Coupled K+–Water Flux through the HERG Potassium Channel Measured by an Osmotic Pulse Method

The streaming potential (Vstream) is a signature feature of ion channels in which permeating ions and water molecules move in a single file. Vstream provides a quantitative measure of the ion and water flux (the water–ion coupling ratio), the knowledge of which is a prerequisite for elucidating the mechanisms of ion permeation. We have developed a method to measure Vstream with the whole-cell patch-clamp configuration. A HEK293 cell stably expressing the HERG potassium channel was voltage clamped and exposed to hyperosmotic solutions for short periods of time (<1 s) by an ultrafast solution switching system (the osmotic pulse [quick jump-and-away] method). The reversal potentials were monitored by a series of voltage ramps before, during, and after the osmotic pulse. The shifts of the reversal potentials immediately after the osmotic jump gave Vstream. In symmetrical K+ solutions (10 mM), the Vstreams measured at different osmolalities showed a linear relationship with a slope of −0.7 mV/ΔOsm, from which the water–ion coupling ratio (n, the ratio of the flux of water to the flux of cations; Levitt, D.G., S.R. Elias, and J.M. Hautman. 1978. Biochim. Biophys. Acta. 512:436–451) was calculated to be 1.4. In symmetrical 100 mM K+ solutions, the coupling ratio was decreased significantly (n = 0.9), indicating that the permeation process through states with increased ion occupancy became significant. We presented a diagrammatic representation linking the water–ion coupling ratio to the mode of ion permeation and suggested that the coupling ratio of one may represent the least hydrated ion flux in the single-file pore

Association between physical activity and metabolic syndrome in middle-aged Japanese: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>Although many studies have reported an association between self-reported physical activity and metabolic syndrome (MetS), there is limited information on the optimal level of physical activity required to prevent MetS. This study aimed to determine the association between objectively measured physical activity and MetS in middle-aged Japanese individuals. We also determined the optimal cutoff value for physical activity required to decrease the risk of developing MetS.</p> <p>Methods</p> <p>A total of 179 men and 304 women, aged between 30 and 64 years, participated in this study. Participants were divided into two groups using the Japanese criteria for MetS as those with MetS or pre-MetS, and those without MetS. Participants were considered to be physically active if they achieved a physical activity level of 23 metabolic equivalents (METs) h/week, measured using a triaxial accelerometer. The association between physical activity and MetS was analyzed using logistic regression with the following covariates: sex, age, sedentary time, low intensity activity, calorie intake, smoking, menopause and body mass index. We also evaluated the factors that determined the association between the prevalence of MetS and pre-MetS and the physical activity cutoff value using classification and regression tree (CART) analysis.</p> <p>Results</p> <p>The odds ratio for MetS and pre-MetS was 2.20 for physically inactive participants (< 23 METs h/week), compared with physically active participants (≥ 23 METs h/week). The corresponding odds ratios for men and women were 2.27 (<it>P </it>< 0.01) and 1.95 (not significant), respectively. CART analyses revealed that moderate-vigorous physical activity of > 26.5 METs h/week was sufficient to decrease the prevalence of MetS and pre-MetS in middle-aged Japanese men and women.</p> <p>Conclusions</p> <p>The results of this cross-sectional study indicate that the Exercise and Physical Activity Reference for Health Promotion 2006 is inversely associated with the prevalence of MetS in men. Our results also suggest that moderate physical activity of > 26.5 METs h/week may decrease the risk of developing MetS and pre-MetS in middle-aged Japanese individuals.</p

Quantitative Assessment of Thyroid Nodules Using Dual-Energy Computed Tomography: Iodine Concentration Measurement and Multiparametric Texture Analysis for Differentiating between Malignant and Benign Lesions

Background and Objectives. Thyroid nodules are increasingly being detected during cross-sectional imaging of the neck and chest. The purpose of this study is to investigate the efficacy of dual-energy computed tomography (DECT) using iodine concentration measurement and multiparametric texture analysis of monochromatic images for differentiating between benign and malignant thyroid nodules. Materials and Methods. This retrospective study included 34 consecutive patients who presented with thyroid nodules and underwent noncontrast DECT between 2015 and 2016. Manual segmentation of each thyroid nodule by monochromatic imaging (40, 60, and 80 keV) was performed, and an in-house developed MATLAB-based texture analysis program was used to extract 41 textures. Iodine material decomposition and CT attenuation slopes were also measured. Histopathologic findings of ultrasound-guided biopsies over a follow-up period of at least one year were used as reference standards. Basic descriptive statistics and areas under receiver operating characteristic curves (AUCs) were evaluated. Results. The 34 nodules comprised 14 benign nodules and 20 malignant nodules. Iodine content and Hounsfield unit curve slopes did not differ significantly between benign and malignant thyroid nodules (P=0.480–0.670). However, significant differences in the texture features of monochromatic images were observed between benign and malignant nodules: histogram mean and median, co-occurrence matrix contrast, gray-level gradient matrix (GLGM) skewness, and mean gradients and variance of gradients for GLGM at 80 keV (P=0.014–0.044). The highest AUC was 0.77, for the histogram mean and median of images acquired at 80 keV. Conclusions. Texture features extracted from monochromatic images using DECT, specifically acquired at high keV, may be a promising diagnostic approach for thyroid nodules. A further large study for incidental thyroid nodules using DECT texture analysis is required to validate our results