628 research outputs found
Simple elbow dislocations: a systematic review of the literature
Objective: To identify if functional treatment is the best available treatment for simple elbow dislocations. Search strategy: Electronic databases MEDLINE, EMBASE, LILACS, and the Cochrane Central Register of Controlled Trials. Selection criteria: Studies were eligible for inclusion if they were trials comparing different techniques for the treatment of simple elbow dislocations. Data analysis: Results were expressed as relative risk for dichotomous outcomes and weighted mean difference for continuous outcomes with 95% confidence intervals. Main results: This review has included data from two trials and three observational comparative studies. Important data were missing from three observational comparative studies and the results from these studies were extracted for this review. No difference was found between surgical treatment of the collateral ligaments and plaster immobilisation of the elbow joint. Better range of movement, less pain, better functional scores, shorter disability and shorter treatment time were seen after functional treatment versus plaster immobilisation
MIR376A is a regulator of starvation-induced autophagy
Background: Autophagy is a vesicular trafficking process responsible for the degradation of long-lived, misfolded or abnormal proteins, as well as damaged or surplus organelles. Abnormalities of the autophagic activity may result in the accumulation of protein aggregates, organelle dysfunction, and autophagy disorders were associated with various diseases. Hence, mechanisms of autophagy regulation are under exploration.
Methods: Over-expression of hsa-miR-376a1 (shortly MIR376A) was performed to evaluate its effects on autophagy. Autophagy-related targets of the miRNA were predicted using Microcosm Targets and MIRanda bioinformatics tools and experimentally validated. Endogenous miRNA was blocked using antagomirs and the effects on target expression and autophagy were analyzed. Luciferase tests were performed to confirm that 3’ UTR sequences in target genes were functional. Differential expression of MIR376A and the related MIR376B was compared using TaqMan quantitative PCR.
Results: Here, we demonstrated that, a microRNA (miRNA) from the DlkI/Gtl2 gene cluster, MIR376A, played an important role in autophagy regulation. We showed that, amino acid and serum starvation-induced autophagy was blocked by MIR376A overexpression in MCF-7 and Huh-7 cells. MIR376A shared the same seed sequence and had overlapping targets with MIR376B, and similarly blocked the expression of key autophagy proteins ATG4C and BECN1 (Beclin 1). Indeed, 3’ UTR sequences in the mRNA of these autophagy proteins were responsive to MIR376A in luciferase assays. Antagomir tests showed that, endogenous MIR376A was participating to the control of ATG4C and BECN1 transcript and protein levels. Moreover, blockage of endogenous MIR376A accelerated starvation-induced autophagic activity. Interestingly, MIR376A and MIR376B levels were increased with different kinetics in response to starvation stress and tissue-specific level differences were also observed, pointing out to an overlapping but miRNA-specific biological role.
Conclusions: Our findings underline the importance of miRNAs encoded by the DlkI/Gtl2 gene cluster in stress-response control mechanisms, and introduce MIR376A as a new regulator of autophagy
Spiking Patterns and Their Functional Implications in the Antennal Lobe of the Tobacco Hornworm Manduca sexta
Bursting as well as tonic firing patterns have been described in various sensory systems. In the olfactory system, spontaneous bursts have been observed in neurons distributed across several synaptic levels, from the periphery, to the olfactory bulb (OB) and to the olfactory cortex. Several in vitro studies indicate that spontaneous firing patterns may be viewed as “fingerprints” of different types of neurons that exhibit distinct functions in the OB. It is still not known, however, if and how neuronal burstiness is correlated with the coding of natural olfactory stimuli. We thus conducted an in vivo study to probe this question in the OB equivalent structure of insects, the antennal lobe (AL) of the tobacco hornworm Manduca sexta. We found that in the moth's AL, both projection (output) neurons (PNs) and local interneurons (LNs) are spontaneously active, but PNs tend to produce spike bursts while LNs fire more regularly. In addition, we found that the burstiness of PNs is correlated with the strength of their responses to odor stimulation – the more bursting the stronger their responses to odors. Moreover, the burstiness of PNs was also positively correlated with the spontaneous firing rate of these neurons, and pharmacological reduction of bursting resulted in a decrease of the neurons' responsiveness. These results suggest that neuronal burstiness reflects a physiological state of these neurons that is directly linked to their response characteristics
Spatial and Temporal Variability of Macroinvertebrates in Spawning and Non-Spawning Habitats during a Salmon Run in Southeast Alaska
Spawning salmon create patches of disturbance through redd digging which can reduce macroinvertebrate abundance and biomass in spawning habitat. We asked whether displaced invertebrates use non-spawning habitats as refugia in streams. Our study explored how the spatial and temporal distribution of macroinvertebrates changed during a pink salmon (Oncorhynchus gorbuscha) spawning run and compared macroinvertebrates in spawning (riffle) and non-spawning (refugia) habitats in an Alaskan stream. Potential refugia included: pools, stream margins and the hyporheic zone, and we also sampled invertebrate drift. We predicted that macroinvertebrates would decline in riffles and increase in drift and refugia habitats during salmon spawning. We observed a reduction in the density, biomass and taxonomic richness of macroinvertebrates in riffles during spawning. There was no change in pool and margin invertebrate communities, except insect biomass declined in pools during the spawning period. Macroinvertebrate density was greater in the hyporheic zone and macroinvertebrate density and richness increased in the drift during spawning. We observed significant invertebrate declines within spawning habitat; however in non-spawning habitat, there were less pronounced changes in invertebrate density and richness. The results observed may be due to spawning-related disturbances, insect phenology, or other variables. We propose that certain in-stream habitats could be important for the persistence of macroinvertebrates during salmon spawning in a Southeast Alaskan stream
Radiographic evaluation of calcaneal fractures: To measure or not to measure
Objective: The aim of this study was to correlate the functional outcome after treatment for displaced intra-articular calcaneal fracture with plain radiography. Design: The design was a prognostic study of a retrospective cohort with concurrent follow-up. Patients: A total of 33 patients with a unilateral calcaneal fracture and a minimum follow-up of 13 months participated. Patients filled in three disease-specific questionnaires, graded their satisfaction and the indication for an arthrodesis was noted. Standardised radiographs were made of the previously injured side and the normal (control) side. Different angles and distances were measured on these radiographs and compared with values described in the literature. The differences in values in angles and distances between the injured and uninjured (control) foot were correlated with the outcome of the questionnaires, and the indication for an arthrodesis. Results: None of the angles correlated with the disease-specific outcome scores. Of the angles only the tibiotalar angle correlated with the VAS (r=0.35, p=0.045) and only the absolute foot height correlated with the indication for an arthrodesis (odds=0.70, CI=0.50-0.99). Conclusion: In this study the radiographic evaluation correlated poorly with the final outcome. Measurements on plain radiographs seem not to be useful in determining outcome after intra-articular calcaneal fractures
Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector
Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente
Central role for MCP-1/CCL2 in injury-induced inflammation revealed by in vitro, in silico, and clinical studies
The translation of in vitro findings to clinical outcomes is often elusive. Trauma/hemorrhagic shock (T/HS) results in hepatic hypoxia that drives inflammation. We hypothesize that in silico methods would help bridge in vitro hepatocyte data and clinical T/HS, in which the liver is a primary site of inflammation. Primary mouse hepatocytes were cultured under hypoxia (1% O 2) or normoxia (21% O2) for 1-72 h, and both the cell supernatants and protein lysates were assayed for 18 inflammatory mediators by Luminex™ technology. Statistical analysis and data-driven modeling were employed to characterize the main components of the cellular response. Statistical analyses, hierarchical and k-means clustering, Principal Component Analysis, and Dynamic Network Analysis suggested MCP-1/CCL2 and IL-1α as central coordinators of hepatocyte-mediated inflammation in C57BL/6 mouse hepatocytes. Hepatocytes from MCP-1-null mice had altered dynamic inflammatory networks. Circulating MCP-1 levels segregated human T/HS survivors from non-survivors. Furthermore, T/HS survivors with elevated early levels of plasma MCP-1 post-injury had longer total lengths of stay, longer intensive care unit lengths of stay, and prolonged requirement for mechanical ventilation vs. those with low plasma MCP-1. This study identifies MCP-1 as a main driver of the response of hepatocytes in vitro and as a biomarker for clinical outcomes in T/HS, and suggests an experimental and computational framework for discovery of novel clinical biomarkers in inflammatory diseases. © 2013 Ziraldo et al
Collagen-Binding Peptidoglycans Inhibit MMP Mediated Collagen Degradation and Reduce Dermal Scarring
Scarring of the skin is a large unmet clinical problem that is of high patient concern and impact. Wound healing is complex and involves numerous pathways that are highly orchestrated, leaving the skin sealed, but with abnormal organization and composition of tissue components, namely collagen and proteoglycans, that are then remodeled over time. To improve healing and reduce or eliminate scarring, more rapid restoration of healthy tissue composition and organization offers a unique approach for development of new therapeutics. A synthetic collagen-binding peptidoglycan has been developed that inhibits matrix metalloproteinase-1 and 13 (MMP-1 and MMP-13) mediated collagen degradation. We investigated the synthetic peptidoglycan in a rat incisional model in which a single dose was delivered in a hyaluronic acid (HA) vehicle at the time of surgery prior to wound closure. The peptidoglycan treatment resulted in a significant reduction in scar tissue at 21 days as measured by histology and visual analysis. Improved collagen architecture of the treated wounds was demonstrated by increased tensile strength and transmission electron microscopy (TEM) analysis of collagen fibril diameters compared to untreated and HA controls. The peptidoglycan's mechanism of action includes masking existing collagen and inhibiting MMP-mediated collagen degradation while modulating collagen organization. The peptidoglycan can be synthesized at low cost with unique design control, and together with demonstrated preclinical efficacy in reducing scarring, warrants further investigation for dermal wound healing
Functional treatment versus plaster for simple elbow dislocations (FuncSiE): a randomized trial
Background. Elbow dislocations can be classified as simple or complex. Simple dislocations are characterized by the absence of fractures, while complex dislocations are associated with fractures. After reduction of a simple dislocation, treatment options include immobilization in a static plaster for different periods of time or so-called functional treatment. Functional treatment is characterized by early active motion within the limits of pain with or without the use of a sling or hinged brace. Theoretically, functional treatment should prevent stiffness without introducing increased joint instability. The primary aim of this randomized controlled trial is to compare early functional treatment versus plaster immobilization following simple dislocations of the elbow. Methods/Design. The design of the study will be a multicenter randomized controlled trial of 100 patients who have sustained a simple elbow dislocation. After reduction of the dislocation, patients are randomized between a pressure bandage for 5-7 days and early functional treatment or a plaster in 90 degrees flexion, neutral position for pro-supination for a period of three weeks. In the functional group, treatment is started with early active motion within the limits of pain. Function, pain, and radiographic recovery will be evaluated at regular intervals over the subsequent 12 months. The primary outcome measure is the Quick Disabilities of the Arm, Shoulder, and Hand score. The secondary outcome measures are the Mayo Elbow Performance Index, Oxford elbow score, pain level at both sides, range of motion of the elbow joint at both sides, rate of secondary interventions and complication rates in both groups (secondary dislocation, instability, relaxation), health-related quality of life (Short-Form 36 and EuroQol-5D), radiographic appearance of the elbow joint (degenerative changes and heterotopic ossifications), costs, and cost-effectiveness. Discussion. The successful completion of this trial will provide evidence on the effectiveness of a functional treatment for the management of simple elbow dislocations. Trial Registration. The trial is registered at the Netherlands Trial Register (NTR2025)
Estimating Impact Forces of Tail Club Strikes by Ankylosaurid Dinosaurs
BACKGROUND: It has been assumed that the unusual tail club of ankylosaurid dinosaurs was used actively as a weapon, but the biological feasibility of this behaviour has not been examined in detail. Ankylosaurid tail clubs are composed of interlocking vertebrae, which form the handle, and large terminal osteoderms, which form the knob. METHODOLOGY/PRINCIPAL FINDINGS: Computed tomographic (CT) scans of several ankylosaurid tail clubs referred to Dyoplosaurus and Euoplocephalus, combined with measurements of free caudal vertebrae, provide information used to estimate the impact force of tail clubs of various sizes. Ankylosaurid tails are modeled as a series of segments for which mass, muscle cross-sectional area, torque, and angular acceleration are calculated. Free caudal vertebrae segments had limited vertical flexibility, but the tail could have swung through approximately 100 degrees laterally. Muscle scars on the pelvis record the presence of a large M. longissimus caudae, and ossified tendons alongside the handle represent M. spinalis. CT scans showed that knob osteoderms were predominantly cancellous, which would have lowered the rotational inertia of the tail club and made it easier to wield as a weapon. CONCLUSIONS/SIGNIFICANCE: Large knobs could generate sufficient force to break bone during impacts, but average and small knobs could not. Tail swinging behaviour is feasible in ankylosaurids, but it remains unknown whether the tail was used for interspecific defense, intraspecific combat, or both
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