845 research outputs found
Diffusion-negative MRI in acute ischemic stroke: a case report
This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens
On the dynamics of WKB wave functions whose phase are weak KAM solutions of H-J equation
In the framework of toroidal Pseudodifferential operators on the flat torus
we begin by proving the closure under
composition for the class of Weyl operators with
simbols . Subsequently, we
consider when where and we exhibit the toroidal version of the
equation for the Wigner transform of the solution of the Schr\"odinger
equation. Moreover, we prove the convergence (in a weak sense) of the Wigner
transform of the solution of the Schr\"odinger equation to the solution of the
Liouville equation on written in the measure sense.
These results are applied to the study of some WKB type wave functions in the
Sobolev space with phase functions in the class
of Lipschitz continuous weak KAM solutions (of positive and negative type) of
the Hamilton-Jacobi equation for with , and to the study of the
backward and forward time propagation of the related Wigner measures supported
on the graph of
A Single-Arm, Proof-Of-Concept Trial of Lopimune (Lopinavir/Ritonavir) as a Treatment for HPV-Related Pre-Invasive Cervical Disease
BACKGROUND:
Cervical cancer is the most common female malignancy in the developing nations and the third most common cancer in women globally. An effective, inexpensive and self-applied topical treatment would be an ideal solution for treatment of screen-detected, pre-invasive cervical disease in low resource settings.
METHODS:
Between 01/03/2013 and 01/08/2013, women attending Kenyatta National Hospital's Family Planning and Gynaecology Outpatients clinics were tested for HIV, HPV (Cervista®) and liquid based cervical cytology (LBC -ThinPrep®). HIV negative women diagnosed as high-risk HPV positive with high grade squamous intraepithelial lesions (HSIL) were examined by colposcopy and given a 2 week course of 1 capsule of Lopimune (CIPLA) twice daily, to be self-applied as a vaginal pessary. Colposcopy, HPV testing and LBC were repeated at 4 and 12 weeks post-start of treatment with a final punch biopsy at 3 months for histology. Primary outcome measures were acceptability of treatment with efficacy as a secondary consideration.
RESULTS:
A total of 23 women with HSIL were treated with Lopimune during which time no adverse reactions were reported. A maximum concentration of 10 ng/ml of lopinavir was detected in patient plasma 1 week after starting treatment. HPV was no longer detected in 12/23 (52.2%, 95%CI: 30.6-73.2%). Post-treatment cytology at 12 weeks on women with HSIL, showed 14/22 (63.6%, 95%CI: 40.6-82.8%) had no dysplasia and 4/22 (18.2%, 95%CI: 9.9-65.1%) were now low grade demonstrating a combined positive response in 81.8% of women of which 77.8% was confirmed by histology. These data are supported by colposcopic images, which show regression of cervical lesions.
CONCLUSIONS:
These results demonstrate the potential of Lopimune as a self-applied therapy for HPV infection and related cervical lesions. Since there were no serious adverse events or detectable post-treatment morbidity, this study indicates that further trials are clearly justified to define optimal regimes and the overall benefit of this therapy.
TRIAL REGISTRATION:
ISRCTN Registry 48776874
FAS-dependent cell death in α-synuclein transgenic oligodendrocyte models of multiple system atrophy
Multiple system atrophy is a parkinsonian neurodegenerative disorder. It is cytopathologically characterized by accumulation of the protein p25α in cell bodies of oligodendrocytes followed by accumulation of aggregated α-synuclein in so-called glial cytoplasmic inclusions. p25α is a stimulator of α-synuclein aggregation, and coexpression of α-synuclein and p25α in the oligodendroglial OLN-t40-AS cell line causes α-synuclein aggregate-dependent toxicity. In this study, we investigated whether the FAS system is involved in α-synuclein aggregate dependent degeneration in oligodendrocytes and may play a role in multiple system atrophy. Using rat oligodendroglial OLN-t40-AS cells we demonstrate that the cytotoxicity caused by coexpressing α-synuclein and p25α relies on stimulation of the death domain receptor FAS and caspase-8 activation. Using primary oligodendrocytes derived from PLP-α-synuclein transgenic mice we demonstrate that they exist in a sensitized state expressing pro-apoptotic FAS receptor, which makes them sensitive to FAS ligand-mediated apoptosis. Immunoblot analysis shows an increase in FAS in brain extracts from multiple system atrophy cases. Immunohistochemical analysis demonstrated enhanced FAS expression in multiple system atrophy brains notably in oligodendrocytes harboring the earliest stages of glial cytoplasmic inclusion formation. Oligodendroglial FAS expression is an early hallmark of oligodendroglial pathology in multiple system atrophy that mechanistically may be coupled to α-synuclein dependent degeneration and thus represent a potential target for protective intervention
Association of CD99 short and long forms with MHC class I, MHC class II and tetraspanin CD81 and recruitment into immunological synapses
<p>Abstract</p> <p>Background</p> <p>CD99, a leukocyte surface glycoprotein, is broadly expressed in many cell types. On the cell surface, CD99 is expressed as two distinct isoforms, a long form and a short form. CD99 has been demonstrated to play a key role in several biological processes, including the regulation of T cell activation. However, the molecular mechanisms by which CD99 participates in such processes are unclear. As CD99 contains a short cytoplasmic tail, it is unlikely that CD99 itself takes part in its multi-functions. Association of CD99 with other membrane proteins has been suggested to be necessary for exerting its functions.</p> <p>Results</p> <p>In this study, we analyzed the association of CD99 with other cell surface molecules involved in T cell activation. We demonstrate the association of MHC class I, MHC class II and tetraspanin CD81 with CD99 molecules on the cell surface. Association of CD99 with its partners was observed for both isoforms. In addition, we determined that CD99 is a lipid raft-associated membrane protein and is recruited into the immunologic synapse during T cell activation. The implication of CD99 on T cell activation was investigated. Inhibition of anti-CD3 induced T cell proliferation by an anti-CD99 monoclonal antibody was observed.</p> <p>Conclusions</p> <p>We provide evidence that CD99 directly interact and form the complex with the MHC class I and II, and tetraspanin CD81, and is functionally linked to the formation of the immunologic synapse. Upon T cell activation, CD99 engagement can inhibit T cell proliferation. We speculate that the CD99-MHC-CD81 complex is a tetraspanin web that plays an important role in T cell activation.</p
Quality of life and mortality from a nephrologist's view: a prospective observational study
<p>Abstract</p> <p>Background</p> <p>Although health-related quality of life (HRQOL) is a potential independent predictor of mortality, nephrologists have shown little interest in HRQOL with respect to mortality in chronic kidney disease (CKD). The aim of this article is to evaluate the impact of HRQOL on mortality in the elderly, who are likely to develop or already have CKD.</p> <p>Methods</p> <p>Among 1,000 randomly sampled participants aged more than 65 years (sourced from the Korean Longitudinal Study on Health and Ageing), 944 subjects were evaluated for HRQOL. HRQOL was assessed using a 36-item Short-Form health survey (SF36). A cumulative survival rate was calculated according to tertiles of SF36 scores and classified by the presence of CKD (estimated GFR <60 ml/min/1.73 m<sup>2</sup>).</p> <p>Results</p> <p>Among 944 subjects, 46.6% had CKD. CKD patients had lower total and physical component scores compared with subjects without CKD. The 3-year cumulative survival rate was 90.0% (non-CKD vs. CKD: 92.6% vs. 87.4%, <it>P </it>= 0.005 by log rank test). After adjusting for multiple variables, a reduced SF36 score (physical and mental components) was a strong predictor of all-cause mortality. Physical components were consistently able to predict mortality after CKD classification, but mental components were statistically significant only in the CKD group.</p> <p>Conclusion</p> <p>In addition to traditional risk factors of mortality, nephrologists should be aware of HRQOL as a predictor of mortality and should make efforts to improve HRQOL in CKD patients.</p
Background Light in Potential Sites for the ANTARES Undersea Neutrino Telescope
The ANTARES collaboration has performed a series of {\em in situ}
measurements to study the background light for a planned undersea neutrino
telescope. Such background can be caused by K decays or by biological
activity. We report on measurements at two sites in the Mediterranean Sea at
depths of 2400~m and 2700~m, respectively. Three photomultiplier tubes were
used to measure single counting rates and coincidence rates for pairs of tubes
at various distances. The background rate is seen to consist of three
components: a constant rate due to K decays, a continuum rate that
varies on a time scale of several hours simultaneously over distances up to at
least 40~m, and random bursts a few seconds long that are only correlated in
time over distances of the order of a meter. A trigger requiring coincidences
between nearby photomultiplier tubes should reduce the trigger rate for a
neutrino telescope to a manageable level with only a small loss in efficiency.Comment: 18 pages, 8 figures, accepted for publication in Astroparticle
Physic
The Spin Structure of the Nucleon
We present an overview of recent experimental and theoretical advances in our
understanding of the spin structure of protons and neutrons.Comment: 84 pages, 29 figure
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