Screen printed electrodes modified with carboxylated multiwall carbon nanotubes for the analysis of hydroquinone and ascorbic acid

Carbon nanotubes (CNT) have demonstrated to be advantageous in electrochemical applications such as in energy storage devices and sensors. The presence of oxygenated carbon species, especially carboxylic acid moieties, together with metallic impurities are identified as chief factors for the catalytic properties of CNTs. The oxygen-containing groups are introduced randomly at the surface of CNTs by strong mineral acid treatment. These factors can be of extreme importance for the construction of biosensors based on carbon nanomaterials. In this study, multiwalled carbon nanotubes (MWCNTs) were chemically shortened and carboxylated by treatment with nitric acid for metal impurities removalusing a method described in the literature, originating MWCNT-COOH. Ethanol suspensions of MWCNT-COOH at different concentrations were used to modify the surfaces of commercially available screen-printed electrodes (SPEs). The SPEs modification with MWCNT-COOH was optimised and it was applied in order to obtain a reproducible electrochemical response. The morphology of the MWCNT-COOH modified SPEs was characterized by Scanning Electron Microscopy. Characterization of the CNT film generated on the surface of the working electrode and stability studies were carried out with potassium hexacyanoferrate. Results are compared with those obtained for commercially available carbon SPE and SPEMWCNT. Effect of solution acidity on the peak current and potential of the substances was studied at pH 3 and 7 where a correlation with the dissociation degree of carboxyl groups at the MWCNTs on the electrode surface occurs. The catalytic properties of the MWCNT-COOH-modified SPEs as well as their analytical advantages as voltammetric detectors are discussed through the analysis of ascorbic acid (AA) and hydroquinone (HQ)

Non-covalent modification of voltammetric SPE sensors

Screen printed electrodes (SPE) are highly attractive as transducers of chemical sensors for the screening of a number of important analytes. The surface modification of these electrodes is easily carried out in order to achieve higher sensitivity. Carbon nanostructures have been extensively used for this purpose, as the number of active sites can be greatly increased. On the other hand, the immobilization of adequate functional groups is usually carried out to increase sensors selectivity through specific interactions between the immobilised chemical moieties and the analyte of interest. Among the techniques used to functionalize electrodes surface, non-covalent modification offer advantages related to the simplicity of the process and the reproducibility of the sensor operation. Recently a dopamine sensor based a perylene tetracarboxylic acid functionalized graphene sheets was developed [1]. In this work, voltammetric response of SPEs modified with CNTs functionalized by noncovalent bond using perylene modified using amino acids such as L-Tryptophan, L-Tyrosine and L-Cysteine is presented. The effect of the concentration ratio of CNT and perylene modified is studied analysing the response of model compounds, such as ascorbic acid and hydroquinone. The performance of these sensors is characterized regarding their catalytic activity

Copy number alterations associated with clinical features in an underrepresented population with breast cancer

As the most incident tumor among women worldwide, breast cancer is a heterogeneous disease. Tremendous efforts have been made to understand how tumor characteristics as histological type, molecular subtype, and tumor microenvironment collectively influence disease diagnosis to treatment, which impact outcomes. Differences between populations and environmental and cultural factors have impacts on the origin and evolution of the disease, as well as the therapeutic challenges that arise due to these factors. We, then, compared copy number variations (CNVs) in mucinous and nonmucinous luminal breast tumors from a Brazilian cohort to investigate major CNV imbalances in mucinous tumors versus non‐mucinous luminal tumors, taking into account their clinical and pathological features.48 breast tumor samples and 48 matched control blood samples from Brazilian women were assessed for CNVs by chromosome microarray. Logistic regression and random forest models were used in order to assess CNVs in chromosomal regions from tumors.CNVs that were identified in chromosomes 1, 5, 8, 17, 19, and 21 classify tumors according to their histological type, ethnicity, disease stage, and familial history.Copy number alterations described in this study provide a better understanding of the landscape of genomic aberrations in mucinous breast cancers that are associated with clinical features.77FAPESP – Fundação de Amparo à Pesquisa Do Estado De São Paulo2013/25683-3; 2015/18830-

Lateral hypothalamic activity indicates hunger and satiety states in humans

Lateral hypothalamic area (LHA) local field potentials (LFPs) were recorded in a Prader–Willi patient undergoing deep brain stimulation (DBS) for obesity. During hunger, exposure to food-related cues induced an increase in beta/ low-gamma activity. In contrast, recordings during satiety were marked by prominent alpha rhythms. Based on these findings, we have delivered alphafrequency DBS prior to and during food intake. Despite reporting an early sensation of fullness, the patient continued to crave food. This suggests that the pattern of activity in LHA may indicate hunger/satiety states in humans but attest to the complexity of conducting neuromodulation studies in obesity

Antitumor potential of the myotoxin BthTX-I from Bothrops jararacussu snake venom: evaluation of cell cycle alterations and death mechanisms induced in tumor cell lines

Abstract\ud \ud Background\ud Phospholipases A2 (PLA2s) are abundant components of snake venoms that have been extensively studied due to their pharmacological and pathophysiological effects on living organisms. This study aimed to assess the antitumor potential of BthTX-I, a basic myotoxic PLA2 isolated from Bothrops jararacussu venom, by evaluating in vitro processes of cytotoxicity, modulation of the cell cycle and induction of apoptosis in human (HL-60 and HepG2) and murine (PC-12 and B16F10) tumor cell lines.\ud \ud \ud Methods\ud The cytotoxic effects of BthTX-I were evaluated on the tumor cell lines HL-60 (promyelocytic leukemia), HepG2 (human hepatocellular carcinoma), PC-12 (murine pheochromocytoma) and B16F10 (murine melanoma) using the MTT method. Flow cytometry technique was used for the analysis of cell cycle alterations and death mechanisms (apoptosis and/or necrosis) induced in tumor cells after treatment with BthTX-I.\ud \ud \ud Results\ud It was observed that BthTX-I was cytotoxic to all evaluated tumor cell lines, reducing their viability in 40 to 50 %. The myotoxin showed modulating effects on the cell cycle of PC-12 and B16F10 cells, promoting delay in the G0/G1 phase. Additionally, flow cytometry analysis indicated cell death mainly by apoptosis. B16F10 was more susceptible to the effects of BthTX-I, with ~40 % of the cells analyzed in apoptosis, followed by HepG2 (~35 %), PC-12 (~25 %) and HL-60 (~4 %).\ud \ud \ud Conclusions\ud These results suggest that BthTX-I presents antitumor properties that may be useful for developing new therapeutic strategies against cancer.The authors would like to thank the financial support provided by the State\ud of São Paulo Research Foundation (FAPESP, grants n. 2010/03243-43 and\ud 2011/23236-4), the Coordination for the Improvement of Higher Education\ud Personnel (CAPES) and the National Council for Scientific and Technological\ud Development (CNPq process n. 476932/2012-2). We are also grateful to\ud Fabiana Rosseto Morais, from FCFRP-USP, for the technical assistance in the\ud flow cytometry analyses. Thanks are also due to the Center for the Study of\ud Venoms and Venomous Animals (CEVAP) of UNESP for enabling the publication\ud of this special collection (CNPq process 469660/2014-7)

Depth of Response in Multiple Myeloma: A Pooled Analysis of Three PETHEMA/GEM Clinical Trials

Purpose To perform a critical analysis on the impact of depth of response in newly diagnosed multiple myeloma (MM). Patients and Methods Data were analyzed from 609 patients who were enrolled in the GEM (Grupo Español de Mieloma) 2000 and GEM2005MENOS65 studies for transplant-eligible MM and the GEM2010MAS65 clinical trial for elderly patients with MM who had minimal residual disease (MRD) assessments 9 months after study enrollment. Median follow-up of the series was 71 months. Results Achievement of complete remission (CR) in the absence of MRD negativity was not associated with prolonged progression-free survival (PFS) and overall survival (OS) compared with near-CR or partial response (median PFS, 27, 27, and 29 months, respectively; median OS, 59, 64, and 65 months, respectively). MRD-negative status was strongly associated with prolonged PFS (median, 63 months; P , .001) and OS (median not reached; P , .001) overall and in subgroups defined by prior transplantation, disease stage, and cytogenetics, with prognostic superiority of MRD negativity versus CR particularly evident in patients with high-risk cytogenetics. Accordingly, Harrell C statistics showed higher discrimination for both PFS and OS in Cox models that included MRD (as opposed to CR) for response assessment. Superior MRD-negative rates after different induction regimens anticipated prolonged PFS. Among 34 MRD-negative patients withMMand a phenotypic pattern of bone marrow involvement similar to monoclonal gammopathy of undetermined significance at diagnosis, the probability of “operational cure” was high; median PFS was 12 years, and the 10-year OS rate was 94%. Conclusion Our results demonstrate that MRD-negative status surpasses the prognostic value of CR achievement for PFS and OS across the disease spectrum, regardless of the type of treatment or patient risk group. MRD negativity should be considered as one of the most relevant end points for transplant-eligible and elderly fit patients with MM