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• Myotonic dystrophy (DM) is an autosomal dominant neuromuscular and multisystem disease. • DM patients may manifest with various speech and language abnormalities. • Speech impairments are related to both cognitive dysfunction and bulbar/vocal muscles weakness and myotonia. • Decrease in speech rate and performance due to myotonia and flaccid dysarthria are present in DM type 1. • Speech and language characteristics in DM could serve as potential markers in clinical trials. Myotonic dystrophy (DM) is an autosomal dominant neuromuscular and multisystem disease that is divided into two types, DM1 and DM2, according to mutations in DMPK and CNBP genes, respectively. DM patients may manifest with various speech and language abnormalities. In this review, we had an overview on speech and language abnormalities in both DM1 and DM2. Our literature search highlights that irrespective of age, all DM patients (i.e. congenital, juvenile, and adult onset DM1 as well as DM2 patients) exhibit various degrees of speech impairments. These problems are related to both cognitive dysfunction (e.g. difficulties in written and spoken language) and bulbar/vocal muscles weakness and myotonia. DM1 adult patients have also a significant decrease in speech rate and performance due to myotonia and flaccid dysarthria, which can improve with warming up. Weakness, tiredness, and hypotonia of oral and velopharyngeal muscles can cause flaccid dysarthria. Hearing impairment also plays a role in affecting speech recognition in DM2. A better understanding of different aspects of speech and language abnormalities in DM patients may provide better characterization of these abnormalities as markers that can be potentially used as outcome measures in natural history studies or clinical trials. [ABSTRACT FROM AUTHOR]

Speckle-tracking echocardiography is a promising tool for evaluating cardiac diastolic dysfunction. A correlation between left atrial strain rate during atrial contraction and the severity of diastolic dysfunction previously has been demonstrated. Because visualization of the left atrial walls is difficult with transesophageal echocardiography, the authors evaluated the use of left ventricular strain rate during atrial contraction as a substitute for left atrial strain rate to intraoperatively measure the extent of cardiac diastolic dysfunction. Retrospective clinical study. Single institutional study. Sixty-six patients who underwent cardiac surgery between January 2018 and January 2021. None. Preoperative echocardiographic reports and intraoperative echocardiographic images of the participants were studied. The correlation of cardiac diastolic dysfunction stage with the peak longitudinal strain rate during late diastole and the time to peak value were evaluated. The late diastolic peak longitudinal strain rate was correlated significantly with the stage of diastolic dysfunction (r = –0.64, p < 0.0001). There was no significant correlation between the stage of diastolic dysfunction and the time to peak value (r = –0.17, p = 0.18). A late diastolic peak longitudinal strain rate <0.68 1/s had a sensitivity of 80% and specificity of 81% for predicting grade 2 or 3 diastolic dysfunction. The late diastolic peak longitudinal strain rate correlates with the severity of diastolic dysfunction in patients undergoing cardiac surgery. [ABSTRACT FROM AUTHOR]

Objectives: Left ventricular diastolic function can be assessed by various methods. Tissue Doppler imaging is among the most commonly used techniques. However, this imaging is angle- dependent, affected by loading conditions, and susceptible to myocardial tethering. Speckle- tracking echocardiography also can measure strain-based indices to assess diastolic function, and it has fewer limitations than tissue Doppler imaging. Using speckle- tracking echocardiography, the authors evaluated the correlation between the stage of diastolic dysfunction and strain-based indices in patients undergoing cardiac surgery to determine whether strain-based indices can be used intraoperatively to identify the extent of left ventricular diastolic dysfunction. Design: Retrospective clinical study. Setting: Single university hospital. Participants: Fifty-eight patients undergoing cardiac surgery (December 2017 to December 2019). Interventions: None. Measurement and Main Result: Preoperative echocardiographic reports and intraoperative echocardiographic images of the participants were studied. The correlation between the stage of left ventricular diastolic dysfunction and strain-based indices (including early diastolic peak longitudinal strain and tissue deceleration time) were evaluated. Early diastolic peak longitudinal strain rate significantly correlated with the stage of diastolic dysfunction (r = –0.7 and p < 0.0001). Tissue deceleration time significantly correlated with the stage of diastolic dysfunction in patients with diastolic abnormality (r = –0.4 and p = 0.02). When patients with normal diastolic function were included, this correlation was not significant (r= –0.25 and p = 0.05). Conclusions: Intraoperatively measured early diastolic peak longitudinal strain rate and tissue deceleration time correlated with the severity of diastolic dysfunction in patients undergoing cardiac surgery. [ABSTRACT FROM AUTHOR]

The effects of inhalation anesthetics on cardiac function and the low correlation between transthoracic and transesophageal echocardiographic measurements may alter the ability of transesophageal echocardiography-derived strain rate during early diastole to detect coronary artery stenosis in anesthetized patients. The authors assessed the correlation between coronary artery stenosis and strain-based parameters during early diastole in heart failure patients with preserved ejection fraction undergoing coronary artery bypass grafting. Retrospective clinical study. Single university hospital. Thirty-two adult patients with preserved ejection fraction undergoing coronary artery bypass grafting between December 2016 and December 2018. None. Transesophageal echocardiography images and coronary artery angiographies of the participants were studied. The correlation between the severity of coronary artery stenosis and strain-based indices measured in the corresponding left ventricular segments were assessed. Receiver operating characteristic curve analysis of strain rate during early diastole was used to predict the presence of coronary artery stenosis ≥70%. Regarding the severity of coronary artery stenosis, it demonstrated a strong and inverse correlation with strain rate during early diastole (r = –0.71, p < 0.001), but showed no significant correlation with time to peak strain rate during early diastole (r = 0.19, p = 0.18). Strain rate during early diastole ≤1.5 s−1 had a sensitivity of 77% and a specificity of 87% for predicting coronary artery stenosis ≥70% (area under the curve, 0.88). Strain rate during early diastole significantly correlates with the severity of coronary artery stenosis in anesthetized patients suffering from heart failure with preserved ejection fraction. [ABSTRACT FROM AUTHOR]

In this paper, the nonlinear forced vibration of single layered graphene sheet including the pre-Stressed effect is studied based on nonlocal elasticity theory. The graphene sheet is located on a viscoelastic foundation based on Kelvin-Voigt model and exposed to thermo-magnetic-mechanical loads. A particle with constant velocity and concentrated load moves on the graphene sheet and applies mechanical shock to it. At first, using nonlinear strain-displacement relations, the geometrical nonlinearity is modeled. Besides, nonlocal plate theory and Hamilton's principle are utilized for deriving the governing equation. In the second step, using Galerkin method, the partial differential equation is transformed to the ordinary differential equation. Then, governing equation is solved based on multiple time scales method. Finally, frequency-response equations under sub-harmonic and super-harmonic stimulation are studied. Emphasizing the effect of nonlinearity, the results for the nondimensional nonlinear frequency versus nondimensional amplitude, the nondimensional phase angle and nondimensional velocity for single layered graphene sheet are plotted. At the end, numerical results are compared with results in the other researches. The results emphasize that the velocity of the nano particle and force amplitude are responsible to make resonance in the system based on a SLGS. Besides, force amplitude can be effective to intensify the effect of the mechanical shock in behavior of SLGS. [ABSTRACT FROM AUTHOR]

Objectives Two-dimensional speckle tracking echocardiography has advantages over tissue Doppler imaging during isovolumetric relaxation for predicting left-ventricular end-diastolic pressure in non-surgical patients. Considering the direct and indirect effects of general anesthesia on hemodynamics, we examined correlations between strain-based indices during isovolumetric relaxation and pulmonary capillary wedge pressure in anesthetized patients. Moreover, we determined applicable cut-off values for strain-based indices to predict pulmonary capillary wedge pressure ≥15 mmHg intraoperatively. Design Retrospective clinical study. Setting Single university hospital. Participants Thirty adult patients with preserved ejection fraction undergoing coronary artery bypass grafting. Interventions None. Measurements and Main Results Two-dimensional speckle tracking echocardiography was used to measure strain rate during isovolumetric relaxation (SR IVR) and to calculate the mitral early diastolic inflow (E) to SR IVR ratio (E/SR IVR). Tissue Doppler imaging was used to calculate the E to early diastolic velocity at the lateral mitral annulus ratio (lateral E/e′). SR IVR and E/SR IVR showed strong correlations with pulmonary capillary wedge pressure (r = 0.80 and 0.73, respectively; p < 0.001 and p < 0.001). Lateral E/e′ correlated with pulmonary capillary wedge pressure (r = 0.42; p < 0.05). SR IVR predicted high pulmonary capillary wedge pressure better than lateral E/e′ did (areas under the receiver operating characteristic curves, 0.94–vs. 0.47, respectively). SR IVR <0.2 s−1 had a sensitivity of 100% and a specificity of 81% for predicting pulmonary capillary wedge pressure ≥15 mmHg. Conclusions SR IVR is superior to tissue Doppler indices for predicting pulmonary capillary wedge pressure intraoperatively in patients with coronary artery disease and preserved ejection fraction. [ABSTRACT FROM AUTHOR]

In this article, wave propagation characteristics of protein lipid nanotubules are covered with respect to scale effects utilizing nonlocal strain gradient theory. The structure is supposed to be modeled as a simply supported beam and the kinematic relations are derived based on the classical beam theory (CBT). Implementing an energy based approach, the Euler-Lagrange equations of the lipid tubules are obtained. Moreover, the final governing equations are solved analytically to achieve the wave frequency and phase velocity of propagated waves. Influences of small size and wave number on the wave dispersion responses of lipid nanotubules are shown in detail in different diagrams for both phase velocity and wave frequency. Also, accuracy of introduced model is verified comparing responses of present model with those of former papers. [ABSTRACT FROM AUTHOR]

In the present article, a nonlocal strain gradient plate model is developed for damping vibration analysis of viscoelastic graphene sheets under hygor-thermal environments. For more accurate analysis of graphene sheets, the proposed theory contains two scale parameters related to the nonlocal and strain gradient effects. Graphene sheet is modeled via a two-variable shear deformation plate theory needless of shear correction factors. Governing equations of a nonlocal strain gradient graphene sheet on viscoelastic substrate are derived via Hamilton’s principle. Differential Quadrature Method (DQM) is implemented to solve the governing equations for different boundary conditions. Effects of different factors such as temperature rise, nonlocal parameter, length scale parameter, elastic foundation and aspect ratio on vibration characteristics a graphene sheets are studied. [ABSTRACT FROM AUTHOR]

This paper proposes a four-variable shear deformation refined plate theory for free vibration analysis of embedded smart plates made of porous magneto-electro-elastic functionally graded (MEE-FG) materials. Magneto-electro-elastic properties of FG plate are supposed to vary through the thickness direction and are estimated through the modified power-law rule in which the porosities with even and uneven type are approximated. The governing differential equations and boundary conditions of embedded porous FG plate under magneto-electrical field are derived through Hamilton's principle based on a four-variable tangential-exponential refined theory which avoids the use of shear correction factors. An analytical solution procedure is used to achieve the natural frequencies of embedded porous FG plate supposed to magneto-electrical field with various boundary condition. Influences of several important parameters such as material graduation exponent, porosity volume fraction, magnetic potential, electric voltage, various boundary conditions, elastic foundation parameters and plate side-to-thickness ratio on natural frequencies of embedded porous MEE-FG plate are investigated and discussed in detail. It is concluded that these parameters play significant roles on the dynamic behavior of porous MEE-FG plates resting on elastic foundation. Presented numerical results can serve as benchmarks for future analyses of MEE-FG plates with porosity phases. [ABSTRACT FROM AUTHOR]

Based on a higher order refined beam model, damping vibration analysis of multi-phase viscoelastic nanocrystalline nanobeams on visco-Pasternak foundation in carried out accounting for nano-grains and nano-voids sizes. For the first time, a contribution of nonlocal and couple stress effects is applied for damping vibration analysis of nanocrystalline nanobeams. In fact, couple stress theory considers grains micro-rotations. While, nonlocal elasticity theory considers long-range interactions between the particles. Viscoelastic medium is described as infinite parallel springs as well as shear and viscous layers. Hamilton’s principle is employed to derive the governing equations and the related boundary conditions which are solved applying an analytical approach. The frequencies are compared with those of nonlocal and couple stress based beams. It is observed that damping frequencies of a nanocrystalline nanobeam are significantly influenced by the grain size, grain rotations, porosities, interface, damping coefficient, surface energy, nonlocality and structural damping. [ABSTRACT FROM AUTHOR]

This paper contains a nonlocal strain gradient theory to capture size effects in wave propagation analysis of compositionally graded smart nanoplates. Shear deformation influences are also covered employing a higher-order shear deformation plate theory. Furthermore, a power law function is used here to describe the material distribution across the thickness of functionally graded (FG) nanoplate. A combination of linear and cosine function is assumed to show the variations of electric and magnetic potentials through the thickness of nanoplate. The nonlocal governing equations of FG-MEE nanoplate have been derived utilizing Hamilton’s principle for MEEMs. Then, attained differential equations are solved by the means of an analytical solution incorporating with an exponential function. After that, wave frequency, phase velocity and escape frequency of FG-MEE nanoplates are derived for each natural mode. Influences of a large variety of parameters including wave number, nonlocal parameter, length scale parameter, electric voltage, magnetic potential and material distribution parameter has been illustrated separately and the results are exactly interpreted to obtain highlights of each figure. [ABSTRACT FROM AUTHOR]

This paper investigates damping vibration characteristics of hygro-thermally affected functionally graded (FG) viscoelastic nanobeams embedded in viscoelastic foundation based on nonlocal strain gradient elasticity theory. The modeling of nanobeam is carried out via a higher order refined beam theory which captures shear deformation influences needless of any shear correction factor. The viscoelastic foundation is consists of Winkler-Pasternak layer together with a viscous layer of infinite parallel dashpots. Power-law model is adopted to describe continuous variation of temperature-dependent material properties of FG nanobeam. The governing equations of nonlocal strain gradient viscoelastic nanobeam in the framework of refined beam theory are obtained using Hamilton’s principle and solved implementing an analytical solution for different boundary conditions. To validate the presented model, the results are compared with those of elastic nanobeams. The effects of linear, shear and viscous layers of foundation, structural damping coefficient, hygro-thermal environment, nonlocal parameter, material characteristic parameter, power-law exponent, mode number, boundary conditions and slenderness ratio on the frequency response of viscoelastic FG nanobeams are investigated. [ABSTRACT FROM AUTHOR]

This paper investigates buckling characteristics of a curved functionally graded (FG) nanobeam based on nonlocal strain gradient elasticity theory accounting the stress for not only the nonlocal stress field but also the strain gradients stress field. The modeling of nanobeam is carried out via a higher order refined beam theory which captures shear deformation influences needless of any shear correction factor. Power-law model is adopted to describe continuous variation of material properties of curved FG nanobeam. The governing equations of nonlocal strain gradient curved FG nanobeam in the framework of refined hyperbolic beam model are obtained using Hamilton’s principle and solved implementing an analytical solution for simply-supported and clamped boundary conditions. To validate the present model, the results are compared with those of straight FG nanobeams by extending the radius of nanobeam to infinity. The effects of nonlocal parameter, length scale parameter, power-law exponent, boundary conditions and slenderness ratio on the buckling response of curved FG nanobeams are investigated. [ABSTRACT FROM AUTHOR]

In this paper, the large-amplitude nonlinear vibration characteristics of functionally graded (FG) Timoshenko beams made of porous material is investigated for the first time. Material properties of FG porous beam are supposed to vary continuously along the thickness according to the rule of mixture which modified to approximate material properties with porosity phases. The governing equations are derived based on Timoshenko beam theory through Hamilton׳s principle and they are solved utilizing both Galerkin׳s method and the method of multiple scales. According to the numerical results, it is revealed that the proposed modeling can provide accurate frequency results of the FG porous beams as compared to the literature. The detailed mathematical derivations are presented and numerical investigations are performed while the emphasis is placed on investigating the effect of the several parameters such as material distribution profile, porosity volume fraction, aspect ratio and mode number on the normalized natural frequencies of the FG porous beams in detail. It is explicitly shown that the vibration behavior of a FG beams is significantly influenced by these effects. Numerical results are presented to serve as benchmarks for future analyses of FG porous beams. [ABSTRACT FROM AUTHOR]

In this paper, the thermal effect on buckling and free vibration characteristics of functionally graded (FG) size-dependent Timoshenko nanobeams subjected to an in-plane thermal loading are investigated by presenting a Navier type solution for the first time. Material properties of FG nanobeam are supposed to be temperature-dependent and vary continuously along the thickness according to the power-law form. The small scale effect is taken into consideration based on nonlocal elasticity theory of Eringen. The nonlocal equations of motion are derived based on Timoshenko beam theory through Hamilton’s principle and they are solved applying analytical solution. According to the numerical results, it is revealed that the proposed modeling can provide accurate frequency results of the FG nanobeams as compared to some cases in the literature. The detailed mathematical derivations are presented and numerical investigations are performed while the emphasis is placed on investigating the effect of the several parameters such as thermal effect, material distribution profile, small scale effects, beam thickness and mode number on the critical buckling temperature and normalized natural frequencies of the temperature-dependent FG nanobeams in detail. It is explicitly shown that the thermal buckling and vibration behavior of a FG nanobeams is significantly influenced by these effects. [ABSTRACT FROM AUTHOR]

In this paper nonlocal Euler–Bernoulli beam theory is employed for vibration analysis of functionally graded (FG) size-dependent nanobeams by using Navier-based analytical method and a semi analytical differential transform method. Two kinds of mathematical models, namely, power law and Mori-Tanaka models are considered. The nonlocal Eringen theory takes into account the effect of small size, which enables the present model to become effective in the analysis and design of nanosensors and nanoactuators. Governing equations are derived through Hamilton's principle and they are solved applying semi analytical differential transform method (DTM). It is demonstrated that the DTM has high precision and computational efficiency in the vibration analysis of FG nanobeams. The good agreement between the results of this article and those available in literature validated the presented approach. The detailed mathematical derivations are presented and numerical investigations are performed while the emphasis is placed on investigating the effect of the several parameters such as small scale effects, different material compositions, mode number and thickness ratio on the normalized natural frequencies of the FG nanobeams in detail. It is explicitly shown that the vibration of a FG nanobeams is significantly influenced by these effects. Numerical results are presented to serve as benchmarks for future analyses of FG nanobeams. [ABSTRACT FROM AUTHOR]

In this paper, the thermal effect on free vibration characteristics of functionally graded (FG) size-dependent nanobeams subjected to an in-plane thermal loading are investigated by presenting a Navier type solution and employing a semi analytical differential transform method (DTM) for the first time. Material properties of FG nanobeam are supposed to vary continuously along the thickness according to the power-law form. The small scale effect is taken into consideration based on nonlocal elasticity theory of Eringen. The nonlocal equations of motion are derived through Hamilton's principle and they are solved applying DTM. According to the numerical results, it is revealed that the proposed modeling and semi analytical approach can provide accurate frequency results of the FG nanobeams as compared to analytical results and also some cases in the literature. The detailed mathematical derivations are presented and numerical investigations are performed while the emphasis is placed on investigating the effect of the several parameters such as thermal effect, material distribution profile, small scale effects, mode number and boundary conditions on the normalized natural frequencies of the temperature-dependent FG nanobeams in detail. It is explicitly shown that the vibration behavior of an FG nanobeams is significantly influenced by these effects. Numerical results are presented to serve as benchmarks for future analyses of FG nanobeams. [ABSTRACT FROM AUTHOR]

In this paper, the thermal effect on free vibration characteristics of functionally graded (FG) size-dependent nanobeams subjected to various types of thermal loading is investigated by presenting a Navier type solution and employing a semi analytical differential transform method (DTM) for the first time. Two kinds of thermal loading, namely, linear temperature rise and nonlinear temperature rise are studied. Material properties of FG nanobeam are supposed to vary continuously along the thickness according to the power-law form and the material properties are assumed to be temperature-dependent. The small scale effect is taken into consideration based on nonlocal elasticity theory of Eringen. The nonlocal equations of motion are derived through Hamilton׳s principle and they are solved applying DTM. According to the numerical results, it is revealed that the proposed modeling and semi analytical approach can provide accurate frequency results of the FG nanobeams as compared to analytical results and also some cases in the literature. The detailed mathematical derivations are presented and numerical investigations are performed while the emphasis is placed on investigating the effect of the several parameters such as thermal effect, material distribution profile, small scale effects, mode number and boundary conditions on the normalized natural frequencies of the temperature-dependent FG nanobeams in detail. It is explicitly shown that the vibration behaviour of a FG nanobeams is significantly influenced by these effects. Numerical results are presented to serve as benchmarks for future analyses of FG nanobeams. [ABSTRACT FROM AUTHOR]

Background: The brush-border enzyme intestinal alkaline phosphatase (IAP) functions as a gut mucosal defense factor and detoxifies different toll-like receptor ligands. This study aimed to determine the therapeutic effects of locally administered calf IAP (cIAP) in a cecal ligation and puncture (CLP) model of polymicrobial sepsis.Methods: C57BL/6 mice underwent CLP followed by intraperitoneal injection of cIAP or normal saline. Blood leukocyte counts, levels of cytokines and liver enzymes, and lung myeloperoxidase activity were determined. Peritoneal lavage fluid (PLF) was assayed for neutrophil infiltration and both aerobic and anaerobic bacterial counts.Results: After intraperitoneal injection, cIAP activity in PLF decreased 50% within 15 min with minimal activity evident at 4 h. Compared with irrigation with normal saline, cIAP irrigation increased the 7-day survival rate in mice undergoing CLP, with maximal effects seen at 25 units of cIAP (0% vs. 46% survival rate, respectively; p < 0.001). cIAP treatment reduced lung inflammation, liver damage and levels of tumor necrosis factor alpha and interleukin-6.Conclusions: Peritoneal irrigation with cIAP significantly enhances survival in a mouse model of peritonitis, likely through reduction of local inflammation and remote organ damage. We suggest that intraperitoneal cIAP irrigation could be a novel therapy for intra-abdominal sepsis. [ABSTRACT FROM AUTHOR]

Abstract: Although there is evidence that diabetes affects seizure susceptibility, the underlying mechanism has not been completely understood. Several studies also suggest a pivotal role for KATP channels in the seizure modulation. The aim of the present study was to evaluate the seizure threshold induced by pentylenetetrazole in diabetic mice at different times (3 days, 1–8 weeks) after induction of diabetes with streptozocin and to examine the possible role of ATP-sensitive potassium (KATP) channels in this manner. Our data showed a time-dependent alteration in the threshold in diabetic mice, reaching a peak on week 2 after streptozocin injection and declining significantly afterwards. The seizure threshold in 8-week diabetic mice was even lower than control levels, though the difference was not significant. The KATP channel opener cromakalim (0.1–30μg/kg, i.p.) significantly increased the seizure threshold in control mice. Although the KATP channel blocker glibenclamide (0.5, 1mg/kg) had no effect, it prevented the effects of the potent dose of cromakalim (30μg/kg) on seizure threshold in control mice. Glibenclamide (1mg/kg, i.p.) also decreased the seizure threshold in 2-week diabetic mice to the control levels which was blocked by pre-treatment with cromakalim (10μg/kg, i.p.). Cromakalim (10μg/kg, i.p.) significantly increased the seizure threshold in 8-week diabetic mice which was inhibited by pre-treatment with glibenclamide (1mg/kg, i.p.). We demonstrated a time-dependent alteration in the pentylenetetrazole-induced seizure threshold in diabetic mice. This phenomenon might be due to the probable alteration in the KATP channel functioning during the diabetic condition. [Copyright &y& Elsevier]

Abstract: Analytical investigation of the free vibration behavior of thin circular functionally graded (FG) plates integrated with two uniformly distributed actuator layers made of piezoelectric (PZT4) material based on the classical plate theory (CPT) is presented in this paper. The material properties of the FG substrate plate are assumed to be graded in the thickness direction according to the power-law distribution in terms of the volume fractions of the constituents and the distribution of electric potential field along the thickness direction of piezoelectric layers is simulated by a quadratic function. The differential equations of motion are solved analytically for clamped edge boundary condition of the plate. The detailed mathematical derivations are presented and numerical investigations are performed while the emphasis is placed on investigating the effect of varying the gradient index of FG plate on the free vibration characteristics of the structure. The results are verified by those obtained from three-dimensional finite element analyses. [Copyright &y& Elsevier]

Abstract: Attenuated responsiveness to adrenoceptor stimulation has been proposed as an important factor underlying cardiovascular complications of cholestasis. We examined isolated papillary muscle responsiveness to α (phenylephrine) and β-adrenoceptor (isoproterenol) agonists in 7-day bile duct-ligated rats. We investigated the role of nitric oxide (NO) and endogenous opioids in papillary muscle hyporesponsiveness to isoproterenol stimulation. In order to evaluate the effect of NO and endogenous opioids, animals were treated with chronic subcutaneous injections of N (ω)-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg/day) or naltrexone (20 mg/kg/day), or isolated papillary muscles were exposed acutely to the same drugs (10−4 and 10−6 M, respectively) in an organ bath. The basal contractile force of papillary muscle, +dT /dt max and −dT /dt max, was significantly decreased in bile duct-ligated rats compared to sham-operated ones (P <0.05, for each value). The concentration–response curve for phenylephrine and isoproterenol demonstrated a reduced maximum effect in bile duct-ligated rats compared to the sham-operated group (P <0.01 and 0.05, respectively). Basal contractile abnormalities of bile duct-ligated rats were corrected by L-NAME or naltrexone treatment, either acute or chronic. While chronic L-NAME treatment resulted in a left-ward shift (P <0.05), it had no effect on the maximum effect in bile duct-ligated rats. Acute L-NAME treatment did not influence isoproterenol responsiveness. Acute and chronic naltrexone treatment resulted in partial and complete correction of the hyporesponsiveness of bile duct-ligated rats, respectively (P <0.05). This investigation demonstrates that the papillary muscles of 7-day bile duct ligated-rats have an impaired basal contractility and hyporesponsiveness to both α and β-adrenoceptor stimulation. It also provides evidence for the involvement of increased opioidergic tone and NO overproduction in cholestasis-induced cardiac impairment. [Copyright &y& Elsevier]

Present manuscript undergoes with the investigation of the wave propagation features of smart magnetostrictive sandwich nanoplates (MSNPs) with regard to the influences of small scale in the context of the so-called nonlocal strain gradient theory (NSGT) of elasticity. The under observation continuous system, i.e. a thin-type one, is modeled via the Kirchhoff-Love theorem incorporated with the dynamic form of the principle of virtual work considering the impacts of both thermal and viscose losses on the dispersion characteristics of the nanostructure. Once the modified size-dependent constitutive equations are inserted into the motion equations, the final governing equations of the problem are attained. Thereafter, an analytical dispersion solution will be employed for the purpose of solving the dynamic problem to extract the wave response of the system. In order to examine the accuracy of the presented results, the natural frequencies obtained from this methodology are compared with those reported in the open literature. According to the presented illustrations, it can be declared that the magnetostriction can affect the dispersion responses of the smart nanoplate in low wave numbers. • The wave propagation features of smart magnetostrictive sandwich nanoplates (MSNPs) are studied using nonlocal strain gradient theory. • The magnetostriction can affect the dispersion responses of the smart nanoplate in low wave numbers. • The dispersion of MSNPs can be amplified by either increasing the length scale parameter or decreasing the nonlocal parameter. • Greater Winkler or Pasternak coefficients enhance the phase velocity values. • For low frequencies, the phase velocity of the system decreases with increasing temperature or damping coefficient. [ABSTRACT FROM AUTHOR]

This article investigates the nonlinear vibration behavior of multiscale nanocomposites nanoshell subjected to hygrothermal environment and resting on elastic foundations. The novelty and contribution of this article is considering a multiscale doubly curved sandwich nanoshell. Three-phase composite nanoshell composes of polymer-Carbon nanotube-fiber (PCF) and polymer-Graphene platelet-fiber (PGF) according to Halpin-Tsai model. Various distributions patterns such as U (uniform), X, A and O are considered. The classical shell theory and nonlocal strain gradient theory including von Kármán strain–displacement relationships are employed to build the size-dependent governing equations. The governing equations of multiscale nanoshell have been implemented by Hamilton's principle and solved by homotopy perturbation method. For investigating correctness and accuracy, this paper is validated by other previous researches. Finally, the effects of different parameters such as temperature rise, various distributions patterns and curvature ratio have been investigated. • Nonlinear vibration behavior of multiscale nanocomposites nanoshell is investigated in hygrothermal environment. • The influence of different parameters such as temperature rise, various distributions patterns, curvature ratio are investigated in detail. • Various distributions patterns such as U (uniform), X, A and O are considered. • Via the classical shell theory and the von Kármán type hypothesis the displacements are expressed. • Nonlocal strain gradient governing equations of multiscale nanoshell have been implemented by employing the Hamilton's principle. • Using the homotopy perturbation method, the equations of motions are solved. • The governing equations of multiscale shell have been derived by implementing Hamilton's principle. [ABSTRACT FROM AUTHOR]

This is the first research on the nonlinear vibration of smart viscoelastic composite doubly curved sandwich shell with flexible core and MR layers with different distribution patterns. By using Reddy's third order shear deformation theory (TSDT), the strains and stresses are obtained. This smart model including multiscale composite layers, flexible core and magnetorheological layer (MR). According to the Halpin-Tsai model three-phase composites layers have been considered. The governing equations of the multiscale doubly curved shell have been derived by implementing the Hamilton's principle. For investigating correctness and accuracy, this paper is validated by other previous studies. The results of this work are validated through the comparison with the results available researches. Finally, the influence of different parameters such as temperature rise, various distributions pattern, magnetic fields, and curvature ratios on nonlinear frequency response are investigated in the details. The results presented that the multiscale doubly curved sandwich shell with flexible core show a complex behavior. [ABSTRACT FROM AUTHOR]

This is the first research on the nonlinear vibration analysis of composite sandwich doubly curved shell with a flexible core integrated with a piezoelectric layer. By using the higher order shear deformable theory (HSDT) for the face sheets and the third-order polynomial theory for the flexible core, the strains and stresses are obtained. It is assumed a smart model including multiscale composite layers shell with a flexible core and magnetorheological layer (MR) that leading up by the nonlinearity of the in-plane and the vertical displacements of the core. Three-phase composites shells with polymer/Carbon nanotube/fiber (PCF) and polymer/Graphene platelet/fiber (PGF) and Shape Memory Alloy (SMA)/matrix either according to Halpin-Tsai model have been considered. The governing equations of multiscale shell have been derived by implementing Hamilton's principle and solved by multiple scale method. For investigating the correctness and accuracy, this paper is validated by other previous researches. Finally, the effect of different parameters such as temperature rise, various distributions pattern, magnetic fields and curvature ratio are explored in detail. [ABSTRACT FROM AUTHOR]

An analytical answer to the natural vibration problem of a composite plate consisted of multi-scale hybrid nanocomposites, is presented here for the first time. In this paper, the constituent material of the structure is made of an epoxy matrix which is reinforced by both macro- and nano-size reinforcements, namely carbon fiber (CF) and carbon nanotube (CNT). The effective material properties like Young's modulus or density are derived utilizing a micromechanical scheme incorporated with the Halpin-Tsai model. To present a more realistic problem, the plate is placed on a two-parameter elastic substrate. Then, on the basis of an energy-based Hamiltonian approach, the equations of motion are derived using the classical theory of plates. Finally, the governing equations will be solved analytically to obtain the natural frequency of the system's oscillation. Afterward, the normalized form of the results will be presented to put emphasis on the impact of each parameter on the dimensionless frequency of nanocomposite plates. It is worth mentioning that the effects of various boundary conditions on the frequency of the plate are covered, too. To show the efficiency of presented modeling, the results of this article are compared to those of former attempts. Numerical results declare that plates fabricated from the hybrid nanocomposites can endure higher frequencies compared with those consisted of conventional composites. [ABSTRACT FROM AUTHOR]

In this research, the post-buckling behaviors of doubly curved composite shells in hygro-thermal environment are investigated by employing multiple scales perturbation method. Three-phase composites shells with polymer/Carbon nanotube/fiber and polymer/Graphene platelet/fiber (PGF) and Shape Memory Alloy (SMA)/matrix according to Halpin-Tsai model are taken into consideration. The displacement-strain of laminated doubly curved shells via third-order shear deformation theory (TSDT) and using von-Kármán nonlinear shell theory is obtained. The governing equations of shallow shell are derived by implementing Hamilton's principle. For investigating correctness and accuracy, this paper is validated with other previous researches. Finally, different parameters such as volume fraction of SMA, temperature rise, various distribution patterns, aspect and curvature ratios are considered in this article. It is found that these parameters have significant effect on the thermal buckling loading. [ABSTRACT FROM AUTHOR]

Present manuscript is mainly arranged to take into consider the influences of nanofillers' aggregation, beam's shear deformation and various boundary conditions on the vibration frequency of multi-scale hybrid nanocomposites in the framework of finite element based Rayleigh-Ritz method. The constituent material is made from three phases, namely polymer matrix, macro-scale carbon fibers and nano-scale carbon nanotubes. Homogenization procedure is procured based on Eshelby-Mori-Tanaka approach incorporated with a micromechanical scheme to obtain the effective material properties via a two-step method. In addition, a new refined higher-order beam theory is introduced to govern shear stress and strain through the thickness direction. Furthermore, influences of different boundary conditions are included, too. The accuracy of the presented finite element formulations is examined by setting a comparison between the dimensionless frequency of multi-scale hybrid nanocomposite beams via both analytical and finite element solutions. Afterwards, parametric studies are adopted to put emphasize on the influence of various terms on the vibrational behaviors of nanocomposite beams. It is reported that influence of different parameters deeply depends on the magnitude of volume fraction of nanofillers inside the inclusions. • Vibration frequency of multi-scale hybrid nanocomposites in the framework of finite element based Rayleigh-Ritz method is investigated. • A new refined higher-order beam theory is introduced to govern shear stress and strain through the thickness direction. • The influences of nanofillers' aggregation, beam's shear deformation and various boundary conditions are considered. • Homogenization procedure is procured based on Eshelby-Mori-Tanaka approach incorporated with a micromechanical scheme. • Comparison of the finite element responses with those achieved from the analytical solution guarantees the accuracy of the presented model. [ABSTRACT FROM AUTHOR]

This is the first research on the free vibration analysis of functionally graded graphene platelets reinforced composite (FG-GPLRC) viscoelastic annular plate resting on the visco-Pasternak foundation and subjected to the nonlinear temperature gradient and mechanical loading within the framework of higher-order shear deformation theory (HSDT). Hamilton's principle is employed to establish governing equations within the framework of HSDT. In this paper, viscoelastic properties are modeled according to Kelvin-Voigt viscoelasticity. The deflection as the function of time can be solved by the fourth-order Runge-Kutta numerical method. Generalized differential quadrature method (GDQM) is applied to obtain a numerical solution. Numerical results are compared with those published in the literature to examine the accuracy and validity of the applied approach. A comprehensive parametric study is accomplished to reveal the influence of the stiffness of the substrate, patterns of temperature rise, axial load, damper and viscoelasticity coefficient, weight fraction and distribution patterns of GPLs and geometric dimensions of GPLs on the frequency response of the structure. The results revealed that applying sinusoidal temperature rise and locating more square-shaped GPLs in the vicinity of the top and bottom surfaces have important effect of the highest natural frequency and buckling load of the FG-GPLRC viscoelastic structure. • Free vibration analysis of FG-GPLRC viscoelastic annular plate is investigated. • The effects of the nonlinear temperature gradient and mechanical load is considered. • Hamilton's principle is employed to establish governing equations of motion within the framework of HSDT. • Viscoelastic properties are modeled according to Kelvin-Voigt viscoelasticity. • The deflection as the function of time can be solved by the fourth-order Runge-Kutta numerical method. [ABSTRACT FROM AUTHOR]

Abstract: In addition to well-known neurobehavioral effects, endogenous cannabinoids exert diverse cardiovascular actions. Recently, they have been suggested to protect the myocardium against ischemia/reperfusion injury. The aim of this study is to examine the contribution of endogenous cannabinoids to cardioprotection afforded by remote ischemic preconditioning. Three groups of remote preconditioned (15 min of mesenteric artery occlusion followed by 15 min of reperfusion) and three groups of sham-operated rats were included in the study. Animals were pretreated intravenously by vehicle, cannabinoid CB1 (AM251, 1 mg/kg) or CB2 (AM630, 1 mg/kg) receptor antagonist 15 min prior to remote preconditioning or sham operation. Myocardial injury was induced by 30 min of coronary artery occlusion followed by 2 h of reperfusion. The resultant arterial hypotension, ventricular arrhythmias, and infarct size were compared among the groups. Remote preconditioning exerted potent cardioprotection manifested as significant reductions in infarct size (P <0.001) as well as number and duration of arrhythmias (P <0.01, 0.01 and 0.05 for premature ventricular contractions, ventricular tachycardias and fibrillations; respectively). The cannabinoid CB1 receptor antagonist pretreatment had no significant effect on ischemia-induced hypotension, arrhythmias or infarct size. On the other hand, the cannabinoid CB2 receptor antagonist pretreatment abolished the protective effects of remote preconditioning on infarct size (P <0.01) and arrhythmias (P <0.01), without any significant effect on ischemia-induced hypotension. The results of this study suggest that endogenous cannabinoids, through acting on cannabinoid CB2 receptors, are involved in the cardioprotective phenomenon of remote ischemic preconditioning, induced by mesenteric artery occlusion and reperfusion. [Copyright &y& Elsevier]

Background/Aims: The clinical relevance of QT prolongation, the most widely recognized cardiac electrophysiological abnormality of cirrhosis, is still undefined. The aim of this study is to examine the susceptibility of chronic (4-week) bile duct-ligated rats to epinephrine-induced arrhythmias. The roles of nitric oxide and endogenous opioids were also evaluated. Methods: Sham-operated and cirrhotic rats were treated with daily subcutaneous administrations of normal saline (1ml/kg/day), l-NAME (a non-selective nitric oxide synthase inhibitor, 3mg/kg/day), and naltrexone (20mg/kg/day) during the fourth week after operation. In order to evaluate the effects of acute nitric oxide synthesis inhibition, additional groups of animals were treated by acute intraperitoneal l-NAME injections (3mg/kg). Arrhythmias were induced by intravenous injections of 10μg/kg epinephrine. Results: Despite QT prolongation (P <0.001), epinephrine induced fewer arrhythmias in cirrhotic rats compared to sham-operated animals (P <0.05). Chronic, but not acute, l-NAME administration corrected the QT prolongation in cirrhotic rats (P <0.001), and restored the susceptibility of cirrhotic rats to arrhythmias (P <0.05). Naltrexone injection without a significant effect on epinephrine-induced arrhythmias corrected QT interval in cirrhotic rats (P <0.001). Conclusions: This study shows that despite QT prolongation, cirrhotic animals are resistant against epinephrine-induced arrhythmias. This resistance is mediated by chronic nitric oxide overproduction. [Copyright &y& Elsevier]

Abstract: The purpose of this study was to investigate the effect of the endogenous cannabinoid anandamide on the nonadrenergic noncholinergic (NANC) relaxant responses to electrical field stimulation in isolated rat corpus cavernosum. The corporal strips were mounted under tension in a standard oxygenated organ bath with guanethidine sulfate (5 μM) and atropine (1 μM) (to produce adrenergic and cholinergic blockade). The strips were precontracted with phenylephrine hydrochloride (7.5 μM) and electrical field stimulation was applied at different frequencies to obtain NANC-mediated relaxation. The expression of CB1, CB2 and vanilloid receptor proteins within the rat corpus cavernosum was evaluated using western blot analysis. The results showed that the relaxant responses to electrical stimulation were significantly enhanced in the presence of anandamide at 1 and 3 μM. The potentiating effect of anandamide (1 μM) on relaxation responses was significantly attenuated by either the selective cannabinoid CB1 receptor antagonist N-(piperidin-1-yl)-5-(4-iodophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide (AM251; 1 μM) or the vanilloid receptor antagonist capsazepine (3 μM), but not by the selective cannabinoid CB2 receptor antagonist 6-iodo-2-methyl-1-[2-(4-morpholinyl) ethyl]-1H-indol-3-yl (4-methoxyphenyl)methanone (AM630; 1 μM). Neither of these antagonists had influence on relaxation responses. Indomethacin (20 μM) had no effect on NANC-mediated relaxation in the presence or absence of anandamide (1 μM). Preincubation with N w-Nitro-l-Arginine Methyl Ester (l-NAME; 1 μM) significantly inhibited the relaxation responses in the presence or absence of 1 μM anandamide. Although at 30 nM, l-NAME did not cause a significant inhibition of relaxant responses individually, it significantly inhibited the potentiating effect of anandamide (1 μM) on relaxation responses. Anandamide (1 μM) had no influence on concentration-dependent relaxant responses to sodium nitroprusside (10 nM–1 mM), a nitric oxide (NO) donor. The western blotting of corporal tissues demonstrated the existence of both vanilloid and CB1 receptors in corporal strips. In conclusion, our results showed that anandamide has a potentiating effect on NANC-mediated relaxation of rat corpus cavernosum through both CB1 and vanilloid receptors and the NO-mediated component of the NANC relaxant responses to electrical stimulation is involved in this enhancement. [Copyright &y& Elsevier]

Abstract: Despite the well-known involvement of the peripheral sympathetic abnormalities in the development of cardiovascular complications of cholestasis, the role of the central sympathetic system is still elusive. The goal of this study was to evaluate the effects of central sympathetic tone reduction, through clonidine administration, on hemodynamic parameters of 7-day bile duct-ligated rats. The contributions of nitric oxide and endogenous opioids were also examined by acute intravenous (10 min before clonidine) or chronic daily subcutaneous administrations of N(ω)-nitro-l-arginine methyl ester (l-NAME, 3 mg/kg) or naltrexone (20 mg/kg). Seven days after bile duct ligation or sham operation, animals were anesthetized with sodium pentobarbital. After hemodynamic stabilization, clonidine (10 μg/kg) was injected intravenously, which elicited an initial hypertension (the peripheral effect) followed by persistent hypotension and bradycardia (the central effects). Cholestatic rats demonstrated significant basal bradycardia (P <0.001) and hypotension (P <0.05), which were corrected by chronic naltrexone but not l-NAME treatment. While the peripheral effect of clonidine was blunted, the central effects were exaggerated in cholestatic rats (P <0.01). Acute l-NAME treatment accentuated the hypertensive phase in sham-operated and cholestatic rats (P <0.05). However, the difference between the two groups was preserved (P <0.01). This treatment attenuated the central effects in both sham-operated and cholestatic rats to the same level (P <0.001). Chronic l-NAME treatment resulted in exaggeration of the peripheral response in cholestatic and central responses in sham-operated rats (P <0.05), and abolished the difference between the groups. Naltrexone treatment had no significant effect on either the central or the peripheral responses to clonidine. This study shows that both central and peripheral hemodynamic responses to clonidine are altered in cholestasis. It also provides evidence that nitric oxide contributes to the development of these abnormalities. [Copyright &y& Elsevier]

Abstract: Cholestasis is associated with vascular changes and in previous studies decreased response of visceral vessels of cholestatic animals to phenylephrine and acetylcholine has been shown. In the present study, the response of mesenteric vascular bed of cholestatic rats to clonidine (an α2-adrenoceptor agonist) was investigated and we also examined the role of endogenous opioids and nitric oxide (NO). Seven-day ligation of bile duct was used as the model to study cholestasis. Six groups of rats, each of which divided into two subgroups (bile duct-ligated and sham-operated), were examined. Three groups of animals were chronically treated with either normal saline, naltrexone (an opioid receptor antagonist, 20 mg/kg/day, s.c.) or aminoguanidine (a selective inducible nitric oxide synthase inhibitor, 150 mg/kg/day, s.c.) for 7 days. After 7 days the response of the mesenteric vascular bed to subsequent doses of clonidine was studied. In other two groups, 7 days after the operation, the response of the mesenteric vascular bed to clonidine in the presence of either yuhimbine, an α2-adrenoceptor antagonist, or N(ω)-nitro-l-arginine methyl ester (l-NAME), a non-selective nitric oxide synthase inhibitor, was studied. In the last group, vasodilation response to sodium nitroprusside (an endothelium-independent vasorelaxant) was evaluated. Clonidine caused vasodilation in a dose-dependent manner by acting on endothelial α2-adrenoceptors since its effect was antagonized by yohimbine, and this vasodilation was through the l-arginine pathway since there was no response in the presence of l-NAME in the perfusate. Compared to sham-operated rats, there was a significant right shift in the clonidine concentration curves of cholestatic animals. Maximum response in cholestatic rats was significantly lower comparing to the sham group (P &#60;0.01) and the dose of clonidine that causes 50% of maximum response (ED50) was significantly higher in cholestatic rats (P &#60;0.05). Vasodilation response to sodium nitroprusside was the same in cholestatic and sham-operated rats. Seven-day treatment with aminoguanidine recovered the effect of cholestasis. Seven-day treatment with naltrexone caused an increase in maximum response (P &#60;0.01) and a decrease in ED50 (P &#60;0.05) in cholestatic rats, while this treatment in sham-operated rats caused a decrease in the maximum response (P &#60;0.01) and an increase in ED50 (P &#60;0.05). This study showed that cholestasis is associated with decreased responsiveness of mesenteric vascular bed to clonidine and the cholestasis-associated NO overproduction and increased level of endogenous opioids may contribute to this process. [Copyright &y& Elsevier]