87 research outputs found

    Gender-based difference in early mortality among patients with ST-segment elevation myocardial infarction: insights from Kermanshah STEMI Registry.

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    Introduction: This study aimed to evaluate the in-hospital mortality of patients with ST-segment elevation myocardial infarction (STEMI), according to gender and other likely risk factors. Methods: This study reports on data relating to 1,484 consecutive patients with STEMI registered from June 2016 to May 2018 in the Western Iran STEMI Registry. Data were collected using a standardized case report developed by the European Observational Registry Program (EORP). The relationship between in-hospital mortality and potential predicting variables was assessed multivariable logistic regression. Differences between groups in mortality rates were compared using chi-square tests and independent t-tests. Results: Out of the 1484 patients, 311(21%) were female. Women were different from men in terms of age (65.8 vs. 59), prevalence of hypertension (HTN) (63.7% vs. 35.4%), diabetes mellitus (DM) (37.7% vs. 16.2%), hypercholesterolemia (36.7% vs. 18.5%) and the history of previous congestive heart failure (CHF) (6.6% vs. 3.0%). Smoking was more prevalent among men (55.9% vs. 13.2%). Although the in-hospital mortality rate was higher in women (11.6% vs. 5.5%), after adjusting for other risk factors, female sex was not an independent predictor for in-hospital mortality. Multivariable analysis identified that age and higher Killip class (≥II) were significantly associated with in-hospital mortality rate. Conclusion: In-hospital mortality after STEMI in women was higher than men. However, the role of sex as an independent predictor of mortality disappeared in regression analysis. The gender based difference in in-hospital mortality after STEMI may be related to the poorer cardiovascular disease (CVD) risk factor profile of the women

    Time-Fractional KdV Equation: Formulation and Solution using Variational Methods

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    In this work, the semi-inverse method has been used to derive the Lagrangian of the Korteweg-de Vries (KdV) equation. Then, the time operator of the Lagrangian of the KdV equation has been transformed into fractional domain in terms of the left-Riemann-Liouville fractional differential operator. The variational of the functional of this Lagrangian leads neatly to Euler-Lagrange equation. Via Agrawal's method, one can easily derive the time-fractional KdV equation from this Euler-Lagrange equation. Remarkably, the time-fractional term in the resulting KdV equation is obtained in Riesz fractional derivative in a direct manner. As a second step, the derived time-fractional KdV equation is solved using He's variational-iteration method. The calculations are carried out using initial condition depends on the nonlinear and dispersion coefficients of the KdV equation. We remark that more pronounced effects and deeper insight into the formation and properties of the resulting solitary wave by additionally considering the fractional order derivative beside the nonlinearity and dispersion terms.Comment: The paper has been rewritten, 12 pages, 3 figure

    Identification of a Negative Allosteric Site on Human α4β2 and α3β4 Neuronal Nicotinic Acetylcholine Receptors

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    Acetylcholine-based neurotransmission is regulated by cationic, ligand-gated ion channels called nicotinic acetylcholine receptors (nAChRs). These receptors have been linked to numerous neurological diseases and disorders such as Alzheimer's disease, Parkinson's disease, and nicotine addiction. Recently, a class of compounds has been discovered that antagonize nAChR function in an allosteric fashion. Models of human α4β2 and α3β4 nicotinic acetylcholine receptor (nAChR) extracellular domains have been developed to computationally explore the binding of these compounds, including the dynamics and free energy changes associated with ligand binding. Through a blind docking study to multiple receptor conformations, the models were used to determine a putative binding mode for the negative allosteric modulators. This mode, in close proximity to the agonist binding site, is presented in addition to a hypothetical mode of antagonism that involves obstruction of C loop closure. Molecular dynamics simulations and MM-PBSA free energy of binding calculations were used as computational validation of the predicted binding mode, while functional assays on wild-type and mutated receptors provided experimental support. Based on the proposed binding mode, two residues on the β2 subunit were independently mutated to the corresponding residues found on the β4 subunit. The T58K mutation resulted in an eight-fold decrease in the potency of KAB-18, a compound that exhibits preferential antagonism for human α4β2 over α3β4 nAChRs, while the F118L mutation resulted in a loss of inhibitory activity for KAB-18 at concentrations up to 100 µM. These results demonstrate the selectivity of KAB-18 for human α4β2 nAChRs and validate the methods used for identifying the nAChR modulator binding site. Exploitation of this site may lead to the development of more potent and subtype-selective nAChR antagonists which may be used in the treatment of a number of neurological diseases and disorders

    Determining Peptide Partitioning Properties via Computer Simulation

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    The transfer of polypeptide segments into lipid bilayers to form transmembrane helices represents the crucial first step in cellular membrane protein folding and assembly. This process is driven by complex and poorly understood atomic interactions of peptides with the lipid bilayer environment. The lack of suitable experimental techniques that can resolve these processes both at atomic resolution and nanosecond timescales has spurred the development of computational techniques. In this review, we summarize the significant progress achieved in the last few years in elucidating the partitioning of peptides into lipid bilayer membranes using atomic detail molecular dynamics simulations. Indeed, partitioning simulations can now provide a wealth of structural and dynamic information. Furthermore, we show that peptide-induced bilayer distortions, insertion pathways, transfer free energies, and kinetic insertion barriers are now accurate enough to complement experiments. Further advances in simulation methods and force field parameter accuracy promise to turn molecular dynamics simulations into a powerful tool for investigating a wide range of membrane active peptide phenomena

    Functional Characterization of a Lipoprotein-Encoding Operon in Campylobacter jejuni

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    Background: Bacterial lipoproteins have important functions in bacterial pathogenesis and physiology. In Campylobacter jejuni, a major foodborne pathogen causing gastroenteritis in humans, the majority of lipoproteins have not been functionally characterized. Previously, we showed by DNA microarray that CmeR, a transcriptional regulator repressing the expression of the multidrug efflux pump CmeABC, modulates the expression of a three-gene operon (cj0089, cj0090, and cj0091) encoding a cluster of lipoproteins in C. jejuni. Methodology/Principal Findings: In this work, we characterized the function and regulation of the cj0089-cj0090-cj0091 operon. In contrast to the repression of cmeABC, CmeR activates the expression of the lipoprotein genes and the regulation is confirmed by immunoblotting using anti-Cj0089 and anti-Cj0091 antibodies. Gel mobility shift assay showed that CmeR directly binds to the promoter of the lipoprotein operon, but the binding is much weaker compared with the promoter of cmeABC. Analysis of different cellular fractions indicated that Cj0089 was associated with the inner membrane, while Cj0091 was located on the outer membrane. Inactivation of cj0091, but not cj0089, significantly reduced the adherence of C. jejuni to INT 407 cells in vitro, indicating that Cj0091 has a function in adherence. When inoculated into chickens, the Cj0091 mutant also showed a defect in early colonization of the intestinal tract, suggesting that Cj0091 contributes to Campylobacter colonization in vivo. It was also shown that Cj0091 was produced and immunogenic in chickens that wer

    Nanomaterials for subsurface application: study of particles retention in porous media

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    The ability to transport nanoparticles through porous media has interesting engineering applications, notably in reservoir capacity exploration and soil remediation. A series of core-flooding experiments were conducted for quantitative analysis of functionalized TiO2 nanoparticles transport through various porous media including calcite, dolomite, silica, and limestone rocks. The adsorption of surfactants on the rock surface and nanoparticle retention in pore walls were evaluated by chemical oxygen demand (COD) and UV–Vis spectroscopy. By applying TiO2 nanoparticles, 49.3 and 68.0 wt.% of surfactant adsorption reduction were observed in pore walls of dolomite and silica rock, respectively. Not surprisingly, the value of nanoparticle deposition for dolomite and silica rocks was near zero, implying that surfactant adsorption is proportional to nanoparticle deposition. On the other hand, surfactant adsorption was increased for other types of rock in presence of nanoparticles. 5.5, 13.5, and 22.4 wt.% of nanoparticle deposition was estimated for calcite, black and red limestone, respectively. By making a connection between physicochemical rock properties and nanoparticle deposition rates, we concluded that the surface roughness of rock has a significant influence on mechanical trapping and deposition of nanoparticles in pore-throats
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