Circulating extracellular vesicles induce monocyte dysfunction and are associated with sepsis and high mortality in cirrhosis

BACKGROUND: Sepsis is common in cirrhosis and is often a result of immune dysregulation. Specific stimuli and pathways of inter-cellular communications between immune cells in cirrhosis and sepsis are incompletely understood. Immune cell-derived Extracellular Vesicles (EV) were studied to understand mechanisms of sepsis in cirrhosis. METHODS: Immune-cell derived EV were measured in cirrhosis patients [Child-Turcotte-Pugh (Child) score A, n=15; B n=16; C n=43 and Child-C with sepsis (n=38)], and healthy controls (HC, n=11). In-vitro and in-vivo functional relevance of EV in cirrhosis and associated sepsis was investigated. RESULTS: Monocyte, neutrophil and hematopoietic stem cells associated EV progressively increased with higher Child score (p0.3, p<0.001), which further increased in Child C sepsis than without sepsis(p<0.001); monocyte EV showing the highest association with disease stage [p=0.013; Odds ratio-4.14(1.34-12.42)]. A threshold level of monocyte EV of 53/µl predicted mortality in patients of Child C with sepsis [Odds ratio-6.2 (2.4-15.9), AUROC=0.76, p<0.01]. In vitro EV from cirrhotic with sepsis compared without sepsis, induced mobilization arrest in healthy monocytes within 4 hours (p=0.004), reduced basal oxygen consumption rate (p<0.001) and induced pro-inflammatory genes (p<0.05). The septic-EV on adoptive transfer to C57/BL6J mice, induced sepsis like condition within 24h with leukocytopenia (p=0.005), intrahepatic inflammation with increased CD11b+ cells (p=0.03) and bone marrow hyperplasia (p<0.01). CONCLUSION: Extracellular vesicles induce functional impairment in circulating monocytes and contribute to the development and perpetuation of sepsis. High levels of monocyte EV correlate with mortality and can help early stratification of sicker patients

Comparing pregnancy, childbirth, and neonatal outcomes in women with different phenotypes of polycystic ovary syndrome and healthy women: a prospective cohort study

The aim of this study was to compare pregnancy, childbirth, and neonatal outcomes in women with different phenotypes of polycystic ovary syndrome (PCOS) with healthy women. A prospective cohort study from the beginning to the end of pregnancy for 41 pregnant women with PCOS (case) and 49 healthy pregnant women (control) was completed. Based on the presence or absence of menstrual dysfunction (M), hyperandrogenism (HA), and polycystic ovaries (PCO) on ultrasound, the PCOS (case) group were divided into three phenotypes (HA + PCO (  = 22), M + PCO (  = 9), HA + M+PCO (  = 10). Pre-eclampsia, gestational diabetes, and lower birth weight among newborns were significantly higher in the PCOS case group compared to the control group especially in the phenotype HA + M+PCO (  < .05). High BMI (  = 2.40; =.03) was the strongest predictor of pre-eclampsia in patients with PCOS. High androgen levels (free androgen index) (  = 13.71, 3.02;  < .05), was the strongest predictor of developing diabetes during pregnancy and reduced birth weight baby, respectively.These results suggest that PCOS, particularly in phenotype HA + M+PCO (  < .05), is a risk factor for adverse pregnancy and neonatal outcomes including gestational diabetes, pre-eclampsia, and reduced weight babies

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Portfolio optimization with structured products under return constraint

A new approach for optimizing risk in a portfolio of financial instruments involving structured products is presented. This paper deals with a portfolio selection model which uses optimization methodology to minimize conditional Value-at-Risk (CVaR ) under return constraint. It focuses on minimizing CVaR rather than on minimizing value-at-Risk VaR, as portfolios with low CVaR necessarily have low VaR as well. We consider a simple investment problem where besides stocks and bonds, the investor can also include structured products into the investment portfolio. Due to possible intermediate payments from structured product, we have to deal with a re-investment problem modeled as a linear optimization problem

Disruptive mood dysregulation disorder: current insights

Raman Baweja, Susan D Mayes, Usman Hameed, James G Waxmonsky Department of Psychiatry, Penn State University College of Medicine, Hershey, PA, USA Abstract: Disruptive mood dysregulation disorder (DMDD) was introduced as a new diagnostic entity under the category of depressive disorders in Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). It was included in DSM-5 primarily to address concerns about the misdiagnosis and consequent overtreatment of bipolar disorder in children and adolescents. DMDD does provide a home for a large percentage of referred children with severe persistent irritability that did not fit well into any DSM, Fourth Edition (DSM-IV) diagnostic category. However, it has been a controversial addition to the DSM-5 due to lack of published validity studies, leading to questions about its validity as a distinct disorder. In this article, the authors discuss the diagnostic criteria, assessment, epidemiology, criticism of the diagnosis, and pathophysiology, as well as treatment and future directions for DMDD. They also review the literature on severe mood dysregulation, as described by the National Institute of Mental Health, as the scientific support for DMDD is based primarily on studies of severe mood dysregulation. Keywords: disruptive mood dysregulation disorder, persistent irritability, temper outbursts&nbsp

Utilization of Granite Powder in Cement Mortar

The world is struggling with the problem of solid waste disposal. Such materials are causing pollution and damages related to it. The industry of dimensional granite stone has contributed to the development of major environmental problems due to waste generation at different stages of mining and processing operations. The complete process involved with granite starting from mining till the finished product contributes to around 60-80% of the worked masses of the mineral mined, the sludge generated being estimated over 30% of the volume of the sawn block. For dealing with the problem of waste generated by the granite production industry, studies are being conducted for the incorporation of granite sludge as partial or complete replacement of aggregates in cement concrete. This paper elaborates on the study conducted to test the compressive strength, flexural strength, pull-off strength, abrasion resistance, drying shrinkage, air and water permeability, rapid chloride permeability, alkalinity and resistance to sulphate attack in concrete specimen

A New Paradigm in Governance: Is It True for E-Governance?

Good governance, E-governance, Information and communication technologies, Impact assessment,

Investigation on compressive strength development and drying shrinkage of ambient cured powder-activated geopolymer concretes

© 2016 Engineers Australia. Geopolymer is an inorganic polymer binding material, generally formed by the reaction between aluminosilicate materials and alkali activator solution. Previous researches on geopolymer concrete around the world suggested that geopolymer concrete possess superior mechanical and durability properties over ordinary Portland cement (OPC) concrete, such as higher indirect tensile strength and resistance to sulphate attack. Generally, fly ash-based geopolymer concrete was cured in elevated temperature for higher early age strength because of their longer setting time in ambient temperature. Published engineering properties of geopolymer concrete cured at ambient temperature are not abundant. In this research, two types of powder-activated geopolymer binders were used as binding material. A detailed study of compressive strength and drying shrinkage of different grades (40, 50, 65 and 80 MPa) of geopolymer and OPC concrete with different workability levels (normal-workable and super-workable) were carried out. All the concrete specimens were cured at standard laboratory temperature. The compressive strength development of geopolymer concrete in early age was relatively lower than OPC concrete; however, the later age strength was significantly higher. The drying shrinkage of geopolymer concrete was similar to OPC concrete of same grade and complied with Australian Standard 1379; however, it was higher than estimated values from Australian Standard 3600. The drying shrinkage results of this study were higher than drying shrinkage of accelerated cured geopolymer concretes in previous investigations. Super workable concrete exhibited higher drying shrinkage than normal workable concrete of same grade