Vaccination against Extracellular Vimentin for Treatment of Urothelial Cancer of the Bladder in Client-Owned Dogs

It was recently shown that targeting extracellular vimentin (eVim) is safe and effective in preclinical models. Here, we report the safety and efficacy in client-owned dogs with spontaneous bladder cancer of CVx1, an iBoost technology-based vaccine targeting eVim in combination with COX-2 inhibition. This was a single-arm prospective phase 1/2 study with CVx1 in 20 client-owned dogs with spontaneous UC which involved four subcutaneous vaccinations with CVx1 at 2-week intervals for induction of antibody titers, followed by maintenance vaccinations at 2-month intervals. Additionally, daily cyclooxygenase (COX)-2 inhibition with meloxicam was given. The response was assessed by antibody titers, physical condition, abdominal ultrasound and thorax X-ray. The primary endpoints were the development of antibody titers, as well as overall survival compared to a historical control group receiving carboplatin and COX-2 inhibition with piroxicam. Kaplan–Meier survival analysis was performed. All dogs developed antibodies against eVim. Titers were adequately maintained for the duration of this study. A median overall survival of 374 days was observed, which was 196 days for the historical control group (p < 0.01). Short-term grade 1–2 toxicity at the injection site and some related systemic symptoms peri-vaccination were observed. No toxicity was observed related to the induced antibody response. A limitation of this study is the single-arm prospective setting. CVx1 plus meloxicam consistently induced efficient antibody titers, was well tolerated and showed prolonged survival. The results obtained merit further development for human clinical care

Road traffic noise and children's inattention

BACKGROUND: An increasing number of children are exposed to road traffic noise levels that may lead to adverse effects on health and daily functioning. Childhood is a period of intense growth and brain maturation, and children may therefore be especially vulnerable to road traffic noise. The objective of the present study was to examine whether road traffic noise was associated with reported inattention symptoms in children, and whether this association was mediated by sleep duration. METHODS: This study was based on the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health. Parental reports of children's inattention at age 8 were linked to modelled levels of residential road traffic noise. We investigated the association between inattention and noise exposure during pregnancy (n = 1934), noise exposure averaged over 5 years (age 3 to 8 years; n = 1384) and noise exposure at age 8 years (n = 1384), using fractional logit response models. The participants were children from Oslo, Norway. RESULTS: An association with inattention at age 8 years was found for road traffic noise exposure at age 8 years (coef = .0083, CI = [.0012, .0154]; 1.2% point increase in inattention score per 10 dB increase in noise level), road traffic noise exposure average for the last 5 years (coef = .0090, CI = [.0016, .0164]; 1.3% point increase/10 dB), and for pregnancy road traffic noise exposure for boys (coef = .0091, CI = [.0010, .0171]), but not girls (coef = -.0021, CI = [-.0094, .0053]). Criteria for doing mediation analyses were not fulfilled. CONCLUSION: Results indicate that road traffic noise has a negative impact on children's inattention. We found no mediation by sleep duration