Frogs adapt to physiologically costly anthropogenic noise.

Human activities impose novel pressures on amphibians, which are experiencing unprecedented global declines, yet population-level responses are poorly understood. A growing body of literature has revealed that noise is an anthropogenic stressor that impacts ecological processes spanning subcellular to ecosystem levels. These consequences can impose novel selective pressures on populations, yet whether populations can adapt to noise is unknown. We tested for adaptation to traffic noise, a widespread sensory 'pollutant'. We collected eggs of wood frogs (Rana sylvatica) from populations from different traffic noise regimes, reared hatchlings under the same conditions, and tested frogs for differences in sublethal fitness-relevant effects of noise. We show that prolonged noise impaired production of antimicrobial peptides associated with defence against disease. Additionally, noise and origin site interacted to impact immune and stress responses. Noise exposure altered leucocyte production and increased baseline levels of the stress-relevant glucocorticoid, corticosterone, in frogs from quiet sites, but noise-legacy populations were unaffected. These results suggest noise-legacy populations have adapted to avoid fitness-relevant physiological costs of traffic noise. These findings advance our understanding of the consequences of novel soundscapes and reveal a pathway by which anthropogenic disturbance can enable adaptation to novel environments.

Evaluation of the neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios in critically ill dogs.

OBJECTIVE: To evaluate whether the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are accurate prognostic indicators and correlate with illness severity scores in critically ill dogs. DESIGN: Prospective observational study from December 2016 to May 2017. SETTING: ICU at a veterinary teaching hospital. ANIMALS: Seventy-two client-owned dogs admitted to the ICU with CBCs and abbreviated and complete acute patient physiologic and laboratory evaluation (APPLEfast and APPLEfull ) scores were enrolled. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The NLR, PLR, APPLEfast , and APPLEfull scores were calculated for each patient on the day of admission. Patients were followed from admission to discharge, and diagnosis, survival, and length of hospitalization were recorded. The patient population was assessed as a whole and as subcategories of patients with neoplastic disease, infectious disease, sepsis, and severe hemorrhage. Dogs with nonseptic disease processes (n = 52) that died had a significantly higher median PLR (P = 0.04) of 441 (range: 106-986) compared to those that survived with a median PLR of 217 (range: 28.4-3225). The PLR was strongly predictive of ICU length of stay in dogs with severe hemorrhage (P = 0.03, Spearman's rho = 0.84). The NLR had a poor positive correlation with APPLEfull score (P = 0.04, Spearman's rho = 0.24), and PLR had a poor negative correlation with APPLEfast score (P = 0.02, Spearman's rho = -0.27). CONCLUSIONS: The PLR correlated with ICU length of stay for patients with severe hemorrhage and with survival for patients with nonseptic disease processes. The PLR and NLR correlated with illness severity as measured by APPLE scores. Future studies with larger sample sizes are warranted to further determine the merit of NLR and PLR as indicators of morbidity, mortality, and illness severity.

Calculation of dose intensity and comparison of published methods using a cohort of canine T-cell lymphoma patients undergoing CHOP-based chemotherapy.

Methods of calculating and reporting dose intensity (DI) of CHOP-based protocols in the veterinary literature vary. The goal of this retrospective study is to examine the prognostic significance of the average percentage of planned DI received in a cohort of canine T-cell lymphoma patients treated with a modified CHOP protocol with corresponding toxicity and efficacy data. Our data set of 40 dogs was analysed using various previously published methods for calculating DI. Median progression-free survival and overall survival were 91 and 196 days, respectively. Receiving a higher percentage of planned DI was not found to be associated with patient outcome. Outcomes remain poor for dogs with T-cell lymphoma treated with CHOP-based chemotherapy irrespective of received DI. Standard methods of DI calculation and reporting should be adopted in veterinary oncology to enable repeatable and rigorous comparisons of published chemotherapy protocols and to ascertain the potential prognostic relevance of DI in canine lymphoma patients.

Evaluation of mechlorethamine, vinblastine, procarbazine, and prednisone for the treatment of resistant multicentric canine lymphoma.

Multi-agent chemotherapy successfully induces remission in most naïve, high-grade canine lymphoma patients; however, disease recurrence is common. MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) is an effective rescue protocol used to re-induce remission, but is associated with gastrointestinal toxicity and can be a less desirable option for patients that previously failed vincristine-containing protocols. Therefore, alternative members of the vinca alkaloid family, such as vinblastine, could be potentially advantageous as substitutes for vincristine to reduce gastrointestinal toxicity and chemoresistance. The objective of this study was to report the clinical outcomes and toxicity of 36 dogs with relapsed or refractory multicentric lymphoma treated with a modified MOPP protocol whereby vincristine was replaced with vinblastine (MVPP). The overall response rate to MVPP was 25% with a median progression free survival of 15 days and a median overall survival of 45 days. MVPP at the prescribed doses resulted in modest and transient clinical benefit, but was well tolerated with no treatment delays or hospitalizations secondary to side effects. Given the minimal toxicity, dose intensification could be considered to improve clinical responses.

Feline eosinophilic sclerosing fibroplasia - a characteristic inflammatory response in sites beyond the gastrointestinal tract: case report and proposed nomenclature.

Case summary: An adult male neutered Russian Blue cat presented for a right-sided nasal mass with bilateral retropharyngeal and right mandibular lymphadenomegaly. Medial retropharyngeal lymph node excision with nasal mass biopsy revealed eosinophilic sclerosing lymphadenitis and eosinophilic and lymphoplasmacytic rhinitis, respectively. Bacterial culture of the lymph node grew Pseudomonas aeruginosa, and treatment with pradofloxacin was started. Despite initial improvement, clinical signs recurred after 9 months, and fine-needle aspirates of the right mandibular and left medial retropharyngeal lymph nodes showed eosinophilic and mastocytic infiltration. Bacterial culture of the left medial retropharyngeal lymph node grew P aeruginosa, and treatment with anti-inflammatory doses of prednisolone and, later, marbofloxacin was instituted. Relevance and novel information: This report describes a case of feline eosinophilic sclerosing lymphadenitis diagnosed outside of the abdominal cavity and is the first case reported to be associated with P aeruginosa. Feline eosinophilic sclerosing lymphadenitis should be considered as a differential for lymphadenopathy occurring in areas other than the abdominal cavity. Feline eosinophilic sclerosing lymphadenitis may develop in cats due to a species-specific inflammatory response to chronic bacterial and fungal infections.

An EHPB1L1 Nonsense Mutation Associated with Congenital Dyserythropoietic Anemia and Polymyopathy in Labrador Retriever Littermates.

In this report, we describe a novel genetic basis for congenital dyserythropoietic anemia and polymyopathy in Labrador Retriever littermates characterized by incidental detection of marked microcytosis, inappropriate metarubricytosis, pelvic limb weakness and muscle atrophy. A similar syndrome has been described in English Springer Spaniel littermates with an early onset of anemia, megaesophagus, generalized muscle atrophy and cardiomyopathy. Muscle histopathology in both breeds showed distinctive pathological changes consistent with congenital polymyopathy. Using whole genome sequencing and mapping to the CanFam4 (Canis lupus familiaris reference assembly 4), a nonsense variant in the EHBP1L1 gene was identified in a homozygous form in the Labrador Retriever littermates. The mutation produces a premature stop codon that deletes approximately 90% of the protein. This variant was not present in the English Springer Spaniels. Currently, EHPB1L1 is described as critical to actin cytoskeletal organization and apical-directed transport in polarized epithelial cells, and through connections with Rab8 and a BIN1-dynamin complex generates membrane vesicles in the endocytic recycling compartment. Furthermore, EHBP1L1 knockout mice die early and develop severe anemia. The connection of EHBP1L1 to BIN1 and DMN2 functions is particularly interesting due to BIN1 and DMN2 mutations being causative in forms of centronuclear myopathy. This report, along with an independent study conducted by another group, are the first reports of an association of EHBP1L1 mutations with congenital dyserythropoietic anemia and polymyopathy.

Congenital dyserythropoiesis and polymyopathy without cardiac disease in male Labrador retriever littermates.

BACKGROUND: Two Labrador retriever littermates were identified based on incidentally noted marked microcytosis and inappropriate metarubricytosis. Muscle atrophy was noted and associated with distinctive pathological findings in biopsy samples from 1 dog studied. The disorder represents a rare clinical entity of suspected congenital dyserythropoiesis and polymyopathy. Clinicopathologic changes were similar to a previously reported syndrome of congenital dyserythropoiesis, congenital polymyopathy, and cardiac disease in 3 related English Springer Spaniel (ESS) dogs, but the dogs reported here did not have apparent cardiac disease. INTERVENTIONS: Bone marrow aspiration, electromyography, muscle biopsies, and an echocardiogram were performed on dog 1. Results supported dyserythropoiesis and congenital polymyopathy similar to reports in ESS dogs, but did not identify obvious cardiac disease. CONCLUSION: The clinicopathologic changes of dyserythropoiesis and polymyopathy provide an easily recognizable phenotype for what appears to be a low morbidity syndrome. Early recognition may decrease unnecessary testing or euthanasia.

Response-based modification of CHOP chemotherapy for canine B-cell lymphoma.

Despite high initial response rates, a subset of dogs with B-cell lymphoma responds less robustly to CHOP-based chemotherapy and experiences shorter survival. One hundred and four dogs with nodal B-cell lymphoma were treated with a response-based CHOP (RBCHOP) protocol modified based on response to individual drugs during the first chemotherapy cycle. Dogs achieving complete (CR) or partial response (PR) at week 3, following treatment with vincristine and cyclophosphamide, received RBCHOP 1 (n = 72), a protocol sequentially rotating vincristine, cyclophosphamide, and doxorubicin. Dogs without a detectable response at week 3 that subsequently achieved CR or PR following treatment with doxorubicin received RBCHOP 2 (n = 14), in which four doses of doxorubicin were given consecutively followed by vincristine and cyclophosphamide. Dogs that failed to respond at week 3 and then to doxorubicin at week 5 assessment were offered rescue chemotherapy (RBCHOP 3, n = 18). Median progression free survival (PFS) and overall survival time (OST) were similar between RBCHOP 1 (PFS 210 days, OST 354 days) and RBCHOP 2 (PFS 220 days, OST 456 days), but significantly shorter for RBCHOP 3 (PFS 34 days, OST 80.5 days, P < 0.001). No presenting signalment nor hematologic variable differentiated patient cohort, however, dogs in RBCHOP 2 and RBCHOP 3 were more likely to have a lymphocytosis at diagnosis (P = 0.02 and 0.04, respectively). Protocol modification based on response during the first cycle resulted in similar toxicity profiles and outcomes to previously published variants of CHOP, and prognosis remained poor for dogs failing to respond during the first treatment cycle.