Psychometric properties of the Polish version of the eight-item Morisky Medication Adherence Scale in hypertensive adults.

Low adherence to pharmacological treatment is often associated with poor blood pressure control, but identification of nonadherent patients in outpatient settings is difficult. The aim of the study was to translate and evaluate the psychometric properties of the Polish version of the structured self-report eight-item Morisky Medication Adherence Scale (MMAS-8) among patients with hypertension. The study was conducted in a family doctor practice between January and July 2015. After a standard "forward-backward" procedure to translate MMAS-8 into Polish, the questionnaire was administered to 160 patients with hypertension. Reliability was tested using a measure of internal consistency (Cronbach's α) and test-retest reliability. Validity was confirmed using known group validity. Three levels of adherence were considered based on the following scores: 0 to <6 (low); 6 to <8 (medium); and 8 (high). Complete questionnaires were returned by 110 respondents (mean age: 60.7 years ±12.6; 54.6% were female). The mean number of pills taken daily was 3.61±4.31. The mean adherence score was 6.42± 2.0. Moderate internal consistency was found (Cronbach's α=0.81), and test-retest reliability was satisfactory (r=0.461-0.905; P<0.001). Reproducibility expressed by Cohen's κ coefficient =0.61 was good. In high-adherent patients, the percentage of well-controlled blood pressure was higher than in low-adherent patients (33.3% vs 19.1%, χ (2)=0.87, P=0.648). Psychometric evaluation of the Polish version of the MMAS-8 indicates that it is a reliable and valid measure tool to detect nonadherent patients. The MMAS-8 may be routinely used to support communication about the medication-taking behavior in hypertensive patients

Are the adverse effects of glitazones linked to induced testosterone deficiency?

<p>Abstract</p> <p>Background</p> <p>Adverse side-effects of the glitazones have been frequently reported in both clinical and animal studies, especially with rosiglitazone (RGZ) and pioglitazone (PGZ), including congestive heart failure, osteoporosis, weight gain, oedema and anaemia. These led to consideration of an evidence-based hypothesis which would explain these diverse effects, and further suggested novel approaches by which this hypothesis could be tested.</p> <p>Presentation of hypothesis</p> <p>The literature on the clinical, metabolic and endocrine effects of glitazones in relation to the reported actions of testosterone in diabetes, metabolic syndrome, and cardiovascular disease is reviewed, and the following unifying hypothesis advanced: "<it>Glitazones induce androgen deficiency in patients with Type 2 Diabetes Mellitus resulting in pathophysiological changes in multiple tissues and organs which may explain their observed clinical adverse effects</it>." This also provides further evidence for the lipocentric concept of diabetes and its clinical implications.</p> <p>Testing of the hypothesis</p> <p>Clinical studies to investigate the endocrine profiles, including measurements of TT, DHT, SHBG, FT and estradiol, together with LH and FSH, in both men and women with T2DM before and after RGZ and PGZ treatment in placebo controlled groups, are necessary to provide data to substantiate this hypothesis. Also, studies on T treatment in diabetic men would further establish if the adverse effects of glitazones could be reversed or ameliorated by androgen therapy. Basic sciences investigations on the inhibition of androgen biosynthesis by glitazones are also warranted.</p> <p>Implications of the hypothesis</p> <p>Glitazones reduce androgen biosynthesis, increase their binding to SHBG, and attenuate androgen receptor activation, thus reducing the physiological actions of testosterone, causing relative and absolute androgen deficiency. This hypothesis explains the adverse effects of glitazones on the heart and other organs resulting from reversal of the action of androgens in directing the maturation of stem cells towards muscle, vascular endothelium, erythroid stem cells and osteoblasts, and away from adipocyte differentiation. The higher incidence of side-effects with RGZ than PGZ, may be explained by a detailed study of the mechanism by which glitazones down-regulate androgen biosynthesis and action, resulting in a state of androgen deficiency.</p

Interactions Between Baclofen and DC-induced Plasticity of Afferent Fibers within the Spinal Cord

The aims of the study were to compare effects of baclofen, a GABA B receptor agonist commonly used as an antispastic drug, on direct current (DC) evoked long-lasting changes in the excitability of afferent fibers traversing the dorsal columns and their terminal branches in the spinal cord, and to examine whether baclofen interferes with the development and expression of these changes. The experiments were performed on deeply anesthetized rats by analyzing the effects of DC before, during and following baclofen administration. Muscle and skin afferent fibers within the dorsal columns were stimulated epidurally and changes in their excitability were investigated following epidural polarization by 1.0\u20131.1 \u3bcA subsequent to i.v. administration of baclofen. Epidural polarization increased the excitability of these fibers during post-polarization periods of at least 1 h. The facilitation was as potent as in preparations that were not pretreated with baclofen, indicating that the advantages of combining epidural polarization with epidural stimulation would not be endangered by pharmacological antispastic treatment with baclofen. In contrast, baclofen-reduced effects of intraspinal stimulation combined with intraspinal polarization (0.3 \u3bcA) of terminal axonal branches of the afferents within the dorsal horn or in motor nuclei, whether administered ionophoretically or intravenously. Effects of DC on monosynaptically evoked synaptic actions of these fibers (extracellular field potentials) were likewise reduced by baclofen. The study thus provides further evidence for differential effects of DC on afferent fibers in the dorsal columns and the preterminal branches of these fibers and their involvement in spinal plasticity

Combining frequency and time domain approaches to systems with multiple spike train input and output

A frequency domain approach and a time domain approach have been combined in an investigation of the behaviour of the primary and secondary endings of an isolated muscle spindle in response to the activity of two static fusimotor axons when the parent muscle is held at a fixed length and when it is subjected to random length changes. The frequency domain analysis has an associated error process which provides a measure of how well the input processes can be used to predict the output processes and is also used to specify how the interactions between the recorded processes contribute to this error. Without assuming stationarity of the input, the time domain approach uses a sequence of probability models of increasing complexity in which the number of input processes to the model is progressively increased. This feature of the time domain approach was used to identify a preferred direction of interaction between the processes underlying the generation of the activity of the primary and secondary endings. In the presence of fusimotor activity and dynamic length changes imposed on the muscle, it was shown that the activity of the primary and secondary endings carried different information about the effects of the inputs imposed on the muscle spindle. The results presented in this work emphasise that the analysis of the behaviour of complex systems benefits from a combination of frequency and time domain methods

Synovial membrane asks for independence

Synovial membrane is traditionally considered as a part of the joint capsule. It, however, differs from fibrous part of the capsule in development, structure, function, vascularisation, innervation and involvement in pathological processes. Moreover, in some areas, it even does not contact with the fibrous capsule. Thus, it appears that the synovial membrane should be considered as an independent organ and not as the lining of the joint capsule.

Formation of synovial joints and articular cartilage

Chondrocytes differentiate from mesenchymal progenitors and produce templates(anlagen) for the developing bones. Chondrocyte differentiation is controlled bySox transcription factors. Templates for the neighbour bones are subsequentlyseparated by conversion of differentiated chondrocytes into non-chondrogeniccells and emergence of interzone in which joints cavitation occurs. A central rolein initiating synovial joint formation plays Wnt-14/beta-catenin signalling pathway.Moreover, bone morphogenetic proteins and growth and differentiation factorsare expressed at the site of joint formation. Joint cavitation is associated withincreased hyaluronic acid synthesis. Hyaluronic acid facilitates tissue separationand creation of a functional joint cavity. According to the traditional view articularcartilage represents part of cartilage anlage that is not replaced by bone throughendochondral ossification. Recent studies indicate, however, that peri-joint mesenchymalcells take part in interzone formation and that these interzone cellssubsequently differentiate into articular chondrocytes and synovial cells. Thus,anlage chondrocytes have a transient character and disappear after cessation ofgrowth plate function while articular chondrocytes have stable and permanentphenotype and function throughout life

Direct current stimulation modulates the excitability of the sensory and motor fibres in the human posterior tibial nerve, with a long-lasting effect on the H-reflex

Several studies demonstrated that transcutaneous direct current stimulation (DCS) may modulate central nervous system excitability. However, much less is known about how DC affects peripheral nerve fibres. We investigated the action of DCS on motor and sensory fibres of the human posterior tibial nerve, with supplementary analysis in acute experiments on rats. In forty human subjects, electric pulses at the popliteal fossa were used to elicit either M-waves or H-reflexes in the Soleus, before (15&nbsp;min), during (10&nbsp;min) and after (30&nbsp;min) DCS. Cathodal or anodal current (2&nbsp;mA) was applied to the same nerve. Cathodal DCS significantly increased the H-reflex amplitude; the post-polarization effect lasted up to ~&nbsp;25&nbsp;min after the termination of DCS. Anodal DCS instead significantly decreased the reflex amplitude for up to ~&nbsp;5&nbsp;min after DCS end. DCS effects on M-wave showed the same polarity dependence but with considerably shorter after-effects, which never exceeded 5&nbsp;min. DCS changed the excitability of both motor and sensory fibres. These effects and especially the long-lasting modulation of the H-reflex suggest a possible rehabilitative application of DCS that could be applied either to compensate an altered peripheral excitability or to modulate the afferent transmission to spinal and supraspinal structures. In animal experiments, DCS was applied, under anaesthesia, to either the exposed peroneus nerve or its Dorsal Root, and its effects closely resembled those found in human subjects. They validate therefore the use of the animal models for future investigations on the DCS mechanisms

Different contributions of primary motor cortex, reticular formation, and spinal cord to fractionated muscle activation

Coordinated movement requires patterned activation of muscles. In this study, we examined differences in selective activation of primate upper limb muscles by cortical and subcortical regions. Five macaque monkeys were trained to perform a reach and grasp task, and electromyogram (EMG) was recorded from 10 to 24 muscles while weak single-pulse stimuli were delivered through microelectrodes inserted in the motor cortex (M1), reticular formation (RF), or cervical spinal cord (SC). Stimulus intensity was adjusted to a level just above threshold. Stimulus-evoked effects were assessed from averages of rectified EMG. M1, RF, and SC activated 1.5 ± 0.9, 1.9 ± 0.8, and 2.5 ± 1.6 muscles per site (means ± SD); only M1 and SC differed significantly. In between recording sessions, natural muscle activity in the home cage was recorded using a miniature data logger. A novel analysis assessed how well natural activity could be reconstructed by stimulus-evoked responses. This provided two measures: normalized vector length L, reflecting how closely aligned natural and stimulus-evoked activity were, and normalized residual R, measuring the fraction of natural activity not reachable using stimulus-evoked patterns. Average values for M1, RF, and SC were L = 119.1 ± 9.6, 105.9 ± 6.2, and 109.3 ± 8.4% and R = 50.3 ± 4.9, 56.4 ± 3.5, and 51.5 ± 4.8%, respectively. RF was significantly different from M1 and SC on both measurements. RF is thus able to generate an approximation to the motor output with less activation than required by M1 and SC, but M1 and SC are more precise in reaching the exact activation pattern required. Cortical, brainstem, and spinal centers likely play distinct roles, as they cooperate to generate voluntary movements. NEW & NOTEWORTHY Brainstem reticular formation, primary motor cortex, and cervical spinal cord intermediate zone can all activate primate upper limb muscles. However, brainstem output is more efficient but less precise in producing natural patterns of motor output than motor cortex or spinal cord. We suggest that gross muscle synergies from the reticular formation are sculpted and refined by motor cortex and spinal circuits to reach the finely fractionated output characteristic of dexterous primate upper limb movements

Total Sitting Time and Sitting Pattern in Postmenopausal Women Differ by Hispanic Ethnicity and are Associated With Cardiometabolic Risk Biomarkers.

Background Sedentary behavior is pervasive, especially in older adults, and is associated with cardiometabolic disease and mortality. Relationships between cardiometabolic biomarkers and sitting time are unexplored in older women, as are possible ethnic differences. Methods and Results Ethnic differences in sitting behavior and associations with cardiometabolic risk were explored in overweight/obese postmenopausal women (n=518; mean±SD age 63±6 years; mean body mass index 31.4±4.8 kg/m2). Accelerometer data were processed using validated machine-learned algorithms to measure total daily sitting time and mean sitting bout duration (an indicator of sitting behavior pattern). Multivariable linear regression was used to compare sitting among Hispanic women (n=102) and non-Hispanic women (n=416) and tested associations with cardiometabolic risk biomarkers. Hispanic women sat, on average, 50.3 minutes less/day than non-Hispanic women (P&lt;0.001) and had shorter (3.6 minutes less, P=0.02) mean sitting bout duration. Among all women, longer total sitting time was deleteriously associated with fasting insulin and triglyceride concentrations, insulin resistance, body mass index and waist circumference; longer mean sitting bout duration was deleteriously associated with fasting glucose and insulin concentrations, insulin resistance, body mass index and waist circumference. Exploratory interaction analysis showed that the association between mean sitting bout duration and fasting glucose concentration was significantly stronger among Hispanic women than non-Hispanic women (P-interaction=0.03). Conclusions Ethnic differences in 2 objectively measured parameters of sitting behavior, as well as detrimental associations between parameters and cardiometabolic biomarkers were observed in overweight/obese older women. The detrimental association between mean sitting bout duration and fasting glucose may be greater in Hispanic women than in non-Hispanic women. Corroboration in larger studies is warranted

Application of extremely compact capillary discharge soft x-ray lasers to dense plasma diagnostics

Includes bibliographical references.Table-top capillary discharge soft x-ray lasers combine the advantages of a small size and a high repetition rate with an extremely high brightness similar to that of their laboratory-size predecessors. When utilized to probe high density plasmas their short wavelength results in a higher critical density, reduced refraction, decreased free-electron absorption, and higher resolution as compared to optical probes. These characteristics allow the design of experiments capable of measuring the evolution of plasmas with density-scale length products that are outside the reach of optical lasers. This paper reviews the use of a 46.9 nm wavelength Ne-like Ar capillary discharge table-top laser in dense plasma diagnostics, and reports soft x-ray laser interferometry results of spot-focus Nd:YAG laser plasmas created at moderate irradiation intensity (~7×1012 W cm-2) with ; ~13 ns pulse width duration laser pulses. The measurements produced electron density maps with densities up to 0.9×1021 cm-3 that show the development of a concave electron density profile that differ significantly from those of a classical expansion. This two-dimensional behavior, that was recently also observed in line-focus plasmas, is analyzed here for the case of spot-focus plasmas with the assistance of hydrodynamic model simulations. The results demonstrate the use of a table-top soft x-ray laser interferometer as a new high resolution tool for the study of high density plasma phenomena and the validation of hydrodynamic codes.This work was supported by the U.S. Department of Energy Grant No. DE-FG03-02NA00062 and by the National Science Foundation. Part of this work was performed under the auspices of the U.S. Department of Energy by the University of California, Lawrence Livermore National Laboratory through the Institute of Laser Science and Application, under Contract No. W-7405-Eng-48