Advances in laryngeal imaging

Imaging and image analysis became an important issue in laryngeal diagnostics. Various techniques, such as videostroboscopy, videokymography, digital kymograpgy, or ultrasonography are available and are used in research and clinical practice. This paper reviews recent advances in imaging for laryngeal diagnostics.     

Cohabitation with a sick cage mate: consequences on behavior and on ehrlich tumor growth

The present study analyzed the effects of cohabitation for 11 days with a sick cage mate on behavior and Ehrlich tumor growth in mice. Pairs of female mice were divided into one control and one experimental group. One mouse of each control pair was kept undisturbed and called 'healthy companion' (HC). One animal of each experimental pair of mice was inoculated (i.p.) with 5 x 10(6) Ehrlich tumor cells, and the other, the object of this study, was called 'sick companion' (SC). The SC mice presented: (1) increased activity in an open field, (2) increased number of entries and of movements within the plus-maze open arms, (3) similar levels of plus-maze closed-arm exploration, (4) a decrease in the exploratory activity in a hole board, (5) a decrease in the number of white but not red blood cells, and (6) similar corticosterone serum levels. Eleven days after cohabitation with a conspecific, HC and SC mice were injected with 5 x10(6) Ehrlich tumor cells. Results showed that SC animals presented decreased resistance to the ascitic form of the Ehrlich tumor. The observed data provide experimental evidence that psychosocial stress induced by cohabitation with a sick cage mate changed at the same time some behavioral and physiological parameters, and decreased resistance to Ehrlich tumor. These data are discussed in the light of a possible neuroimmune system interaction.     

Elevated pressure selectively blunts flow-evoked vasodilatation in rat mesenteric small arteries

BACKGROUND AND PURPOSE: The present study investigated mechanisms underlying impaired endothelium-dependent vasodilatation elicited by elevating the intraluminal pressure in rat mesenteric small arteries. EXPERIMENTAL APPROACH: Arterial segments (internal diameter 316+/-2 microm, n=86) were mounted in a pressure myograph. The effect of elevating pressure from 50 to 120 mmHg for 1 h before resetting it to 50 mmHg was studied on endothelium-dependent vasodilatation. KEY RESULTS: In arteries constricted with U46619 in the presence of indomethacin, shear stress generated by flow, evoked vasodilatation that was abolished by an inhibitor of nitric oxide (NO) synthase, asymmetric dimethylarginine (1 mM), whereas acetylcholine-induced vasodilatation was unchanged. After elevation of intraluminal pressure for 1 h and then resetting it to 50 mmHg, vasodilatation induced by shear stress and the NO donor, S-nitrosopenicillamine was inhibited, while vasodilatation induced by a guanylyl cyclase activator, BAY 412272, and acetylcholine was unaltered. Superoxide levels sensitive to polyethylene glycol superoxide dismutase were increased in segments exposed to elevated pressure. A superoxide scavenger, tempol (300 microM), a general endothelin receptor antagonist, SB 217242 and the selective ET(A) receptor antagonist, BQ 123 preserved shear stress-evoked vasodilatation. CONCLUSIONS AND IMPLICATIONS: The present study shows that transient exposure to an elevated intraluminal pressure selectively inhibits flow-evoked NO-mediated vasodilatation, probably through activation of endothelin receptors and increased formation of superoxide. In contrast, elevation of pressure did not affect the acetylcholine-evoked endothelium-derived hyperpolarizing factor type vasodilatation in mesenteric small arteries.     

Physiologically relevant measurements of nitric oxide in cardiovascular research using electrochemical microsensors

Nitric oxide (NO) plays an important role in the regulation of blood flow. Pharmacological tools and a series of other techniques have been developed for studying the NO/L-arginine pathway, but it has proved difficult to make a quantitative link between effect and tissue NO concentration. NO microsensors have been applied with success for the measurement of NO in suspensions of mitochondria and cells, such as platelets and leukocytes, and in cell cultures, which together with other interventions or measurements are particularly useful for the examination of cell signalling related to the NO/L-arginine pathway. In isolated vascular segments, studies using the NO microsensor have defined the relationship between NO concentration and relaxation and revealed residual NO release in the presence of NO synthase inhibitors. Moreover, simultaneous measurements of NO concentration and vasorelaxation in isometric preparations have shown that agonist-induced relaxation is L-arginine dependent and NO release is reduced in hypertension. By placing NO microsensors in catheters, it is possible to measure NO in the living animal and man. This approach has been applied for the measurements of NO concentration in relation to increases in flow, erection, in conditions of hypoxia, and in endotoxemia. However, further methodological development of NO microsensors is necessary to avoid the influence of changes in temperature, pH and oxygen on the measurements.     

Flexible Theoretical Calculation of Loop Length and Area Density of Weft-Knitted Structures: Part II

A simple and flexible method for theoretical calculation of the main structural parameters of various weft-knitted fancy and combined patterns is presented in this article. It is especially important for patterns containing different elements, such as loops, floats of different lengths, tucks, and tuck stitches. Measurement of an actual average length of the loop in these fabrics is complicated because it is necessary to disassemble precisely one pattern repeat to measure the yarn length and divide it by the number of elements in this pattern repeat. For large and complex pattern repeats, this is difficult and usually gives a high number of errors. It is very important to have lengths of structural elements as it helps to predict the main physical properties of knitted fabrics and their mechanical behaviour, which is especially important for protective textiles. The main idea of the proposed method, based on Čiukas geometrical model, is to calculate lengths of various structural elements or even their parts separately, taking into account the number of needle bars and their formation principle, which gives great flexibility to such modelling. The proposed theoretical formulas can be used for various patterned weft-knitted structures containing not only loops but tucks, floats of different lengths, or additional yarns; they give very few errors in empirical calculations and are easy to use.     

Stock price reaction to the drug development setbacks in the pharmaceutical industry

BackgroundInvestments in pharmaceutical companies remain challenging due to the inherent uncertainties of risk assessment.ObjectivesOur paper aims to assess the impact of the drug development setbacks (DDS) on the stock price of pharmaceutical companies while taking into account the company’s financial situation, pipeline size and trend of the stock price before the DDS.MethodsThe model-based clustering based on finite Gaussian mixture modeling was employed to identify the clusters of pharmaceutical companies with homogenous parameters. An artificial neural network was constructed to aid the prediction of the positive mean rate of return 120 days after the DDS.ResultsOur results reveal that a higher pipeline size and a lower rate of return before the DDS, as well as a lower ratio of the market value of the equity and the book value of the total liabilities, are associated with a positive mean rate of return 120 days after the DDS.ConclusionIn general, the DDS have a negative impact on the company’s stock price, but this risk can be minimized by investors choosing the companies that satisfy certain criteria. Graphical abstractOpen in a separate windowThe higher pipeline size(spip) and lower rate of return before (srr) the drug development setback (DDS) and the Market Value of Equity/Book Value of Total Liabilities ratio (sx4) are associated with a positive mean rate of return 120 days after the DDS.Electronic supplementary materialThe online version of this article (10.1007/s40199-020-00349-6) contains supplementary material, which is available to authorized users.     

Role for Tyrosine Kinases in Contraction of Rat Penile Small Arteries

IntroductionThe devasting effect of cancer and treatment thereof contribute to sexual dysfunction. Recently, a series of tyrosine kinase inhibitors have been approved either as add-on or for targeted treatment of cancer. However, tyrosine kinases are not only important for cell growth and proliferation, but also in regulation of vascular tone.AimThe present study investigated whether tyrosine kinases contribute to contractility in rat penile arteries, and addressed whether they are involved in calcium entry and/or related to the RhoA/Rho-kinase pathway.MethodsSegments of the rat dorsal penile artery were mounted in microvascular myographs for simultaneous measurements of intracellular calcium concentration ([Ca²⁺]_i) and tension, and tyrosine kinase activity, and phosphorylation of 20-kDa myosin light chain (MLC₂₀) was measured in dorsal penile artery homogenates.Main Outcome MeasuresIn vitro evidence for contractility and changes in intracellular Ca²⁺ in small penile arteries.ResultsSodium vanadate (Na₃VO₄, 1 mM), a tyrosine phosphatase inhibitor, increased [Ca²⁺]_i and tension. A l-type calcium channel blocker, nifedipine (1 µM), markedly reduced Na₃VO₄-evoked increases in [Ca²⁺]_i and tension. A thromboxane analog, U46619, increased TK activity. In contrast to the inactive analogue, genistein, a general TK inhibitor, concentration-dependently reduced both U46619-evoked contraction, and [Ca²⁺]_i. U46619-induced contraction was markedly inhibited by tyrphostin A23 and bis-tyrphostin, whereas there was no effect of the tyrosine kinase c-Src inhibitor, herbimycin A. Tyrphostin A23 suppressed U46619-mediated phosphorylation of MLC₂₀.ConclusionsThis study suggests that activation of tyrosine kinases is involved in contraction of rat penile smooth muscle probably by regulation of calcium entry through l-type calcium channels. These findings may have implications for the selections of novel add on anticancer treatments, e.g., inhibitors of tyrosine kinases, and for novel approaches to treat erectile dysfunction. Villalba N, Kun A, Stankevicius E, and Simonsen U. Role for tyrosine kinases in contraction of rat penile small arteries.     

Femtosecond laser micro‐machined polyimide films for cell scaffold applications

Engineering of sophisticated synthetic 3D scaffolds that allow controlling behaviour and location of the cells requires advanced micro/nano‐fabrication techniques. Ultrafast laser micro‐machining employing a 1030‐nm wavelength Yb:KGW femtosecond laser and a micro‐fabrication workstation for micro‐machining of commercially available 12.7 and 25.4 μm thickness polyimide (PI) film was applied. Mechanical properties of the fabricated scaffolds, i.e. arrays of differently spaced holes, were examined via custom‐built uniaxial micro‐tensile testing and finite element method simulations. We demonstrate that experimental micro‐tensile testing results could be numerically simulated and explained by two‐material model, assuming that 2–6 μm width rings around the holes possessed up to five times higher Young's modulus and yield stress compared with the rest of the laser intacted PI film areas of ‘dog‐bone’‐shaped specimens. That was attributed to material modification around the micro‐machined holes in the vicinity of the position of the focused laser beam track during trepanning drilling. We demonstrate that virgin PI films provide a suitable environment for the mobility, proliferation and intercellular communication of human bone marrow mesenchymal stem cells, and discuss how cell behaviour varies on the micro‐machined PI films with holes of different diameters (3.1, 8.4 and 16.7 μm) and hole spacing (30, 35, 40 and 45 μm). We conclude that the holes of 3.1 μm diameter were sufficient for metabolic and genetic communication through membranous tunneling tubes between cells residing on the opposite sides of PI film, but prevented the trans‐migration of cells through the holes. Copyright © 2016 John Wiley & Sons, Ltd.