Engineered lentivector targeting of dendritic cells for in vivo immunization

We report a method of inducing antigen production in dendritic cells by in vivo targeting with lentiviral vectors that specifically bind to the dendritic cell–surface protein DC-SIGN. To target dendritic cells, we enveloped the lentivector with a viral glycoprotein from Sindbis virus engineered to be DC-SIGN–specific. In vitro, this lentivector specifically transduced dendritic cells and induced dendritic cell maturation. A high frequency (up to 12%) of ovalbumin (OVA)-specific CD8+ T cells and a significant antibody response were observed 2 weeks after injection of a targeted lentiviral vector encoding an OVA transgene into naive mice. This approach also protected against the growth of OVA-expressing E.G7 tumors and induced regression of established tumors. Thus, lentiviral vectors targeting dendritic cells provide a simple method of producing effective immunity and may provide an alternative route for immunization with protein antigens

Selective Molecular Alterations in the Autophagy Pathway in Patients with Lewy Body Disease and in Models of α-Synucleinopathy

Lewy body disease is a heterogeneous group of neurodegenerative disorders characterized by α-synuclein accumulation that includes dementia with Lewy bodies (DLB) and Parkinson's Disease (PD). Recent evidence suggests that impairment of lysosomal pathways (i.e. autophagy) involved in α-synuclein clearance might play an important role. For this reason, we sought to examine the expression levels of members of the autophagy pathway in brains of patients with DLB and Alzheimer's Disease (AD) and in α-synuclein transgenic mice.By immunoblot analysis, compared to controls and AD, in DLB cases levels of mTor were elevated and Atg7 were reduced. Levels of other components of the autophagy pathway such as Atg5, Atg10, Atg12 and Beclin-1 were not different in DLB compared to controls. In DLB brains, mTor was more abundant in neurons displaying α-synuclein accumulation. These neurons also showed abnormal expression of lysosomal markers such as LC3, and ultrastructural analysis revealed the presence of abundant and abnormal autophagosomes. Similar alterations were observed in the brains of α-synuclein transgenic mice. Intra-cerebral infusion of rapamycin, an inhibitor of mTor, or injection of a lentiviral vector expressing Atg7 resulted in reduced accumulation of α-synuclein in transgenic mice and amelioration of associated neurodegenerative alterations.This study supports the notion that defects in the autophagy pathway and more specifically in mTor and Atg7 are associated with neurodegeneration in DLB cases and α-synuclein transgenic models and supports the possibility that modulators of the autophagy pathway might have potential therapeutic effects

Nurses\u27 Perceptions of Barriers and Facilitators Affecting the Shaken Baby Syndrome Education Initiative: An Exploratory Study of a Massachusetts Public Policy

Objective: To assess nurses\u27 perceptions of barriers to and facilitators of implementation of the shaken baby syndrome (SBS) public policy. Background: A legislative Act providing for the prevention of SBS was passed in Massachusetts in November 2006. A stipulation of this Act was the provision of a program to educate parents/guardians of newborns about SBS prevention. The Conceptual Model of Nursing and Health Policy (Fawcett & Russell, 2001; Russell & Fawcett, 2005) and the Neuman Systems Model (Neuman & Fawcett, 2011) guided this study. Methods: A cross-sectional survey of 13 Massachusetts birthing hospitals was completed using a Web-based survey (hosted by Qualtrics, Provo, Utah). Selected hospital, nurse, patient, and guideline characteristics were analyzed using descriptive, bivariate, and logistic regression analyses. Qualitative analysis was completed for responses to two open-ended survey questions. Results: Hospital nurses\u27 responses (N≈922, 155 responded) revealed barriers to and facilitators of SBS guideline implementation. The disadvantage of Web-based surveys as they relate to the challenges of enlisting cooperation, and a lack of direct access to the nurses may have attributed to the low response rate for this study. Themes from the qualitative analysis revealed a lack of SBS brochures, and an inability to provide SBS education for non-English speaking parents/guardians as barriers to SBS education. Nurses who agreed or strongly agreed that there were SBS brochures available in different languages were three times more likely (OR=3.04) to always implement each of the SBS guidelines (P=0.012, 95% CI=1.27-7.27) compared to those nurses who disagreed or strongly disagreed. An atmosphere of supportive leadership facilitated implementation of the SBS guidelines by nurses. This hospital characteristic had a significant effect on nurses\u27 provision of the SBS brochure (OR=3.275, P=0.045, 95% CI=1.02-10.44), and documentation about SBS education in the medical record (OR=7.90, P=0.010, 95% CI=1.62-38.45). Conclusion: A lack of SBS brochures in different languages and inability to provide SBS education for non-English speaking parents/guardians were perceived by nurses to be barriers to implementation of SBS education. The results of this study can be used to inform future research. A larger sample size would help to improve the generalizability of study findings

Going Wi-Fi in Canada: municipal and community initiatives

Urban community Wi-Fi in Canada is at a nascent stage; active non-profit groups through dedicated volunteers, support the development or deployment of Wi-Fi services in community spaces throughout their regions. This article discusses recent initiatives

Iridoids from Gardenia jasminoides

The dichloromethane extract of the air-dried flowers of Gardenia jasminoides Ellis. afforded a new iridoid natural product (1), and a diastereomeric mixture of two new iridoids (2a and 2b) in a 2 : 1 ratio. Their structures were elucidated by extensive 1D and 2D NMR spectroscopy. Antimicrobial tests on 1 indicated that it was moderately active against Candida albicans; slightly active against E. coli, Pseudomonas aeruginosa, Staphylococcus. aureus, and Trichophyton mentagrophytes; and inactive against Bacillus subtilis and Aspergillus niger

Unintentional Window Falls in Children and Adolescents.

OBJECTIVE: Unintentional window falls represent a preventable source of injury and death in children. Despite major campaigns in some larger cities, there continue to be unintentional falls from windows throughout the United States. We aimed to identify risk factors and trends in unintentional window falls in the pediatric population in a national and regional sample. METHODS: A retrospective analysis of annual ED visits from the National Electronic Injury Surveillance System (NEISS) using product codes specific to windows, as well as patient encounters for unintentional window falls from January 2007 - August 2017 using site-specific trauma registries from 10 tertiary care children\u27s hospitals in New England. National and state-specific census population estimates were used to compute rates per 100,000 population. RESULTS: There were 38,840 ED visits and 496 regional patients who unintentionally fell from a window across the study period between 0-17 years old. The majority of falls occurred in children under the age of 6, and were related to falls from a second story or below. A decreased trend in national ED visits was seen, but no change in rates over time for regional trauma center encounters. A high number of falls were found to occur in smaller cities surrounding metropolitan areas and from single family residences. CONCLUSIONS: Falls from windows represent a low proportion of overall types of unintentional sources of injury in children, but are a high-risk for severe disability. These results provide updated epidemiologic data for targeted intervention programs, as well as raise awareness for continued education and advocacy