Safety profile of the adjuvanted recombinant zoster vaccine: Pooled analysis of two large randomised phase 3 trials

Background

The ZOE-50 (NCT01165177) and ZOE-70 (NCT01165229) phase 3 clinical trials showed that the adjuvanted recombinant zoster vaccine (RZV) was ≥90% efficacious in preventing herpes zoster in adults. Here we present a comprehensive overview of the safety data from these studies.

Neuronal protein-tyrosine phosphatase 1B hinders sensory-motor functional recovery and causes affective disorders in two different focal ischemic stroke models

Ischemic brain injury causes neuronal death and inflammation. Inflammation activates protein-tyrosine phosphatase 1B (PTP1B). Here, we tested the significance of PTP1B activation in glutamatergic projection neurons on functional recovery in two models of stroke: by photothrombosis, focal ischemic lesions were induced in the sensorimotor cortex (SM stroke) or in the peri-prefrontal cortex (peri-PFC stroke). Elevated PTP1B expression was detected at 4 days and up to 6 weeks after stroke. While ablation of PTP1B in neurons of neuronal knockout (NKO) mice had no effect on the volume or resorption of ischemic lesions, markedly different effects on functional recovery were observed. SM stroke caused severe sensory and motor deficits (adhesive removal test) in wild type and NKO mice at 4 days, but NKO mice showed drastically improved sensory and motor functional recovery at 8 days. In addition, peri-PFC stroke caused anxiety-like behaviors (elevated plus maze and open field tests), and depression-like behaviors (forced swimming and tail suspension tests) in wild type mice 9 and 28 days after stroke, respectively, with minimal effect on sensory and motor function. Peri-PFC stroke-induced affective disorders were associated with fewer active (FosB⁺) neurons in the PFC and nucleus accumbens but more FosB⁺ neurons in the basolateral amygdala, compared to sham-operated mice. In contrast, mice with neuronal ablation of PTP1B were protected from anxiety-like and depression-like behaviors and showed no change in FosB⁺ neurons after peri-PFC stroke. Taken together, our study identifies neuronal PTP1B as a key component that hinders sensory and motor functional recovery and also contributes to the development of anxiety-like and depression-like behaviors after stroke. Thus, PTP1B may represent a novel therapeutic target to improve stroke recovery. All procedures for animal use were approved by the Animal Care and Use Committee of the University of Ottawa Animal Care and Veterinary Service (protocol 1806) on July 27, 2018.Key Words: adhesive removal test, anxiety, depression, elevated plus maze, forced swimming test, Iba1, interleukin-1β, microglia, open field test, tail suspension test, tumor necrosis factor-α

Chinese Library Classification No. R453; R741; R364.5     

A study of 10 cases of velopharyngeal incompetence treated by flap pharyngoplasty

Velopharyngeal incompetence (VPI) is a condition of incomplete closure of V.P. port area, normally formed by velum and posterior pharyngeal watt. The condition primarily results in various types of speech defects, which form- the main complaint of the patient. We have studied 10 cases of VPI due to various causes and the speech improvement obtained by flap pharyngoplasty procedures. The results have been evaluated with a follow-up of six months. Highly encouraging results only indicate a more frequent need to undertake such surgery without any hesitation if the ENT surgeon is familiar with and has an adequate exposure to this simple and effective procedure.     

Successful immune reconstitution decreases leukemic relapse and improves survival in recipients of unrelated cord blood transplantation.

Allogeneic hematopoietic stem cell transplantation (HSCT) is established therapy for selected patients with acute leukemia. After transplantation, antileukemic immune responses are believed to eliminate residual leukemia cells and decrease the likelihood of relapse. However, the clinical effect of successful antigen-specific immune reconstitution after HSCT on the likelihood of leukemic relapse and overall survival is not known. Pediatric recipients of unrelated cord blood transplants who underwent transplantation for acute leukemia were sequentially evaluated for their development of antigen-specific T-lymphocyte immunity to herpes viruses. The clinical effect of a positive antigen-specific response on relapse-free survival was determined. The presence of an antigen-specific response resulted in a relapse-free survival advantage (P = .0001), which was primarily due to a decrease in leukemic relapse (P = .003). Proportional hazards modeling for time to relapse and time to relapse or death defined 3 variables that were strongly associated with a poor outcome: female gender, poor remission status before transplantation, and negative antigen-specific T-lymphocyte proliferation. Notably neither acute nor chronic graft-versus-host disease had any effect on the incidence of leukemic relapse. Successful antigen-specific immune reconstitution after unrelated cord blood transplantation results in decreased leukemic relapse and improved overall survival.     

Alexithymia in Holocaust Survivors with and Without PTSD

Alexithymia was measured in non-treatment seeking, community-dwelling Holocaust survivors using the Toronto Alexithymia Scale—Twenty Item Version (TAS-20). Scores of survivors with (n = 30) and without (n = 26) posttraumatic stress disorder (PTSD) were compared, and associations among alexithymia, severity of trauma, and severity of PTSD symptoms were determined. Survivors with PTSD had significantly higher scores on the TAS-20 compared to survivors without PTSD. TAS-20 scores were significantly associated with severity of PTSD symptoms, but not with severity of trauma. This study adds to our knowledge of the relationship between alexithymia and trauma by demonstrating that this characteristic is related to the presence of posttraumatic symptoms and not simply exposure to trauma.     

印度结核病流行病学:综述

印度的结核病形势可以用高患病率、高发病率高传染率来描述。自二十世纪50年代以来在印度不同地区进行的疾病监测报告显示:涂阳肺结核患病率为0.6-7.6/1000,培阳肺结核患病率为1.7-9.8/1000,培阳和/或涂阳结核患病率为1.8-12.7/1000。从已进行的有限的研究资料分析,涂阳肺结核的发病率在1.0-1.6/1000之间,培阳肺结核发病率在1.0-2.5/1000之间。根据不同时期在不同地区进行的结核菌素监测估计,结核年感染率(ARTI)为1-2%。在2000-2003年进行的全国范围研究估计,平均ARTI为1.5%。多数在第3级卫生保健中心进行的研究显示在结核病例中人类免疫缺陷病毒(HIV)血清阳性率在增加,不同研究的结果介于0.4%-28.8%之间。新病例中耐多药(MDR)率相对较低,约0.5-5.3%之间。但在复治病例中MDR为8%-67%。     

Ascorbic acid (vitamin C) modulates the mutagenic effects produced by an alkylating agent in vivo

Recent reports suggest that ascorbic acid (vitamin C) inhibits tumorigenesis as well as exerts a protective effect against mutagenesis in vitro; however, there is no information on its ability to affect gene mutations induced in vivo. In this study, we have investigated the antimutagenic effects of ascorbic acid on the frequency of 6-thioguanine-resistant (6-TGr) T-lymphocytes produced in Fischer 344 rats dosed with the direct-acting alkylating agent, N-ethyl-N-nitrosourea (ENU). The freqeuncy of 6-TG^r T-lymphocytes from the spleen measured five weeks after ENU treatment indicated that ENU produced a substantial mutagenic response. Pretreatment and/or post-treatment of rats with ascorbic acid administered in the drinking water appeared to inhibit the response, but the inhibition was statistically significant only when data from the various dosing schedules were pooled. In addition, there was no clear dose-dependency to the inhibitory effect of ascorbic acid. To further evaluate the time effects of the vitamin supplement on ENU mutagenicity, rats were exposed to the mutagen together with ascorbic acid, which was given continuously for the entire duration of the experiment. At specific times after ENU treatment, the frequency of 6-TG^r T-cells was determined in lymphocytes isolated from the spleen and the thymus. Time-dependent increases in the frequency of 6-TG^r T-cells were observed with ENU treatment; ascorbic acid significantly reduced the ENU-mediated mutagenic responses, most dramatically in the spleen at weeks 6 and 8 (P < 0.0001), and to a lesser extent in the thymus (P < 0.01 at week 6 and P < 0.006 at week 8). Our data suggest that ascorbic acid intake affects the in vivo mutagenicity of ENU, a direct-acting mutagen/carcinogen, and that the reported inhibitory effects of the antioxidant on carcinogenesis may be partially mediated by its effects on mutagenesis. Although it is difficult to extrapolate from rodent studies to humans, the results presented suggest an explanation for epidemiological data that link vitamin C ingestion with decreased cancer risk. © 1994 Wiley-Liss, Inc.