ZEB1 is a Subgroup-Specific Marker of Prognosis and Potential Drug Target in Medulloblastoma.

Medulloblastoma (MB) is a malignant brain tumor that afflicts mostly children and adolescents and presents four distinct molecular subgroups, known as WNT, SHH, Group 3, and Group 4. ZEB1 is a transcription factor that promotes the expression of mesenchymal markers while restraining expression of epithelial and polarity genes. Because of ZEB1 involvement in cerebellum development, here we investigated the role of ZEB1 in MB. We found increased expression of ZEB1 in MB tumor samples compared to normal cerebellar tissue. Expression was higher in the SHH subgroup when compared to all other MB molecular subgroups. High ZEB1 expression was associated with poor prognosis in Group 3 and Group 4, whereas in patients with WNT tumors poorer prognosis were related to lower ZEB1 expression. There was a moderate correlation between ZEB1 and MYC expression in Group 3 and Group 4 MB. Treatment with the immunomodulator and histone deacetylase (HDAC) inhibitor fingolimod (FTY720) reduced ZEB1 expression specifically in D283 cells, which are representative of Group 3 and Group 4 MB. These findings reveal novel subgroup-specific associations of ZEB1 expression with survival in patients with MB and suggest that ZEB1 expression can be reduced by pharmacological agents that target HDAC activity.

Histone Deacetylase Inhibitors in Pediatric Brain Cancers: Biological Activities and Therapeutic Potential.

Brain cancers are the leading cause of cancer-related deaths in children. Biological changes in these tumors likely include epigenetic deregulation during embryonal development of the nervous system. Histone acetylation is one of the most widely investigated epigenetic processes, and histone deacetylase inhibitors (HDACis) are increasingly important candidate treatments in many cancer types. Here, we review advances in our understanding of how HDACis display antitumor effects in experimental models of specific pediatric brain tumor types, i.e., medulloblastoma (MB), ependymoma (EPN), pediatric high-grade gliomas (HGGs), and rhabdoid and atypical teratoid/rhabdoid tumors (ATRTs). We also discuss clinical perspectives for the use of HDACis in the treatment of pediatric brain tumors.

Fingolimod (FTY720) reduces viability and survival and increases histone H3 acetylation in medulloblastoma cells.

Histone deacetylase inhibitors (HDACis) are epigenetic agents that display antitumor activities in experimental medulloblastoma (MB). Fingolimod (FTY720), an immunosuppressant agent currently used in the treatment of multiple sclerosis, also has anticancer actions and can act as an HDACi. Here we examined whether fingolimod can inhibit human MB cell viability and survival, and if the effects are accompanied by increased histone acetylation. D283 and DAOY MB cells were treated with different doses of fingolimod. Cell viability was assessed by cell counting in a hemocytometer, and cell survival was analyzed with a colony formation assay. Histone H3 acetylation was measured with an enzyme-linked immunosorbent assay (ELISA). Fingolimod at 7.5 or 10 µM, but not at 5 µM, induced a significant reduction in cell viability in D283 and DAOY cultures, and similar results were observed for inhibition of cell survival. In both cell lines, fingolimod also led to a significant increase in the levels of acetylated H3. These findings provide preliminary evidence indicating that fingolimod induces antitumor activities in MB, possibly through a mechanism which increases H3 histone acetylation.

Lifestyle, quality of life, nutritional status and headache in school-age children.

BACKGROUND: Headache has been described as a factor with significant negative impact on the quality of life of school-aged children with a high risk of developing in chronic and persistent form in adulthood. Among other headache associated triggers or aggravating factors, lifestyle and obesity has been investigated, but results are still conflicting. OBJECTIVE: To evaluate the prevalence of headache in school-aged children and its relationship to anthropometric characteristics, lifestyle, and quality of life. METHODS: A cross-sectional study was conducted in six schools located in two cities in southern Brazil, involving 750 students aged 7 to 14 years. Information was collected on sociodemographic characteristics, clinical variables (presence of headache and menarche), anthropometric data, lifestyle, and quality of life. RESULTS: A total of 185 (24.7%) students reported having headache crises in the last 3 months. Among students aged 10 to 14 years, presence of headache was associated with female sex, affecting 32.2% of girls vs. 23.3% of boys (p = 0.042, chi-square test). Anthropometric parameters (data on overweight/obesity) were consistent with national prevalence rates, and there was no association between Body Mass Index (BMI) and headache. Regarding lifestyle, 2.0% of students reported smoking and 1.6% consuming alcohol occasionally, and neither was associated with headache. Quality of life, especially aspects of social life, appeared to be affected by the presence of headache. CONCLUSION: This study found a high prevalence of headache in school-aged children, which was associated with female students aged 10-14 years and quality of life.

Introducción: Dolor de cabeza se ha descrito como un factor con impacto negativo significativo en la calidad de vida de los niños en edad escolar, con alto riesgo de desarrollar la forma crónica y persistente en la edad adulta. Entre otros factores desencadenantes o agravantes asociados, se ha investigado el estilo de vida y la obesidad, pero los resultados siguen siendo contradictorios. Objetivo: Evaluar la prevalencia de dolor de cabeza en niños en edad escolar y su relación con las características antropométricas, estilo de vida y calidad de vida. Métodos: Un estudio transversal se llevó a cabo en seis escuelas ubicadas en dos ciudades del sur de Brasil, con la participación de 750 estudiantes de 7 a 14 años. Se obtuvo información sobre características sociodemográficas, variables clínicas (presencia de dolor de cabeza y la menarquia), datos antropométricos, estilo de vida y calidad de vida. Resultados: Un total de 185 (24,7%) estudiantes reportaron tener crisis de dolor de cabeza en los últimos 3 meses. Entre los estudiantes de 10 a 14 años, presencia de dolor de cabeza se asoció con el sexo femenino, que afecta a un 32,2% de niñas frente a un 23,3% de los varones (p = 0,042, chi-cuadrado). Parámetros antropométricos (datos de sobrepeso/ obesidad) fueron consistentes con las tasas nacionales de prevalencia, y no hubo asociación entre el Índice de Masa Corporal (IMC) y dolor de cabeza. En cuanto a estilo de vida, 2,0% de los estudiantes reportaron fumar y un 1,6% el consumo de alcohol de vez en cuando, y no se asoció con dolor de cabeza. La calidad de vida, especialmente los aspectos de la vida social, parece estar afectada por la presencia de dolor de cabeza. Conclusión: Este estudio encontró una alta prevalencia de dolor de cabeza en niños en edad escolar, que se asoció con estudiantes de 10-14 años y la calidad de vida.

Lifestyle, quality of life, nutritional status and headache in school-aged children / Estilo de vida, calidad de vida, estado nutricional y dolor de cabeza en edad escolar

BACKGROUND: Headache has been described as a factor with significant negative impact on the quality of life of school-aged children with a high risk of developing in chronic and persistent form in adulthood. Among other headache associated triggers or aggravating factors, lifestyle and obesity has been investigated, but results are still conflicting. OBJECTIVE: To evaluate the prevalence of headache in school-aged children and its relationship to anthropometric characteristics, lifestyle, and quality of life. METHODS: A cross-sectional study was conducted in six schools located in two cities in southern Brazil, involving 750 students aged 7 to 14 years. Information was collected on sociodemographic characteristics, clinical variables (presence of headache and menarche), anthropometric data, lifestyle, and quality of life. RESULTS: A total of 185 (24.7%) students reported having headache crises in the last 3 months. Among students aged 10 to 14 years, presence of headache was associated with female sex, affecting 32.2% of girls vs. 23.3% of boys (p = 0.042, chi-square test). Anthropometric parameters (data on overweight/obesity) were consistent with national prevalence rates, and there was no association between Body Mass Index (BMI) and headache. Regarding lifestyle, 2.0% of students reported smoking and 1.6% consuming alcohol occasionally, and neither was associated with headache. Quality of life, especially aspects of social life, appeared to be affected by the presence of headache. CONCLUSION: This study found a high prevalence of headache in school-aged children, which was associated with female students aged 10-14 years and quality of life (AU)

Introducción: Dolor de cabeza se ha descrito como un factor con impacto negativo significativo en la calidad de vida de los niños en edad escolar, con alto riesgo de desarrollar la forma crónica y persistente en la edad adulta. Entre otros factores desencadenantes o agravantes asociados, se ha investigado el estilo de vida y la obesidad, pero los resultados siguen siendo contradictorios. Objetivo: Evaluar la prevalencia de dolor de cabeza en niños en edad escolar y su relación con las características antropométricas, estilo de vida y calidad de vida. Métodos: Un estudio transversal se llevó a cabo en seis escuelas ubicadas en dos ciudades del sur de Brasil, con la participación de 750 estudiantes de 7 a 14 años. Se obtuvo información sobre características sociodemográficas, variables clínicas (presencia de dolor de cabeza y la menarquia), datos antropométricos, estilo de vida y calidad de vida. Resultados: Un total de 185 (24,7%) estudiantes reportaron tener crisis de dolor de cabeza en los últimos 3 meses. Entre los estudiantes de 10 a 14 años, presencia de dolor de cabeza se asoció con el sexo femenino, que afecta a un 32,2% de niñas frente a un 23,3% de los varones (p = 0,042, chi-cuadrado). Parámetros antropométricos (datos de sobrepeso/ obesidad) fueron consistentes con las tasas nacionales de prevalencia, y no hubo asociación entre el Índice de Masa Corporal (IMC) y dolor de cabeza. En cuanto a estilo de vida, 2,0% de los estudiantes reportaron fumar y un 1,6% el consumo de alcohol de vez en cuando, y no se asoció con dolor de cabeza. La calidad de vida, especialmente los aspectos de la vida social, parece estar afectada por la presencia de dolor de cabeza. Conclusión: Este estudio encontró una alta prevalencia de dolor de cabeza en niños en edad escolar, que se asoció con estudiantes de 10-14 años y la calidad de vida (AU)

Cardiovascular disease risk in women with migraine.

BACKGROUND: Studies suggest a higher prevalence of unfavourable cardiovascular risk factors amongst migraineurs, but results have been conflicting. The aim of this study was to investigate traditional and newly recognized risk factors as well as other surrogate markers of cardiovascular risk in obese and normal weight women with migraine. METHODS: Fifty-nine adult female probands participated in this case-control study. The sample was divided into normal weight and obese migraineurs and age- and body mass index-matched control groups. The following cardiovascular risk factors were analyzed: serum levels of lipids, fasting glucose, and insulin; insulin resistance; blood pressure; smoking (categorized as current, past or never); Framingham 10-year risk of general cardiovascular disease score; C-reactive protein; family history of cardiovascular disease; physical activity; sleep disturbances; depression; and bioelectrical impedance phase angle. The means of continuous variables were compared using Student's t-test for independent samples or the Mann-Whitney U-test (for 2 groups) and ANOVA or the Kruskal-Wallis test (for 4 groups) depending on the distribution of data. RESULTS: All migraineurs were sedentary irrespective of nutritional status. Migraineurs had higher depression scores and shorter sleep duration, and obese migraineurs, in particular, had worse sleep quality scores. Insulin resistance and insulinaemia were associated with obesity, and obese migraineurs had lower HDL-c than normal weight controls and migraineurs. Also, the Framingham risk score was higher in obese migraineurs. CONCLUSION: These findings suggest that female migraineurs experience marked inactivity, depression, and some sleep disturbance, that higher insulin resistance and insulinaemia are related to obesity, and that obesity and migraine probably exert overlapping effects on HDL-c levels and Framingham 10-year cardiovascular risk.

Body mass index, abdominal obesity, body fat and migraine features in women / Índice de masa corporal, obesidad abdominal, grasa y las características de la migraña en mujeres

Background: Studies seeking to establish an association between migraine and anthropometric parameters have thus far been inconclusive. Furthermore, drugs used for migraine prophylaxis may be associated with changes in body weight. Objective: To investigate the potential association of anthropometric parameters and body fat percentage with attack patterns and use of prophylactic medication in migraineurs. Methods: Cross-sectional study that assessed the body mass index, waist circumference, body fat percentage and related clinical variables (characteristics of attacks and the use of prophylactic medication) in female outpatients with migraine. Results: 166 female migraineurs aged > 18 years (mean age, 45 ± 14 years) were included in the study. Migraine without aura was most prevalent (71.7%). Mean body mass index and body fat percentage were 27.8±6.0 kg/m2 and 36.4 ± 8.3% respectively. Body mass index and waist circumference were weakly correlated with frequency of attacks over 6 months (rs = 0.162, p < 0.05 and rs = 0.187, p < 0.05 respectively). These correlations remains weak considering only premenopausal women, but disappear in the older women. Stratification of analysis by migraine type field shows a moderate correlation between migraine with aura and frequency of attacks over 6 months and body mass index (rs = 0.369, p < 0.05), as well as waist circumference (rs = 0.423, p < 0.01). Patients who were on prophylactic medication had higher body mass index, waist circumference, and body fat percentage values (p < 0.01, Student t-test). Conclusion: This study revealed a potential, though tenuous association between migraine and anthropometric parameters and frequency of attacks, which does not reflect on the duration, severity, and disability of attacks, with patterns differing by migraine type, reproductive age and prophylactic medication (AU)

Introducción: Los estudios que tratan de establecer una asociación entre la migraña y los parámetros antropométricos hasta ahora han sido poco concluyentes. Además, los fármacos utilizados para la profilaxis de la migraña pueden estar asociados con cambios en el peso corporal. Objetivos: Investigar la posible asociación de los parámetros antropométricos y el porcentaje de grasa corporal con patrones de ataque y el uso de la profilaxis en los pacientes con migraña. Métodos: Estudio transversal que evaluó el índice de masa corporal, circunferencia de cintura, porcentaje de grasa corporal y las variables clínicas (características de los ataques y uso de medicación) en mujeres con migraña. Resultados: 166 mujeres con migraña > 18 años (edad media, 45 ± 14 años) fueron incluidos en el estudio. Migraña sin aura era más frecuente (71,7%). La media del índice de masa corporal y porcentaje de grasa corporal fueron 27,8 ± 6,0 kg/m2 y 36,4 ± 8,3%, respectivamente. Índice de masa corporal y la circunferencia de cintura se correlacionaron débilmente con la frecuencia de los ataques durante 6 meses (rs = 0,162, p < 0,05 y r = 0,187, p < 0,05, respectivamente). Estas correlaciones se mantiene débil considerando sólo las mujeres premenopáusicas, pero desaparecen en las mujeres mayores. La estratificación de los análisis por tipo migraña muestra una correlación moderada entre la migraña con aura y la frecuencia de los ataques de más de 6 meses y el índice de masa corporal (rs = 0,369, p < 0,05), así como la circunferencia de cintura (rs = 0,423, p < 0,01) . Los pacientes que estaban tomando medicamentos profilácticos tuvieron un mayor índice de masa corporal, circunferencia de la cintura, y los valores de porcentaje de grasa corporal (p < 0,01, prueba t de Student). Conclusiones: Este estudio reveló un potencial, aunque débil asociación entre la migraña y los parámetros antropométricos y la frecuencia de ataques, que no refleja la duración, la gravedad y la incapacidad de los ataques, que tienen diferentes modelos según el tipo de migraña, la edad reproductiva y la medicación profiláctica (AU)

Body mass index, abdominal obesity, body fat and migraine features in women.

BACKGROUND: Studies seeking to establish an association between migraine and anthropometric parameters have thus far been inconclusive. Furthermore, drugs used for migraine prophylaxis may be associated with changes in body weight. OBJECTIVE: To investigate the potential association of anthropometric parameters and body fat percentage with attack patterns and use of prophylactic medication in migraineurs. METHODS: Cross-sectional study that assessed the body mass index, waist circumference, body fat percentage and related clinical variables (characteristics of attacks and the use of prophylactic medication) in female outpatients with migraine. RESULTS: 166 female migraineurs aged ≥18 years (mean age, 45 ± 14 years) were included in the study. Migraine without aura was most prevalent (71.7%). Mean body mass index and body fat percentage were 27.8±6.0 kg/m² and 36.4 ± 8.3% respectively. Body mass index and waist circumference were weakly correlated with frequency of attacks over 6 months (rs = 0.162, p < 0.05 and rs = 0.187, p < 0.05 respectively). These correlations remains weak considering only premenopausal women, but disappear in the older women. Stratification of analysis by migraine type field shows a moderate correlation between migraine with aura and frequency of attacks over 6 months and body mass index (rs = 0.369, p < 0.05), as well as waist circumference (rs = 0.423, p < 0.01). Patients who were on prophylactic medication had higher body mass index, waist circumference, and body fat percentage values (p < 0.01, Student t-test). CONCLUSION: This study revealed a potential, though tenuous association between migraine and anthropometric parameters and frequency of attacks, which does not reflect on the duration, severity, and disability of attacks, with patterns differing by migraine type, reproductive age and prophylactic medication.

Introducción: Los estudios que tratan de establecer una asociación entre la migraña y los parámetros antropométricos hasta ahora han sido poco concluyentes. Además, los fármacos utilizados para la profilaxis de la migraña pueden estar asociados con cambios en el peso corporal. Objetivos: Investigar la posible asociación de los parámetros antropométricos y el porcentaje de grasa corporal con patrones de ataque y el uso de la profilaxis en los pacientes con migraña. Métodos: Estudio transversal que evaluó el índice de masa corporal, circunferencia de cintura, porcentaje de grasa corporal y las variables clínicas (características de los ataques y uso de medicación) en mujeres con migraña. Resultados: 166 mujeres con migraña ≥18 años (edad media, 45 ± 14 años) fueron incluidos en el estudio. Migraña sin aura era más frecuente (71,7%). La media del índice de masa corporal y porcentaje de grasa corporal fueron 27,8 ± 6,0 kg/m2 y 36,4 ± 8,3%, respectivamente. Índice de masa corporal y la circunferencia de cintura se correlacionaron débilmente con la frecuencia de los ataques durante 6 meses (rs = 0,162, p < 0,05 y r = 0,187, p < 0,05, respectivamente). Estas correlaciones se mantiene débil considerando sólo las mujeres premenopáusicas, pero desaparecen en las mujeres mayores. La estratificación de los análisis por tipo migraña muestra una correlación moderada entre la migraña con aura y la frecuencia de los ataques de más de 6 meses y el índice de masa corporal (rs = 0,369, p < 0,05), así como la circunferencia de cintura (rs = 0,423, p < 0,01) . Los pacientes que estaban tomando medicamentos profilácticos tuvieron un mayor índice de masa corporal, circunferencia de la cintura, y los valores de porcentaje de grasa corporal (p < 0,01, prueba t de Student). Conclusiones: Este estudio reveló un potencial, aunque débil asociación entre la migraña y los parámetros antropométricos y la frecuencia de ataques, que no refleja la duración, la gravedad y la incapacidad de los ataques, que tienen diferentes modelos según el tipo de migraña, la edad reproductiva y la medicación profiláctica.

Dietary aspects of migraine trigger factors.

The significance of dietary factors as triggers for migraines is controversial, and the assessment of this topic is complex and inconclusive. In order to evaluate the published evidence on dietary triggers, a critical review of the literature was performed by conducting a search for food item descriptors linked to migraines in the PubMed and SciELO databases. Reviews and relevant references cited within the articles that resulted from the search were also included. Of the 45 studies reviewed, 16 were population studies that involved the association between migraines and eating habits or the prevalence of related dietary factors; 12 involved interventions or analyzed observational prospective cohorts; and 17 were retrospective studies. Approximately 30 dietary triggers were explored in total, although only seven of these were addressed experimentally. In the prospective studies, patients were instructed to keep a diary; two of these studies involved dietary interventions. Conclusions that are based on nonpharmacological prophylactic strategies with a scientific basis and that show an association between certain dietary factors and the triggering of migraines are limited by the lack of prospective studies with clear experimental designs. Nevertheless, the high frequency of possible specific dietary triggers validates efforts to elucidate the involvement of food-related factors in precipitating migraines.

Prevalência de anticorpos antimicrossomais em pacientes com esclerose múltipla / Prevalence of antimicrosomal antibodies in patients with multiple sclerosis

O objetivo deste estudo consiste em avaliar a prevalência de anticorpos antimicrossomais (AAM), a função tireóidea e a ocorrência de sintomas relacionados ao hipotireoidismo em pacientes com esclerose multipla (EM). Em um grupo de 21 pacientes com EM, foi realizado exameclínico, foram dosados o TSH, T4 e T4 livre e pesquisados AAM. A média de idade foi 41,05 anos e a média de tempo de doença foi 85,9 meses. Os sintomas relacionados ao hipotireoidismo foram fadiga, fraqueza, letargia e parestesias. Os AAM foram encontrados em 4 pacientes (19 por cento). O tempo de doença foi dividido em três períodos: <60 meses (3 pacientes AAM+/7AAM-), 60-120 meses (8 pacientes AAM-) e >120 meses (1 paciente AAM+/2 AAM-). Dois pacientes apresentaram níveis de T4 livre diminuídos, porém com T4 e TSH normais. Em 1 paciente, constatou-se hipotireoidismo subclínico, e em outro, hipotireoidismo clássico. Conclui-se que na avaliação dos pacientes com EM, em vista da falta de precisão na avaliação clínica do hipotireoidismo ocasionada pela sobreposição de sintomas referentes à EM, devam ser incorporadas as dosagens das provas de função tireóidea (PFT) e dos AAM.

[Prevalence of antimicrosomal antibodies in patients with multiple sclerosis]. / Prevalência de anticorpos antimicrossomais em pacientes com esclerose múltipla.

The aim of this study was to assess the prevalence of Antimicrosomal Antibodies AMA, thyroid function and the occurrence of hypothyroidism symptoms in patients with Multiple Sclerosis (MS). Clinical examination was carried out in 21 MS patients; thyroid-stimulating hormone (TSH), thyroxine (T4), free T4 and AMA were measured. Mean age was 41.05 years. Hypothyroidism symptoms included fatigue, weakness, lethargy and paresthesia. AMA were found in four patients (19%). Three categories of disease duration were considered: <60 months (3 patients AMA+; 7 AMA-), 60-120 months (8 patients AMA-), and >120 months (1 patient AMA+; 2 AMA-). Two patients presented decreased free T4 levels, but there was no associated decrease in T4 and TSH levels. In two patients, a mild increase in TSH levels was observed: one presented normal T4 levels (subclinical hypothyroidism) and the other one had low free T4 levels (classical hypothyroidism). We conclude that AMA measurement and thyroid function tests should become part of the routine assessment of MS patients, in view of the inaccuracy currently observed in the assessment of clinical hypothyroidism as a result of the superposition of hypothyroidism and MS signs and symptoms.

Alterações neurológicas em pacientes submetidos a transplante hepático: análise de 30 casos consecutivos / Neurologic alterations in patients submitted to liver transplantation: analysis of 30 consecutive cases

As complicações neurológicas em transplante hepático (TxH) são importante causa de morbi-mortalidade, pois as intercorrências podem resultar de fatores prévios ao TxH, de alterações trans-operatórias, de dificuldades com os imunossupressores, coagulopatias e infecções do período pós-operatório. Nós analisamos , retrospectivamente, a cronologia, as causas e as frequências das alterações neurológicas de 30 pacientes adultos submetidos a TxH e constatamos que nossos resultados diferem ligeiramente dos apresentados em outras séries.