High frequencies of telomeric associations, chromosome aberrations, and sister chromatid exchanges in ulcerative colitis

Chromosome instability provides a predisposing background to malignancy, contributing to the crucial genetic changes in multistep carcinogenesis. The aim of this work was to analyze chromosome instability in patients with ulcerative colitis (UC) to achieve a better understanding of the increased risk for colorectal cancer. METHODS: Peripheral blood lymphocyte cultures from 20 untreated UC patients and 24 controls were used to study chromosome instability by assessing telomeric associations (TAS), chromosome aberrations (CA), and sister chromatid exchanges (SCE). RESULTS: Mean frequencies of TAS and CA were significantly increased in UC patients compared to controls (p < 0.001). Chromosomes 10, 11, 21, 16, and 19 were the most frequently involved in TAS. A total of 104 CA clustered in 66 breakpoints could be exactly localized. Seven nonrandom bands significantly affected in UC patients were found (p < 0.004), showing a significant correlation with the location of cancer breakpoints (p < 0.003), particularly with colorectal carcinoma rearrangements. SCE analysis showed higher levels in patients compared to controls (p < 0.006), but no differences were observed in cell cycle kinetics. CONCLUSIONS: Our results demonstrate the presence of an unstable genome in UC patients that could be related to the cancer development observed in this disease.Fil: Cottliar, Alejandra. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Fundia, Ariela Freya. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; ArgentinaFil: Boerr, Luis. Hospital de Gastroenterología “Bonorino Udaondo,; ArgentinaFil: Sambuelli, Alicia. Hospital de Gastroenterología “Bonorino Udaondo,; ArgentinaFil: Negreira, Silvia. Hospital de Gastroenterología “Bonorino Udaondo,; ArgentinaFil: Gil, Anibal. Hospital de Gastroenterología “Bonorino Udaondo,; ArgentinaFil: Gomez, Juan Carlos. Provincia de Buenos Aires. Hospital Interzonal General de Agudos Gral. San Martin; ArgentinaFil: Chopita, Nestor. Provincia de Buenos Aires. Hospital Interzonal General de Agudos Gral. San Martin; ArgentinaFil: Bernedo, Alberto. Provincia de Buenos Aires. Hospital Interzonal General de Agudos Gral. San Martin; ArgentinaFil: Slavutsky, Irma Rosa. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Academia Nacional de Medicina de Buenos Aires. Instituto de Investigaciones Hematológicas "Mariano R. Castex"; Argentin

Natural History of MYH7-Related Dilated Cardiomyopathy

BACKGROUND Variants in myosin heavy chain 7 (MYH7) are responsible for disease in 1% to 5% of patients with dilated cardiomyopathy (DCM); however, the clinical characteristics and natural history of MYH7-related DCM are poorly described. OBJECTIVES We sought to determine the phenotype and prognosis of MYH7-related DCM. We also evaluated the influence of variant location on phenotypic expression. METHODS We studied clinical data from 147 individuals with DCM-causing MYH7 variants (47.6% female; 35.6 +/- 19.2 years) recruited from 29 international centers. RESULTS At initial evaluation, 106 (72.1%) patients had DCM (left ventricular ejection fraction: 34.5% +/- 11.7%). Median follow-up was 4.5 years (IQR: 1.7-8.0 years), and 23.7% of carriers who were initially phenotype-negative developed DCM. Phenotypic expression by 40 and 60 years was 46% and 88%, respectively, with 18 patients (16%) first diagnosed at <18 years of age. Thirty-six percent of patients with DCM met imaging criteria for LV noncompaction. During follow-up, 28% showed left ventricular reverse remodeling. Incidence of adverse cardiac events among patients with DCM at 5 years was 11.6%, with 5 (4.6%) deaths caused by end-stage heart failure (ESHF) and 5 patients (4.6%) requiring heart transplantation. The major ventricular arrhythmia rate was low (1.0% and 2.1% at 5 years in patients with DCM and in those with LVEF of <= 35%, respectively). ESHF and major ventricular arrhythmia were significantly lower compared with LMNA-related DCM and similar to DCM caused by TTN truncating variants. CONCLUSIONS MYH7-related DCM is characterized by early age of onset, high phenotypic expression, low left ventricular reverse remodeling, and frequent progression to ESHF. Heart failure complications predominate over ventricular arrhythmias, which are rare. (C) 2022 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation

As crenças e o contexto vital afetam o envolvimento dos pais na educação infantil?

Los estudios sobre la implicación de los padres son abundantes, aunque menos investigaciones analizan qué es lo que los lleva a implicarse. Por ello, se ha tomado como referencia el modelo desarrollado por Hoover-Dempsey y Sandler y la revisión del mismo de Walker, Wilkins, Sandler y Hoover-Dempsey para analizar la implicación en la escuela y el hogar de 100 progenitores (28 padres y 72 madres) con hijos preescolares, y la relación entre estas formas de implicación y sus variables moderadoras, en concreto, su construcción de rol (i.e. sus creencias sobre su papel y la valencia de la escuela) y el contexto vital (i.e. tener tiempo/energía y conocimientos/habilidades para implicarse). Se usaron las escalas presentadas en Walker et al. Los objetivos eran analizar la construcción de rol, el contexto vital y la implicación según el sexo de los participantes y su nivel de estudios; y analizar las relaciones entre la construcción de rol, la percepción del contexto vital y la implicación. Los datos indicaron que los padres percibían tener menos tiempo y energía que las madres. A medida que aumentaba su nivel de estudios, padres y madres opinaban que contaban con más conocimientos sobre el colegio y más habilidades para comunicarse con sus hijos en temas relativos a la escuela. No se hallaron diferencias significativas en la implicación según el sexo o el nivel educativo de los progenitores. Los conocimientos y habilidades percibidas se relacionaron significativamente con la implicación de los progenitores. Estos resultados tienen claras connotaciones educativas.Studies on parental involvement are numerous but less research has been done analyzing what drives parents to get involved. That is why we have used the model developed by Hoover-Dempsey, and Sandler and its revision by Walker, Wilkins, Sandler and Hoover-Dempsey, to study parental involvement at home and at school. Participants were 100 parents (28 fathers and 72 mothers) who had preschool children. Scales informed in Walker et al were used. We related parental involvement at home and at school to parental role construction variables (i.e. beliefs about their role and about school valence) and parental life context (i.e. have time/energy and knowledge/skills to get involved). Our aims were to study parents’ role construction, life context and involvement depending on their gender and their education; and to analyse the relationships between role construction, life context and involvement. Data showed that fathers perceived that they had less time and energy than mothers. As their education increased, parents thought that they had more knowledge about school and more skills to communicate with their children about school. There were no significant differences in parental involvement depending on gender and education. Parental knowledge and skills were significantly related to parental involvement. These results have clear implications in education

Volcanic ash-driven worsening of mucosal inflammation in an experimental colitis model

Particulate matter exposure and related chemical changes in drinking water have been associated with health problems and inflammatory disorders. This study aimed to examine the effect of orally administered ash-water dilution on the gut of mice under normal and inflammatory conditions. Balb/c mice received ash-released soluble and dust-suspended components in the drinking water for 14 days. On day 7, animals were intrarectally instilled with TNBS in ethanol or flagellin from Salmonella typhimurium in PBS. At sacrifice, colon segments were collected and histologic damage, mRNA expression and cytokine levels in tissue were evaluated. In addition, these parameters were also evaluated in IL-10 null mice. We found that mice that received 5% w. fine-ash dilution in the drinking water worsened colitis signs. Weight loss, shortening of the colon, tissue edema with mucosa and submucosa cell infiltration and production of pro-inflammatory cytokines and chemokines were enhanced compared to control mice. A more pronounced inflammation was observed in IL-10 null mice. In addition, markers of NLRP3-dependent inflammasome activation were found in animals exposed to ash. In conclusion, ingestion of contaminated water with dust-suspended particulate matter enhanced the inflammatory response in the gut, probably due to alteration of the gut barrier and promoting an intense contact with the luminal content. This study critically appraises the response for fine particulate matter in uncommon illnesses reported for volcanic ash pollution. We suggest actions to enable better prediction and assessment the health impacts of volcanic eruptions.Fil: Orsini Delgado, María Lucía. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Sambuelli, Alicia. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Negreira, Silvia. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: Gil, Anibal. Gobierno de la Ciudad de Buenos Aires. Hospital de Gastroenterología "Dr. Carlos B. Udaondo"; ArgentinaFil: D'Elia, Leandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; ArgentinaFil: Smaldini, Paola Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Docena, Guillermo H.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; Argentin

Indices de actividad en la enfermedad de Crohn. Revisión crítica y evaluación de su utilidad en el manejo clínico

No se ha definido aún un método gold standard para cuantificar la actividad de la enfermedad de Crohn, por lo que es necesario unificar criterios a través de un consenso mundial. Cada uno de los índices descriptos para tal fin han sido criticados. En el presente trabajo realizamos una revisión de los criterios actualmente utilizados para evaluar la actividad de la enfermedad, destacamos las controversias existentes y los temas que aún requieren ser investigados, y analizamos su utilidad en base a nuestra experiencia

Prevalence of primary sclerosing cholangitis in patients with ulcerative colitis and the risk of developing malignancies. A large prospective study

Background/aim: primary sclerosing cholangitis (PSC) is associated with ulcerative colitis (UC) and seems to be a risk factor for colon cancer. However, taking into account that no data are available in South American population, we analyzed the prevalence of PSC in 1.333 patients with UC and the risk for developing colon cancer. Material: patients with persistent increases of alkaline phosphatase were studied by cholangiography and liver biopsy. To assess the risk of colon cancer, each patient with PSC and UC was matched with two control patients with UC without PSC of the same age, gender, extent and duration of UC. Results: the whole prevalence of PSC was 2.9% (39 patients) reaching 6.2% in extensive colitis. Seven (18 %) out of 39 patients with PSC developed colorectal carcinoma compared with 2 out of 78 (2.6%) in the control group (p=0.006). The cumulative risk of colorectal carcinoma was 11% and 18% after 10 and 20 years in the PSC group compared with 2% and 7% in the control group, respectively (p=0.002). Conclusion: this is the first prospective study performed in Latin America showing that the prevalence of PSC in patients with UC is similar to that reported in the Anglo-Saxon population. Patients with UC and PSC have a high risk of colorectal cancer

Optimization and upscaling of spin coating with organosilane monolayers for low-k pore sealing

© 2016 Elsevier B.V. For porous low-k film to be integrated into the next generation of interconnects, the pores need to be sealed against metal ions and barrier precursors. Self-assembled monolayers (SAMs) from organosilane precursor are spin coated onto 300 mm k = 2.2 low-k wafers. Two solvents, propylene glycol monomethyl ether acetate (PGMEA) and methanol with different dielectric constant of 8.3 and 20.1, are evaluated in terms of SAMs layer quality and sealing efficiency at coupon level. SAMs deposited from PGMEA show better sealing than SAMs deposited from methanol and therefore are selected for upscaling. Full wafer spin coating results show that a concentration of 0.05 mM or below results in a partial coverage and a tilt angle as high as 70° from the backbone to the normal. Aggregation is observed for all tested concentrations and is worse for higher concentrations, which is possibly induced by the non-negligible presence of water in PGMEA solvents. In order to test the sealing efficiency of the SAMs layer against metal barrier precursors, MnN films by chemical vapor deposition (CVD) and TaNx/Ta (TNT) films by physical vapor deposition (PVD) are deposited on SAM coated low-k wafers. HfO2is also deposited by Atomic layer deposition (ALD), which is not considered as a barrier but to test the sealing against ALD precursors. Depth profiling Rutherford Backscattering Spectrometry (RBS) measurements indicate an effective sealing of SAMs against CVD and ALD precursors but not against PVD barrier.status: publishe