Membrane vesicles, current state-of-the-art: emerging role of extracellular vesicles

Release of membrane vesicles, a process conserved in both prokaryotes and eukaryotes, represents an evolutionary link, and suggests essential functions of a dynamic extracellular vesicular compartment (including exosomes, microparticles or microvesicles and apoptotic bodies). Compelling evidence supports the significance of this compartment in a broad range of physiological and pathological processes. However, classification of membrane vesicles, protocols of their isolation and detection, molecular details of vesicular release, clearance and biological functions are still under intense investigation. Here, we give a comprehensive overview of extracellular vesicles. After discussing the technical pitfalls and potential artifacts of the rapidly emerging field, we compare results from meta-analyses of published proteomic studies on membrane vesicles. We also summarize clinical implications of membrane vesicles. Lessons from this compartment challenge current paradigms concerning the mechanisms of intercellular communication and immune regulation. Furthermore, its clinical implementation may open new perspectives in translational medicine both in diagnostics and therapy

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 < 100 mmHg (n = 1127), estimated glomerular filtration rate < 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

Impacts of climate change on the municipal water management system in the Kingdom of Bahrain: Vulnerability assessment and adaptation options

An assessment of the vulnerability of the municipal water management system to the impacts of climate change in the Kingdom of Bahrain, manifested by the increase in demands due to increase in temperatures, is conducted using a dynamic mathematical model representing the water sector in the kingdom. The model is developed using WEAP software and was calibrated and validated by historical matching utilizing data for the period 2000–2012. The model is used in the evaluation of the municipal water sector performance in terms of municipal water demands and their associated cost without and with climate change impacts scenarios for the period 2012–2030. The impact of climate change on the municipal water system is quantified as the difference between the two scenarios in three selected cost indicators: financial (production, conveyance and distribution costs), economic (natural gas asset consumption by desalination plants), and environmental (CO2 emissions by desalination plants). The vulnerability assessment indicated that the current municipal water management system in Bahrain is generally inefficient and associated with relatively high costs, which are expected to increase with time under the current policies and management approach focusing on supply-side management. The increase in temperature will increase these already high costs, and would exacerbate the water management challenges in Bahrain. However, these mounting challenges also present an opportune moment for Bahrain to review its current water resources management approaches and practices and to integrate climate change adaptation measures into its water planning and policies. In order to build an adaptive management capacity of the municipal water management system in Bahrain, a number of management interventions are proposed and evaluated, individually and combined, for their effectiveness in enhancing the efficiency of the management system using the developed dynamic model. These are: reduction of the leakage percentage in the municipal water distributions network and reducing per capita water consumption by raising water awareness among consumers and installing water saving devices in residential units. The evaluation results indicate that there is a large potential for reducing the municipal water demand and its associated cost, especially when all the three are combined; by the year 2030 it is estimated that the cumulative financial saving would be about US$ 2.9 Billion, the cumulative reduction in CO2 emission would be about 19.7 Million tons, and the preservation of the kingdom’s limited natural gas reserves would be about 4 Billion m3. In addition, a major reduction in desalination brine discharge to the marine environment and reduction of generated wastewater and their associated collection and treatment cost could be achieved from the implementation of these interventions. Adopting such management interventions will not only enhance the efficiency of the municipal water management system, but it will also help the Kingdom in its efforts in reducing its greenhouse gasses emissions. It is recommended that similar climate change vulnerability and adaptation analysis is extended to the whole water sector in Bahrain to include other major water consuming sectors (i.e., agricultural, industrial, and tourism sectors) and their sources of water (i.e., groundwater and wastewater) in Bahrain. Keywords: Desalination, CO2 emissions, Natural gas consumption, WEAP modeling, Awareness, Water saving devices, Distribution network leakag

Complexation of Biologically Active Aromatic Compounds with DNA in the Presence of Theophylline

1H NMR measurements (500 MHz) have been used to determine the equilibrium hetero-association constants of theophylline (THP) with various biologically active aromatic compounds (daunomycin, novantrone, ethidium bromide, proflavine, norfloxacin) and the complexation constants of THP with both single- and double-stranded oligonucleotides in solution. The results provide a quantitative estimation of the effect of THP on the binding of aromatic ligands with DNA, and a determination of the fraction of aromatic ligand removed from DNA on addition of THP