ObjeCtiveTo determine the most efficacious treatment for eradication of Helicobacter pylori with the lowest likelihood of some common adverse events among pre-recommended and newer treatment regimens.

Disseminated superficial actinic porokeratosis (DSAP) is an autosomal dominantly inherited epidermal keratinization disorder whose etiology remains unclear. We performed exome sequencing in one unaffected and two affected individuals from a DSAP family. The mevalonate kinase gene (MVK) emerged as the only candidate gene located in previously defined linkage regions after filtering against existing SNP databases, eight HapMap exomes and 1000 Genomes Project data and taking into consideration the functional implications of the mutations. Sanger sequencing in 57 individuals with familial DSAP and 25 individuals with sporadic DSAP identified MVK mutations in 33% and 16% of these individuals (cases), respectively. All 14 MVK mutations identified in our study were absent in 676 individuals without DSAP. Our functional studies in cultured primary keratinocytes suggest that MVK has a role in regulating calcium-induced keratinocyte differentiation and could protect keratinocytes from apoptosis induced by type A ultraviolet radiation. Our results should help advance the understanding of DSAP pathogenesis.

Computational hemodynamics studies of aortic dissections usually combine patient-specific geometries with idealized or generic boundary conditions. In this study we present a comprehensive methodology for simulations of hemodynamics in type B aortic dissection (TBAD) based on fully patient-specific boundary conditions. Methods: Pre-operative 4D flow magnetic resonance imaging (MRI) and Doppler-wire pressure measurements (pre-and post-operative) were acquired from a TBAD patient. These data were used to derive boundary conditions for computational modelling of flow before and after thoracic endovascular repair (TEVAR). Validations of the computational results were performed by comparing predicted flow patterns with pre-TEVAR 4D flow MRI, as well as pressures with in vivo measurements. Results and Conclusion: Comparison of instantaneous velocity streamlines showed a good qualitative agreement with 4D flow MRI. Quantitative comparison of predicted pressures with pressure measurements revealed a maximum difference of 11 mmHg (-9.7%). Furthermore, our model correctly predicted the reduction of true lumen pressure from 74/115 mmHg pre-TEVAR to 64/107 mmHg post-TEVAR (diastolic/systolic pressures at entry tear level), compared to the corresponding measurements of 72/118 mmHg and 64/114 mmHg. This demonstrates that pre-TEVAR 4D flow MRI can be used to tune boundary conditions for post-TEVAR hemodynamic analyses.

In order for computational fluid dynamics to provide quantitative parameters to aid in the clinical assessment of type B aortic dissection, the results must accurately mimic the hemodynamic environment within the aorta. The choice of inlet velocity profile (IVP) therefore is crucial; however, idealised profiles are often adopted, and the effect of IVP on hemodynamics in a dissected aorta is unclear. This study examined two scenarios with respect to the influence of IVP—using (a) patient-specific data in the form of a three-directional (3D), through-plane (TP) or flat IVP; and (b) non-patient-specific flow waveform. The results obtained from nine simulations using patient-specific data showed that all forms of IVP were able to reproduce global flow patterns as observed with 4D flow magnetic resonance imaging. Differences in maximum velocity and time-averaged wall shear stress near the primary entry tear were up to 3% and 6%, respectively, while pressure differences across the true and false lumen differed by up to 6%. More notable variations were found in regions of low wall shear stress when the primary entry tear was close to the left subclavian artery. The results obtained with non-patient-specific waveforms were markedly different. Throughout the aorta, a 25% reduction in stroke volume resulted in up to 28% and 35% reduction in velocity and wall shear stress, respectively, while the shape of flow waveform had a profound influence on the predicted pressure. The results of this study suggest that 3D, TP and flat IVPs all yield reasonably similar velocity and time-averaged wall shear stress results, but TP IVPs should be used where possible for better prediction of pressure. In the absence of patient-specific velocity data, effort should be made to acquire patient’s stroke volume and adjust the applied IVP accordingly.

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Heme oxygenase-1 (HO-1), the inducible isoform of heme oxygenase (HO), has raised a lot of concerns in recent years due to its multiple functions. HO-1 was found to be a pivotal cytoprotective, antioxidant, anti-apoptotic, immunosuppressive, as well as anti-inflammatory molecule. Recent studies have clarified its significant functions in many diseases with substantial findings. In autoimmune diseases, HO-1 may have promising therapeutic potential. Here, we briefly reviewed recent advances in this field, aiming at hopefully exploring the potential therapeutic roles of HO-1, and design HO-1-based strategies for the treatment of autoimmune diseases.

No abstract

CYP2C19 LOF alleles were associated with a diminished platelet response to clopidogrel treatment. Patients carrying CYP2C19 LOF alleles who are treated with clopidogrel may trend toward a poor prognosis after ET.