HOPX homeobox methylation in differentiated thyroid cancer and its clinical relevance

Background: The inactivation of the tumor-suppressor homeodomain-only protein X (HOPX) usually involves promoter methylation in several cancer types. This study aimed to investigate the HOPX-β mRNA expression and promoter methylation and their clinical relevance in differentiated thyroid cancer (DTC). Patients and methods: Clinicopathological data and paraffin-embedded thyroid tumor tissues from 21 patients with DTC and 6 with benign tumors (T) and their non-tumor parenchyma (NT) were investigated. Tumor cell lines (FTC238, FTC236 and WRO) were treated with demethylating agent. HOPX-β mRNA expression was assessed by qRT-PCR and methylation status by Q-MSP. Thyroid cancer data from Cancer Genome Atlas (TCGA) was also collected. Results: HOPX-β mRNA re-expression in two cell lines treated with demethylating agent was observed concomitantly with reduced promoter methylation. Reduced mRNA expression in T group compared to their NT was observed, and reduced protein expression in T compared to NT was observed in three cases. Low mRNA expression with high methylation status was detected in 6/14 DTC samples. High methylation status was associated with older age at diagnosis, recurrent or progressive disease and with the presence of new neoplasm event post initial therapy while hyper-methylation correlated with worse overall survival, worse disease-free status and older age. Conclusion: A moderate coupling of downregulation of HOPX-β mRNA expression in DTC followed by high HOPX-β promoter methylation was observed however; high HOPX promoter methylation status was associated with the worse prognosis of DTC patients

Representações sociais de Agentes Comunitários de Saúde acerca do consumo de drogas

Este artigo discute as representações sociais de Agentes Comunitários de Saúde (ACS) acerca do consumo de drogas, como recorte de um estudo qualitativo de cunho etnográfico, cuja produção dos dados ocorreu no período de janeiro/2006 a janeiro/2007. Um conjunto de técnicas foi aplicado para profissionais que atuam numa Unidade Básica de Saúde de Salvador-BA, dentre eles 22 ACS. A Teoria das Representações Sociais foi adotada como eixo teórico, e gênero como categoria de análise. Os ACS reconhecem a proximidade e o envolvimento das mulheres com o fenômeno das drogas na comunidade onde moram e atuam, porém não adotam em seu trabalho nenhuma ação direcionada para tal problemática. As representações sociais apreendidas reproduzem estereótipos e preconceitos em relação às drogas e às pessoas usuárias de drogas, vinculadas, sobretudo, ao sexo e classe social, assinalando a invisibilidade do consumo de drogas como um problema de saúde para o grupo estudado.Este artículo discute las representaciones sociales de Agentes Comunitarios de Salud (ACS) respecto del consumo de drogas, como elemento integrante de un estudio cualitativo, de cuño etnográfico, cuyos datos fueron recogidos en el período de enero 2006 - enero 2007. Se aplicó un conjunto de técnicas en profesionales con actuación en una Unidad Básica de Salud de Salvador, BA, Brasil, de los cuales 22 eran ACS. La Teoría de las Representaciones Sociales fue adoptada como eje teórico y el género como categoría de análisis. Los ACS reconocen la proximidad y el grado de compromiso de las mujeres con el fenómeno de las drogas en la comunidad en donde viven y actúan; no obstante no adopten en su trabajo ninguna acción direccionada hacia tal problemática. Las representaciones sociales aprehendidas reproducen estereotipos y preconceptos en relación a las drogas y a las personas usuarias vinculadas, sobre todo al sexo y clase social y señalan la invisibilidad del consumo de drogas como un problema de salud para el grupo estudiado.This paper discusses on the social representations of community health agents (CHAs) about drug use as part of a qualitative, ethnographic study with data collected by means of a set of research techniques among health professionals including 22 CHAs in a basic health unit in Salvador, Bahia (Brazil) from January, 2006 to January, 2007. The Theory of Social Representations was adopted as the theoretical framework whereas gender was the chosen analytical category. CHAs were found to recognize the women's proximity and participation in the drug phenomenon in the community where they live and act, although they take no professional measures towards such an issue. Their social representations were shown to reproduce stereotypes and prejudices towards drug users and drug use, especially gender- and social class-related, while highlighting the invisibility of drug use as a health problem for the population under study

Síndrome de aspiração meconial - experiência de um centro terciário

Resumo: Introdução: Aproximadamente 5% dos recém-nascidos com evidência de mecónio no líquido amniótico desenvolvem a síndrome de aspiração meconial (SAM). Objectivos: Conhecer os dados demográficos, a morbilidade e mortalidade na dependência da SAM e identificar possíveis factores de risco. Métodos: : Estudo retrospectivo dos recém-nascidos com SAM nascidos num hospital terciário entre 1 de Janeiro de 1997 e 31 de Dezembro de 2008. Resultados: A SAM foi responsável por 1,4% das admissões na Unidade de Cuidados Intensivos Neonatais (UCIN), verificando-se uma tendência para o decréscimo no número de internamentos ao longo dos anos, principalmente dos casos com líquido amniótico tingido de mecónio. No período de estudo foram analisados 72 recém-nascidos: 55,6% do sexo feminino, 62,5% com parto por cesariana, 93% com idade gestacional > 36 semanas e 91,2% com peso ao nascimento > 2500 g. 69% dos recém-nascidos apresentaram Índice de Apgar < 7 no 1. ° minuto e 23,6% Índice de Apgar < 7 no 5.° minuto; bradicardia fetal foi observada em 26,4% dos recém-nascidos e taquicardia em 1,4%. A presença de mecónio no líquido amniótico condicionou o desenvolvimento de hipóxia (58,3%), necessidade de ventilação mecânica (43,1%), acidose respiratória e/ou metabólica (30,6%), hipertensão pulmonar (11,1%) e encefalopatia hipóxico-isquémica (29,2%). A taxa de mortalidade foi de 2,8%. A presença de mecónio espesso esteve associada a maiores taxas de morbilidade e mortalidade. Conclusão: O número de internamentos por SAM tem vindo a diminuir principalmente devido ao decréscimo das admissões por líquido amniótico tingido de mecónio, enquanto o número de casos de mecónio espesso tem permanecido constante ao longo dos anos. O Índice de Apgar < 7 no 1. ° minuto e a presença de sinais de sofrimento fetal durante o trabalho de parto apresentaram relação com a SAM. A morbilidade associada à SAM permanece significativa. Abstract: Background: Approximately 5% of infants born with a meconium-stained amniotic fluid (MSAF) develop meconium aspiration syndrome (MAS). Aim: The aims of this study were to analyse demographic data, morbidity and mortality associated with MAS and to identify possible risk factors. Methods: Retrospective chart review of newborns with MAS delivered at a tertiary centre from January 1st, 1997 to December 31st, 2008. Results: MAS was responsible for 1.4% of all Neonatal Intensive Care Unit (NICU) admissions, with a trend towards a decreasing incidence during the study duration, especially in the cases of thin meconium. Seventy two newborns were analysed during the study period: 55.6% (n = 40) were of the female gender, 62.5% were delivered by caesarean section, 93% had > 36 weeks of gestational age and 91.2% had a birth weight over 2500 g. Sixty-nine percent had an Apgar score < 7 at 1 minute and 23.6% an Apgar score < 7 at 5 minutes; foetal bradicardia was present in 26.4% of the newborns and tachycardia in 1.4%. The presence of meconium was associated with severe asphyxia and carried a bad prognosis with an increased risk of developing hypoxia (58.3%), need of mechanical ventilatory support (43.1%), respiratory and/or metabolic acidosis (30.6%), pulmonary hypertension (11.1%) and hypoxic ischemic encephalopathy (29.2%). The mortality rate was 2.8%. Thick meconium was associated with higher morbidity and mortality rates. Conclusion: The number of admissions for MAS has been decreasing mostly because of a lower admission rate due to thin meconium; the number of cases with thick meconium has remained constant throughout the years. An Apgar score < 7 at 1 minute and signs of foetal distress during labour were associated with MAS. The MAS related morbidity remains significant. Palavras-chave: Síndrome de aspiração meconial, Factores de risco, Morbilidade, Mortalidade, Keywords: Meconium aspiration syndrome, Risk factors, Morbidity, Mortalit

A novel splicing mutation causes analbuminemia in a Portuguese boy.

Analbuminemia is a rare autosomal recessive disorder manifested by the absence or severe reduction of circulating serum albumin in homozygous or compound heterozygous subjects. It is an allelic heterogeneous defect, caused by a variety of mutations within the albumin gene. The analbuminemic condition was suspected in a Portuguese boy who presented with low albumin level (about 3.8 g/L) and a significant hypercholesterolemia, but with no clinical findings. The albumin gene was screened by single strand conformational polymorphism and heteroduplex analysis and submitted to direct DNA sequencing. The proband was found to be homozygous for a previously unreported G>A change at position c.1289+1, the first base of intron 10, which inactivates the strongly conserved GT dinucleotide at the 5' splice site consensus sequence of the intron. The effect of this mutation was evaluated by examining the cDNA obtained by RT-PCR from the albumin mRNA extracted from proband's leukocytes. The splicing defect results in the skipping of the preceding exon. The subsequent reading frame-shift in exon 11 produces a premature stop codon located 33 codons downstream the 5' end of the exon. This extensive cDNA alteration is responsible for the analbuminemic trait. Both parents were found to be heterozygous for the same mutation. DNA and cDNA sequence analysis established the diagnosis of congenital analbuminemia in the proband. The effects of the so far identified splice-site mutations in the albumin gene are discussed

Systemic steroids have a role in treating esophageal strictures in pediatric eosinophilic esophagitis

Background: The role of systemic steroids in the treatment of esophageal strictures in children with Eosinophilic Esophagitis (EoE) is poorly defined. Aims: To describe a cohort of children with EoE-associated esophageal strictures responding to systemic steroids. Methods: Retrospective review of medical records of children with EoE and moderate (&lt;9 mm) to severe (&lt;6 mm) strictures, who responded clinically and endoscopically to systemic steroids. Results: Twenty children (median age 10.6 ± 4.2 years; 17 males) from nine centers in six countries were included in the analysis; 16 had moderate and four, severe strictures; 18 had dysphagia or bolus impaction; median diagnostic delay was 8 months (IQR 3.5–35). Eighteen patients received oral systemic steroids (mean dose 1.4 mg/kg/day) for a median of 4 weeks, while two initially received IV steroids. All patients showed clinical improvement and 15/20 became asymptomatic. Stricture resolution at endoscopy was found in 19/20, while histological resolution of EoE (&lt;15 eos/hpf) in 13/20. Only minor side effects were reported: hyperphagia (10/20); weight gain (5/20); hyperactivity (2/20) and acne (1/20). Esophageal dilation was required in 3/20 patients during a median follow-up of 48.5 months (IQR 26.7–73.2). Conclusion: Children with EoE and esophageal strictures, may benefit from the use of a short course of systemic steroids, avoiding mechanical dilation