De novo UBE2A mutations are recurrently acquired during chronic myeloid leukemia progression and interfere with myeloid differentiation pathways.

Despite the advent of tyrosine kinase inhibitors, a proportion of chronic myeloid leukemia patients in chronic phase fail to respond to imatinib or to second-generation inhibitors and progress to blast crisis. Until now, improvements in the understanding of the molecular mechanisms responsible for chronic myeloid leukemia transformation from chronic phase to the aggressive blast crisis remain limited. Here we present a large parallel sequencing analysis of 10 blast crisis samples and of the corresponding autologous chronic phase controls that reveals, for the first time, recurrent mutations affecting the ubiquitin-conjugating enzyme E2A gene (UBE2A, formerly RAD6A). Additional analyses on a cohort of 24 blast crisis, 41 chronic phase as well as 40 acute myeloid leukemia and 38 atypical chronic myeloid leukemia patients at onset confirmed that UBE2A mutations are specifically acquired during chronic myeloid leukemia progression, with a frequency of 16.7% in advanced phases. In vitro studies show that the mutations here described cause a decrease in UBE2A activity, leading to an impairment of myeloid differentiation in chronic myeloid leukemia cells.

Metronidazole-induced hepatotoxicity in a patient with xeroderma pigmentosum: A case report.

RATIONALE: Whereas metronidazole-induced hepatotoxicity is quite rare in the general population, in individuals carrying a nucleotide excision repair disorder, namely Cockayne syndrome, there is a high risk of developing this complication. PATIENT CONCERNS: We report the case of a 44-year-old man, affected by xeroderma pigmentosum, who was admitted to the hospital presenting aspiration pneumoniae caused by worsening dysphagia and with severe hepatotoxicity during the hospitalization. DIAGNOSES: Acute hepatitis, which was leading to acute liver failure, occurred during antibiotic treatment with metronidazole and ceftazidime with an elevation of liver enzymes consistent with hepatocellular damage pattern. INTERVENTIONS: Hydration with glucose 5% solution, pantoprazole and vitamin K were administered, meanwhile other causes of hepatitis were ruled out and the ongoing antibiotic treatment was stopped suspecting a drug-induced liver injury. OUTCOMES: Liver function nearly completely recovered 1 month later with a first rapid improvement, within few days, of aminotransferases and coagulation studies, and slower of cholestatic enzymes. LESSONS: We describe the first case available in the literature of hepatotoxicity associated with metronidazole treatment in a xeroderma pigmentosum patient. Clinicians therefore, based on this report and according to the possible underlying mechanism shared by other genetic diseases characterized by alterations in the pathway of DNA-repair, should consider such adverse event also in patients affected by this rare disease.

Estructura factorial de la “Escala de actitudes y creencias”: réplica del estudio de Heman y Niebler / The factorial structure of the “Scale of Attitudes and Beliefs”: a replication of Heman and Niebler´s study

El objetivo de la investigación es confirmar la estructura psicométrica de la versión en español de la Escala de actitudes y creencias, en una muestra de 1.286 estudiantes que pertenecen a una institución educativa mexicana. Previamente, Heman y Niebler (2011) habían identificado en una muestra de 800 estudiantes universitarios mexicanos, una solución de tres factores (Tolerancia a la frustración, Demandas de éxito y comodidad y Aprobación) con índices de consistencia interna ≥ 0,89. Los resultados del análisis factorial y de fiabilidad de nuestra investigación confirman los mismos tres factores, con niveles de consistencia interna ≥ 0,78. Se concluye que el instrumento es válido y fiable para la evaluación del contenido irracional de las creencias en estudiantes mexicanos

The main objective of this study was to confirm the psychometric structure of the Spanish version of Elli´s Scale of Attitudes and Beliefs in a sample of 1,286 students belonging to a different Mexican university from the one in the study by Heman and Niebler (2011). In their sample of 800 Mexican college students, Heman and Niebler found a three factor solution (frustration tolerance, demands and approval) with reliability coefficients above .89. Results of factor and reliability analysis in our study confirm the same factors with internal consistency levels ≥ .78. We conclude that the instrument is valid and reliable for the evaluation of the content of irrational beliefs in Mexican students