56 research outputs found
Comparative effectiveness of conservative and pharmacological interventions for chronic non-specific neck pain : Protocol of a systematic review and network meta-analysis
BACKGROUND: Neck Pain (NP) has been ranked as one of the top chronic pain conditions in terms of prevalence and years lived with disability in the latest Global Burden of Disease. NP has remarkable socio-economic consequences however, research efforts are limited. Discrepancies among guidelines recommendations on management of chronic neck pain exist. The purpose of this study protocol is to provide the methods for a review with network meta-analysis to identify the most effective interventions for chronic neck pain. METHODS: The following databases will be searched from their inception to February 2019: Cochrane Controlled Trials Register (CENTRAL), PubMed, CINAHL, Scopus, ISI Web of Science and PEDro.Randomized controlled trials (RCTs) on pharmacological and not pharmacological interventions will be included and their risk of bias will be evaluated using the Cochrane Risk of bias tool. Primary outcomes will be reduction in pain and disability. A network meta-analysis will be carried out and pairwise meta-analysis will be conducted using Stata 15 software. Grading of recommendations assessment, development, and evaluation (GRADE) will be applied to assess quality of the body of the evidence. RESULTS: The results of this review will be submitted to a peer-review journal for publication. CONCLUSION: This network meta-analysis will provide a comprehensive review on the most effective treatments for the management of chronic neck pain providing key evidence-based information to patients, clinicians and other relevant stakeholders. Registration: PROSPERO (registration number CRD42019124501)
A common mechanism of defective channel trafficking underlying DFNA2 hearing loss result in different cell surface expression levels of KCNQ4 mutants
KCNQ4 mutations underlie DFNA2, a subtype of autosomal dominant hearing loss. We had previously
identified the pore-region p.G296S mutation that impaired channel activity in two manners: it greatly
reduced surface expression and abolished channel function. Moreover, G296S mutant exerted a strong
dominant-negative effect on potassium currents by reducing the channel expression at the cell surface
representing the first study to identify a trafficking-dependent dominant mechanism for the loss of
KCNQ4 channel function in DFNA2.
Here, we have investigated the pathogenic mechanism associated with all the described KCNQ4
mutations (F182L, W242X, E260K, D262V, L274H, W276S, L281S, G285C, G285S and G321S) that are
located in different domains of the channel protein. F182L mutant showed a wild type-like cell-surface
distribution in transiently transfected NIH3T3 fibroblasts and the recorded currents in Xenopus oocytes
resembled those of the wild-type. The remaining KCNQ4 mutants abolished potassium currents, but
displayed distinct levels of defective cell-surface expression in NIH3T3 as quantified by flow citometry.
Co-localization studies revealed these mutants were retained in the ER, unless W242X, which showed a
clear co-localization with Golgi apparatus. Interestingly, this mutation results in a truncated KCNQ4
protein at the S5 transmembrane domain, before the pore region, that escapes the protein quality
control in the ER but does not reach the cell surface at normal levels.
Currently we are investigating the trafficking behaviour and electrophysiological properties of several
KCNQ4 truncated proteins artificially generated in order to identify specific motifs involved in channel
retention/exportation. Altogether, our results indicate that a defect in KCNQ4 trafficking is the
common mechanism underlying DFNA
po 298 myc favours the onset of tumour initiating cells by inducing epigenetic reprogramming of mammary epithelial cells towards a stem cell like state
Introduction Breast cancer consists of highly heterogenous tumours whose cell of origin resulted difficult to be defined. Recent findings highlighted the possibility that tumor-initiating cells (TICs) may arise from dedifferentiation of lineage-committed cells, by reactivation of multipotency in response to oncogenic insults. MYC is the most frequently amplified oncogene in breast cancer and the activation of MYC pathway has been associated with the basal-like subtype, which is characterised by poor survival and lack of a specific therapeutic strategy. Although MYC has been considered a driver oncogene in breast cancer, its mechanism of action in tumour initiation has been poorly addressed. Material and methods To evaluate the role of MYC in perturbing cell identity of somatic cells, we transduced hTERT-immortalised human mammary epithelial cells (IMEC) with a retroviral vector expressing low levels of the exogenous c-Myc. The effect of MYC overexpression was evaluated by performing morphological analysis and gene expression profiling. To verify whether MYC overexpression could enrich for cells with functional stem cell-like properties, we performed mammospheres assay. ChIP-seq analyses were performed to profile chromatin modifications and MYC binding in IMEC WT, -MYC and mammospheres. To determine whether MYC-reprogrammed IMEC were enriched for TICs, we performed in vivo injection in NOD/SCID mice and assessed long-term tumorigenic potential by performing serial transplantation assay. To assess the clinical relevance of our findings, we investigated the expression of MYC-dependent oncogenic signature in a database of breast cancer patients. Results and discussions Overexpression of MYC induces transcriptional repression of lineage-specifying transcription factors, causing decommissioning of luminal-specific enhancers. Of note, MYC-driven dedifferentiation supports the onset of a basal/stem cell-like state by inducing the activation of de novo enhancers, which drive the transcriptional activation of oncogenic pathways. MYC-driven epigenetic reprogramming favours the formation and maintenance of TICs endowed with metastatic capacity. Moreover, oncogenic pathways activated by MYC-modulated enhancers are associated with basal-like breast cancer in patients with a poor prognosis. Conclusion MYC-driven tumour initiation relies on a cell reprogramming process, which is mediated by activation of MYC-dependent oncogenic enhancers, thus establishing a therapeutic rational for treating basal-like breast cancers
Temperature Dependence of Solar Light Assisted CO2 Reduction on Ni Based Photocatalyst
Methanation of CO2 by H-2 can be in the future an important reaction to store the surplus of renewable electricity during production peaks. The catalytic thermal CO2 methanation (the Sabatier reaction) can be carried out at temperatures above 250 degrees C using Ni supported on silica-alumina (Ni/SiO2-Al2O3). Recently it has been observed that this exothermic reaction can be promoted by solar light irradiation of Ni/SiO2-Al2O3 at initial near ambient temperatures. In the present work we provide a study of the influence of the initial temperature on the photoassisted Ni/SiO2-Al2O3 methanation of CO2, under conditions in which the dark reaction is not observed. An increase of the photoassisted methanation rate with the initial temperature in the range from ambient to 150 degrees C has been observed. The reaction kinetics for lower initial temperatures exhibited an induction period not observed for reactions performed at higher temperatures. The results are discussed in terms of the operation of plasmon photo activation in which the energy of photons is thermalised in a confined space of the active nanoparticles leading to locally high temperatures and the simultaneous photogeneration of electrons and positive holes.Albero Sancho, J.; GarcÃa Gómez, H.; Corma Canós, A. (2016). Temperature Dependence of Solar Light Assisted CO2 Reduction on Ni Based Photocatalyst. Topics in Catalysis. 59(8-9):787-791. doi:10.1007/s11244-016-0550-xS787791598-9Hammarstrom L, Hammes-Schiffer S (2009) Artificial photosynthesis and solar fuels. Acc Chem Res 42:1859–1860Schlögl R (2015) The revolution continues: energiewende 2.0. Angew Chem Int Ed 54:4436–4439Herron JA, Kim J, Upadhye AA, Huber GW, Maravelias CT (2015) A general framework for the assessment of solar fuel technologies. Energy Environ Sci 8:126–157Hoekman SK, Broch A, Robbins C, Purcell R (2010) CO2 recycling by reaction with renewably-generated hydrogen. Int J Greenh Gas Control 4:44–50Hoch LB, Wood TE, O’Brien PG, Liao K, Reyes LM, Mims CA, Ozin GA (2014) The rational design of a single-component photocatalyst for gas-phase CO2 reduction using both UV and visible light. Adv Sci 1:1400010–1400013Sastre F, Puga AV, Liu L, Corma A, Garcia H (2014) Complete photocatalytic reduction of CO2 to methane by H2 under solar light irradiation. J Am Chem Soc 136:6798–6801Melsheimer J, Guo W, Ziegler D, Wesemann M, Schlögl R (1991) Methanation of carbon dioxide over Ru/titania at room temperature: explorations for a photoassisted catalytic reaction. Catal Lett 11:157–168O’Brien PG, Sandhel A, Wood TE, Jelle AA, Hoch LB, Perovic DD, Mims CA, Ozin GA (2014) Photomethanation of gaseous CO2 over Ru/silicon nanowire catalysts with visible and near-infrared photons. Adv Sci 1:1400001–1400007Ghuman KK, Wood TE, Hoch LB, Mims CA, Ozin GA, Singh CV (2015) Illuminating CO2 reduction on frustrated Lewis pair surfaces: investigating the role of surface hydroxides and oxygen vacancies on nanocrystalline In2O3−x(OH)y. Phys Chem Chem Phys 17:14623–14635Wei W, Jinlong G (2011) Methanation of carbon dioxide: an overview. Front Chem Sci Eng 5:2–10Scaiano JC, Stamplecoskie K (2013) Can surface plasmon fields provide a new way to photosensitize organic photoreactions? Custom applications. J Phys Chem Lett 4:1177–1187Fasciani C, Alejo CJB, Grenier M, Netto-Ferreira JC, Scaiano JC (2011) High-temperature organic reactions at room temperature using plasmon excitation: decomposition of dicumyl peroxide. Org Lett 13:204–207Leadbeater NE (2010) Microwave heating as a tool for sustainable chemistry. CRC Press, Boca Rato
Latrogenic keratectasia following laser in situ keratomileusis
To evaluate keratectasia after laser in situ keratomileusis (LASIK) for high myopia
Latrogenic keratectasia following laser in situ keratomileusis
To evaluate keratectasia after laser in situ keratomileusis (LASIK) for high myopia
Determination of diphenyl-ether herbicides and metabolites in natural waters using high performance liquid chromatography with diod array tandem mass spectrometric detection.
A method for the identification and quantification of neutral diphenyl-ether (DPhE) (aclonifen, bifenox, fluoroglycofen, lactofen, oxyfluorfen) and acid metabolites (acifluorfen, bifenox acid, fomesafen) at a low nanogram per liter concentration level in natural water is presented. These herbicides and their metabolites were determined in drinking water, groundwater, and river water. The analytes were isolated from water samples by solid-phase extraction (SPE) on Carbograph-1 cartridges and analyzed with reversed phase high-performance liquid chromatography (RP-HPLC) using UV detection at a wavelength of 290 nm. The isolation procedure separated the acid DPhE from neutral DPhE during the elution from Carbograph-1 cartridge using dichloromethane:methanol (80.20, v/v) for neutral compounds and dichloromethane:methanol (80:20, v/v) acidified with 25 mmol/l of formic acid for the anionic metabolites. Quantification was performed by generation of an external calibration curve. High recoveries (>85%) of extraction were obtained for all the compounds. The method detection limit ranged from 4.1 to 8.7 ng/l for drinking water, from 5.1 to 9.5 ng/l for groundwater and from 17.5 to 36.2 ng/l for river water. This method involves confirmatory analysis by tandem mass spectrometry (MS-MS) in selected reaction monitoring (SRM) mode. Conditions for MS-MS detection of characteristic daughter ions formed by collision-induced dissociation of the parent ion are described. The final samples were analyzed by HPLC-MS-MS utilizing a heat-assisted electrospray interface (turbo ion spray) (TISP) for acid DPhE and a heated nebulizer (HN) interface for neutral DPhE. Quantification was performed by generation of an internal calibration curve. Excellent method precision was demonstrated with a relative standard deviation of less than 18% for all analytes at all concentration levels. Application of the method for detecting DPhE herbicide residues in a real-world groundwater samples was demonstrated
Ocular mucous membrane pemphigoid after Lyell syndrome: occasional finding or predisposing event?
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