Temporal Regulation of Rapamycin on Memory CTL Programming by IL-12

Mammalian target of rapamycin (mTOR) is a master regulator of cell growth. Recent reports have defined its important role in memory cytotoxic T lymphocyte (CTL) differentiation in infections and memory programming. We report that rapamycin regulated memory CTL programming by IL-12 to a similar level in a wide range of concentrations, and the enhanced memory CTLs by rapamycin were functional and provided similar protection against Listeria Monocytogenes challenge compared to the control. In addition, rapamycin-experienced CTLs went through substantially enhanced proliferation after transfer into recipients. Furthermore, the regulatory function of rapamycin on CD62L expression in memory CTLs was mainly contributed by the presence of rapamycin in the first 24-hr of stimulation in vitro, whereas the effective window of rapamycin on the size of memory CTLs was determined between 24 to 72 hrs. In conclusion, rapamycin regulates IL-12-driven programming of CTLs to a similar level in a wide range of concentrations, and regulates the phenotype and the size of memory CTLs in different temporal windows

A Single Nucleotide Change Affects Fur-Dependent Regulation of sodB in H. pylori

Helicobacter pylori is a significant human pathogen that has adapted to survive the many stresses found within the gastric environment. Superoxide Dismutase (SodB) is an important factor that helps H. pylori combat oxidative stress. sodB was previously shown to be repressed by the Ferric Uptake Regulator (Fur) in the absence of iron (apo-Fur regulation) [1]. Herein, we show that apo regulation is not fully conserved among all strains of H. pylori. apo-Fur dependent changes in sodB expression are not observed under iron deplete conditions in H. pylori strains G27, HPAG1, or J99. However, Fur regulation of pfr and amiE occurs as expected. Comparative analysis of the Fur coding sequence between G27 and 26695 revealed a single amino acid difference, which was not responsible for the altered sodB regulation. Comparison of the sodB promoters from G27 and 26695 also revealed a single nucleotide difference within the predicted Fur binding site. Alteration of this nucleotide in G27 to that of 26695 restored apo-Fur dependent sodB regulation, indicating that a single base difference is at least partially responsible for the difference in sodB regulation observed among these H. pylori strains. Fur binding studies revealed that alteration of this single nucleotide in G27 increased the affinity of Fur for the sodB promoter. Additionally, the single base change in G27 enabled the sodB promoter to bind to apo-Fur with affinities similar to the 26695 sodB promoter. Taken together these data indicate that this nucleotide residue is important for direct apo-Fur binding to the sodB promoter

Impact of purposefully designed learning activities in the case of information literacy self-efficacy

Objectives: Developing information literacy skills of medical students is one of the basic skills to become lifelong learners. Method: The study focuses on the development of a first year integrated information literacy course for medical students during three consecutive years. Students filled in a validated information literacy self-efficacy scale for medicine at the beginning and at the end of the course. Results: Integrating a search-report has a significant positive effect. For ‘Medical information literacy skills’, a positive difference is found for the academic year in which a peer review was introduced. Integrating personal experience has an undeniable impact and should be stimulated in the educational design in higher education. Performing a peer review impacts information literacy self-efficacy related to the specific medical information literacy skills and should be further integrated in the course. Teachers need to evaluate the impact of course development continuously, as not all adaptations always have the expected impact

Effects of Maternity Care Coordination on Pregnancy Outcomes: Propensity-Weighted Analyses

BACKGROUND: Care coordination services that link pregnant women to health-promoting resources, avoid duplication of effort, and improve communication between families and providers have been endorsed as a strategy for reducing disparities in adverse pregnancy outcomes, however empirical evidence regarding the effects of these services is contradictory and incomplete. This study investigates the effects of maternity care coordination on pregnancy outcomes in North Carolina. METHODS: Birth certificate and Medicaid claims data were analyzed for 7,124 women delivering live infants in North Carolina from October 2008 through September 2010, of whom 2,255 received Maternity Care Coordination (MCC) services. Propensity-weighted analyses were conducted to reduce the influence of selection bias in evaluating program participation. Sensitivity analyses compared these results to conventional OLS analyses. RESULTS: The unadjusted preterm birth rate was lower among women who received MCC services (7.0 percent compared to 8.3 percent among controls). Propensity-weighted analyses demonstrated that women receiving services had a 1.8 percentage point reduction in preterm birth risk; p<0.05). MCC services were also associated with lower pregnancy weight gain (p=0.10). No effects of MCC were seen for birthweight. CONCLUSIONS: These findings suggest that coordination of care in pregnancy can significantly reduce the risk of preterm delivery among Medicaid-enrolled women. Further research evaluating specific components of care coordination services and their effects on preterm birth risk among racial/ethnic and geographic subgroups of Medicaid enrolled mothers could inform efforts to reduce disparities in pregnancy outcome

Deep neural network to locate and segment brain tumors outperformed the expert technicians who created the training data

Purpose: Deep learning (DL) algorithms have shown promising results for brain tumor segmentation in MRI. However, validation is required prior to routine clinical use. We report the first randomized and blinded comparison of DL and trained technician segmentations. Approach: We compiled a multi-institutional database of 741 pretreatment MRI exams. Each contained a postcontrast T1-weighted exam, a T2-weighted fluid-attenuated inversion recovery exam, and at least one technician-derived tumor segmentation. The database included 729 unique patients (470 males and 259 females). Of these exams, 641 were used for training the DL system, and 100 were reserved for testing. We developed a platform to enable qualitative, blinded, controlled assessment of lesion segmentations made by technicians and the DL method. On this platform, 20 neuroradiologists performed 400 side-by-side comparisons of segmentations on 100 test cases. They scored each segmentation between 0 (poor) and 10 (perfect). Agreement between segmentations from technicians and the DL method was also evaluated quantitatively using the Dice coefficient, which produces values between 0 (no overlap) and 1 (perfect overlap). Results: The neuroradiologists gave technician and DL segmentations mean scores of 6.97 and 7.31, respectively (p  <  0.00007). The DL method achieved a mean Dice coefficient of 0.87 on the test cases. Conclusions: This was the first objective comparison of automated and human segmentation using a blinded controlled assessment study. Our DL system learned to outperform its “human teachers” and produced output that was better, on average, than its training data