135 research outputs found
A mathematical model of the metabolic and perfusion effects on cortical spreading depression
Cortical spreading depression (CSD) is a slow-moving ionic and metabolic
disturbance that propagates in cortical brain tissue. In addition to massive
cellular depolarization, CSD also involves significant changes in perfusion and
metabolism -- aspects of CSD that had not been modeled and are important to
traumatic brain injury, subarachnoid hemorrhage, stroke, and migraine.
In this study, we develop a mathematical model for CSD where we focus on
modeling the features essential to understanding the implications of
neurovascular coupling during CSD. In our model, the sodium-potassium--ATPase,
mainly responsible for ionic homeostasis and active during CSD, operates at a
rate that is dependent on the supply of oxygen. The supply of oxygen is
determined by modeling blood flow through a lumped vascular tree with an
effective local vessel radius that is controlled by the extracellular potassium
concentration. We show that during CSD, the metabolic demands of the cortex
exceed the physiological limits placed on oxygen delivery, regardless of
vascular constriction or dilation. However, vasoconstriction and vasodilation
play important roles in the propagation of CSD and its recovery. Our model
replicates the qualitative and quantitative behavior of CSD --
vasoconstriction, oxygen depletion, extracellular potassium elevation,
prolonged depolarization -- found in experimental studies.
We predict faster, longer duration CSD in vivo than in vitro due to the
contribution of the vasculature. Our results also help explain some of the
variability of CSD between species and even within the same animal. These
results have clinical and translational implications, as they allow for more
precise in vitro, in vivo, and in silico exploration of a phenomenon broadly
relevant to neurological disease.Comment: 17 pages including 9 figures, accepted by PLoS On
Recommended from our members
Redirecting research efforts on the diversification-performance linkage: The search for synergy
We review the literature on the diversification-performance (D-P) relationship to a) propose that the time is ripe for a renewed attack on understanding the relationship between diversification and firm performance, and b) outline a new approach to attacking the question. Our paper makes four main contributions. First, through a review of the literature we establish the inherent complexities in the D-P relationship and the methodological challenges confronted by the literature in reaching its current conclusion of a non-linear relationship between diversification and performance. Second, we argue that to better guide managers the literature needs to develop along a complementary path – whereas past research has often focused on answering the big question of does diversification affect firm performance, this second path would focus more on identifying the precise micro-mechanisms through which diversification adds or subtracts value. Third, we outline a new approach to the investigation of this topic, based on (a) identifying the precise underlying mechanisms through which diversification affects performance; (b) identifying performance outcomes that are “proximate” to the mechanism that the researcher is studying, and (c) identifying an appropriate research design that can enable a causal claim. Finally, we outline a set of directions for future research
Effectiveness of dual-task functional power training for preventing falls in older people: Study protocol for a cluster randomised controlled trial
Background: Falls are a major public health concern with at least one third of people aged 65 years and over falling at least once per year, and half of these will fall repeatedly, which can lead to injury, pain, loss of function and independence, reduced quality of life and even death. Although the causes of falls are varied and complex, the age-related loss in muscle power has emerged as a useful predictor of disability and falls in older people. In this population, the requirements to produce explosive and rapid movements often occurs whilst simultaneously performing other attention-demanding cognitive or motor tasks, such as walking while talking or carrying an object. The primary aim of this study is to determine whether dual-task functional power training (DT-FPT) can reduce the rate of falls in community-dwelling older people. Methods/Design: The study design is an 18-month cluster randomised controlled trial in which 280 adults aged =65 years residing in retirement villages, who are at increased risk of falling, will be randomly allocated to: 1) an exercise programme involving DT-FPT, or 2) a usual care control group. The intervention is divided into 3 distinct phases: 6 months of supervised DT-FPT, a 6-month 'step down' maintenance programme, and a 6-month follow-up. The primary outcome will be the number of falls after 6, 12 and 18 months. Secondary outcomes will include: lower extremity muscle power and strength, grip strength, functional assessments of gait, reaction time and dynamic balance under single- and dual-task conditions, activities of daily living, quality of life, cognitive function and falls-related self-efficacy. We will also evaluate the cost-effectiveness of the programme for preventing falls. Discussion: The study offers a novel approach that may guide the development and implementation of future community-based falls prevention programmes that specifically focus on optimising muscle power and dual-task performance to reduce falls risk under 'real life' conditions in older adults. In addition, the 'step down' programme will provide new information about the efficacy of a less intensive maintenance programme for reducing the risk of falls over an extended period. Trial registration: Australian New Zealand Clinical Trials Registry: ACTRN12613001161718. Date registered 23 October 2013
Validation of the western ontario rotator cuff index in patients with arthroscopic rotator cuff repair: A study protocol
<p>Abstract</p> <p>Background</p> <p>Arthroscopic rotator cuff repair is described as being a successful procedure. These results are often derived from clinical general shoulder examinations, which are then classified as 'excellent', 'good', 'fair' or 'poor'. However, the cut-off points for these classifications vary and sometimes modified scores are used.</p> <p>Arthroscopic rotator cuff repair is performed to improve quality of life. Therefore, disease specific health-related quality of life patient-administered questionnaires are needed. The WORC is a quality of life questionnaire designed for patients with disorders of the rotator cuff. The score is validated for rotator cuff disease, but not for rotator cuff repair specifically.</p> <p>The aim of this study is to investigate reliability, validity and responsiveness of WORC in patients undergoing arthroscopic rotator cuff repair.</p> <p>Methods/Design</p> <p>An approved translation of the WORC into Dutch is used. In this prospective study three groups of patients are used: 1. Arthroscopic rotator cuff repair; 2. Disorders of the rotator cuff without rupture; 3. Shoulder instability.</p> <p>The WORC, SF-36 and the Constant Score are obtained twice before therapy is started to measure reliability and validity. Responsiveness is tested by obtaining the same tests after therapy.</p
Delayed gadolinium-enhanced MRI of meniscus (dGEMRIM) and cartilage (dGEMRIC) in healthy knees and in knees with different stages of meniscus pathology
A Comprehensive Examination of Changes in Psychological Flexibility Following Acceptance and Commitment Therapy for Chronic Pain
Myocyte membrane and microdomain modifications in diabetes: determinants of ischemic tolerance and cardioprotection
Hypercapnia potentiates renal vasoconstriction during hemorrhagic hypotension in awake rabbits
- …