Mechanical ventilation modulates TLR4 and IRAK-3 in a non-infectious, ventilator-induced lung injury model

<p>Abstract</p> <p>Background</p> <p>Previous experimental studies have shown that injurious mechanical ventilation has a direct effect on pulmonary and systemic immune responses. How these responses are propagated or attenuated is a matter of speculation. The goal of this study was to determine the contribution of mechanical ventilation in the regulation of Toll-like receptor (TLR) signaling and interleukin-1 receptor associated kinase-3 (IRAK-3) during experimental ventilator-induced lung injury.</p> <p>Methods</p> <p>Prospective, randomized, controlled animal study using male, healthy adults Sprague-Dawley rats weighing 300-350 g. Animals were anesthetized and randomized to spontaneous breathing and to two different mechanical ventilation strategies for 4 hours: high tidal volume (V_T) (20 ml/kg) and low V_T(6 ml/kg). Histological evaluation, TLR2, TLR4, <it>IRAK3 </it>gene expression, IRAK-3 protein levels, inhibitory kappa B alpha (IκBα), tumor necrosis factor-alpha (<it>TNF-α</it>) and interleukin-6 (<it>IL6</it>) gene expression in the lungs and TNF-α and IL-6 protein serum concentrations were analyzed.</p> <p>Results</p> <p>High V_Tmechanical ventilation for 4 hours was associated with a significant increase of TLR4 but not TLR2, a significant decrease of <it>IRAK3 </it>lung gene expression and protein levels, a significant decrease of IκBα, and a higher lung expression and serum concentrations of pro-inflammatory cytokines.</p> <p>Conclusions</p> <p>The current study supports an interaction between TLR4 and IRAK-3 signaling pathway for the over-expression and release of pro-inflammatory cytokines during ventilator-induced lung injury. Our study also suggests that injurious mechanical ventilation may elicit an immune response that is similar to that observed during infections.</p

Expression and activity profiles of DPP IV/CD26 and NEP/CD10 glycoproteins in the human renal cancer are tumor-type dependent

[Background] Cell-surface glycoproteins play critical roles in cell-to-cell recognition, signal transduction and regulation, thus being crucial in cell proliferation and cancer etiogenesis and development. DPP IV and NEP are ubiquitous glycopeptidases closely linked to tumor pathogenesis and development, and they are used as markers in some cancers. In the present study, the activity and protein and mRNA expression of these glycoproteins were analysed in a subset of clear-cell (CCRCC) and chromophobe (ChRCC) renal cell carcinomas, and in renal oncocytomas (RO).[Methods] Peptidase activities were measured by conventional enzymatic assays with fluorogen-derived substrates. Gene expression was quantitatively determined by qRT-PCR and membrane-bound protein expression and distribution analysis was performed by specific immunostaining.Peer reviewe

Expression and function of human hemokinin-1 in human and guinea pig airways

<p>Abstract</p> <p>Background</p> <p>Human hemokinin-1 (hHK-1) and endokinins are peptides of the tachykinin family encoded by the <it>TAC4 </it>gene. <it>TAC4 </it>and hHK-1 expression as well as effects of hHK-1 in the lung and airways remain however unknown and were explored in this study.</p> <p>Methods</p> <p>RT-PCR analysis was performed on human bronchi to assess expression of tachykinin and tachykinin receptors genes. Enzyme immunoassay was used to quantify hHK-1, and effects of hHK-1 and endokinins on contraction of human and guinea pig airways were then evaluated, as well as the role of hHK-1 on cytokines production by human lung parenchyma or bronchi explants and by lung macrophages.</p> <p>Results</p> <p>In human bronchi, expression of the genes that encode for hHK-1, tachykinin NK₁-and NK₂-receptors was demonstrated. hHK-1 protein was found in supernatants from explants of human bronchi, lung parenchyma and lung macrophages. Exogenous hHK-1 caused a contractile response in human bronchi mainly through the activation of NK₂-receptors, which blockade unmasked a NK₁-receptor involvement, subject to a rapid desensitization. In the guinea pig trachea, hHK-1 caused a concentration-dependant contraction mainly mediated through the activation of NK₁-receptors. Endokinin A/B exerted similar effects to hHK-1 on both human bronchi and guinea pig trachea, whereas endokinins C and D were inactive. hHK-1 had no impact on the production of cytokines by explants of human bronchi or lung parenchyma, or by human lung macrophages.</p> <p>Conclusions</p> <p>We demonstrate endogenous expression of <it>TAC4 </it>in human bronchi, the encoded peptide hHK-1 being expressed and involved in contraction of human and guinea pig airways.</p

Micromechanical Properties of Injection-Molded Starch–Wood Particle Composites

The micromechanical properties of injection molded starch–wood particle composites were investigated as a function of particle content and humidity conditions. The composite materials were characterized by scanning electron microscopy and X-ray diffraction methods. The microhardness of the composites was shown to increase notably with the concentration of the wood particles. In addition,creep behavior under the indenter and temperature dependence were evaluated in terms of the independent contribution of the starch matrix and the wood microparticles to the hardness value. The influence of drying time on the density and weight uptake of the injection-molded composites was highlighted. The results revealed the role of the mechanism of water evaporation, showing that the dependence of water uptake and temperature was greater for the starch–wood composites than for the pure starch sample. Experiments performed during the drying process at 70°C indicated that the wood in the starch composites did not prevent water loss from the samples.Peer reviewe

Crohn's disease Activity: Abdominal Computed Tomography Histopathology Correlation

Purpose: Crohn's disease is a type of inflammatory bowel disease affecting estimated 4 million people worldwide. Therapy stratification of Crohn's disease (CD) is mainly based on the inflammatory activity being assessed by endoscopic biopsy and clinical criteria. Cross-sectional imaging allows for the assessment of structural characteristics of the entire gastrointestinal tract including small bowel loops and may provide potential non-invasive image-based biomarkers for the inflammatory activity of CD. The aim of this study was to explore the predictive value of Computed Tomography-based morphologic patterns for inflammatory activity in CD

The utility of in-bore multiparametric magnetic resonance-guided biopsy in men with negative multiparametric magnetic resonance-ultrasound software-based fusion targeted biopsy.

To evaluate the utility of in-bore multiparametric magnetic resonance-guided biopsy of the prostate (IB) in patients with visible lesion/s and previous negative software-based multiparametric magnetic resonance imaging/ultrasonography fusion-targeted biopsy of the prostate (FTB). We retrospectively analysed prospectively maintained database including consecutive men undergoing IB from March 2013 to October 2017 in 2 European centres expert in this procedure. We selected men with the following criteria: No previous treatment for prostate cancer (CaP), multiparametric magnetic resonance imaging (mpMRI) lesion(s) PIRADS score ≥ 3, FTB showing no clinically significant cancer (csCaP), and subsequent IB. Patient's characteristics, mpMRI findings, biopsy technique, and histopathological results were extracted. The primary outcome was to determine the detection rate of csCaP, defined as any Gleason pattern ≥ 4. A multivariable analysis was performed to identify predictors of positive findings at IB. Fifty-three men were included. Median age was 68 years (interquartile range [IQR] 64-68), median Prostate-Specific Antigen (PSA) was 7.6 ng/ml (IQR 5.2-10.9), and median prostate volume was 59 ml (IQR 44-84). Fifty-six lesions with PIRADS score 3 in 9 cases (16%), 4 in 30 cases (54%), and 5 in 17 cases (30%) were detected. FTB was performed in all cases using a transrectal approach with 3 different platforms (Toshiba, Koelis, and Artemis). Median time between FTB and IB was 3 months (IQR 1-7). A median of 2 cores per lesion were collected with IB (IQR 2-3). No cancer, clinically insignificant and clinically significant cancer were found in 33 (59%), 9 (16%), and 14 (25%) targeted lesions, respectively. Median maximum cancer core length and maximum positive percentage were 9 mm (3-13) and 55% (21%-80%). The only predictor of csCaP on IB was prostate volume (P = 0.026) with an ideal cut-off at 70 ml. One in 4 patients with previous negative FTB, IB was able to detect csCaP. According to this study, IB would be of particularly useful in patients with large glands

Diagnostic accuracy of pulmonary CT Angiography at low tube voltage: Intraindividual comparison of a normal-dose protocol at 120 kVp and a low-dose protocol at 80 kVp using reduced amount of contrast medium in a simulation study

The intraindividual comparison of diagnostic accuracy with normal-dose and simulated low-dose pulmonary CTA protocols revealed no difference under experimental conditions

Use of a Speech-Generating Device for Hospitalized Postoperative Patients with Head and Neck Cancer Experiencing Speechlessness

Purpose/Objectives: To test the feasibility of using a programmable speech-generating device (PSGD) in hospitalized adults with head and neck cancer experiencing speechlessness. Design: Time-series design. Setting: Tertiary care institution, inpatient setting. Sample: 9 female and 12 male postoperative patients (mean age = 62 years) experiencing speechlessness as a result of a surgical intervention to treat head and neck cancer. Methods: Patients participated in a communication intervention that incorporated use of a PSGD during their hospital stay. Data about PSGD use and functionality- and technology-related issues were collected. Satisfaction and usability of the PSGD were rated with the Satisfaction and Usability Instrument. Main Research Variables: Use of, satisfaction with, and usability of the PSGD. Findings: Participants demonstrated significant improvement in ability to use the PSGD over a four-day period for all communication functions assessed. Results indicated that participants were quite satisfied with using the device and considered the technology to be quite important during the postoperative period. PSGD messages generated by participants via the hospital call system were understood by clerks. However, participants admitted to intensive care units experienced issues associated with accessibility of the device. Conclusions: Participants demonstrated proficient and independent use of the PSGD to communicate programmed messages; however, other strategies were necessary to meet their communication needs as the postoperative period progressed. Additional research on technologic communication options and strategies to tailor technology to meet the needs of speechless patients is warranted. Implications for Nursing: PSGDs may offer a more reliable option to facilitate communication between patients and nurses during the postoperative period. Technology should be tailored to meet speechless patients\u27 unique needs as they progress through the rehabilitation process