Impaired Hyperemic Response to Exercise Post Stroke

Individuals with chronic stroke have reduced perfusion of the paretic lower limb at rest; however, the hyperemic response to graded muscle contractions in this patient population has not been examined. This study quantified blood flow to the paretic and non-paretic lower limbs of subjects with chronic stroke after submaximal contractions of the knee extensor muscles and correlated those measures with limb function and activity. Ten subjects with chronic stroke and ten controls had blood flow through the superficial femoral artery quantified with ultrasonography before and immediately after 10 second contractions of the knee extensor muscles at 20, 40, 60, and 80% of the maximal voluntary contraction (MVC) of the test limb. Blood flow to the paretic and non-paretic limb of stroke subjects was significantly reduced at all load levels compared to control subjects even after normalization to lean muscle mass. Of variables measured, increased blood flow after an 80% MVC was the single best predictor of paretic limb strength, the symmetry of strength between the paretic and non-paretic limbs, coordination of the paretic limb, and physical activity. The impaired hemodynamic response to high intensity contractions was a better predictor of lower limb function than resting perfusion measures. Stroke-dependent weakness and atrophy of the paretic limb do not explain the reduced hyperemic response to muscle contraction alone as the response is similarly reduced in the non-paretic limb when compared to controls. These data may suggest a role for perfusion therapies to optimize rehabilitation post stroke

Evaluation of Vascular Control Mechanisms Utilizing Video Microscopy of Isolated Resistance Arteries of Rats

This protocol describes the use of in vitro television microscopy to evaluate vascular function in isolated cerebral resistance arteries (and other vessels), and describes techniques for evaluating tissue perfusion using Laser Doppler Flowmetry (LDF) and microvessel density utilizing fluorescently labeled Griffonia simplicifolia (GS1) lectin. Current methods for studying isolated resistance arteries at transmural pressures encountered in vivo and in the absence of parenchymal cell influences provide a critical link between in vivo studies and information gained from molecular reductionist approaches that provide limited insight into integrative responses at the whole animal level. LDF and techniques to selectively identify arterioles and capillaries with fluorescently-labeled GS1 lectin provide practical solutions to enable investigators to extend the knowledge gained from studies of isolated resistance arteries. This paper describes the application of these techniques to gain fundamental knowledge of vascular physiology and pathology in the rat as a general experimental model, and in a variety of specialized genetically engineered designer rat strains that can provide important insight into the influence of specific genes on important vascular phenotypes. Utilizing these valuable experimental approaches in rat strains developed by selective breeding strategies and new technologies for producing gene knockout models in the rat, will expand the rigor of scientific premises developed in knockout mouse models and extend that knowledge to a more relevant animal model, with a well understood physiological background and suitability for physiological studies because of its larger size

Hyperoxia Causes Mitochondrial Fragmentation in Pulmonary Endothelial Cells by Increasing Expression of Pro-Fission Proteins

Objective—We explored mechanisms that alter mitochondrial structure and function in pulmonary endothelial cells (PEC) function after hyperoxia. Approach and Results—Mitochondrial structures of PECs exposed to hyperoxia or normoxia were visualized and mitochondrial fragmentation quantified. Expression of pro-fission or fusion proteins or autophagy-related proteins were assessed by Western blot. Mitochondrial oxidative state was determined using mito-roGFP. Tetramethylrhodamine methyl ester estimated mitochondrial polarization in treatment groups. The role of mitochondrially derived reactive oxygen species in mt-fragmentation was investigated with mito-TEMPOL and mitochondrial DNA (mtDNA) damage studied by using ENDO III (mt-tat-endonuclease III), a protein that repairs mDNA damage. Drp-1 (dynamin-related protein 1) was overexpressed or silenced to test the role of this protein in cell survival or transwell resistance. Hyperoxia increased fragmentation of PEC mitochondria in a time-dependent manner through 48 hours of exposure. Hyperoxic PECs exhibited increased phosphorylation of Drp-1 (serine 616), decreases in Mfn1 (mitofusion protein 1), but increases in OPA-1 (optic atrophy 1). Pro-autophagy proteins p62 (LC3 adapter–binding protein SQSTM1/p62), PINK-1 (PTEN-induced putative kinase 1), and LC3B (microtubule-associated protein 1A/1B-light chain 3) were increased. Returning cells to normoxia for 24 hours reversed the increased mt-fragmentation and changes in expression of pro-fission proteins. Hyperoxia-induced changes in mitochondrial structure or cell survival were mitigated by antioxidants mito-TEMPOL, Drp-1 silencing, or inhibition or protection by the mitochondrial endonuclease ENDO III. Hyperoxia induced oxidation and mitochondrial depolarization and impaired transwell resistance. Decrease in resistance was mitigated by mito-TEMPOL or ENDO III and reproduced by overexpression of Drp-1. Conclusions—Because hyperoxia evoked mt-fragmentation, cell survival and transwell resistance are prevented by ENDO III and mito-TEMPOL and Drp-1 silencing, and these data link hyperoxia-induced mt-DNA damage, Drp-1 expression, mt-fragmentation, and PEC dysfunction

Two Weeks of Ischemic Conditioning Improves Walking Speed and Reduces Neuromuscular Fatigability in Chronic Stroke Survivors

This pilot study examined whether ischemic conditioning (IC), a noninvasive, cost-effective, and easy-to-administer intervention, could improve gait speed and paretic leg muscle function in stroke survivors. We hypothesized that 2 wk of IC training would increase self-selected walking speed, increase paretic muscle strength, and reduce neuromuscular fatigability in chronic stroke survivors. Twenty-two chronic stroke survivors received either IC or IC Sham on their paretic leg every other day for 2 wk (7 total sessions). IC involved 5-min bouts of ischemia, repeated five times, using a cuff inflated to 225 mmHg on the paretic thigh. For IC Sham, the cuff inflation pressure was 10 mmHg. Self-selected walking speed was assessed using the 10-m walk test, and paretic leg knee extensor strength and fatigability were assessed using a Biodex dynamometer. Self-selected walking speed increased in the IC group (0.86 ± 0.21 m/s pretest vs. 1.04 ± 0.22 m/s posttest, means ± SD; P\u3c 0.001) but not in the IC Sham group (0.92 ± 0.47 m/s pretest vs. 0.96 ± 0.46 m/s posttest; P= 0.25). Paretic leg maximum voluntary contractions were unchanged in both groups (103 ± 57 N·m pre-IC vs. 109 ± 65 N·m post-IC; 103 ± 59 N·m pre-IC Sham vs. 108 ± 67 N·m post-IC Sham; P = 0.81); however, participants in the IC group maintained a submaximal isometric contraction longer than participants in the IC Sham group (278 ± 163 s pre-IC vs. 496 ± 313 s post-IC, P = 0.004; 397 ± 203 s pre-IC Sham vs. 355 ± 195 s post-IC Sham; P = 0.46). The results from this pilot study thus indicate that IC training has the potential to improve walking speed and paretic muscle fatigue resistance poststroke

Improving the quality of written information available at weekends in a paediatric hospital: the TRANSMIT sheet.

The clinical outcomes at weekends are worse than during the week in a hospital setting. There are many potential factors which influence this. High quality communication between the weekday teams and the on call weekend staff could help improve clinical outcomes at weekends, but there are no validated forms of communication that have been established in a paediatric hospital setting. The casenotes of all medical patients (n=119) were prospectively evaluated across all medical wards in a large paediatric hospital over three weekends, to establish the quality of information available to on call teams. Following introduction of structured documentation, known as a TRANSMIT (including Tasks, Respiratory, Anticipated problems, Nutrition, Sepsis, Medication, Intravenous access, Transfer/discharge) sheet, the audit was repeated (n=111). A qualitative survey of junior doctors using TRANSMIT was carried out after introduction. Prior to the introduction of the structured documentation (TRANSMIT sheet) an accurate problem list was present in 56% (67/119), and an adequate written management plan in 63% (75/119). Following introduction, an improvement in the notes was seen, with accurate problem lists in 82% (91/111) and an adequate plan in 76% (84/111). Improvements in the quantity and quality of information available to weekend on call medical staff were noted. The use of a structured documentation (TRANSMIT sheet) can improve the quality of written information available to on-call teams in a paediatric hospital setting. A retrospective qualitative assessment of junior doctors using TRANSMIT sheets showed an improvement in both the quantity and quality of information available to on call staff at weekends

Ischemic Conditioning Increases Strength and Volitional Activation of Paretic Muscle in Chronic Stroke: A Pilot Study

7siIschemic conditioning (IC) on the arm or leg has emerged as an intervention to improve strength and performance in healthy populations, but the effects on neurologic populations are unknown. The purpose of this study was to quantify the effects of a single session of IC on knee extensor strength and muscle activation in chronic stroke survivors. Maximal knee extensor torque measurements and surface EMG were quantified in 10 chronic stroke survivors (>1 year post-stroke) with hemiparesis before and after a single session of IC or Sham on the paretic leg. IC consisted of five minutes of compression with a proximal thigh cuff (inflation pressure = 225 mmHg for IC or 25 mmHg for Sham) followed by five minutes of rest. This was repeated five times. Maximal knee extensor strength, EMG magnitude, and motor unit firing behavior were measured before and immediately after IC or Sham. IC increased paretic leg strength by 10.6plus minus8.5 Nm while no difference was observed in the Sham group (change in Sham = 1.3plus minus2.9 Nm; p = 0.001 IC vs. Sham). IC-induced increases in strength were accompanied by a 31plus minus15% increase in the magnitude of muscle EMG during maximal contractions and a 5% decrease in motor unit recruitment thresholds during sub-maximal contractions. Individuals who had the most asymmetry in strength between their paretic and non-paretic legs had the largest increases in strength (r2= 0.54). This study provides evidence that a single session of IC can increase strength through improved muscle activation in chronic stroke survivors.openembargoed_20190204Hyngstrom, Allison S; Murphy, Spencer A; Nguyen, Jennifer; Schmit, Brian D; Negro, Francesco; Gutterman, David D; Durand, Matthew JHyngstrom, Allison S; Murphy, Spencer A; Nguyen, Jennifer; Schmit, Brian D; Negro, Francesco; Gutterman, David D; Durand, Matthew

The Surface Water and Ocean Topography Satellite Mission - An Assessment of Swath Altimetry Measurements of River Hydrodynamics

The Surface Water and Ocean Topography (SWOT) satellite mission, scheduled for launch in 2020 with development commencing in 2015, will provide a step-change improvement in the measurement of terrestrial surface water storage and dynamics. In particular, it will provide the first, routine two-dimensional measurements of water surface elevations, which will allow for the estimation of river and floodplain flows via the water surface slope. In this paper, we characterize the measurements which may be obtained from SWOT and illustrate how they may be used to derive estimates of river discharge. In particular, we show (i) the spatia-temporal sampling scheme of SWOT, (ii) the errors which maybe expected in swath altimetry measurements of the terrestrial surface water, and (iii) the impacts such errors may have on estimates of water surface slope and river discharge, We illustrate this through a "virtual mission" study for a approximately 300 km reach of the central Amazon river, using a hydraulic model to provide water surface elevations according to the SWOT spatia-temporal sampling scheme (orbit with 78 degree inclination, 22 day repeat and 140 km swath width) to which errors were added based on a two-dimension height error spectrum derived from the SWOT design requirements. Water surface elevation measurements for the Amazon mainstem as may be observed by SWOT were thereby obtained. Using these measurements, estimates of river slope and discharge were derived and compared to those which may be obtained without error, and those obtained directly from the hydraulic model. It was found that discharge can be reproduced highly accurately from the water height, without knowledge of the detailed channel bathymetry using a modified Manning's equation, if friction, depth, width and slope are known. Increasing reach length was found to be an effective method to reduce systematic height error in SWOT measurements

Mitigating Safety Concerns and Profit/Production Losses for Chemical Process Control Systems Under Cyberattacks via Design/Control Methods

One of the challenges for chemical processes today, from a safety and profit standpoint, is the potential that cyberattacks could be performed on components of process control systems. Safety issues could be catastrophic; however, because the nonlinear systems definition of a cyberattack has similarities to a nonlinear systems definition of faults, many processes have already been instrumented to handle various problematic input conditions. Also challenging is the question of how to design a system that is resilient to attacks attempting to impact the production volumes or profits of a company. In this work, we explore a process/equipment design framework for handling safety issues in the presence of cyberattacks (in the spirit of traditional HAZOP thinking), and present a method for bounding the profit/production loss which might be experienced by a plant under a cyberattack through the use of a sufficiently conservative operating strategy combined with the assumption that an attack detection method with characterizable time to detection is available

The water quality of the River Enborne, UK: observations from high-frequency Monitoring in a rural, lowland river system

This paper reports the results of a 2-year study of water quality in the River Enborne, a rural river in lowland England. Concentrations of nitrogen and phosphorus species and other chemical determinands were monitored both at high-frequency (hourly), using automated in situ instrumentation, and by manual weekly sampling and laboratory analysis. The catchment land use is largely agricultural, with a population density of 123 persons km−2. The river water is largely derived from calcareous groundwater, and there are high nitrogen and phosphorus concentrations. Agricultural fertiliser is the dominant source of annual loads of both nitrogen and phosphorus. However, the data show that sewage effluent discharges have a disproportionate effect on the river nitrogen and phosphorus dynamics. At least 38% of the catchment population use septic tank systems, but the effects are hard to quantify as only 6% are officially registered, and the characteristics of the others are unknown. Only 4% of the phosphorus input and 9% of the nitrogen input is exported from the catchment by the river, highlighting the importance of catchment process understanding in predicting nutrient concentrations. High-frequency monitoring will be a key to developing this vital process understanding