Severity of degenerative lumbar spinal stenosis affects pelvic rigidity during walking

To understand the role of compensation mechanisms in the development and treatment of symptomatic degenerative lumbar spinal stenosis (DLSS), pelvic stability during walking should be objectively assessed in the context of clinical parameters.; To determine the association among duration of symptoms, lumbar muscle atrophy, disease severity, pelvic stability during walking, and surgical outcome in patients with DLSS scheduled for decompression surgery.; Prospective observational study with intervention.; Patients with symptomatic DLSS.; Oswestry Disability Index score; duration of symptoms; lumbar muscle atrophy; severity grade; pelvis rigidity during walking.; Patients with symptomatic DLSS were analyzed on the day before surgery and 10 weeks and 12 months postoperatively. Duration of symptoms was categorized as: <2years, <5years, and >5years. Muscle atrophy at the stenosis level was categorized according to Goutallier. Bilateral cross-sectional areas of the erector spinae and psoas muscles were quantified from magnetic resonance imaging. Stenosis grade was assessed using the Schizas classification. Pelvic tilt was measured in standing radiographs. Pelvic rigidity during walking was assessed as root mean square of the pelvic acceleration in each direction (anteroposterior, mediolateral, and vertical) normalized to walking speed measured using an inertial sensor attached to the skin between the posterior superior iliac spine.; Body mass index but not duration of symptoms, lumbar muscle atrophy, pelvic rigidity, and stenosis grade explained changes in Oswestry Disability Index from before to after surgery. Patients with greater stenosis grade had greater pelvic rigidity during walking. Lumbar muscle atrophy did not correlate with pelvic rigidity during walking. Patients with lower stenosis grade had greater muscle atrophy and patients with smaller erector spinae and psoas muscle cross-sectional areas had a greater pelvis tilt.; Greater pelvic rigidity during walking may represent a compensatory mechanism of adopting a protective body position to keep the spinal canal more open during walking and hence reduce pain. Pelvic rigidity during walking may be a useful screening parameter for identifying early compensating mechanisms. Whether it can be used as a parameter for personalized treatment planning or outcome prognosis necessitates further evaluation

Inertial Sensor-Based Gait and Attractor Analysis as Clinical Measurement Tool: Functionality and Sensitivity in Healthy Subjects and Patients With Symptomatic Lumbar Spinal Stenosis

Objective: To determine if the attractor for acceleration gait data is similar among healthy persons defining a reference attractor; if exercise-induced changes in the attractor in patients with symptomatic lumbar spinal stenosis (sLSS) are greater than in healthy persons; and if the exercise-induced changes in the attractor are affected by surgical treatment.Methods: Twenty-four healthy subjects and 19 patients with sLSS completed a 6-min walk test (6MWT) on a 30-m walkway. Gait data were collected using inertial sensors (RehaGait®;) capturing 3-dimensional foot accelerations. Attractor analysis was used to quantify changes in low-pass filtered acceleration pattern (δM) and variability (δD) and their combination as attractor-based index (δF = δM* δD) between the first and last 30 m of walking. These parameters were compared within healthy persons and patients with sLSS (preoperatively and 10 weeks and 12 months postoperatively) and between healthy persons and patients with sLSS. The variability in the attractor pattern among healthy persons was assessed as the standard deviation of the individual attractors.Results: The attractor pattern differed greatly among healthy persons. The variability in the attractor between subjects was about three times higher than the variability around the attractor within subject. The change in gait pattern and variability during the 6MWT did not differ significantly in patients with sLSS between baseline and follow-up but differed significantly compared to healthy persons.Discussion: The attractor for acceleration data varied largely among healthy subjects, and hence a reference attractor could not be generated. Moreover, the change in the attractor and its variability during the 6MWT differed between patients and elderly healthy persons but not between repeated assessments. Hence, the attractor based on low-pass filtered signals as used in this study may reflect pathology specific differences in gait characteristics but does not appear to be sufficiently sensitive to serve as outcome parameter of decompression surgery in patients with sLSS

General Destabilizing Effects of Eutrophication on Grassland Productivity at Multiple Spatial Scales

Eutrophication is a widespread environmental change that usually reduces the stabilizing effect of plant diversity on productivity in local communities. Whether this effect is scale dependent remains to be elucidated. Here, we determine the relationship between plant diversity and temporal stability of productivity for 243 plant communities from 42 grasslands across the globe and quantify the effect of chronic fertilization on these relationships. Unfertilized local communities with more plant species exhibit greater asynchronous dynamics among species in response to natural environmental fluctuations, resulting in greater local stability (alpha stability). Moreover, neighborhood communities that have greater spatial variation in plant species composition within sites (higher beta diversity) have greater spatial asynchrony of productivity among communities, resulting in greater stability at the larger scale (gamma stability). Importantly, fertilization consistently weakens the contribution of plant diversity to both of these stabilizing mechanisms, thus diminishing the positive effect of biodiversity on stability at differing spatial scales. Our findings suggest that preserving grassland functional stability requires conservation of plant diversity within and among ecological communities

Delayed mGluR5 activation limits neuroinflammation and neurodegeneration after traumatic brain injury

<p>Abstract</p> <p>Background</p> <p>Traumatic brain injury initiates biochemical processes that lead to secondary neurodegeneration. Imaging studies suggest that tissue loss may continue for months or years after traumatic brain injury in association with chronic microglial activation. Recently we found that metabotropic glutamate receptor 5 (mGluR5) activation by (<it>RS</it>)-2-chloro-5-hydroxyphenylglycine (CHPG) decreases microglial activation and release of associated pro-inflammatory factors <it>in vitro</it>, which is mediated in part through inhibition of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Here we examined whether delayed CHPG administration reduces chronic neuroinflammation and associated neurodegeneration after experimental traumatic brain injury in mice.</p> <p>Methods</p> <p>One month after controlled cortical impact traumatic brain injury, C57Bl/6 mice were randomly assigned to treatment with single dose intracerebroventricular CHPG, vehicle or CHPG plus a selective mGluR5 antagonist, 3-((2-Methyl-4-thiazolyl)ethynyl)pyridine. Lesion volume, white matter tract integrity and neurological recovery were assessed over the following three months.</p> <p>Results</p> <p>Traumatic brain injury resulted in mGluR5 expression in reactive microglia of the cortex and hippocampus at one month post-injury. Delayed CHPG treatment reduced expression of reactive microglia expressing NADPH oxidase subunits; decreased hippocampal neuronal loss; limited lesion progression, as measured by repeated T2-weighted magnetic resonance imaging (at one, two and three months) and white matter loss, as measured by high field <it>ex vivo </it>diffusion tensor imaging at four months; and significantly improved motor and cognitive recovery in comparison to the other treatment groups.</p> <p>Conclusion</p> <p>Markedly delayed, single dose treatment with CHPG significantly improves functional recovery and limits lesion progression after experimental traumatic brain injury, likely in part through actions at mGluR5 receptors that modulate neuroinflammation.</p

Mechanisms Underlying Interferon-γ-Induced Priming of Microglial Reactive Oxygen Species Production.

Microglial priming and enhanced reactivity to secondary insults cause substantial neuronal damage and are hallmarks of brain aging, traumatic brain injury and neurodegenerative diseases. It is, thus, of particular interest to identify mechanisms involved in microglial priming. Here, we demonstrate that priming of microglia with interferon-γ (IFN γ) substantially enhanced production of reactive oxygen species (ROS) following stimulation of microglia with ATP. Priming of microglial ROS production was substantially reduced by inhibition of p38 MAPK activity with SB203580, by increases in intracellular glutathione levels with N-Acetyl-L-cysteine, by blockade of NADPH oxidase subunit NOX2 activity with gp91ds-tat or by inhibition of nitric oxide production with L-NAME. Together, our data indicate that priming of microglial ROS production involves reduction of intracellular glutathione levels, upregulation of NADPH oxidase subunit NOX2 and increases in nitric oxide production, and suggest that these simultaneously occurring processes result in enhanced production of neurotoxic peroxynitrite. Furthermore, IFNγ-induced priming of microglial ROS production was reduced upon blockade of Kir2.1 inward rectifier K+ channels with ML133. Inhibitory effects of ML133 on microglial priming were mediated via regulation of intracellular glutathione levels and nitric oxide production. These data suggest that microglial Kir2.1 channels may represent novel therapeutic targets to inhibit excessive ROS production by primed microglia in brain pathology

Clarifying the effect of biodiversity on productivity in natural ecosystems with longitudinal data and methods for causal inference

Causal effects of biodiversity on ecosystem functions can be estimated using experimental or observational designs - designs that pose a tradeoff between drawing credible causal inferences from correlations and drawing generalizable inferences. Here, we develop a design that reduces this tradeoff and revisits the question of how plant species diversity affects productivity. Our design leverages longitudinal data from 43 grasslands in 11 countries and approaches borrowed from fields outside of ecology to draw causal inferences from observational data. Contrary to many prior studies, we estimate that increases in plot-level species richness caused productivity to decline: a 10% increase in richness decreased productivity by 2.4%, 95% CI [-4.1, -0.74]. This contradiction stems from two sources. First, prior observational studies incompletely control for confounding factors. Second, most experiments plant fewer rare and non-native species than exist in nature. Although increases in native, dominant species increased productivity, increases in rare and non-native species decreased productivity, making the average effect negative in our study. By reducing the tradeoff between experimental and observational designs, our study demonstrates how observational studies can complement prior ecological experiments and inform future ones

Functional limitations after lateral column lengthening osteotomy of the calcaneus are associated with lower quality of life

The purpose of this study was to quantify limitations in sagittal ankle range of motion (ROM) at least two years after lateral column lengthening osteotomy of the calcaneus (LLC) and their implications regarding quality of life.; Fifteen patients with a mean follow-up of 80 ± 27 months after LLC and 15 age-matched healthy persons participated in this study. Ankle joint complex ROM in plantarflexion and dorsiflexion was measured bilaterally using a goniometer and fluoroscopy (patients only). Quality of life was assessed using the short-form health questionnaire (SF36). Differences in ROM parameters (for the tibiotalar and subtalar joint) between sides (affected vs. unaffected) and between groups (patient vs. controls) and the relationship between ROM parameters and quality of life scores were assessed.; ROM of the ankle joint complex on the affected side in patients was smaller than on the contralateral side (goniometer and fluoroscopy) and in healthy persons (goniometer; all P < .05). Among patients, SF36 total and pain scores, respectively, correlated with ROM of the subtalar joint (fluoroscopy; R = 0.379, P = 0.039 and R = 0.537, P = 0.001). Among patients and healthy persons, those with smaller dorsiflexion (goniometer) had lower quality of life scores.; The smaller sagittal ROM of the affected ankle joint complex compared with the contralateral foot and healthy controls was mainly explained by limitations in the tibiotalar joint. Because of its association with quality of life, ROM should be considered in the treatment and rehabilitation planning in patients who are candidates for LLC

Effects of idiopathic flatfoot deformity on knee adduction moments during walking

Introduction: Flatfoot deformity is commonly characterized by a subtalar valgus, a low medial longitudinal arch, and abduction of the forefoot. Although flatfoot deformity has been associated with lower first (KAM1) and second (KAM2) peak knee adduction moments during walking, the biomechanical connection remains unknown. Research question: We hypothesized that hindfoot eversion, lateral calcaneal shift correlate with KAM1 and forefoot abduction and arch height with KAM2, due to the lateralization of the ground reaction force vector resulting from shifted heel and forefoot in flatfoot deformity. Methods: Gait data from 103 children with flatfoot deformity who underwent three-dimensional gait analysis with the Oxford Foot Model were retrospectively included. Children with knee varus/valgus, in- and out-toeing were excluded. Fifteen healthy children with a rectus foot type were also collected from the database. Lateral calcaneal shift was defined as the distance between the projection of the ankle joint center onto the calcaneal axis and the midpoint of the calcaneal axis formed by the medial and lateral calcaneal markers. A subgroup of children with idiopathic flatfoot deformity that had received corrective surgery was also identified. Statistical analysis included Pearson's correlations and independent and paired t-tests (α <.05). Results: When compared to a norm cohort, flatfooted children had significant lower KAM1 and KAM2 (t-test, P <.001). Lateral calcaneal shift correlated with KAM1 and KAM2 (r = 0.42, p <.001 and r = 0.32, P <.001, respectively). Arch height correlated with KAM2 (r = 0.23, p = 0.017). KAM1 and KAM2 normalized after surgery and the change in KAM1 correlated with the change in lateral calcaneal shift for children who underwent corrective surgery. Significance: Lateral calcaneal shift explains the reduction of KAM1 by lateralization of the point of force application in flatfooted children. It is recommended to consider the lateral calcaneal shift when investigating KAM in gait analysis research

Inertial Sensor-Based Gait and Attractor Analysis as Clinical Measurement Tool: Functionality and Sensitivity in Healthy Subjects and Patients With Symptomatic Lumbar Spinal Stenosis

Objective: To determine if the attractor for acceleration gait data is similar among healthy persons defining a reference attractor; if exercise-induced changes in the attractor in patients with symptomatic lumbar spinal stenosis (sLSS) are greater than in healthy persons; and if the exercise-induced changes in the attractor are affected by surgical treatment. Methods: Twenty-four healthy subjects and 19 patients with sLSS completed a 6-min walk test (6MWT) on a 30-m walkway. Gait data were collected using inertial sensors (RehaGait; ®;; ) capturing 3-dimensional foot accelerations. Attractor analysis was used to quantify changes in low-pass filtered acceleration pattern (δM) and variability (δD) and their combination as attractor-based index (δF = δM; *; δD) between the first and last 30 m of walking. These parameters were compared within healthy persons and patients with sLSS (preoperatively and 10 weeks and 12 months postoperatively) and between healthy persons and patients with sLSS. The variability in the attractor pattern among healthy persons was assessed as the standard deviation of the individual attractors. Results: The attractor pattern differed greatly among healthy persons. The variability in the attractor between subjects was about three times higher than the variability around the attractor within subject. The change in gait pattern and variability during the 6MWT did not differ significantly in patients with sLSS between baseline and follow-up but differed significantly compared to healthy persons. Discussion: The attractor for acceleration data varied largely among healthy subjects, and hence a reference attractor could not be generated. Moreover, the change in the attractor and its variability during the 6MWT differed between patients and elderly healthy persons but not between repeated assessments. Hence, the attractor based on low-pass filtered signals as used in this study may reflect pathology specific differences in gait characteristics but does not appear to be sufficiently sensitive to serve as outcome parameter of decompression surgery in patients with sLSS