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Williams syndrome (WS) is a neurodevelopmental genetic disorder, due to a 7q11.23 hemizygous deletion. WS has a characteristic neurocognitive profile that includes intellectual disability (ID). Haploinsufficiency of some of the deleted genes is partially associated with the cognitive phenotype. The aim of this paper is to determine the differences in the microRNA (miRNA) expression in WS patients, using a neural cell model from the patients olfactory neuroepithelium (ONE), and to establish the relationship with those genes involved in neurodevelopment and neural function. To assess these goals, we made a comparative analysis of the miRNAs expression profile between WS patients and controls. Through an in silico analysis, we established potential pathways and targets associated with neural tissue. The expression profile shows 14 dysregulated miRNAs, including nervous system (NS)-rich miRNAs such as miR-125b, let-7c and miR-200. Most of these miRNAs have potential targets associated with NS functions while others have been reported to have specific neuronal functions. These data suggest that miRNAs widely contribute to the regulation of neurodevelopmental intrinsic processes, and that specific miRNAs could participate in WS neurobiology.

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Introducción: La quimioterapia tiene indicaciones precisas, su diferimiento puede influir en el resultado del tratamiento, algunas causas son originadas por la situación clínica del paciente, otras médicas y administrativas. Objetivo: Identificar las principales causas que originan diferimiento en la administración de quimioterapia en pacientes pediátricos con cáncer. Metodología: Estudio observacional, prospectivo, se incluyeron 200 pacientes de un mes a 16 años 11 meses de edad, con enfermedades hemato-oncológicas. Se investigaron las causas de diferimiento mediante una lista de cotejo y observación directa durante tres meses. Las variables investigadas fueron: inasistencia del paciente al tratamiento, causas médicas, administrativas y situación clínica del paciente. El análisis estadístico se realizó con medidas de tendencia central. Resultados: El diferimiento de la administración de quimioterapia fue de 13.5%, la principal causa fue la inasistencia a la aplicación del tratamiento con 10.5%, seguido de la punción lumbar traumática 1.5% y neutropenia 1%. Discusión: En 5.5% de las ausencias no se obtuvo el motivo de la inasistencia. El diferimiento puede influir en el resultado del tratamiento ya que la no administración de los medicamentos de acuerdo al programa establecido puede favorecer el surgimiento de clonas resistentes a las drogas que se administran como quimioterapia, teniendo como consecuencia la pérdida del control de la enfermedad. Conclusiones: Se deben implementar estrategias con la ayuda del equipo multidisciplinario para localizar al paciente y recordar a sus padres la cita, así como sensibilizarlos de la importancia al cumplimiento del tratamiento en las fechas establecidas.

Introduction: Chemotherapy has precise indications; deferring it might influence the treatment outcomes. Some causes are originated for clinical situations of patients and others for medical or administrative reasons. Objective: To identify the main causes that deferring chemotherapy administration originates in pediatric patients with cancer. Methodology: Observational and prospective study included 200 patients from 11 months to 16 years and 11 months old with hemato-onchology disorders. Causes of deferring therapy were researched throughout a check list and direct observation during 3 months. The researched variables were: not showing up to the treatment visit, medical causes, administrative reasons, and clinical causes related to patients. Statistical analysis was done with measures of central tendency. Results: Causes of deferring chemotherapy administration were: 13.5% due to not showing up to the treatment visit with 10.5%, followed by 1.5% traumatic lumbar puncture, and 1% due to neutropenia. Discussion: The motive of not showing up in 5.5% was not obtained. Deferring might influence the treatment outcome because the lack of administration might favor the beginning of drug resistant colonies to chemotherapy, having as a consequence losing control of the disease. Conclusions: Some strategies should be implemented with the help of a multidisciplinary team to reach patients and remind their parents their appointment, as well as let them know about the importance of compliance of treatment in booked dates.

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Asian-American (AA) variants of human papillomavirus 16 (HPV-16) are linked to a high incidence of cervical cancer in Mexico, with some evidence strongly suggesting that they are more oncogenic than European (E) variants, including their association with younger women and their higher associated risk of cervical cancer. Differences in the regulation of viral E6/E7 oncogene transcription by the E2 protein may be involved in the higher oncogenicity of AA variants. In E variants, E6/E7 oncogene transcription is repressed by the E2 protein and is frequently up-regulated by the destruction of the E2 gene during viral integration. In contrast, the E2 gene is retained in full in most AA-positive carcinomas, raising the possibility of alternative mechanisms for increasing viral oncogene transcription. The authors investigated whether the higher oncogenicity of AA variants is linked to differences in E6/E7 oncogene transcription and the mechanism of E2 deactivation. E6/E7 and E1/E2 transcripts were explored by RT-PCR in 53 HPV-16-positive cervical carcinomas, 39 retaining (20 European and 19 AA) and 14 having lost (12 European and 2 AA) the E1/E2 genes, and transcription repression activity of the AA E2 genes was tested in four cell lines that constitutively express the beta-galactosidase reporter or E6/E7 genes driven by the viral long control region. E6/E7 oncogene transcripts were found in all carcinomas, but only those positive for AA variants with E1/E2 genes had complete E2 transcripts. E2 transcripts were down-regulated by splicing in E-positive carcinomas retaining E1/E2. AA E2 genes were impaired for repression of E6/E7 oncogene transcription in vivo. These results suggest that E6/E7 oncogene expression starts earlier in AA than E variant infections, since E variants need E2 to be destroyed or down-regulated.

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