ERK1/2 is activated in non-small-cell lung cancer and associated with advanced tumours

Activation of the ERK1/2 pathway is involved in malignant transformation both in vitro and in vivo. Little is known about the role of activated ERK1/2 in non-small cell lung cancer (NSCLC). The purpose of this study was to characterise the extent of the activation of ERK1/2 by immunohistochemistry in patients with NSCLC, and to determine the relationship of ERK1/2 activation with clinicopathological variables. Specimens from 111 patients with NSCLC (stages I-IV) were stained for P-ERK. Staining for epidermal growth factor receptor (EGFR) and Ki-67 was also performed. In all, 34% of the tumour specimens showed activation for ERK1/2, while normal lung epithelial tissue was consistently negative. There was a strong statistical correlation between nuclear and cytoplasmic P-ERK staining and advanced stages (P<0.05 and P<0.001, respectively), metastatic hilar or mediastinal lymph nodes (P<0.01, P<0.001), and higher T stages (P<0.01, P<0.001). We did not find correlation of nuclear or cytoplasmic P-ERK staining with either EGFR expression or Ki-67 expression. Total ERK1/2 expression was evaluated with a specific ERK1/2 antibody and showed that P-ERK staining was not due to ERK overexpression but rather to hyperactivation of ERK1/2. Patients with a positive P-ERK cytoplasmic staining had a significant lower survival (P<0.05). However, multivariate analysis did not show significant survival difference. Our study indicates that nuclear and cytoplasmic ERK1/2 activation positively correlates with stage, T and lymph node metastases, and thus, is associated with advanced and aggressive NSCLC tumours

EPAC-lung: pooled analysis of circulating tumour cells in advanced non-small cell lung cancer

Introduction: We assessed the clinical validity of circulating tumour cell (CTC) quantification for prognostication of patients with advanced non-small cell lung cancer (NSCLC) by undertaking a pooled analysis of individual patient data. Methods: Nine European NSCLC CTC centres were asked to provide reported/unreported pseudo-anonymised data for patients with advanced NSCLC who participated in CellSearch CTC studies from January 2003 to March 2017. We used Cox regression models, stratified by centres, to establish the association between CTC count and survival. We assessed the added value of CTCs to prognostic clinicopathological models using likelihood ratio (LR) statistics and c-indices. Results: Seven out of nine eligible centres provided data for 550 patients with prognostic information for overall survival. CTC counts of ≥2 and ≥ 5 per 7·5 mL were associated with reduced progression-free survival (≥2 CTCs: hazard ratio [HR] = 1.72, p &lt; 0·001; ≥5 CTCs: HR = 2.21, p &lt; 0·001) and overall survival (≥2 CTCs: HR = 2·18, p &lt; 0·001; ≥5 CTCs: HR = 2·75, p &lt; 0·001), respectively. Survival prediction was significantly improved by addition of baseline CTC count to LR clinicopathological models (log-transformed CTCs p &lt; 0·001; ≥2 CTCs p &lt; 0·001; ≥5 CTCs p ≤ 0·001 for both survival end-points), whereas moderate improvements were observed with the use of c-index models. There was some evidence of between-centre heterogeneity, especially when examining continuous counts of CTCs. Conclusions: These data confirm CTCs as an independent prognostic indicator of progression-free survival and overall survival in advanced NSCLC and also reveal some evidence of between-centre heterogeneity. CTC count improves prognostication when added to full clinicopathological predictive models

SLAM algorithm applied to robotics assistance for navigation in unknown environments

<p>Abstract</p> <p>Background</p> <p>The combination of robotic tools with assistance technology determines a slightly explored area of applications and advantages for disability or elder people in their daily tasks. Autonomous motorized wheelchair navigation inside an environment, behaviour based control of orthopaedic arms or user's preference learning from a friendly interface are some examples of this new field. In this paper, a Simultaneous Localization and Mapping (SLAM) algorithm is implemented to allow the environmental learning by a mobile robot while its navigation is governed by electromyographic signals. The entire system is part autonomous and part user-decision dependent (semi-autonomous). The environmental learning executed by the SLAM algorithm and the low level behaviour-based reactions of the mobile robot are robotic autonomous tasks, whereas the mobile robot navigation inside an environment is commanded by a Muscle-Computer Interface (MCI).</p> <p>Methods</p> <p>In this paper, a sequential Extended Kalman Filter (EKF) feature-based SLAM algorithm is implemented. The features correspond to lines and corners -concave and convex- of the environment. From the SLAM architecture, a global metric map of the environment is derived. The electromyographic signals that command the robot's movements can be adapted to the patient's disabilities. For mobile robot navigation purposes, five commands were obtained from the MCI: turn to the left, turn to the right, stop, start and exit. A kinematic controller to control the mobile robot was implemented. A low level behavior strategy was also implemented to avoid robot's collisions with the environment and moving agents.</p> <p>Results</p> <p>The entire system was tested in a population of seven volunteers: three elder, two below-elbow amputees and two young normally limbed patients. The experiments were performed within a closed low dynamic environment. Subjects took an average time of 35 minutes to navigate the environment and to learn how to use the MCI. The SLAM results have shown a consistent reconstruction of the environment. The obtained map was stored inside the Muscle-Computer Interface.</p> <p>Conclusions</p> <p>The integration of a highly demanding processing algorithm (SLAM) with a MCI and the communication between both in real time have shown to be consistent and successful. The metric map generated by the mobile robot would allow possible future autonomous navigation without direct control of the user, whose function could be relegated to choose robot destinations. Also, the mobile robot shares the same kinematic model of a motorized wheelchair. This advantage can be exploited for wheelchair autonomous navigation.</p

Study protocol for the multicentre cohorts of Zika virus infection in pregnant women, infants, and acute clinical cases in Latin America and the Caribbean: the ZIKAlliance consortium.

BACKGROUND: The European Commission (EC) Horizon 2020 (H2020)-funded ZIKAlliance Consortium designed a multicentre study including pregnant women (PW), children (CH) and natural history (NH) cohorts. Clinical sites were selected over a wide geographic range within Latin America and the Caribbean, taking into account the dynamic course of the ZIKV epidemic. METHODS: Recruitment to the PW cohort will take place in antenatal care clinics. PW will be enrolled regardless of symptoms and followed over the course of pregnancy, approximately every 4 weeks. PW will be revisited at delivery (or after miscarriage/abortion) to assess birth outcomes, including microcephaly and other congenital abnormalities according to the evolving definition of congenital Zika syndrome (CZS). After birth, children will be followed for 2 years in the CH cohort. Follow-up visits are scheduled at ages 1-3, 4-6, 12, and 24 months to assess neurocognitive and developmental milestones. In addition, a NH cohort for the characterization of symptomatic rash/fever illness was designed, including follow-up to capture persisting health problems. Blood, urine, and other biological materials will be collected, and tested for ZIKV and other relevant arboviral diseases (dengue, chikungunya, yellow fever) using RT-PCR or serological methods. A virtual, decentralized biobank will be created. Reciprocal clinical monitoring has been established between partner sites. Substudies of ZIKV seroprevalence, transmission clustering, disabilities and health economics, viral kinetics, the potential role of antibody enhancement, and co-infections will be linked to the cohort studies. DISCUSSION: Results of these large cohort studies will provide better risk estimates for birth defects and other developmental abnormalities associated with ZIKV infection including possible co-factors for the variability of risk estimates between other countries and regions. Additional outcomes include incidence and transmission estimates of ZIKV during and after pregnancy, characterization of short and long-term clinical course following infection and viral kinetics of ZIKV. STUDY REGISTRATIONS: clinicaltrials.gov NCT03188731 (PW cohort), June 15, 2017; clinicaltrials.gov NCT03393286 (CH cohort), January 8, 2018; clinicaltrials.gov NCT03204409 (NH cohort), July 2, 2017

Identidad, territorio y promocion de la salud

El presente trabajo se enmarca dentro de un proyecto de extensión que se desarrolla durante el 2012, acreditado y financiado por la UNLP, denominado “Identidad, territorio y salud. Construcción de identidades colectivas y transferencia institucional en torno al primer nivel de atención en el Barrio Federal de Ensenada”. Este barrio cuenta con una población aproximada de 480 habitantes y está ubicado en la zona de Gran La Plata, Pcia. de Buenos Aires. El objetivo del trabajo consiste en fortalecer la apropiación y promoción de la salud colectiva, entendida ésta como un proceso construido históricamente por cada sociedad, que se crea y recrea en todos los aspectos de la vida cotidiana de los sujetos. La propuesta metodológica se sustenta en un proceso dialógico entre los sujetos involucrados: vecinos de barrio Federal y los integrantes del equipo del trabajo extensionista. Desde este marco (pedagógico horizontal) desarrollamos actividades grupales de carácter lúdico-recreativo, que a primera vista no aparentan tener una relación con el proceso salud-enfermedad, propio del imaginario social, pero implícitamente, estarían abarcando y generando cambios en el significado asignado del mismo. Partimos de la idea de fortalecer el sentirse bien, no en el estricto sentido biológico, sino como aquella capacidad para crear momentos y actividades con pares en un mismo territorio y generando lazos entre vecinos y entre éstos y la institución de salud del barrio. De este modo, las actividades se desarrollan principalmente en la sala de espera de la unidad sanitaria y en la plaza circundante. Hemos definido tres líneas de trabajo: artístico, narrativo-plástico y de producción audiovisual y medioambiente. En los encuentros se trabaja con diferentes recursos, propios de disciplinas como música, plástica, teatro, danza, escultura, circo, artes audiovisuales, literatura, entre otros. El carácter interdisciplinario de este proyecto, conformado por estudiantes de las carreras de Trabajo Social y Antropología, un artista escultor y dirigido y coordinado por docentes y graduados de las Facultades de Ciencias Medicas, Humanidades y Ciencias de la Educación y Trabajo Social, enriquece las perspectivas de abordaje y fortalece la visión social, integral y colectiva de la salud. Consolidar acciones identitarias del barrio, generadas a partir de la promoción de la salud, es el principal desafío a alcanzar

Characterization of Italian honeys (Marche Region) on the basis of their mineral content and some typical quality parameters

<p>Abstract</p> <p>Background</p> <p>The characterization of three types of Marche (Italy) honeys (Acacia, Multifloral, Honeydew) was carried out on the basis of the their quality parameters (pH, sugar content, humidity) and mineral content (Na, K, Ca, Mg, Cu, Fe, and Mn). Pattern recognition methods such as principal components analysis (PCA) and linear discriminant analysis (LDA) were performed in order to classify honey samples whose botanical origins were different, and identify the most discriminant parameters. Lastly, using ANOVA and correlations for all parameters, significant differences between diverse types of honey were examined.</p> <p>Results</p> <p>Most of the samples' water content showed good maturity (98%) whilst pH values were in the range 3.50 – 4.21 confirming the good quality of the honeys analysed. Potassium was quantitatively the most relevant mineral (mean = 643 ppm), accounting for 79% of the total mineral content. The Ca, Na and Mg contents account for 14, 3 and 3% of the total mineral content respectively, while other minerals (Cu, Mn, Fe) were present at very low levels. PCA explained 75% or more of the variance with the first two PC variables. The variables with higher discrimination power according to the multivariate statistical procedure were Mg and pH. On the other hand, all samples of acacia and honeydew, and more than 90% of samples of multifloral type have been correctly classified using the LDA. ANOVA shows significant differences between diverse floral origins for all variables except sugar, moisture and Fe.</p> <p>Conclusion</p> <p>In general, the analytical results obtained for the Marche honeys indicate the products' high quality. The determination of physicochemical parameters and mineral content in combination with modern statistical techniques can be a useful tool for honey classification.</p

Inadequate control of thyroid hormones sensitizes to hepatocarcinogenesis and unhealthy aging

An inverse correlation between thyroid hormone levels and longevity has been reported in several species and reduced thyroid hormone levels have been proposed as a biomarker for healthy aging and metabolic fitness. However, hypothyroidism is a medical condition associated with compromised health and reduced life expectancy. Herein, we show, using wild-type and the Pax8 ablated model of hypothyroidism in mice, that hyperthyroidism and severe hypothyroidism are associated with an overall unhealthy status and shorter lifespan. Mild hypothyroid Pax8 +/- mice were heavier and displayed insulin resistance, hepatic steatosis and increased prevalence of liver cancer yet had normal lifespan. These pathophysiological conditions were precipitated by hepatic mitochondrial dysfunction and oxidative damage accumulation. These findings indicate that individuals carrying mutations on PAX8 may be susceptible to develop liver cancer and/or diabetes and raise concerns regarding the development of interventions aiming to modulate thyroid hormones to promote healthy aging or lifespan in mammals

Cancer Genes Hypermethylated in Human Embryonic Stem Cells

Developmental genes are silenced in embryonic stem cells by a bivalent histone-based chromatin mark. It has been proposed that this mark also confers a predisposition to aberrant DNA promoter hypermethylation of tumor suppressor genes (TSGs) in cancer. We report here that silencing of a significant proportion of these TSGs in human embryonic and adult stem cells is associated with promoter DNA hypermethylation. Our results indicate a role for DNA methylation in the control of gene expression in human stem cells and suggest that, for genes repressed by promoter hypermethylation in stem cells in vivo, the aberrant process in cancer could be understood as a defect in establishing an unmethylated promoter during differentiation, rather than as an anomalous process of de novo hypermethylation