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About the destruction involving (mini)materials: Deterioration strategies, impacting on aspects, enviromentally friendly impacts.
BACKGROUND Activation of the PI3K/AKT/mTOR pathway through loss of phosphatase and tensin homolog (PTEN) occurs in approximately 50% of patients with metastatic castration-resistant prostate cancer (mCRPC). Recent evidence suggests that combined inhibition of the androgen receptor (AR) and AKT may be beneficial in mCRPC with PTEN loss. PATIENTS AND METHODS mCRPC patients who previously failed abiraterone and/or enzalutamide, received escalating doses of AZD5363 (capivasertib) starting at 320 mg twice daily (b.i.d.) given 4 days on and 3 days off, in combination with enzalutamide 160 mg daily. The co-primary endpoints were safety/tolerability and determining the maximum tolerated dose and recommended phase II dose; pharmacokinetics, antitumour activity, and exploratory biomarker analysis were also evaluated. RESULTS Sixteen patients were enrolled, 15 received study treatment and 13 were assessable for dose-limiting toxicities (DLTs). Patients were treated at 320, 400, and 480 mg b.i.d. dose levels of capivasertib. The recommended phase II dose identified for capivasertib was 400 mg b.i.d. with 1/6 patients experiencing a DLT (maculopapular rash) at this level. The most common grade ≥3 adverse events were hyperglycemia (26.7%) and rash (20%). Concomitant administration of enzalutamide significantly decreased plasma exposure of capivasertib, though this did not appear to impact pharmacodynamics. Three patients met the criteria for response (defined as prostate-specific antigen decline ≥50%, circulating tumour cell conversion, and/or radiological response). Responses were seen in patients with PTEN loss or activating mutations in AKT, low or absent AR-V7 expression, as well as those with an increase in phosphorylated extracellular signal-regulated kinase (pERK) in post-exposure samples. CONCLUSIONS The combination of capivasertib and enzalutamide is tolerable and has antitumour activity, with all responding patients harbouring aberrations in the PI3K/AKT/mTOR pathway. CLINICAL TRIAL NUMBER NCT02525068. RESEARCH QUESTION Repeated implantation failure (RIF) is a major limiting factor in assisted reproductive technology. As miR-145 (also known as MIR145) is up-regulated in patients with RIF, this study asked, what is the molecular mechanism underlying the affect of miR-145 on embryo implantation in RIF? DESIGN Ishikawa cells were infected with lentivirus containing miR-145 and miR-145 NC. Massive transcriptome data analyses and bioinformatics analysis were used to search for a potential candidate target of miR-145. The expression of the potential candidate target was detected using quantitative reverse transcription PCR (qRT-PCR) and western blotting in the Ishikawa cells infected with lentivirus containing miR-145 or miR-145 NC. Subsequently, a dual luciferase reporter assay was performed to verify whether the potential candidate target was a novel direct target of miR-145. In addition, expression of PAI-1 (plasminogen activator inhibitor 1, also known as SERPINE1) in endometrial tissue from women with RIF and in control endometrial tissue was examined using qRT-PCR and immunohistochemistry. RESULTS Based on massive transcriptome data analyses and bioinformatics analysis, PAI-1 was regarded as a potential candidate target of miR-145. miR-145 overexpression was achieved in Ishikawa cells. PAI-1 was confirmed as a direct target of miR-145 by bioinformatic analysis, qRT-PCR, western blotting and dual luciferase reporter assay. Further, results from the clinical sample indicated that at both the mRNA and protein levels, PAI-1 expression was down-regulated in endometrial tissues from women with RIF compared with control group women, and this was negatively related to miR-145 expression. CONCLUSIONS The study results suggests that miR-145 may target and down-regulate PAI-1 expression and influence embryo implantation in women with RIF who are undergoing IVF. OBJECTIVE To adapt the ICU Mobility Scale (IMS) to the area of intensive care units (ICU) in Spain and to evaluate the metric properties of the Spanish version of the IMS (IMS-Es). METHOD Descriptive metric study developed in two phases. Phase 1, adaptation to Spanish of the IMS by a team of nurses and physiotherapists (translation, pilot, backtranslation and agreement). Phase 2, analysis of metric properties (convergent, divergent and predictive validity, interobserver reliability, sensitivity and minimum important difference) of the IMS-Es. Patient characteristics (Barthel, Charlson, BMI, sex), sedation/agitation level (RASS), ICU and hospital stays, survival, quality of life (SF-12), muscle weakness (MRC-SS) and mobility (IMS-Es) were recorded in the patients of the MOviPre national multicentre study. RESULTS After obtaining the IMS-Es, it was implemented in 645 patients from 80 Spanish ICUs between April and June 2017. Convergent validity moderate correlation between IMS-Es and MRC-SS (r=.389; P less thenence 2-point difference cut-off point, 91.1% sensitivity and 100.0% specificity. CONCLUSIONS The IMS-Es is useful, valid and reliable for implementation by ICU nurses and physiotherapists in assessing the mobility of critical patients. OBJECTIVE To analyze the percentage of collagen fibers and mast cell density in the left ventricular myocardium of autopsied patients with and without hypertensive heart disease. METHODS Thirty fragments of left ventricular myocardium were obtained from individuals autopsied at the Clinical Hospital of the Federal University of Triângulo Mineiro (UFTM) in the period from 1987 to 2017. Individuals were divided into two groups those with hypertensive heart disease (HD) and those with no heart disease (ND). Subjects were also assessed according to age, gender and race (white and non-white). read more Collagen fibers were quantified by computed morphometry and mast cell density was assessed by immunohistochemical methods. RESULTS There were significantly more collagen fibers in the left ventricle in the HD group than in the ND group (p less then 0.001). Mast cell density was significantly higher in the left ventricle of individuals with HD immunolabeled with anti-chymase and anti-tryptase antibodies (p=0.02) and also of those immunolabeled only with anti-tryptase antibodies (p=0.
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