Gilmorebyrne3583

arotid artery atherosclerosis, suggesting that this imaging modality may be useful for routine imaging workups and provide comprehensive information for both the vessel wall and lumen.BACKGROUND The global burden of hepatitis B virus (HBV) infection in terms of morbidity and mortality is immense. Novel treatments that can induce a protective immune response are urgently needed to effectively control the HBV epidemic and eventually eradicate chronic HBV infection. METHODS We designed and evaluated an HBV therapeutic vaccine consisting of a novel Toll-like receptor 7 (TLR7) agonist T7-EA, an Alum adjuvant and a recombinant HBsAg protein. We used RNA-seq, ELISA and hTLR7/8 reporting assays to characterize T7-EA in vitro and real-time PCR to evaluate the tissue-retention characteristics in vivo. To evaluate the adjuvant potential, we administrated T7-EA intraperitoneally in a formulation with an Alum adjuvant and HBsAg in normal and HBV mice, then, we evaluated the HBsAg-specific immune responses by ELISA and Elispot assays. RESULTS T7-EA acted as an hTLR7-specific agonist and induced a similar gene expression pattern as an unmodified TLR7 ligand when Raw 264.7 cells were exposed to T7-EA; however, T7-EA was more potent than the unmodified TLR7 ligand. In vivo studies showed that T7-EA had tissue-retaining activity with stimulating local cytokine and chemokine expression for up to 7 days. T7-EA could induce Th1-type immune responses, as evidenced by an increased HBsAg-specific IgG2a titer and a T-cell response in normal mice compared to mice received traditional Alum-adjuvant HBV vaccine. Importantly, T7-EA could break immune tolerance and induce persistent HBsAg-specific antibody and T-cell responses in an HBV mouse model. CONCLUSIONS T7-EA might be a candidate adjuvant in a prophylactic and therapeutic HBV vaccine.BACKGROUND In the context of task shifting, a promoted approach to healthcare delivery in resource-poor settings, trained community health workers (CHWs) have been shown to be effective in delivering quality care of malaria for febrile under-5 children. While their effectiveness has been documented, the fidelity of implementation (FOI) has not been adequately studied. By understanding and measuring whether an intervention has been performed with fidelity, researchers and practitioners gain a better understanding of how and why an intervention works, and the extent to which outcomes can be improved. The objective of this study was to assess the FOI of a recommended protocol for malaria care by CHWs in a resource-poor setting in Nigeria. METHODS Thirty-five female CHWs who participated in a 3-day training on home management of malaria among under-5 children were studied. They managed 1,646 children over the implementation period and then underwent evaluation via a one-time hospital-based observation by the traiatment initiation counseling of caregivers (p = 0.002). CONCLUSIONS Studying intervention fidelity stands to identify the shortcomings of implementation and specific areas to target for improvement in future adoption or implementation. This study concludes that future trainings should emphasize clinical evaluation and post-treatment counseling of caregivers by CHWs to ensure the best outcome for children.BACKGROUND Diagnosis of perinatal anomalies is a stressful experience that can negatively affect mothers, families, health-care systems, and societies. Perinatal palliative care (PPC) is a new development in maternity services which focuses on emotional, spiritual, social, and symptom management and provides care for women and families with fetal anomaly diagnosis. Therefore, this study aimed to develop a service package for women with fetal anomaly diagnosis in socio-cultural context of Iran. METHODS This research is an exploratory mixed methods study with the qualitative-quantitative sequencing design that consists of four sequential phases. In the first phase, following a qualitative approach, the researcher will explore the needs and experiences of women with fetal anomaly diagnosis, their families, health care providers and policy-makers. At the second phase, based on the review of the literature, Program, guideline, service package and protocol for care of women and their families after perinatal anomaly diagnosis will be identified in other countries. In the third phase, recommendations from qualitative phase and literature review will be combined, the initial protocol of the palliative care service package for perinatal anomaly diagnosis will be identified and prioritized. In the fourth phase, the opinion of experts about this service package will be collected by using RAND/UCLA Appropriateness Method technique and the applicability of the service package's recommendations in clinical settings will be determined. DISCUSSION The results of this Mixed Methods study are expected response the needs and experiences of the women with perinatal anomaly diagnosis being met in the socio-cultural context of Iran and a service package for palliative care of these women developed.BACKGROUND We have reported that polydatin (PD) alleviates mitochondrial dysfunction in rat models of sepsis-induced acute kidney injury (SI-AKI), but the mechanism is not well understood. Here, we investigated the role of Parkin-mediated mitophagy in the protective effects of PD in SI-AKI in mice. METHODS Sepsis was induced in the mice by caecal ligation and puncture. Mitophagy was determined by mitochondrial mass. NLRP3 inflammasome activation was determined by NLRP3, ASC and caspase-1. Mitophagy was blocked by treatment with mitochondrial division inhibitor-1 and Parkin knockout. KEY RESULTS PD treatment increased the sepsis-induced loss of mitochondrial mass, indicating the upregulation of mitophagy. Furthermore, PD treatment mediated Parkin translocation from the cytoplasm to the mitochondria. This suggests that Parkin-mediated mitophagy is an underlying mechanism. This was confirmed by the suppression of PD-induced mitophagy in Parkin-/- mice and in mice that were treated with a mitophagy inhibitor. PD-induced Parkin translocation and mitophagy were blocked by inhibiting SIRT1; thus, activation of SIRT1 might be an important molecular mechanism that is triggered by PD. Additionally, PD treatment protected against sepsis-induced kidney injury. Barasertib cost These effects were blocked by inhibition of Parkin-dependent mitophagy. Furthermore, PD also protected against mitochondrial dysfunction and mitochondria-dependent apoptosis, and the effect was blocked when Parkin-dependent mitophagy was inhibited. Finally, PD suppressed NLRP3 inflammasome activation that was also dependent on Parkin-mediated mitophagy. CONCLUSIONS These findings indicate that Parkin-mediated mitophagy is important for the protective effect of PD in SI-AKI, and the underlying mechanisms include the inhibition of mitochondrial dysfunction and NLRP3 inflammasome activation.