Hop-family Helicobacter outer membrane adhesins form a novel class of Type 5-like secretion proteins with an interrupted ß-barrel domain.

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 ß-strands at the C-terminus and one at the N-terminus. Folding and outer membrane localization of the C-terminal ß-domain critically depends on a predicted transmembrane ß-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 ß-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 ß-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.

Drug-eluting stent placement versus coronary artery bypass surgery for unprotected left main coronary artery disease: A meta-analysis of randomized controlled trials.

BACKGROUND: Coronary artery bypass grafting (CABG) is the standard of care for treating left main coronary lesions. However, recently published randomized controlled trials (RCT) have shown conflicting results. We sought to compare clinical outcomes of percutaneous coronary intervention (PCI) with drug-eluting stent placement to CABG using a meta-analysis of randomized controlled trials. METHODS: A systemic search of Pubmed, Scopus, Cochrane library, and Clinicaltrials.gov was performed for randomized controlled trials comparing PCI with CABG in patients with left main stenosis. Data were analyzed using random effect models and Mantel-Haenszel methods. The primary outcome was major adverse cardiovascular and cerebral events (MACCE). The secondary outcomes were myocardial infarction, stroke, cardiac, and all-cause mortality. A subgroup analysis based on SYNTAX score was also performed. RESULTS: A total of 4595 patients (2297 in the PCI group and 2298 in the CABG group) from five RCTs were included in the analysis. There were significant differences in MACCE (odds ratio [OR] 1.36, confidence interval [CI] 95%, 1.18-1.58, p-value: < 0.0001) and repeat revascularization (OR 1.85, CI 95%, 1.53-2.23, p-value: < 0.00001) favoring CABG. There were no significant differences in the incidence of myocardial infarction, stroke, or cardiac and all-cause mortality. Based on SYNTAX score, CABG was superior in terms of MACCE only in the subgroup with SYNTAX score of 33 or more. CONCLUSIONS: CABG results in fewer MACCE and need for repeat revascularization than PCI in patients with unprotected left main disease.

Salinity legacy: Foliar microbiome's history affects mutualist-conferred salinity tolerance.

The rapid human-driven changes in the environment during the Anthropocene have placed extreme stress on many plants and animals. Beneficial interactions with microorganisms may be crucial for ameliorating these stressors and facilitating the ecosystem services host organisms provide. Foliar endophytes, microorganisms that reside within leaves, are found in essentially all plants and can provide important benefits (e.g., enhanced drought tolerance or resistance to herbivory). However, it remains unclear how important the legacy effects of the abiotic stressors that select on these microbiomes are for affecting the degree of stress amelioration provided to their hosts. To elucidate foliar endophytes' role in host-plant salt tolerance, especially if salinity experienced in the field selects for endophytes that are better suited to improve the salt tolerance of their hosts, we combined field collections of 90 endophyte communities from 30 sites across the coastal Everglades with a manipulative growth experiment assessing endophyte inoculation effects on host-plant performance. Specifically, we grew >350 red mangrove (Rhizophora mangle) seedlings in a factorial design that manipulated the salinity environment the seedlings experienced (freshwater vs. saltwater), the introduction of field-collected endophytes (live vs. sterilized inoculum), and the legacy of salinity stress experienced by these introduced endophytes, ranging from no salt stress (0 parts per thousand [ppt] salinity) to high salt stress (40 ppt) environments. We found that inoculation with field-collected endophytes significantly increased mangrove performance across almost all metrics examined (15%-20% increase on average), and these beneficial effects typically occurred when the endophytes were grown in saltwater. Importantly, our study revealed the novel result that endophyte-conferred salinity tolerance depended on microbiome salinity legacy in a key coastal foundation species. Salt-stressed mangroves inoculated with endophyte microbiomes from high-salinity environments performed, on average, as well as plants grown in low-stress freshwater, while endophytes from freshwater environments did not relieve host salinity stress. Given the increasing salinity stress imposed by sea level rise and the importance of foundation species like mangroves for ecosystem services, our results indicate that consideration of endophytic associations and their salinity legacy may be critical for the successful restoration and management of coastal habitats.

Ethnomedicinal landscape: distribution of used medicinal plant species in Nepal.

BACKGROUND: The risk of losing traditional knowledge of medicinal plants and their use and conservation is very high. Documenting knowledge on distribution and use of medicinal plants by different ethnic groups and at spatial scale on a single platform is important from a conservation planning and management perspective. The sustainable use, continuous practice, and safeguarding of traditional knowledge are essential. Communication of such knowledge among scientists and policy makers at local and global level is equally important, as the available information at present is limited and scattered in Nepal. METHODS: In this paper, we aimed to address these shortcomings by cataloguing medicinal plants used by indigenous ethnic groups in Nepal through a systematic review of over 275 pertinent publications published between 1975 and July 2021. The review was complemented by field visits made in 21 districts. We determined the ethnomedicinal plants hotspots across the country and depicted them in heatmaps. RESULTS: The heatmaps show spatial hotspots and sites of poor ethnomedicinal plant use documentation, which is useful for evaluating the interaction of geographical and ethnobotanical variables. Mid-hills and mountainous areas of Nepal hold the highest number of medicinal plant species in use, which could be possibly associated with the presence of higher human population and diverse ethnic groups in these areas. CONCLUSION: Given the increasing concern about losing medicinal plants due to changing ecological, social, and climatic conditions, the results of this paper may be important for better understanding of how medicinal plants in use are distributed across the country and often linked to specific ethnic groups.

Computed tomography pulmonary angiography is overused to diagnose pulmonary embolism in the emergency department of academic community hospital.

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.

Primary Idiopathic Osteoarthropathy: Could It Be Related to Alcoholism?

Background. Hypertrophic osteoarthropathy (HOA) is a syndrome characterized by abnormal proliferation of the skin and bony structures at the distal extremities resulting in digital clubbing, periosteal bony reaction, and joint effusion. It can be primary (idiopathic) without any clear identifiable etiology as well as secondary to variety of systemic diseases most notably lung pathology. Case Presentation. We describe a rare case of primary idiopathic osteoarthropathy in a male patient who presented with severe pain and tenderness in his legs. His history was significant for long standing alcoholism. Physical examination showed severe fingers and toes clubbing. He reported similar changes in his mother. Clinical and radiological findings were remarkable for distal leg tenderness and diffuse periosteal bony reactions, respectively. Computerized tomography scan failed to show any pathology apart from fatty liver infiltration. In the absence of obesity or diabetes, this was consistent with alcoholic steatosis. He was started on nonsteroidal anti-inflammatory drug which dramatically improved his symptoms. Conclusion. Primary hypertrophic osteoarthropathy should be considered in a previously healthy person presenting with bony pain and finger clubbing especially after ruling out the common secondary causes. Moreover, alteration of prostaglandin metabolism secondary to alcoholic consumption might be a contributing factor.

Laparoscopic esophageal myotomy versus pneumatic dilation in the treatment of idiopathic achalasia: a meta-analysis of randomized controlled trials.

BACKGROUND: Achalasia 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. METHODS: A 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. RESULTS: A 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). CONCLUSION: PD was as effective as LEM in relieving symptoms of achalasia in the long-term.

Carbon Dioxide versus Air Insufflation in Gastric Endoscopic Submucosal Dissection: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND/AIMS: Endoscopic 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. METHODS: A 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. RESULTS: Four 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.

Impact of cyclosporine A use in the prevention of reperfusion injury in acute myocardial infarction: A meta-analysis.

BACKGROUND: Reperfusion injury is an important limiting factor associated with revascularization in acute myocardial infarction (AMI). Various therapies have been tried in an attempt to prevent reperfusion injury, but the search has been elusive. The role of cyclosporine A (CsA) in the prevention of reperfusion injury in AMI is still not clear. The objective of this study was to find out whether CsA is beneficial in reducing reperfusion injury in acute ST elevation myocardial infarction. METHODS: We performed a systematic search of Pubmed, Scopus, clinicaltrial.gov, and Cochrane Database for randomized control trials (RCT) measuring the effect of CsA in AMI compared to a placebo. The Mantel-Haenszel method and random effect model were used to analyze the data. A total of 1,566 patients (776 in the CsA group and 790 in the placebo group), who participated in 5 RCTs were included in our meta-analysis. RESULTS: We did not find any significant differences between the CsA and placebo groups in terms of all-cause death (odds ratio [OR] 1.21, 95% confidence interval [CI] 0.78-1.87) and cardiovascular death (OR 1.05, 95% CI 0.66-2.49). 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.

Structural Insights into Polymorphic ABO Glycan Binding by Helicobacter pylori.

The Helicobacter pylori adhesin BabA binds mucosal ABO/Le(b) 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 Le(b) 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 Le(b)-expressing mice, providing perspectives on possible H. pylori eradication therapies.

Expression, purification and X-ray crystallographic analysis of the Helicobacter pylori blood group antigen-binding adhesin BabA.

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 Šresolution from a crystal that belonged to space group P21, with unit-cell parameters a = 50.96, b = 131.41, c = 123.40 Å, α = 90.0, ß = 94.8, γ = 90.0°, and which was predicted to contain two BabA(25-460)-nanobody complexes per asymmetric unit.