Randomized comparison between a forced air system and warm water bath for resuscitation of neonatal hypothermic calves with or without oral administration of caffeine.

BACKGROUND: Hypothermia is a cause of neonatal calf death in cold climates. Practical and effective rewarming methods are important for bovine health within affected regions. HYPOTHESIS/OBJECTIVES: To compare the rewarming rate and blood analytes (glucose, lactate, and cortisol) of calves resuscitated with forced air with warm water bath, with or without oral administration of caffeine. ANIMALS: Twenty healthy neonatal Holstein bull calves. METHODS: In this randomized, prospective study, calves born healthy and without history of dystocia were cooled to 32°C rectal temperature then thermally resuscitated using either forced air rewarming or warm water bath (40°C) with or without oral administration of caffeine. Rectal temperatures were used to quantify recovery rate. Measurements of glucose, lactate, and cortisol were recorded for every 2°C change in rectal temperature. RESULTS: Rectal temperature decline (0.03°C per minute) and total cooling time (191.0 ± 33.3 minutes) did not significantly differ among treatment groups. Calves were successfully resuscitated to 38°C by either method. Time required to euthermia using warm water was significantly faster (0.1°C per minute; 64.3 ± 17.8 minute; P < .05) than forced air (0.05°C per minute; 123.1 ± 20.0 minutes). Caffeine had no significant effect on resuscitation rate (P = .14; 95% CI, -0.002 to 0.024) in either treatment; however, caffeine was associated with reduced time to euthermia by 8.3 and 10.8 minutes, respectively. Changes in metabolic variables (glucose, lactate, and cortisol), were inversely related to rectal temperature with no statistical significance among rewarming methods. CONCLUSIONS AND CLINICAL IMPORTANCE: Although warm water submersion is faster, forced air rewarming is an effective alternative for restoration of euthermia.

Assessing stakeholders' opinions on sharing antimicrobial susceptibility testing data from animals is key to developing a centralized database and dashboard tool.

OBJECTIVE: To present, analyze, and discuss stakeholders' opinions regarding sharing antimicrobial susceptibility testing (AST) data from animals into a centralized database and dashboard tool that would collect, aggregate, store, and analyze this type of data from veterinary diagnostic laboratories (VDLs) across the country. SAMPLE: 1 in-person focus group (9 participants), 9 virtual focus groups (49 participants), and online pre- and postmeeting surveys (76 and 35 participants, respectively). METHODS: Focus groups and surveys were conducted to assess the opinions of veterinarians, producers, researchers, diagnosticians, and government officials. RESULTS: A strong majority of stakeholders recognize AMR as a serious concern for both human and animal health and see several benefits in establishing a centralized AMR database; however, several concerns were raised associated with data confidentiality, security, curation, and harmonization. In the interest of alleviating those concerns, among other items, stakeholders suggested education and training of data users, providers, and the public in addition to assuring strong data confidentiality protections. CLINICAL RELEVANCE: Stakeholder engagement is a critical component of all stages of development, implementation, and utilization of an AMR database and dashboard tool that could be used to inform antimicrobial stewardship in veterinary medicine. This assessment of stakeholders' needs and concerns can be used to help guide future recommendations for data legal protections as well as a data confidentiality and security framework. Maintaining open communication on data usage, storage, and security as well as involvement and education of data providers, users, and the public will remain key to enabling development of an AMR database and dashboard tool for domesticated animals.

Salmonella enterica induces biogeography-specific changes in the gut microbiome of pigs.

Swine are a major reservoir of an array of zoonotic Salmonella enterica subsp. enterica lineage I serovars including Derby, Typhimurium, and 4,[5],12:i:- (a.k.a. Monophasic Typhimurium). In this study, we assessed the gastrointestinal (GI) microbiome composition of pigs in different intestinal compartments and the feces following infection with specific zoonotic serovars of S. enterica (S. Derby, S. Monophasic, and S. Typhimurium). 16S rRNA based microbiome analysis was performed to assess for GI microbiome changes in terms of diversity (alpha and beta), community structure and volatility, and specific taxa alterations across GI biogeography (small and large intestine, feces) and days post-infection (DPI) 2, 4, and 28; these results were compared to disease phenotypes measured as histopathological changes. As previously reported, only S. Monophasic and S. Typhimurium induced morphological alterations that marked an inflammatory milieu restricted to the large intestine in this experimental model. S. Typhimurium alone induced significant changes at the alpha- (Simpson's and Shannon's indexes) and beta-diversity levels, specifically at the peak of inflammation in the large intestine and feces. Increased community dispersion and volatility in colonic apex and fecal microbiomes were also noted for S. Typhimurium. All three Salmonella serovars altered community structure as measured by co-occurrence networks; this was most prominent at DPI 2 and 4 in colonic apex samples. At the genus taxonomic level, a diverse array of putative short-chain fatty acid (SCFA) producing bacteria were altered and often decreased during the peak of inflammation at DPI 2 and 4 within colonic apex and fecal samples. Among all putative SCFA producing bacteria, Prevotella showed a broad pattern of negative correlation with disease scores at the peak of inflammation. In addition, Prevotella 9 was found to be significantly reduced in all Salmonella infected groups compared to the control at DPI 4 in the colonic apex. In conclusion, this work further elucidates that distinct swine-related zoonotic serovars of S. enterica can induce both shared (high resilience) and unique (altered resistance) alterations in gut microbiome biogeography, which helps inform future investigations of dietary modifications aimed at increasing colonization resistance against Salmonella through GI microbiome alterations.

Prevalence of antibiotic use for dogs and cats in United States veterinary teaching hospitals, August 2020.

BACKGROUND: Awareness of prescribing practices helps identify opportunities to improve antibiotic use (AU). OBJECTIVES: To estimate AU prevalence in dogs and cats in U.S. veterinary teaching hospitals (VTHs) and identify antibiotic drugs commonly prescribed, indications for use, and evidence of bacterial infection. ANIMALS: Medical record data were collected from dogs and cats examined at 14 VTHs. METHODS: Data were collected from VTH medical records of dogs and cats examined by primary care, urgent care, emergency and critical care, internal medicine, and surgery services on a single day during August 13-September 3, 2020. Data included signalment; clinical service; inpatient or outpatient status; clinical conditions; diagnostic tests; evidence of bacterial infection; intended reason for AU; name and route of antibiotics prescribed. RESULTS: Of 883 dogs and cats, 322 (36.5%) were prescribed at least 1 antibiotic. Among 285 antibiotics administered systemically intended for treatment of infection, 10.9% were prescribed without evidence of infection. The most common class of antibiotics presribed for systemic administration was potentiated penicillin for dogs (115/346, 33.3%) and cats (27/80, 33.8%). For dogs and cats, first-generation cephalosporins (93/346, 26.9% and 11/80, 13.8%, respectively) and fluoroquinolones (51/346, 14.7% and 19/80, 23.8%, respectively) was second or third most-prescribed. Common AU indications included skin, respiratory, and urinary conditions, and perioperative use. CONCLUSIONS AND CLINICAL IMPORTANCE: Collaborative data collection provides a sustainable methodology to generate national AU prevalence estimates and bring attention to areas requiring additional research and detailed data collection. These efforts can also identify practice improvement opportunities in settings where future veterinarians are trained.

Comparison of turbidometric immunoassay, refractometry, and gamma-glutamyl transferase to radial immunodiffusion for assessment of transfer of passive immunity in high-risk beef calves.

BACKGROUND: Attainment of adequate transfer of passive immunity (TPI) is critical to health of calves; however, studies comparing available tools for measurement of TPI in individual beef animals are limited. OBJECTIVES: To report agreement between 4 tests evaluating individual TPI status in beef calves. ANIMALS: One hundred ninety-six beef calves born to cows and heifers presenting for calving management or dystocia. METHODS: Retrospective study to assess serum immunoglobulin (IgG) concentrations via turbidimetric immunoassay (TI), gamma-glutamyl transferase (GGT), serum total protein (TP), and single radial immunodiffusion (RID; reference standard). Test agreement was evaluated using Passing-Bablok regression, Bland-Altman analysis, Cohen's kappa, and receiver operating characteristic (ROC) curves with and without covariate adjustment to determine optimal thresholds. RESULTS: Correlation between RID and test results varied: TI, ρ = 0.757; TP, ρ = 0.715; GGT: ρ = 0.413. For the TI compared to RID, regression analysis identified a constant (intercept = -0.51 [CI: -2.63, 3.05]) and proportional (slope = 1.87 [CI: 1.69, 2.08]) bias. Based on ROC, TI concentrations of ≤9.89 and ≤13.76 g/L, and TP concentrations of ≤5.5 and ≤6.0 g/dL, indicated IgG concentrations <18.0 and <25.0 g/L, respectively. CONCLUSIONS AND CLINICAL IMPORTANCE: Within this cohort of calves, TI demonstrated the best correlation with RID; however, significant bias was identified which led to frequent underestimation of IgG concentration. Serum total protein demonstrated less correlation with RID but had less misclassification than TI. Both TI and TP demonstrated less correlation for calves that received colostrum replacement prompting clinical awareness of colostrum type when evaluating individual TPI in beef calves.

Comparison of turbidometric immunoassay and brix refractometry to radial immunodiffusion for assessment of colostral immunoglobulin concentration in beef cattle.

BACKGROUND: Colostral immunoglobulin G (IgG) concentration is critical to the attainment of adequate transfer of passive immunity in cattle, however, studies comparing available tools for measurement of colostral IgG concentration in beef cattle are limited. OBJECTIVES: To report the agreement between 3 commercially available tests for evaluating IgG concentration in beef colostrum. ANIMALS: Two hundred six beef-breed cows hospitalized for calving management or dystocia. METHODS: Retrospective study to assess IgG of whole colostrum measured stall-side via turbidimetric immunoassay (TI) and brix refractometry (BRIX), compared to fat separated (FS) analysis via single radial-immunodiffusion (RID; reference standard), TI-FS and BRIX-FS. Test performance was assessed using Passing Bablock regression, Bland-Altman analysis, and area under the curve to determine optimal thresholds. RESULTS: Correlation between RID and TI-FS, BRIX-FS, or BRIX was similar (Spearman's ρ = 0.717, 0.715, 0.716, respectively) but correlation for TI was poor (ρ = 0.586). Regression analysis identified a substantial constant (-214.75 [CI: -272.03 to -178.07]) and proportional (13.24 [CI: 11.81-15.37]) bias between the RID and TI-FS which was similar for TI. TI-FS concentrations of 28.47, 38.75, and 50.62 g/L, BRIX-FS of ≤21.9%, ≤24.0%, and ≤27.4%, and BRIX of ≤21.3%, ≤23.8%, and ≤26.4% indicated IgG concentrations <50, <100, and <150 g/L, respectively; appropriate cutoffs for TI could not be generated. CONCLUSIONS AND CLINICAL IMPORTANCE: Both TI and TI-FS demonstrated a large constant and proportional bias compared to RID; BRIX and BRIX-FS were well correlated with RID and remain a reliable method for estimation of colostral IgG concentration in beef cattle.

Direct interaction of small non-coding RNAs CjNC140 and CjNC110 optimizes expression of key pathogenic phenotypes of Campylobacter jejuni.

Small non-coding RNAs (sRNAs) are important players in modulating gene expression in bacterial pathogens, but their functions are largely undetermined in Campylobacter jejuni, an important cause of foodborne gastroenteritis in humans. In this study, we elucidated the functions of sRNA CjNC140 and its interaction with CjNC110, a previously characterized sRNA involved in the regulation of several virulence phenotypes of C. jejuni. Inactivation of CjNC140 increased motility, autoagglutination, L-methionine concentration, autoinducer-2 production, hydrogen peroxide resistance, and early chicken colonization, indicating a primarily inhibitory role of CjNC140 for these phenotypes. Apart from motility, all these effects directly contrasted the previously demonstrated positive regulation by CjNC110, suggesting that CjNC110 and CjNC140 operate in an opposite manner to modulate physiologic processes in C. jejuni. RNAseq and northern blotting further demonstrated that expression of CjNC140 increased in the absence of CjNC110, while expression of CjNC110 decreased in the absence of CjNC140, suggesting a possibility of their direct interaction. Indeed, electrophoretic mobility shift assay demonstrated a direct binding between the two sRNAs via GA- (CjNC110) and CU- (CjNC140) rich stem-loops. Additionally, RNAseq and follow-up experiments identified that CjNC140 positively regulates p19, which encodes a key iron uptake transporter in Campylobacter. Furthermore, computational analysis revealed both CjNC140 and CjNC110 are highly conserved in C. jejuni, and the predicted secondary structures support CjNC140 as a functional homolog of the iron regulatory sRNA, RyhB. These findings establish CjNC140 and CjNC110 as a key checks-and- balances mechanism in maintaining homeostasis of gene expression and optimizing phenotypes critical for C. jejuni pathobiology. IMPORTANCE Gene regulation is critical to all aspects of pathogenesis of bacterial disease, and small non-coding RNAs (sRNAs) represent a new frontier in gene regulation of bacteria. In Campylobacter jejuni, the role of sRNAs remains largely unexplored. Here, we investigate the role of two highly conserved sRNAs, CjNC110 and CjNC140, and demonstrate that CjNC140 displays a primarily inhibitory role in contrast to a primarily activating role for CjNC110 for several key virulence-associated phenotypes. Our results also revealed that the sRNA regulatory pathway is intertwined with the iron uptake system, another virulence mechanism critical for in vivo colonization. These findings open a new direction for understanding C. jejuni pathobiology and identify potential targets for intervention for this major foodborne pathogen.

Impact of multi-drug resistance on clinical outcomes of dogs with corneal ulcers infected with Staphylococcus pseudintermedius.

Objective: Compare characteristics and clinical outcomes of dogs with infectious keratitis from Staphylococcus pseudintermedius considered to be multidrug-resistant (MDR) or not. Procedures: Staphylococcus pseudintermedius isolated as the primary pathogen from canine patients with ulcerative keratitis were considered MDR if resistant to at least one agent in three or more classes of antibiotics. Medical records were reviewed for history, patients' characteristics, clinical appearance, therapeutic interventions, and clinical outcomes. Results: Twenty-eight dogs (28 eyes) were included. Compared to non-MDR cases, MDR diagnosis was significantly more common in dogs with recent (≤30 days) anesthesia (7/15 vs. 1/13, P = 0.038) and more common in non-brachycephalic dogs (8/15 vs. 2/13, P = 0.055). Clinical appearance (ulcer size/depth, anterior chamber reaction, etc.) did not differ significantly between groups (P ≥ 0.055). Median (range) time to re-epithelialization was longer in MDR vs. non-MDR eyes [29 (10-47) vs. 22 (7-42) days] but the difference was not significant (P = 0.301). Follow-up time was significantly longer in dogs with MDR keratitis [47 (29-590) vs. 29 (13-148) days, P = 0.009]. No other significant differences were noted between MDR and non-MDR eyes in regard to time for ulcer stabilization [4 (1-17) days vs. 4 (1-12), P = 0.699], number of eyes requiring surgical stabilization (7/15 vs. 7/13, P = 0.246) or enucleation (1/15 vs. 2/13, P = 1.000), success in maintaining globe (14/15 vs. 11/13, P = 0.583) or success in maintaining vision (12/15 vs. 10/13, P = 1.000). Conclusions: MDR infections may prolong corneal healing time but did not appear to affect overall clinical outcomes in dogs with bacterial keratitis. Further research is warranted in a larger canine population and other bacterial species.

Ultrasonography and digital radiography findings in sheep with clinical disease associated with small ruminant lentivirus infection.

Digital radiography and ultrasonographic images were used in this case series to evaluate 4 ewes from a single flock for chronic weight loss and ill-thrift. On examination, all displayed tachypnea, dyspnea, coughing, and normothermia with abnormal thoracic auscultations. Three of the 4 animals were diagnosed with chronic respiratory disease associated with Maedi-visna (MV) infection confirmed via serologic testing. Diagnostic thoracic imaging identified characteristics consistent with pathological lesions associated with interstitial pneumonia in the 3 MV affected animals; these findings were absent in the animal that tested negative for MV. Key clinical message: Diagnostic imaging may be useful to clinicians looking to obtain further visualization of lung pathologies and as a reliable means of detecting thoracic lesions indicative of interstitial pneumonia on-farm. These results can be used to aid the practitioner in determining appropriate further diagnostic testing and treatment strategies while awaiting confirmatory test results for diagnosis of MV.

Résultats de l'échographie et de la radiographie numérique chez des ovins atteints d'une maladie clinique associée à une infection à lentivirus des petits ruminants. La radiographie numérique et les images échographiques ont été utilisées dans cette série de cas pour évaluer quatre brebis d'un seul troupeau présentant une perte de poids chronique et un retard de croissance. À l'examen, tous les animaux présentaient une tachypnée, une dyspnée, une toux et étaient normothermiques avec des auscultations thoraciques anormales. Trois des quatre animaux ont été diagnostiqués avec une maladie respiratoire chronique associée à une infection Maedi-visna (MV) confirmée via des tests sérologiques. L'imagerie thoracique diagnostique a identifié des caractéristiques compatibles avec des lésions pathologiques associées à une pneumonie interstitielle chez les trois animaux atteints de MV; ces résultats étaient absents chez l'animal qui a été testé négatif pour MV.Message clinique clé :L'imagerie diagnostique peut être utile aux cliniciens qui cherchent à obtenir une visualisation plus poussée des pathologies pulmonaires et comme un moyen fiable de détecter les lésions thoraciques indiquant une pneumonie interstitielle à la ferme. Ces résultats peuvent être utilisés pour aider le praticien à déterminer d'autres tests de diagnostic appropriés et des stratégies de traitement en attendant les résultats des tests de confirmation pour le diagnostic de MV.(Traduit par Dr Serge Messier).

Pharmacokinetic and pharmacodynamic properties of pantoprazole in calves.

Introduction: Development of abomasal ulceration is a large concern, especially within calves; however, there is a paucity of research into the use of gastro protectants in ruminant species. Proton pump inhibitors, such as pantoprazole, are widely used in humans and companion animals. Their efficacy in ruminant species is undetermined. The objectives of this study were to 1) estimate the plasma pharmacokinetic parameters for pantoprazole in neonatal calves after three days of intravenous (IV) or subcutaneous (SC) administration, and 2) measure the effect pantoprazole had on abomasal pH over the treatment period. Methods: Pantoprazole was administered to 6 Holstein-Angus cross bull calves at a dose of 1 mg/kg (IV) or 2 mg/kg (SC), once a day (every 24 h) for three days. Plasma samples were collected over a 72 h period and analyzed via HPLC-UV for determining pantoprazole concentrations. Pharmacokinetic parameters were derived via non-compartmental analysis. Abomasal (n= 8) samples were collected via abomasal cannulas over a 12 h period, per calf per day. Abomasal pH was determined via a bench top pH analyzer. Results: Following Day 1 of IV administration, plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 199.9 mL/kg/h, 1.44 h, and 0.51 L/kg, respectively. On Day 3 of IV administration, the reported values were 192.9 mL/kg/h, 2.52 h, and 1.80 L/kg mL, respectively. Elimination half-life and volume of distribution (V/F) of pantoprazole following SC administration were estimated at 1.81 h and 0.55 L/kg, respectively, on Day 1; and 2.99 h and 2.82 L/kg, respectively, on Day 3. Discussion: The reported values for IV administration were similar to those previously reported in calves. SC administration appears to be well absorbed and tolerated. The sulfone metabolite was detectable for 36 h after the last administration for both routes. Abomasal pH was significantly higher than the pre-pantoprazole pH 4, 6, and 8 h after administration in both the IV and SC groups. Further studies of pantoprazole as a treatment/preventative for abomasal ulcers are warranted.

Surveillance of antimicrobial resistance in veterinary medicine in the United States: Current efforts, challenges, and opportunities.

Antimicrobial resistance (AMR) is a global problem facing human, animal, plant, and environmental health by threatening our ability to effectively treat bacterial infections with antimicrobials. In the United States, robust surveillance efforts exist to collect, analyze, and disseminate AMR data in human health care settings. These tools enable the development of effective infection control methods, the detection of trends, and provide the evidence needed to guide stewardship efforts to reduce the potential for emergence and further spread of AMR. However, in veterinary medicine, there are currently no known equivalent tools. This paper reviews efforts in the United States related to surveillance of AMR in veterinary medicine and discusses the challenges and opportunities of using data from veterinary diagnostic laboratories to build a comprehensive AMR surveillance program that will support stewardship efforts and help control AMR in both humans and animals.

Use of Thoracic Ultrasonography to Improve Disease Detection in Experimental BRD Infection.

Bovine respiratory disease (BRD) is caused by complex interactions between viral and bacterial pathogens, host immune status, and environmental stressors. In both clinical and research settings, current methods for detecting BRD in calves commonly focus on visual indicators such as attitude, nasal discharge, and cough, in addition to vital signs such as rectal temperature and respiration rate. Recently, thoracic ultrasonography (TUS) has become more commonly used in clinical settings, in addition to physical examination to diagnose BRD. To assess the value of performing TUS during experimental BRD infection, 32 calves were challenged with bovine respiratory syncytial virus, to mimic a viral infection, and 30 calves were infected with Mannheimia haemolytica, to mimic a bacterial infection. TUS was performed at regular intervals using a standardized method and scoring system in addition to daily clinical scoring. Although overall correlations between clinical scores and TUS scores were generally weak (maximum R2 = 0.3212), TUS identified calves with abnormal lung pathology that would have otherwise been misclassified on the basis of clinical scoring alone, both on arrival and throughout the studies. In addition, TUS had an increased correlation with gross lung pathology on necropsy (maximum R2 = 0.5903), as compared to clinical scoring (maximum R2 = 0.3352). Our results suggest that TUS can provide additional information on calf health at enrollment and throughout a study and may provide an alternative to terminal studies, due to the high correlation with lung pathology at necropsy.

Meropenem Administered via Intravenous Regional Limb Perfusion for Orthopedic Sepsis in Horses: A Clinical Retrospective Study.

Septic synovitis is a critical orthopedic condition in horses. Early intervention is key, with antibiotic therapy typically initiated prior to culture and susceptibility reports becoming available. The pharmacokinetics of several antibiotics have been studied in horses for use in intravenous regional limb perfusion (IVRLP) for septic synovitis, including the carbapenem antibiotic, meropenem. For a variety of factors, some veterinary clinicians may select IVRLP meropenem as therapy for these cases. Meropenem is a vital antibiotic in human medicine, making veterinary use divisive. However, verifying the efficacy of meropenem contrasted to other IVRLP antibiotics is essential for appropriate antimicrobial stewardship. To investigate this, equine patient medical records at a single veterinary teaching hospital were examined. Cases treated with meropenem or gentamicin via IVRLP for septic synovitis were retrospectively analyzed for demographics, diagnostics, treatments, outcomes, and adverse effects. Twenty-three meropenem and 37 gentamicin treated horses were analyzed; demographic information was similar between groups. In the meropenem group, nine horses received meropenem only; the remainder received another antibiotic initially then changed to meropenem. Structures infected included joints (meropenem = 13, gentamicin = 17), tendon sheaths (meropenem = 5, gentamicin = 8) and navicular bursae (meropenem = 2, gentamicin = 6). Overall survival to discharge was 86% (52/60), with meropenem 91% (21/23) and gentamicin 84% (31/37), with no statistically significant differences noted between meropenem or gentamicin groups for overall survival to discharge or outcome after discharge. Twenty-four of 26 bacterial isolates obtained from culture were reported as sensitive to imipenem, a carbapenem antibiotic similar to meropenem. Reported susceptibility to other antibiotics such as ceftiofur (n = 22/26), ampicillin (n = 18/26), amikacin (n = 15/26), or gentamicin (n = 12/26) was also frequently present. In the population of this study, antimicrobial activity augmented with IVRLP using either meropenem or gentamicin both appear to be an effective treatment for septic synovial structures, therefore, less critical antimicrobials may be a viable and more judicious treatment option.

Preliminary Investigation of Bovine Whole Blood Xenotransfusion as a Therapeutic Modality for the Treatment of Anemia in Goats.

Anemia requiring whole blood transfusion for appropriate treatment is a common clinical presentation of caprine patients to veterinary practitioners; however, identifying suitable blood donors in goat herds can be challenging. In other veterinary species, the practice of xenotransfusion, where blood from 1 species is transfused to another, is used in emergency settings. Due to their ability to donate large volumes of whole blood, cattle could be an ideal source for xenotransfusion of goats. In this study 2 healthy goats were transfused with bovine whole blood. The goats were then monitored for adverse effects and the presence of bovine erythrocyte post-xenotransfusion. Afterward, 15 caprine-bovine combinations were evaluated for compatibility via cross-matching. Both goats tolerated xenotransfusion, although transient reactions were observed. Of the 15 cross-match combinations, 11 of the major cross matches were compatible, and all minor cross matches were also compatible. While future work is necessary to refine this technique, xenotransfusion of goats with cattle blood may be a therapeutic modality for the treatment of caprine anemia.

Pharmacokinetics and Tissue Levels of Pantoprazole in Neonatal Calves After Intravenous Administration.

Background: Neonatal calves are at risk of developing abomasal ulceration, but there is a lack of pharmacokinetic data for potential anti-ulcerative therapies, such as pantoprazole, in ruminant species. Objective: The study objectives were to estimate plasma pharmacokinetic parameters for pantoprazole in neonatal dairy calves after intravenous (IV) administration. A secondary objective was to quantify the concentrations of pantoprazole in edible tissues after IV dosing. Methods: Pantoprazole was administered to 9 neonatal Holstein calves at a dose of 1 mg/kg IV. Plasma samples were collected over 24 h and analyzed via HPLC-MS for determining pantoprazole concentrations. Pharmacokinetic parameters were derived via non-compartmental analysis. Tissue samples were collected at 1, 3, and 5 days after administration and analyzed via HPLC-MS. Results: Following IV administration, plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 4.46 mL/kg/min, 2.81 h, and 0.301 L/kg, respectively. The global extraction ratio was estimated at 0.053 ± 0.015. No pantoprazole was detected in the edible tissues 1, 3, or 5 days after administration. A metabolite, pantoprazole sulfone was detected in all the edible tissues 1 and 3 days after administration. Conclusion: The reported plasma clearance for pantoprazole is less than that reported for alpacas but higher than reported in foals. The elimination half-life in calves appears to be longer than observed in foals and alpacas. While pantoprazole sulfone was detected in the tissues after IV administration, further research is needed as to the metabolism and potential tissue accumulation of other pantoprazole metabolites in calves. Future pharmacodynamic studies are necessary to determine the efficacy of pantoprazole on abomasal acid suppression in calves.

Role of metAB in Methionine Metabolism and Optimal Chicken Colonization in Campylobacter jejuni.

Campylobacter jejuni is a zoonotic pathogen and is one of the leading causes of human gastroenteritis worldwide. C. jejuni IA3902 (representative of the sheep abortion clone) is genetically similar to C. jejuni W7 (representative of strain type NCTC 11168); however, there are significant differences in the ability of luxS mutants of these strains to colonize chickens. LuxS is essential for the activated methyl cycle and generates homocysteine for conversion to l-methionine. Comparative genomics identified differential distribution of the genes metA and metB, which function to convert homoserine for downstream production of l-methionine, between IA3902 and W7, which could enable a secondary pathway for l-methionine biosynthesis in a W7 ΔluxS but not in an IA3902 ΔluxS strain. To test the hypothesis that the genes metA and metB contribute to l-methionine production and chicken colonization by Campylobacter, we constructed two mutants for phenotypic comparison, the W7 ΔmetAB ΔluxS and IA3902 ΔluxS::metAB mutants. Quantitative reverse transcription-PCR and tandem mass spectrometry protein analysis were used to validate MetAB transcription and translation as present in the IA3902 ΔluxS::metAB mutant and absent in the W7 ΔmetAB ΔluxS mutant. Time-resolved fluorescence resonance energy transfer fluorescence assays demonstrated that l-methionine and S-adenosyl methionine concentrations decreased in the W7 ΔmetAB ΔluxS mutant and increased in the IA3902 ΔluxS::metAB mutant. Assessment of chicken colonization revealed that the IA3902 ΔluxS::metAB strain partially rescued the colonization defect of the IA3902 ΔluxS strain, while the W7 ΔmetAB ΔluxS strain showed significantly decreased colonization compared to that of the wild-type and the W7 ΔluxS strain. These results indicate that the ability to maintain l-methionine production in vivo, conferred by metA and metB in the absence of luxS, is critical for normal chicken colonization by C. jejuni.

Clinical presentations and antimicrobial susceptibilities of Corynebacterium cystitidis associated with renal disease in four beef cattle.

BACKGROUND: Renal disease caused by Corynebacterium cystitidis in beef cattle may be misclassified as Corynebacterium renale, and limited information about C. cystitidis infections in beef cattle currently is available. OBJECTIVE: To describe clinical presentation, diagnosis, minimum inhibitory concentrations (MICs), and outcome of renal disease caused by C. cystitidis in beef cattle. METHODS: Retrospective case series. ANIMALS: Four client-owned beef cattle. RESULTS: All affected cattle had anorexia as a primary complaint. Of the 3 that had ante-mortem diagnostic tests performed, all had pyelonephritis based on azotemia in combination with urinalysis and ultrasonographic findings. Cultures yielded C. cystitidis which was identified by biochemical testing, 16S RNA sequencing, and mass spectrometry. All affected cattle deteriorated despite aggressive treatment, indicating that C. cystitidis infections in beef cattle may carry a poor prognosis. Bacterial isolates collected from the 4 cattle showed similarities in MICs for ampicillin, florfenicol, gentamicin, neomycin, sulfadimethoxine, trimethoprim sulfonamide, and tylosin. CONCLUSIONS AND CLINICAL IMPORTANCE: Corynebacterium cystitidis should be considered in the differential diagnosis of cattle with renal disease. Definitive diagnosis of C. cystitidis as compared to C. renale may be challenging.

Small Noncoding RNA CjNC110 Influences Motility, Autoagglutination, AI-2 Localization, Hydrogen Peroxide Sensitivity, and Chicken Colonization in Campylobacter jejuni.

Small noncoding RNAs (ncRNAs) are involved in many important physiological functions in pathogenic microorganisms. Previous studies have identified the presence of noncoding RNAs in the major zoonotic pathogen Campylobacter jejuni; however, few have been functionally characterized to date. CjNC110 is a conserved ncRNA in C. jejuni, located downstream of the luxS gene, which is responsible for the production of the quorum sensing molecule autoinducer-2 (AI-2). In this study, we utilized strand specific high-throughput RNAseq to identify potential targets or interactive partners of CjNC110 in a sheep abortion clone of C. jejuni These data were then utilized to focus further phenotypic evaluation of the role of CjNC110 in motility, autoagglutination, quorum sensing, hydrogen peroxide sensitivity, and chicken colonization in C. jejuni Inactivation of the CjNC110 ncRNA led to a statistically significant decrease in autoagglutination ability as well as increased motility and hydrogen peroxide sensitivity compared to the wild-type. Extracellular AI-2 detection was decreased in ΔCjNC110; however, intracellular AI-2 accumulation was significantly increased, suggesting a key role of CjNC110 in modulating the transport of AI-2. Notably, ΔCjNC110 also showed a decreased ability to colonize chickens. Complementation of CjNC110 restored all phenotypic changes back to wild-type levels. The collective results of the phenotypic and transcriptomic changes observed in our data provide valuable insights into the pathobiology of C. jejuni sheep abortion clone and strongly suggest that CjNC110 plays an important role in the regulation of energy taxis, flagellar glycosylation, cellular communication via quorum sensing, oxidative stress tolerance, and chicken colonization in this important zoonotic pathogen.