21 research outputs found

    Additional file 1 of Association between muscle quality index and periodontal disease among American adults aged ≥ 30 years: a cross-sectional study and mediation analysis

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    Additional file 1: Supplementary Figure 1. Dose-response relationship between MQIarm and periodontitis. A. is for the continuous variable of MQIarm, and B is the categorical variable of MQIarm. Supplementary Figure 2. Dose-response relationship between MQIapp and periodontitis. A. is for the continuous variable of MQIapp, and B is the categorical variable of MQIapp. Supplementary Figure 3. The association between MQIarm and periodontitis stratified by sex. Supplementary Figure 4. The association between MQIapp and periodontitis stratified by sex. Supplementary Table 1. Threshold Effect Analysis between MQIapp and periodontitis. Supplementary Table 2. Threshold Effect Analysis between MQIarm and periodontitis

    Constraint-induced aphasia therapy in post-stroke aphasia rehabilitation: A systematic review and meta-analysis of randomized controlled trials

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    <div><p>Background</p><p>Constraint-induced aphasia therapy (CIAT) has been widely used in post-stroke aphasia rehabilitation. An increasing number of clinical controlled trials have investigated the efficacy of the CIAT for the post-stroke aphasia.</p><p>Purpose</p><p>To systematically review the randomized controlled trials (RCTs) concerning the effect of the CIAT in post-stroke patients with aphasia, and to identify the useful components of CIAT in post-stroke aphasia rehabilitation.</p><p>Methods</p><p>A computerized database search was performed through five databases (Pubmed, EMbase, Medline, ScienceDirect and Cochrane library). Cochrane handbook domains were used to evaluate the methodological quality of the included RCTs.</p><p>Results</p><p>Eight RCTs qualified in the inclusion criteria. Inconsistent results were found in comparing the CIAT with conventional therapies without any component from the CIAT based on the results of three RCTs. Five RCTs showed that the CIAT performed equally well as other intensive aphasia therapies, in terms of improving language performance. One RCT showed that therapies embedded with social interaction were likely to enhance the efficacy of the CIAT.</p><p>Conclusion</p><p>CIAT may be useful for improving chronic post-stroke aphasia, however, limited evidence to support its superiority to other aphasia therapies. Massed practice is likely to be a useful component of CIAT, while the role of “constraint” is needed to be further explored. CIAT embedded with social interaction may gain more benefits.</p></div

    Measurement of Blood Protease Kinetic Parameters with Self-Assembled Monolayer Ligand Binding Assays and Label-Free MALDI-TOF MS

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    We report novel ligand binding assay (LBA) surface modalities that permit plasma protease catalytic efficiency (<i>k</i><sub>cat</sub>/<i>k</i><sub>m</sub>) determination by MALDI-TOF MS without the use of liquid chromatography or internal standards such as chemical or metalized labels. Two model LBAs were constructed on planar self-assembled monolayers (SAMs) and used to evaluate the clinically relevant metalloprotease ADAMTS-13 kinetics in plasma. The SAM chemistries were designed to improve biosampling efficiency by minimization of nonspecific adsorption of abundant proteins present at ∼100 000× the concentration of the endogenous enzyme. In the first protocol, in-solution digestion of the ADAMTS-13 substrate (vWF<i>h</i>) was performed with immunoaffinity enrichment of the reaction substrate and product to SAM arrays. The second configuration examined protease <i>k</i><sub>cat</sub>/<i>k</i><sub>m</sub> via a surface digestion modality where different substrates were covalently immobilized to the SAM at controlled surface density for optimized protease screens. The results show the MALDI-TOF MS LBA platforms provide limits of quantitation to ∼1% protease activity (∼60 pM enzyme concentration) in <1 h analysis time, a ∼16× improvement over other MS-based LBA formats. Implementation of a vacuum-sublimed MALDI matrix provided good MALDI-TOF MS intra- and interday repeatability, ∼1.2 and ∼6.6% RSD, respectively. Platform reliability permitted <i>k</i><sub>cat</sub>/<i>k</i><sub>m</sub> determination without internal standards with observed values ∼10× improved versus conventional fluorophoric assays. Application of the assays to 12 clinical plasma samples demonstrated proof-of-concept for clinical applications. Overall, this work demonstrates that rationally designed surface chemistries for MALDI-TOF MS may serve as an alternative, label-free methodology with potential for a wide range of biotechnology applications related to targeted enzyme molecular diagnostics

    Surface Preparation Strategies for Improved Parallelization and Reproducible MALDI-TOF MS Ligand Binding Assays

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    Immunoassays are employed in academia and the healthcare and biotech industries for high-throughput, quantitative screens of biomolecules. We have developed monolayer-based immunoassays for MALDI-TOF MS. To improve parallelization, we adapted the workflow to photolithography-generated arrays. Our work shows Parylene-C coatings provide excellent “solvent pinning” for reagents and biofluids, enabling sensitive MS detection of immobilized components. With a unique MALDI-matrix crystallization technique we show routine interassay RSD <10% at picomolar concentrations and highlight platform compatibility for relative and label-free quantitation applications. Parylene-arrays provide high sample densities and promise screening throughputs exceeding 1000 samples/h with modern liquid-handlers and MALDI-TOF systems

    Top-Down Mass Spectrometry on Tissue Extracts and Biofluids with Isoelectric Focusing and Superficially Porous Silica Liquid Chromatography

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    Top-down mass spectrometry (MS) has emerged as a powerful complement to peptide-based proteomics. Despite advancements, the field has had limited application to clinical proteomics investigations due to the complexity and poor dynamic range of chromatography used to separate intact proteins from tissue and biofluids. To address these limitations, we developed a two-dimensional (2D) chromatography platform that includes isoelectric focusing (IEF) through immobilized pH gradient and superficially porous liquid chromatography (SPLC). Analysis of standard proteins demonstrates compatibility of IEF-SPLC processing and high resolving-power MS analysis with results showing ∼7.0 femtomole detection limits and linear spectral response for proteins fractionated over ∼4 log sample loads. For proteins from heart myofibrils and cerebrospinal fluid (CSF), compared to one-dimensional SPLC-MS, the 2D IEF-SPLC-MS platform resulted in a 5–6× increase in the number of unique monoisotopic masses observed <30 kDa and an ∼4× improved mass range enabling the observation of proteins >200 kDa. In the heart myofibrils, common protein proteoforms observed were associated with phosphorylation of contractile proteins with results showing that quantitative evaluation of their PTM stoichiometry was possible despite differentially modified forms being fractionated into separate p<i>I</i> compartments. In CSF, diverse protein mutations and PTM classes were also observed, including differentially glycosylated protein forms separated to different p<i>I</i>. Results also demonstrate that by the generation of IEF-SPLC protein libraries by fraction collection, the platform enables prospective protein identification and proteoform analysis investigations by complementary top-down and bottom-up strategies. Overall, the 2D platform presented may provide the speed, dynamic range, and detection limits necessary for routine characterization of proteoform-based biomarkers from biofluids and tissues
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