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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   
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Melatonin, the main hormone produced by the pineal gland, is secreted in a circadian manner (24‐hr period), and its oscillation influences several circadian biological rhythms, such as the regulation of clock genes expression (chronobiotic effect) and the modulation of several endocrine functions in peripheral tissues. Assuming that the circadian synchronization of clock genes can play a role in the regulation of energy metabolism and it is influenced by melatonin, our study was designed to assess possible alterations as a consequence of melatonin absence on the circadian expression of clock genes in the epididymal adipose tissue of male Wistar rats and the possible metabolic repercussions to this tissue. Our data show that pinealectomy indeed has impacts on molecular events: it abolishes the daily pattern of the expression of Clock, Per2, and Cry1 clock genes and Pparγ expression, significantly increases the amplitude of daily expression of Rev‐erbα, and affects the pattern of and impairs adipokine production, leading to a decrease in leptin levels. However, regarding some metabolic aspects of adipocyte functions, such as its ability to synthesize triacylglycerols from glucose along 24 hr, was not compromised by pinealectomy, although the daily profile of the lipogenic enzymes expression (ATP‐citrate lyase, malic enzyme, fatty acid synthase, and glucose‐6‐phosphate dehydrogenase) was abolished in pinealectomized animals.  相似文献   
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The fat mass and obesity-associated gene (FTO) rs9939609 A-allele is linked to obesity and dyslipidemia, yet the independent influence of this polymorphism on blood lipids remains equivocal. We examined the influence of the FTO rs9939609 polymorphism on fasting and postprandial blood lipids in individuals homozygous for the risk A-allele or T-allele with similar anthropometric and demographic characteristics. 12 AA and 12 TT males consumed a standardized meal after fasting overnight. Blood samples were collected at baseline (−1.5 h), before the meal (0 h), and for five hours postprandially to measure lipid, glucose, and insulin concentrations. Time-averaged total area under the curve (TAUC) values (0–5 h) were calculated and compared between genotypes. Fasting triacylglycerol (TG), high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, total cholesterol, non-esterified fatty acid (NEFA), glucose, and insulin concentrations were similar between groups (p ≥ 0.293). TAUC for TG was similar in AAs and TTs (95% confidence interval (CI) −0.52 to 0.31 mmol/L/h; p = 0.606). Likewise, TAUC values were similar for NEFA (95% CI −0.04 to 0.03 mmol/L/h; p = 0.734), glucose (95% CI −0.41 to 0.44 mmol/L/h; p = 0.951), and insulin (95% CI −6.87 to 2.83 pmol/L/h; p = 0.395). Blood lipids are not influenced by the FTO rs9939609 polymorphism, suggesting the FTO-dyslipidemia link is mediated by adiposity and weight management is important in preventing FTO-related lipid variations.  相似文献   
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IntroductionThis article deals with the occurrence of health problems due to gunshot wounds to the face among military police officers, in the metropolitan region of Rio de Janeiro, who were submitted to surgery at the Oral and Maxillofacial Surgery and Traumatology Clinic of Hospital Central da Polícia Militar.ObjectiveTo identify the profile of patients submitted to surgery as a result of gunshot wounds, the anatomical distribution of maxillofacial fractures, the identified sequelae and complications, the health specialties involved in the rehabilitation of these patients, and to discuss the social, emotional and work performance-related effects of work among these subjects.MethodsA retrospective epidemiological study was carried out based on secondary data from military police officers who were submitted to surgery at Hospital Central da Polícia Militar due to gunshot wounds from June 2003 to December 2017.ResultsDuring the study period, 778 surgeries were performed in the operating room by the Oral and Maxillofacial Surgery and Traumatology service at Hospital Central da Polícia Militar, 186 of which were due to gunshot wounds (23.9%). All patients were males and the mean age 34.7 years. Bone segment loss was the most common sequela. Facial esthetic impairment and reports of insomnia were the most often identified late consequences of impact on health and social life. Regarding the occupational impacts of the sustained injury, the mean time away from work due to medical leave for the treatment of maxillofacial injuries was 11.7 months.ConclusionThe treatment of gunshot wounds patients with facial injuries requires multiple surgical interventions and their rehabilitation requires the involvement of different health specialties. Further studies are needed to qualitatively analyze the impact of this type of facial trauma on the patients' lives and their social consequences.  相似文献   
8.

Objective

To analyse and understand vaccination hesitancy discourses, particularly those of people who have decided not to vaccinate their sons and daughters.

Methods

Qualitative study of five individual interviews and two focus groups with people who chose not to vaccinate their children in the province of Granada (Spain).

Results

Mothers and fathers manifest a system of health beliefs different to the biomedical paradigm. From an ethical point of view, they justify their position based on the right to autonomy and responsibility for their decisions. Alleged specific reasons: they doubt administration of several vaccines simultaneously at an early age in a systematic way and without individualising each case; they fear adverse effects and do not understand the variations of the vaccination schedule.

Conclusions

These vaccination hesitancy discourses respond to the individual vs collective conflict; parents defend their right to bring up their children without any interference from the state and focus their responsibility on the individual welfare of their sons and daughters, regardless of the consequences that their actions might have on the collective. In their management of risks, they consider those derived from vaccination more relevant than the individual or collective consequences of not doing so. The vaccines generating most doubts are the more controversial ones within the scientific world. Transparency in communication of adverse effects; authorities respect for other health/disease concepts; banishment of the term “anti-vaccines” from the media and scientific vocabulary, and developing spaces for dialogue are bridges to be built.  相似文献   
9.
The outbreaks of rabies in humans transmitted by Desmodus rotundus in 2004 and 2005, in the northeast of the Brazilian State of Para, eastern Amazon basin, made this a priority area for studies on this zoonosis. Given this, the present study provides data on this phenomenon in an urban context, in order to assess the possible circulation of the classic rabies virus (RABV) among bat species in Capanema, a town in the Amazon basin. Bats were collected, in 2011, with mist nets during the wet and dry seasons. Samples of brain tissue and blood were collected for virological and serological survey, respectively. None of the 153 brain tissue samples analyzed tested positive for RABV infection, but 50.34% (95% CI: 45.67-55.01%) of the serum samples analyzed were seropositive. Artibeus planirostris was the most common species, with a high percentage of seropositive individuals (52.46%, 95% CI: 52.31 52.60%). Statistically, equal proportions of seropositive results were obtained in the rainy and dry seasons (c2 = 0.057, d.f. = 1, p = 0.88). Significantly higher proportions of males (55.96%, 95% CI: 48.96-62.96%) and adults (52.37%, 95% CI: 47.35-57.39%) were seropositive. While none of the brain tissue samples tested positive for infection, the high proportion of seropositive specimens indicates that RABV may be widespread in this urban area.  相似文献   
10.
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  相似文献   
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