Spontaneous coronary artery rupture treated on a beating heart.

Primary spontaneous coronary artery rupture (SCAR) without any underlying condition is a rare disorder. The acute and often dramatic nature of hemopericardium with cardiac tamponade advocates immediate pericardial drainage or surgical intervention with timely recognition of coronary artery rupture. This is the first case report of primary SCAR successfully treated on a beating heart without cardiopulmonary bypass.

Corrigendum: Insight Into the Interaction Between RNA Polymerase and VPg for Murine Norovirus Replication.

[This corrects the article DOI: 10.3389/fmicb.2018.01466.].

Insight Into the Interaction Between RNA Polymerase and VPg for Murine Norovirus Replication.

Norovirus (NoV) is a leading cause of epidemic acute non-bacterial gastroenteritis, and replicates through virion protein genome-linked (VPg)-primed or de novo RNA synthesis by RNA-dependent RNA polymerase (RdRp). VPg is a multifunctional protein that plays crucial roles in viral protein translation and genome replication. However, the interaction between the RdRp and this multifunctional VPg in NoV replication has been unknown. In this study, VPg derived from murine NoV (MNV) was found to mediate the formation of higher-order multimers or tubular fibrils of MNV RdRp, which led to significantly enhanced polymerase activity in vitro. The replication of MNV mutants containing a VPg-binding defective RdRp, based on the crystal structure of an RdRp-VPg(1-73) complex, was completely blocked in a cell culture system. Our data suggest that the interaction between RdRp and VPg plays a crucial role in the multimerization-mediated RdRp activity in vivo and consequently in MNV replication, which can provide a new target of therapeutic intervention for NoV outbreaks.

Recurrent mitral paravalvular leak: benefits of leak site repair compared to re-replacement.

BACKGROUND: Mitral paravalvular leak (PVL) recurrence after surgical correction has not been well demonstrated. The aims of this study were to evaluate the long-term results of surgical mitral PVL correction, including recurrent PVL, and to elucidate the factors - including surgical technique - that affect the risk of recurrent PVL. METHODS: Eighty-six patients who underwent surgical treatment for mitral PVL were enrolled in this study. Thirty-six patients underwent leak site repair (MVP group), and 50 patients underwent re-replacement (MVR group). Leak site repair was the preferred method and was performed whenever possible. The mean follow-up duration was 58.6±44.1 months (0.1-156.5 months). RESULTS: Operative mortality occurred in 7 patients (8.1%). There were no significant differences in operative mortality or postoperative complications between the groups. Overall survival rates at 5 and 10 years were 67.9% and 48.3%, respectively, without intergroup differences. Recurrent PVL without any evidence of infective endocarditis was found in 25 patients (29.1%). Five- and 10-year PVL-free rates were 69.9% and 18.3%, respectively. The mortality rate of reoperation for recurrent PVL was 35.2% (6/17). The risk factors of recurrent PVL were the MVR group (hazard ratio: 2.865, 95% CI: 1.077-7.619) and presence of extensive dehiscence (>25% of annulus: 2.861, 95% CI: 1.163-7.038). CONCLUSIONS: Recurrent PVL was not infrequent after surgical correction of mitral PVL, and reoperation may be a high-risk procedure. Leak site repair, if it could be performed, would be a good surgical option for mitral PVL because re-replacement was a risk factor for recurrence of PVL.

Genome Modeling System: A Knowledge Management Platform for Genomics.

In this work, we present the Genome Modeling System (GMS), an analysis information management system capable of executing automated genome analysis pipelines at a massive scale. The GMS framework provides detailed tracking of samples and data coupled with reliable and repeatable analysis pipelines. The GMS also serves as a platform for bioinformatics development, allowing a large team to collaborate on data analysis, or an individual researcher to leverage the work of others effectively within its data management system. Rather than separating ad-hoc analysis from rigorous, reproducible pipelines, the GMS promotes systematic integration between the two. As a demonstration of the GMS, we performed an integrated analysis of whole genome, exome and transcriptome sequencing data from a breast cancer cell line (HCC1395) and matched lymphoblastoid line (HCC1395BL). These data are available for users to test the software, complete tutorials and develop novel GMS pipeline configurations. The GMS is available at https://github.com/genome/gms.

Time-dependent expression of osteoblast marker genes in human primary cells cultured on microgrooved titanium substrata.

OBJECTIVE: This study aimed to investigate the influence of titanium surface-etched microgrooves and ridges on the time-dependent expression of osteoblast marker genes and proteins of human primary cells undergoing osteoblast differentiation. MATERIALS AND METHODS: Fifteen-, 30-, and 60-µm wide, and 3.5- and 10-µm deep-etched microgrooves and ridges were fabricated on titanium substrata using photolithography and subsequent acid etching, and were used as the experimental groups (E15/3.5, E30/10, and E60/10), whereas the smooth and acid-etched titanium were used as the control (NE0 and E0). Time-dependent mRNA and protein expression of type I collagen α1, alkaline phosphatase, runt-related transcription factor 2, osterix, osteocalcin, osteopontin, bone sialoprotein II, and osteonectin after 7, 14, 21, and 28 days of osteogenic culture was analyzed using quantitative real-time PCR, RT-PCR, western blotting, and protein quantitation. Student's t-test, one-way analysis of variance, and Pearson's correlation analysis were used for statistics. RESULTS: Etched microgrooves and ridges induced significantly lower levels of type I collagen α1 gene expression at day 14, and an extreme increase in osteopontin gene expression at days 21 and 28 compared with smooth control. However, the expression levels of the other osteoblast marker genes and proteins analyzed in this study correspond with previously reported expression patterns of cells on variously modified titanium surfaces during osteoblast differentiation and bone formation. CONCLUSION: This study indicates that etched microgrooves and ridges on titanium substrata induce both typical and unique time-dependent expression patterns of the osteoblast marker genes and proteins analyzed in this study.

Computational tools for metabolic engineering.

A great variety of software applications are now employed in the metabolic engineering field. These applications have been created to support a wide range of experimental and analysis techniques. Computational tools are utilized throughout the metabolic engineering workflow to extract and interpret relevant information from large data sets, to present complex models in a more manageable form, and to propose efficient network design strategies. In this review, we present a number of tools that can assist in modifying and understanding cellular metabolic networks. The review covers seven areas of relevance to metabolic engineers. These include metabolic reconstruction efforts, network visualization, nucleic acid and protein engineering, metabolic flux analysis, pathway prospecting, post-structural network analysis and culture optimization. The list of available tools is extensive and we can only highlight a small, representative portion of the tools from each area.

Adjusting phenotypes by noise control.

Genetically identical cells can show phenotypic variability. This is often caused by stochastic events that originate from randomness in biochemical processes involving in gene expression and other extrinsic cellular processes. From an engineering perspective, there have been efforts focused on theory and experiments to control noise levels by perturbing and replacing gene network components. However, systematic methods for noise control are lacking mainly due to the intractable mathematical structure of noise propagation through reaction networks. Here, we provide a numerical analysis method by quantifying the parametric sensitivity of noise characteristics at the level of the linear noise approximation. Our analysis is readily applicable to various types of noise control and to different types of system; for example, we can orthogonally control the mean and noise levels and can control system dynamics such as noisy oscillations. As an illustration we applied our method to HIV and yeast gene expression systems and metabolic networks. The oscillatory signal control was applied to p53 oscillations from DNA damage. Furthermore, we showed that the efficiency of orthogonal control can be enhanced by applying extrinsic noise and feedback. Our noise control analysis can be applied to any stochastic model belonging to continuous time Markovian systems such as biological and chemical reaction systems, and even computer and social networks. We anticipate the proposed analysis to be a useful tool for designing and controlling synthetic gene networks.

Fan-out in gene regulatory networks.

BACKGROUND: In synthetic biology, gene regulatory circuits are often constructed by combining smaller circuit components. Connections between components are achieved by transcription factors acting on promoters. If the individual components behave as true modules and certain module interface conditions are satisfied, the function of the composite circuits can in principle be predicted. RESULTS: In this paper, we investigate one of the interface conditions: fan-out. We quantify the fan-out, a concept widely used in electrical engineering, to indicate the maximum number of the downstream inputs that an upstream output transcription factor can regulate. The fan-out is shown to be closely related to retroactivity studied by Del Vecchio, et al. An efficient operational method for measuring the fan-out is proposed and shown to be applied to various types of module interfaces. The fan-out is also shown to be enhanced by self-inhibitory regulation on the output. The potential role of an inhibitory regulation is discussed. CONCLUSIONS: The proposed estimation method for fan-out not only provides an experimentally efficient way for quantifying the level of modularity in gene regulatory circuits but also helps characterize and design module interfaces, enabling the modular construction of gene circuits.

Modified tricuspid ring annuloplasty to reduce residual regurgitation in functional tricuspid regurgitation.

We describe a modified technique of tricuspid ring annuloplasty to reduce postoperative residual regurgitation in patients with functional tricuspid regurgitation; first, an adjustable segmental tricuspid annuloplasty is performed to obtain coaptation of the valve leaflets with two 5-0 monofilament annular sutures, and then a prosthetic ring of the same size as the competent valve area is implanted with continuous 3-0 polypropylene sutures.

Influence of the CYP3A5 and MDR1 genetic polymorphisms on the pharmacokinetics of tacrolimus in healthy Korean subjects.

AIMS: To determine the frequencies of the genotypes of CYP3A5 and MDR1 and to examine the influence of the polymorphisms of these genes on tacrolimus pharmacokinetics in the Korean population. METHODS: Twenty-nine healthy Koreans who participated in the previous tacrolimus pharmacokinetic study were genotyped for CYP3A4*1B, CYP3A5*3, MDR1 c.1236C-->T, MDR1 c.2677G-->A/T and MDR1 c.3435C-->T. The relationship between the genotypes so obtained and tacrolimus pharmacokinetics observed in the previous study was examined. RESULTS: No subject in this study had the CYP3A4*1B variant. The observed frequencies of CYP3A5*1/*1, *1/*3, and *3/*3 were 0.069 [confidence interval (CI) -0.023, 0.161], 0.483 (CI 0.301, 0.665) and 0.448 (CI 0.267, 0.629), respectively. AUC(0-infinity) for the CYP3A5*1/*1 or *1/*3 genotype was 131.5 +/- 44.8 ng h ml(-1) (CI 109.6, 153.5), which was much lower compared with the CYP3A5*3/*3 genotype of 323.8 +/- 129.3 ng h ml(-1) (CI 253.5, 394.1) (P = 2.063E-07). Similarly, C(max) for the CYP3A5*1/*1 or *1/*3 genotype was 11.8 +/- 3.4 ng ml(-1) (CI 10.1, 13.5), which was also much lower compared with the CYP3A5*3/*3 genotype of 24.4 +/- 12.3 ng ml(-1) (CI 17.8, 31.1) (P = 0.0001). However, there was no significant difference in tacrolimus pharmacokinetics among the MDR1 diplotypes of CGC-CGC, CGC-TTT, CGC-TGC, TTT-TGC or TTT-TTT (P = 0.2486). CONCLUSIONS: This study shows that the CYP3A5*3 genetic polymorphisms may be associated with the individual difference in tacrolimus pharmacokinetics. An individualized dosage regimen design incorporating such genetic information would help increase clinical efficacy of the drug while reducing adverse drug reactions.

Role of therapy or monitoring in preventing progression to gastric cancer.

It is generally accepted that intestinal-type gastric adenocarcinoma arises through a multistep process originating with chronic gastritis, progressing through stages of atrophy, intestinal metaplasia, and dysplasia and finally invasive carcinoma. This sequential process, known as the "Correa cascade" is in many instances initiated by Helicobacter pylori infection and perpetuated by a number of environmental and host factors. Given that the development of carcinoma can be the end point of this sequential process, there is great interest in determining which if any of these steps may be reversible. Clinical studies have shown that the eradication of H. pylori can lead to resolution of chronic gastritis, and a few studies have suggested some improvement in gastric atrophy. Intestinal metaplasia, however, does not appear to be as reversible. Nevertheless, results of several intriguing studies of high-risk populations support the notion that eradication of H. pylori may decrease or delay progression to gastric carcinoma despite the inability to reverse all mucosal damage. The applicability of these findings to low-risk countries such as the United States and the United Kingdom remain uncertain. Currently, in the United States, there is no widely accepted screening program for H. pylori infection in asymptomatic individuals, and consensus regarding surveillance for gastric intestinal metaplasia or dysplasia is lacking. The purpose of this report is to evaluate the available data regarding the epidemiology of H. pylori and associated carcinoma, discuss relevant human and animal data that address eradication strategies in the prevention of gastric carcinoma, and finally discuss current recommendations regarding screening programs aimed at high-risk populations.

Purification and characterization of a 28-kDa major protein from ginseng root.

A major protein was isolated from ginseng root (Panax ginseng C.A. Meyer) using a combination of ammonium sulfate fractionation, gel filtration chromatography, ion-exchange FPLC, and fast performance liquid chromatofocusing. Electrophoretic and gel permeation chromatographic studies revealed that the major protein, GMP, is composed of two subunits of approximately 28 kDa. During purification, it was found that the elution profiles of GMP from gel filtration chromatography were significantly different, depending on the ionic strength of buffers used. GMP in a buffer of low ionic strength was isolated as a complex with carbohydrate, which could be only dissociated at high ionic strength. Carbohydrate composition in GMP detected by gas chromatography varied, depending on the isolation method of the protein from ginseng roots. These results suggest that carbohydrates are bound non-covalently to GMP whose amino acid composition analysis showed high amounts of acidic amino acids.

Human plasma is directly bacteriocidal against Helicobacter pylori in vitro, potentially explaining the decreased detection of Helicobacter pylori during acute upper GI bleeding.

BACKGROUND: The rapid urease test is the preferred method for detection of H pylori in patients with uncomplicated ulcer disease undergoing EGD. However, the sensitivity of this test when performed during upper GI bleeding has been questioned. It has been suggested that false-negative results occur, resulting from buffering effects of blood. The direct effect of blood was evaluated on H pylori growth in ex vivo and in vitro systems. METHODS: Antral biopsy specimens obtained from 100 consecutive patients undergoing EGD were cultured with and without autologous blood, and RUT results at 5, 15, and 30 minutes were compared. In addition, H pylori bacterial cultures of a virulent laboratory strain were incubated with blood or blood components from 5 patients who were H pylori positive and 5 who were H pylori negative. The effect of blood on H pylori growth was determined by rapid urease test and direct bacterial plating with colony-forming unit determination. RESULTS: Three hundred antral biopsy specimens from 100 patients were divided into 900 fragments for rapid urease test evaluation. There was no statistical difference in rapid urease test results for biopsy fragments tested immediately, cultured in blood, or cultured in phosphate-buffered saline solution. In contrast, in vitro studies demonstrated that whole blood and plasma effectively killed H pylori, whereas neutrophils and mononuclear cells had no detrimental effect on H pylori growth. CONCLUSION: Human plasma contains factors that kill H pylori in vitro. This may be a possible explanation for the lower-than-expected rapid urease test detection of H pylori during active upper GI bleeding.