MicroRNA-383 located in frequently deleted chromosomal locus 8p22 regulates CD44 in prostate cancer.

A major genomic alteration in prostate cancer (PCa) is frequent loss of chromosome (chr) 8p with a common region of loss of heterozygosity (LOH) at chr8p22 locus. Genomic studies implicate this locus in the initiation of clinically significant PCa and with progression to metastatic disease. However, the genes within this region have not been fully characterized to date. Here we demonstrate for the first time that a microRNA component of this region-miR-383-is frequently downregulated in prostate cancer, has a critical role in determining tumor-initiating potential and is involved in prostate cancer metastasis via direct regulation of CD44, a ubiquitous marker of PCa tumor-initiating cells (TICs)/stem cells. Expression analyses of miR-383 in PCa clinical tissues established that low miR-383 expression is associated with poor prognosis. Functional data suggest that miR-383 regulates PCa tumor-initiating/stem-like cells via CD44 regulation. Ectopic expression of miR-383 inhibited tumor-initiating capacity of CD44+ PCa cells. Also, 'anti-metastatic' effects of ectopic miR-383 expression were observed in a PCa experimental metastasis model. In view of our results, we propose that frequent loss of miR-383 at chr8p22 region leads to tumor initiation and prostate cancer metastasis. Thus, we have identified a novel finding that associates a long observed genomic alteration to PCa stemness and metastasis. Our data suggest that restoration of miR-383 expression may be an effective therapeutic modality against PCa. Importantly, we identified miR-383 as a novel PCa tissue diagnostic biomarker with a potential that outperforms that of serum PSA

Increased blood glucose is related to disturbed cerebrovascular pressure reactivity after traumatic brain injury.

BACKGROUND: Increased blood glucose and impaired pressure reactivity (PRx) after traumatic brain injury (TBI) are both known to correlate with unfavorable patient outcome. However, the relationship between these two variables is unknown. METHODS: To test the hypothesis that increased blood glucose leads to increased PRx, we retrospectively analyzed data from 86 traumatic brain injured patients admitted to the Neurocritical Care Unit. Data analyzed included arterial glucose concentration, intracranial pressure (ICP), cerebral perfusion pressure (CPP) and end-tidal CO2. PRx was calculated as the moving correlation coefficient between averaged (10 seconds) arterial blood pressure and ICP. One arterial glucose concentration and one time-aligned PRx value were obtained for each patient, during each day until the fifth day after ictus. RESULTS: Mean arterial glucose concentrations during the first 5 days since ictus were positively correlated with mean PRx (Pearson correlation coefficient = 0.25, p = 0.02). The correlation was strongest on the first day after injury (Pearson correlation coefficient = 0.47, p = 0.008). CONCLUSION: Our preliminary findings indicate that increased blood glucose may impair cerebrovascular reactivity, potentially contributing to a mechanistic link between increased blood glucose and poorer outcome after TBI.This is the author accepted manuscript. The final version is available from Springer via http://dx.doi.org/10.1007/s12028-014-0042-

Clinical report of cervical arthroplasty in management of spondylotic myelopathy in Chinese

OBJECTIVES: To investigate clinical effects and manual operational point of Bryan cervical disc prosthesis in Chinese, to observe the stability and range of movement (ROM) post-operatively. METHODS AND MATERIALS: From 2003,12 to 2005,12, Bryan disc prosthesis replacement applied in 83 cases (102 levels) of cervical spondylotic myelopathy (CSM) after anterior decompression in our hospital. Clinical (JOA grade and Odom's scale) and radiological (X-ray of flexion, extension; left and right bending position) follow-up was performed. Systemic radiographic study about stability and ROM of replaced level post operationally were measured. CT or MRI scans were applied in all cases to evaluate the signs of the prosthesis deflexion and hetero-ossification in the replaced levels. RESULTS: At least 12 months follow-up were done in 65/83 of these paients. All of 83 patients were improved according to Odsm's scale. JOA score increased from average 8.7 to 15.5. There was no prosthesis subsidence. Replaced segment achieved stability and restored partial of normal ROM 4.73°(3.7°–5.9°) early postoperation and 8.12°(5.8°–13.6°) more than 12 months postoperation in flex and extension position. No obvious loss of lordosis was found. CT or MRI follow-up shows position deflexion of the prosthesis metal endplates (<1.5 mm) in 14/77 levels and (1.5~3 mm) in 4/77. heter-ossification was found in the replaced levels only in 2 cases. CONCLUSION: Byran cervical disc prosthesis restored motion to the level of the intact segment in flexion-extension and lateral bending in post-operative images. At the same time, it can achieve good anterior decompression treatment effect and immediate stability in replaced 1 or 2 levels, and which is a new choice for the treatment of CSM

Methods for specifying the target difference in a randomised controlled trial : the Difference ELicitation in TriAls (DELTA) systematic review

Peer reviewedPublisher PD

Measurement of the cross-section and charge asymmetry of WW bosons produced in proton-proton collisions at s=8\sqrt{s}=8 TeV with the ATLAS detector

This paper presents measurements of the $W^+ \rightarrow \mu^+\nu$ and $W^- \rightarrow \mu^-\nu$ cross-sections and the associated charge asymmetry as a function of the absolute pseudorapidity of the decay muon. The data were collected in proton--proton collisions at a centre-of-mass energy of 8 TeV with the ATLAS experiment at the LHC and correspond to a total integrated luminosity of 20.2~\mbox{fb^{-1}}. The precision of the cross-section measurements varies between 0.8% to 1.5% as a function of the pseudorapidity, excluding the 1.9% uncertainty on the integrated luminosity. The charge asymmetry is measured with an uncertainty between 0.002 and 0.003. The results are compared with predictions based on next-to-next-to-leading-order calculations with various parton distribution functions and have the sensitivity to discriminate between them.Comment: 38 pages in total, author list starting page 22, 5 figures, 4 tables, submitted to EPJC. All figures including auxiliary figures are available at https://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/STDM-2017-13

The efficacy of surgical decompression before 24 hours versus 24 to 72 hours in patients with spinal cord injury from T1 to L1 – with specific consideration on ethics: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>There is no clear evidence that early decompression following spinal cord injury (SCI) improves neurologic outcome. Such information must be obtained from randomized controlled trials (RCTs). To date no large scale RCT has been performed evaluating the timing of surgical decompression in the setting of thoracolumbar spinal cord injury. A concern for many is the ethical dilemma that a delay in surgery may adversely effect neurologic recovery although this has never been conclusively proven. The purpose of this study is to compare the efficacy of early (before 24 hours) verse late (24–72 hours) surgical decompression in terms of neurological improvement in the setting of traumatic thoracolumbar spinal cord injury in a randomized format by independent, trained and blinded examiners.</p> <p>Methods</p> <p>In this prospective, randomized clinical trial, 328 selected spinal cord injury patients with traumatic thoracolumbar spinal cord injury are to be randomly assigned to: 1) early surgery (before 24 hours); or 2) late surgery (24–72 hours). A rapid response team and set up is prepared to assist the early treatment for the early decompressive group. Supportive care, i.e. pressure support, immobilization, will be provided on admission to the late decompression group. Patients will be followed for at least 12 months posttrauma.</p> <p>Discussion</p> <p>This study will hopefully assist in contributing to the question of the efficacy of the timing of surgery in traumatic thoracolumbar SCI.</p> <p>Trial Registration</p> <p><b>RCT registration number: ISRCTN61263382</b></p

Search for chargino-neutralino production with mass splittings near the electroweak scale in three-lepton final states in √s=13 TeV pp collisions with the ATLAS detector

A search for supersymmetry through the pair production of electroweakinos with mass splittings near the electroweak scale and decaying via on-shell W and Z bosons is presented for a three-lepton final state. The analyzed proton-proton collision data taken at a center-of-mass energy of √s=13  TeV were collected between 2015 and 2018 by the ATLAS experiment at the Large Hadron Collider, corresponding to an integrated luminosity of 139  fb−1. A search, emulating the recursive jigsaw reconstruction technique with easily reproducible laboratory-frame variables, is performed. The two excesses observed in the 2015–2016 data recursive jigsaw analysis in the low-mass three-lepton phase space are reproduced. Results with the full data set are in agreement with the Standard Model expectations. They are interpreted to set exclusion limits at the 95% confidence level on simplified models of chargino-neutralino pair production for masses up to 345 GeV

Search for direct stau production in events with two hadronic tau-leptons in root s=13 TeV pp collisions with the ATLAS detector

A search for the direct production of the supersymmetric partners ofτ-leptons (staus) in final stateswith two hadronically decayingτ-leptons is presented. The analysis uses a dataset of pp collisions corresponding to an integrated luminosity of139fb−1, recorded with the ATLAS detector at the LargeHadron Collider at a center-of-mass energy of 13 TeV. No significant deviation from the expected StandardModel background is observed. Limits are derived in scenarios of direct production of stau pairs with eachstau decaying into the stable lightest neutralino and oneτ-lepton in simplified models where the two staumass eigenstates are degenerate. Stau masses from 120 GeV to 390 GeV are excluded at 95% confidencelevel for a massless lightest neutralino

Nicotine signals through muscle-type and neuronal nicotinic acetylcholine receptors in both human bronchial epithelial cells and airway fibroblasts

BACKGROUND: Non-neuronal cells, including those derived from lung, are reported to express nicotinic acetylcholine receptors (nAChR). We examined nAChR subunit expression in short-term cultures of human airway cells derived from a series of never smokers, ex-smokers, and active smokers. METHODS AND RESULTS: At the mRNA level, human bronchial epithelial (HBE) cells and airway fibroblasts expressed a range of nAChR subunits. In multiple cultures of both cell types, mRNA was detected for subunits that constitute functional muscle-type and neuronal-type pentomeric receptors. Two immortalized cell lines derived from HBE cells also expressed muscle-type and neuronal-type nAChR subunits. Airway fibroblasts expressed mRNA for three muscle-type subunits (α1, δ, and ε) significantly more often than HBE cells. Immunoblotting of HBE cell and airway fibroblast extracts confirmed that mRNA for many nAChR subunits is translated into detectable levels of protein, and evidence of glycosylation of nAChRs was observed. Some minor differences in nAChR expression were found based on smoking status in fibroblasts or HBE cells. Nicotine triggered calcium influx in the immortalized HBE cell line BEAS2B, which was blocked by α-bungarotoxin and to a lesser extent by hexamethonium. Activation of PKC and MAPK p38, but not MAPK p42/44, was observed in BEAS2B cells exposed to nicotine. In contrast, nicotine could activate p42/44 in airway fibroblasts within five minutes of exposure. CONCLUSIONS: These results suggest that muscle-type and neuronal-type nAChRs are functional in airway fibroblasts and HBE cells, that prior tobacco exposure does not appear to be an important variable in nAChR expression, and that distinct signaling pathways are observed in response to nicotine