Myocardial perfusion in real-time using power modulation. In vivo evidence for microcirculatory damage after acute myocardial infarction

BACKGROUND: The effect of beta-radiation on extra-stent vascular remodeling in patients with in-stent restenosis has not been studied. The correlation between the extent of extra-stent plaque proliferation and that of intimal hyperplasia (IH) in in-stent restenosis in patients who received beta-radiation therapy as well as conventional therapy has also not been studied. METHODS: We evaluated the extra-stent remodeling in diffuse in-stent restenosis between a beta-radiation therapy patient group (188Re-MAG3, n=50) and a control group (n=9) by applying serial intravascular ultrasound (IVUS) analysis. Matching (post-intervention and follow-up) images were acquired at the follow-up lesion site and were available in 44 of 50 patients who received radiation therapy and in seven of nine control patients. RESULTS: There was a significant increase of the external elastic membrane (EEM) area in both groups: 16.4 +/- 3.3 mm2 post-intervention to 17.1 +/- 3.3 mm2 at follow-up, P=0.001 in the radiation therapy group, and 16.8 +/- 4.0 mm2 post-intervention to 17.4 +/- 4.1 mm2 at follow-up, P=0.008 in the control group. There were no statistically significant differences of the Delta EEM area between the two groups: 0.7 +/- 0.4 mm2 in the radiation therapy group vs. 0.6 +/- 0.4 mm2 in the control group, P=0.389. The Delta IH area correlated with the Delta EEM area in the control group (r=0.826, P=0.022), but not in the radiation therapy group (r=0.016, P=0.919). CONCLUSIONS: The findings of this IVUS study were that positive remodeling (increased EEM area) occurred equally in both control and irradiated patients with in-stent restenosis. The extent of remodeling was directly in proportion to IH in the control group, but no such relationship existed in the irradiated patient group.     

Mycobacterium tuberculosis Gyrase Inhibitors as a New Class of Antitubercular Drugs

One way to speed up the TB drug discovery process is to search for antitubercular activity among compound series that already possess some of the key properties needed in anti-infective drug discovery, such as whole-cell activity and oral absorption. Here, we present MGIs, a new series of Mycobacterium tuberculosis gyrase inhibitors, which stem from the long-term efforts GSK has dedicated to the discovery and development of novel bacterial topoisomerase inhibitors (NBTIs). The compounds identified were found to be devoid of fluoroquinolone (FQ) cross-resistance and seem to operate through a mechanism similar to that of the previously described NBTI GSK antibacterial drug candidate. The remarkable in vitro and in vivo antitubercular profiles showed by the hits has prompted us to further advance the MGI project to full lead optimization.     

Changes in physical activity,diet, and body weight across the education and employment transitions of early adulthood: A systematic review and meta‐analysis

Early adulthood is a time when individuals go through important life transitions, such as moving from high school into higher education or employment, but the impact of these life transitions on changes in body weight, diet, and physical activity is not known. We searched six electronic databases to July 2019 for longitudinal observational studies providing data on adiposity, diet, and/or physical activity across education or employment transitions in young people aged between 15 and 35 years. We found 19 studies, of which 17 assessed changes in physical activity, three body weight, and five diet or eating behaviours. Meta‐analysis (n=9) found that leaving high school was associated with a decrease of ?7.04 (95% CI, ?11.26, ?2.82) min/day of moderate‐to‐vigorous physical activity. Three studies reported increases in body weight on leaving high school. A small number of studies suggested decreases in diet quality on leaving high school (n=2/4 papers) and leaving university (n=1) but not on starting employment (n=1). Studies suggested no change in physical activity on leaving university (n=4) but decreases in physical activity on starting employment (n=2/3). The transition of leaving high school is an important time to support individuals to prevent decreases in physical activity and gains in body weight.     

Implicit and explicit self-esteem and their reciprocal relationship with symptoms of depression and social anxiety: A longitudinal study in adolescents

Background and Objectives

A negative self-view is a prominent factor in most cognitive vulnerability models of depression and anxiety. Recently, there has been increased attention to differentiate between the implicit (automatic) and the explicit (reflective) processing of self-related evaluations. This longitudinal study aimed to test the association between implicit and explicit self-esteem and symptoms of adolescent depression and social anxiety disorder. Two complementary models were tested: the vulnerability model and the scarring effect model.

Method

Participants were 1641 first and second year pupils of secondary schools in the Netherlands. The Rosenberg Self-Esteem Scale, self-esteem Implicit Association Test and Revised Child Anxiety and Depression Scale were completed to measure explicit self-esteem, implicit self-esteem and symptoms of social anxiety disorder (SAD) and major depressive disorder (MDD), respectively, at baseline and two-year follow-up.

Results

Explicit self-esteem at baseline was associated with symptoms of MDD and SAD at follow-up. Symptomatology at baseline was not associated with explicit self-esteem at follow-up. Implicit self-esteem was not associated with symptoms of MDD or SAD in either direction.

Limitations

We relied on self-report measures of MDD and SAD symptomatology. Also, findings are based on a non-clinical sample.

Conclusions

Our findings support the vulnerability model, and not the scarring effect model. The implications of these findings suggest support of an explicit self-esteem intervention to prevent increases in MDD and SAD symptomatology in non-clinical adolescents.     

Identification of a common immune signature in murine and human systemic Salmonellosis

Despite the importance of Salmonella infections in human and animal health, the target antigens of Salmonella-specific immunity remain poorly defined. We have previously shown evidence for antibody-mediating protection against invasive Salmonellosis in mice and African children. To generate an overview of antibody targeting in systemic Salmonellosis, a Salmonella proteomic array containing over 2,700 proteins was constructed and probed with immune sera from Salmonella-infected mice and humans. Analysis of multiple inbred mouse strains identified 117 antigens recognized by systemic antibody responses in murine Salmonellosis. Importantly, many of these antigens were independently identified as target antigens using sera from Malawian children with Salmonella bacteremia, validating the study of the murine model. Furthermore, vaccination with SseB, the most prominent antigenic target in Malawian children, provided mice with significant protection against Salmonella infection. Together, these data uncover an overlapping immune signature of disseminated Salmonellosis in mice and humans and provide a foundation for the generation of a protective subunit vaccine.