CYP26B1-related disorder: expanding the ends of the spectrum through clinical and molecular evidence.

CYP26B1 metabolizes retinoic acid in the developing embryo to regulate its levels. A limited number of individuals with pathogenic variants in CYP26B1 have been documented with a varied phenotypic spectrum, spanning from a severe manifestation involving skull anomalies, craniosynostosis, encephalocele, radio-humeral fusion, oligodactyly, and a narrow thorax, to a milder presentation characterized by craniosynostosis, restricted radio-humeral joint mobility, hearing loss, and intellectual disability. Here, we report two families with CYP26B1-related phenotypes and describe the data obtained from functional studies of the variants. Exome and Sanger sequencing were used for variant identification in family 1 and family 2, respectively. Family 1 reflects a mild phenotype, which includes craniofacial dysmorphism with brachycephaly (without craniosynostosis), arachnodactyly, reduced radioulnar joint movement, conductive hearing loss, learning disability-and compound heterozygous CYP26B1 variants: (p.[(Pro118Leu)];[(Arg234Gln)]) were found. In family 2, a stillborn fetus presented a lethal phenotype with spina bifida occulta, hydrocephalus, poor skeletal mineralization, synostosis, limb defects, and a synonymous homozygous variant in CYP26B1: c.1083C > A. A minigene assay revealed that the synonymous variant created a new splice site, removing part of exon 5 (p.Val361_Asp382del). Enzymatic activity was assessed using a luciferase assay, demonstrating a notable reduction in exogenous retinoic acid metabolism for the variant p.Val361_Asp382del. (~ 3.5 × decrease compared to wild-type); comparatively, the variants p.(Pro118Leu) and p.(Arg234Gln) demonstrated a partial loss of metabolism (1.7× and 2.3× reduction, respectively). A proximity-dependent biotin identification assay reaffirmed previously reported ER-resident protein interactions. Additional work into these interactions is critical to determine if CYP26B1 is involved with other biological events on the ER. Immunofluorescence assay suggests that mutant CYP26B1 is still localized in the endoplasmic reticulum. These results indicate that novel pathogenic variants in CYP26B1 result in varying levels of enzymatic activity that impact retinoic acid metabolism and relate to the distinct phenotypes observed.

Newborn with bilateral congenital cataracts: Never forget congenital rubella syndrome.

A term, growth-restricted newborn presented with a sepsis-like picture, persistent pulmonary hypertension and bilateral cataracts. Initial review of prenatal and family history, as well as microbiological investigations were noncontributory. Following lenticular extraction, viral examination of the lenses confirmed the presence of rubella. Congenital rubella syndrome (CRS) presents with a constellation of signs and symptoms that overlap with many other conditions. The presence of bilateral cataracts in a newborn is a rare finding and this case is used to review the broad etiology of congenital cataracts. We propose a structured diagnostic approach for clinicians, remembering that CRS is a rare but possible etiology. The early diagnosis of CRS in this case, allowed us to initiate appropriate management and preventive measurements.

Alveolar capillary dysplasia with misalignment of the pulmonary veins and hypoplastic left heart sequence caused by an in frame deletion within FOXF1.

Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACDMPV) is a rare, autosomal dominant disorder of interstitial lung development, leading to pulmonary hypertension, and death in infancy. Associated features include malformations of the heart, gastrointestinal tract, and genitourinary system. ACDMPV is caused by heterozygous variants in the FOXF1 gene or microdeletions involving FOXF1. We present a male infant with ACDMPV, hypoplastic left heart sequence (HLHS), duodenal atresia, and imperforate anus due to a de novo, in frame deletion in FOXF1: c.209_214del (p.Thr70_Leu71del). Previous reports have suggested that microdeletions involving FOXF1 are associated with ACDMPV with congenital heart defects, including HLHS, gastrointestinal atresias, and other anomalies; whereas likely pathogenic variants within FOXF1 have not been reported with ACDMPV and HLHS. This is the first patient reported with ACDMPV, HLHS, imperforate anus, and duodenal atresia associated with a likely pathogenic variant in the FOXF1 gene.

A produção de conhecimento sobre mulheres indígenas no campo da saúde

Este trabalho tem como objetivo analisar a produção científica das revistas de Saúde Pública e de Saúde Coletiva, referente a saúde da mulher indígena, de 2005 a 2016. As produções científicas foram escolhidas devido ao fator de impacto dos periódicos. A proposta é averiguar, a partir da crítica feminista, os discursos reiterados sobre a temática no campo da Saúde. Nos interessa investigar se as mulheres indígenas são apresentadas nessas publicações de maneira integral, ou seja, considerando suas especificidades, experiências e histórias de vida enquanto mulheres e indígenas ou se são de maneira genérica – focalizando apenas à atenção para questões epidemiológicas.

Nosocomial infections in brazilian pediatric patients: using a decision tree to identify high mortality groups

Nosocomial infections (NI) are frequent events with potentially lethal outcomes. We identified predictive factors for mortality related to NI and developed an algorithm for predicting that risk in order to improve hospital epidemiology and healthcare quality programs. We made a prospective cohort NI surveillance of all acute-care patients according to the National Nosocomial Infections Surveillance System guidelines since 1992, applying the Centers for Disease Control and Prevention 1988 definitions adapted to a Brazilian pediatric hospital. Thirty-eight deaths considered to be related to NI were analyzed as the outcome variable for 754 patients with NI, whose survival time was taken into consideration. The predictive factors for mortality related to NI (p < 0.05 in the Cox regression model) were: invasive procedures and use of two or more antibiotics. The mean survival time was significantly shorter (p < 0.05 with the Kaplan-Meier method) for patients who suffered invasive procedures and for those who received two or more antibiotics. Applying a tree-structured survival analysis (TSSA), two groups with high mortality rates were identified: one group with time from admission to the first NI less than 11 days, received two or more antibiotics and suffered invasive procedures; the other group had the first NI between 12 and 22 days after admission and was subjected to invasive procedures. The possible modifiable factors to prevent mortality involve invasive devices and antibiotics. The TSSA approach is helpful to identify combinations of predictors and to guide protective actions to be taken in continuous-quality-improvement programs.

Nosocomial infections in Brazilian pediatric patients: using a decision tree to identify high mortality groups.

Nosocomial infections (NI) are frequent events with potentially lethal outcomes. We identified predictive factors for mortality related to NI and developed an algorithm for predicting that risk in order to improve hospital epidemiology and healthcare quality programs. We made a prospective cohort NI surveillance of all acute-care patients according to the National Nosocomial Infections Surveillance System guidelines since 1992, applying the Centers for Disease Control and Prevention 1988 definitions adapted to a Brazilian pediatric hospital. Thirty-eight deaths considered to be related to NI were analyzed as the outcome variable for 754 patients with NI, whose survival time was taken into consideration. The predictive factors for mortality related to NI (p < 0.05 in the Cox regression model) were: invasive procedures and use of two or more antibiotics. The mean survival time was significantly shorter (p < 0.05 with the Kaplan-Meier method) for patients who suffered invasive procedures and for those who received two or more antibiotics. Applying a tree-structured survival analysis (TSSA), two groups with high mortality rates were identified: one group with time from admission to the first NI less than 11 days, received two or more antibiotics and suffered invasive procedures; the other group had the first NI between 12 and 22 days after admission and was subjected to invasive procedures. The possible modifiable factors to prevent mortality involve invasive devices and antibiotics. The TSSA approach is helpful to identify combinations of predictors and to guide protective actions to be taken in continuous-quality-improvement programs.

Influence of jejunoileal and common limb length on weight loss following Roux-en-Y gastric bypass.

BACKGROUND: Capella surgery is one of the technical variations of Roux-en-Y gastric bypass. The method includes the preparation of an alimentary (Roux) limb with a standardized length (110 cm) in order to induce deficiencies in the absorption of macronutrients and thereby contribute to weight loss. The recognized variation in jejunoileal length in humans (approximately 4 to 9 m) is not considered, although this range correlates with the wide variation in the length of the common limb. METHODS: In order to assess the influence of variations in jejunoileal and common limb lengths on weight loss, intra-operative measurements were made of these segments on 100 patients undergoing Capella surgery. Patients were followed for a period of 1 year. Statistical analysis included subdivisions of the population by gender and body mass index. RESULTS: Average jejunoileal length was 671.4 +/- 115.7 cm (434-990 cm). Average common limb length was 505.3 +/- 113.3 cm (268-829 cm). No correlation was detected between jejunoileal length and weight loss at 6 months or 1 year following surgery. A weak negative correlation was detected between weight loss and common limb length at 1 year following surgery in male and super-obese patients. CONCLUSIONS: Jejunoileal and common limb length vary widely in gastric bypass patients. To make modifications in the alimentary and/or biliopancreatic limb length, surgeons must consider the variability of the jejunoileal and common limb length.

Human disorganization complex, as a polytopic blastogenesis defect: a new case.

We describe a baby girl of 4,000 g and 55 cm with supernumerary, malformed, and partially duplicated lower limbs, malformed and partially duplicated pelvis, spina bifida, coccygeal dermal sinus, ectopic anus located in the right buttock, duplicated internal genitalia, rectovaginal fistula, ileal atresia, Meckel diverticulum, and various renal system anomalies. We think that this phenotype is a new case of disorganization in humans (DsH) and postulate that this condition constitutes a polytopic defect of the blastogenesis. In this case, the presence of a malformation pattern involving structures in different parts of the body and organs derived from all of the germ layers, suggests that the pathogenetic event most probably occurred during blastogenesis affecting various progenitors fields.

Qualidades psicométricas da escala de qualidade de vida para pacientes com esquizofrenia: escala QLS-BR / Psychometric qualities of the quality of life scale for schizophrenic patients: scale QLS-BR

Objetivos: Analisar as qualidades psicométricas de validade e confiabilidade da versão brasileira da Escala de Qualidade de Vida (QLS) de Heinrichs et al., elaborada especificamente para avaliação da qualidade de vida de pacientes com diagnótico de esquizofrenia. Método: O estudo das qualidades psicométricas da escala incluiu a avaliação dos seguintes aspectos: 1) validade de constructo da escala através da análise fatorial; 2) análise da sua consistência interna através do coeficiente alfa de Cronbach; 3) correlação de Pearson entre os itens e a escala global; 4) validade concominante através da correlação de Pearson entre as escalas QLS-BR e WHOQOL-bref; 5) confiabilidade teste-reteste por meio da correlação de Spearman; 6) confiabilidade interavaliador através do coeficiente kappa ponderado; e 7) confiabilidade das respostas dos pacientes por meio do teste de McNemar. Resultados: A análise fatorial indicou a distribuição dos itens da escala em três fatores que explicaram 63 por cento da variância, identificados como: 1) rede social, 2) nível ocupacional e 3) funções intrapsíquicas e relações interpessoais. O coeficiente alfa de Cronbach para consistência interna do instrumento mostrou valores acima de 0,85 para a escala global e fatores. As medidas de confiabilidade teste-reteste indicaram uma correlação significativa de 0,85. Para a confiabilidade interavaliador, a estimativa kappa variou de 0,67 a 1 para os 21 itens da escala. A confiabilidade das respostas dos pacientes foi satisfatória, pois não se obtiveram diferenças significativas entre as respostas dadas às mesmas questões em dois momentos diferentes da entrevista. Com relação à validade concominante, a escala QLS-BR não apresentou correlação significativa com a escala WHOQOL-bref, provavelmente devido às diferenças de formato, modo de avaliação e de população-alvo. Conclusão: A análise das qualidades psicométricas da versão brasileira da escala QLS mostrou que esta escala possui índices adequados de fidedignidade e validade. Estes resultados justificam a utilização da escala no contexto brasileiro.