Sliding hernia simulating esophageal tumor on computed tomography.

Diaphragmatic hernias are the most common abnormalities of gastrointestinal system especially in elderly patients. The radiographic findings of diaphragmatic hernias on esophagram are well known, but when incidentally found in an asymptomatic patient on axial computed tomography (CT) sections, the appearance of diaphragmatic hernia may mimic many other conditions. Our purpose is to present the CT findings of sliding hernia in an incidentally found asymptomatic patient, and to differentiate it from the other abnormalities that can be located in the distal paraesophageal area with the same appearance characteristics.     

Results of Surgery in General Surgical Patients Receiving Warfarin: Retrospective Analysis of 61 Patients

The aim of this study is to investigate postoperative complications, mortality rates, and to determine the factors affecting mortality on the patients receiving warfarin therapy preoperatively, as well as comparing the results obtained from emergency and elective surgeries. Surgical outcomes of 61 patients on long-term oral anticoagulation with warfarin who underwent surgery in our center were retrospectively reviewed over an 8-year period. Thirty-three (54.1%) patients were female, with a mean age of 53 years. Mitral valve replacement (62.3%) was the most frequent indication for chronic anticoagulation therapy. Twelve out of 61 (19.2%) patients underwent emergency surgery; 59 (96.7%) operations were classified as major surgery. We did not observe any thromboembolic events on patients receiving our bridging therapy protocol. Cardiopulmonary dysfunction (CPD; 19.7%) and hemorrhage (16.4%) were the most encountered postoperative complications. Presence of CPD, bleeding, endocarditis, and mortality were statistically significant for emergency surgeries when compared with the results obtained from elective surgeries. There were 5 (8.2%) deaths observed during follow-up. It was found that advanced age, prolonged duration of operations, and presence of CPD had a statistically significant effect on mortality (P < 0.05). The patients receiving oral anticoagulant had high postoperative complication and mortality rates. This case was more evident in emergency surgeries. It is recommendable that as mortality is more apparent in the patients who undergo emergency surgeries—being older, having long duration of operations as well as CPD. Therefore during the postoperative follow-up process, the patients should be closely monitored.Key words: Emergency, Postoperative complications, Morbidity, Mortality, WarfarinThromboembolism is a major global health concern contributing to more than 0.5 million deaths in Europe and up to 300,000 deaths in the United States each year.¹ Versatile arrays of anticoagulant and/or anti-aggregant agents are available. They are used to treat and prevent thrombosis occurring as a result of venous stasis, valvular heart disease, prosthetic valves, atrial fibrillation, or myocardial infarction. After using these medications, patients who require elective or emergency surgery represent a specific population; moreover, they are prone to developing either excessive bleeding or thrombosis.The annual incidence of major bleeding as a result of oral anticoagulant (OAC) use is reported between 2 and 5%.² Patients on OAC may require elective or sometimes emergency surgical or invasive procedures. There is no consensus on standard protocol to follow for those who require perioperative management.³In the current literature, there are limited numbers of studies regarding the discussions about the operations in general surgery patient population receiving warfarin treatments. In this retrospective study, our aim was to document the complications and outcomes of general surgical procedures implemented on patients receiving warfarin. Along with the comparison of the emergency and elective surgeries performed, we also aimed to determine the factors affecting mortality.     

Pulmonary arteriovenous malformation in children

Although pulmonary arteriovenous malformations (PAVM) are relatively rare in children, they are important in the differential diagnosis of common pulmonary problems, such as hypoxemia, hemoptysis and dyspnea on exertion. We report the cases of two PAVM patients with different presentations and describe the treatment strategies.     

Rewiring yeast sugar transporter preference through modifying a conserved protein motif

Utilization of exogenous sugars found in lignocellulosic biomass hydrolysates, such as xylose, must be improved before yeast can serve as an efficient biofuel and biochemical production platform. In particular, the first step in this process, the molecular transport of xylose into the cell, can serve as a significant flux bottleneck and is highly inhibited by other sugars. Here we demonstrate that sugar transport preference and kinetics can be rewired through the programming of a sequence motif of the general form G-G/F-XXX-G found in the first transmembrane span. By evaluating 46 different heterologously expressed transporters, we find that this motif is conserved among functional transporters and highly enriched in transporters that confer growth on xylose. Through saturation mutagenesis and subsequent rational mutagenesis, four transporter mutants unable to confer growth on glucose but able to sustain growth on xylose were engineered. Specifically, Candida intermedia gxs1 Phe³⁸Ile³⁹Met⁴⁰, Scheffersomyces stipitis rgt2 Phe³⁸ and Met⁴⁰, and Saccharomyces cerevisiae hxt7 Ile³⁹Met⁴⁰Met³⁴⁰ all exhibit this phenotype. In these cases, primary hexose transporters were rewired into xylose transporters. These xylose transporters nevertheless remained inhibited by glucose. Furthermore, in the course of identifying this motif, novel wild-type transporters with superior monosaccharide growth profiles were discovered, namely S. stipitis RGT2 and Debaryomyces hansenii 2D01474. These findings build toward the engineering of efficient pentose utilization in yeast and provide a blueprint for reprogramming transporter properties.Molecular transporter proteins facilitate monosaccharide uptake and serve as the first step in catabolic metabolism. In this capacity, the preferences, regulation, and kinetics of these transporters ultimately dictate total carbon flux (1–3); and optimization of intracellular catabolic pathways only increases the degree to which transport exerts control over metabolic flux (4, 5). Thus, monosaccharide transport profiles and rates are important design criteria and a driving force to enable metabolic engineering advances, ultimately resulting in a biorefinery concept whereby biomass is converted via microbes into a diverse set of molecules (6–10). Among possible host organisms, Saccharomyces cerevisiae is an emerging industrial organism with well-developed genetic tools and established industrial processes and track record (11–16). However, S. cerevisiae lacks an endogenous xylose catabolic pathway and thus is unable to natively use the second most abundant sugar in lignocellulosic biomass. Decades of research have been focused on improving xylose catabolic pathways in recombinant S. cerevisiae (17–22), but less work has been focused on the first committed step of the process—xylose transport, an outstanding limitation in the efficient conversion of lignocellulosic sugars (23, 24).In S. cerevisiae, monosaccharide uptake is mediated by transporters belonging to the major facilitator superfamily (MFS) (25, 26), a ubiquitous group of proteins found across species (27). The predominant transporters in yeast are members of the HXT family (28) and are marked by efficient hexose transport (29) with lower affinities to xylose thus contributing to diauxic growth and flux limitation when attempting pentose utilization in recombinant S. cerevisiae (30). Previous efforts have attempted to identify heterologous transporters with a higher affinity for xylose over glucose (31–36). However, the vast majority of these transporters are either nonfunctional, not efficient, or not xylose specific (24, 37). Furthermore, nearly all known wild-type transporters that enable growth on xylose in yeast confer higher growth rates on glucose than on xylose (24, 37). As an alternative to bioprospecting, we have previously reported that xylose affinity and exponential growth rates on xylose can be improved via directed evolution of Candida intermedia glucose-xylose symporter 1 (GXS1) and Scheffersomyces stipitis xylose uptake 3 (XUT3) (38). These results demonstrated that mutations at specific residues (e.g., Phe⁴⁰ in C. intermedia GXS1) can have a significant impact on the carbohydrate selectivity of these MFS transporters. The fact that single amino acid substitutions can have such a significant impact on transport phenotype (38–40) indicates how simple homology based searches can be ineffective at identifying efficient xylose transporters (35, 36). However, evidence of natural xylose exclusivity is seen in the Escherichia coli xylE transporter that has recently been crystallized (41). The sequence-function flexibility of MFS transporters potentiates the capability to rewire hexose transporters from being glucose favoring, xylose permissive into being xylose-exclusive transporters.In this work, we report on the discovery of a conserved Gly³⁶-Gly³⁷-Val³⁸-Leu³⁹-Phe⁴⁰-Gly⁴¹ motif surrounding the previously identified Phe⁴⁰ residue of C. intermedia GXS1 that controls transporter efficiency and selectivity. By evaluating 46 different heterologously expressed transporters, we find that this motif is conserved among functional transporters and highly enriched in transporters that confer growth on xylose, taking the general form G-G/F-XXX-G. We conduct saturation mutagenesis on Val³⁸, Leu³⁹, and Phe⁴⁰ within the variable region of this motif in C. intermedia GXS1 to demonstrate control of sugar selectivity. Next, we combine xylose-favoring mutations to create a unique mutant version of gxs1 that transports xylose, but not glucose. Finally, we demonstrate the importance of this motif in the capacity to rewire the sugar preference of other hexose transporters including S. cerevisiae hexose transporter 7 (HXT7) and S. stipitis glucose transporter/sensor (RGT2, similar to S. cerevisiae RGT2). This work serves to increase our understanding of the structure–function relationships for molecular transporter engineering and demonstrates complete rewiring of hexose transporters into transporters that prefer xylose as a substrate.