Non-pathogenic Borrelia burgdorferi expressing Treponema pallidum TprK and Tp0435 antigens as a novel approach to evaluate syphilis vaccine candidates

Background

Syphilis is resurgent in many developed countries and still prevalent in developing nations. Current and future control campaigns would benefit from the development of a vaccine, but although promising vaccine candidates were identified among the putative surface-exposed integral outer membrane proteins of the syphilis spirochete, immunization experiments in the rabbit model using recombinant antigens have failed to fully protect animals upon infectious challenge. We speculated that such recombinant immunogens, purified under denaturing conditions from Escherichia coli prior to immunization might not necessarily harbor their original structure, and hypothesized that enhanced protection would result from performing similar immunization/challenge experiments with native antigens.

Health Care Utilization After Ventricular Tachycardia Ablation: A Propensity Score-Matched Cohort Study

Background

Catheter ablation of ventricular tachycardia (VT) can reduce the burden of ventricular arrhythmia (VA) but its effect on health care utilization and costs after such therapy is poorly known. We sought to compare the rates of cardiovascular (CV)-related hospitalizations, survival, and health care costs in patients with recurrent VT treated either with VT ablation or with medical therapy.

Identification and human exposure prediction of two aldehyde oxidase-mediated metabolites of a methylquinoline-containing drug candidate

1. Aldehyde oxidase (AO enzymes)-mediated oxidation predominantly occurs at a carbon atom adjacent to the nitrogen on aromatic azaheterocycles. In the current report, we identified that AO enzymes oxidation took place at both the C-2 and C-4 positions of the methylquinoline moiety of Compound A based on data from mass spectrometric analysis, AO enzymes “litmus” test, and comparison with authentic standards.

2. To assess the potential for inadequate coverage for these two AO enzyme-mediated metabolites in nonclinical safety studies, given concerns due to differences in AO enzymes expression between preclinical species and humans, the human circulating levels of the two AO enzyme-mediated metabolites were predicted prospectively using in vitro and in vivo models. Both formation clearance and elimination clearance of the two metabolites were predicted based on in vitro to in vivo correlation and comparison with in vivo data from rats.

3. The result showed that the 4-OH metabolite of Compound A would account for less than 3% of the total drug-related exposure in human plasma, while the exposure to the 2-oxo metabolite would be relatively high (～70%).

4. The predicted human exposure levels for the two metabolites are in similar ranges as those observed in monkeys. These data taken together support the advancement to clinical development of Compound A.     

The journeys of three ASPIRE winning medical schools toward excellence in student assessment

Abstract

Introduction: ASPIRE Excellence Awards in Student Assessment are offered to medical schools with innovative and comprehensive assessment programmes adjudged by international experts, using evidence-based criteria.

The journeys of three ASPIRE-winning medical schools toward “assessment excellence” are presented. These schools include Aga Khan University Medical College (AKU-MC), Pakistan, Southern Illinois University School of Medicine (SIUSOM), USA, and University of Leeds School of Medicine, UK.

Methods: The unfolding journeys highlighting achievements, innovations, and essential components of each assessment programme were compared to identify differences and commonalities.

Results: Cultural contextual differences included developed-versus-developing country, east-west, type of regulatory bodies, and institutional-versus-national certifying/licensing examinations, which influence curricula and assessments.

In all, 12 essential commonalities were found: alignment with institutional vision; sustained assessment leadership; stakeholder engagement; communication between curriculum and assessment; assessment-for-learning and feedback; longitudinal student profiling of outcome achievement; assessment rigor and robustness; 360° feedback from-and-to assessment; continuous enrichment through rigorous quality assurance; societal sensitivity; influencing others; and a “wow factor.”

Conclusions: Although the journeys of the three medical schools were undertaken in different cultural contexts, similar core components highlight strong foundations in student assessment. The journeys continue as assessment programmes remain dynamic and measurement science expands. This article may be helpful to other institutions pursuing excellence in assessment.     

Intervention for arch obstruction after the Norwood procedure: Prevalence,associated factors,and practice variability

Objective

Arch obstruction after the Norwood procedure is common and contributes to mortality. We determined the prevalence, associated factors, and practice variability of arch reintervention and assessed whether arch reintervention is associated with mortality.

Posting,texting, and related social risk behavior while high

Abstract

Background: Posting on social media can have lasting consequences in one’s social life and career. Research has not yet focused on social media or more modern forms of communication as social risk factors for individuals high on drugs. This study aims to examine prevalence and correlates of engaging in social media posting and related behavior while high. Methods: We examined data from 872 adults (39.8% female) who were surveyed entering electronic dance music (EDM) parties in New York City and reported lifetime illegal drug use. Participants were asked whether they were ever high on a drug while (1) posting on social media, (2) calling or texting someone, and (3) being in a photo. Those answering affirmatively were also asked whether they later regretted the behavior. We examined demographic and drug-related correlates of these behaviors. Results: Of the participants, 34.3% posted on social media while high (with 21.4% regretting it), 55.9% had texted or called someone while high (with 30.5% regretting it), and 47.6% had been in a photo while high (with 32.7% regretting it). Females and young adults (ages 18–24) were at high risk for posting on social media while high and at higher risk for engaging in more of these behaviors. Past-month marijuana users in particular were at increased risk for engaging in each of these behaviors. Conclusion: Engaging in these behaviors while high on drugs appears to be prevalent, and prevention and harm reduction efforts should seek to prevent or reduce likelihood of social harm that can result from such situations.     

Effect of sensorineural hearing loss on neurocognitive and adaptive functioning in survivors of pediatric embryonal brain tumor

Journal of Neuro-Oncology - Survivors of pediatric embryonal brain tumors (BT) are at high risk for sensorineural hearing loss (SNHL) associated with neurocognitive decline. However, previous...