brooks, Marjory B. AU - Lynch, Alex M. T2 - JOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE AB - Abstract Objective To describe a population of sick dogs administered rivaroxaban monitored with a rivaroxaban‐calibrated anti‐Xa activity assay (aXa). Design Descriptive retrospective study. Setting Two veterinary teaching hospitals. Animals Client‐owned dogs administered rivaroxaban and monitored with aXa from January 2018 to January 2020 were eligible for study. Interventions None. Measurements and Main Results Medical records were reviewed and 19 dogs with a variety of underlying disease processes were identified. Rivaroxaban was administered to 12 of 19 dogs (63%) with confirmed thrombosis, 4 of 19 dogs (21%) with a strong clinical suspicion of thrombosis, and in 3 of 19 dogs (16%) with no current evidence of thrombosis. The median rivaroxaban dose administered was 0.96 mg/kg/day (0.62–1.58 mg/kg/day), with 15 of 19 dogs (79%) receiving rivaroxaban once daily. Clopidogrel was concurrently administered to 11 of 19 dogs (58%). Complete or partial thrombus resolution was identified in 5 of 12 (42%) and 3 of 12 (25%) dogs, respectively. Rivaroxaban appeared safe, with only 1 of 19 dogs (5%), concurrently administered clopidogrel, developing evidence of mild hematuria. Posttreatment monitoring revealed that 8 of 19 dogs (42%) had aXa below the target (aXa range of 150–250 ng/ml associated with effective treatment and prevention of venous thrombosis in people). The remaining 3 to 19 dogs (16%) achieved this range, and 8 of 19 dogs (42%) exceeded the range. No significant relationship between the initial rivaroxaban dose administered and the corresponding aXa result was identified. There were also no significant differences in baseline clinicopathological variables in dogs in which aXa fell within or outside this range. Conclusions aXa was most commonly measured in dogs receiving rivaroxaban with confirmed or suspected thrombosis. Dogs in this study received a range of rivaroxaban dosages and attained variable aXa values that were not directly correlated with dosage. DA - 2022/4/20/ PY - 2022/4/20/ DO - 10.1111/vec.13199 SP - SN - 1476-4431 KW - anticoagulant KW - canine KW - thromboprophylaxis KW - venous thrombosis ER - TY - JOUR TI - Correlation of cytology to histology in a case of canine granulomatous colitis in a Boxer dog AU - Sims, C.S. AU - Nagle, J. AU - Tolbert, M.K. AU - Anderson, K. AU - Linder, K. AU - Neel, J. T2 - Veterinary Clinical Pathology AB - A 2-year-old castrated male mixed breed dog presented to the North Carolina State Veterinary Teaching Hospital for chronic diarrhea with hematochezia and weight loss. Cytology performed on a rectal scraping revealed macrophages containing magenta, light pink, and variably blue granular inclusions, and phagocytosed material concerning for infectious organisms. Histopathology was consistent with granulomatous colitis and identified intra-histiocytic bacterial organisms, confirmed by fluorescent in situ hybridization (FISH)-tissue culture-confirmed Escherichia coli. Based on these findings, a diagnosis of granulomatous colitis was made. The patient was successfully treated with oral enrofloxacin, and near-complete remission of signs was achieved within 6 weeks. This report describes a case of granulomatous colitis in a mixed breed dog, and is the first published description of the cytologic features of this uncommon disease, offering a valuable cytologic-histologic correlation. In this case, the cytology was helpful in identifying features consistent with granulomatous colitis and prioritizing the differential diagnoses and diagnostic plan. DA - 2022/// PY - 2022/// DO - 10.1111/vcp.13058 VL - 50 IS - S1 SP - 83-87 UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-85117248282&partnerID=MN8TOARS ER - TY - JOUR TI - Discharge summaries provided to owners of pets newly diagnosed with cancer exceed recommended readability levels AU - Medland, Julia E. AU - Marks, Steven L. AU - Intile, Joanne L. T2 - JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION AB - Abstract OBJECTIVE To analyze the readability of discharge summaries distributed to owners of pets newly diagnosed with cancer. SAMPLE 118 discharge summaries provided to pet owners following initial consultation. PROCEDURES A database search identified records of new patients that had been presented to the North Carolina State Veterinary Hospital medical oncology service between June 2017 and January 2019. Owner-directed portions of the summaries provided at the time of discharge were copied and pasted into a document and stripped of all identifying information. Readability of summaries was assessed with the use of 2 previously established readability calculators: the Flesch-Kincaid Grade Level (FKGL) and Flesch Reading Ease (FRE) tests. RESULTS Mean ± SD FKGL was 11.9 ± 1.1 (median, 11.9; range, 8.6 to 15.5; target ≤ 6), and the mean ± SD FRE score was 43 ± 5.9 (median, 42.7; range, 25.5 to 58.1; target ≥ 60). There were no significant differences in FKGL or FRE scores among discharge summaries for patients with the 4 most common tumor types diagnosed or the described treatment options. Ninety-three percent (110/118) of summaries were scored as difficult or very difficult to read. CLINICAL RELEVANCE Owner-directed written information regarding a diagnosis of cancer at a single teaching hospital exceeded readability levels recommended by the American Medical Association and NIH and was above the average reading level of most US adults. Efforts to improve readability are an important component of promoting relationship-centered care and may improve owner compliance and patient outcomes. DA - 2022/3/15/ PY - 2022/3/15/ DO - 10.2460/javma.21.09.0410 VL - 260 IS - 6 SP - 657-661 SN - 1943-569X ER - TY - JOUR TI - EFFECTS OF TRICAINE METHANESULFONATE IN A MANAGED COLLECTION OF MOON JELLYFISH (AURELIA AURITA) AU - Gorges, Melinda A. AU - Martinez, Kassandra M. AU - Labriola, Nicholas F. AU - Phillips, Brianne E. AU - Christian, Larry Shane AU - Chen, Emile P. AU - Posner, Lysa P. AU - Lewbart, Gregory A. AU - Dombrowski, Daniel S. T2 - JOURNAL OF ZOO AND WILDLIFE MEDICINE AB - The moon jellyfish (Aurelia aurita) is a scyphozoan frequently maintained in public and private aquaria. Little research has been conducted to investigate the effects of various drugs, such as anesthetics, in this species. Tricaine methanesulfonate (MS-222), a common immersion anesthetic for fish and amphibians, was evaluated in a managed population of moon jellyfish. Twenty-four clinically healthy jellyfish were assigned into three groups of eight for trials of 0.3 g/L MS-222 (low concentration [LC]), 0.6 g/L MS-222 (high concentration [HC]), and a saltwater control. The goal was to evaluate the effects of MS-222 administration on moon jellyfish movement and response to stimuli. Movement and response to stimuli were measured via rocking and probe stimulus tests and observations of bell contraction quality and body tone. These tests were performed at baseline and throughout both drug exposure and recovery periods. A threshold drug effect was defined based on systematic scoring criteria. Additionally, elastomer tags were administered to four of eight animals in each MS-222 group to evaluate response to tag placement after drug exposure. Threshold drug effect was achieved in six of eight individuals in the LC group and eight of eight individuals in the HC group. The LC group had median threshold and recovery times of 12.2 and 10.1 min, respectively, while the HC group had median threshold and recovery times of 4.0 and 19.9 min, respectively. The HC group had significantly faster time to threshold drug effect (P < 0.001) and longer recovery times (P= 0.005) than the LC group. In both the LC and HC tagged group, three of four jellyfish had no reaction to tag placement. All animals recovered uneventfully, and there were no mortalities. MS-222 at 0.3 and 0.6 g/L decreased movement and response to stimuli in moon jellyfish. DA - 2022/3// PY - 2022/3// DO - 10.1638/2021-0028 VL - 53 IS - 1 SP - 100-107 SN - 1937-2825 ER - TY - JOUR TI - Targeting KIT by frameshifting mRNA transcripts as a therapeutic strategy for aggressive mast cell neoplasms AU - Snider, Douglas B. AU - Arthur, Greer K. AU - Falduto, Guido H. AU - Olivera, Ana AU - Ehrhardt-Humbert, Lauren C. AU - Smith, Emmaline AU - Smith, Cierra AU - Metcalfe, Dean D. AU - Cruse, Glenn T2 - MOLECULAR THERAPY AB - Activating mutations in c-KIT are associated with the mast cell (MC) clonal disorders cutaneous mastocytosis and systemic mastocytosis and its variants, including aggressive systemic mastocytosis, MC leukemia, and MC sarcoma. Currently, therapies inhibiting KIT signaling are a leading strategy to treat MC proliferative disorders. However, these approaches may have off-target effects, and in some patients, complete remission or improved survival time cannot be achieved. These limitations led us to develop an approach using chemically stable exon skipping oligonucleotides (ESOs) that induce exon skipping of precursor (pre-)mRNA to alter gene splicing and introduce a frameshift into mature KIT mRNA transcripts. The result of this alternate approach results in marked downregulation of KIT expression, diminished KIT signaling, inhibition of MC proliferation, and rapid induction of apoptosis in neoplastic HMC-1.2 MCs. We demonstrate that in vivo administration of KIT targeting ESOs significantly inhibits tumor growth and systemic organ infiltration using both an allograft mastocytosis model and a humanized xenograft MC tumor model. We propose that our innovative approach, which employs well-tolerated, chemically stable oligonucleotides to target KIT expression through unconventional pathways, has potential as a KIT-targeted therapeutic alone, or in combination with agents that target KIT signaling, in the treatment of KIT-associated malignancies. DA - 2022/1/5/ PY - 2022/1/5/ DO - 10.1016/j.ymthe.2021.08.009 VL - 30 IS - 1 SP - 295-310 SN - 1525-0024 ER - TY - JOUR TI - Regulation of Trafficking and Signaling of the High Affinity IgE Receptor by Fc epsilon RI beta and the Potential Impact of Fc epsilon RI beta Splicing in Allergic Inflammation AU - Arthur, Greer K. AU - Cruse, Glenn T2 - INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES AB - Mast cells are tissue-resident immune cells that function in both innate and adaptive immunity through the release of both preformed granule-stored mediators, and newly generated proinflammatory mediators that contribute to the generation of both the early and late phases of the allergic inflammatory response. Although mast cells can be activated by a vast array of mediators to contribute to homeostasis and pathophysiology in diverse settings and contexts, in this review, we will focus on the canonical setting of IgE-mediated activation and allergic inflammation. IgE-dependent activation of mast cells occurs through the high affinity IgE receptor, FcεRI, which is a multimeric receptor complex that, once crosslinked by antigen, triggers a cascade of signaling to generate a robust response in mast cells. Here, we discuss FcεRI structure and function, and describe established and emerging roles of the β subunit of FcεRI (FcεRIβ) in regulating mast cell function and FcεRI trafficking and signaling. We discuss current approaches to target IgE and FcεRI signaling and emerging approaches that could target FcεRIβ specifically. We examine how alternative splicing of FcεRIβ alters protein function and how manipulation of splicing could be employed as a therapeutic approach. Targeting FcεRI directly and/or IgE binding to FcεRI are promising approaches to therapeutics for allergic inflammation. The characteristic role of FcεRIβ in both trafficking and signaling of the FcεRI receptor complex, the specificity to IgE-mediated activation pathways, and the preferential expression in mast cells and basophils, makes FcεRIβ an excellent, but challenging, candidate for therapeutic strategies in allergy and asthma, if targeting can be realized. DA - 2022/1// PY - 2022/1// DO - 10.3390/ijms23020788 VL - 23 IS - 2 SP - SN - 1422-0067 KW - mast cell KW - IgE receptor KW - Fc epsilon RI beta KW - antisense therapy KW - allergy KW - asthma KW - exon skipping ER - TY - JOUR TI - Intestinal changes and immune responses during Clostridium perfringens-induced necrotic enteritis in broiler chickens AU - Daneshmand, Ali AU - Kermanshahi, Hassan AU - Mohammed, Javid AU - Sekhavati, Mohammad Hadi AU - Javadmanesh, Ali AU - Ahmadian, Monireh AU - Alizadeh, Marzieh AU - Razmyar, Jamshid AU - Kulkarni, Raveendra R. T2 - POULTRY SCIENCE AB - Clostridium perfringens-induced necrotic enteritis (NE) is an economically important disease of broiler chickens. The present study evaluated the effect of C. perfringens on the intestinal histomorphometry, enteric microbial colonization, and host immune responses using 3 experimental NE reproduction methods. The experimental groups consisted of 1) unchallenged Control diet (corn-soybean meal), 2) Control diet + Eimera inoculation at d 11 followed by C. perfringens challenge at d 15 (ECp), 3) Wheat-based diet + C. perfringens challenge (WCp), and 4) Wheat-based diet + Eimeria inoculation followed by C. perfringens challenge (WECp). The results showed that chickens receiving ECp and WECp had reduced (P < 0.05) bird performance coupled with enteric gross lesions and epithelial damage at d 17 and 24 of age compared to unchallenged control birds. These ECp and WECp administered birds also had increased (P < 0.05) ileal colonization by clostridia and E. coli at d 17 and 24, while the resident Lactobacillus counts were reduced (P < 0.05) at d 24 of age. Furthermore, at d 24, jejunal transcription of IL-6, IL-10, annexin-A1 and IL-2 genes was upregulated (P < 0.05) in the ECp group, whereas the transcription of TNF receptor associated factor (TRAF)-3 gene was increased (P < 0.05) in WECp treated birds when compared to unchallenged control group. Additionally, stimulation of chicken splenocytes and cecal tonsilocytes with virulent C. perfringens bacilli or their secretory proteins resulted in a higher (P < 0.05) frequency of T cells and their upregulation of MHC-II molecule, as determined by flow cytometry. These findings suggest that C. perfringens, while inducing epithelial damage and changes in microbiota, can also trigger host immune responses. Furthermore, NE reproduction methods using coccidia with or without the wheat-based dietary predisposition seem to facilitate an optimal NE reproduction in broiler chickens and thus, may provide better avenues for future C. perfringens research. DA - 2022/3// PY - 2022/3// DO - 10.1016/j.psj.2021.101652 VL - 101 IS - 3 SP - SN - 1525-3171 KW - Necrotic enteritis KW - Clostridium perfringens KW - broiler chicken KW - histomorphometry KW - immune response ER - TY - JOUR TI - Avian Macrophage Responses to Virulent and Avirulent Clostridium perfringens AU - Kulkarni, Raveendra R. AU - Gaghan, Carissa AU - Mohammed, Javid T2 - PATHOGENS AB - The present study evaluated the avian macrophage responses against Clostridium perfringens that varied in their ability to cause necrotic enteritis in chickens. Strains CP5 (avirulent-netB+), CP1 (virulent-netB+), and CP26 (highly virulent-netB+tpeL+) were used to evaluate their effect on macrophages (MQ-NCSU cells) and primary splenic and cecal tonsil mononuclear cells. The bacilli (whole cells) or their secretory products from all three strains induced a significant increase in the macrophage transcription of Toll-like receptor (TLR)21, TLR2, interleukin (IL)-1β, inducible nitric oxide synthase (iNOS), and CD80 genes as well as their nitric oxide (NO) production and major histocompatibility complex (MHC)-II surface expression compared to an unstimulated control. The CP1 and CP26-induced expression of interferon (IFN)γ, IL-6, CD40 genes, MHC-II upregulation, and NO production was significantly higher than that of CP5 and control groups. Furthermore, splenocytes and cecal tonsillocytes stimulated with bacilli or secretory products from all the strains showed a significant increase in the frequency of macrophages, their surface expression of MHC-II and NO production, while CP26-induced responses were significantly higher for the rest of the groups. In summary, macrophage interaction with C. perfringens can lead to cellular activation and, the ability of this pathogen to induce macrophage responses may depend on its level of virulence. DA - 2022/1// PY - 2022/1// DO - 10.3390/pathogens11010100 VL - 11 IS - 1 SP - SN - 2076-0817 KW - macrophages KW - Clostridium perfringens KW - virulence KW - chicken KW - necrotic enteritis KW - immune response ER - TY - JOUR TI - Evidence of sheep and abattoir environment as important reservoirs of multidrug-resistant Salmonella and extended-spectrum beta-lactamase Escherichia coli AU - Atlaw, N.A. AU - Keelara, S. AU - Correa, M. AU - Foster, D. AU - Gebreyes, W. AU - Aidara-Kane, A. AU - Harden, L. AU - Thakur, S. AU - Fedorka-Cray, P.J. T2 - International Journal of Food Microbiology AB - The increase in antimicrobial-resistant (AMR) foodborne pathogens, including E. coli and Salmonella in animals, humans, and the environment, is a growing public health concern. Among animals, cattle, pigs, and chicken are reservoirs of these pathogens worldwide. There is a knowledge gap on the prevalence and AMR of foodborne pathogens in small ruminants (i.e., sheep and goats). This study investigates the prevalence and antimicrobial resistance of extended-spectrum beta-lactamase (ESBL) E. coli and Salmonella from sheep and their abattoir environment in North Carolina. We conducted a year-round serial cross-sectional study and collected a total of 1128 samples from sheep (n = 780) and their abattoir environment (n = 348). Sheep samples consisted of feces, cecal contents, carcass swabs, and abattoir resting area feces. Environmental samples consisted of soil samples, lairage swab, animal feed, and drinking water for animals. We used CHROMAgar EEC with 4 μg/ml of Cefotaxime for isolating ESBL E. coli, and ESBL production was confirmed by double-disk diffusion test. Salmonella was isolated and confirmed using standard methods. All of the confirmed isolates were tested against a panel of 14 antimicrobials to elucidate susceptibility profiles. The prevalence of ESBL E. coli and Salmonella was significantly higher in environmental samples (47.7% and 65.5%) compared to the sheep samples (19.5% and 17.9%), respectively (P < 0.0001). We recovered 318 ESBL E. coli and 368 Salmonella isolates from sheep and environmental samples. More than 97% (310/318) of ESBL E. coli were multidrug-resistant (MDR; resistant to ≥3 classes of antimicrobials). Most Salmonella isolates (77.2%, 284/368) were pansusceptible, and 10.1% (37/368) were MDR. We identified a total of 24 different Salmonella serotypes by whole genome sequencing (WGS). The most common serotypes were Agona (19.8%), Typhimurium (16.2%), Cannstatt (13.2%), Reading (13.2%), and Anatum (9.6%). Prevalence and percent resistance of ESBL E. coli and Salmonella isolates varied significantly by season and sample type (P < 0.0001). The co-existence of ESBL E. coli in the same sample was associated with increased percent resistance of Salmonella to Ampicillin, Chloramphenicol, Sulfisoxazole, Streptomycin, and Tetracycline. We presumed that the abattoir environment might have played a great role in the persistence and dissemination of resistant bacteria to sheep as they arrive at the abattoir. In conclusion, our study reaffirms that sheep and their abattoir environment act as important reservoirs of AMR ESBL E. coli and MDR Salmonella in the U.S. Further studies are required to determine associated public health risks. DA - 2022/2/16/ PY - 2022/2/16/ DO - 10.1016/j.ijfoodmicro.2021.109516 VL - 363 SP - 109516 SN - 1879-3460 UR - http://dx.doi.org/10.1016/j.ijfoodmicro.2021.109516 KW - Salmonella KW - Abattoir KW - Sheep KW - Antimicrobial susceptibility KW - Prevalence ER - TY - JOUR TI - A flow cytometric method for enumeration and speciation of coccidia affecting broiler chickens AU - Adams, Daniel S. AU - Kulkarni, Raveendra R. AU - Mohammed, Javid P. AU - Crespo, Rocio T2 - VETERINARY PARASITOLOGY AB - Production losses, mortality, and control measures associated with coccidiosis, caused by Eimera species, cost the broiler industry over $14 billion a year. Current means to distinguish Eimeria species such as oocyst morphology, pre-patent period and site of infection are subjective, labor intensive or unsuitable for high-throughput applications. Although Polymerase Chain Reaction (PCR) techniques have been validated, the target gene cannot differentiate relative abundance of each species in mixed infections. In this study, we developed a non-antibody-based flow cytometry high throughput method to simultaneously enumerate and speciate four Eimeria species, E. acervulina, E. mitis, E. maxima, and E. tenella, using commercial coccidia vaccine as well as field fecal samples. Our findings showed that the four Eimeria oocyst populations could be distinctly speciated based on their size and granularity (shape) via scatter plotting. These distinct populations were sorted and confirmed by quantitative real-time PCR assay. Finally, the flow cytometry findings were applied to enumerate and speciate oocysts from fecal samples collected from commercial broiler flocks vaccinated for coccidiosis at day of hatch and the results were validated against the conventional manual method of floatation and microscopic examination. Collectively, the findings of this study suggested that non-antibody based Flow Cytometry technique can be successful in the simultaneous enumeration and speciation of coccidia. Further development and validation is needed to make this diagnostic tool useful for field applications at a much larger scale as well as to speciate other Eimeria species. DA - 2022/1// PY - 2022/1// DO - 10.1016/j.vetpar.2021.109634 VL - 301 SP - SN - 1873-2550 KW - Flow cytometry KW - Eimeria KW - Coccidiosis KW - Oocyst KW - Quantification ER -