DNA Vaccines Encoding Antigen Targeted to MHC Class II Induce Influenza-Specific CD8+ T Cell Responses, Enabling Faster Resolution of Influenza Disease

Current influenza vaccines are effective but imperfect, failing to cover against emerging strains of virus and requiring seasonal administration to protect against new strains. A key step to improving influenza vaccines is to improve our understanding of vaccine induced protection. Whilst it is clear that antibodies play a protective role, vaccine induced CD8+ T cells can improve protection. To further explore the role of CD8+ T cells we used a DNA vaccine that encodes antigen dimerised to an immune cell targeting module. Immunising CB6F1 mice with the DNA vaccine in a heterologous prime boost regime with the seasonal protein vaccine improved the resolution of influenza disease compared to protein alone. This improved disease resolution was dependent on CD8+ T cells. However, DNA vaccine regimes that induced CD8+ T cells alone were not protective and did not boost the protection provided by protein. The MHC targeting module used was an anti-I-Ed single chain antibody specific to the BALB/c strain of mice. To test the role of MHC targeting we compared the response between BALB/c, C57BL/6 mice and an F1 cross of the two strains (CB6F1). BALB/c mice were protected, C57BL/6 were not and the F1 had an intermediate phenotype; showing that the targeting of antigen is important in the response. Based on these findings, and in agreement with other studies using different vaccines, we conclude that in addition to antibody, inducing a protective CD8 response is important in future influenza vaccines

The Global Health interactive Curricula Experience (iCE) Platform & App : Technology that Enables Inter-professional Innovation

Global Health Initiatives Committee (GHIC) Serves the Jefferson community as the premier point of engagement for students & faculty interested in medical and public health issues that transcend national boundaries Creates an institutional focus on preparing students for public service careers in population health and public policy at local, national, and global levels To enable all TJU faculty to: - Deliver global health education, in a friendly, interactive format - Does not require an expert to deliver - Can be used in very small or large pieces depending on your need

Building Interprofessional Global Health Infrastructure at a University and Health System: Navigating Challenges and Scaling Successes

Mission: Global Jefferson will create sustainable programs of global distinction through collaboration that position Jefferson as a local and international destination and resource for education, research, and clinical activities. Global Jefferson is supported by the Associate Provost for Global Affairs, part of the Office of the Provost. Global activity at Jefferson includes: Global Health Initiatives Committee (GHIC) Service Learning Global Research & Exchange between institutions Pre-clinical, translational, clinical, and applied research Poster presented at: 8th Annual Global Health Conference of the Consortium of Universities for Global Health (CUGH)https://jdc.jefferson.edu/globalhealthposters/1000/thumbnail.jp

Gefäßchirurgische Ausbildung in endovaskulärer Technik in Lausanne

Zusammenfassung: Zwischen 1995 und 2005 wuchs die Anzahl der jährlich von uns mit endovaskulären Techniken versorgten Aortenaneurysmen (EVAR) von 0 auf 50, und dies auf allen Stufen der Aorta. Zu unserer Organisation gehören ein breites Team von Chirurgen, ein Lager mit 3kompletten Familien von Endoprothesen (gerade Endoprothesen, konische Endoprothesen, und Bifurkationen), ein mobiler Wagen mit Zubehör (Einführungsbestecke, Führungsdrähte, Katheter, Ballone etc.) und ein Apparat auf Rädern für die intravaskuläre Ultraschalluntersuchung (IVUS). Letzterer erlaubt es zusammen mit einer mobilen Durchleuchtungsanlage (C-Bogen), in jedem Operationssaal unserer Institution endovaskulär Aneurysmen zu analysieren, und dies in der Regel ohne Angiographie bzw. Kontrastmittel. Deshalb sind wir nicht mehr auf eine ausgiebige bildgebende präoperative Abklärung potenzieller Kandidaten für eine endovaskuläre Sanierung von Aneurysmen angewiesen und können rupturierte Aneurysmen der Bauchaorta oder der thorakalen Aorta ohne Verzug behandeln. Bei der endovaskulären Sanierung von Aortenaneurysmen unterscheiden wir zwischen Prozessschritten (Indikationsstellung, Darstellung der Zugangsgefäße, Ausmessen mittels IVUS und Roadmapping mittels Durchleuchtung, Implantatwahl, Implantatinsertion, Positionierung, Implantatabwurf, Erfolgsbeurteilung, Rekonstruktion der Zugangsgefäße und Nachkontrolle) und Kompetenzstufen (Assistent, Oberarzt, Leitender Arzt). Unsere ultraschallgestützte Technik zur endovaskulären Sanierung von Aneurysmen wurde mittels IVUS-Transporter und Telementoring erfolgreich auch anderen Institutionen zur Verfügung gestell

“That little doorway where I could suddenly start shouting out”: barriers and enablers to the disclosure of distressing voices

Hearing distressing voices is a key feature of psychosis. The time between voice onset and disclosure may be crucial as voices can grow in complexity. This study investigated barriers and enablers to early voice disclosure. Interviews with 20 voice hearers underwent Thematic Analysis. Beliefs about the effect of disclosure on self and others acted as a barrier and enabler to voices being discussed. Voice hearing awareness should be increased amongst young people, the public and care services. To support earlier disclosure measures need to increase skill amongst those likely to be disclosed to

Long-Term Potentiation: One Kind or Many?

Do neurobiologists aim to discover natural kinds? I address this question in this chapter via a critical analysis of classification practices operative across the 43-year history of research on long-term potentiation (LTP). I argue that this 43-year history supports the idea that the structure of scientific practice surrounding LTP research has remained an obstacle to the discovery of natural kinds

Sociological and Human Developmental Explanations of Crime: Conflict or Consensus

This paper examines multidisciplinary correlates of delinquency in an attempt to integrate sociological and environmental theories of crime with human developmental and biological explanations of crime. Structural equation models are applied to assess links among biological, psychological, and environmental variables collected prospectively from birth through age 17 on a sample of 800 black children at high risk for learning and behavioral disorders. Results show that for both males and females, aggression and disciplinary problems in school during adolescence are the strongest predictors of repeat offense behavior. Whereas school achievement and family income and stability are also significant predictors of delinquency for males, early physical development is the next strongest predictor for females. Results indicate that some effects on delinquency also vary during different ages. It is suggested that behavioral and learning disorders have both sociological and developmental correlates and that adequate educational resources are necessary to ensure channels of legitimate opportunities for high-risk youths

Short-term efficacy of physical interventions in osteoarthritic knee pain. A systematic review and meta-analysis of randomised placebo-controlled trials.

BACKGROUND: Treatment efficacy of physical agents in osteoarthritis of the knee (OAK) pain has been largely unknown, and this systematic review was aimed at assessing their short-term efficacies for pain relief. METHODS: Systematic review with meta-analysis of efficacy within 1-4 weeks and at follow up at 1-12 weeks after the end of treatment. RESULTS: 36 randomised placebo-controlled trials (RCTs) were identified with 2434 patients where 1391 patients received active treatment. 33 trials satisfied three or more out of five methodological criteria (Jadad scale). The patient sample had a mean age of 65.1 years and mean baseline pain of 62.9 mm on a 100 mm visual analogue scale (VAS). Within 4 weeks of the commencement of treatment manual acupuncture, static magnets and ultrasound therapies did not offer statistically significant short-term pain relief over placebo. Pulsed electromagnetic fields offered a small reduction in pain of 6.9 mm [95% CI: 2.2 to 11.6] (n = 487). Transcutaneous electrical nerve stimulation (TENS, including interferential currents), electro-acupuncture (EA) and low level laser therapy (LLLT) offered clinically relevant pain relieving effects of 18.8 mm [95% CI: 9.6 to 28.1] (n = 414), 21.9 mm [95% CI: 17.3 to 26.5] (n = 73) and 17.7 mm [95% CI: 8.1 to 27.3] (n = 343) on VAS respectively versus placebo control. In a subgroup analysis of trials with assumed optimal doses, short-term efficacy increased to 22.2 mm [95% CI: 18.1 to 26.3] for TENS, and 24.2 mm [95% CI: 17.3 to 31.3] for LLLT on VAS. Follow-up data up to 12 weeks were sparse, but positive effects seemed to persist for at least 4 weeks after the course of LLLT, EA and TENS treatment was stopped. CONCLUSION: TENS, EA and LLLT administered with optimal doses in an intensive 2-4 week treatment regimen, seem to offer clinically relevant short-term pain relief for OAK

Accounting Problems Under the Excess Profits Tax

DNA vaccines based on subunits from pathogens have several advantages over other vaccine strategies. DNA vaccines can easily be modified, they show good safety profiles, are stable and inexpensive to produce, and the immune response can be focused to the antigen of interest. However, the immunogenicity of DNA vaccines which is generally quite low needs to be improved. Electroporation and co-delivery of genetically encoded immune adjuvants are two strategies aiming at increasing the efficacy of DNA vaccines. Here, we have examined whether targeting to antigen-presenting cells (APC) could increase the immune response to surface envelope glycoprotein (Env) gp120 from Human Immunodeficiency Virus type 1 (HIV- 1). To target APC, we utilized a homodimeric vaccine format denoted vaccibody, which enables covalent fusion of gp120 to molecules that can target APC. Two molecules were tested for their efficiency as targeting units: the antibody-derived single chain Fragment variable (scFv) specific for the major histocompatilibility complex (MHC) class II I-E molecules, and the CC chemokine ligand 3 (CCL3). The vaccines were delivered as DNA into muscle of mice with or without electroporation. Targeting of gp120 to MHC class II molecules induced antibodies that neutralized HIV-1 and that persisted for more than a year after one single immunization with electroporation. Targeting by CCL3 significantly increased the number of HIV-1 gp120-reactive CD8(+) T cells compared to non-targeted vaccines and gp120 delivered alone in the absence of electroporation. The data suggest that chemokines are promising molecular adjuvants because small amounts can attract immune cells and promote immune responses without advanced equipment such as electroporation.Funding Agencies|Research Council of Norway; Odd Fellow</p