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Chlamydia pneumoniae (C. pneumoniae) infection in humans is universal and causes various respiratory infectious diseases, making a safe and effective preventive vaccine essential. In this study, a multi-epitope vaccine with CTLA-4 extracellular structure was constructed by an immunoinformatics approach. Since MOMP protein is the major extracellular protein in C. pneumoniae and has good immunogenicity and high conservation, we selected the MOMP protein of C. pneumoniae as the antigen target, predicted the T and B cell epitopes of the MOMP protein and then connected the CTLA-4 extracellular structure with the predicted dominant epitopes by various linkers to construct a multi-epitope vaccine. The biochemical characterization of the multi-epitope vaccine showed its immunogenicity and anti-allergic properties. The tertiary structure of this vaccine, along with molecular docking, molecular dynamics simulation, and principal component analysis, showed that the multi-epitope vaccine structure interacted with B7 (B7-1, B7-2) and toll-like receptors (TLR-2, TLR-4). Ultimately, the vaccine was cloned and effectively expressed in silico on an insect baculovirus expression vector (pFastBac1). These analyses showed that the designed vaccine could potentially target antigen-presenting cells and was immune to C. pneumoniae, which provided novel strategies for developing the vaccine. [ABSTRACT FROM AUTHOR]

Fecobionics is an integrated device that has shown promise for assessment of anorectal function. We used a wireless Fecobionics prototype to visualize defecatory patterns and to compute volume–pressure, contraction work, and flow. Twelve normal subjects were studied. The probe was 10 cm-long and contained pressure sensors and electrodes for impedance planimetry. Pressures, diameters, and volume data during defecation were analyzed. The bag was distended inside rectum to the urge-to-defecate level where after the subjects were asked to evacuate. The contraction work and defecatory flow were computed from the volume changes during expulsion. The minimum anal diameter during the evacuation was 17.6 ± 1.5 mm. The middle diameter recording was 10–20% lower than the front diameter channels and 10–20% bigger than the rear channels. The bag volume at urge correlated with the minimum diameter (r = 0.63). The diameter-pressure and volume–pressure loops were counterclockwise with phases of bag filling, isometric contraction, ejection and anal passage. The defecatory contraction work was 3520 ± 480 mL × cmH2O. The maximum flow during defecation was 302 ± 33 mL/s. The flow was associated with the anal diameter (r = 0.84) but not with the rectoanal pressure gradient (r = 0.14). Volume–pressure loops have a tremendous impact on the understanding of cardiopulmonary pathophysiology. Future studies will shed light on potential clinical impact in defecatory pathophysiology. [ABSTRACT FROM AUTHOR]

Background: Ivabradine improves cardiac function and clinical outcomes in chronic heart failure (HF) by reducing heart rate (HR), but there is a lack of real-world data on its effectiveness and safety in Chinese patients. Methods: We designed a prospective, multicenter, observational study of Chinese adults with HF and left ventricular systolic dysfunction, resting HR ≥ 75 beats per minute (bpm), and an indication for ivabradine treatment. An interim analysis was performed using a cut-off date of 31 October 2019. The primary outcome was change in HR at 6 months after the initiation of ivabradine. Secondary endpoints included change in New York Heart Association (NYHA) functional class; quality of life (QoL), measured using the Kansas City Cardiomyopathy Questionnaire (KCCQ); and adverse events (AEs). Results: Overall, 655 subjects were included in the interim analysis. Mean reduction in HR from baseline was 13.2 (95% confidence interval [CI] 11.2–15.2) bpm at Month 1, and 14.5 (95% CI 11.8–17.2) bpm at Month 6 (p < 0.001 for both changes). NYHA functional class and KCCQ scores improved significantly over time (p < 0.001 for all comparisons with baseline), indicating amelioration of symptoms and better QoL, respectively. Forty-four subjects (6.7%) reported a total of 60 ivabradine-related AEs, most frequently phosphenes and bradycardia (both n = 6, 0.9%). Conclusion: Treatment with ivabradine for 6 months effectively reduced HR and improved functional class and QoL in Chinese patients with chronic HF. Treatment was well tolerated. Clinical Trial Registration: ISRCTN11703380; registered on 8 November 2016. [ABSTRACT FROM AUTHOR]

Diverticulosis results from the development of pouch-like structures, called diverticula, over the colon. The etiology of the disease is poorly understood resulting in a lack of effective treatment approaches. It is well known that mechanical stress plays a major role in tissue remodeling, yet its role in diverticulosis has not been studied. Here, we used computational mechanics to investigate changes in stress distribution engendered over the colon tissue by the presence of a pouch-like structure. The objectives of the study were twofold: (1) observe how stress distribution changes around a single pouch and (2) evaluate how stress elevation correlates with the size of the pouch. Results showed that high stresses are concentrated around the neck of a pouch, and their values and propagation increase with the size of the pouch neck rather than the pouch surface area. These findings suggest that stress distribution may change in diverticulosis and a vicious cycle may occur where pouch size increases due to stress elevation, which in turn elevates stress further and so on. Significant luminal pressure reduction would be necessary to maintain stress at normal level according to our results and therapeutic approaches aimed directly at reducing stress should rather be sought after. [ABSTRACT FROM AUTHOR]

Fulminant myocarditis is primarily caused by infection with any number of a variety of viruses. It arises quickly, progresses rapidly, and may lead to severe heart failure or circulatory failure presenting as rapid-onset hypotension and cardiogenic shock, with mortality rates as high as 50%-70%. Most importantly, there are no treatment options, guidelines or an expert consensus statement. Here, we provide the first expert consensus, the Chinese Society of Cardiology Expert Consensus Statement on the Diagnosis and Treatment of Fulminant Myocarditis, based on data from our recent clinical trial (NCT03268642). In this statement, we describe the clinical features and diagnostic criteria of fulminant myocarditis, and importantly, for the first time, we describe a new treatment regimen termed life support-based comprehensive treatment regimen. The core content of this treatment regimen includes (i) mechanical life support (applications of mechanical respirators and circulatory support systems, including intraaortic balloon pump and extracorporeal membrane oxygenation, (ii) immunological modulation by using sufficient doses of glucocorticoid, immunoglobulin and (iii) antiviral reagents using neuraminidase inhibitor. The proper application of this treatment regimen may and has helped to save the lives of many patients with fulminant myocarditis. [ABSTRACT FROM AUTHOR]

With the advances of IT technology, all businesses are disrupted by digitalization and have to adapt and transform. The role of IT has gone beyond computing. The capability of Information management is critical to the organizational strategy. At the same time, the finance function is undergoing massive transformation, with the IT function building systems and solutions for the new environment. Budget, as one of the key management tool of the finance function, has been pushed by digitalization to provide real time information and enhance decision making and value to the business. Based on a case study, the authors discuss the integration of the IT system with the budgetary control system in support of the strategy of the company, and a dynamic model of the process was built. The underlying mechanism linking IT to strategy is also discussed. In this way, the authors prove that when properly integrated with budget of the finance function, IT can move from computation technology to become capabilities that create value for business. [ABSTRACT FROM AUTHOR]

Diverticulosis is a structural alteration of the colon tissue characterized by the development of pouch-like structures called diverticula. It afflicts a significant portion of the population in Western countries, with a higher prevalence among the elderly. Diverticulosis is believed to be the result of a synergetic interaction between inherent tissue weakness, diet, colonic microstructure, motility, and genetic factors. A validated etiology has, however, not yet been established. Non-surgical treatment is currently lacking due to this poor understanding, and surgical colon resection is the only long-term solution following recurrent complications. With rising prevalence, the burden of diverticulosis on patients and hospital resources has increased over the past several years. More efficient and less invasive treatment approaches are, thus, urgently needed. Animal models of diverticulosis are crucial to enable a preclinical assessment and evaluation of such novel approaches. This review discusses the animal models of diverticulosis that have been proposed to date. The current models require either a significant amount of time to develop diverticulosis, present a relatively low success rate, or seriously deteriorate the animals' systemic health. Recommendations are thus provided to address these pitfalls through the selection of a suitable animal and the combination of multiple risk factors for diverticulosis. [ABSTRACT FROM AUTHOR]

Mortality during follow-up after acute Type B aortic dissection is substantial with aortic expansion observed in over 59% of the patients. Lumen pressure differential is considered a prime contributing factor for aortic dilation after propagation. The objective of the study was to evaluate the relationship between changes in vessel geometry with and without lumen pressure differential post propagation in an ex vivo porcine model with comparison with patient clinical data. A pulse duplicator system was utilized to propagate the dissection within descending thoracic porcine aortic vessels for set proximal (%circumference of the entry tear: 40%, axial length: 2 cm) and re-entry (50% of distal vessel circumference) tear geometry. Measurements of lumen pressure differential were made along with quantification of vessel geometry ( n = 16). The magnitude of mean lumen pressure difference measured after propagation was low (~ 5 mmHg) with higher pressures measured in false lumen and as anticipated the pressure difference approached zero after the creation of distal re-entry tear. False lumen Dissection Ratio (FDR) defined as arc length of dissected wall divided by arc length of dissection flap, had mean value of 1.59 ± 0.01 at pressure of 120/80 mmHg post propagation with increasing values with increase in pulse pressure that was not rescued with the creation of distal re-entry tear ( p < 0.01). An average FDR of 1.87 ± 0.27 was measured in patients with acute Type B dissection. Higher FDR value (FDR = 1 implies zero dissection) in the presence of distal re-entry tear demonstrates an acute change in vessel morphology in response to the dissection independent of local pressure changes challenges the re-apposition of the aortic wall. [ABSTRACT FROM AUTHOR]

Installing an inducer upstream of the main impeller is an effective approach for improving the anti-cavitation performance of a highspeed centrifugal pump. For a high-speed centrifugal pump with an inducer, the number of inducer blades can affect its internal flow and external performance. We studied the manner in which the number of inducer blades can affect the anti-cavitation characteristics and external performance of a centrifugal pump. We first use the Rayleigh-Plesset equation and the mixture model to simulate the vaporliquid flow in a centrifugal pump with an inducer, and then predict its external performance. Finally, we tested the external performance of a centrifugal pump with 2-, 3-and 4-bladed inducers, respectively. The results show that the simulations of external performance in a centrifugal pump are in accordance with our experiments. Based on this, we obtained vapor volume fraction distributions for the inducer, the impeller, and in the corresponding whole flow parts. We discovered that the vapor volume fraction of a centrifugal pump with a 3-bladed inducer is less than that of a centrifugal pump with 2-or 4-bladed inducers, which means that a centrifugal pump with a 3-bladed inducer has a better external and anti-cavitation performance. [ABSTRACT FROM AUTHOR]

The anti-cavitation performance of a high-speed centrifugal pump with a splitter-bladed inducer is investigated under different flow rates and different inlet pressures. Simulations and external characteristics experiments are carried out. Static pressure and the vapor volume fraction distributions on the inducer and the impeller of the pump under various operation conditions are obtained. The results show that the cavitation developments on the impeller and on the inducer with the flow rates are reverse, while the development of the inlet pressure on the inducer and the impeller is the same. Cavitation on the impeller increases with the increase of flow rates, and it extends to the near passages with rotating, while cavitation on the inducer is more complex than that on the impeller. Cavitation at the inlet of the inducer decreases with the increase of flow rates, while cavitation at the outlet of the inducer is opposite. The results also show that cavitation development on the impeller and on the inducer with the inlet pressure is the same. Cavitation both decreases with the increase of the inlet pressure at the same flow rate. Furthermore, asymmetric cavitation on the impeller and on the inducer is both observed. And the asymmetric degree of cavitation on the impeller is higher than that on the inducer. [ABSTRACT FROM AUTHOR]

A high-speed centrifugal pump with a splitter-blade inducer is investigated in this work. The flow with rotating cavitation is numerically simulated, external characteristics are subjected to experimental tests, and the internal flow is visualized. These procedures are conducted to obtain the pressure, velocity, and vapor volume fraction distribution in the inducer and the impeller of the centrifugal pump. Bubble occurrence, development, and collapse are also observed. The predicted H- Q and η- Q curves agree with the experimental results of external characteristics. The calculated vapor volume fraction also agrees with the experimental results obtained from the visualization system. The mechanism of bubble evolution and the anti-cavitation performance of the high-speed centrifugal pump with a splitter-blade inducer are clearly elucidated. [ABSTRACT FROM AUTHOR]

Background: Bariatric surgery using laparoscopic techniques is the most effective treatment for morbid obesity. The objective of the study is to assess the safety and efficacy of a novel laparoscopic reversible gastric restrictive (RGR) device in a group of obese dogs. An implant was also performed in a cadaver to assess implant feasibility in a human. Methods: Four obese mongrel dogs were subjected to RGR implantation for 3 months followed by recovery for an additional 6 weeks after device removal. Food intake, body weight, radiographic barium imaging, and gastric endoscopy were used to monitor RGR performance before implant, after implant, and implant removal. An additional RGR laparoscopic implantation procedure was performed in a human cadaver. Results: The implanted obese dogs exhibited a significant decrease in food intake and body weight over 3 months with the RGR device. The reduction of food intake was sustained at an average of 46 % after implant and the excess weight loss reached an average of 75 % at the end of 12 weeks with recovery to approximately 78 % of baseline after 6 weeks of implant removal. Barium imaging and gastric endoscopy both confirmed passage for food through the restrictive device channel in the stomach. The RGR device was successfully implanted laparoscopically on the cadaver stomach in less than an hour. Conclusions: The RGR device is laparoscopically deliverable and removable with effective and sustainable weight loss over a 12-week period in an obese dog model. The implant is also technically feasible in man. [ABSTRACT FROM AUTHOR]

Angiotensin II (ANGII) plays an important role in the pathogenesis of atherosclerosis by inducing proliferation of vascular smooth muscle cells (VSMCs). In our study, we observed the effects of valsartan on proliferation of cultured VSMCs treated with or without ANGII by cell counting and methyl thiazolyl tetrazolium (MTT) assay, and detected the expression of mitofusin 2 (Mfn2), a newly discovered cell proliferation inhibitor and a related cell proliferation signaling pathway protein by Western blotting. ANGII at a concentration of 10 mol/L significantly stimulated VSMCs proliferation, down-regulated the expression of Mfn2 and up-regulated the expression of Raf and ERK1/2. Valsartan inhibited such effects of ANGII at concentrations of 10 and 10 mol/L, but not at 10 mol/L. Valsartan had no significant effect on the proliferation of untreated VSMCs. These results suggest that valsartan inhibits ANGII-induced proliferation of VSMCs in vitro via Mfn2-Ras-Raf-ERK/MAPK signaling pathway. [ABSTRACT FROM AUTHOR]

Background: Gastric restrictive procedures are considered effective weight loss treatment for severe obesity. The aim of the study was to evaluate the efficacy and safety of a reversible implant that renders a partial restriction of stomach in a canine model. Methods: The device was comprised of two longitudinal parallel non-compressive plates with two C-rings to create a small gastric pouch that opposed gastric distension. Three groups of non-obese mongrel dogs were included: group I ( n = 6) underwent surgical implant for 6 weeks, group II ( n = 6) underwent surgical implant for 6 weeks, followed by surgical removal of the implant and additional monitoring for 5 weeks, and group III ( n = 5) served as sham-operated controls for groups I and II. Food intake and body weight were monitored, and the stomachs were examined histologically postmortem. Results: The average food intake was significantly decreased by 38.2% in group I as compared to group III throughout the 6 weeks of surgical implant ( P < 0.05). The implanted dogs showed a progressive weight loss as compared to sham, which reached 21% by the end of 6 weeks. In group II, after 5 weeks of implant removal, the body weights recovered to approximately 96% of baseline. Histological evidence of the implant site at the gastric walls revealed no significant structural changes, tissue ischemia, hemorrhage, or necrosis. Conclusion: Our results validate the feasibility of a reversible gastric restriction implant in a non-obese canine model, with the potential for achieving significant weight loss within 6 weeks and with no injury to the gastric wall. [ABSTRACT FROM AUTHOR]

Quality protein maize (QPM) is a high lysine-containing corn that is based on genetic modification of the opaque2 ( o2) mutant. In QPM, modifier genes convert the starchy endosperm of o2 to the vitreous phenotype of wild type maize. There are multiple, unlinked o2 modifier loci ( Opm) in QPM and their nature and mode of action are unknown. We previously identified seven Opm QTLs and characterized 16 genes that are differentially up-regulated at a significant level in K0326Y QPM, compared to the starchy endosperm mutant W64A o2. In order to further characterize these Opm QTLs and the genes up-regulated in K0326Y QPM, we created a population of 314 recombinant inbred lines (RILs) from a cross between K0326Y QPM and W64A o2. The RILs were characterized for three traits associated with endosperm texture: vitreousness, density and hardness. Genetic linkage analysis of the RIL population confirmed three of the previously identified QTLs associated with o2 endosperm modification in K0326Y QPM. Many of the genes up-regulated in K0326Y QPM showed substantially higher levels of expression in vitreous compared with opaque RILs. These included genes associated with the upstream regulation of the ethylene response pathway, and a gene encoding a regulatory subunit of pyrophosphate-dependent fructose-6-phosphate 1-phosphotransferase, an adaptive enzyme of the glycolytic pathway. [ABSTRACT FROM AUTHOR]

Oxalic acid is an essential virulence factor of Sclerotinia sclerotiorum that elicits wilting symptoms in infected host plants. Foliar wilting in response to oxalic acid is known to be dependent on an increase in stomatal conductance. To determine whether stomatal regulation controls susceptibility to S. sclerotiorum, abscisic acid-insensitive and open stomata mutants of Arabidopsis thaliana were analyzed. Whereas abscisic acid-insensitive mutants were hypersusceptible to S. sclerotiorum, open stomata mutants were as susceptible as wild type. It was concluded that stomatal regulation does not control susceptibility to S. sclerotiorum because open stomata mutants are known to only impair guard cells whereas abscisic acid-insensitive mutants also affect other cell types. Guard cell-independent processes also control sensitivity to oxalic acid because oxalic acid was more toxic to abscisic acid-insensitive mutants than to open stomata mutants. To explore a possible mechanism of toxicity, production of reactive oxygen species was measured in plant cells after exposure to oxalic acid. Oxalic acid was found to elicit reactive oxygen species production independently of abscisic acid. Nevertheless, cancellation of reactive oxygen species elicitation after co-stimulation of wild-type guard cells with oxalic acid and abscisic acid provided evidence for antagonistic interaction between both molecules. [ABSTRACT FROM AUTHOR]