Mutant KRAS promotes malignant pleural effusion formation

Malignant pleural effusion (MPE) is the lethal consequence of various human cancers metastatic to the pleural cavity. However, the mechanisms responsible for the development of MPE are still obscure. Here we show that mutant KRAS is important for MPE induction in mice. Pleural disseminated, mutant KRAS bearing tumour cells upregulate and systemically release chemokine ligand 2 (CCL2) into the bloodstream to mobilize myeloid cells from the host bone marrow to the pleural space via the spleen. These cells promote MPE formation, as indicated by splenectomy and splenocyte restoration experiments. In addition, KRAS mutations are frequently detected in human MPE and cell lines isolated thereof, but are often lost during automated analyses, as indicated by manual versus automated examination of Sanger sequencing traces. Finally, the novel KRAS inhibitor deltarasin and a monoclonal antibody directed against CCL2 are equally effective against an experimental mouse model of MPE, a result that holds promise for future efficient therapies against the human condition

Comparison of the In Vitro and In Vivo Electrochemical Performance of Bionic Electrodes

The electrochemical performance of platinum electrodes was assessed in vitro and in vivo to determine the impact of electrode implantation and the relevance of in vitro testing in predicting in vivo behaviour. A significant change in electrochemical response was seen after electrode polarisation. As a result, initial in vitro measurements were poor predictors of subsequent measurements performed in vitro or in vivo. Charge storage capacity and charge density measurements from initial voltammetric measurements were not correlated with subsequent measurements. Electrode implantation also affected the electrochemical impedance. The typically reported impedance at 1 kHz was a very poor predictor of electrode performance. Lower frequencies were significantly more dependent on electrode properties, while higher frequencies were dependent on solution properties. Stronger correlations in impedance at low frequencies were seen between in vitro and in vivo measurements after electrode activation had occurred. Implanting the electrode increased the resistance of the electrochemical circuit, with bone having a higher resistivity than soft tissue. In contrast, protein fouling and fibrous tissue formation had a minimal impact on electrochemical response. In vivo electrochemical measurements also typically use a quasi-reference electrode, may operate in a 2-electrode system, and suffer from uncompensated resistance. The impact of these experimental conditions on electrochemical performance and the relevance of in vitro electrode assessment is discussed. Recommended in vitro testing protocols for assessing bionic electrodes are presented

Development of a safe dexamethasone-eluting electrode array for cochlear implantation

Objectives: Cochlear implantation can result in trauma leading to increased tissue response and loss of residual hearing. A single intratympanic application of the corticosteroid dexamethasone is sometimes used clinically during surgery to combat the potential effect of trauma on residual hearing. This project looked at the safety and efficacy of dexamethasone eluted from an intracochlear array in vivo. Methods: Three trials were conducted using normal hearing adult guinea pigs implanted with successive iterations of dexamethasone-eluting (DX1, DX2, and DX3) or non-eluting (control) intracochlear electrode arrays. The experimental period for each animal was 90 days during which hearing tests were performed at multiple time points. Results: There was no significant difference between matched control array and dexamethasone array groups in terms of spiral ganglion neuron density, organ of Corti condition, or fibrosis and ossification. A cochleostomy seal was present in all implanted cochleae. There were no differences in the degree of hearing threshold shifts between DX1 and DX3 and their respective control arrays. Cochleae implanted with DX2 arrays showed less hearing loss and marginally better spiral ganglion neuron survival than their control array counterparts. Post-explant inspection of the DX2 and DX3 arrays revealed a difference in pore density following dexamethasone elution. Conclusion: The dexamethasone doses used were safe in the guinea pig cochlea. Dexamethasone did not inhibit formation of a cochleostomy seal. The level of hearing protection afforded by dexamethasone eluting from an intracochlear array may depend upon the degree of elution and level of trauma inflicted.10 page(s

Her-2 protein expression, cellular localization, and gene amplification in colorectal carcinoma

This study was sought to evaluate the relationship between Her-2 protein expression, cellular localization, gene amplification, and other clinicopathologic parameters in colorectal carcinomas. Her-2 protein expression and gene amplification were assessed in paraffin sections from 106 primary colorectal adenocarcinoma cases using immunohistochemistry and fluorescence in situ hybridization. Both membranous and cytoplasmic immunostaining was evaluated. The results were correlated with each other and with tumor grade, stage, and overall survival. Membranous and cytoplasmic protein expression was identified in 6 (5.6%) and 13 (12.26%) cases, respectively. Gene amplification was detected in 4 (3.7%) cases. There was a high concordance between membranous protein expression and gene amplification (kappa = 0.791). No apparent association with any of the clinicopathologic parameters was identified. Membranous Her-2 protein expression and gene amplification are encountered in a small subset of colorectal carcinomas and are highly concordant events. Cytoplasmic protein expression might be either artifactual or it might represent a cross-reacting protein or a precursor form of the mature protein

Solution processable tungsten polyoxometalate as highly effective cathode interlayer for improved efficiency and stability polymer solar cells

We report for the first time the use of a water-soluble, tungsten polyoxometalate H3PW12O40 (PW12-POM) as an efficient cathode interlayer incorporated into poly(3-hexylthiophene):[6,6]- phenyl-C61-butyric acid methyl ester (P3HT:PCBM-61) polymer solar cells. The short circuit photocurrent density of the PW12-POM modified device is enhanced by ∼40% the open circuit voltage increases from 0.61 V to 0.65 V and the fill factor from 0.36 to 0.41, resulting to a power conversion efficiency enhancement of ∼70% (from 1.57% for the reference to 2.7% for the PW12-POM modified device). The improvement is attributed to enhanced electron transfer/extraction at the PW12-POM/Al interface as a result of the favorable interfacial energy level alignment and possible enhancement of the local electric field due to the nanoscale morphology of the PW12-POM layer, as evidenced by AFM measurements. A reduced degradation rate was measured for PW12-POM modified devices stored in dark and measured in ambient conditions. Taking into account the advantageous solution processability of PW12-POM, the large increase in the device efficiency and the improvement of their stability, we manifest that PW12-POM has highly desirable properties in order to be embedded as cathode interlayer in organic photovoltaic cells.</p

The Polyphenolic Composition of Extracts Derived from Different Greek Extra Virgin Olive Oils Is Correlated with Their Antioxidant Potency

Olive oil possesses a predominant role in the diet of countries around the Mediterranean basin, whereas it is a known constituent of several sectors of human culture. The polyphenolic composition of olive oil seems to be a key factor in its beneficial biological properties. Based on the above, the aim of this study was to correlate the polyphenolic composition of five extracts derived from a Greek olive oil variety with their antioxidant potency and antimutagenic activities in vitro with chemical-based techniques and cell culture-based assays. According to the results obtained, the polyphenol samples with higher concentration of hydroxytyrosol (HT) were more potent in antioxidant and antimutagenic activity in vitro, as indicated by their ability to scavenge ABTS⋅+ radical and to protect the strand of plasmid DNA from free radical-induced breaking compared to the corresponding samples with higher levels of tyrosol (T) and its derivatives. However, this observation was not evident in the cell culture model (i.e., the HeLa cervical cancer cell line) to which the tested extracts were administered. Specifically, the T-rich extracts more effectively increased endogenous GSH levels measured by flow cytometry than did the HT-rich compounds. Also, olive oil compounds contributed variously to the expression of genes implicated in the cell antioxidant machinery, as indicated by quantitative PCR. Therefore, the relationship between structure and function in redox regulation is complex and merits the combination of tests. Given that factors like the production and storage regimen of the plants are major determinants of the composition of the generated extracts, we propose that specific conditions should be adopted in order to achieve their maximum biological activity. These results followed by others in the same direction could provide a solid basis for the production of functional foods enriched in olive oil extracts with potential antioxidant action in vivo

Nanostructured metal oxides as cathode interfacial layers for hybrid-polymer electronic devices

We report the use of nanostructured metal oxides as cathode interfacial layers for improved performance hybrid polymer electronic devices such as light-emitting diodes (PLEDs) and solar cells. In particular, we employ a stoichiometric (WO3) and a partially reduced tungsten metal oxide (WOx) (x&lt;3), both deposited as very thin layers between an aluminum (Al) cathode and the active polymer layer in hybrid PLEDs and achieve improved PLED device performance reflected as an increase in the current density and luminance and a reduction of the operating voltage. On the other hand, we investigate the use of a stoichiometric tungsten oxide layer as a thin cathode interfacial layer in hybrid polymer photovoltaic cells (Hy-PVs). We demonstrate improved photovoltaic cell performance, primarily as a result of the substantial increase in the short-circuit photocurrent. The improved PLED device characteristics are attributed to enhanced electron injection that primarily results from the lowering of the effective interfacial barrier, as evidenced by photovoltaic open circuit voltage measurements, and improved electron transfer. On the other hand, the observed improvement in the hybrid solar cell performance is primarily attributed to its enhanced internal quantum efficiency, most likely due to the improved electron transport and extraction at the active layer/WO3/Al interface and the reduction of the corresponding contact series resistance. Correlation between the metal oxide surface morphology and the device performance is also investigated and will be discussed

Vulnerability variables among octogenerian myeloma patients: a single-center analysis of 110 patients

In the era of an aging population, an increasing number of patients are diagnosed with multiple myeloma at an age of ≥80. The frailty of this population as a result of coexisting comorbidities and age-related organ impairment is a significant management challenge. The aim of our study was to analyze the disease characteristics, frailty scores and toxicity profile in relation to patient outcomes. Among 827 consecutive, newly diagnosed, symptomatic patients treated since 01 January 2000, we analyzed the characteristics and outcomes of the 110 who were ≥80. Median survival was 21 months, and early mortality within 2 months from diagnosis was 20%. Several factors were associated with inferior survival, whereas in the multivariate analysis, estimated glomerular filtration rate (eGFR) &amp;lt; 30 ml/min/1.73m 2 and LDH ≥250 IU/L were independently associated with poor overall survival. These patients are a distinct frail subset of the general myeloma population who require individualized approach. © 2019, © 2019 Informa UK Limited, trading as Taylor &amp; Francis Group