Common determinants of antimicrobial resistance in sequential episodes of sexually transmitted shigellosis in men who have sex with men: a cross-sectional study

Background

In high-income nations, men who have sex with men (MSM) are at increased risk of shigellosis. A sublineage of Shigella flexneri serotype 3a was recently shown to have spread worldwide in MSM, driven by mobilisable azithromycin resistance. Since then, the serotype 2a and the species S sonnei have become epidemic in the UK. We aimed to determine whether these subsequent outbreaks were also attributable to epidemic sublineages in MSM and mobilisable antimicrobial resistance.

Analysis of the HD-GYP domain cyclic dimeric GMP phosphodiesterase reveals a role in motility and the enzootic life cycle of Borrelia burgdorferi

HD-GYP domain cyclic dimeric GMP (c-di-GMP) phosphodiesterases are implicated in motility and virulence in bacteria. Borrelia burgdorferi possesses a single set of c-di-GMP-metabolizing enzymes, including a putative HD-GYP domain protein, BB0374. Recently, we characterized the EAL domain phosphodiesterase PdeA. A mutation in pdeA resulted in cells that were defective in motility and virulence. Here we demonstrate that BB0374/PdeB specifically hydrolyzed c-di-GMP with a K_m of 2.9 nM, confirming that it is a functional phosphodiesterase. Furthermore, by measuring phosphodiesterase enzyme activity in extracts from cells containing the pdeA pdeB double mutant, we demonstrate that no additional phosphodiesterases are present in B. burgdorferi. pdeB single mutant cells exhibit significantly increased flexing, indicating a role for c-di-GMP in motility. Constructing and analyzing a pilZ pdeB double mutant suggests that PilZ likely interacts with chemotaxis signaling. While virulence in needle-inoculated C3H/HeN mice did not appear to be altered significantly in pdeB mutant cells, these cells exhibited a reduced ability to survive in Ixodes scapularis ticks. Consequently, those ticks were unable to transmit the infection to naïve mice. All of these phenotypes were restored when the mutant was complemented. Identification of this role of pdeB increases our understanding of the c-di-GMP signaling network in motility regulation and the life cycle of B. burgdorferi.     

Branching Pattern of the Cerebral Arterial Tree

Quantitative data on branching patterns of the human cerebral arterial tree are lacking in the 1.0–0.1 mm radius range. We aimed to collect quantitative data in this range, and to study if the cerebral artery tree complies with the principle of minimal work (Law of Murray). To enable easy quantification of branching patterns a semi-automatic method was employed to measure 1,294 bifurcations and 2,031 segments on 7 T-MRI scans of two corrosion casts embedded in a gel. Additionally, to measure segments with a radius smaller than 0.1 mm, 9.4 T-MRI was used on a small cast section to characterize 1,147 bifurcations and 1,150 segments. Besides MRI, traditional methods were employed. Seven hundred thirty-three bifurcations were manually measured on a corrosion cast and 1,808 bifurcations and 1,799 segment lengths were manually measured on a fresh dissected cerebral arterial tree. Data showed a large variation in branching pattern parameters (asymmetry-ratio, area-ratio, length-radius-ratio, tapering). Part of the variation may be explained by the variation in measurement techniques, number of measurements and location of measurement in the vascular tree. This study confirms that the cerebral arterial tree complies with the principle of minimum work. These data are essential in the future development of more accurate mathematical blood flow models. Anat Rec, 302:1434–1446, 2019. © 2018 The Authors. The Anatomical Record published by Wiley Periodicals, Inc. on behalf of American Association of Anatomists.     

Determinants of outcomes following outpatient placement of implantable cardioverter defibrillators in a Medicare Advantage population

Background

Recipients of ICD are likely to have several risk factors that could interfere with successful use of implantable cardioverter defibrillators (ICDs).

Hypothesis

Age, sex, and factors indicated in claims are associated with one‐year mortality and complications after ICD placement.

Methods

Adult Medicare Advantage patients who underwent outpatient ICD implantation from January 2014 to September 2015 were included. Age, sex, Charlson Comorbidity Index (CCI), prior year hospitalization and emergency department (ED) visit, diabetes, heart failure, ischemic heart disease, and indicators of the need for pacing were evaluated as risk factors. Mortality and device‐related complications (lead and nonlead) were assessed at one‐year post‐procedure using Kaplan‐Meier and Cox Proportional Hazard analysis.

Results

Among 8450 patients who underwent implantation, 1‐year event‐free survival was 80.1%, based on an overall composite measure of complications and mortality. Adjusted survival analysis showed that age ≥ 65, male sex, incremental increase in CCI, heart failure, prior year hospitalization, ED visit, and prior year pacing procedure were significant predictors of mortality. Age ≥ 65, male sex, and prior year hospitalization were significant predictors of a composite measure of device‐related complications. CCI and prior hospitalization were significant predictors of a composite measure of any adverse outcome.

Conclusions

Results suggest most patients in an older population do not experience adverse outcomes in the year following ICD implantation. The risk of mortality may be greater in men, patients over the age of 65, and patients with greater general morbidity, heart failure, or a history of a pacing procedure.