Search

Objective Small molecule inhibitors able to bind to gp120 and prevent CD4-induced HIV-1 envelope conformational change provide an important class of inhibitors. Currently, only Fostemsavir is approved for HAART, which makes this class of inhibitors attractive candidates for prevention. We assessed the activity of DS003 (BMS-599793), an analogue of BMS-378806, in different mucosal tissues and elucidated its mechanism of action. Design Pre-clinical analysis was performed with human mucosal tissue models as surrogates of in vivo activity. Methods Antiviral efficacy of DS003 was assessed in mucosal tissue explants (ecto-cervical, penile and colorectal) and in trans-infection models (co-cultures of dendritic or mucosal migratory cells with CD4+T cells) with several dosing times (2 h, 24 h and sustained) and in combination with a fusion inhibitor. Binding of DS003 to gp120 was assessed by flow cytometry and bio-layer interferometry and further probed in competitive studies using soluble CD4 (sCD4) and an anti-CD4 induced antibody, 17b. Results In all models, the inhibitory activity of DS003 was increased with longer periods of exposure and by combination with a fusion inhibitor. Pre-exposure to sCD4 impeded DS003 binding to viral envelope (Env). In contrast, DS003 did not impact subsequent binding of sCD4. Furthermore, sCD4-induced epitope exposure as assessed by 17b binding was significantly reduced in the presence of DS003. Conclusion DS003 inhibits HIV-1 infection by binding to or near the CD4 binding site of gp120, preventing CD4-induced conformational change essential for viral fusion. These data highlight the potential of DS003 for development as a pre-exposure prophylaxis candidate.

BACKGROUND: HIV-1 CRF01_AE is dominant in Thailand where RV144 vaccine trial was conducted. To study immune correlates of protection in ongoing trials, CRF01_AE derived reagents are essential. Here we present a panel of 14 HIV-1 infectious molecular clones (IMC) identified from different stages of infection, and characterization of their neutralization sensitivity using two standard assays. METHODS: One full-length IMC was constructed using a transmitted-founder virus to express Renilla luciferase (LucR) reporter gene and full-length envelopes (envs) of exogenous HIV-1. A panel of IMCs was generated, expressing envs of viruses from acute (Fiebig stages I/II and I-IV) and chronic (>Febig VI) infection. Neutralization assays were performed using TZM-bl or A3R5 cell lines, and sera or monoclonal antibodies (mAbs). Wilcoxon matched-paired test was used to assess neutralization differences between assays and reagents; correlation coefficients were evaluated by linear regression. RESULTS: Neutralization potency observed was significantly higher in the A3R5 assay when testing mAbs and serum pools (p

The objective of this study was to assess the implementation of recommendations of the Institute of Medicine (IOM) report, The Future of Nursing: Leading Change, Advancing Health.In 2010, the IOM made a series of recommendations aimed at transforming the role of nurses in healthcare delivery.We conducted a multiyear survey, in 2011 and 2013, with nurse leaders who were members of the American Organization of Nurse Executives, the National Nursing Centers Consortium, or the Visiting Nurses Association of America.When comparing 2013 to 2011, we find progress in instituting the IOM's recommendations in 3 areas: (1) raising the proportion of employed RNs with at least a bachelor's degree; (2) expanding the proportion of healthcare institutions with nurse residency programs; and (3) offering opportunities for continuing nurse educationOur findings suggest that healthcare organizations are transforming to support the recommendations of the IOM.

Objective: To determine whether foreign-educated nurses (FENs) perceived they were treated equitably in the U.S. workplace during the last period of high international recruitment from 2003 to 2007. Background: With experts predicting that isolated nursing shortages could return as soon as 2015, it is important to examine the lessons learned during the last period of high international recruitment in order to anticipate and address problems that may be endemic to such periods. In this baseline study, we asked FENs who were recruited to work in the United States between 2003 and 2007 about their hourly wages; clinical and cultural orientation to the United States; wages, benefits, and shift or unit assignments; and job satisfaction. Methods: In 2008, we administered a survey to FENs who were issued VisaScreen certificates by the Commission on Graduates of Foreign Nursing Schools International between 2003 and 2007. We measured four outcomes of interest (hourly wages, job satisfaction, adequacy of orientation, and perceived discrimination) and conducted descriptive and regression analyses to determine if country of education and recruitment model were correlated with the outcomes. Results: We found that 51% of respondents reported receiving insufficient orientation and 40% reported at least one discriminatory practice with regard to wages, benefits, or shift or unit assignments, FENs educated in low-income countries and those recruited by staffing agencies were significantly more likely than other FENs to report that they receive inequitable treatment compared with their U.S. counterparts. Conclusions: These findings raise both practical and ethical concerns that should interest those striving to create positive health care workplace environments and to ensure staff retention. Health care leaders should take steps to ensure that FENs are, and perceive that they are, treated equitably

The 2010 recommendation that the proportion of registered nurses with BSN (bachelor of science in nursing) degrees in the nursing workforce should increase from the current 40% to 80% by the year 2020 has shifted the focus on nurses educational progression from state legislatures-where changes in entry-level requirements were debated for decades-to the executive suites of large healthcare providers. The recommendation, contained in the report titled The Future of Nursing: Leading Change, Advancing Health, by the Robert Wood Johnson Foundation Initiative on the Future of Nursing at the Institute of Medicine, suggests that human resources policies for nurses have the potential to double the rates of college degree completions (IOM, 2010). We surveyed 447 nurse executives in hospitals, nurse-led clinics, and home and hospice companies to explore the current practices of healthcare employers with regard to this recommendation. Almost 80% of respondents reported that their institution either preferred or required newly hired nurses to have a bachelor's degree, and 94% of the facilities offered some level of tuition reimbursement. Only 25%, however, required their nurses to earn a BSN or offered salary differentials on the basis of educational attainment (9%). We conclude that if employers are serious about wanting a more highly educated nurse workforce, they need to adopt requirements for degree completion and wage differentials in the coming years. The likelihood that such policies will be widely adopted, however, is dramatically affected by the dynamics of nursing supply and demand.

The objective of this study was to determine the prevalence of hospital RN residencies and the associated factors.The 2010 Institute of Medicine/Robert Wood Johnson Foundation report, The Future of Nursing: Leading Change, Advancing Health, recommends the adoption of nurse residency programs.Members of the American Organization of Nurse Executives were surveyed, and covariates were identified.We found approximately 36.9% of all hospitals in our study offered a nurse residency in 2011. Associated covariates included not-for-profit status, midsize, and location in the South. Hospitals that offer residency programs were more likely to have other training programs.Findings suggest that residencies have been widely supported even in times of economic recession. It is important to track the expansion of these programs and to initiate research to examine the long-term impacts of residencies on nurse retention and clinical outcomes.