RESUMO
BACKGROUND: Copy number variation on chromosome 15q11.2 (BP1-BP2) causes deletion of CYFIP1, NIPA1, NIPA2 and TUBGCP5; it also affects brain structure and elevates risk for several neurodevelopmental disorders that are associated with dendritic spine abnormalities. In rodents, altered cyfip1 expression changes dendritic spine morphology, motivating analyses of human neuronal cells derived from iPSCs (iPSC-neurons). METHODS: iPSCs were generated from a mother and her offspring, both carrying the 15q11.2 (BP1-BP2) deletion, and a non-deletion control. Gene expression in the deletion region was estimated using quantitative real-time PCR assays. Neural progenitor cells (NPCs) and iPSC-neurons were characterized using immunocytochemistry. RESULTS: CYFIP1, NIPA1, NIPA2 and TUBGCP5 gene expression was lower in iPSCs, NPCs and iPSC-neurons from the mother and her offspring in relation to control cells. CYFIP1 and PSD95 protein levels were lower in iPSC-neurons derived from the CNV bearing individuals using Western blot analysis. At 10 weeks post-differentiation, iPSC-neurons appeared to show dendritic spines and qualitative analysis suggested that dendritic morphology was altered in 15q11.2 deletion subjects compared with control cells. CONCLUSIONS: The 15q11.2 (BP1-BP2) deletion is associated with reduced expression of four genes in iPSC-derived neuronal cells; it may also be associated altered iPSC-neuron dendritic morphology.
RESUMO
INTRODUCCIÓN: estudios previos reportan la validación y correspondencia, o ambas, del índice tobillo brazo oscilométrico frente al índice tobillo brazo con Doppler, pero este último no corresponde al patrón de oro. OBJETIVO: determinar la validez de criterio del índice tobillo brazo oscilométrico comparado con la ecografía dúplex arterial de miembros inferiores para detectar enfermedad arterial periférica. METODOLOGÍA: estudio de evaluación de tecnologías diagnósticas realizado por muestreo transversal. De manera consecutiva, se reclutaron 101 personas del Instituto del Corazón de Bucaramanga con mínimo un factor de riesgo cardiovascular. Se midió el índice tobillo brazo oscilométrico con equipo OMRON (marca registrada) M7 HEM 780 y posteriormente se hizo ecografía dúplex arterial de miembros inferiores, esta última patrón de oro; los evaluadores estaban enmascarados. RESULTADOS: las mediciones repetidas de la presión arterial en cada miembro, mostraron una reproducibilidad casi perfecta, pues sus coeficientes de correlación intraclase son superiores a 0,86 y el acuerdo del método fue adecuado más o menos 15 mm Hg, para la mayoría de las mediciones. Según el análisis de la curva ROC, el punto de corte < 1,1 del índice tobillo brazo oscilométrico, cuenta con sensibilidad alta (96,3 porciento), especificidad baja (< 23,81 porciento) y calidad de la sensibilidad moderada (0,67); los puntos de corte inferiores a < 0,9 cursan con especificidad alta (> 90,48 porciento), sensibilidad regular (< 70,37 porciento), valores predictivos positivos, negativos y eficiencia moderados (> 70,37 porciento), razón de probabilidad positiva cercana o superior al ideal (7-10), moderada calidad de la sensibilidad (0,58), sustancial calidad de la especificidad (0,66-0,78) y eficiencia o capacidad discriminatoria (0,62-0,67)...
INTRODUCTION: previous studies reported validation and/or correspondence of ankle-brachial index measured by OMRON (ABIO) versus an ABI measured by Doppler, but the latter is not the gold standard. OBJECTIVE: to determine the criterion validity of ABIO versus arterial duplex ultrasonography of lower extremities (ADULE) in detecting peripheral arterial disease (PAD). METHODS: evaluation study of diagnostic technologies by cross sampling. One hundred one persons with at least one cardiovascular risk factor were recruited consecutively from the Heart Institute in Bucaramanga. The ABIO was measured with the OMRON® HEM 780 equipment, and the ADULE was measured as gold standard; evaluators were blinded. RESULTS: repeated measurements of blood pressure in each extremity showed almost perfect reproducibility, as their correlation coefficients were above 0.86 and the agreement of the method was adequate more or less 15 mm Hg, for most measurements. According to ROC curve analysis, the cutoff for ABIO < 1.1 had high sensitivity (96.3 percentaje), low specificity (< 23.81 percentaje) and moderate quality of sensitivity (0.67); cutoff points lower than 0.9 have high specificity (> 90.48 percentaje), moderate sensibility (<70.37 percentaje), moderate predictive positive and negative values and efficiency (> 70.37 percentage), positive likelihood ratio close to or above the ideal (7-10), moderate quality of sensibility (0.58), substantial quality of specificity (0.66-0.78) and efficiency or discriminatory ability (0.62-0.67)...
