Gait kinematic analysis in patients with a mild form of central cord syndrome

<p>Abstract</p> <p>Background</p> <p>Central cord syndrome (CCS) is considered the most common incomplete spinal cord injury (SCI). Independent ambulation was achieved in 87-97% in young patients with CCS but no gait analysis studies have been reported before in such pathology. The aim of this study was to analyze the gait characteristics of subjects with CCS and to compare the findings with a healthy age, sex and anthropomorphically matched control group (CG), walking both at a self-selected speed and at the same speed.</p> <p>Methods</p> <p>Twelve CCS patients and a CG of twenty subjects were analyzed. Kinematic data were obtained using a three-dimensional motion analysis system with two scanner units. The CG were asked to walk at two different speeds, at a self-selected speed and at a slower one, similar to the mean gait speed previously registered in the CCS patient group. Temporal, spatial variables and kinematic variables (maximum and minimum lower limb joint angles throughout the gait cycle in each plane, along with the gait cycle instants of occurrence and the joint range of motion - ROM) were compared between the two groups walking at similar speeds.</p> <p>Results</p> <p>The kinematic parameters were compared when both groups walked at a similar speed, given that there was a significant difference in the self-selected speeds (p < 0.05). Hip abduction and knee flexion at initial contact, as well as minimal knee flexion at stance, were larger in the CCS group (p < 0.05). However, the range of knee and ankle motion in the sagittal plane was greater in the CG group (p < 0.05). The maximal ankle plantar-flexion values in stance phase and at toe off were larger in the CG (p < 0.05).</p> <p>Conclusions</p> <p>The gait pattern of CCS patients showed a decrease of knee and ankle sagittal ROM during level walking and an increase in hip abduction to increase base of support. The findings of this study help to improve the understanding how CCS affects gait changes in the lower limbs.</p

Analysis of jak2 catalytic function by peptide microarrays: The role of the JH2 domain and V617F mutation

Janus kinase 2 (JAK2) initiates signaling from several cytokine receptors and is required for biological responses such as erythropoiesis. JAK2 activity is controlled by regulatory proteins such as Suppressor of Cytokine Signaling (SOCS) proteins and protein tyrosine phosphatases. JAK2 activity is also intrinsically controlled by regulatory domains, where the pseudokinase (JAK homology 2, JH2) domain has been shown to play an essential role. The physiological role of the JH2 domain in the regulation of JAK2 activity was highlighted by the discovery of the acquired missense point mutation V617F in myeloproliferative neoplasms (MPN). Hence, determining the precise role of this domain is critical for understanding disease pathogenesis and design of new treatment modalities. Here, we have evaluated the effect of inter-domain interactions in kinase activity and substrate specificity. By using for the first time purified recombinant JAK2 proteins and a novel peptide micro-array platform, we have determined initial phosphorylation rates and peptide substrate preference for the recombinant kinase domain (JH1) of JAK2, and two constructs comprising both the kinase and pseudokinase domains (JH1-JH2) of JAK2. The data demonstrate that (i) JH2 drastically decreases the activity of the JAK2 JH1 domain, (ii) JH2 increased the Kmfor ATP (iii) JH2 modulates the peptide preference of JAK2 (iv) the V617F mutation partially releases this inhibitory mechanism but does not significantly affect substrate preference or Kmfor ATP. These results provide the biochemical basis for understanding the interaction between the kinase and the pseudokinase domain of JAK2 and identify a novel regulatory role for the JAK2 pseudokinase domain. Additionally, this method can be used to identify new regulatory mechanisms for protein kinases that provide a better platform for designing specific strategies for therapeutic approaches

Characterization of Yeast Extracellular Vesicles: Evidence for the Participation of Different Pathways of Cellular Traffic in Vesicle Biogenesis

Background: Extracellular vesicles in yeast cells are involved in the molecular traffic across the cell wall. In yeast pathogens, these vesicles have been implicated in the transport of proteins, lipids, polysaccharide and pigments to the extracellular space. Cellular pathways required for the biogenesis of yeast extracellular vesicles are largely unknown. Methodology/Principal Findings: We characterized extracellular vesicle production in wild type (WT) and mutant strains of the model yeast Saccharomyces cerevisiae using transmission electron microscopy in combination with light scattering analysis, lipid extraction and proteomics. WT cells and mutants with defective expression of Sec4p, a secretory vesicleassociated Rab GTPase essential for Golgi-derived exocytosis, or Snf7p, which is involved in multivesicular body (MVB) formation, were analyzed in parallel. Bilayered vesicles with diameters at the 100–300 nm range were found in extracellular fractions from yeast cultures. Proteomic analysis of vesicular fractions from the cells aforementioned and additional mutants with defects in conventional secretion pathways (sec1-1, fusion of Golgi-derived exocytic vesicles with the plasm

Combinatorial hydrogel library enables identification of materials that mitigate the foreign body response in primates

The foreign body response is an immune-mediated reaction that can lead to the failure of implanted medical devices and discomfort for the recipient. There is a critical need for biomaterials that overcome this key challenge in the development of medical devices. Here we use a combinatorial approach for covalent chemical modification to generate a large library of variants of one of the most widely used hydrogel biomaterials, alginate. We evaluated the materials in vivo and identified three triazole-containing analogs that substantially reduce foreign body reactions in both rodents and, for at least 6 months, in non-human primates. The distribution of the triazole modification creates a unique hydrogel surface that inhibits recognition by macrophages and fibrous deposition. In addition to the utility of the compounds reported here, our approach may enable the discovery of other materials that mitigate the foreign body response.Leona M. and Harry B. Helmsley Charitable Trust (3-SRA-2014-285-M-R)United States. National Institutes of Health (EB000244)United States. National Institutes of Health (EB000351)United States. National Institutes of Health (DE013023)United States. National Institutes of Health (CA151884)United States. National Institutes of Health (P41EB015871-27)National Cancer Institute (U.S.) (P30-CA14051

Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction &gt;0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease

Building microscopic soccer balls with evaporating colloidal fakir drops

\u3cp\u3eEvaporation-driven particle self-assembly can be used to generate three-dimensional microstructures. We present a unique method to create colloidal microstructures in which we can control the amount of particles and their packing fraction. To this end, we evaporate colloidal dispersion droplets on a special type of superhydrophobic microstructured surface, on which the droplet remains in Cassie-Baxter state during the entire evaporative process. The remainders of the droplet consist of a massive spherical cluster of the microspheres, with diameters ranging from a few tens up to several hundreds of microns. We present scaling arguments to show how the final particle packing fraction of these balls depends on the dynamics of the droplet evaporation, particle size, and number of particles in the system.\u3c/p\u3

Understanding cultural significance, the edible mushrooms case

RefereedBackground: Cultural significance is a keystone in quantitative ethnobiology, which offers the possibility to make inferences about traditional nomenclature systems, use, appropriation and valuing of natural resources. In the present work, using as model the traditional mycological knowledge of Zapotecs from Oaxaca, Mexico, we analyze the cultural significance of wild edible resources. Methods In 2003 we applied 95 questionnaires to a random sample of informants. With this data we integrated the Edible Mushroom Cultural Significance Index. This index included eight variables: frequency of mention, perceived abundance, use frequency, taste, multifunctional food use, knowledge transmission, health and economy. Data were analyzed in an inductive perspective using ordination and grouping techniques to reveal the behavior of species in a cultural multivariate dimension. Results: In each variable the species had different conducts. Cantharellus cibarius s.l. was the species with most frequency of mention. Pleurotus sp. had the highest perceived abundance. C. cibarius s.l. was the most frequently consumed species. Gomphus clavatus was the most palatable species and also ranked highest in the multifunctional food index. Cortinarius secc.Malacii sp. had the highest traditional importance. Only Tricholoma magnivelare was identified as a health enhancer. It also had the most economic importance. According to the compound index, C. cibarius s.l., the Amanita caesarea complex, Ramaria spp. and Neolentinus lepideus were the mushrooms with highest cultural significance. Multivariate analysis showed that interviewees identify three main groups of mushrooms: species with high traditional values, frequent consumption and known by the majority; species that are less known, infrequently consumed and without salient characteristics; and species with low traditional values, with high economic value and health enhancers. Conclusion: The compound index divided the cultural significance into several cultural domains and showed the causes that underlie this phenomenon. This approach can be used in cross-cultural studies because it brings a list with the relative position of species among a cultural significance gradient. This list is suitable for comparisons and also it is flexible because cultural variables can be included or removed to adjust it to the nature of the different cultures or resources under study