Primary Ureteral Hemangiosarcoma in a dog.

BACKGROUND: Primary ureteral neoplasia in dogs is extremely rare. To the best of the authors' knowledge, this is the second documented case of a primary ureteral hemangiosarcoma. This case report describes the clinical and pathological findings of a primary distal ureteral hemangiosarcoma. CASE PRESENTATION: A 12-year-old spayed female goldendoodle was presented with a history of polyuria and weight loss. Abdominal radiographs revealed a large cranial abdominal mass. Abdominal ultrasound and computed tomography (CT) identified a left sided distal ureteral mass with secondary hydroureter and a left lateral hepatic mass with no evidence of connection or diffuse metastasis. A left ureteronephrectomy, partial cystectomy, and left lateral liver lobectomy were performed. Histopathology was consistent with primary ureteral hemangiosarcoma and a hepatocellular carcinoma. Adjunctive therapy including chemotherapy was discussed but declined. CONCLUSION: Due to its rarity, the authors of this case presentation believe that ureteral hemangiosarcoma should be included as a differential diagnosis when evaluating a ureteral mass. With the unknown, and suspected poor prognosis, routine monitoring with adjunctive therapy should be considered.

Extended long-term radiographic and functional comparison of tibial plateau leveling osteotomy vs tibial tuberosity advancement for cranial cruciate ligament rupture in the dog.

OBJECTIVE: To report extended long-term outcomes of dogs with cranial cruciate ligament rupture treated by tibial plateau leveling osteotomy (TPLO) or tibial tuberosity advancement (TTA). STUDY DESIGN: Retrospective clinical cohort study. ANIMALS: Client-owned dogs with ≥3 years follow-up (118 dogs, 166 stifles). METHODS: Records from June 2012 to May 2015 were reviewed. Follow-up examination and radiography were performed in dogs meeting the inclusion criteria. Measures of outcomes included a radiographic osteoarthritis score (preoperative, 8 weeks postoperative, and ≥3 years postoperative), the Canine Brief Pain Inventory, and the Canine Orthopedic Index. RESULTS: Ninety-four dogs treated with TPLO (133 stifles) and 24 dogs treated with TTA (33 stifles) met the inclusion criteria. All dogs underwent meniscal release or partial medial meniscectomy. Osteoarthritis score progressed more after TTA (P = .003) and in dogs with bilateral surgery (P = .022). Long-term outcomes that were better after TPLO compared with TTA included average pain in the last 7 days (P = .007), interference with walking (P = .010), morning stiffness (P = .004), jumping (P = .003) and climbing (P = .040), limping during mild activities (P = .001), and overall quality of life (P = .045). CONCLUSION: Osteoarthritis progressed more after TTA and in dogs with bilateral stifle surgery. Dogs treated with TPLO subjectively seemed to have less pain and fewer mobility issues. CLINICAL SIGNIFICANCE: Tibial plateau leveling osteotomy provides a better long-term radiographic and functional outcome than TTA.

Why scientific societies should involve more early-career researchers.

Early-career researchers (ECRs) make up a large portion of the academic workforce. Yet, most leadership positions in scientific societies are held by senior scientists, and ECRs have little to no say over the decisions that will shape the future of research. This article looks at the level of influence ECRs have in 20 scientific societies based in the US and UK, and provides guidelines on how societies can successfully include ECRs in leadership roles.

Recruitment of patients with Chronic Obstructive Pulmonary Disease (COPD) from the Clinical Practice Research Datalink (CPRD) for research.

Databases of electronic health records (EHR) are not only a valuable source of data for health research but have also recently been used as a medium through which potential study participants can be screened, located and approached to take part in research. The aim was to assess whether it is feasible and practical to screen, locate and approach patients to take part in research through the Clinical Practice Research Datalink (CPRD). This is a cohort study in primary care. The CPRD anonymised EHR database was searched to screen patients with Chronic Obstructive Pulmonary Disease (COPD) to take part in a research study. The potential participants were contacted via their General Practitioner (GP) who confirmed their eligibility. Eighty two practices across Greater London were invited to the study. Twenty-six (31.7%) practices consented to participate resulting in a pre-screened list of 988 patients. Of these, 632 (63.7%) were confirmed as eligible following the GP review. Two hundred twenty seven (36%) response forms were received by the study team; 79 (34.8%) responded 'yes' (i.e., they wanted to be contacted by the research assistant for more information and to talk about enrolling in the study), and 148 (65.2%) declined participation. This study has shown that it is possible to use EHR databases such as CPRD to screen, locate and recruit participants for research. This method provides access to a cohort of patients while minimising input needed by GPs and allows researchers to examine healthcare usage and disease burden in more detail and in real-life settings.

Crying infant with painful toes.

Our patient's sleepless parents sought care for their infant's mysteriously injured toes.

Positive Allosteric Modulation of mGluR5 Accelerates Extinction Learning but Not Relearning Following Methamphetamine Self-Administration.

Recent studies have implicated glutamate neurotransmission as an important substrate for the extinction of conditioned behaviors, including responding for drug reinforcement. Positive allosteric modulation of the type-5 metabotropic glutamate receptor (mGluR5) in particular has emerged as a treatment strategy for the enhancement of extinction of drug-motivated behaviors. Here, we investigated the effects of the mGluR5 positive allosteric modulator CDPPB, a compound known for its cognitive enhancing effects in rodents, on extinction learning in rats with different histories of methamphetamine (METH) training. Rats were trained to self-administer METH under two conditions: 16 daily sessions of short access (90 min/day, ShA), or eight daily sessions of short access followed by eight sessions of long access (6 h/day, LgA). Control rats self-administered sucrose pellets in daily 30 min sessions. Next, rats were administered vehicle or 30 mg/kg CDPPB prior to seven consecutive daily extinction sessions, subjected to additional extinction sessions to re-establish a post-treatment baseline, and then tested for reinstatement of behavior in the presence of METH- or sucrose-paired cues. Rats were then subjected to a second series of extinction sessions, preceded by vehicle or 30 mg/kg CDPPB, and an additional test for cue-triggered reinstatement. CDPPB treatment resulted in a more rapid extinction of responding on the active lever, especially in the early sessions of the first extinction sequence. However, treatment effects were minimal during subsequent cue reinstatement tests and non-existent during the second series of extinction sessions. Rats with histories of ShA, LgA, and sucrose training expressed similar behavioral sensitivities to CDPPB, with LgA rats demonstrating a modestly higher treatment effect. Positive allosteric modulation of mGluR5 may therefore have some beneficial effects on efforts to facilitate extinction learning and reduce methamphetamine seeking.

Mutants of plasminogen activator inhibitor-1 designed to inhibit neutrophil elastase and cathepsin G are more effective in vivo than their endogenous inhibitors.

Neutrophil elastase and cathepsin G are abundant intracellular neutrophil proteinases that have an important role in destroying ingested particles. However, when neutrophils degranulate, these proteinases are released and can cause irreparable damage by degrading host connective tissue proteins. Despite abundant endogenous inhibitors, these proteinases are protected from inhibition because of their ability to bind to anionic surfaces. Plasminogen activator inhibitor type-1 (PAI-1), which is not an inhibitor of these proteinases, possesses properties that could make it an effective inhibitor of neutrophil proteinases if its specificity could be redirected. PAI-1 efficiently inhibits surface-sequestered proteinases, and it efficiently mediates rapid cellular clearance of PAI-1-proteinase complexes. Therefore, we examined whether PAI-1 could be engineered to inhibit and clear neutrophil elastase and cathepsin G. By introducing specific mutations in the reactive center loop of wild-type PAI-1, we generated PAI-1 mutants that are effective inhibitors of both proteinases. Kinetic analysis shows that the inhibition of neutrophil proteinases by these PAI-1 mutants is not affected by the sequestration of neutrophil elastase and cathepsin G onto surfaces. In addition, complexes of these proteinases and PAI-1 mutants are endocytosed and degraded by lung epithelial cells more efficiently than either the neutrophil proteinases alone or in complex with their physiological inhibitors, alpha1-proteinase inhibitor and alpha1-antichymotrypsin. Finally, the PAI-1 mutants were more effective in reducing the neutrophil elastase and cathepsin G activities in an in vivo model of lung inflammation than were their physiological inhibitors.