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141.

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.

Methods

Adults aged ≥50 (ZOE-50) and ≥70 (ZOE-70) years were randomly vaccinated with RZV or placebo. Safety analyses were performed on the pooled total vaccinated cohort, consisting of participants receiving at least one dose of RZV or placebo. Solicited and unsolicited adverse events (AEs) were collected for 7 and 30?days after each vaccination, respectively. Serious AEs (SAEs) were collected from the first vaccination until 12?months post-last dose. Fatal AEs, vaccination-related SAEs, and potential immune-mediated diseases (pIMDs) were collected during the entire study period.

Results

Safety was evaluated in 14,645 RZV and 14,660 placebo recipients. More RZV than placebo recipients reported unsolicited AEs (50.5% versus 32.0%); the difference was driven by transient injection site and solicited systemic reactions that were generally seen in the first week post-vaccination. The occurrence of overall SAEs (RZV: 10.1%; Placebo: 10.4%), fatal AEs (RZV: 4.3%; Placebo: 4.6%), and pIMDs (RZV: 1.2%; Placebo: 1.4%) was balanced between groups. The occurrence of possible exacerbations of pIMDs was rare and similar between groups. Overall, except for the expected local and systemic symptoms, the safety results were comparable between the RZV and Placebo groups irrespective of participant age, gender, or race.

Conclusions

No safety concerns arose, supporting the favorable benefit-risk profile of RZV.  相似文献   
142.
Microglia, the innate immune cells of the CNS, perform critical inflammatory and noninflammatory functions that maintain normal neural function. For example, microglia clear misfolded proteins, elaborate trophic factors, and regulate and terminate toxic inflammation. In Alzheimer’s disease (AD), however, beneficial microglial functions become impaired, accelerating synaptic and neuronal loss. Better understanding of the molecular mechanisms that contribute to microglial dysfunction is an important objective for identifying potential strategies to delay progression to AD. The inflammatory cyclooxygenase/prostaglandin E2 (COX/PGE2) pathway has been implicated in preclinical AD development, both in human epidemiology studies and in transgenic rodent models of AD. Here, we evaluated murine models that recapitulate microglial responses to Aβ peptides and determined that microglia-specific deletion of the gene encoding the PGE2 receptor EP2 restores microglial chemotaxis and Aβ clearance, suppresses toxic inflammation, increases cytoprotective insulin-like growth factor 1 (IGF1) signaling, and prevents synaptic injury and memory deficits. Our findings indicate that EP2 signaling suppresses beneficial microglia functions that falter during AD development and suggest that inhibition of the COX/PGE2/EP2 immune pathway has potential as a strategy to restore healthy microglial function and prevent progression to AD.  相似文献   
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Objective: To assess the quality of images and video clips of fetal central nervous (CNS) structures obtained by ultrasound and transmitted via tele-ultrasound from Brazil to Australia.

Methods: In this cross-sectional study, 15 normal singleton pregnant women between 20 and 26 weeks were selected. Fetal CNS structures were obtained by images and video clips. The exams were transmitted in real-time using a broadband internet and an inexpensive video streaming device. Four blinded examiners evaluated the quality of the exams using the Likert scale. We calculated the mean, standard deviation, mean difference, and p values were obtained from paired t tests.

Results: The quality of the original video clips was slightly better than that observed by the transmitted video clips; mean difference considering all observers = 0.23 points. In 47/60 comparisons (78.3%; 95% CI?=?66.4–86.9%) the quality of the video clips were judged to be the same. In 182/240 still images (75.8%; 95% CI?=?70.0–80.8%) the scores of transmitted image were considered the same as the original.

Conclusion: We demonstrated that long distance tele-ultrasound transmission of fetal CNS structures using an inexpensive video streaming device provided images of subjective good quality.  相似文献   
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