Human mammary tumor virus (HMTV) in endometrial carcinoma.

OBJECTIVE: Human mammary tumor virus (HMTV) is 90% to 98% homologous to mouse mammary tumor virus, the etiological agent of mammary tumors in mice. Human mammary tumor virus sequences were found in 40% of the breast cancers studied in both American and Australian women. In addition, 10% of endometrial carcinomas studied in Australian women also contained HMTV sequences. We have explored the possibility that endometrial cancer of American women may also contain HMTV. METHODS/MATERIALS: Nested polymerase chain reactions, radioactive internal probing, and sequencing were used to establish the presence of unique nucleotide sequences of HMTV in human genomic DNA. The genomic DNAs were tested to guarantee that they were free of murine DNA. Immunohistochemistry with a monoclonal antibody specific for HMTV envelope protein demonstrated that HMTV sequences were translated. RESULTS: Thirteen (23.2%) of 56 of the endometrial cancers studied contained HMTV sequences and proteins. Human mammary tumor virus sequences and protein were not detected in the 33 normal endometria studied. CONCLUSION: Human mammary tumor virus, an agent with high homology to mouse mammary tumor virus, was found in 23.2% of the endometrial cancers studied, thus opening the possibility of a pathogenic role.

Forecasting emergency department crowding: an external, multicenter evaluation.

STUDY OBJECTIVE: We apply a previously described tool to forecast emergency department (ED) crowding at multiple institutions and assess its generalizability for predicting the near-future waiting count, occupancy level, and boarding count. METHODS: The ForecastED tool was validated with historical data from 5 institutions external to the development site. A sliding-window design separated the data for parameter estimation and forecast validation. Observations were sampled at consecutive 10-minute intervals during 12 months (n=52,560) at 4 sites and 10 months (n=44,064) at the fifth. Three outcome measures-the waiting count, occupancy level, and boarding count-were forecast 2, 4, 6, and 8 hours beyond each observation, and forecasts were compared with observed data at corresponding times. The reliability and calibration were measured following previously described methods. After linear calibration, the forecasting accuracy was measured with the median absolute error. RESULTS: The tool was successfully used for 5 different sites. Its forecasts were more reliable, better calibrated, and more accurate at 2 hours than at 8 hours. The reliability and calibration of the tool were similar between the original development site and external sites; the boarding count was an exception, which was less reliable at 4 of 5 sites. Some variability in accuracy existed among institutions; when forecasting 4 hours into the future, the median absolute error of the waiting count ranged between 0.6 and 3.1 patients, the median absolute error of the occupancy level ranged between 9.0% and 14.5% of beds, and the median absolute error of the boarding count ranged between 0.9 and 2.8 patients. CONCLUSION: The ForecastED tool generated potentially useful forecasts of input and throughput measures of ED crowding at 5 external sites, without modifying the underlying assumptions. Noting the limitation that this was not a real-time validation, ongoing research will focus on integrating the tool with ED information systems.

Design of novel histone-derived antimicrobial peptides.

Previous studies have identified several naturally occurring antimicrobial peptides derived from histone proteins. This research aimed to design novel histone-derived antimicrobial peptides (HDAPs). To this end, three novel peptides (DesHDAP1, DesHDAP2, and DesHDAP3) were designed based on a histone-DNA crystal structure and structural properties of buforin II, the best characterized naturally occurring HDAP. Molecular dynamics simulations and circular dichroism spectroscopy were used to further support the predicted structure and potential nucleic acid interactions of these three designed peptides. The antibacterial activity of the three peptides was then verified experimentally against a series of bacterial strains using a radial diffusion assay. One of these peptides is the first known fragment of histone H3 with antibacterial properties. Optical density measurements of bacterial cells exposed to the designed peptides implied that at least two of the novel peptides can induce cell death without causing significant membrane permeabilization, as observed for buforin II. The antibacterial potency of these designed HDAPs does not appear to correlate with their overall alpha-helical content, unlike previous observations for analogs of buforin II. However, the most potent designed peptide, DesHDAP1, shares a markedly similar circular dichroism spectrum with buforin II. These results demonstrate the potential of using histone structures as a framework for designing novel antimicrobial peptides. As well, these studies represent an important starting point for a broader characterization of properties shared by HDAPs.