236 research outputs found
Comparing the positive results of carpal tunnel syndrome surgery in two groups of patients with and without splint
Background: Carpal tunnel syndrome is a common condition in which the median nerve passes through the carpal tunnel is compressed. Then, gradual paralysis occurs. This study aimed to compare patient outcomes after surgery for carpal tunnel syndrome in both groups with and without splint. Methods: This study was conducted in Isfahan University of Medical Sciences, Iran, in Kashani hospital during 2011. 64 patients underwent surgery for carpal tunnel syndrome were selected and randomly divided into two groups of 32. For the first group, splints were considered after the surgery and for the second group, as the control group, splint was not given. Patients within 3, 6 and 12 weeks after surgery were followed and healing in the sense of motion and pain based on the visual analogue scale (VAS) measures were examined. Findings: Sensory conflict scores at the 3rd and 6th weeks in the group with splint were higher than the group without it; but, 12 weeks after the treatment, the results were identical. In any cases, motor involvement was not seen. At the 3rd week after the treatment, the mean pain score in the group without splint was higher than with splint group. The results of the 6th week after the treatment in both groups were almost identical; but, at the 12th week after the treatment, changes in pain intensity was not significantly different between the two groups (P = 0.97). Conclusion: Splinting after the surgical release of the median nerve probably causes a delay in the recovery of sensory, motor and pain; but due to the effect of material of used splint, the result is still uncertain and further broader interventions needs to be done in this regard
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Characterizing heterogeneity in leukemic cells using single-cell gene expression analysis
Background: A fundamental challenge for cancer therapy is that each tumor contains a highly heterogeneous cell population whose structure and mechanistic underpinnings remain incompletely understood. Recent advances in single-cell gene expression profiling have created new possibilities to characterize this heterogeneity and to dissect the potential intra-cancer cellular hierarchy. Results: Here, we apply single-cell analysis to systematically characterize the heterogeneity within leukemic cells using the MLL-AF9 driven mouse model of acute myeloid leukemia. We start with fluorescence-activated cell sorting analysis with seven surface markers, and extend by using a multiplexing quantitative polymerase chain reaction approach to assay the transcriptional profile of a panel of 175 carefully selected genes in leukemic cells at the single-cell level. By employing a set of computational tools we find striking heterogeneity within leukemic cells. Mapping to the normal hematopoietic cellular hierarchy identifies two distinct subtypes of leukemic cells; one similar to granulocyte/monocyte progenitors and the other to macrophage and dendritic cells. Further functional experiments suggest that these subtypes differ in proliferation rates and clonal phenotypes. Finally, co-expression network analysis reveals similarities as well as organizational differences between leukemia and normal granulocyte/monocyte progenitor networks. Conclusions: Overall, our single-cell analysis pinpoints previously uncharacterized heterogeneity within leukemic cells and provides new insights into the molecular signatures of acute myeloid leukemia. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0525-9) contains supplementary material, which is available to authorized users
Simulation of Emergency Spill of MTBE into Surface Water Reservoir and Remediation Techniques using Modified CE-QUAL-W2 Model: A Case Study for Gheshlagh Reservoir
Due to the importance and widespread applications of oil products as well as their threats to surface water bodies in Iran, it is inevitable to apply suitable simulation models to develop management plans, actions, and appropriate scenarios . There are two modified versions of CE-QUAL-W2 and both can be used for simulations of emergency pills of toxic waste in transpotation roadways. In this research, both modified versions were employed to simulate the fate of Methyl tert-butyl ether (MTBE) (a gasoline oxygenated addetive) during an emergency spill. As a case study, the application of both models was used to evaluate the MTBE emergy spill that occurred on March 2003 near Khalifeh Torkhan river. Several remediation techniques including artificial turbulent, mixing, and aeration were used during the simulation study. Results showed that the modified version of the model (CE-QUAL-W2) depicted a better temporal and spatial distribution of MTBE pollution in reservoir compared compared to the first version of the model. Multiple scenarios were simulated in this study under various meteorological, hydrological, and MTBE loading for Gheshlagh reservoir. The simulation results showed that lower air temperature and higher wind speed are among the factors that reduces the reservoir recovery time. In addition,, another parameter that found to decrease the recovery time of Gheshlagh reservoir is an increase in reservoir inflow and/or outflow rate
A rewiring model of intratumoral interaction networks.
Intratumoral heterogeneity (ITH) has been regarded as a key cause of the failure and resistance of cancer therapy, but how it behaves and functions remains unclear. Advances in single-cell analysis have facilitated the collection of a massive amount of data about genetic and molecular states of individual cancer cells, providing a fuel to dissect the mechanistic organization of ITH at the molecular, metabolic and positional level. Taking advantage of these data, we propose a computational model to rewire up a topological network of cell-cell interdependences and interactions that operate within a tumor mass. The model is grounded on the premise of game theory that each interactive cell (player) strives to maximize its fitness by pursuing a rational self-interest strategy, war or peace, in a way that senses and alters other cells to respond properly. By integrating this idea with genome-wide association studies for intratumoral cells, the model is equipped with a capacity to visualize, annotate and quantify how somatic mutations mediate ITH and the network of intratumoral interactions. Taken together, the model provides a topological flow by which cancer cells within a tumor cooperate or compete with each other to downstream pathogenesis. This topological flow can be potentially used as a blueprint for genetically intervening the pattern and strength of cell-cell interactions towards cancer control
A comparative study of qualitative and quantitative dynamic models of biological regulatory networks
Network model of immune responses reveals key effectors to single and co-infection dynamics by a respiratory bacterium and a gastrointestinal helminth
Co-infections alter the host immune response but how the systemic and local processes at the site of infection interact is still unclear. The majority of studies on co-infections concentrate on one of the infecting species, an immune function or group of cells and often focus on the initial phase of the infection. Here, we used a combination of experiments and mathematical modelling to investigate the network of immune responses against single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminth Trichostrongylus retortaeformis. Our goal was to identify representative mediators and functions that could capture the essence of the host immune response as a whole, and to assess how their relative contribution dynamically changed over time and between single and co-infected individuals. Network-based discrete dynamic models of single infections were built using current knowledge of bacterial and helminth immunology; the two single infection models were combined into a co-infection model that was then verified by our empirical findings. Simulations showed that a T helper cell mediated antibody and neutrophil response led to phagocytosis and clearance of B. bronchiseptica from the lungs. This was consistent in single and co-infection with no significant delay induced by the helminth. In contrast, T. retortaeformis intensity decreased faster when co-infected with the bacterium. Simulations suggested that the robust recruitment of neutrophils in the co-infection, added to the activation of IgG and eosinophil driven reduction of larvae, which also played an important role in single infection, contributed to this fast clearance. Perturbation analysis of the models, through the knockout of individual nodes (immune cells), identified the cells critical to parasite persistence and clearance both in single and co-infections. Our integrated approach captured the within-host immuno-dynamics of bacteria-helminth infection and identified key components that can be crucial for explaining individual variability between single and co-infections in natural populations
Perturbation Centrality and Turbine: A Novel Centrality Measure Obtained Using a Versatile Network Dynamics Tool
Analysis of network dynamics became a focal point to understand and predict
changes of complex systems. Here we introduce Turbine, a generic framework
enabling fast simulation of any algorithmically definable dynamics on very
large networks. Using a perturbation transmission model inspired by
communicating vessels, we define a novel centrality measure: perturbation
centrality. Hubs and inter-modular nodes proved to be highly efficient in
perturbation propagation. High perturbation centrality nodes of the Met-tRNA
synthetase protein structure network were identified as amino acids involved in
intra-protein communication by earlier studies. Changes in perturbation
centralities of yeast interactome nodes upon various stresses well
recapitulated the functional changes of stressed yeast cells. The novelty and
usefulness of perturbation centrality was validated in several other model,
biological and social networks. The Turbine software and the perturbation
centrality measure may provide a large variety of novel options to assess
signaling, drug action, environmental and social interventions. The Turbine
algorithm is available at: http://www.turbine.linkgroup.huComment: 21 pages, 4 figues, 1 table, 58 references + a Supplement of 52
pages, 10 figures, 9 tables and 39 references; Turbine algorithm is available
at: http://www.turbine.linkgroup.h
Single-Cell Transcriptional Analysis of Normal, Aberrant, and Malignant Hematopoiesis in Zebrafish
Hematopoiesis culminates in the production of functionally heterogeneous blood cell types. In zebrafish, the lack of cell surface antibodies has compelled researchers to use fluorescent transgenic reporter lines to label specific blood cell fractions. However, these approaches are limited by the availability of transgenic lines and fluorescent protein combinations that can be distinguished. Here, we have transcriptionally profiled single hematopoietic cells from zebrafish to define erythroid, myeloid, B, and T cell lineages. We also used our approach to identify hematopoietic stem and progenitor cells and a novel NK-lysin 4+ cell type, representing a putative cytotoxic T/NK cell. Our platform also quantified hematopoietic defects in rag2E450fs mutant fish and showed that these fish have reduced T cells with a subsequent expansion of NK-lysin 4+ cells and myeloid cells. These data suggest compensatory regulation of the innate immune system in rag2E450fs mutant zebrafish. Finally, analysis of Myc-induced T cell acute lymphoblastic leukemia showed that cells are arrested at the CD4+/CD8+ cortical thymocyte stage and that a subset of leukemia cells inappropriately reexpress stem cell genes, including bmi1 and cmyb. In total, our experiments provide new tools and biological insights into single-cell heterogeneity found in zebrafish blood and leukemia
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