Tissue "valve-over-valve" implantation in previous mechanical Bentall.

The authors present a case report about the elective replacement of a mechanical Bentall with a bioprosthetic valve. The authors describe a technique whereby the mechanical valve is "broken" off its mechanism and the new valve is sutured in the old cuff.

Occlusion following the deployment of MANTA VCD after TAVR.

BACKGROUND: We present a complication following the deployment of the MANTA vascular closure device (VCD) following a transcatheter aortic valve replacement procedure which resulted in occlusion of the common femoral artery. AIMS: To address possible complications associated with MANTA VCD. RESULTS: This was addressed by ballooning the site from the contralateral side which re-established flow. CONCLUSION: We believe this is the first report to address this kind of complication and may prove useful as more of the MANTA devices are being used in multiple procedures.

Improving the discovery of rare variants associated with alcohol problems by leveraging machine learning phenotype prediction and functional information.

Alcohol use disorder (AUD) is moderately heritable with significant social and economic impact. Genome-wide association studies (GWAS) have identified common variants associated with AUD, however, rare variant investigations have yet to achieve well-powered sample sizes. In this study, we conducted an interval-based exome-wide analysis of the Alcohol Use Disorder Identification Test Problems subscale (AUDIT-P) using both machine learning (ML) predicted risk and empirical functional weights. This research has been conducted using the UK Biobank Resource (application number 30782.) Filtering the 200k exome release to unrelated individuals of European ancestry resulted in a sample of 147,386 individuals with 51,357 observed and 96,029 unmeasured but predicted AUDIT-P for exome analysis. Sequence Kernel Association Test (SKAT/SKAT-O) was used for rare variant (Minor Allele Frequency (MAF) < 0.01) interval analyses using default and empirical weights. Empirical weights were constructed using annotations found significant by stratified LD Score Regression analysis of predicted AUDIT-P GWAS, providing prior functional weights specific to AUDIT-P. Using only samples with observed AUDIT-P yielded no significantly associated intervals. In contrast, ADH1C and THRA gene intervals were significant (False discovery rate (FDR) <0.05) using default and empirical weights in the predicted AUDIT-P sample, with the most significant association found using predicted AUDIT-P and empirical weights in the ADH1C gene (SKAT-O P Default = 1.06 x 10 -9 and P Empirical weight = 6.25 x 10 -11 ). These findings provide evidence for rare variant association of the ADH1C gene with the AUDIT-P and highlight the successful leveraging of ML to increase effective sample size and prior empirical functional weights based on common variant GWAS data to refine and increase the statistical significance in underpowered phenotypes.

The Schistosoma mansoni hepatic egg granuloma provides a favorable microenvironment for sustained growth of Leishmania donovani.

Parasitic co-infections are prevalent in many parts of the world. However, relatively little is known about how an underlying infection may impact on the host's ability to control a newly acquired parasite, especially if both infect the same organ. We have studied this using an experimental co-infection model in C57BL/6 mice involving Schistosoma mansoni and Leishmania donovani, two important human pathogens affecting the liver. We show that mice with established S. mansoni infections fail to control L. donovani growth in the liver and spleen. The failure occurs despite the development of a functional anti-L. donovani Th1 response that can mediate granuloma formation and effective clearance of amastigotes from foci of infection in the hepatic parenchyma. Instead, anti-leishmanial immunity fails within the S. mansoni egg granuloma, consistent with a lack of L. donovani granuloma assembly in this tissue microenvironment and consequent lack of NO production. Persisting amastigote replication in the S. mansoni egg granulomas may thus explain the increased L. donovani burden in the liver and spleen. These results may have implications for human S. mansoni and L. donovani co-infections and also demonstrate that granulomatous tissue responses to helminth organisms can form a discrete niche facilitating survival of intracellular pathogens.