The prevalence of autoimmune diseases (ADs) worldwide has rapidly increased over the past few decades. Thus, in addition to the classical risk factors for ADs, such as genetic polymorphisms, ...infections and smoking, environmental triggers have been considered. Recent sequencing-based approaches have revealed that patients with extra-intestinal ADs, such as multiple sclerosis, rheumatoid arthritis, type 1 diabetes and systemic lupus erythematosus, have distinct gut microbiota compositions compared to healthy controls. Faecal microbiota transplantation or inoculation with specific microbes in animal models of ADs support the hypothesis that alterations of gut microbiota influence autoimmune responses and disease outcome. Here, we describe the compositional and functional changes in the gut microbiota in patients with extra-intestinal AD and discuss how the gut microbiota affects immunity. Moreover, we examine how the gut microbiota might be modulated in patients with ADs as a potential preventive or therapeutic approach.
Hydrogels actuators (HAs) that can reversibly respond to stimuli have applications in diverse fields. However, faster response rates and improved control over actuation timing and location are ...required to fulfill their potential. To address these criteria, we synthesized near-infrared light-driven HAs by interfacing genetically engineered elastin-like polypeptides with reduced-graphene oxide sheets. The resulting nanocomposites exhibited rapid and tunable motions controlled by light position, intensity, and path, including finger-like flexing and crawling. This work demonstrates the ability of rationally designed proteins to be combined with synthetic nanoparticles for the creation of macroscale functional materials.
Myocardial dysfunction in end stage cirrhotic liver disease, termed cirrhotic cardiomyopathy, is a long known, but little understood comorbidity seen in ∼50% of adults and children who present for ...liver transplantation. Structural, functional, hemodynamic and electrocardiographic aberrations that occur in the heart as a direct consequence of a damaged liver, is associated with multi-organ failure and increased mortality and morbidity in patients undergoing surgical procedures such as porto-systemic shunt placement and liver transplantation. Despite its clinical significance and rapid advances in science and pharmacotherapy, there is yet no specific treatment for this disease. This may be due to a lack of understanding of the pathogenesis and mechanisms behind how a cirrhotic liver causes cardiac pathology. This review will focus specifically on insights into the molecular mechanisms that drive this liver-heart interaction. Deeper understanding of the etio-pathogenesis of cirrhotic cardiomyopathy will allow us to design and test treatments that can be targeted to prevent and/or reverse this co-morbid consequence of liver failure and improve health care delivery and outcomes in patients with cirrhosis.
Objective Broad application of endovascular aneurysm repair (EVAR) has led to a rapid decline in open aneurysm repair (OAR) and improved patient survival, albeit at a higher overall cost of care. The ...aim of this report is to evaluate national trends in the incidence of unruptured and ruptured abdominal aortic aneurysms (AAAs), their management by EVAR and OAR, and to compare overall patient characteristics and clinical outcomes between these two approaches. Methods A retrospective analysis of the cross-sectional National Inpatient Sample (2000-2010) was used to evaluate patient characteristics and outcomes related to EVAR and OAR for unruptured and ruptured AAAs. Data were extrapolated to represent population-level statistics through the use of data from the U.S. Census Bureau. Comparisons between groups were made with the use of descriptive statistics. Results There were 101,978 patients in the National Inpatient Sample affected by AAAs over the 11-year span of this study; the average age was 73 years, 21% were women, and 90% were white. Overall in-hospital mortality rate was 7%, with a median length of stay (LOS) of 5 days and median hospital charges of $58,305. In-hospital mortality rate was 13 times greater for ruptured patients, with a median LOS of 9 days and median charges of $84,744. For both unruptured and ruptured patients, EVAR was associated with a lower in-hospital mortality rate (4% vs 1% for unruptured and 41% vs 27% for ruptured; P < .001 for each), shorter median LOS (7 vs 2; 9 vs 6; P < .001) but a 27%-36% increase in hospital charges. Conclusions The overall use of EVAR has risen sharply in the past 10 years (5.2% to 74% of the total number of AAA repairs) even though the total number of AAAs remains stable at 45,000 cases per year. In-hospital mortality rates for both ruptured and unruptured cases have fallen by more than 50% during this time period. Lower mortality rates and shorter LOS despite a 27%-36% higher cost of care continues to justify the use of EVAR over OAR. For patients with suitable anatomy, EVAR should be the preferred management of both ruptured and unruptured AAAs.
Research efforts in trust evaluation has evolved to provide security in Wireless Sensor Networks (WSNs), while being dependent on external parameters and network topology. Existing node level trust ...evaluation in WSNs evaluate trust over 1-hop assuring trustworthiness of an immediate node. This paper proposes trust evaluation using the intrinsic property of a node memory over a multihop scenario which also evaluates the route. The work proposes a multihop trust evaluation protocol using TEAM and TEAP algorithms. Two proposed trust evaluation models each are proposed using normative and empirical methods in multihop algorithms. The proposed methodology establishes a trusted destination node along with trusted nodes in the route. The efficacy of the proposed work and its implementation is demonstrated using extensive experiments and the results illustrate consistency and resilience against node memory tampering.
We compared the angiotensin receptor-neprilysin inhibitor LCZ696 with enalapril in patients who had heart failure with a reduced ejection fraction. In previous studies, enalapril improved survival in ...such patients.
In this double-blind trial, we randomly assigned 8442 patients with class II, III, or IV heart failure and an ejection fraction of 40% or less to receive either LCZ696 (at a dose of 200 mg twice daily) or enalapril (at a dose of 10 mg twice daily), in addition to recommended therapy. The primary outcome was a composite of death from cardiovascular causes or hospitalization for heart failure, but the trial was designed to detect a difference in the rates of death from cardiovascular causes.
The trial was stopped early, according to prespecified rules, after a median follow-up of 27 months, because the boundary for an overwhelming benefit with LCZ696 had been crossed. At the time of study closure, the primary outcome had occurred in 914 patients (21.8%) in the LCZ696 group and 1117 patients (26.5%) in the enalapril group (hazard ratio in the LCZ696 group, 0.80; 95% confidence interval CI, 0.73 to 0.87; P<0.001). A total of 711 patients (17.0%) receiving LCZ696 and 835 patients (19.8%) receiving enalapril died (hazard ratio for death from any cause, 0.84; 95% CI, 0.76 to 0.93; P<0.001); of these patients, 558 (13.3%) and 693 (16.5%), respectively, died from cardiovascular causes (hazard ratio, 0.80; 95% CI, 0.71 to 0.89; P<0.001). As compared with enalapril, LCZ696 also reduced the risk of hospitalization for heart failure by 21% (P<0.001) and decreased the symptoms and physical limitations of heart failure (P=0.001). The LCZ696 group had higher proportions of patients with hypotension and nonserious angioedema but lower proportions with renal impairment, hyperkalemia, and cough than the enalapril group.
LCZ696 was superior to enalapril in reducing the risks of death and of hospitalization for heart failure. (Funded by Novartis; PARADIGM-HF ClinicalTrials.gov number, NCT01035255.).
Since last two decades, the major cancer research has focused on understanding the characteristic properties and mechanism of formation of Cancer stem cells (CSCs), due to their ability to initiate ...tumor growth, self-renewal property and multi-drug resistance. The discovery of the mechanism of acquisition of stem-like properties by carcinoma cells via epithelial-mesenchymal transition (EMT) has paved a way towards a deeper understanding of CSCs and presented a possible avenue for the development of therapeutic strategies. In spite of years of research, various challenges, such as identification of CSC subpopulation, lack of appropriate experimental models, targeting cancer cells and CSCs specifically without harming normal cells, are being faced while dealing with CSCs. Here, we discuss the biology and characteristics of CSCs, mode of acquisition of stemness (via EMT) and development of multi-drug resistance, the role of tumor niche, the process of dissemination and metastasis, therapeutic implications of CSCs and necessity of targeting them. We emphasise various strategies being developed to specifically target CSCs, including those targeting biomarkers, key pathways and microenvironment. Finally, we focus on the challenges that need to be subdued and propose the aspects that need to be addressed in future studies in order to broaden the understanding of CSCs and develop novel strategies to eradicate them in clinical applications.
Graphical Abstract
Cancer Stem Cells(CSCs) have gained much attention in the last few decades due to their ability to initiate tumor growth and, self-renewal property and multi-drug resistance. Here, we represent the CSC model of cancer, Characteristics of CSCs, acquisition of stemness and metastatic dissemination of cancer, Therapeutic implications of CSCs and Various strategies being employed to target and eradicate CSCs.
Despite the accepted health benefits of consuming dietary fiber, little is known about the mechanisms by which fiber deprivation impacts the gut microbiota and alters disease risk. Using a ...gnotobiotic mouse model, in which animals were colonized with a synthetic human gut microbiota composed of fully sequenced commensal bacteria, we elucidated the functional interactions between dietary fiber, the gut microbiota, and the colonic mucus barrier, which serves as a primary defense against enteric pathogens. We show that during chronic or intermittent dietary fiber deficiency, the gut microbiota resorts to host-secreted mucus glycoproteins as a nutrient source, leading to erosion of the colonic mucus barrier. Dietary fiber deprivation, together with a fiber-deprived, mucus-eroding microbiota, promotes greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium. Our work reveals intricate pathways linking diet, the gut microbiome, and intestinal barrier dysfunction, which could be exploited to improve health using dietary therapeutics.
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•Characterized synthetic bacterial communities enable functional insights in vivo•Low-fiber diet promotes expansion and activity of colonic mucus-degrading bacteria•Purified prebiotic fibers do not alleviate degradation of the mucus layer•Fiber-deprived gut microbiota promotes aggressive colitis by an enteric pathogen
Regular consumption of dietary fiber helps prevent erosion of the intestinal mucus barrier by the gut microbiome, blunting pathogen infection and reducing the incidence of colitis.
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