Measurement of Secondary Structure Changes in Poly-L-lysine and Lysozyme during Acoustically Levitated Single Droplet Drying Experiments by In Situ Raman Spectroscopy.

Drying processes such as spray drying, as commonly used in the pharmaceutical industry to convert protein-based drugs into their particulate form, can lead to an irreversible loss of protein activity caused by protein secondary structure changes. Due to the nature of these processes (high droplet number, short drying time), an in situ investigation of the structural changes occurring during a real drying process is hardly possible. Therefore, an approach for the in situ investigation of the expected secondary structural changes during single droplet protein drying in an acoustic levitator by time-resolved Raman spectroscopy was developed and is demonstrated in this paper. For that purpose, a self-developed NIR-Raman sensor generates and detects the Raman signal from the levitated solution droplet. A mathematical spectral reconstruction by multiple Voigt functions is used to quantify the relative secondary structure changes occurring during the drying process. With the developed setup, it was possible to detect and quantify the relative secondary structure changes occurring during single droplet drying experiments for the two chosen model substances: poly-L-lysine, a homopolypeptide widely used as a protein mimic, and lysozyme. Throughout drying, an increase in the ß-sheet structure and a decrease in the other two structural elements, α-helix, and random coil, could be identified. In addition, it was observed that the degree of structural changes increased with increasing temperature.

Preoperative risk evaluation of postoperative morbidity in IBD patients--impact of the POSSUM score.

BACKGROUND: The aim of this study was to assess the morbidity and mortality of patients undergoing surgery for inflammatory bowel disease (IBD) with special focus of the predictive value of the Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (POSSUM) scoring system for preoperative risk adjustment of postoperative morbidity. METHODS: The operative notes and hospital files of 191 patients with IBD were analyzed. The POSSUM scoring system was used to predict morbidity rates after surgery. The physiological sub-score of the POSSUM score was analyzed with regard to its ability to predict postoperative complications. RESULTS: The overall complication rate was 27.7%, and the mortality was 0.5%. The morbidity rate predicted by POSSUM was 28.4% and the mortality rate 7.2%. The mean POSSUM-phys sub-score in patients without the major complications (anastomotic leakages, peritonitis, bleeding) was significant lower compared to patients with at least one of these complications (14.7 vs. 18.6; p < 0.001). Regarding the major complications separately, there were significant differences in the POSSUM-phys scores in patients developing a sepsis (14.1 vs. 23.4; p < 0.001) and/or a peritonitis (14.8 vs. 19.2; p = 0.05), whereas patients developing an anastomotic leakage/suture dehiscence or a postoperative bleeding did not differ significantly. CONCLUSION: POSSUM was an accurate predictor of morbidity in IBD patients and overpredicted mortality. The POSSUM-phys score is a promising instrument for identifying patients at increased risk of developing major postoperative complications after surgery for IBD.

ADAMTS13 activity is decreased in a septic porcine model. Significance for glomerular thrombus deposition.

During sepsis, the balance between abundantly secreted von Willebrand factor (VWF) and the activity of its size regulating protease ADAMTS13 is assumed to be involved in coagulation abnormalities. We aimed to establish a porcine model with haemorrhagic shock with consecutive sepsis and hypothesised that a decreased ADAMTS13-activity as well as an altered VWF multimer pattern is associated with renal failure. Animals (n=21) were subjected to haemorrhagic shock. After volume replacement, intraperitoneal Escherichia coli sepsis was induced. Blood samples were drawn at baseline, after haemorrhage and sepsis induction. Directly postmortem we examined renal tissue by JONES-silver, CD61, VWF and fibrin staining for characterisation of thrombi. Renal failure was analysed by scoring PAS-stained sections for acute tubular damage. Glomerular microthrombi were observed in six of 21 septic animals. Porcine ADAMTS13 activity declined significantly during sepsis, accompanied by a drop-off in platelet count. At 12 hours after sepsis induction, ADAMTS13 activity was significantly diminished compared to sham controls, and an elevated acute tubular damage score was associated with an increased proportion of high-molecular-weight VWF multimers. Compared to baseline the proportion of high-molecular-weight VWF multimers increased significantly in septic animals. Similar to human sepsis, diminished ADAMTS13 activity was observed in a septic porcine model associated with a shift to rather thrombogenic VWF multimers and deposition of microthrombi. Therefore, this porcine model seems to be appropriate for performing functional and therapeutic studies in sepsis-associated ADAMTS13 deficiency.

Responses to prospective payment by rural New Mexico hospitals.

A cross-sectional study is used to determine how rural New Mexico hospitals altered service diversification, inpatient service emphasis, and service promotion during Medicare's prospective payment system (PPS) transition and posttransition phases. Results suggest that the hospitals implemented distinct strategies in response to PPS. The posttransition strategies were examined for their association with improved revenue and utilization indicators. Few of the service diversification and promotional strategies were consistent predictors of performance. Emphasis on fine-tuning inpatient services was the most promising predictor of higher utilization and revenue measures. The implications for other rural hospitals are discussed.

Health promotion and allied health professionals: considerations for program design.

There is growing public and corporate interest in health promotion programs. Available literature suggests that health promotion may contribute to greater longevity and life satisfaction while resulting in lower health care costs. Allied health professionals are perfectly positioned to make the difference between a successful or unsuccessful health promotion effort, whether in their own lives or in the lives of patients. However, allied health professionals need to commit themselves to making behavior changes to improve their own health so that they can effectively assist patients in making similar changes. These ideas are demonstrated through a study of an employee health promotion program for allied health professionals in a health maintenance organization.