Minimally traumatic extraction of fractured bilateral maxillary canine teeth using a piezoelectric surgical unit in an African lion (Panthera leo).

IMPORTANCE: Canine extraction of large carnivores can pose significant risk due to extensive tissue damage during aggressive bone reduction. This report highlights a rare instance in which the use of a piezoelectric surgical unit (PSU) for maxillary canine extraction in a large carnivore resulted in successful outcomes with minimal tissue damage. CASE PRESENTATION: A 10-year-old male African lion presented with decreased appetite because of bilateral maxillary canine fractures. Intraoral radiographs revealed enlarged root canals and periapical radiolucency of the fractured canines, leading to a diagnosis of periapical periodontitis and pulpitis. To extract the right maxillary canine, conventional method using hand instrument failed to achieve adequate luxation, necessitating the use of the flat blade of the PSU to sever the periodontal ligament. The left maxillary canine was extracted using PSU from the beginning, and the extraction time was markedly shortened by using PSU without additional alveolar bone damage or bleeding. CONCLUSION AND RELEVANCE: This case demonstrated that utilizing PSU for canine extraction in a lion resulted in periodontal ligament separation, reducing damage to the alveolar bone and shortening surgical time. It suggests the promising application of PSU in tooth extraction for large wild animals, indicating its potential significance in veterinary dentistry.

Immunogenicity and Cross-Protection Efficacy of a Genotype F-Derived Attenuated Virus Vaccine Candidate against Mumps Virus in Mice.

Mumps virus (MuV) causes an acute contagious human disease characterized by swelling of the parotid glands. Despite the near elimination of mumps in many countries, the disease has recurred, even in vaccinated populations, especially adolescents. Immunization effectivity of the genotype A vaccine strain Jeryl Lynn (JL) is declining as genotype A is no longer predominant; therefore, a new vaccine strain and booster vaccine are required. We generated a cell culture-adapted MuV genotype F called F30 and evaluated its immunogenicity and cross-protective activity against diverse genotypes. F30 genome nucleotide sequence determination revealed changes in the NP, L, SH, and HN genes, leading to five amino acid changes compared to a minimally passaged stock (F10). F30 showed delayed growth, smaller plaque size in Vero cells, and lower neurotoxicity in neonatal mice than F10. Furthermore, F30 was immunogenic to other genotypes, including the JL vaccine strain, with higher efficacy than that of JL for homologous and heterologous immunization. Further, F30 exhibited cross-protective immunity against MuV genotypes F and G in Ifnar-/- mice after a third immunization with F30 following two doses of JL. Our data suggest that the live-attenuated virus F30 could be an effective booster vaccine to control breakthrough infections and mumps epidemics.

A comparative analysis of canine pancreatic lipase tests for diagnosing pancreatitis in dogs.

IMPORTANCE: Early diagnosis of canine pancreatitis is challenging due to non-specific clinical signs. Currently, abdominal ultrasonography and measurement of canine pancreatic lipase (cPL) have been employed for the diagnosis of pancreatitis. OBJECTIVE: Many qualitative and quantitative commercial cPL tests have been developed and used in veterinary clinics. This study aimed to compare three different methodologies SNAP cPL, Spec cPL, and Vcheck cPL tests to assess the concordance of these assays. METHODS: Fifty serum samples were collected from 36 dogs with or without pancreatitis and subjected to SNAP cPL, Spec cPL, and Vcheck cPL tests. Agreement and correlation coefficients were calculated between the test results, and correlations were determined during the management of the patients. RESULTS: The results of the three cPL assays were strongly correlated in 47/50 serum samples (94%). Cohen's kappa analysis between the Spec cPL and Vcheck cPL showed near perfect agreement (κ = 0.960, p < 0.001), SNAP cPL and Vcheck cPL (κ = 0.920, p < 0.001), and Spec cPL and SNAP cPL (κ = 0.880, p < 0.001). The correlation coefficients (r) between data from Spec cPL and Vcheck cPL tests was calculated by Spearman's correlation test (r = 0.958, p < 0.001). Furthermore, the patterns of change in serum cPL concentrations determined using Spec cPL and Vcheck cPL were significantly consistent during the monitoring period in 11 patients. CONCLUSIONS AND RELEVANCE: Our data illustrated that Spec cPL and Vcheck cPL tests are compatible for clinical use in the diagnosis and monitoring of canine pancreatitis.

Selective Binding of Tannic Acid-Conjugated Lipid Nanovesicles to Proline-Rich Proteins Enhances Transdermal Lipophilic-Antioxidant Delivery.

Tannic acid (TA) possesses a notable ability to adhere to proline-rich proteins that make up skin cells and the extracellular matrix (ECM) in the skin tissue. Drug carriers with this specific adhesion ability exhibit improved drug delivery efficiency on the skin. Taking advantage of this, this study presents skin-adhesive TA-conjugated lipid nanovesicles (TANVs) for enhanced transdermal antioxidant delivery. We found that TANVs exhibited selective intermolecular interactions with keratinocyte proline-rich proteins (KPRPs) and collagen that makes up skin cells by hydrogen bonding and van der Waals interactions, further enabling the strong bonding to macroscopic skin itself and ECM. We used vitamin E (α-tocopherol), which is known to effectively reduce oxidative stress but has limited skin penetration, as a drug to verify improved in vitro delivery and therapeutic efficacy. The evaluation revealed that the antioxidant-loaded TANVs exerted excellent scavenging effects against reactive oxygen species induced by ultraviolet light or peroxides in the skin, thereby enabling the development of an active drug delivery system for dermal therapy.

Evaluation of Non-invasive Fat Reduction Using a Resistive Electric Transfer-based Radiofrequency Device With Multi-channel Handpieces.

BACKGROUND/AIM: Various devices for non-invasive body shape correction are being developed along with the growth of the beauty industry. Radiofrequency (RF) can selectively reduce subcutaneous fat without causing skin damage. The efficacy of the procedure can be improved by applying RF to a large area simultaneously with multiple handpieces. This study evaluated the safety and efficacy of a new RF device with multi-channel handpieces. MATERIALS AND METHODS: In ex vivo experiments, the RF device was used to treat porcine tissue comprising the skin, subcutaneous, and muscle layers. The device's safety was evaluated by temperature measurements of porcine tissue and histological analysis. In in vivo experiments, the dorsal skin of pigs was treated with the RF device. The safety and efficacy of the device were evaluated by measuring the skin temperature, subcutaneous fat layer thickness, and conducting histological analysis. RESULTS: The skin temperature did not exceed the set temperature during treatment, and skin damage was not observed in histologic analysis in both ex vivo and in vivo experiments. In in vivo experiments, the subcutaneous fat layer thickness and subcutaneous lipocyte size were decreased after treatment. In addition, the fibrous tissue between subcutaneous lipocytes was increased in the RF treatment group compared with the non-treatment group. CONCLUSION: The RF device used in this study effectively reduced the size of subcutaneous lipocytes and increased fibrous tissue without skin damage. Therefore, the safe and effective use of this device for non-invasive fat reduction may be possible in clinical settings.

Perioperative nivolumab versus observation in patients with renal cell carcinoma undergoing nephrectomy (PROSPER ECOG-ACRIN EA8143): an open-label, randomised, phase 3 study.

BACKGROUND: The standard of care for patients with intermediate-to-high risk renal cell carcinoma is partial or radical nephrectomy followed by surveillance. We aimed to investigate use of nivolumab before nephrectomy followed by adjuvant nivolumab in patients with high-risk renal cell carcinoma to determine recurrence-free survival compared with surgery only. METHODS: In this open-label, randomised, phase 3 trial (PROSPER EA8143), patients were recruited from 183 community and academic sites across the USA and Canada. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-1, with previously untreated clinical stage T2 or greater or Tany N+ renal cell carcinoma of clear cell or non-clear cell histology planned for partial or radical nephrectomy. Selected patients with oligometastatic disease, who were disease free at other disease sites within 12 weeks of surgery, were eligible for inclusion. We randomly assigned (1:1) patients using permuted blocks (block size of 4) within stratum (clinical TNM stage) to either nivolumab plus surgery, or surgery only followed by surveillance. In the nivolumab group, nivolumab 480 mg was administered before surgery, followed by nine adjuvant doses. The primary endpoint was investigator-reviewed recurrence-free survival in patients with renal cell carcinoma assessed in all randomly assigned patients regardless of histology. Safety was assessed in all randomly assigned patients who started the assigned protocol treatment. This trial is registered with ClinicalTrials.gov, NCT03055013, and is closed to accrual. FINDINGS: Between Feb 2, 2017, and June 2, 2021, 819 patients were randomly assigned to nivolumab plus surgery (404 [49%]) or surgery only (415 [51%]). 366 (91%) of 404 patients assigned to nivolumab plus surgery and 387 (93%) of 415 patients assigned to surgery only group started treatment. Median age was 61 years (IQR 53-69), 248 (30%) of 819 patients were female, 571 (70%) were male, 672 (88%) were White, and 77 (10%) were Hispanic or Latino. The Data and Safety Monitoring Committee stopped the trial at a planned interim analysis (March 25, 2022) because of futility. Median follow-up was 30·4 months (IQR 21·5-42·4) in the nivolumab group and 30·1 months (21·9-41·8) in the surgery only group. 381 (94%) of 404 patients in the nivolumab plus surgery group and 399 (96%) of 415 in the surgery only group had renal cell carcinoma and were included in the recurrence-free survival analysis. As of data cutoff (May 24, 2023), recurrence-free survival was not significantly different between nivolumab (125 [33%] of 381 had recurrence-free survival events) versus surgery only (133 [33%] of 399; hazard ratio 0·94 [95% CI 0·74-1·21]; one-sided p=0·32). The most common treatment-related grade 3-4 adverse events were elevated lipase (17 [5%] of 366 patients in the nivolumab plus surgery group vs none in the surgery only group), anaemia (seven [2%] vs nine [2%]), increased alanine aminotransferase (ten [3%] vs one [<1%]), abdominal pain (four [1%] vs six [2%]), and increased serum amylase (nine [2%] vs none). 177 (48%) patients in the nivolumab plus surgery group and 93 (24%) in the surgery only group had grade 3-5 adverse events due to any cause, the most common of which were anaemia (23 [6%] vs 19 [5%]), hypertension (27 [7%] vs nine [2%]), and elevated lipase (18 [5%] vs six [2%]). 48 (12%) of 404 patients in the nivolumab group and 40 (10%) of 415 in the surgery only group died, of which eight (2%) and three (1%), respectively, were determined to be treatment-related. INTERPRETATION: Perioperative nivolumab before nephrectomy followed by adjuvant nivolumab did not improve recurrence-free survival versus surgery only followed by surveillance in patients with high-risk renal cell carcinoma. FUNDING: US National Institutes of Health National Cancer Institute and Bristol Myers Squibb.

Initial screening for dental abnormalities identified by labial and buccal photographs in dogs and cats.

OBJECTIVE: To evaluate the dental abnormalities by visually assessing the labial and buccal photographs in dogs and cats and analyze their prevalence based on age and breed. ANIMALS: 1,096 client-owned dogs and 775 client-owned cats. METHODS: Data were collected from patients who visited 26 private veterinary clinics from January to December 2022. Each animal was evaluated through dental photographs taken from the labial and buccal sides. Correlations between the prevalence of the identified dental abnormalities and age, craniofacial type, and breed, were analyzed. RESULTS: Calculus, discoloration, epulis, fractured teeth, gingival recession, gingivitis, malocclusion, missing teeth, and persistent deciduous teeth could be identified by analyzing the dental photographs in both dogs and cats. Enamel defects in dogs and tooth resorption in cats could be identified. Brachycephalic dogs had a significantly higher prevalence of malocclusion (OR, 1.93; 95% CI, 1.36 to 2.75) and missing teeth (OR, 3.63; 95% CI, 2.71 to 4.91) compared to nonbrachycephalic dogs. Brachycephalic cats had a significantly higher prevalence of fractured teeth (OR, 1.95; 95% CI, 1.24 to 3.04) and a lower prevalence of gingival recession (OR, 0.30; 95% CI, 0.15 to 0.55) compared to nonbrachycephalic cats. Calculus, persistent deciduous teeth, and possibly gingivitis could be identified in dogs and cats by analyzing labial and buccal photographs. The assessment of some dental abnormalities such as fractured teeth, missing teeth, and tooth resorption can be limited without a complete dental examination under anesthesia. CLINICAL RELEVANCE: Although the assessment of dental conditions may be underestimated, the data on the prevalence of the dental abnormalities evaluated through the photographs could be utilized for screening dental diseases.

A novel acrylic orthodontic device for treatment of linguoverted mandibular canine teeth in small dogs.

Linguoverted mandibular canine teeth (LMC) is a common malocclusion in dogs. Several inclined bite-plane techniques using acrylic resin have been introduced to correct LMC in dogs. Although these techniques have suggested modifications to overcome shortcomings, there are still limitations; e.g., high technical sensitivity, as the viscous acrylic resin must still be fabricated in the oral cavity. The authors developed a novel method for small-breed dogs that uses a doughy acrylic resin form to achieve an easy intraoral design and extraoral fabrication. Eight small-breed dogs were presented to evaluate and treat malocclusion causing palatal trauma. First, a Class-1 malocclusion with linguoversion of the mandibular canine teeth (6 dogs with unilateral LMC and 2 dogs with bilateral) was diagnosed based on oral examination. Dogs were treated with the new method using a doughy acrylic resin form for 6 to 7 wk and had posttreatment follow-up 1 y after the procedure. All treated canine teeth were in correct positions 1 y after the appliances were removed. Key clinical message: The authors believe that the new method using a doughy acrylic resin form could be a good alternative for veterinarians to use when treating LMC.

Un nouveau dispositif orthodontique en acrylique pour le traitement des canines mandibulaires linguoverties chez les petits chiens. Les canines mandibulaires linguoverties (LMC) sont une malocclusion courante chez le chien. Plusieurs techniques de plan de morsure incliné utilisant de la résine acrylique ont été introduites pour corriger la LMC chez le chien. Bien que ces techniques aient suggéré des modifications pour surmonter les lacunes, elles présentent encore des limites; par exemple, une sensibilité technique élevée, car la résine acrylique visqueuse doit encore être fabriquée dans la cavité buccale. Les auteurs ont développé une nouvelle méthode pour les chiens de petite race qui utilise une forme pâteuse de résine acrylique pour obtenir une conception intra-orale et une fabrication extra-orale faciles. Huit chiens de petite race ont été présentés pour évaluer et traiter une malocclusion provoquant un traumatisme palatin. Tout d'abord, une malocclusion de classe 1 avec linguoversion des canines mandibulaires (6 chiens avec LMC unilatérale et 2 chiens avec bilatérale) a été diagnostiquée sur la base d'un examen oral. Les chiens ont été traités avec la nouvelle méthode en utilisant une forme pâteuse de résine acrylique pendant 6 à 7 semaines et ont fait l'objet d'un suivi post-traitement 1 an après la procédure. Toutes les canines traitées étaient dans la bonne position un an après le retrait des appareils.Message clinique clé:Les auteurs estiment que la nouvelle méthode utilisant une forme pâteuse de résine acrylique pourrait être une bonne alternative que les vétérinaires pourraient utiliser lors du traitement du LMC.(Traduit par Dr Serge Messier).

Outcomes of root canal treatments with three different sealers for 120 fractured maxillary fourth premolar teeth in small-to medium-sized dogs.

Introduction: Tooth fracture is one of the most common traumatic maxillofacial injuries in dogs and cats. For fractures with pulp exposure occurring in functionally important teeth, the literature indicates that root canal treatment (RCT) is an effective therapy option that may be the remedy of choice before extraction. The most commonly reported fractures in the United States involve canine teeth; however, fractures of the maxillary fourth premolars are more common in Korea, where there are many small-and medium-sized dogs. RCT mechanically and chemically removes pulp tissue and bacteria (cleaning and shaping) from the infected root canal, and obturates the root canal with filling material to restore tooth functionality without inflammation. Various techniques, instruments, and materials used in humans have been modified for application in veterinary dentistry. Methods: This study analyzed the results of RCT of the maxillary fourth premolar in 120 small-and medium-sized dogs (weighing less than 25 kg) using three different sealers (silicone-based sealer, bioceramic sealer, and calcium hydroxide-based sealer) through a simple application of the single-cone technique. Results: The overall success rate of RCT in maxillary fourth premolars was 90.83%, with 8.33% no evidence of failure (NEF) and 0.83% failure. Discussion: There were no significant differences between the three different sealers. Furthermore, preexisting periapical lesion (PAL) was reconfirmed as a factor in reducing the success rate of RCT. In addition, the working length and master apical file of each root were analyzed in our study as a novel reference for endodontic veterinarians.

Sublethal Effects of Spirotetramat, Cyantraniliprole, and Pymetrozine on Aphis gossypii (Hemiptera: Aphididae).

The toxicity and sublethal effects of three insecticides (spirotetramat, cyantraniliprole, and pymetrozine) on Aphis gossypii, a major agricultural pest, were investigated. The nymphal stage showed greater susceptibility than the adult stage to all the insecticides, with a difference of up to 8.9 times at the LC50 of spirotetramat. The effects of sublethal concentrations (LC10, LC30, LC50, and LC70) of the insecticides on the on the developmental period, survival rate, adult longevity, fecundity, and deformity rate were compared with those of the control. Compared with the control, cyantraniliprole and pymetrozine did not significantly affect the developmental period in the parental or F1 generation when applied at the nymphal stage at any concentration. Nonviable nymphs occurred in the F1 generation when both nymphs and adults were treated with spirotetramat and cyantraniliprole but not in the F2 generation. The age-specific maternity (lxmx) of A. gossypii treated with sublethal concentrations (LC10, LC30) decreased with increasing concentration. Spirotetramat at the LC30 resulted in significant differences in all life table parameters (R0, rm, λ, T, DT) compared with those of the control. Similarly, compared with that of the control (43.8), the net reproductive rate (R0) significantly decreased for all the insecticides except cyantraniliprole at the LC10 (37.5). Therefore, this study indicated that sublethal concentrations (over the LC30) of spirotetramat, cyantraniliprole, or pymetrozine might be useful for the density management of A. gossypii.

Evaluation of Biocompatibility and Healing Properties of Dural Substitutes Produced by Electrospinning Technology.

BACKGROUND/AIM: Dural reconstruction is a critical process after neurosurgical procedures. Improper dural repair leads to serious side-effects, such as cerebrospinal fluid leakage or infection. This is why it is important to properly repair the dura using a dural substitute, and research into dural substitutes is ongoing. The ideal dural substitute should be non-toxic, biocompatible, and capable of maintaining adequate tension and preventing cerebrospinal fluid leakage for extended periods in vivo. This study evaluated the biocompatibility and healing properties of Safe-Seal, poly-L-lactic acid synthetic bioabsorbable dural substitute produced by electrospinning technology. MATERIALS AND METHODS: Safe-Seal, was created by electrospinning, which is a technique for nanofiberizing polymers into three-dimensional structures, and its cytotoxicity was evaluated. The animal study used 30 rats, divided into three groups assessed at two time points (4 and 12 weeks). The study groups were a negative control group with no treatment, an experimental group with Safe-Seal (TDM Co. Ltd., Gwangju, Republic of Korea) implantation, and a positive control group with a commercial product, Redura® (Medprin Biotech, Frankfurt, Germany) implantation. RESULTS: Safe-Seal exhibited no cytotoxic or adverse effects in the in vivo animal study. Histologically, Safe-Seal displayed less inflammatory cell infiltration, less adhesion to brain tissue, and connectivity with the surrounding dura mater as compared to the negative control group and without any significant differences from Redura® in all evaluation criteria. CONCLUSION: Safe-Seal presented adequate biocompatibility in vivo and contributed to the healing of the dura mater at a similar level to that of Redura® when applied to dural defects.

Deciphering the virome of Chunkung (Cnidium officinale) showing dwarfism-like symptoms via a high-throughput sequencing analysis.

BACKGROUND: Viruses have notable effects on agroecosystems, wherein they can adversely affect plant health and cause problems (e.g., increased biosecurity risks and economic losses). However, our knowledge of their diversity and interactions with specific host plants in ecosystems remains limited. To enhance our understanding of the roles that viruses play in agroecosystems, comprehensive analyses of the viromes of a wide range of plants are essential. High-throughput sequencing (HTS) techniques are useful for conducting impartial and unbiased investigations of plant viromes, ultimately forming a basis for generating further biological and ecological insights. This study was conducted to thoroughly characterize the viral community dynamics in individual plants. RESULTS: An HTS-based virome analysis in conjunction with proximity sampling and a tripartite network analysis were performed to investigate the viral diversity in chunkung (Cnidium officinale) plants. We identified 61 distinct chunkung plant-associated viruses (27 DNA and 34 RNA viruses) from 21 known genera and 6 unclassified genera in 14 known viral families. Notably, 12 persistent viruses (7 DNA and 5 RNA viruses) were exclusive to dwarfed chunkung plants. The detection of viruses from the families Partitiviridae, Picobirnaviridae, and Spinareoviridae only in the dwarfed plants suggested that they may contribute to the observed dwarfism. The co-infection of chunkung by multiple viruses is indicative of a dynamic and interactive viral ecosystem with significant sequence variability and evidence of recombination. CONCLUSIONS: We revealed the viral community involved in chunkung. Our findings suggest that chunkung serves as a significant reservoir for a variety of plant viruses. Moreover, the co-infection rate of individual plants was unexpectedly high. Future research will need to elucidate the mechanisms enabling several dozen viruses to co-exist in chunkung. Nevertheless, the important insights into the chunkung virome generated in this study may be relevant to developing effective plant viral disease management and control strategies.

Treatment of an Infrabony Defect of a Maxillary Canine Tooth Using Enamel Matrix Derivatives with Allogeneic Bone Augmentation in a Dog.

A 5-year-old Miniature Dachshund was presented having an infrabony pocket on the palatal aspect of the right maxillary canine tooth. The bony defect had worsened despite previous closed root planing and administration of a perioceutic agent. A second surgery using an allogeneic cancellous bone augmentation with an enamel matrix derivative was performed in the infrabony defect following open root planing. Eight months after the periodontal surgery, the osseous defect showed healing by improved periodontal probing measurements and increased radiopacity using dental radiography and computed tomography.

Application of modified porcine xenograft by collagen coating in the veterinary field: pre-clinical and clinical evaluations.

Introduction: This study aimed to identify a collagen-coating method that does not affect the physicochemical properties of bone graft material. Based on this, we developed a collagen-coated porcine xenograft and applied it to dogs to validate its effectiveness. Methods: Xenografts and collagen were derived from porcine, and the collagen coating was performed through N-ethyl-N'-(3- (dimethylamino)propyl) carbodiimide/N-hydroxysuccinimide (EDC/NHS) activation. The physicochemical characteristics of the developed bone graft material were verified through field emission scanning electron microscope (FE-SEM), brunauer emmett teller (BET), attenuated total reflectance-fourier transform infrared (ATR-FTIR), and water absorption test. Subsequently, the biocompatibility and bone healing effects were assessed using a rat calvarial defect model. Results: The physicochemical test results confirmed that collagen coating increased bone graft materials' surface roughness and fluid absorption but did not affect their porous structure. In vivo evaluations revealed that collagen coating had no adverse impact on the bone healing effect of bone graft materials. After confirming the biocompatibility and effectiveness, we applied the bone graft materials in two orthopedic cases and one dental case. Notably, successful fracture healing was observed in both orthopedic cases. In the dental case, successful bone regeneration was achieved without any loss of alveolar bone. Discussion: This study demonstrated that porcine bone graft material promotes bone healing in dogs with its hemostatic and cohesive effects resulting from the collagen coating. Bone graft materials with enhanced biocompatibility through collagen coating are expected to be widely used in veterinary clinical practice.

Randomized, Double-Blind Phase III Study of Pazopanib Versus Placebo in Patients With Metastatic Renal Cell Carcinoma Who Have No Evidence of Disease After Metastasectomy: ECOG-ACRIN E2810.

PURPOSE: Patients with no evidence of disease (NED) after metastasectomy for renal cell carcinoma are at high risk of recurrence. Pazopanib is an inhibitor of vascular endothelial growth factor receptor and other kinases that improves progression-free survival in patients with metastatic RCC (mRCC). We conducted a randomized, double-blind, placebo-controlled multicenter study to test whether pazopanib would improve disease-free survival (DFS) in patients with mRCC rendered NED after metastasectomy. PATIENTS AND METHODS: Patients with NED after metastasectomy were randomly assigned 1:1 to receive pazopanib 800 mg once daily versus placebo for 52 weeks. The study was designed to observe an improvement in DFS from 25% to 45% with pazopanib at 3 years, corresponding to 42% reduction in the DFS event rate. RESULTS: From August 2012 to July 2017, 129 patients were enrolled. The study was unblinded after 83 DFS events (92% information). The study did not meet its primary end point. An updated analysis at 60.5-month median follow-up from random assignment (95% CI, 59.3 to 71.0) showed that the 3-year DFS was 27.4% (95% CI, 17.9 to 41.7) for pazopanib and 21.9% (95% CI, 13.3 to 36.2) for placebo. Hazard ratio (HR) for DFS was 0.90 ([95% CI, 0.60 to 1.34]; Pone-sided = .29) in favor of pazopanib. Three-year overall survival (OS) was 81.9% (95% CI, 72.7 to 92.2) for pazopanib and 91.4% (95% CI, 84.4 to 98.9) for placebo. The HR for OS was 2.55 (95% CI, 1.23 to 5.27) in favor of placebo (Ptwo-sided = .012). Health-related quality-of-life measures deteriorated in the pazopanib group during the treatment period. CONCLUSION: Pazopanib did not improve DFS as the primary end point compared with blinded placebo in patients with mRCC with NED after metastasectomy. In addition, there was a concerning trend favoring placebo in OS.

Dental erosion following clopidogrel administration in a dog: A case-based study.

A 10-year-old neutered male Chihuahua presented with unilateral dental erosion that occurred after several months of oral medications mixed with honey. A pH test was performed on all oral medications administered to the dogs to determine the cause of enamel erosion. Among the medications, the only acidic medication was clopidogrel (pH 2.65). To evaluate the effect of clopidogrel on the tooth surface under the same conditions as in the present patient, an additional preliminary study was designed in which two extracted teeth of another dog were immersed in a clopidogrel-honey mixture or only in honey. After a 3-week soaking of the extracted tooth in the clopidogrel-honey mixture, field-emission scanning electron microscope analysis revealed a rougher surface, whereas energy-dispersive X-ray spectroscopy analysis showed a reduced Ca/C ratio compared to the control tooth. In this case, prolonged exposure of the tooth surface to clopidogrel may be a cause of dental erosion.

Oral bacteria may affect conjunctival microorganisms in brachycephalic dogs: a preliminary study.

OBJECTIVE: To evaluate the prevalence of oral bacteria in the conjunctiva of brachycephalic and nonbrachycephalic dogs. ANIMALS: 12 brachycephalic (9.58 ± 3.55 years) and 12 nonbrachycephalic (8.33 ± 4.92 years) dogs without systemic disease, regardless of breed and sex, were included in the study, and half of the dogs in each group had periodontitis. METHODS: This prospective study investigated clinical data including craniofacial ratio, ophthalmic examination results, and periodontal status of the included dogs. Bacterial samples were collected by swabbing the oral mucosa and conjunctival surfaces. The presence and quantity of bacteria were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, 16S rRNA sequencing analysis, and the 10-fold dilution method. Statistical analyses were performed to assess correlations and factors influencing the presence of oral bacteria in the conjunctiva. RESULTS: The most common bacteria in the conjunctival flora in both groups were Micrococcus luteus, Corynebacterium spp, and Staphylococcus spp. The prevalence of oral bacteria on the conjunctival surface was 33%, with a significantly higher incidence in brachycephalic dogs (P = .027). Oral bacteria detected in the conjunctiva were predominantly Frederiksenia canicola, Neisseria spp, and Moraxella spp. Multiple regression analysis identified age, craniofacial ratio, and gingival index as factors influencing the presence of oral bacteria in the conjunctival flora. CLINICAL RELEVANCE: Oral resident bacteria have often been isolated from severe infectious corneal ulcers. This study provided evidence that brachycephalic dogs may require dental prophylaxis to reduce their oral bacterial load and that the association of oral bacteria in ocular diseases should be considered.

Complete genome sequence of a new putative member of the genus Pelarspovirus that infects Quercus aliena Blume in South Korea.

The complete nucleotide sequence of a newly discovered virus infecting Quercus aliena Blume, tentatively named "quercus leafroll virus" (QLRV), was determined through high-throughput and Sanger sequencing. The sequence comprises 3,940 nucleotides, has five open reading frames, and has a typical pelarspovirus genome organization, with neither 3' polyadenylation nor a 5' cap. The proteins encoded by QLRV share 17.9 to 44.2% amino acid sequence identity with known pelarspovirus proteins. The highest amino acid sequence identity values for the RNA-dependent RNA polymerase (RdRp) and coat protein were 67.5% and 55.2%, respectively, which are below the current thresholds for pelarspovirus species demarcation. On the basis of these results, we propose classifying QLRV as a new member of the genus Pelarspovirus, family Tombusviridae.

Complete nucleotide sequence of chrysanthemum virus D, a polero-like virus.

A putative new polerovirus, named "chrysanthemum virus D" (ChVD), was detected in a Chrysanthemum morifolium plant in South Korea. The virus was identified by high-throughput sequencing and confirmed by reverse transcription polymerase chain reaction. The entire ChVD genome is composed of 5,963 nucleotides and contains seven open reading frames (ORF0-5 and ORF3a), which are arranged similarly to those of other poleroviruses. These ORFs encode the putative proteins P0-5 and P3a, respectively. Pairwise amino acid sequence comparisons showed that the ChVD P0-5 and P3a proteins have 30.45-75% sequence identity to the corresponding proteins of other members of the genus Polerovirus. Since one of the species demarcation criteria for the genus Polerovirus is > 10% difference in the amino acid sequence of any gene product, the sequence comparisons indicate that ChVD represents a new species in this genus. Phylogenetic analysis of the P1-P2 and P3 amino acid sequences further indicate that ChVD is a novel polerovirus.

Leflunomide for the Treatment of Immune-Mediated Uveitis in a Dog.

A 5 yr old castrated male bichon frise presented with chronic bilateral uveitis that had previously been controlled with systemic steroid administration for 6 mo, resulting in weight gain, polyuria, and polydipsia. To control the uveitis without systemic side effects, oral cyclosporine was started after discontinuing oral steroid, but discontinued one month later because of severe vomiting. Leflunomide (2 mg/kg q 12 hr) was initiated, and the uveitis symptoms resolved after 2 mo. The dose was tapered according to the remission of clinical signs, with no relapse during the following 13 mo. Leflunomide therapy was then discontinued due to vomiting caused by severe gastroenteritis and pancreatitis, and topical prednisolone monotherapy was continued . At 8 mo after discontinuation of leflunomide, bilateral uveitis recurred, and leflunomide therapy was resumed. However, the patient lost vision due to the progression of clinical signs at 33 mo after commencing leflunomide, and evisceration of the glaucomatous right eye was performed at 43 mo. Histopathologic examination revealed lymphocyte and plasma cell infiltration and melanin-laden macrophages in the uveal tissue, and the patient was diagnosed with immune-mediated uveitis. This case indicated that oral leflunomide may be a viable treatment option for canine idiopathic immune-mediated uveitis.