Globally, respiratory syncytial virus (RSV) is a major cause of death in children under 1 year of age, yet no vaccine is available. We have generated a novel RSV live attenuated vaccine candidate containing mutations in the L and G proteins.

Objective. To conduct and evaluate the outcomes of a pharmacy faculty and preceptor development program to foster self-awareness and self-confidence. Methods. A faculty and preceptor development intervention was implemented in a multi-campus college of pharmacy to promote and assess for improvements in self-awareness and self-confidence. Faculty members and preceptors were surveyed regarding their self-perceptions and confidence at baseline and following an intervention in which they completed the Birkman Method self-assessment and participated in a training program with an active-learning component. A longitudinal follow-up survey was conducted to assess the long-term impacts of the intervention. Results. Faculty members and preceptors experienced significant improvements in self-awareness from baseline following the development intervention. They also experienced increases in self-confidence related to coaching. A survey evaluating the longitudinal impact of the intervention indicated a positive association between receiving a sufficient level of Birkman Method training and improved ability of both faculty members and preceptors to manage professional relationships. Similarly, a positive association was identified between the sufficiency of training and preceptors' confidence in their ability to manage personal relationships and stress following the intervention. Conclusion. Faculty members and preceptors teach students to be more self-aware and confident, yet both groups often need to grow in these areas themselves. A faculty and preceptor development intervention using the Birkman Method self-assessment is one approach to facilitating growth in these educators' self-awareness and self-confidence.

Eine Vollwandresektion im Kolon und Rektum ist einer endoskopischen Submukosadissektion (ESD) im Hinblick auf Kuration, En-bloc-Resektion und R0-Status überlegen. Das Full-Thickness-Device (FTRD, Ovesco, Germany) ist das erste kommerziell erhältliche endoskopische System, das eine peritoneale Verschlusstechnik mit nachfolgender Vollwandresektion in einem Schritt realisiert.

Duchenne muscular dystrophy is a monogenic disease potentially treatable by gene replacement. Use of recombinant adeno-associated virus (AAV) will ultimately require a vascular approach to broadly transduce muscle cells. We tested the impact of preexisting MV antibodies on microdystrophin expression following vascular delivery to nonhuman primates. Rhesus macaques were treated by isolated limb perfusion using a fluoroscopically guided catheter. In addition to serostatus stratification, the animals were placed into one of the three immune suppression groups: no immune suppression, prednisone, and triple immune suppression (prednisone, tacrolimus, and mycophenolate mofetil). The animals were analyzed for transgene expression at 3 or 6 months. Microdystrophin expression was visualized in MV, rhesus serotype 74 sero-negative animals (mean: 48.0 +/- 20.8%) that was attenuated in sero-positive animals (19.6 +/- 18.7%). Immunosuppression did not affect transgene expression. Importantly, removal of MV binding antibodies by plasmapheresis in MV sero-positive animals resulted in high-level transduction (60.8 +/- 18.0%), which is comparable with that of MV sero-negative animals (53.7 +/- 7.6%), whereas non-pheresed sero-positive animals demonstrated significantly lower transduction levels (10.1 +/- 6.0%). These data support the hypothesis that removal of AAV binding antibodies by plasnnapheresis permits successful and sustained gene transfer in the presence of preexisting immunity (natural infection) to MV.

ObjectiveIn the face of an outbreak of pigeon paramyxovirus (PPMV), a vaccination response study was undertaken to determine if pigeons in Australia would produce a serological response similar to that considered protective in chickens.DesignA vaccination study evaluated serological response and safety criteria in groups of 20 pigeons.MethodsOne group served as unvaccinated controls; one group was vaccinated with a live V4 strain of Newcastle disease virus (NDV) and subsequently revaccinated 28 days later with an inactivated La Sota strain vaccine; the third group was vaccinated twice with the inactivated La Sota strain vaccine 28 days apart. Serum was collected from the birds for serology 28, 56, 120 and 196 days after each treatment. Safety of the vaccines was determined using observation of the birds and body weight change. Serology was performed using three variations of the haemagglutination inhibition (HI) test, including chicken red blood cells (RBC) with either V4 NDV or PPMV as the antigen and pigeon RBC with V4 NDV as the antigen. A commercial NDV ELISA test was also used.ResultsAt 28 days after the second vaccination, the geometric mean titres were 6.8 and 7.3 for the live/inactivated vaccine regimen and the inactivated/inactivated regimen, respectively. The serological response of birds vaccinated with the inactivated/inactivated regimen was significantly greater than that of the controls for all of the serological tests used.ConclusionVaccination of pigeons with two doses of chicken NDV vaccine 28 days apart was safe and resulted in antibody levels considered protective for NDV in chickens.

Finding mechanisms of viral resistance and new ways to tackle chronic hepatitis will help find a cure for this disease. In 'Bench to Bedside', Christopher Walker and Benoît Callendret highlight studies showing that overcoming immune exhaustion during chronic infection by blocking several inhibitory pathways of T cells may restore an adequate immune response. In 'Bedside to Bench', Lawrence Corey, Joshua Schiffer and John Scott discuss recent advances in antiviral therapy with protease inhibitors and the findings of a mathematical model that predicts possible single and double mutations prior to antiviral therapy.

, 6ra15 (2009); 1 Sci Transl Med , et al. Janaiah Kota in Nonhuman Primates Follistatin Gene Delivery Enhances Muscle Growth and Strength http://stm.sciencemag.org/content/1/6/6ra15.full.html figures, can be found at: and other services, including high-resolution A complete electronic version of this article http://stm.sciencemag.org/content/suppl/2009/11/06/1.6.6ra15.DC1.html "Supplementary Material" can be found at: Supporting Online Material http://stm.sciencemag.org/content/1/6/6ra15.full.html#ref-list-1 , 16 of which can be accessed free: cites 46 articles This article http://stm.sciencemag.org/content/1/6/6ra15.full.html#related-urls 1 articles hosted by HighWire Press; see: cited by This article has been http://www.sciencemag.org/about/permissions.dtl in whole or in part can be found at: reproduce this article permission to of this article or about obtaining reprints Information about obtaining

Ultraviolet (UV) germicidal air disinfection is an engineering method used to control the airborne transmission of pathogenic microorganisms in high-risk settings. Despite the recent emergence of respiratory viral pathogens such as SARS and avian influenza viruses, UV disinfection of pathogenic viral aerosols has not been examined. Hence, we characterized the UV disinfection of viral aerosols using the bacteriophage MS2, adenovirus, and coronavirus. Our objectives were to characterize the effect of nebulization and air sampling on the survival of important viral pathogens, quantitatively characterize and estimate the UV susceptibility of pathogenic viral aerosols, and evaluate the effect of relative humidity (RH) on the susceptibility of viral aerosols, to 254 nm UV-C. The viruses were aerosolized into an experimental chamber using a six-jet Collison nebulizer, exposed to 254 nm UV, and sampled using an AGI-30 liquid impinger. Both the MS2 and adenovirus aerosols were very resistant to UV air disinfection, with a reduction of less than 1 logarithm in viable viral aerosols at a UV dose of 2608 microW s/cm2. The susceptibility of coronavirus aerosols was 7-10 times that of the MS2 and adenovirus aerosols. Unlike bacterial aerosols, there was no significant protective effect of high RH on UV susceptibility of the tested viral aerosols. We confirmed that the UV disinfection rate differs greatly between viral aerosols and viruses suspended in liquid.

The hepatitis C virus (HCV) infects approximately three percent of the world's population. Some individuals resolve the infection spontaneously, but the majority develop persistent viremia that often causes progressive liver disease. There is an emerging consensus that cellular immune responses are essential for spontaneous resolution of acute hepatitis C and long-term protection from persistent infection. This review focuses on the recent advances in understanding mechanisms of protective immunity and why they fail in most infected individuals. The distinct yet complementary role of CD4+ and CD8+ T lymphocytes in this process is highlighted.

Mutations in the p53 tumor-suppressor gene contribute to the development of skin cancer, and the spectrum of mutations in this gene correlates with specific physical and chemical carcinogens in the environment. Cosmetics may contain alcohols and/or aloe emodin (AE). Although these compounds are not carcinogenic when applied to the skin, they may increase the carcinogenicity of ultraviolet (UV) radiation. We investigated whether ethanol (EtOH) and AE alone or combined with UV radiation cause mutations in the p53 gene. In the absence of UV radiation, C3H/HeN mice chronically treated for up to 33 wk with AE in 25% EtOH-in-water vehicle or vehicle alone failed to develop tumors and had no mutations in exons 4-8 of the p53 gene. UV radiation alone induced skin tumors, which had mutations predominantly in p53 exons 5 and 8. In contrast, mutations arising in UV + EtOH-or UV + AE-treated groups were more broadly distributed throughout the p53 gene. Mutations were found in exons 4, 6, and 7, as well as in exons 5 and 8. This altered distribution of mutations across the p53 DNA sequence more closely resembles the pattern observed in TP53 from human skin tumors at sun-exposed sites than that in the p53 gene of mice treated with UV alone. Thus, treatment with UV radiation in combination with two chemicals not thought to be carcinogenic, alcohol, and AE results in a broader distribution of mutations in a critical tumor-suppressor gene.

We have conducted an analysis of genetic alterations in spontaneous murine melanoma cell line B16F0 and its two metastatic clones, B16F1 and B16F10 and the carcinogen-induced murine melanoma cell lines CM519, CM3205, and K1735. We found that unlike human melanomas, the murine melanoma cell lines did not have activating mutations in the Braf oncogene at exon 11 or 15. However, there were distinct patterns of alterations in the ras, Ink4a/Arf, and p53 genes in the two melanoma groups. In the spontaneous B16 melanoma cell lines, expression of p16Ink4a and p19Arf tumor suppressor proteins was lost as a consequence of a large deletion spanning Ink4a/Arf exons 1α, 1β, and 2. In contrast, the carcinogen-induced melanoma cell lines expressed p16Ink4a but had inactivating mutations in either p19Arf (K1735) or p53 (CM519 and CM3205). Inactivation of p19Arf or p53 in carcinogen-induced melanomas was accompanied by constitutive activation of mitogen-activated protein kinases (MAPKs) and/or mutation-associated activation of N-ras. These results indicate that genetic alterations in p16Ink4a/p19Arf, p53 and ras-MAPK pathways can cooperate in the development of murine melanoma.

In the first preventative human immunodeficiency virus (HIV) vaccine study to be carried out in Africa, 40 HIV-seronegative Ugandan volunteers were randomly assigned to receive a canarypox vector containing HIV-1 clade B (env and gag-pro) antigens (ALVAC-HIV; n = 20), control vector containing the rabies virus glycoprotein G gene (n = 10), or saline placebo (n = 10). Cytotoxic T lymphocyte activity against target cells expressing clade A, B, and D antigens was assessed using standard chromium-release and confirmatory interferon-gamma enzyme-linked immunospot (ELISPOT) assays. Neutralizing antibody responses to cell line-adapted strains and primary isolates in all 3 clades were also tested. Twenty percent of vaccine recipients generated detectable cytolytic responses to either Gag or Env, and 45% had vaccine-induced HIV-specific CD8(+) T cell responses, as measured by the ELISPOT assay. In contrast, only 5% of the control group had vaccine-specific responses. Neutralizing antibodies against primary and laboratory-adapted HIV-1 clade B strains were seen in 10% and 15% of vaccine recipients, respectively, but responses against clades A and D were not detected. Although the immunogenicity of this clade B-based vaccine was low, ALVAC-HIV elicited CD8(+) T cell responses with detectable cross-activity against clade A and D antigens in a significant proportion of vaccine recipients.