Identification of prefoldin amplification (1q23.3-q24.1) in bladder cancer using comparative genomic hybridization (CGH) arrays of urinary DNA

Array-CGH represents a comprehensive tool to discover genomic disease alterations that could potentially be applied to body fluids. In this report, we aimed at applying array-CGH to urinary samples to characterize bladder cancer. Methods: Urinary DNA from bladder cancer patients and controls were hybridized on 44K oligonucleotide arrays. Validation analyses of identified regions and candidates included fluorescent in situ hybridization (FISH) and immunohistochemistry in an independent set of bladder tumors spotted on custom-made tissue arrays (n = 181). Results: Quality control of array-CGH provided high reproducibility in dilution experiments and when comparing reference pools. The most frequent genomic alterations (minimal recurrent regions) among bladder cancer urinary specimens included gains at 1q and 5p, and losses at 10p and 11p. Supervised hierarchical clustering identified the gain at 1q23.3-q24.1 significantly correlated to stage (p = 0.011), and grade (p = 0.002). The amplification and overexpression of Prefoldin (PFND2), a selected candidate mapping to 1q23.3-q24.1, correlated to increasing stage and tumor grade by means of custom-designed and optimized FISH (p = 0.013 and p = 0.023, respectively), and immunohistochemistry (p ≤0.0005 and p = 0.011, respectively), in an independent set of bladder tumors included in tissue arrays. Moreover, PFND2 overexpression was significantly associated with poor disease-specific survival (p ≤0.0005). PFND2 was amplified and overexpressed in bladder tumors belonging to patients providing urinary specimens where 1q23.3q24.1 amplification was detected by array-CGH. Conclusions: Genomic profiles of urinary DNA mirrowed bladder tumors. Molecular profiling of urinary DNA using array-CGH contributed to further characterize genomic alterations involved in bladder cancer progression. PFND2 was identified as a tumor stratification and clinical outcome prognostic biomarker for bladder cancer patientsSupported by grants (SAF2009-13035 and SAF2012-40206) from the Spanish Ministry of Education and Culture (to Dr Sánchez-Carbayo). Virginia López is recipient of a predoctoral award from the Spanish Ministry of Education and Cultur

Virtualization of assessment instruments for activities outside the classroom: questionnaires en route during visits to companies in the chemical sector

En el proyecto desarrollado se ha buscado la implementación de herramientas m-learning que permitan la virtualización del proceso de evaluación de las competencias adquiridas por los estudiantes de Grado en las actividades realizadas fuera del aula, específicamente, visitas a empresas del sector químico. Gracias a este proyecto se ha pretendido sustituir la herramienta habitual de evaluación para este tipo de actividad (redacción de una memoria) por un instrumento interactivo tipo aplicación móvil –smartphones o tablets-. Esta virtualización permite al estudiante completar una evaluación tipo test una vez finalizada la actividad docente, aprovechando el tiempo del desplazamiento desde la planta industrial visitada hasta el punto de origen. Dos aplicaciones informáticas han sido evaluadas como soporte de las potenciales herramientas de evaluación (Kahoot y iSpringSuite), logrando alcanzar los objetivos propuestos en el proyecto.In the developed project, the implementation of m-learning tools that allow the virtualization of the evaluation process of the competences acquired by the students of Degree in the activities carried out outside the classroom, specifically, visits to companies in the chemical sector. Thanks to this project, it has been tried to replace the usual evaluation tool for this type of activity (writing a report) with an interactive instrument such as a mobile application -smartphones or tablets-. This virtualization allows the student to complete a test type evaluation once the teaching activity has finished, taking advantage of the time of the trip from the industrial plant visited to the point of origin. Two computer applications have been evaluated as support for the potential assessment tools (Kahoot and iSpringSuite), achieving the objectives proposed in the project

Challenges and Opportunities to Scale Up Cardiovascular Disease Secondary Prevention in Latin America and the Caribbean.

In the Americas, CVD represents about 38% of noncommunicable disease deaths. A roadmap for secondary prevention in Latin America and the Caribbean is warranted. Simple and practical guidelines should be developed and implemented. PAHO proposes a realistic and efficient prevention coalition plan in Latin America to fight CVD. The inclusion of the health system through health workers is highly recommended for a successful nationwide preventive program

Integrated molecular signaling involving mitochondrial dysfunction and alteration of cell metabolism induced by tyrosine kinase inhibitors in cancer

Cancer cells have unlimited replicative potential, insensitivity to growth-inhibitory signals, evasion of apoptosis, cellular stress, and sustained angiogenesis, invasiveness and metastatic potential. Cancer cells adequately adapt cell metabolism and integrate several intracellular and redox signaling to promote cell survival in an inflammatory and hypoxic microenvironment in order to maintain/expand tumor phenotype. The administration of tyrosine kinase inhibitor (TKI) constitutes the recommended therapeutic strategy in different malignancies at advanced stages. There are important interrelationships between cell stress, redox status, mitochondrial function, metabolism and cellular signaling pathways leading to cell survival/death. The induction of apoptosis and cell cycle arrest widely related to the antitumoral properties of TKIs result from tightly controlled events involving different cellular compartments and signaling pathways. The aim of the present review is to update the most relevant studies dealing with the impact of TKI treatment on cell function. The induction of endoplasmic reticulum (ER) stress and Ca2+ disturbances, leading to alteration of mitochondrial function, redox status and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) signaling pathways that involve cell metabolism reprogramming in cancer cells will be covered. Emphasis will be given to studies that identify key components of the integrated molecular pattern including receptor tyrosine kinase (RTK) downstream signaling, cell death and mitochondria-related events that appear to be involved in the resistance of cancer cells to TKI treatments.This study was funded by Institute of Health Carlos III (ISCiii) (PI16/00090, PI19/00838 and PI19/01266), Spanish Ministry of Economy and Competitiveness (BFU2016-80006-P), Andalusian Ministry of Economy, Innovation, Science and Employment (BIO-216 and CTS-6264), Andalusian Ministry of Equality, Health and Social Policies (PI-0198-2016) and Valencian Ministry of Education, Culture and Sports (PROMETEO/2019/027). P de la C-O was supported by FPU predoctoral fellowship (FPU17/00026) from Spanish Ministry of Education, Culture and Sports. E N-V was supported by the the predoctoral i-PFIS IIS-enterprise contract in science and technologies in health (IFI18/00014) from ISCiii. We thank the Biomedical Research Network Center for Cardiovascular Diseases (CIBERcv), and the Biomedical Research Network Center for Liver and Digestive Diseases (CIBERehd) founded by the ISCiii and co-financed by European Regional Development Fund (ERDF) "A way to achieve Europe" for their financial support

Trophic ecology of Gymnodactylus geckoides Spix, 1825 (Squamata, Phyllodactylidae) from Caatinga, Northeastern Brazil

The diet of lizards is mainly composed of arthropods. It can be affected by biotic and abiotic factors, which influence the energy supply provided by the composition of the animal´s diet. The richness and abundance of many arthropod species can be influenced by environmental seasonality, especially in the Caatinga ecoregion, due to the rainfall regimes. The present study aims to describe aspects of the seasonal and morphological variation in the lizard Gymnodactylus geckoides diet and their energy content. We collected 157 individuals (63 females, 68 males, and 26 juveniles) at the Catimbau National Park, Northeastern Brazil, of which 72 were analyzed for the dry season and 59 for the rainy season. Our data indicates Isoptera to be the most common prey in G. geckoides’s diet. Energy content, prey number was higher in the dry season, whereas prey volume and glycogen content increased in the rainy season. Proteins and lipids did not show marked differences. The present study represents the first effort to understand variations in G. geckoide’s trophic ecology, indicating that this specie presents a wide variation in their diet, especially when considering seasonal factors, revealing their needs and restrictions according to prey availability and environmental conditions

Chronic virus infections supress atopy but not asthma in a set of children from a large latin american city: a cross-section study

<p>Abstract</p> <p>Background</p> <p>The prevalence of allergic diseases has increased over recent decades in affluent countries, but remains low in rural populations and some non-affluent countries. An explanation for these trends is that increased exposure to infections may provide protection against the development of allergy. In this work we investigated the association between exposure to viral infections in children living in urban Brazil and the prevalence of atopy and asthma.</p> <p>Methods</p> <p>School age children living in poor neighborhoods in the city of Salvador were studied. Data on asthma symptoms and relevant risk factors were obtained by questionnaire. Skin prick tests (SPTs) were performed to seven aeroallergens, and specific IgE was measured to four of these. Viral infections were determined by the presence of specific IgG in serum to Herpes simplex (HSV), Herpes zoster (HZV), Epstein-Barr (EBV), and Hepatitis A (HAV) viruses.</p> <p>Results</p> <p>A total of 644 (49.7%) children had at least one allergen-specific IgE> 0.35 kU/L and 489 (37.7%) had specific IgE> 0.70 kU/L. A total of 391 (30.2%) children were skin test positive (SPT+), and 295 (22.8%) children were asthmatic. The seroprevalence of viral infections was 88.9% for EBV, 55.4% for HSV, 45.5% for VZV and 17.5% for HAV. Negative associations were observed between SPT+ and HSV (OR = 0.64, CI = 0.51, 0.82) and EBV (OR = 0.63, CI = 0.44, 0.89) infections, but no associations were seen between viral infections and the presence of allergen-specific IgE or asthma.</p> <p>Conclusion</p> <p>These data do not support previous data showing a protective effect of HAV against atopy, but did show inverse associations between SPT+ (but not specific IgE+) and infections with HSV and EBV. These findings suggest that different viral infections may protect against SPT+ in different settings and may indicate an immunoregulatory role of such infections on immediate hypersensitivity responses. The data provide no support for a protective effect of viral infections against asthma in this population.</p

La carta de Jerusalén: un nuevo paradigma en el cuidado de los niños y adolescentes alérgicos en las escuelas de Latinoamérica

De acuerdo con la Organización Mundial de la Salud, las enfermedades alérgicas ocupan el sexto lugar entre las enfermedades infantiles y representan un tercio de las enfermedades crónicas en los niños. En 1 de cada 5 niños, la enfermedad alérgica se manifiesta en la edad escolar

Dissociation between skin test reactivity and anti-aeroallergen IgE: Determinants among urban Brazilian children.

BACKGROUND: The dissociation between specific IgE and skin prick test reactivity to aeroallergens, a common finding in populations living in low and middle-income countries, has important implications for the diagnosis and treatment of allergic diseases. Few studies have investigated the determinants of this dissociation. In the present study, we explored potential factors explaining this dissociation in children living in an urban area of Northeast Brazil, focusing in particular on factors associated with poor hygiene. METHODS: Of 1445 children from low income communities, investigated for risk factors of allergies, we studied 481 with specific IgE antibodies to any of Blomia tropicalis, Dermatophagoides pteronyssinus, Periplaneta americana and Blatella germanica allergens. Data on demographic, environmental and social exposures were collected by questionnaire; serum IgG and stool examinations were done to detect current or past infections with viral, bacterial, protozoan and intestinal helminth pathogens. We measured atopy by skin prick testing (SPT) and specific IgE (sIgE) to aerollergens in serum (by ImmunoCAP). SIgE reactivity to B. tropicalis extract depleted of carbohydrates was measured by an in-house ELISA. Total IgE was measured by in house capture ELISA. SNPs were typed using Illumina Omni 2.5. RESULTS: Negative skin prick tests in the presence of specific IgE antibodies were frequent. Factors independently associated with a reduced frequency of positive skin prick tests were large number of siblings, the presence of IgG to herpes simplex virus, Ascaris lumbricoides and Trichuris trichiura infections, living in neighborhoods with infrequent garbage collection, presence of rodents and cats in the household and sIgE reactivity to glycosylated B. tropicalis allergens. Also, SNP on IGHE (rs61737468) was negatively associated with SPT reactivity. CONCLUSIONS: A variety of factors were found to be associated with decreased frequency of SPT such as unhygienic living conditions, infections, total IgE, IgE response to glycosylated allergens and genetic polymorphisms, indicating that multiple mechanisms may be involved. Our data, showing that exposures to an unhygienic environment and childhood infections modulate immediate allergen skin test reactivity, provide support for the "hygiene hypothesis"