179 research outputs found

    Virtual reality rehabilitation in patients with chronic obstructive pulmonary disease: A randomized controlled trial

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    Purpose: This study compared the effects of inpatient-based rehabilitation program of patients with chronic obstructive pulmonary disease (COPD) using non-immersive virtual reality (VR) training with a traditional pulmonary rehabilitation program. The aims of this study were to determine 1) whether rehabilitation featuring both VR as well as exercise training provides benefits over exercise training (ET) alone and 2) whether rehabilitation featuring VR training instead of exercise training provides equivalent benefits. Patients and Methods: The study recruited 106 patients with COPD to a 2-week high-intensity, five times a week intervention. Randomized into three groups, 34 patients participated in a traditional pulmonary rehabilitation program including endurance exercise training (ET), 38 patients participated in traditional pulmonary rehabilitation, including both endurance exercise training and virtual reality training (ET+VR) and 34 patients participated in pulmonary rehabilitation program including virtual reality training but no endurance exercise training (VR). The traditional pulmonary rehabilitation program consisted of fitness exercises, resistance respiratory muscle and relaxation training. Xbox 360Âź and KinectÂź Adventures software were used for the VR training of lower and upper body strength, endurance, trunk control and dynamic balance. Comparison of the changes in the Senior Fitness Test was the primary outcome. Analysis was performed using linear mixed-effects models. Results: The comparison between ET and ET+VR groups showed that ET+VR group was superior to ET group in Arm Curl (p<0.003), Chair stand (p<0.008), Back scratch (p<0.002), Chair sit and reach (p<0.001), Up and go (p<0.000), 6-min walk test (p<0.011). Whereas, the comparison between ET and VR groups showed that VR group was superior to ET group in Arm Curl (p<0.000), Chair stand (p<0.001), 6-min walk test (p<0.031). Conclusion: Results suggest that pulmonary rehabilitation program supplemented with VR training is beneficial intervention to improve physical fitness in patients with COPD

    Low-Cost Data Acquisition Card for School-Network Cosmic Ray Detectors

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    The Cosmic Ray Observatory Project (CROP) at University of Nebraska/Lincoln and the Washington Area Large-scale Time coincidence Array (WALTA) at University of Washington/Seattle are among several outreach projects siting cosmic-ray detectors at local high schools in cities around North America, to study the origins and interactions of high-energy cosmic rays. In a collaboration between QuarkNet, the outreach program based at Fermilab, CROP, and WALTA, a low-cost data acquisition electronics card has been developed to collect and synchronize the data from each detector site. The cost for each card is under US$500 for parts, functionally replacing much more expensive electronics crates and modules at each high school site. The card has 4 analog discriminator inputs for photo-multiplier tube signals, a 4-channel Time-to-Digital converter for local coincidence and time-over-threshold measurements at 0.75 ns resolution, programmable trigger logic via a CPLD and microcontroller, and a built-in low-cost GPS receiver/antenna module (via external cable) to provide event trigger time stamps at better than 100 ns accuracy. Temperature sensors and a barometer are also integrated to record environmental data along with the counter data. The card connects to any PC or laptop via a standard RS-232 serial port for data output and control. The microcontroller and CPLD are field programmable and therefore make the card functionality flexible and easy to upgrade.Comment: 4 pages, 4 figures, 1 table. Presented by R. J. Wilkes at "IEEE-NSS 2003", Paper N8-1, Portland, OR, November 2003. Submitted to Trans. IEE

    Hydrostatic Level Sensors as High Precision Ground Motion Instrumentation for Tevatron and Other Energy Frontier Accelerators

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    Particle accelerators pushed the limits of our knowledge in search of the answers to most fundamental questions about micro-world and our Universe. In these pursuits, accelerators progressed to higher and higher energies and particle beam intensities as well as increasingly smaller and smaller beam sizes. As the result, modern existing and planned energy frontier accelerators demand very tight tolerances on alignment and stability of their elements: magnets, accelerating cavities, vacuum chambers, etc. In this article we describe the instruments developed for and used in such accelerators as Fermilab's Tevatron (FNAL, Batavia, IL USA) and for the studies toward an International Linear Collider (ILC). The instrumentation includes Hydrostatic Level Sensors (HLS) for very low frequency measurements. We present design features of the sensors, outline their technical parameters, describe test and calibration procedures and discuss different regimes of operation. Experimental results of the ground motion measurements with these detectors will be presented in subsequent paper

    Sialylated N-glycans mediate monocyte uptake of extracellular vesicles secreted from Plasmodium falciparum-infected red blood cells

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    Glycoconjugates on extracellular vesicles (EVs) play a vital role in internalization and mediate interaction as well as regulation of the host immune system by viruses, bacteria, and parasites. During their intraerythrocytic life-cycle stages, malaria parasites, Plasmodium falciparum (Pf) mediate the secretion of EVs by infected red blood cells (RBCs) that carry a diverse range of parasitic and host-derived molecules. These molecules facilitate parasite-parasite and parasite-host interactions to ensure parasite survival. To date, the number of identified Pf genes associated with glycan synthesis and the repertoire of expressed glycoconjugates is relatively low. Moreover, the role of Pf glycans in pathogenesis is mostly unclear and poorly understood. As a result, the expression of glycoconjugates on Pf-derived EVs or their involvement in the parasite life-cycle has yet to be reported. Herein, we show that EVs secreted by Pf-infected RBCs carry significantly higher sialylated complex N-glycans than EVs derived from healthy RBCs. Furthermore, we reveal that EV uptake by host monocytes depends on N-glycoproteins and demonstrate that terminal sialic acid on the N-glycans is essential for uptake by human monocytes. Our results provide the first evidence that Pf exploits host sialylated N-glycans to mediate EV uptake by the human immune system cells

    Enhanced firing of locus coeruleus neurons and SK channel dysfunction are conserved in distinct models of prodromal Parkinson's disease

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    Parkinson’s disease (PD) is clinically defined by the presence of the cardinal motor symptoms, which are associated with a loss of dopaminergic nigrostriatal neurons in the substantia nigra pars compacta (SNpc). While SNpc neurons serve as the prototypical cell-type to study cellular vulnerability in PD, there is an unmet need to extent our efforts to other neurons at risk. The noradrenergic locus coeruleus (LC) represents one of the first brain structures affected in Parkinson’s disease (PD) and plays not only a crucial role for the evolving non-motor symptomatology, but it is also believed to contribute to disease progression by efferent noradrenergic deficiency. Therefore, we sought to characterize the electrophysiological properties of LC neurons in two distinct PD models: (1) in an in vivo mouse model of focal α-synuclein overexpression; and (2) in an in vitro rotenone-induced PD model. Despite the fundamental differences of these two PD models, α-synuclein overexpression as well as rotenone exposure led to an accelerated autonomous pacemaker frequency of LC neurons, accompanied by severe alterations of the afterhyperpolarization amplitude. On the mechanistic side, we suggest that Ca(2+)-activated K(+) (SK) channels are mediators of the increased LC neuronal excitability, as pharmacological activation of these channels is sufficient to prevent increased LC pacemaking and subsequent neuronal loss in the LC following in vitro rotenone exposure. These findings suggest a role of SK channels in PD by linking α-synuclein- and rotenone-induced changes in LC firing rate to SK channel dysfunction

    Identification of the A293 (AVE1231) Binding Site in the Cardiac Two-Pore-Domain Potassium Channel TASK-1: a Common Low Affinity Antiarrhythmic Drug Binding Site

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    Background/Aims: The two-pore-domain potassium channel TASK-1 regulates atrial action potential duration. Due to the atrium-specific expression of TASK-1 in the human heart and the functional upregulation of TASK-1 currents in atrial fibrillation (AF), TASK-1 represents a promising target for the treatment of AF. Therefore, detailed knowledge of the molecular determinants of TASK-1 inhibition may help to identify new drugs for the future therapy of AF. In the current study, the molecular determinants of TASK-1 inhibition by the potent and antiarrhythmic compound A293 (AVE1231) were studied in detail. Methods: Alanine-scanning mutagenesis together with two-electrode voltage-clamp recordings were combined with in silico docking experiments. Results: Here, we have identified Q126 located in the M2 segment together with L239 and N240 of the M4 segment as amino acids essential for the A293-mediated inhibition of TASK‑1. These data indicate a binding site which is different to that of A1899 for which also residues of the pore signature sequence and the late M4 segments are essential. Using in silico docking experiments, we propose a binding site at the lower end of the cytosolic pore, located at the entry to lateral side fenestrations of TASK-1. Strikingly, TASK-1 inhibition by the low affinity antiarrhythmic TASK‑1 blockers propafenone, amiodarone and carvedilol was also strongly diminished by mutations at this novel binding site. Conclusion: We have identified the A293 binding site in the central cavity of TASK-1 and propose that this site might represent a conserved site of action for many low affinity antiarrhythmic TASK-1 blockers

    Observing Virtual Arms that You Imagine Are Yours Increases the Galvanic Skin Response to an Unexpected Threat

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    Multi-modal visuo-tactile stimulation of the type performed in the rubber hand illusion can induce the brain to temporarily incorporate external objects into the body image. In this study we show that audio-visual stimulation combined with mental imagery more rapidly elicits an elevated physiological response (skin conductance) after an unexpected threat to a virtual limb, compared to audio-visual stimulation alone. Two groups of subjects seated in front of a monitor watched a first-person perspective view of slow movements of two virtual arms intercepting virtual balls rolling towards the viewer. One group was instructed to simply observe the movements of the two virtual arms, while the other group was instructed to observe the virtual arms and imagine that the arms were their own. After 84 seconds the right virtual arm was unexpectedly “stabbed” by a knife and began “bleeding”. This aversive stimulus caused both groups to show a significant increase in skin conductance. In addition, the observation-with-imagery group showed a significantly higher skin conductance (p<0.05) than the observation-only group over a 2-second period shortly after the aversive stimulus onset. No corresponding change was found in subjects' heart rates. Our results suggest that simple visual input combined with mental imagery may induce the brain to measurably temporarily incorporate external objects into its body image

    Al-Gazali skeletal dysplasia constitutes the lethal end of ADAMTSL2-related disorders

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    First published: 10 March 2023. OnlinePublLethal short-limb skeletal dysplasia Al-Gazali type (OMIM %601356) is an ultra-rare disorder previously reported in only three unrelated individuals. The genetic etiology for Al-Gazali skeletal dysplasia has up until now been unknown. Through international collaborative efforts involving seven clinical centers worldwide, a cohort of nine patients with clinical and radiographic features consistent with short-limb skeletal dysplasia Al-Gazali type was collected. The affected individuals presented with moderate intrauterine growth restriction, relative macrocephaly, hypertrichosis, large anterior fontanelle, short neck, short and stiff limbs with small hands and feet, severe brachydactyly, and generalized bone sclerosis with mild platyspondyly. Biallelic disease-causing variants in ADAMTSL2 were detected using massively parallel sequencing (MPS) and Sanger sequencing techniques. Six individuals were compound heterozygous and one individual was homozygous for pathogenic variants in ADAMTSL2. In one of the families pathogenic variants were detected in parental samples only. Overall, this study sheds light on the genetic cause of Al-Gazali skeletal dysplasia and identifies it as a semi-lethal part of the spectrum of ADAMTSL2-related disorders. Furthermore, we highlight the importance of meticulous analysis of the pseudogene region of ADAMTSL2 where disease-causing variants might be located.Dominyka Batkovskyte, Fiona McKenzie, Fulya Taylan, Pelin Ozlem Simsek-Kiper, Sarah M Nikkel, Hirofumi Ohashi, Roger E Stevenson, Thuong Ha, Denise P Cavalcanti, Hiroyuki Miyahara, Steven A Skinner, Miguel A Aguirre, ZĂŒhal Akçören, Gulen Eda Utine, Tillie Chiu, Kenji Shimizu, Anna Hammarsjö, Koray Boduroglu, Hannah W Moore, Raymond J Louie, Peer Arts, Allie N Merrihew, Milena Babic, Matilda R Jackson, Nikos Papadogiannakis, Anna Lindstrand, Ann Nordgren, Christopher P Barnett, Hamish S Scott, Andrei S Chagin, Gen Nishimura, and Giedre Grigelionien
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