Hyper-IgE syndrome (HIES) is a rare primary immunodeficiency characterized by elevated levels of immunoglobulin E (IgE), eczematous dermatitis, cold abscesses, and recurrent infections of the lung ...and skin caused by Staphylococcus aureus. The dominant form is characterized by nonimmunologic features including skeletal, connective tissue, and pulmonary abnormalities in addition to recurrent infections and eczema. Omalizumab is a humanized recombinant monoclonal antibody against IgE. Several studies reported clinical improvement with omalizumab in patients with severe atopic eczema with high serum IgE level. We present the case of a 37-year-old male with HIES and cutaneous manifestations, treated with humanized recombinant monoclonal antibodies efalizumab and omalizumab. After therapy for 4 years, we observed diminished eczema and serum IgE levels.
•Panama Canal Watershed is one of the most important hydrological systems worldwide.•HJ-Biplot approach proves to be an efficient tool for water quality studies.•HJ-Biplot approach allowed a robust ...classification of sampling points.•HJ-Biplot has very few restrictions and good performance for matrices inspection.•The multivariate HJ-Biplot allows relating physicochemical and biological variables.
Water quality is a sensitive topic of worldwide concern that is defined by a series of physical, chemical and biological characteristics. The complex nature for studying water quality requires finding simple models to identify the variables that influence it the most. Therefore, the use of multivariate analysis techniques will be of immense help to find relationships and conclusions which aid us to determine the state of water quality through biological, physical and chemical indicators. In this investigation, the following variables were evaluated: Temperature, pH, transparency, turbidity, nitrates, orthophosphates, phosphorus, total nitrogen, chlorophyll a, solar radiation, dissolved oxygen and microcystins. These determined water quality at the sample sites, Gamboa and Paraiso. The results obtained through the application of a two-way multivariate analysis method called HJ-Biplot reflect variableś relationships of chemical, physical and biological compositions. Furthermore, results conform two clusters of sample points that satisfactorily match to the region seasons. Cluster 1 is characterized by the presence of the following variables: pH, transparency, chlorophyll a, oxygen and temperature. On the other hand, cluster 2 comprises the following variables: nitrate, orthophosphates, turbidity and P-total. They are all parameters that suffer variations in the rainy season, and that, in turn, can influence the presence of ciabobacteria with toxigenic potential. Furthermore, this study demonstrates that the multivariate statistical methods are valuable for interpreting complex data sets, specifically, for water quality monitoring network.
The incidence of breast cancer increases with age until menopause, and breast cancer is more aggressive in younger women. The existence of epidemiological links between breast cancer and aging ...indicates that both processes share some common mechanisms of development. Oxidative stress is associated with both cancer susceptibility and aging. Here we observed that ERBB2-positive breast cancer, which developed in genetically heterogeneous ERBB2-positive transgenic mice generated by a backcross, is more aggressive in chronologically younger than in older mice (differentiated by the median survival of the cohort that was 79 weeks), similar to what occurs in humans. In this cohort, we estimated the oxidative biological age using a mathematical model that integrated several subphenotypes directly or indirectly related to oxidative stress. The model selected the serum levels of HDL-cholesterol and magnesium and total AKT1 and glutathione concentrations in the liver. The grade of aging was calculated as the difference between the predicted biological age and the chronological age. This comparison permitted the identification of biologically younger and older mice compared with their chronological age. Interestingly, biologically older mice developed more aggressive breast cancer than the biologically younger mice. Genomic regions on chromosomes 2 and 15 linked to the grade of oxidative aging were identified. The levels of expression of Zbp1 located on chromosome 2, a gene related to necroptosis and inflammation, positively correlated with the grade of aging and tumour aggressiveness. Moreover, the pattern of gene expression of genes linked to the inflammation and the response to infection pathways was enriched in the livers of biologically old mice. This study shows part of the complex interactions between breast cancer and aging.
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•Breast cancer developed by genetically heterogeneous mice was more aggressive in chronologically younger than in older mice.•We estimated the biological age integrating subphenotypes related to oxidative stress.•Biologically older mice developed more aggressive breast cancer than the biologically younger mice.•We identified QTLs genomic regions on chromosomes 2 and 15 linked to the grade of oxidative aging.•The pattern of gene expression in the liver of biologically old mice is enriched in inflammation and response to infection pathways.
An essential question in cancer is why individuals with the same disease have different clinical outcomes. Progress toward a more personalized medicine in cancer patients requires taking into account ...the underlying heterogeneity at different molecular levels.
Here, we present a model in which there are complex interactions at different cellular and systemic levels that account for the heterogeneity of susceptibility to and evolution of ERBB2-positive breast cancers. Our model is based on our analyses of a cohort of mice that are characterized by heterogeneous susceptibility to ERBB2-positive breast cancers. Our analysis reveals that there are similarities between ERBB2 tumors in humans and those of backcross mice at clinical, genomic, expression, and signaling levels. We also show that mice that have tumors with intrinsically high levels of active AKT and ERK are more resistant to tumor metastasis. Our findings suggest for the first time that a site-specific phosphorylation at the serine 473 residue of AKT1 modifies the capacity for tumors to disseminate. Finally, we present two predictive models that can explain the heterogeneous behavior of the disease in the mouse population when we consider simultaneously certain genetic markers, liver cell signaling and serum biomarkers that are identified before the onset of the disease.
Considering simultaneously tumor pathophenotypes and several molecular levels, we show the heterogeneous behavior of ERBB2-positive breast cancer in terms of disease progression. This and similar studies should help to better understand disease variability in patient populations.
The data presented in this article are related to the research paper entitled “The biological age linked to oxidative stress modifies breast cancer aggressiveness” (M.M. Sáez-Freire, A. Blanco-Gómez, ...S. Castillo-Lluva, A. Gómez-Vecino, J.M. Galvis-Jiménez, C. Martín-Seisdedos, M. Isidoro-García, L. Hontecillas-Prieto, M.B. García-Cenador, F.J. García-Criado, M.C. Patino-Alonso, P. Galindo-Villardón, J.H. Mao, C. Prieto, A. Castellanos-Martín, L. Kaderali, J. Pérez-Losada). The data shown were obtained from a population of transgenic mice, MMTV-Erbb2/Neu, with different susceptibility to breast cancer and a mixed genetic background generated by backcrossing. It was observed that the aggressiveness of breast cancer negatively correlates with age, being lower in chronologically old mice, similar to what occurs in humans. Given that oxidative stress is associated with tumour susceptibility and the degree of aging, the association between the aggressiveness of breast cancer and multiple intermediate phenotypes directly or indirectly related to oxidative stress was studied. Using a mathematical model, we defined biological age and the degree of aging as the difference between biological and chronological ages. As a result, we observed that biologically old mice predominated among those that developed the disease early on, that is, those that were chronologically young. We then identified the specific and common genetic components of Quantitative Trait loci or QTL associated with different evolution of breast cancer, the intermediate phenotypes related to oxidative stress studied, the biological age and the degree of aging. Lastly, we showed that the expression pattern in the livers of biologically old mice were enriched in signalling pathways related to inflammation and response to infections; whereas the biologically young mice exhibited enriched pathways related to mitochondrial activity. For the explanation and discussion of these data refer to the research article cited above.
Cardiotoxicity due to anthracyclines (CDA) affects cancer patients, but we cannot predict who may suffer from this complication. CDA is a complex trait with a polygenic component that is mainly ...unidentified. We propose that levels of intermediate molecular phenotypes (IMPs) in the myocardium associated with histopathological damage could explain CDA susceptibility, so variants of genes encoding these IMPs could identify patients susceptible to this complication. Thus, a genetically heterogeneous cohort of mice (
= 165) generated by backcrossing were treated with doxorubicin and docetaxel. We quantified heart fibrosis using an Ariol slide scanner and intramyocardial levels of IMPs using multiplex bead arrays and QPCR. We identified quantitative trait loci linked to IMPs (ipQTLs) and cdaQTLs via linkage analysis. In three cancer patient cohorts, CDA was quantified using echocardiography or Cardiac Magnetic Resonance. CDA behaves as a complex trait in the mouse cohort. IMP levels in the myocardium were associated with CDA. ipQTLs integrated into genetic models with cdaQTLs account for more CDA phenotypic variation than that explained by cda-QTLs alone. Allelic forms of genes encoding IMPs associated with CDA in mice, including AKT1, MAPK14, MAPK8, STAT3, CAS3, and TP53, are genetic determinants of CDA in patients. Two genetic risk scores for pediatric patients (
= 71) and women with breast cancer (
= 420) were generated using machine-learning Least Absolute Shrinkage and Selection Operator (LASSO) regression. Thus, IMPs associated with heart damage identify genetic markers of CDA risk, thereby allowing more personalized patient management.
Numerosos estudios han contribuido a impulsar la investigación sobre enfoques de aprendizaje en el ámbito universitario. El enfoque adoptado por los estudiantes frente a la realización de la tarea ...puede ser superficial o profundo y tiende a cambiar en función de diferentes variables contextuales. El objetivo principal de este trabajo fue estudiar el tipo de enfoque de aprendizaje que presentan los estudiantes de las áreas de Ciencias Sociales y Jurídicas y Ciencias de la Salud de la Universidad de Salamanca. La muestra objeto de estudio estuvo compuesta por 518 alumnos del área de Ciencias Sociales y Jurídicas y 300 alumnos de Ciencias de la Salud. Se utilizó el cuestionario R-SPQ-2F yse midieron las diferencias entre los enfoques deaprendizajeylasáreas de conocimiento estudiadas a través de la prueba U de Mann-Whitney para muestras independientes. Para visualizar las relaciones entre los enfoques de aprendizaje y las áreas de conocimiento, se llevó a cabo el análisis multivariante Manova-Biplot. Los hallazgos obtenidos muestran que el enfoque profundo y el enfoque superficial son prácticamente independientes. El enfoque profundo predomina en el área de ciencias de la salud y se constatan diferencias significativas en este enfoque entre los estudiantes de Ciencias de la Salud y los estudiantes de Ciencias Sociales y Jurídicas.
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