Zobrazení zdroje stránky Alsvelasquez1855

Numerous candidate vaccines against cytomegalovirus (CMV) infection and disease are in development. Whereas the previous article [1] provides background and opinions about the issues relating to vaccination, this article provides specifics about the vaccines in active development, as reported at a National Institutes of Health-sponsored meeting in Bethesda on September 4-6, 2018. Here, vaccine developers provide synopses of their candidate vaccines to immunize women to protect against congenital CMV disease and to prevent the consequences of CMV disease in recipients of transplanted organs or hematopoietic stem calls. The projects are presented here roughly in the descending order of their stage of development in the opinion of the first author. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.Human cytomegalovirus (HCMV) is the most common infectious cause of infant birth defects and an etiology of significant morbidity and mortality in solid organ and hematopoietic stem cell transplant recipients. [https://www.selleckchem.com/products/afuresertib-gsk2110183.html GSK2110183] There is tremendous interest in developing a vaccine or immunotherapeutic to reduce the burden of HCMV-associated disease, yet after nearly a half-century of research and development in this field we remain without such an intervention. Defining immune correlates of protection is a process that enables targeted vaccine/immunotherapeutic discovery and informed evaluation of clinical performance. Outcomes in the HCMV field have previously been measured against a variety of clinical end points, including virus acquisition, systemic replication, and progression to disease. Herein we review immune correlates of protection against each of these end points in turn, showing that control of HCMV likely depends on a combination of innate immune factors, antibodies, and T-cell responses. Furthermore, protective immune responses are heterogeneous, with no single immune parameter predicting protection against all clinical outcomes and stages of HCMV infection. A detailed understanding of protective immune responses for a given clinical end point will inform immunogen selection and guide preclinical and clinical evaluation of vaccines or immunotherapeutics to prevent HCMV-mediated congenital and transplant disease. © The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.Cytomegalovirus (CMV) remains an important pathogen in the transplant population. As such, the US Food and Drug Administration has published a guidance to encourage and inform the development of therapeutics for the treatment and prevention of CMV disease in this population. This review summarizes important phase 3 trial design considerations for industry and provides rationale for some of the recommendations included in the guidance. Published by Oxford University Press for the Infectious Diseases Society of America 2020.BACKGROUND Several cytomegalovirus (CMV) vaccine candidates are under development. To reduce the burden of congenital CMV infection, potential strategies under consideration include vaccination of adult women, adolescent girls, and/or young children (both sexes). METHODS We reviewed 5 studies that used infectious disease modeling to assess the potential impact of vaccination for preventing congenital CMV infection. All models assumed CMV vaccination would prevent primary infection and 2 models also assumed prevention of reinfections and reactivations. RESULTS Despite differences in structure, assumptions, and population data, infant vaccination (both sexes) was the optimal strategy in all models, but in 1 model vaccinating seronegative women at 19-21 years of age was also optimal (for duration of vaccine protection ≥8 years). In 3 models, infant vaccination increased average age at primary infection as a result of decreased secondary transmission (herd immunity) combined with waning vaccine-induced immunity. This effect could increase the risk of congenital CMV infections in populations where primary CMV infection occurs early in childhood but could be minimized by administering a second dose of vaccine during adolescence. CONCLUSIONS Understanding vaccine efficacy and duration of immunity, and how these might vary depending on CMV serostatus and age at vaccination, will be key to defining CMV vaccination strategies. Published by Oxford University Press for the Infectious Diseases Society of America 2020.OBJECTIVES The aim of this systematic review was to provide an overview of the oral and maxillofacial solitary fibrous tumor (SFT) in order to determine its clinicopathologic characteristics and biological behavior. METHODS We conducted a systematic review in May 2019 in multiple databases. Cases diagnosed as SFT in the oral cavity and maxillofacial complex were included. RESULTS Seventy-three published articles were included in our systematic review, corresponding to a total of 154 cases. SFT showed a slight female predilection (53.2%), and the cheek mucosa/cheek, tongue, and palate were the most affected anatomical sites. The mean size of SFT in the oral cavity and maxillofacial region at diagnosis was 1.4 cm. Histologic features of malignancy by morphologic analysis (P  less then  .001) were significantly associated with a larger tumor size. Surgical excision was the most frequent therapeutic modality. Recurrence and metastasis were uncommon findings in our sample. CONCLUSIONS Histologic features of malignancy can be important parameters of tumor behavior. Adequate surgical treatment and long-term follow-up are required for these cases. © American Journal of Hypertension, Ltd 2020. All rights reserved. For permissions, please email journals.permissions@oup.com.Recently, protease-activated receptor 2 (PAR2) has been proved to be involved in the inflammatory response including osteoarthritis (OA). In the present study, we found that PAR2 antagonist could remarkably improve the pathological condition of OA rats in vivo. In addition, we also found that PAR2 antagonist could suppress the production of inflammatory factors (TNF-α and Cox-2), decrease the levels of MMP-1 and MMP-13, and restrain the levels of P62 proteins and aggravate the expression of LC3-II both in vivo and in vitro. Besides, in vitro, PAR2 antagonist could increase the proliferation and colony formation of chondrocytes induced with IL-1β. Moreover, PAR2 antagonist could decrease the expression of expressions of p-p38, p-IκBα and p-NF-κB in vitro. However, PAR2 agonist exhibited the opposite effects. Furthermore, SB203580, a p38 MAPK inhibitor, could remarkably promote the proliferation of chondrocytes induced with IL-1β, could alleviate the production of TNF-α and Cox-2, could down-regulate the protein expressions of MMP-1 and MMP-13, and could decrease the expression of P62 and increase the expressions of LC3-II of chondrocytes induced with IL-1β.