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Chronic rhinitis (CR) is a frustrating clinical syndrome in dogs and our understanding of the disease pathogenesis in is limited. Increasingly, host-microbe interactions are considered key drives of clinical disease in sites of persistent mucosal inflammation such as the nasal and oral cavities. Therefore, we applied next generation sequencing tools to interrogate abnormalities present in the nose of dogs with CR and compared immune and microbiome profiles to those of healthy dogs. Host nasal cell transcriptomes were evaluated by RNA sequencing, while microbial communities were assessed by 16S rRNA sequencing. Correlation analysis was then used to identify significant interactions between nasal cell transcriptomes and the nasal microbiome and how these interactions were altered in animals with CR. Notably, we observed significant downregulation of multiple genes associated with ciliary function in dogs with CR, suggesting a previously undetected role for ciliary dysfunction in this syndrome. We also found significant upregulation of immune genes related to the TNF-α and interferon pathways. The nasal microbiome was also significantly altered in CR dogs, with overrepresentation of several potential pathobionts. Interactome analysis revealed significant correlations between bacteria in the genus Porphyromonas and the upregulated host inflammatory responses in dogs with CR, as well as defective ciliary function which was correlated with Streptococcus abundance. These findings provide new insights into host-microbe interactions in a canine model of CR and indicate the presence of potentially causal relationships between nasal pathobionts and the development of nasal inflammation and ciliary dysfunction.
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Treatment of Mycoplasma spp. pneumonia has rarely been described in domestic ferrets (Mustela putorius furo). A 10-month-old, 0.53 kg, female spayed domestic ferret was presented for oxygen-dependent, chronic dyspnea of one-month's duration. Physical examination findings included dyspnea, tachypnea, increased bronchovesicular sounds bilaterally, and an intermittent non-productive cough. Bloodwork abnormalities included a mild leukocytosis (8.6×103/µL), mild neutrophilia (4.0×103/µL), mild hypoalbuminemia (2.7 g/dL), mild hyperglobulinemia (3.3 g/dL), mild hyponatremia (147 mEq/L), and mild hypochloremia (111.4 mEq/L). Radiographs revealed a marked diffuse bronchial pattern with peribronchial cuffing, a mild main pulmonary artery bulge, distended caudal lobar pulmonary arteries, and decreased serosal detail within the abdomen. An echocardiogram revealed indications of moderate pulmonary hypertension and systolic anterior motion of the mitral valve. Polymerase chain reaction testing for Mycoplasma spp. was positive, and treatment was initiated with doxycycline (10 mg/kg PO q 12 h for 16 weeks), prednisolone (0.4 mg/kg PO q 12 h for 13 weeks, tapered to 0.2 mg/kg PO q 12 h for two weeks, then eventually increased to 0.7 mg/kg PO q 12 h until further notice), sildenafil (0.3 mg/kg PO q 24 h for 13 weeks), and oxygen supplementation via an oxygen cage for six weeks. On repeat echocardiogram eleven weeks after initiation of doxycycline therapy, the pulmonary hypertension had resolved. At follow up six months later, the ferret was stable on previously prescribed medications and did not require oxygen supplementation. Mycoplasma spp. and pulmonary hypertension should be considered in cases of respiratory distress in ferrets.
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Antibacterianos , Hurones , Hipertensión Pulmonar , Animales , Femenino , Hipertensión Pulmonar/veterinaria , Antibacterianos/uso terapéutico , Neumonía por Mycoplasma/veterinaria , Neumonía por Mycoplasma/tratamiento farmacológico , Neumonía por Mycoplasma/diagnóstico , Doxiciclina/uso terapéutico , Prednisolona/uso terapéutico , Citrato de Sildenafil/uso terapéuticoRESUMEN
Chronic inflammatory enteropathy (CIE) is a common condition in dogs causing recurrent or persistent gastrointestinal clinical signs. Pathogenesis is thought to involve intestinal mucosal inflammatory infiltrates, but histopathological evaluation of intestinal biopsies from dogs with CIE fails to guide treatment, inform prognosis, or correlate with clinical remission. We employed single-cell RNA sequencing to catalog and compare the diversity of cells present in duodenal mucosal endoscopic biopsies from 3 healthy dogs and 4 dogs with CIE. Through characterization of 35,668 cells, we identified 31 transcriptomically distinct cell populations, including T cells, epithelial cells, and myeloid cells. Both healthy and CIE samples contributed to each cell population. T cells were broadly subdivided into GZMAhigh (putatively annotated as tissue resident) and IL7Rhigh (putatively annotated as non-resident) T cell categories, with evidence of a skewed proportion favoring an increase in the relative proportion of IL7Rhigh T cells in CIE dogs. Among the myeloid cells, neutrophils from CIE samples exhibited inflammatory (SOD2 and IL1A) gene expression signatures. Numerous differentially expressed genes were identified in epithelial cells, with gene set enrichment analysis suggesting enterocytes from CIE dogs may be undergoing stress responses and have altered metabolic properties. Overall, this work reveals the previously unappreciated cellular heterogeneity in canine duodenal mucosa and provides new insights into molecular mechanisms which may contribute to intestinal dysfunction in CIE. The cell type gene signatures developed through this study may also be used to better understand the subtleties of canine intestinal physiology in health and disease.
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Enfermedades de los Perros , Duodeno , Perfilación de la Expresión Génica , Análisis de la Célula Individual , Transcriptoma , Animales , Perros , Duodeno/patología , Duodeno/inmunología , Duodeno/metabolismo , Enfermedades de los Perros/genética , Enfermedades de los Perros/inmunología , Enfermedades de los Perros/patología , Mucosa Intestinal/inmunología , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Enfermedad Crónica , Masculino , Femenino , Linfocitos T/inmunología , Linfocitos T/metabolismoRESUMEN
Bile acids (BA) are important metabolites secreted into the intestinal lumen and impacted by luminal microbes and dietary intake. Prior studies in humans and rodents have shown that BAs are immunologically active and that primary and secondary BAs have distinct immune properties. Therefore, the composition of the gut BA pool may influence GI inflammatory responses. The current study investigated the relative immune modulatory properties of primary (cholic acid, CA) and secondary BAs (lithocholic acid, LCA) by assessing their effects on canine macrophage cytokine secretion and BA receptor (TGR5) expression. In addition, RNA sequencing was used to further interrogate how CA and LCA differentially modulated macrophage responses to LPS (lipopolysaccharide). We found that exposure to either CA or LCA influenced LPS-induced cytokine production via macrophages similarly, with suppression of TNF-α secretion and enhancement of IL-10 secretion. Neither BA altered the expression of the BA receptor TGR5. Transcriptomic analysis revealed that CA activated inflammatory signaling pathways in macrophages involving type II interferon signaling and the aryl hydrocarbon receptor, whereas LCA activated pathways related to nitric oxide signaling and cell cycle regulation. Thus, we concluded that both primary and secondary BAs are active modulators of macrophage responses in dogs, with differential and shared effects evident with sequencing analysis.
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Extraskeletal osteosarcoma (EOSA) in dogs is a rare malignant mesenchymal tumor of somatic soft tissues or more commonly visceral organs with a poor prognosis. In dogs, EOSAs have been described as arising from multiple locations, but differently from humans, never from a main vessel. In this report, we describe the first case of an EOSA arising from the post-hepatic caudal vena cava in a 7-year-old male neutered mix breed dog. This report focuses on the description of the diagnostic challenges to obtain a preoperative diagnosis, highlights the importance of histopathology for a correct diagnosis, and introduces a new differential diagnosis for an animal presenting with a suspected thrombus of the vena cava.
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BACKGROUND: Diet may induce clinical remission in dogs with chronic enteropathy (CE). Elemental diets (EDs), providing protein as amino acids, modulate intestinal immunity and microbiome in rodents and humans. HYPOTHESIS: Evaluate the impact of an amino acid-based kibble (EL) on CE clinical activity and gastrointestinal (GI)-relevant variables. ANIMALS: Client-owned dogs (n = 23) with inadequately controlled CE. METHODS: Prospective, uncontrolled clinical trial. Diagnostic evaluation including upper and lower GI endoscopy was performed before study entry. Canine chronic enteropathy clinical activity index (CCECAI), serum biomarkers, and fecal microbiome were evaluated before and after 2 weeks of EL. Dogs with stable or improved CE remained in the study for another 6 weeks. Pre- and post-EL clinical and microbiological variables were compared statistically using a mixed model. RESULTS: After 2 weeks of EL, 15 of 22 dogs (68%; 95% confidence interval [CI], 47%-84%) consuming the diet were classified as responders with a median (range) decrease in CCECAI from 6 (3-12) to 2 (0-9; P < .001). Fourteen of 15 responders and 2/7 nonresponders at 2 weeks completed the trial; all 16 were experiencing adequate control at week 8 with a median CCECAI of 2 (0-3). In total, 16/23 dogs (70%; 95% CI, 49%-84%) were responders. Feeding EL caused shifts in fecal bacterial communities, which differed between responders and nonresponders. Serum biomarker concentrations were unchanged throughout the study apart from serum alkaline phosphatase activity. CONCLUSIONS: Exclusive feeding of EL improved clinical signs in 16 of 23 dogs with uncontrolled CE. Fecal microbiome shifts were associated with response to diet and may represent a mechanism for clinical improvement.
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Enfermedades de los Perros , Enfermedades Inflamatorias del Intestino , Animales , Perros , Biomarcadores , Dieta/veterinaria , Enfermedades de los Perros/diagnóstico , Alimentos Formulados , Enfermedades Inflamatorias del Intestino/veterinaria , Estudios ProspectivosRESUMEN
OBJECTIVES: A diagnosis of congenital heart disease (CHD) during fetal life or infancy can be devastating for parents, resulting in significant psychological stressors. The goals of this study were to (1) assess maternal resolution and adaptation to a new diagnosis of CHD, (2) explore how maternal resolution and adaptation relates to psychological well-being and (3) evaluate whether specific illness parameters impact resolution status. METHODS: This cross-sectional study evaluated resolution to diagnosis in the first 6 months of life for mothers of children with CHD. Mothers completed a Reaction to Diagnosis Interview (RDI) and psychological surveys assessing stress, depression, and coping skills. The RDI invites parents to discuss the diagnosis, changes in their thoughts and feelings since the diagnosis, and reflections on why they think they have a child with a medical condition. A chart review of the child recording illness parameters was also performed. RESULTS: Thirty-six mothers participated in this study. Twelve of their children had a prenatal diagnosis of CHD (33.3%). Seventeen mothers (47.2%) were unresolved to the diagnosis of CHD in their child, regardless of the timing or severity of the diagnosis. Twenty-four participants (68.6%) had significant or highly significant life stress and 9 participants (25.7%) had clinical concerns or met criteria for Post-Traumatic Stress Disorder. Nineteen mothers (55.9%) were at risk for clinical depression. Mothers unresolved to the diagnosis had higher rates of post-traumatic stress than those resolved to the diagnosis (47.1% vs. 10.5%, p = 0.03). Mothers of infants with a prenatal diagnosis of CHD reported significantly lower rates of life stress despite higher severity of heart defects (p = 0.02). CONCLUSIONS FOR PRACTICE: Mothers of infants with CHD have similar proportions of resolution to diagnosis compared to mothers of children with other chronic diseases. They experience a high rate of symptoms of life stress, post-traumatic stress and clinical depression. Symptoms of post-traumatic stress are higher in mothers unresolved to the diagnosis. Identification of those at highest risk for poor adaptation to the diagnosis may allow for targeted psychological support services for those most vulnerable.
A diagnosis of congenital heart disease can result in significant parental stress and negatively impact parental and child bonding. Our study demonstrates that parents of infants with cardiac disease experience high rates of life stress, post-traumatic stress and clinical depression. Mothers unresolved to the diagnosis have higher rates of post-traumatic stress. Those who received a prenatal diagnosis had lower life stress despite greater disease severity. Identification of mothers at highest risk for poor adaptation to the diagnosis may allow for targeted psychological support services for those most vulnerable.
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Adaptación Psicológica , Cardiopatías Congénitas , Niño , Lactante , Femenino , Embarazo , Humanos , Estudios Transversales , Cardiopatías Congénitas/diagnóstico , Madres/psicología , Padres/psicología , Estrés Psicológico/diagnóstico , Estrés Psicológico/psicologíaRESUMEN
BACKGROUND: Eradication of intramucosal Escherichia coli correlates with remission of periodic acid-Schiff-positive E coli-associated granulomatous colitis (GC). Treatment failures attributed to multidrug resistant (MDR) bacteria necessitate alternative approaches. HYPOTHESIS/OBJECTIVES: Determine clinical outcome of E coli-associated GC in dogs treated based on antimicrobial susceptibility profiling and characterize E coli phylogeny and resistance mechanisms. ANIMALS: Twenty Boxers and 4 French Bulldogs with E coli-associated GC. METHODS: Culture, antimicrobial susceptibility profiling, and molecular characterization of E coli were performed and response to treatment was evaluated. RESULTS: Initial biopsy sample culture yielded fluoroquinolone-sensitive (FQ-S) E coli from 9/24 dogs and fluoroquinolone-resistant (FQ-R) E coli from 15/24. All but 1 FQ-R E coli were MDR with susceptibility to macrophage-penetrating antimicrobials restricted to carbapenems in 13/15 dogs. Of 22/24 treated based on susceptibility profiling, 8/9 FQ-S dogs had complete initial clinical response (CR) during fluoroquinolone (FQ) treatment, whereas 9/13 FQ-R dogs had complete or partial response (PR) during meropenem or doxycycline treatment. In 5/9 FQ-S and 12/13 FQ-R dogs with follow-up ≥3 months, CR was sustained in 5/5 FQ-S (median, 25 months; range, 4-46) whereas 6/12 FQ-R had long-term CR (median, 59 months; range 15-102), 4/12 PR (median, 19 months; range, 5-65), and 2/12 had no response (NR). Four dogs with long-term follow-up died within 4 years of diagnosis, including 2 euthanized for refractory colitis. Escherichia coli were genetically diverse. Fluoroquinolone resistance was associated with mutations in gyrA and parC, with plasmid-mediated resistance less common. CONCLUSIONS AND CLINICAL IMPORTANCE: Antimicrobial treatment guided by susceptibility profiling was associated with positive long-term outcomes in >80% of cases. Fluoroquinolone-resistance was widespread and not clonal. Further study is required to optimize treatment for dogs with MDR E coli-associated GC.
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Enfermedad de Crohn , Enfermedades de los Perros , Infecciones por Escherichia coli , Animales , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Enfermedad de Crohn/tratamiento farmacológico , Enfermedad de Crohn/veterinaria , Enfermedades de los Perros/tratamiento farmacológico , Perros , Farmacorresistencia Bacteriana , Farmacorresistencia Bacteriana Múltiple , Escherichia coli , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/veterinaria , Fluoroquinolonas/uso terapéutico , Pruebas de Sensibilidad Microbiana/veterinariaRESUMEN
BACKGROUND: Tylosin is commonly prescribed to dogs with diarrhea. Orally administered antibiotics may alter the intestinal microbiota, which is responsible for crucial key bile acid (BA) biotransformation reactions. OBJECTIVES: To prospectively evaluate the impact of tylosin administration on fecal microbiota and unconjugated bile acids (UBAs) over time. ANIMALS: Sixteen healthy adult dogs. METHODS: Prospective, randomized controlled clinical trial. Dogs were randomized to receive 20 mg/kg of tylosin or a placebo capsule PO q12h for 7 days while undergoing daily fecal scoring. Fecal samples were collected on days 0, 7, 21, and 63. The microbiota was assessed using quantitative PCR and 16S rRNA gene sequencing. Unconjugated BAs were assessed using gas chromatography-mass spectrometry (GC-MS). RESULTS: Fecal scores were unchanged during placebo and tylosin administration. In the placebo group, no significant changes were observed in fecal microbiota or UBA concentrations. Day 7 samples from tylosin-exposed dogs exhibited decreased bacterial diversity (observed species, Chao1, Shannon, P < .001) characterized by decreases in anaerobes Fusobacteriaceae (linear discriminant analysis [LDA] score, 5.03) and Veillonellaceae (LDA score, 4.85). Primary UBA concentrations were increased at day 21 (median, [range]; 7.42, [0.67-18.77] µg/kg; P = .04) and day 63 (3.49 [0-28.43] µg/kg; P = .02) compared to day 0 (.14 [.03-1.19] µg/kg) in dogs receiving tylosin. At day 63, bacterial taxa were not significantly different compared to day 0, but the extent of microbial recovery was individualized. CONCLUSIONS AND CLINICAL IMPORTANCE: Tylosin causes fecal dysbiosis in healthy dogs with corresponding shifts in fecal UBAs. Changes did not uniformly resolve after discontinuation of tylosin.
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Ácidos y Sales Biliares/química , Perros/microbiología , Heces/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Tilosina/farmacología , Administración Oral , Animales , Antibacterianos/farmacología , Femenino , MasculinoRESUMEN
OBJECTIVE: To describe acute respiratory distress syndrome (ARDS) and septic shock in a cat with disseminated toxoplasmosis. CASE SUMMARY: A 2-year-old neutered male domestic shorthair cat was presented for acute respiratory distress. At the time of presentation it had been receiving cyclosporine for treatment of eosinophilic dermatitis. Thoracic radiographs revealed severe mixed nodular interstitial and alveolar patterns. An endotracheal wash was performed, which confirmed a diagnosis of pulmonary toxoplasmosis. Despite initial treatment with oxygen supplementation and intravenous clindamycin, the cat developed refractory hypoxemia and hypotension requiring mechanical ventilation and vasopressor support within 24 hours of hospital admission. Cardiac arrest occurred 56 hours after admission. Necropsy was performed and histopathology revealed protozoal organisms disseminated throughout the heart, lungs, liver, and brain. NEW OR UNIQUE INFORMATION PROVIDED: The clinical and necropsy findings presented here are consistent with ARDS secondary to disseminated toxoplasmosis in a cat. This is the first detailed report of ARDS in a cat. Toxoplasma titer testing and antimicrobial prophylaxis should be considered in cats prior to immunosuppressive treatment with cyclosporine.
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Enfermedades de los Gatos/parasitología , Enfermedades Pulmonares Parasitarias/veterinaria , Síndrome de Dificultad Respiratoria/veterinaria , Choque Séptico/veterinaria , Toxoplasmosis Animal/complicaciones , Animales , Antibacterianos/uso terapéutico , Enfermedades de los Gatos/etiología , Enfermedades de los Gatos/patología , Enfermedades de los Gatos/terapia , Gatos , Clindamicina/uso terapéutico , Ciclosporina/efectos adversos , Resultado Fatal , Huésped Inmunocomprometido , Inmunosupresores/efectos adversos , Enfermedades Pulmonares Parasitarias/complicaciones , Enfermedades Pulmonares Parasitarias/patología , Masculino , Oxígeno/uso terapéutico , Síndrome de Dificultad Respiratoria/etiología , Choque Séptico/etiología , Choque Séptico/terapia , Toxoplasmosis Animal/patologíaRESUMEN
OBJECTIVES: To evaluate the veterinary student learning outcome of 2 methods of equine rectal examination training. STUDY DESIGN: Randomized prospective study. SAMPLE POPULATION: Veterinary students (3rd and 4th year; n = 40) and practicing equine veterinarians (n = 10). METHODS: Year 1: Group 1 (n = 11) and Group 2 students (n = 10) received skilled instructor (SI) and laparoscopic-guidance (LG), respectively, during rectal exam instruction. All students were tested on rectal identification of 4 abdominal organs. Year 2: One group of students (n = 19) was trained and subsequently tested using each technique, first SI, followed by LG. Subjective evaluation of laparoscopy as a teaching tool was achieved with veterinary students and equine practitioners. RESULTS: A significantly greater percentage of students having LG compared to SI were able to correctly identify the left kidney (Year 1) and the spleen, cecum, and right ovary (Year 2). A significantly greater proportion of LG trained students in years 1 and 2 (100% and 95%, respectively) were also able to identify 75% of organs compared with SI (27% and 21%, respectively). Both students and veterinarians uniformly provided favorable feedback for LG in teaching rectal palpation skills. CONCLUSION: The LG method of equine rectal examination instruction resulted in improved learning for identification of several key abdominal organs compared with SI.