Summary
The Helicobacter pylori adhesin BabA binds mucosal ABO/Leb blood group (bg) carbohydrates. BabA facilitates bacterial attachment to gastric surfaces, increasing strain virulence and forming a recognized risk factor for peptic ulcers and gastric cancer. High sequence variation causes BabA functional diversity, but the underlying structural-molecular determinants are unknown. We generated X-ray structures of representative BabA isoforms that reveal a polymorphic, three-pronged Leb binding site. Two diversity loops, DL1 and DL2, provide adaptive control to binding affinity, notably ABO versus O bg preference. H. pylori strains can switch bg preference with single DL1 amino acid substitutions, and can coexpress functionally divergent BabA isoforms. The anchor point for receptor binding is the embrace of an ABO fucose residue by a disulfide-clasped loop, which is inactivated by reduction. Treatment with the redox-active pharmaceutic N-acetylcysteine lowers gastric mucosal neutrophil infiltration in H. pylori-infected Leb-expressing mice, providing perspectives on possible H. pylori eradication therapies.
Background: Pulmonary embolism (PE) is a common disease in the USA responsible for up to 10% of hospital mortality. Modified wells score (MWS) and D-dimer assay are used to categorize patients into high or low probability of PE. Patient with high probability need Computed tomography pulmonary angiography (CTPA), while patients with low probability and low D-dimer can safely forgo the CTPA. Objectives: The aim of this study was to investigate the rate of inappropriate CTPA use in the emergency department of a community teaching hospital. Methods: A retrospective chart review of adult patients who underwent CTPA for suspected PE in the emergency department for 2015 was done. CTPA use was considered inappropriate if MWS was less than or equal to 4 and D-dimer was either not ordered or its value was less than 500 μg/L. Bivariate analysis with Fisher’s exact tests and Student’s t-tests as well as multivariate logistic regression analysis were done to examine relationship between study explanatory variables and study outcome.
Results: 295 patients were included in the study. The mean age was 51.2(±14.5) years, 68.8% were females. The prevalence of PE was 5.4% and 41% of the CTPAs -were inappropriately ordered. Males were twice (OR 2.1; 95% CI 1.2, 3.6) as likely as females to have an inappropriately ordered CTPA after controlling for a high MWS, age, and tobacco history.
Conclusion: CTPA is overused to diagnose PE in the emergency department. Quality improvement projects are needed to encourage physicians to adhere to the current guidelines.
The human stomach pathogen Helicobacter pyloriattaches to healthy and inflamed gastric tissue through members of a paralogous family of 'Helicobacter outer membrane proteins' (Hops), including adhesins BabA, SabA, HopQ, LabA and HopZ. Hops share a conserved 25 kDa C-terminal region that is thought to form an autotransporter-like transmembrane domain. Instead, our results show that Hops contain a non-continuous transmembrane domain, composed of seven predicted β-strands at the C-terminus and one at the N-terminus. Folding and outer membrane localization of the C-terminal β-domain critically depends on a predicted transmembrane β-strand within the first 16 N-terminal residues. The N-terminus is shown to reside in the periplasm, and our crystal and small angle X-ray scattering structures for the SabA extracellular domain reveal a conserved coiled-coil stem domain that connects to transmembrane β-strand 1 and 2. Taken together, our data show that Hop adhesins represent a novel outer membrane protein topology encompassing an OmpA-like 8-stranded β-barrel that is interrupted by a 15-108 kDa domain inserted inside the first extracellular loop. The insertion of large, folded domains in an extracellular loop is unprecedented in bacterial outer membrane proteins and is expected to have important consequences on how these proteins reach the cell surface.
Background/AimsEndoscopic submucosal dissection (ESD) with air insufflation is commonly used for the staging and treatment of early gastric carcinoma. However, carbon dioxide (CO2) use has been shown to cause less post-procedural pain and fewer adverse events. The objective of this study was to compare the post-procedural pain and adverse events associated with CO2 and air insufflation in ESD.MethodsA systematic search was conducted for randomized control trials (RCTs) comparing the two approaches in ESD. The Mantel-Haenszel method was used to analyze the data. The mean difference (MD) and odds ratio (OR) were used for continuous and categorical variables, respectively.ResultsFour RCTs with a total of 391 patients who underwent ESD were included in our meta-analysis. The difference in maximal post-procedural pain between the two groups was statistically significant (MD, -7.41; 95% confidence interval [CI], -13.6 – -1.21; p=0.020). However, no significant differences were found in the length of procedure, end-tidal CO2, rate of perforation, and postprocedural hemorrhage between the two groups. The incidence of overall adverse events was significantly lower in the CO2 group (OR, 0.51; CI, 0.32–0.84; p=0.007).Conclusions:CO2 insufflation in gastric ESD is associated with less post-operative pain and discomfort, and a lower risk of overall adverse events compared with air insufflation.
Background: Reperfusion injury is an important limiting factor associated with revascularization in acute myocardial infarction (AMI (OR 1.05,. Similarly, we did not find any significant differences in terms of cardiogenic shock, recurrent ischemia and myocardial infarction, heart failure and echocardiographic outcomes. Conclusions: Cyclosporine A is not helpful in preventing reperfusion injury in AMI. (Cardiol J 2017; 24, 1: 43-50)
Helicobacter pylori is a human pathogen that colonizes about 50% of the world's population, causing chronic gastritis, duodenal ulcers and even gastric cancer. A steady emergence of multiple antibiotic resistant strains poses an important public health threat and there is an urgent requirement for alternative therapeutics. The blood group antigen-binding adhesin BabA mediates the intimate attachment to the host mucosa and forms a major candidate for novel vaccine and drug development. Here, the recombinant expression and crystallization of a soluble BabA truncation (BabA 25-460 ) corresponding to the predicted extracellular adhesin domain of the protein are reported. X-ray diffraction data for nanobody-stabilized BabA 25-460 were collected to 2.25 Å resolution from a crystal that belonged to space group P2 1 , with unit-cell parameters a = 50.96, b = 131.41, c = 123.40 Å , = 90.0, = 94.8, = 90.0 , and which was predicted to contain two BabA 25-460 -nanobody complexes per asymmetric unit.
BackgroundAchalasia is a primary esophageal motility disorder of unknown etiology associated with abnormalities in peristalsis and lower esophageal sphincter relaxation. The disease is incurable; however, definitive treatment procedures like pneumatic dilation (PD)/balloon dilation and laparoscopic esophageal myotomy (LEM) are performed to relieve dysphagia and related symptoms. Currently, there is paucity of data comparing the outcomes of these procedures. The aim of this meta-analysis is to compare the short- and long-term success rates of PD and LEM.MethodsA thorough systematic search of PubMed, Scopus, clinicaltrials.gov, and Cochrane library was conducted for randomized controlled trials (RCTs) comparing the outcomes of PD versus LEM in the treatment of achalasia. The Mantel-Haenszel method and random effect model were used to analyze the data. RCTs with outcome data at 3-month, 1-year, and 5-year intervals were analyzed.ResultsA total of 437,378 and 254 patients at 3-month, 1-year, and 5-year intervals were analyzed for outcome data. At 3 months and 1 year, PD was not as effective as LEM (odds ratio [OR]: 0.50; confidence interval [CI] 0.31–0.82; P = 0.009 and OR: 0.47; CI 0.22–0.99; P = 0.21) but at 5 years, one procedure was non-inferior to the other (OR: 0.62; 0.33–1.19; P = 0.34).ConclusionPD was as effective as LEM in relieving symptoms of achalasia in the long-term.
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