Human papillomavirus (HPV) is the most prevalent sexually transmitted disease in the United States, and can cause cancer with persistent infection. The most common cancer caused by HPV is cervical carcinoma with an average of 12,000 cases reported every year in the U.S. Worldwide, over 500,000 cases of cervical cancer are reported yearly with over 250,000 deaths attributed to the disease. Although much is known about the serious health risks associated with HPV infection, there is still much to be discovered about how HPV binds and enters target cells. Understanding how HPV infects will lead to strategies and therapies for reducing the number of infections and HPV-related diseases, including cancers. The HPV viral particle is composed of two viral proteins, L1 and L2. Data suggest that binding of the viral capsid to cells is dependent on the L1 protein. We hypothesize that this initial binding to a heparan sulfate is composed of two independent events: the first results in a structural change that exposes a hidden portion of the L1 protein leading to a second binding event on the heparan sulfate. Our experiments tested if this “hidden” portion of L1 is necessary for infection and explored the nature of this binding. We generated a peptide with the sequence of the “hidden” portion of L1. Infection of HaCaT cells in the presence of this peptide is highly reduced. Our results suggest that the binding of the L1 C-terminal domain is dependent on amino acid sequence, and is necessary for infection.
Background: The Modified Early Warning Score (MEWS) has been proposed to warn healthcare providers of potentially serious adverse events. We evaluated this scoring system during unplanned escalation of care in hospitalized surgical patients during a 1-year period. Methods: Following institutional review board approval, all consecutive, unplanned surgical admissions into the surgical intensive care unit (SICU) during 2016 were entered into this study. MEWS and patient demographics during bedside evaluation for SICU admission were extracted from electronic medical records. Logistic regression was used to analyze the association of MEWS with the incidence of future mortality. P values were set at <0.01 for statistical significance. Results: In this series of 263 consecutive patients, the incidence of mortality following unplanned escalation of care was 29.3% (confidence interval [CI] 24.1% to 35.0%), ranging from 22% to 57%, with all positive MEWS values. The association of MEWS with future mortality was not statistically significant (P=0.0107). A misclassification rate of 0.29 (CI 0.24 to 0.35) was observed with this association. Conclusion: MEWS provided no clinical benefit as an early warning system, as mortality was elevated throughout the MEWS scale in this clinical setting. The high misclassification rate indicates MEWS does not provide discriminatory support for patients at risk for mortality.
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