Efficacy, Stability, and Biosafety of Sifuvirtide Gel as a Microbicide Candidate against HIV-1

Sifuvirtide is a proven effective HIV-1 entry inhibitor and its safety profile has been established for systemic administration. The present study evaluated the potential of sifuvirtide formulated in a universal gel for topical use as a microbicide candidate for preventing sexual transmission of HIV. Our data showed that sifuvirtide formulated in HEC gel is effective against HIV-1 B, C subtypes, CRF07_BC and CRF01_AE, the latter two recombinants represents the most prevalent strains in China. In addition, we demonstrated that sifuvirtide in gel is stable for at least 8 weeks even at 40°C, and did not cause the disruption of integrity of mucosal epithelial surface, or the up-regulation of inflammatory cytokines both in vitro or in vivo. These results suggest that sifuvirtide gel is an effective, safe and stable product, and should be further tested as a vaginal or rectal microbicide in pre-clinical model or clinical trial for preventing HIV sexual transmission

Evaluation Method, Dataset Size or Dataset Content: How to Evaluate Algorithms for Image Matching?

Most vision papers have to include some evaluation work in order to demonstrate that the algorithm proposed is an improvement on existing ones. Generally, these evaluation results are presented in tabular or graphical forms. Neither of these is ideal because there is no indication as to whether any performance differences are statistically significant. Moreover, the size and nature of the dataset used for evaluation will obviously have a bearing on the results, and neither of these factors are usually discussed. This paper evaluates the effectiveness of commonly used performance characterization metrics for image feature detection and description for matching problems and explores the use of statistical tests such as McNemar’s test and ANOVA as better alternatives

Residents' perceptions of a night float system

Background. A Night Float (NF) system has been implemented by many institutions to address increasing concerns about residents' work hours. The purpose of our study was to examine the perceptions of residents towards a NF system. Methods. A 115-item questionnaire was developed to assess residents' perceptions of the NF rotation as compared with a regular call month. The categories included patient care, education, medical errors, and overall satisfaction. Internal Medicine housestaff (post-graduate years 1-3) from three hospital settings at the University of Pittsburgh completed the questionnaire. Results. The response rate was 90% (n = 149). Of these, 74 had completed the NF rotation. The housestaff felt that the quality of patient care was improved because of NF (41% agreed and 18% disagreed). A majority also felt that better care was provided by a rested physician in spite of being less familiar with the patient (46% agreed and 21% disagreed). Most felt that there was less emphasis on education (65%) and more emphasis on service (52%) during NF. Overall, the residents felt more rested during their call months (83%) and strongly supported the 80-hour workweek requirement (77%). Conclusion. Housestaff felt that the overall quality of patient care was improved by a NF system. The perceived improved quality of care by a rested physician coupled with a perceived decrease in the emphasis on education may have significant implications in housestaff training. © 2009 Jasti et al; licensee BioMed Central Ltd

Serum immunoglobulin G, M and A response to Cryptosporidium parvum in Cryptosporidium-HIV co-infected patients

<p>Abstract</p> <p>Background</p> <p><it>Cryptosporidium parvum</it>, the protozoan parasite, causes a significant enteric disease in immunocompromised hosts such as HIV patients. The present study was aimed to compare serum IgG, IgM and IgA responses to crude soluble antigen of <it>C. parvum </it>in HIV seropositive and seronegative patients co-infected with <it>Cryptosporidium </it>and to correlate the responses with symptomatology.</p> <p>Methods</p> <p><it>Cryptosporidium parvum </it>specific serum antibody (IgG, IgM and IgA) responses were assessed by ELISA in 11 HIV seropositive <it>Cryptosporidium </it>positive (Group I), 20 HIV seropositive <it>Cryptosporidium </it>negative (Group II), 10 HIV seronegative <it>Cryptosporidium </it>positive (Group III), 20 HIV seronegative <it>Cryptosporidium </it>negative healthy individuals (Group IV) and 25 patients with other parasitic diseases (Group V).</p> <p>Results</p> <p>A positive IgG and IgA antibody response was observed in significantly higher number of <it>Cryptosporidium </it>infected individuals (Gp I and III) compared to <it>Cryptosporidium </it>un-infected individuals (Gp II, IV and V) irrespective of HIV/immune status. Sensitivity of IgG ELISA in our study was found to be higher as compared to IgM and IgA ELISA. The number of patients with positive IgG, IgM and IgA response was not significantly different in HIV seropositive <it>Cryptosporidium </it>positive patients with diarrhoea when compared to patients without diarrhoea and in patients with CD4 counts <200 when compared to patients with CD4 counts >200 cells/μl.</p> <p>Conclusion</p> <p>The study showed specific serum IgG and IgA production in patients infected with <it>Cryptosporidium</it>, both HIV seropositive and seronegative as compared to uninfected subjects suggesting induction of <it>Cryptosporidium </it>specific humoral immune response in infected subjects. However, there was no difference in number of patients with positive response in HIV seropositive or seronegative groups indicating that HIV status may not be playing significant role in modulation of <it>Cryptosporidium </it>specific antibody responses. The number of patients with positive IgG, IgM and IgA response was not significantly different in patients with or without history of diarrhoea thereby indicating that <it>Cryptosporidium </it>specific antibody responses may not be necessarily associated with protection from symptomatology.</p

Validation of the Cognitive Assessment of Later Life Status (CALLS) instrument: a computerized telephonic measure

<p>Abstract</p> <p>Background</p> <p>Brief screening tests have been developed to measure cognitive performance and dementia, yet they measure limited cognitive domains and often lack construct validity. Neuropsychological assessments, while comprehensive, are too costly and time-consuming for epidemiological studies. This study's aim was to develop a psychometrically valid telephone administered test of cognitive function in aging.</p> <p>Methods</p> <p>Using a sequential hierarchical strategy, each stage of test development did not proceed until specified criteria were met. The 30 minute Cognitive Assessment of Later Life Status (CALLS) measure and a 2.5 hour in-person neuropsychological assessment were conducted with a randomly selected sample of 211 participants 65 years and older that included equivalent distributions of men and women from ethnically diverse populations.</p> <p>Results</p> <p>Overall Cronbach's coefficient alpha for the CALLS test was 0.81. A principal component analysis of the CALLS tests yielded five components. The CALLS total score was significantly correlated with four neuropsychological assessment components. Older age and having a high school education or less was significantly correlated with lower CALLS total scores. Females scored better overall than males. There were no score differences based on race.</p> <p>Conclusion</p> <p>The CALLS test is a valid measure that provides a unique opportunity to reliably and efficiently study cognitive function in large populations.</p

Heart rate variability (HRV) and muscular system activity (EMG) in cases of crash threat during simulated driving of a passenger car

Objectives: The aim of the study was to verify whether simultaneous responses from the muscular and circulatory system occur in the driver's body under simulated conditions of a crash threat. Materials and Methods: The study was carried out in a passenger car driving simulator. The crash was included in the driving test scenario developed in an urban setting. In the group of 22 young male subjects, two physiological signals - ECG and EMG were continuously recorded. The length of the RR interval in the ECG signal was assessed. A HRV analysis was performed in the time and frequency domains for 1-minute record segments at rest (seated position), during undisturbed driving as well as during and several minutes after the crash. For the left and right side muscles: m. trapezius (TR) and m. flexor digitorum superficialis (FDS), the EMG signal amplitude was determined. The percentage of maximal voluntary contraction (MVC) was compared during driving and during the crash. Results: As for the ECG signal, it was found that in most of the drivers changes occurred in the parameter values reflecting HRV in the time domain. Significant changes were noted in the mean length of RR intervals (mRR). As for the EMG signal, the changes in the amplitude concerned the signal recorded from the FDS muscle. The changes in ECG and EMG were simultaneous in half of the cases. Conclusion: Such parameters as mRR (ECG signal) and FDS-L amplitude (EMG signal) were the responses to accident risk. Under simulated conditions, responses from the circulatory and musculoskeletal systems are not always simultaneous. The results indicate that a more complete driver's response to a crash in road traffic is obtained based on parallel recording of two physiological signals (ECG and EMG)

Fitness of Escherichia coli during Urinary Tract Infection Requires Gluconeogenesis and the TCA Cycle

Microbial pathogenesis studies traditionally encompass dissection of virulence properties such as the bacterium's ability to elaborate toxins, adhere to and invade host cells, cause tissue damage, or otherwise disrupt normal host immune and cellular functions. In contrast, bacterial metabolism during infection has only been recently appreciated to contribute to persistence as much as their virulence properties. In this study, we used comparative proteomics to investigate the expression of uropathogenic Escherichia coli (UPEC) cytoplasmic proteins during growth in the urinary tract environment and systematic disruption of central metabolic pathways to better understand bacterial metabolism during infection. Using two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE) and tandem mass spectrometry, it was found that UPEC differentially expresses 84 cytoplasmic proteins between growth in LB medium and growth in human urine (P<0.005). Proteins induced during growth in urine included those involved in the import of short peptides and enzymes required for the transport and catabolism of sialic acid, gluconate, and the pentose sugars xylose and arabinose. Proteins required for the biosynthesis of arginine and serine along with the enzyme agmatinase that is used to produce the polyamine putrescine were also up-regulated in urine. To complement these data, we constructed mutants in these genes and created mutants defective in each central metabolic pathway and tested the relative fitness of these UPEC mutants in vivo in an infection model. Import of peptides, gluconeogenesis, and the tricarboxylic acid cycle are required for E. coli fitness during urinary tract infection while glycolysis, both the non-oxidative and oxidative branches of the pentose phosphate pathway, and the Entner-Doudoroff pathway were dispensable in vivo. These findings suggest that peptides and amino acids are the primary carbon source for E. coli during infection of the urinary tract. Because anaplerosis, or using central pathways to replenish metabolic intermediates, is required for UPEC fitness in vivo, we propose that central metabolic pathways of bacteria could be considered critical components of virulence for pathogenic microbes