822 research outputs found

    Locomotor adaptability in persons with unilateral transtibial amputation

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    Background Locomotor adaptation enables walkers to modify strategies when faced with challenging walking conditions. While a variety of neurological injuries can impair locomotor adaptability, the effect of a lower extremity amputation on adaptability is poorly understood. Objective Determine if locomotor adaptability is impaired in persons with unilateral transtibial amputation (TTA). Methods The locomotor adaptability of 10 persons with a TTA and 8 persons without an amputation was tested while walking on a split-belt treadmill with the parallel belts running at the same (tied) or different (split) speeds. In the split condition, participants walked for 15 minutes with the respective belts moving at 0.5 m/s and 1.5 m/s. Temporal spatial symmetry measures were used to evaluate reactive accommodations to the perturbation, and the adaptive/de-adaptive response. Results Persons with TTA and the reference group of persons without amputation both demonstrated highly symmetric walking at baseline. During the split adaptation and tied post-adaptation walking both groups responded with the expected reactive accommodations. Likewise, adaptive and de-adaptive responses were observed. The magnitude and rate of change in the adaptive and de-adaptive responses were similar for persons with TTA and those without an amputation. Furthermore, adaptability was no different based on belt assignment for the prosthetic limb during split adaptation walking. Conclusions Reactive changes and locomotor adaptation in response to a challenging and novel walking condition were similar in persons with TTA to those without an amputation. Results suggest persons with TTA have the capacity to modify locomotor strategies to meet the demands of most walking conditions despite challenges imposed by an amputation and use of a prosthetic limb

    Lithium interactions with non-steroidal anti-inflammatory drugs and diuretics – A review

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    Background: Lithium is often used in bipolar disorder and occasionally in unipolar depression. Non-steroidal anti-inflammatory drugs (NSAIDs) and diuretics are frequently prescribed and their interaction with lithium is based mainly in few small studies. Objectives: Conduct a review, identify different interaction patterns and discuss treatment options. Methods: Three searches were made in PubMed in January 2016: 1) using the keywords “lithium” [and] “non-steroidal anti-inflammatory”; 2) using the keywords “lithium” [and] “diuretics” and the filter “title/abstract”; 3) using the terms “lithium” [and] “toxicity” and the filters “title” [and] “review”. From the 293 remaining articles, 10 were selected. Another search in Scielo.org was made, using the term “lítio” and the filter “Psiquiatria”. Two articles were selected from the initial 53. Six textbooks were added to expand the evidence, achieving a total of 18 references. Results: The majority of NSAIDs and diuretics rises lithium levels, specially thiazides. However, some show great variability or no interaction at all, and others even decrease lithium levels. Discussion: Lower-doses, shorter durations, lithium adjustments and levels' follow-ups are recommended, especially in elderly and multiple co-morbid patients

    A Proposal for a Near Detector Experiment on the Booster Neutrino Beamline: FINeSSE: Fermilab Intense Neutrino Scattering Scintillator Experiment

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    219 pages219 pagesUnderstanding the quark and gluon substructure of the nucleon has been a prime goal of both nuclear and particle physics for more than thirty years and has led to much of the progress in strong interaction physics. Still the flavor dependence of the nucleon's spin is a significant fundamental question that is not understood. Experiments measuring the spin content of the nucleon have reported conflicting results on the amount of nucleon spin carried by strange quarks. Quasi-elastic neutrino scattering, observed using a novel detection technique, provides a theoretically clean measure of this quantity. The optimum neutrino beam energy needed to measure the strange spin of the nucleon is 1 GeV. This is also an ideal energy to search for neutrino oscillations at high Δm2\Delta m^2 in an astrophysically interesting region. Models of the r-process in supernovae which include high-mass sterile neutrinos may explain the abundance of neutron-rich heavy metals in the universe. These high-mass sterile neutrinos are outside the sensitivity region of any previous neutrino oscillation experiments. The Booster neutrino beamline at Fermilab provides the world's highest intensity neutrino beam in the 0.5-1.0 GeV energy range, a range ideal for both of these measurements. A small detector located upstream of the MiniBooNE detector, 100 m from the recently commissioned Booster neutrino source, could definitively measure the strange quark contribution to the nucleon spin. This detector, in conjunction with the MiniBooNE detector, could also investigate νμ\nu_{\mu} disappearance in a currently unexplored, cosmologically interesting region

    The degradation of p53 and its major E3 ligase Mdm2 is differentially dependent on the proteasomal ubiquitin receptor S5a.

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    p53 and its major E3 ligase Mdm2 are both ubiquitinated and targeted to the proteasome for degradation. Despite the importance of this in regulating the p53 pathway, little is known about the mechanisms of proteasomal recognition of ubiquitinated p53 and Mdm2. In this study, we show that knockdown of the proteasomal ubiquitin receptor S5a/PSMD4/Rpn10 inhibits p53 protein degradation and results in the accumulation of ubiquitinated p53. Overexpression of a dominant-negative deletion of S5a lacking its ubiquitin-interacting motifs (UIM)s, but which can be incorporated into the proteasome, also causes the stabilization of p53. Furthermore, small-interferring RNA (siRNA) rescue experiments confirm that the UIMs of S5a are required for the maintenance of low p53 levels. These observations indicate that S5a participates in the recognition of ubiquitinated p53 by the proteasome. In contrast, targeting S5a has no effect on the rate of degradation of Mdm2, indicating that proteasomal recognition of Mdm2 can be mediated by an S5a-independent pathway. S5a knockdown results in an increase in the transcriptional activity of p53. The selective stabilization of p53 and not Mdm2 provides a mechanism for p53 activation. Depletion of S5a causes a p53-dependent decrease in cell proliferation, demonstrating that p53 can have a dominant role in the response to targeting S5a. This study provides evidence for alternative pathways of proteasomal recognition of p53 and Mdm2. Differences in recognition by the proteasome could provide a means to modulate the relative stability of p53 and Mdm2 in response to cellular signals. In addition, they could be exploited for p53-activating therapies. This work shows that the degradation of proteins by the proteasome can be selectively dependent on S5a in human cells, and that this selectivity can extend to an E3 ubiquitin ligase and its substrate

    A Method for Analyzing the Ubiquitination and Degradation of Aurora-A

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    The cell cycle machinery consists of regulatory proteins that control the progression through the cell cycle ensuring that DNA replication alternates with DNA segregation in mitosis to maintain cell integrity. Some of these key regulators have to be degraded at each cell cycle to prevent cellular dysfunction. Mitotic exit requires the inactivation of cyclin dependent kinase1 (cdk1) and it is the degradation of the cyclin subunit that inactivates the kinase. Cyclin degradation has been well characterized and it was shown that it is ubiquitin proteasome pathway that leads to the elimination of cyclins. By now, many other regulatory proteins were shown to be degraded by the same pathway, among them members of the aurora kinase family, degraded many other regulatory proteins. Aurora kinases are involved in mitotic spindle formation as well as in cytokinesis. The abundance and activity of the kinase is precisely regulated during the cell cycle. To understand how proteolysis regulates transitions through the cell cycle we describe two assays for ubiquitination and degradation of xenopus aurora kinase A using extracts from xenopus eggs or somatic cell lines

    A pilot survey of post-deployment health care needs in small community-based primary care clinics

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    <p>Abstract</p> <p>Background</p> <p>Relatively little is known regarding to what extent community-based primary care physicians are encountering post-deployment health care needs among veterans of the Afghanistan or Iraq conflicts and their family members.</p> <p>Methods</p> <p>This pilot study conducted a cross-sectional survey of 37 primary care physicians working at small urban and suburban clinics belonging to a practice-based research network in the south central region of Texas.</p> <p>Results</p> <p>Approximately 80% of the responding physicians reported caring for patients who have been deployed to the Afghanistan or Iraq war zones, or had a family member deployed. Although these physicians noted a variety of conditions related to physical trauma, mental illnesses and psychosocial disruptions such as marital, family, financial, and legal problems appeared to be even more prevalent among their previously deployed patients and were also noted among family members of deployed veterans.</p> <p>Conclusions</p> <p>Community-based primary care physicians should be aware of common post-deployment health conditions and the resources that are available to meet these needs.</p

    Salvage Cryotherapy for Radiation-Recurrent Prostate Cancer: Outcomes and Complications

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    Potentially curative salvage options for radio-recurrent prostate cancer include prostatectomy, brachytherapy, high-intensity focused ultrasound, and cryotherapy. Salvage cryoablation technology, surgical technique, oncologic outcomes, and complication rates have improved dramatically over the past few decades, shifting this treatment modality from investigational status to an established therapeutic option. In this review, we focus on the most up-to-date oncologic and functional outcomes, as well as complications of salvage cryotherapy for radiation-recurrent prostate cancer
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