Accurate detection of uniparental disomy and microdeletions by SNP array analysis in myelodysplastic syndromes with normal cytogenetics.

Progress in the management of patients with myelodysplastic syndromes (MDS) has been hampered by the inability to detect cytogenetic abnormalities in 40-60% of cases. We prospectively analyzed matched pairs of bone marrow and buccal cell (normal) DNA samples from 51 MDS patients by single nucleotide polymorphism (SNP) arrays, and identified somatically acquired clonal genomic abnormalities in 21 patients (41%). Among the 33 patients with normal bone marrow cell karyotypes, 5 (15%) had clonal, somatically acquired aberrations by SNP array analysis, including 4 with segmental uniparental disomies (UPD) and 1 with three separate microdeletions. Each abnormality was detected more readily in CD34+ cells than in unselected bone marrow cells. Paired analysis of bone marrow and buccal cell DNA from each patient was necessary to distinguish true clonal genomic abnormalities from inherited copy number variations and regions with apparent loss of heterozygosity. UPDs affecting chromosome 7q were identified in two patients who had a rapidly deteriorating clinical course despite a low-risk International Prognostic Scoring System score. Further studies of larger numbers of patients will be needed to determine whether 7q UPD detected by SNP array analysis will identify higher risk MDS patients at diagnosis, analogous to those with 7q cytogenetic abnormalities

Adjustable Gastric Banding Conversion to One Anastomosis Gastric Bypass: Data Analysis of a Multicenter Database

Introduction: One anastomosis gastric bypass (OAGB) has been proposed as a rescue technique for laparoscopic adjustable gastric banding (LAGB) poor responders. Aim: We sought to analyze, complications, mortality, and medium-term weight loss results after LAGB conversion to OAGB. Methods: Data analysis of an international multicenter database. Results: One hundred eighty-nine LAGB-to-OAGB operations were retrospectively analyzed. Eighty-seven (46.0%) were converted in one stage. Patients operated on in two stages had a higher preoperative body mass index (BMI) (37.9 vs. 41.3 kg/m2, p = 0.0007) and were more likely to have encountered technical complications, such as slippage or erosions (36% vs. 78%, p < 0.0001). Postoperative complications occurred in 4.8% of the patients (4.6% and 4.9% in the one-stage and the two-stage group, respectively). Leak rate, bleeding episodes, and mortality were 2.6%, 0.5%, and 0.5%, respectively. The final BMI was 30.2 at a mean follow-up of 31.4 months. Follow-up at 1, 3, and 5 years was 100%, 88%, and 70%, respectively. Conclusion: Conversion from LAGB to OAGB is safe and effective. The one-stage approach appears to be the preferred option in non-complicate cases, while the two-step approach is mostly done for more complicated cases.info:eu-repo/semantics/publishedVersio

MSH3 polymorphisms and protein levels affect CAG repeat instability in huntington's disease mice

Expansions of trinucleotide CAG/CTG repeats in somatic tissues are thought to contribute to ongoing disease progression through an affected individual's life with Huntington's disease or myotonic dystrophy. Broad ranges of repeat instability arise between individuals with expanded repeats, suggesting the existence of modifiers of repeat instability. Mice with expanded CAG/CTG repeats show variable levels of instability depending upon mouse strain. However, to date the genetic modifiers underlying these differences have not been identified. We show that in liver and striatum the R6/1 Huntington's disease (HD) (CAG)~100 transgene, when present in a congenic C57BL/6J (B6) background, incurred expansion-biased repeat mutations, whereas the repeat was stable in a congenic BALB/cByJ (CBy) background. Reciprocal congenic mice revealed the Msh3 gene as the determinant for the differences in repeat instability. Expansion bias was observed in congenic mice homozygous for the B6 Msh3 gene on a CBy background, while the CAG tract was stabilized in congenics homozygous for the CBy Msh3 gene on a B6 background. The CAG stabilization was as dramatic as genetic deficiency of Msh2. The B6 and CBy Msh3 genes had identical promoters but differed in coding regions and showed strikingly different protein levels. B6 MSH3 variant protein is highly expressed and associated with CAG expansions, while the CBy MSH3 variant protein is expressed at barely detectable levels, associating with CAG stability. The DHFR protein, which is divergently transcribed from a promoter shared by the Msh3 gene, did not show varied levels between mouse strains. Thus, naturally occurring MSH3 protein polymorphisms are modifiers of CAG repeat instability, likely through variable MSH3 protein stability. Since evidence supports that somatic CAG instability is a modifier and predictor of disease, our data are consistent with the hypothesis that variable levels of CAG instability associated with polymorphisms of DNA repair genes may have prognostic implications for various repeat-associated diseases

Simulador de negocios Capstone planeación estratégica de Digby en la industria de los sensores

En el presente documento de obtención de grado se analizan los resultados de la empresa Digby como parte la industria de sensores dentro del simulador de negocios CAPSTONE de CAPSIM, cuyo objetivo es recrear el diseño de una estrategia y la toma de decisiones dentro de una organización. Dentro del primer capítulo se encuentra el marco teórico donde se definen los conceptos necesarios para entender y desarrollar una estrategia dentro de una empresa, además de lo anterior se podrán encontrar una serie de análisis de casos en los que se aplica la teoría revisada previamente. En el segundo apartado se describe la industria de los sensores dentro de CAPSTONE. Además, se detalla la estructura de Digby como organización, su modelo de negocios, así como la planeación estratégica en la que se definen los objetivos de cada una de las áreas, el organigrama de la empresa y responsabilidad del equipo directivo de la misma. Del capítulo número tres al seis se revisan, analizan e interpretan los resultados obtenidos por la empresa Digby durante los ocho periodos de simulación, además se comparan con los que obtuvo la competencia. En el capítulo siete se encuentran las conclusiones a las que llegó el equipo después de la obtención de los resultados finales de la simulación, también se exponen las experiencias y aprendizajes de los distintos miembros del equipo a través de los distintos cursos de la asignatura de Investigación, Desarrollo e Innovación (IDI) y la maestría en el ITESO. Durante la realización del presente trabajo se acrecentó la experiencia en el manejo de una organización por parte de un equipo directivo mediante la práctica en la toma de decisiones de diferentes áreas de una compañía, así como del análisis del entorno económico e industrial.ITESO, A.C

Concurrent Outbreak of Norovirus Genotype I and Enterotoxigenic Escherichia coli on a U.S. Navy Ship following a Visit to Lima, Peru

An outbreak of norovirus (NoV) genotype I and Enterotoxigenic Escherichia coli (ETEC) occurred among US Navy Ship personnel following a visit to Lima, Peru, in June 2008. Visiting a specific area in Lima was significantly associated with illness. While ETEC and NoV are commonly recognized as causative agents of outbreaks, co-circulation of both pathogens has been rarely observed in shipboard outbreaks

Ears of the Armadillo: Global Health Research and Neglected Diseases in Texas

Neglected tropical diseases (NTDs) have\ud been recently identified as significant public\ud health problems in Texas and elsewhere in\ud the American South. A one-day forum on the\ud landscape of research and development and\ud the hidden burden of NTDs in Texas\ud explored the next steps to coordinate advocacy,\ud public health, and research into a\ud cogent health policy framework for the\ud American NTDs. It also highlighted how\ud U.S.-funded global health research can serve\ud to combat these health disparities in the\ud United States, in addition to benefiting\ud communities abroad

Social, Clinical and Microbiological Differential Characteristics of Tuberculosis among Immigrants in Spain

BACKGROUND: To identify the differential tuberculosis (TB) characteristics within the immigrant population with respect to natives in Spain. METHODOLOGY/PRINCIPAL FINDINGS: A prospective cohort study design was implemented to examine the TB cases diagnosed and starting standard antituberculous treatment in Spain, between January 1st 2006 and March 31st 2007. A logistic regression analysis was performed to determine differential characteristics. 1,490 patients were included in the study population, 1,048 natives and 442 (29.7%) immigrants. According to the multivariate analysis, the following variables were significantly associated with immigrant TB cases: younger age (OR = 3.79; CI:2.16-6.62), living in group situation (OR = 7.61; CI:3.38-12.12), lower frequency of disabled (OR:0.08; CI:0.02-0.26) and retired (OR:0.21; CI:0.09-0.48) employment status, lower frequency of pulmonary disease presentation (OR = 0.47; CI:0.24-0.92), primary or emergency care admission (OR = 1.80; CI:1.05-3.06 and OR = 2.16; CI:1.36-3.45), drug resistance (OR = 1.86; CI:1.01-3.46), treatment default (OR:2.12; CI:1.18-3.81), lower frequency of alcohol and cigarette consumption (OR = 2.10; CI:1.42-3.11 and OR = 2.85; CI:2.10-3.87 respectively), more directly observed treatment (OR = 1.68; CI:1.04-2.69), and poor understanding of TB disease and its treatment (OR = 3.11; CI:1.86-5.20). The low percentage of primary MDR-TB in the native population (0.1% vs. 2.2% of immigrants) should be noted. CONCLUSIONS/SIGNIFICANCE: The differences show the need to introduce specific strategies in the management of TB within the immigrant population, including the improvement of social and work conditions