Multiple outcome meta-analysis of gene-expression data in inflammatory bowel disease

We performed a multivariate meta-analysis of microarray data in Crohn's disease (CD) and Ulcerative colitis (UC), which are the main forms of inflammatory bowel disease (IBD). They share similar symptoms but differ in the location and extent of inflammation and in complications. We identified 249 differentially expressed genes (DEGs) in CD and 38 in UC at a false discovery rate of 1%. 20 of the DEGs were common to both diseases. A multivariate test identified 260 DEGs associated with IBD, 53 of which were not found in any of the disorders. We identified important molecular pathways implicated in the pathogenesis of IBD, such as the JAK/STAT and interferon-gamma signaling pathways, genes involved in cell adhesion, apoptosis and carcinogenesis. Among others, BCAT1 and GZMB are interesting novel DEGs that deserve further investigation in experimental models. The method could also be useful to other cases of meta-analysis of gene expression data

ITGB2 mutation combined with deleted ring 21 chromosome in a child with leukocyte adhesion deficiency

Leukocyte adhesion deficiency type 1(LAD-1) is a rare autosomal recessive primary immunodeficiency caused by defects in the ITGB2 gene located on chromosome 21q22. Clinically, LAD-1 patients are characterized by recurrent infections, slow wound healing and dystrophic scars after skin injuries, associated with persistent neutrophilia. The severity of symptoms is related to the level of CD11/CD18 expression on patients’ leucocytes and those with less than 1% expression treated with hematopoietic stem cell transplant (HSCT). We present a child affected by LAD-1 who received HSCT from a matched unrelated donor. Molecular analysis revealed apparent homozygosis for a point mutation in the ITGB2 gene, only the mother however was carrier of the mutation. Cytogenetic and FISH analysis showed the presence of a de-novo ring chromosome 21. Whole Genome Analysis with the Affymetrix GeneChip Human Mapping 250K NspI array confirmed in the child the presence of a de novo deletion of the chromosomal region 21q22.3-qter, where the ITGB2 gene maps. While HSCT resulted in successful engraftment and correction of the immunodeficiency, all the phenotypic features of ring (21) syndrome with a deletion of a 4.6Mb (including 69 genes) clearly remained unchange

Measuring Accessibility Using Gravity and Radiation Models

Since the presentation of the radiation model, much work has been done to compare its findings with those obtained from gravitational models. These comparisons always aim at measuring the accuracy with which the models reproduce the mobility described by origin–destination matrices. This has been done at different spatial scales using different datasets, and several versions of the models have been proposed to adjust to various spatial systems. However, the models, to our knowledge, have never been compared with respect to policy testing scenarios. For this reason, here we use the models to analyse the impact of the introduction of a new transportation network, a bus rapid transport system, in the city of Teresina in Brazil. We do this by measuring the estimated variation in the trip distribution, and formulate an accessibility to employment indicator for the different zones of the city. By comparing the results obtained with the two approaches, we are able to not only better assess the goodness of fit and the impact of this intervention, but also understand reasons for the systematic similarities and differences in their predictions

Hidrogym practice effects: The perception of Wellness of participants in a Community Outreach project

Los objetivos del presente estudio fueron identificar la percepción de mejora de los efectos percibidos por practicantes de hidrogimnasia y verificar posibles asociaciones entre éstos con el tiempo de práctica y la edad. Participaron 62 individuos con edad media de 50,8 años (+ 14,1). Como instrumento fue empleado un cuestionario construido para la investigación. Para el análisis de datos fue utilizado el análisis de contenido y los testes no paramétricos Prova U de Mann Whitney y Kruskal Wallis. Se encontró que el indicador "disposición" presentó el mayor índice de mejora en la percepción de bienestar y que los indicadores vinculados a los aspectos físico-funcionales tuvieron mayor número de citación. El indicador diminución de peso corporal no demostró índice de “mucha mejora”. Aquellos que practicaban hacia seis meses o más evidenciaron mejores escores en: estado de humor, calidad del sueño, nivel de estrés y relacionamiento ocupacional. Quienes tenían 61 años o más demostraron peores percepciones en el nivel de estrés y dolor articular. Se concluye que la práctica de hidrogimnasia contribuye para la mejora de la percepción de bienestar en los aspectos psicológicos, físico-funcionales y sociales. Y que aspectos relacionados a edad y tiempo de práctica pueden interferir en esta percepción.The aims of the study were to identify the effects of improvement perceived by hidrogym practitioners and to verify possible associations between these and the time and age of practice. 62 people with average age of 50,80 years old (+ 14,05) participated of this study. An instrument built for this research was used for data collection. The content analysis and the non-parametric testes U the Mann Whitney and Kruskal Wallis were used for data analysis. The results showed that the indicator "disposition" presented the best perception of wellness, though the physical-functional aspects presented more number of cited indicators. The weight diminution indicator did not show index of "much improvement". The participants who had practiced at least six months evidenced better scores in: mood, sleep quality, stress levels and occupational relationship. The participants who were 61 years old or more showed worse perceptions in stress level and articulate pain. In conclusion, hidrogym practice helps to the wellness perception improvement in the psychological, physical-functional and social aspects. Furthermore, aspects related to age group and time of practice could interfere in wellness perception.Facultad de Humanidades y Ciencias de la Educació

Hidrogym practice effects: The perception of Wellness of participants in a Community Outreach project

Los objetivos del presente estudio fueron identificar la percepción de mejora de los efectos percibidos por practicantes de hidrogimnasia y verificar posibles asociaciones entre éstos con el tiempo de práctica y la edad. Participaron 62 individuos con edad media de 50,8 años (+ 14,1). Como instrumento fue empleado un cuestionario construido para la investigación. Para el análisis de datos fue utilizado el análisis de contenido y los testes no paramétricos Prova U de Mann Whitney y Kruskal Wallis. Se encontró que el indicador "disposición" presentó el mayor índice de mejora en la percepción de bienestar y que los indicadores vinculados a los aspectos físico-funcionales tuvieron mayor número de citación. El indicador diminución de peso corporal no demostró índice de “mucha mejora”. Aquellos que practicaban hacia seis meses o más evidenciaron mejores escores en: estado de humor, calidad del sueño, nivel de estrés y relacionamiento ocupacional. Quienes tenían 61 años o más demostraron peores percepciones en el nivel de estrés y dolor articular. Se concluye que la práctica de hidrogimnasia contribuye para la mejora de la percepción de bienestar en los aspectos psicológicos, físico-funcionales y sociales. Y que aspectos relacionados a edad y tiempo de práctica pueden interferir en esta percepción.The aims of the study were to identify the effects of improvement perceived by hidrogym practitioners and to verify possible associations between these and the time and age of practice. 62 people with average age of 50,80 years old (+ 14,05) participated of this study. An instrument built for this research was used for data collection. The content analysis and the non-parametric testes U the Mann Whitney and Kruskal Wallis were used for data analysis. The results showed that the indicator "disposition" presented the best perception of wellness, though the physical-functional aspects presented more number of cited indicators. The weight diminution indicator did not show index of "much improvement". The participants who had practiced at least six months evidenced better scores in: mood, sleep quality, stress levels and occupational relationship. The participants who were 61 years old or more showed worse perceptions in stress level and articulate pain. In conclusion, hidrogym practice helps to the wellness perception improvement in the psychological, physical-functional and social aspects. Furthermore, aspects related to age group and time of practice could interfere in wellness perception.Facultad de Humanidades y Ciencias de la Educació

Hidrogym practice effects: The perception of Wellness of participants in a Community Outreach project

Los objetivos del presente estudio fueron identificar la percepción de mejora de los efectos percibidos por practicantes de hidrogimnasia y verificar posibles asociaciones entre éstos con el tiempo de práctica y la edad. Participaron 62 individuos con edad media de 50,8 años (+ 14,1). Como instrumento fue empleado un cuestionario construido para la investigación. Para el análisis de datos fue utilizado el análisis de contenido y los testes no paramétricos Prova U de Mann Whitney y Kruskal Wallis. Se encontró que el indicador "disposición" presentó el mayor índice de mejora en la percepción de bienestar y que los indicadores vinculados a los aspectos físico-funcionales tuvieron mayor número de citación. El indicador diminución de peso corporal no demostró índice de “mucha mejora”. Aquellos que practicaban hacia seis meses o más evidenciaron mejores escores en: estado de humor, calidad del sueño, nivel de estrés y relacionamiento ocupacional. Quienes tenían 61 años o más demostraron peores percepciones en el nivel de estrés y dolor articular. Se concluye que la práctica de hidrogimnasia contribuye para la mejora de la percepción de bienestar en los aspectos psicológicos, físico-funcionales y sociales. Y que aspectos relacionados a edad y tiempo de práctica pueden interferir en esta percepción.The aims of the study were to identify the effects of improvement perceived by hidrogym practitioners and to verify possible associations between these and the time and age of practice. 62 people with average age of 50,80 years old (+ 14,05) participated of this study. An instrument built for this research was used for data collection. The content analysis and the non-parametric testes U the Mann Whitney and Kruskal Wallis were used for data analysis. The results showed that the indicator "disposition" presented the best perception of wellness, though the physical-functional aspects presented more number of cited indicators. The weight diminution indicator did not show index of "much improvement". The participants who had practiced at least six months evidenced better scores in: mood, sleep quality, stress levels and occupational relationship. The participants who were 61 years old or more showed worse perceptions in stress level and articulate pain. In conclusion, hidrogym practice helps to the wellness perception improvement in the psychological, physical-functional and social aspects. Furthermore, aspects related to age group and time of practice could interfere in wellness perception.Facultad de Humanidades y Ciencias de la Educació

Gemcitabine-releasing mesenchymal stromal cells inhibit in vitro proliferation of human pancreatic carcinoma cells

BACKGROUND AIMS: Pancreatic cancer (pCa) is a tumor characterized by a fibrotic state and associated with a poor prognosis. The observation that mesenchymal stromal cells (MSCs) migrate toward inflammatory micro-environments and engraft into tumor stroma after systemic administration suggested new therapeutic approaches with the use of engineered MSCs to deliver and produce anti-cancer molecules directly within the tumor. Previously, we demonstrated that without any genetic modifications, MSCs are able to deliver anti-cancer drugs. MSCs loaded with paclitaxel by exposure to high concentrations release the drug both in vitro and in vivo, inhibiting tumor proliferation. On the basis of these observations, we evaluated the ability of MSCs (from bone marrow and pancreas) to uptake and release gemcitabine (GCB), a drug widely used in pCa treatment. METHODS: MSCs were primed by 24-h exposure to 2000 ng/mL of GCB. The anti-tumor potential of primed MSCs was then investigated by in vitro anti-proliferation assays with the use of CFPAC-1, a pancreatic tumor cell line sensitive to GCB. The uptake/release ability was confirmed by means of high-performance liquid chromatography analysis. A cell-cycle study and secretome evaluation were also conducted to better understand the characteristics of primed MSCs. RESULTS: GCB-releasing MSCs inhibit the growth of a human pCa cell line in vitro. CONCLUSIONS: The use of MSCs as a "trojan horse" can open the way to a new pCa therapeutic approach; GCB-loaded MSCs that integrate into the tumor mass could deliver much higher concentrations of the drug in situ than can be achieved by intravenous injection

Tangled Nature: A model of emergent structure and temporal mode among co-evolving agents

Understanding systems level behaviour of many interacting agents is challenging in various ways, here we'll focus on the how the interaction between components can lead to hierarchical structures with different types of dynamics, or causations, at different levels. We use the Tangled Nature model to discuss the co-evolutionary aspects connecting the microscopic level of the individual to the macroscopic systems level. At the microscopic level the individual agent may undergo evolutionary changes due to mutations of strategies. The micro-dynamics always run at a constant rate. Nevertheless, the system's level dynamics exhibit a completely different type of intermittent abrupt dynamics where major upheavals keep throwing the system between meta-stable configurations. These dramatic transitions are described by a log-Poisson time statistics. The long time effect is a collectively adapted of the ecological network. We discuss the ecological and macroevolutionary consequences of the adaptive dynamics and briefly describe work using the Tangled Nature framework to analyse problems in economics, sociology, innovation and sustainabilityComment: Invited contribution to Focus on Complexity in European Journal of Physics. 25 page, 1 figur

Generation of three iPSC lines from fibroblasts of a patient with Aicardi Goutières Syndrome mutated in TREX1

Fibroblasts from a patient with Aicardi Gouti\ue8res Syndrome (AGS) carrying a compound heterozygous mutation in TREX1, were reprogrammed into induced pluripotent stem cells (iPSCs) to establish isogenic clonal stem cell lines: UNIBSi006-A, UNIBSi006-B, and UNIBSi006-C. Cells were transduced using the episomal Sendai viral vectors, containing human OCT4, SOX2, c-MYC and KLF4 transcription factors. The transgene-free iPSC lines showed normal karyotype, expressed pluripotent markers and displayed in vitro differentiation potential toward cells of the three embryonic germ layers

Reply to Ghirardello et al Letter to the Editor

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