Papel de la citogenética y de la genética molecular en la detección de la clonalidad en las eosinofilias

[ES]La presencia de eosinofilia crónica es un hallazgo poco frecuente, pero de gran relevancia clínica. Para su correcto enfoque diagnóstico y terapéutico es importante definir un algoritmo clínico en el que se deben incluir el estudio de las alteraciones de los genes BCR, ABL1, JAK2, PDGFRA, PDGFRB y FGFR1, así como descartar la presencia de clonalidad T. Las hemopatías mieloides y linfoides con reordenamientos de los genes PDGFRA o PDGFRB son enfermedades poco frecuentes, pero no excepcionales. Es difícil determinar su incidencia en nuestro medio, pero podríamos estimarla en torno a 0,1/100.000 habitantes/año. Las NMP con fusión FIP1L1-PDGFRA son el 2,2% de todas las NMP, mientras que la incidencia de las NMP con reordenamiento del gen PDGFRB se sitúa en torno al 1,8% de todas las NMP. Los enfermos con fusión PDGFRA/FIP1L1 se caracterizan por ser varones de edad media, con hepatoesplenomegalia y a nivel biológico tienen leucocitosis con eosinofilia, anemia y trombopenia. En nuestra serie, todos los enfermos tratados con imatinib a 100 mg/d respondieron al tratamiento y han mantenido la respuesta durante años. Los enfermos con reordenamiento del gen PDGFRB suelen ser varones, de edad avanzada y a nivel biológico destaca la presencia de anemia y leucocitosis con eosinofilia. La alteración citogenética más frecuente es la t(5;12), con fusión de los genes PDFGRB y ETV6. En ocasiones los enfermos con reordenamientos de PDGFRB tenían pérdidas de 5q asociadas. En nuestra serie, la mayoría de los enfermos tratados con imatinib respondieron a una dosis de 400 mg/d y la respuesta se ha mantenido en la mayoría de ellos.La aplicación de los microarrays genómicos al estudio de las eosinofilias crónicas permite la detección de alteraciones cromosómicas en el 76% de los pacientes con enfermedades mieloproliferativas. Las alteraciones más frecuentes son las pérdidas genéticas, fundamentalmente en 20q13.13 y 11q13.3. Los enfermos con reordenamiento del PDGFRA tenían pérdidas en 19p13.11, mientras que en la leucemia mieloide crónica son frecuentes las pérdidas en 8q24.3. Estos cambios no se observan de los enfermos con eosinofilia asociada a LNH-T ni en las eosinofilias reactivas

The effectiveness of acceptance and commitment therapy on psychological capital and psychological well-being of patients with thalassemia: a quasi-experimental study

Background: This study aimed to investigate the effectiveness of Acceptance and Commitment Therapy (ACT) on psychological capital and psychological well-being of patients with thalassemia. Methods: This study was a quasi-experimental trial with a pretest-posttest design along with a control group. The statistical population included all patients with thalassemia referred to the office of the Thalassemia Association located in Mohammad Kermanshahi Hospital in Kermanshah. Thirty patients were selected as the sample by targeted sampling method and then randomly assigned to experimental and control groups equally (each n=15). The instruments included Ryff psychological well-being questionnaire and Luthan’s Psychological Capital Questionnaire. After performing the pretest, the experimental group underwent an ACT intervention, while the control group received no treatment. Data were analyzed using SPSS software version 21 according to analysis of covariance (ANCOVA). Results: There was a significant difference between the mean of psychological well-being and psychological capital variables in both experimental and control groups (P=0.014 and P=0.005 respectively). By eliminating the effect of pre-test psychological capital scores as a covariate variable, the main effect of the independent variable on post-test psychological capital scores was significant (F=53.601, P=0.001). By eliminating the effect of pre-test psychological capital scores as a covariate variable, the main effect of the independent variable on post-test psychological well-being scores was significant (F=181.34, P=0.001). Conclusion: ACT was effective on the psychological capital and the psychological well-being of thalassemia patients. Moreover, ACT can be used to improve the psychological capital and psychological well-being of patients with thalassemia

The role of professors and students in developing and revising the universities curriculum in Afghanistan

The main aim of this research is the professors and students involvement in the main decision-making of developing and revising the Afghanistan university curriculum? The researcher has used the latest studies related to this issue in other countries for the field research, a mixed-method (quantitative and qualitative), were used. The results of previous studies in other countries indicate that the role of professors and students in Developing or revising the university curriculum are highly significant, the present study indicates that despite the efforts of the Afghan Ministry of Higher Education in revising the curriculum, there are still significant issues. In achieving an ideal curriculum, otherwise, the curriculum would face serious challenges

Photocatalytic Removal of Methylbenzene Vapors by MnO2/Al2O3/Fe2O3 Nano composite

Methyl benzene, which has carcinogenic effects, is a volatile organic compound that is widely used in various industries. Nano composites of Mno2/Al203/Fe203, which is a new photocatalyst, have not been applied to remove contaminants from air streams. Therefore, the aim of the present study was to investigate the photocatalytic removal of ethyl benzene by using this nano composite activated by visible light. Morphological characteristics of the synthesized Nano composite in a sol-gel method are determined through XRD, FTIR, and SEM. Through the photocatalyst process and by the use of visible light radiation, the synthesized Nano composite is used to degrade ethyl benzene in the gas phase. In order to estimate the main effects and interaction ones and to optimize the experiment numbers, the response surface method was used. Operational parameters investigated in the study are the initial concentration of contaminants, relative humidity, and the residence time, which were considered in three levels; further, the experiments were designed by Design Expert version 9 software. The results show the Nano composite particle sizes were less than 82 nanometers. The findings also indicate that relative humidity and residence time were effective parameters in removal efficiency of ethyl benzene. This Nano composite, at the optimal conditions, was capable of removing 98.72% of the pollutants, with an initial content of 300 ppm. MnO2/Al2O3/Fe2O3 Nano composite is a suitable catalyst to remove ethyl benzene from air streams. Among the features of the Nano composite are reaction at room temperature and lower production dangerous byproducts, which are the main advantages of this Nano composite as compared with other nano composites

Photocatalytic Removal of Methylbenzene Vapors by MnO2/Al2O3/Fe2O3 Nano composite

Methyl benzene, which has carcinogenic effects, is a volatile organic compound that is widely used in various industries. Nano composites of Mno2/Al203/Fe203, which is a new photocatalyst, have not been applied to remove contaminants from air streams. Therefore, the aim of the present study was to investigate the photocatalytic removal of ethyl benzene by using this nano composite activated by visible light. Morphological characteristics of the synthesized Nano composite in a sol-gel method are determined through XRD, FTIR, and SEM. Through the photocatalyst process and by the use of visible light radiation, the synthesized Nano composite is used to degrade ethyl benzene in the gas phase. In order to estimate the main effects and interaction ones and to optimize the experiment numbers, the response surface method was used. Operational parameters investigated in the study are the initial concentration of contaminants, relative humidity, and the residence time, which were considered in three levels; further, the experiments were designed by Design Expert version 9 software. The results show the Nano composite particle sizes were less than 82 nanometers. The findings also indicate that relative humidity and residence time were effective parameters in removal efficiency of ethyl benzene. This Nano composite, at the optimal conditions, was capable of removing 98.72% of the pollutants, with an initial content of 300 ppm. MnO2/Al2O3/Fe2O3 Nano composite is a suitable catalyst to remove ethyl benzene from air streams. Among the features of the Nano composite are reaction at room temperature and lower production dangerous byproducts, which are the main advantages of this Nano composite as compared with other nano composites

Effect of ghrelin on serum metabolites in Alzheimer’s disease model rats; a metabolomics studies based on 1H-NMR technique

Objective(s): Alzheimer’s disease (AD) is dysfunction of the central nervous system and as a neurodegenerative disease. The objective of this work is to investigate metabolic profiling in the serum of animal models of AD compared to healthy controls and then to peruse the role of ghrelin as a therapeutic approach for the AD.Materials and Methods: Nuclear magnetic resonance (NMR) technique was used for identification of metabolites that are differentially expressed in the serum of a rat model of the AD with or without ghrelin treatment. Using multivariate statistical analysis, models were built and indicated.Results: There were significant differences and high predictive power between AD and ghrelin-treated groups. The area under curve (AUC) of receiver operating characteristic (ROC) curve and Q2 were 0.870 and 0.759, respectively. A biomarker panel consisting of 14 metabolites was identified to discriminate the AD from the control group. Another panel of 12 serum metabolites was used to differentiate AD models from treated models. Conclusion: Both panels had good agreements with clinical diagnosis. Analysis of the results displayed that ghrelin improved memory and cognitive abilities. Affected pathways by ghrelin included oxidative stress, and osteoporosis pathways and vascular risk factors

Photocatalytic Removal of Methylbenzene Vapors by MnO2/Al2O3/Fe2O3 Nano composite

Methyl benzene, which has carcinogenic effects, is a volatile organic compound that is widely used in various industries. Nano composites of Mno2/Al203/Fe203, which is a new photocatalyst, have not been applied to remove contaminants from air streams. Therefore, the aim of the present study was to investigate the photocatalytic removal of ethyl benzene by using this nano composite activated by visible light. Morphological characteristics of the synthesized Nano composite in a sol-gel method are determined through XRD, FTIR, and SEM. Through the photocatalyst process and by the use of visible light radiation, the synthesized Nano composite is used to degrade ethyl benzene in the gas phase. In order to estimate the main effects and interaction ones and to optimize the experiment numbers, the response surface method was used. Operational parameters investigated in the study are the initial concentration of contaminants, relative humidity, and the residence time, which were considered in three levels; further, the experiments were designed by Design Expert version 9 software. The results show the Nano composite particle sizes were less than 82 nanometers. The findings also indicate that relative humidity and residence time were effective parameters in removal efficiency of ethyl benzene. This Nano composite, at the optimal conditions, was capable of removing 98.72% of the pollutants, with an initial content of 300 ppm. MnO2/Al2O3/Fe2O3 Nano composite is a suitable catalyst to remove ethyl benzene from air streams. Among the features of the Nano composite are reaction at room temperature and lower production dangerous byproducts, which are the main advantages of this Nano composite as compared with other nano composites

Mutations in TP53 and JAK2 are independent prognostic biomarkers in B-cell precursor acute lymphoblastic leukaemia

[EN]Background: In B-cell precursor acute lymphoblastic leukaemia (B-ALL), the identification of additional genetic alterations associated with poor prognosis is still of importance. We determined the frequency and prognostic impact of somatic mutations in children and adult cases with B-ALL treated with Spanish PETHEMA and SEHOP protocols. Methods: Mutational status of hotspot regions of TP53, JAK2, PAX5, LEF1, CRLF2 and IL7R genes was determined by next-generation deep sequencing in 340 B-ALL patients (211 children and 129 adults). The associations between mutation status and clinicopathological features at the time of diagnosis, treatment outcome and survival were assessed. Univariate and multivariate survival analyses were performed to identify independent prognostic factors associated with overall survival (OS), event-free survival (EFS) and relapse rate (RR). Results: A mutation rate of 12.4% was identified. The frequency of adult mutations was higher (20.2% vs 7.6%, P=0.001). TP53 was the most frequently mutated gene (4.1%), followed by JAK2 (3.8%), CRLF2 (2.9%), PAX5 (2.4%), LEF1 (0.6%) and IL7R (0.3%). All mutations were observed in B-ALL without ETV6-RUNX1 (P=0.047) or BCR-ABL1 fusions (P<0.0001). In children, TP53mut was associated with lower OS (5-year OS: 50% vs 86%, P=0.002) and EFS rates (5-year EFS: 50% vs 78.3%, P=0.009) and higher RR (5-year RR: 33.3% vs 18.6% P=0.037), and was independently associated with higher RR (hazard ratio (HR)=4.5; P=0.04). In adults, TP53mut was associated with a lower OS (5-year OS: 0% vs 43.3%, P=0.019) and a higher RR (5-year RR: 100% vs 61.4%, P=0.029), whereas JAK2mut was associated with a lower EFS (5-year EFS: 0% vs 30.6%, P=0.035) and a higher RR (5-year RR: 100% vs 60.4%, P=0.002). TP53mut was an independent risk factor for shorter OS (HR=2.3; P=0.035) and, together with JAK2mut, also were independent markers of poor prognosis for RR (TP53mut: HR=5.9; P=0.027 and JAK2mut: HR=5.6; P=0.036). Conclusions: TP53mut and JAK2mut are potential biomarkers associated with poor prognosis in B-ALL patients.European Commision (EC). Funding FP7/SP1/HEALTH. Project Code: 30624

Genome-wide DNA copy number analysis of acute lymphoblastic leukemia identifies new genetic markers associated with clinical outcome

Altres ajuts: FUCALHH 2013; HUS272U13; GRS 994/A/14, BIO/SA10/14, BIO/SA31/13; Fundación Española de Hematología y Hemoterapia (FEHH), Universidad Pedagógica y Tecnológica de Colombia 223-2011Identifying additional genetic alterations associated with poor prognosis in acute lymphoblastic leukemia (ALL) is still a challenge. Aims: To characterize the presence of additional DNA copy number alterations (CNAs) in children and adults with ALL by whole-genome oligonucleotide array (aCGH) analysis, and to identify their associations with clinical features and outcome. Array-CGH was carried out in 265 newly diagnosed ALLs (142 children and 123 adults). The NimbleGen CGH 12x135K array (Roche) was used to analyze genetic gains and losses. CNAs were analyzed with GISTIC and aCGHweb software. Clinical and biological variables were analyzed. Three of the patients showed chromothripsis (cth6, cth14q and cth15q). CNAs were associated with age, phenotype, genetic subtype and overall survival (OS). In the whole cohort of children, the losses on 14q32.33 (p = 0.019) and 15q13.2 (p = 0.04) were related to shorter OS. In the group of children without good- or poor-risk cytogenetics, the gain on 1p36.11 was a prognostic marker independently associated with shorter OS. In adults, the gains on 19q13.2 (p = 0.001) and Xp21.1 (p = 0.029), and the loss of 17p (p = 0.014) were independent markers of poor prognosis with respect to OS. In summary, CNAs are frequent in ALL and are associated with clinical parameters and survival. Genome-wide DNA copy number analysis allows the identification of genetic markers that predict clinical outcome, suggesting that detection of these genetic lesions will be useful in the management of patients newly diagnosed with ALL