22q11 Copy Number Variations in a Brazilian Cohort of Children with Congenital Heart Disorders.

Introduction: Congenital heart disease (CHD) is the most common type of congenital defect reported to be one of the leading causes of mortality in the first year of life. Microdeletion and microduplication syndromes (MMS) are associated with cardiac malformations. Understanding which genetic factors are involved in these conditions directly impacts treatment decisions. We aimed to identify the occurrence of genetic alterations and their association with MMS in CHD pediatric patients evaluated in a reference service of Southern Brazil. Methods: Participants were recruited during 2010 in the intensive care unit of a pediatric hospital. MMs and regions of chromosome 22 were screened by SALSA MLPA Probemix P245 Microdeletion Syndromes-1A kit for detection of copy number variations (CNVs). Results: MMS were detected in 11 from 207 patients (5.3%). Heterozygous deletion in the 22q11.2 chromosome region was the most prevalent CNV (5 from 11 patients). Also, atypical RTDR1 deletion and 22q11.2 duplication were detected. MLPA was able to reveal microdeletions in SNRPN and NF1 genes in patients with a normal karyotype and FISH. Conclusion: Our study reports the prevalence and variability of genomic alterations associated with MMS in CHD pediatric patients. The results by MLPA are of great help in planning and specialized care.

Flexible Multiplane Structured Illumination Microscope with a Four-Camera Detector.

Fluorescence microscopy provides an unparalleled tool for imaging biological samples. However, producing high-quality volumetric images quickly and without excessive complexity remains a challenge. Here, we demonstrate a four-camera structured illumination microscope (SIM) capable of simultaneously imaging multiple focal planes, allowing for the capture of 3D fluorescent images without any axial movement of the sample. This setup allows for the acquisition of many different 3D imaging modes, including 3D time lapses, high-axial-resolution 3D images, and large 3D mosaics. We imaged mitochondrial motions in live cells, neuronal structure in Drosophila larvae, and imaged up to 130 µm deep into mouse brain tissue. After SIM processing, the resolution measured using one of the four cameras improved from 357 nm to 253 nm when using a 30×/1.05 NA objective.

A child with cat-eye syndrome and oculo-auriculo-vertebral spectrum phenotype: A discussion around molecular cytogenetic findings.

Cat eye syndrome (CES) is a rare chromosomal disorder that may be evident at birth. A small supernumerary chromosome is present, frequently has 2 centromeres, is bisatellited, and represents an inv dup(22)(q11) in those affected. It's known that the 22q11 region is associated with disorders involving higher and lower gene dosages. Conditions such as CES, 22q11 microduplication syndrome (Dup22q11) and oculoauriculovertebral spectrum phenotype (OAVS) may share genes belonging to this same region, which is known to have a predisposition to chromosomal rearrangements. The conditions, besides being related to chromosome 22, also share similar phenotypes. Here we have added a molecular evaluation update and results found of the first patient described with CES and OAVS phenotype, trying to explain the potential mechanism involved in the occurrence of this association.

Fluorescence microscopy datasets for training deep neural networks.

BACKGROUND: Fluorescence microscopy is an important technique in many areas of biological research. Two factors that limit the usefulness and performance of fluorescence microscopy are photobleaching of fluorescent probes during imaging and, when imaging live cells, phototoxicity caused by light exposure. Recently developed methods in machine learning are able to greatly improve the signal-to-noise ratio of acquired images. This allows researchers to record images with much shorter exposure times, which in turn minimizes photobleaching and phototoxicity by reducing the dose of light reaching the sample. FINDINGS: To use deep learning methods, a large amount of data is needed to train the underlying convolutional neural network. One way to do this involves use of pairs of fluorescence microscopy images acquired with long and short exposure times. We provide high-quality datasets that can be used to train and evaluate deep learning methods under development. CONCLUSION: The availability of high-quality data is vital for training convolutional neural networks that are used in current machine learning approaches.

Mismatch negativity in children with complaints of learning difficulties / Mismatch Negativity en niños con quejas de dificultades de aprendizaje

INTRODUCTION: Mismatch Negativity (MMN) is an electrophysiological measure of hearing that reflects the skills of auditory discrimination and central auditory processing. OBJECTIVE: To analyze MMN results in children with complaints of learning difficulties and to compare the results with children without complaints of learning difficulties. MATERIALS AND METHODS: Cross-sectional and comparative study. The sample consisted of 105 male and female children, aged between 8 and 11 years and 11 months, 3rd to 5th graders at Elementary School. The study group consisted of 35 children with learning difficulties and the control group, of 70 children without complaints. All children underwent pure-tone threshold audiometry (PTTA), vocal audiometry, acoustic immittance measurements and Mismatch Negativity (MMN) evaluations. RESULTS: The mean latency of MMN was 213.3ms in the right ear and 215.2ms in the left in the study group, and 169.3ms in the right ear and 170.4ms in the left in the control group. The mean MMN latency was significantly higher in the study group compared to the control group (p<.001). The mean amplitude of MMN in the study group was 5.76μV in the right ear and 5.62μV in the left, while in the control it was 5.01μV in the right ear and 5.22μV in the left. CONCLUSIONS: In the study sample, children with complaints of learning difficulties had significantly higher mean significances than those without the same complaints

ANTECEDENTES Y OBJETIVO: La Mismatch Negativity (MMN) es una medida electrofisiológica de la audición que refleja las habilidades de discriminación auditiva y el procesamiento auditivo central. El objetivo de este estudio fue analizar los resultados de la MMN en los niños con quejas de dificultades de aprendizaje, y comparar los resultados con niños sin quejas de dificultades de aprendizaje. MATERIALES Y MÉTODOS: Estudio transversal y comparativo. La muestra fue constituida por 105 niños de ambos sexos, con edad comprendidas entre 8 y 11 años y 11 meses, 3.ª a 5.ª series de la enseñanza fundamental. El grupo de estudio fue constituido por 35 niños con dificultades de aprendizaje y el grupo control, de 70 niños sin quejas. Todos los niños fueron sometidos a la audiometría tonal liminar (PTTA), a la audiometría vocal, a las medidas de imitancia acústica y a la MMN. RESULTADOS: La latencia media de la MMN fue de 213,3ms en el oído derecho y 215,2ms en el izquierdo en el grupo de estudio, y 169,3ms en el oído derecho y 170,4ms en el izquierdo en el grupo control. La latencia media de la MMN fue significativamente mayor en el grupo de estudio en comparación con el grupo control (p < 0,001). La amplitud media de la MMN en el grupo de estudio fue de 5,76μV en el oído derecho y de 5,62μV en el oído izquierdo, mientras que en el control fue de 5,01μV en el oído derecho y 5,22μV en el oído izquierdo. CONCLUSIONES: En la muestra estudiada, los niños con quejas de dificultades de aprendizaje tuvieron significados significativamente mayores que aquellas sin las mismas quejas

Nasal fistula, epidermal cyst and hypernatremia in a girl presenting holoprosencephaly due to a rare ZIC2 point mutation.

Holoprosencephaly is the most common brain malformation in humans and it is a complex genetic disorder. We report on a patient with holoprosencephaly caused by a rare ZIC2 mutation presenting a bifid nose associated with a nasal fistula and an epidermal cyst, besides hypernatremia. The patient was a 1 year and 4 months old girl that developed an important neuropsychomotor delay. Currently, she uses a wheelchair to move around and only emits sounds. Computed tomography (CT) scan revealed a semilobar holoprosencephaly and a Dandy-Walker variant. Head magnetic resonance imaging also disclosed corpus callosum agenesis and prefrontal subarachnoid space enlargement. On physical examination at 1 year and 4 months of age, we verified growth retardation, microcephaly, bilateral epicantic fold, upslanting palpebral fissures, bifid nose, and limbs spasticity secondary to hypertonia. Later, she began to present hypernatremia; however, its precise cause was not identified. At 6 years and 10 months of age, a nasal fistula was suspected. Facial CT scan showed an epidermal cyst at cartilaginous portion of the nasal septum. High resolution GTG-Banding karyotype was normal. However, molecular analysis through direct sequencing technique showed a mutation at regulatory region of the ZIC2 gene: c.1599*954T > A, a genetic variation previously described only in a Brazilian patient. Our patient presented findings still not reported in literature among patients with holoprosencephaly, including those with ZIC2 mutations. Thus, the spectrum of abnormalities associated to ZIC2 mutations may be broader and include other defects as those observed in our patient.

Imaging Membrane Curvature inside a FcεRI-Centric Synapse in RBL-2H3 Cells Using TIRF Microscopy with Polarized Excitation.

Total internal reflection fluorescence microscopy with polarized excitation (P-TIRF) can be used to image nanoscale curvature phenomena in live cells. We used P-TIRF to visualize rat basophilic leukemia cells (RBL-2H3 cells) primed with fluorescent anti-dinitrophenyl (anti-DNP) immunoglobulin E (IgE) coming into contact with a supported lipid bilayer containing mobile, monovalent DNP, modeling an immunological synapse. The spatial relationship of the IgE-bound high affinity IgE receptor (FcεRI) to the ratio image of P-polarized excitation and S-polarized excitation was analyzed. These studies help correlate the dynamics of cell surface molecules with the mechanical properties of the plasma membrane during synapse formation.

Imaging of Biological Cells Using Luminescent Silver Nanoparticles.

The application of luminescent silver nanoparticles as imaging agents for neural stem and rat basophilic leukemia cells was demonstrated. The experimental size dependence of the extinction and emission spectra for silver nanoparticles were also studied. The nanoparticles were functionalized with fluorescent glycine dimers. Spectral position of the resonance extinction and photoluminescence emission for particles with average diameters ranging from 9 to 32 nm were examined. As the particle size increased, the spectral peaks for both extinction and the intrinsic emission of silver nanoparticles shifted to the red end of the spectrum. The intrinsic photoluminescence of the particles was orders of magnitude weaker and was spectrally separated from the photoluminescence of the glycine dimer ligands. The spectral position of the ligand emission was independent of the particle size; however, the quantum yield of the nanoparticle-ligand system was size-dependent. This was attributed to the enhancement of the ligand's emission caused by the local electric field strength's dependence on the particle size. The maximum quantum yield determined for the nanoparticle-ligand complex was (5.2 ± 0.1) %. The nanoparticles were able to penetrate cell membranes of rat basophilic leukemia and neural stem cells fixed with paraformaldehyde. Additionally, toxicity studies were performed. It was found that towards rat basophilic leukemia cells, luminescent silver nanoparticles had a toxic effect in the silver atom concentration range of 10-100 µM.

Emerging drugs for the treatment of mucopolysaccharidoses.

INTRODUCTION: Despite being reported for the first time almost one century ago, only in the last few decades effective have treatments become available for the mucopolysaccharidoses (MPSs), a group of 11 inherited metabolic diseases that affect lysosomal function. These diseases are progressive, usually severe, and, in a significant number of cases, involve cognitive impairment. AREAS COVERED: This review will not cover established treatments such as bone marrow/hematopoietic stem cell transplantation and classic intravenous enzyme replacement therapy (ERT), whose long-term outcomes have already been published (MPS I, MPS II, and MPS VI), but it instead focuses on emerging therapies for MPSs. That includes intravenous ERT for MPS IVA and VII, intrathecal ERT, ERT with fusion proteins, substrate reduction therapy, gene therapy, and other novel approaches. EXPERT OPINION: The available treatments have resulted in improvements for several disease manifestations, but they still do not represent a cure for these diseases; thus, it is important to develop alternative methods to approach the unmet needs (i.e. bone disease, heart valve disease, corneal opacity, and central nervous system (CNS) involvement). The work in progress with novel approaches makes us confident that in 2017, when MPS will commemorate 100 years of its first report, we will be much closer to an effective cure for these challenging conditions.

Gómez-López-Hernández syndrome in a child born to consanguineous parents: new evidence for an autosomal-recessive pattern of inheritance?

BACKGROUND: Gómez-López-Hernández syndrome is a rare genetic disease characterized by scalp alopecia with trigeminal anesthesia, brachycephaly or turribrachycephaly, midface retrusion, and rhombencephalosynapsis. We report the second case with this condition who presented with consanguineous parents. PATIENT: This boy was evaluated shortly after birth because of suspected craniosynostosis. He was the only son of healthy, consanguineous parents (his maternal grandmother and his paternal great-grandfather were siblings). His examination was notable for turribrachycephaly, prominent forehead, bilateral parietotemporal alopecia, midfacial retrusion, anteverted nostrils, micrognathia, low-set and posteriorly rotated ears, and short neck with redundant skin. Radiographs and tridimensional computed tomography scan of skull revealed lambdoid craniosynostosis. Brain magnetic resonance imaging revealed complete rhombencephalosynapsis, aqueductal stenosis, fused colliculi, abnormal superior cerebellar penducle, mild ventriculomegaly, and dysgenesis of the corpus callosum. CONCLUSIONS: Since its first description, 34 patients with this condition have been reported. The etiology of Gómez-López-Hernández syndrome is unknown. However, it is noteworthy that the patient in this report presented with a family history of consanguinity because this finding reinforces the possibility of an autosomal-recessive inheritance for this condition.

Late prematurity: a systematic review.

OBJECTIVE: this study aimed to review the literature regarding late preterm births (34 weeks to 36 weeks and 6 days of gestation) in its several aspects. SOURCES: the MEDLINE, LILACS, and Cochrane Library databases were searched, and the references of the articles retrieved were also used, with no limit of time. DATA SYNTHESIS: numerous studies showed a recent increase in late preterm births. In all series, late preterm comprised the majority of preterm births. Studies including millions of births showed a strong association between late preterm birth and neonatal mortality. A higher mortality in childhood and among young adults was also observed. Many studies found an association with several neonatal complications, and also with long-term disorders and sequelae: breastfeeding problems, cerebral palsy, asthma in childhood, poor school performance, schizophrenia, and young adult diabetes. Some authors propose strategies to reduce late preterm birth, or to improve neonatal outcome: use of antenatal corticosteroids, changes in some of the guidelines for early delivery in high-risk pregnancies, and changes in neonatal care for this group. CONCLUSIONS: numerous studies show greater mortality and morbidity in late preterm infants compared with term infants, in addition to long-term disorders. More recent studies evaluated strategies to improve the outcomes of these neonates. Further studies on these strategies are needed.

Necessidades de confiança percecionadas pelos pais das crianças hospitalizadas / Needs for trust perceived by parents of hospitalized children

A hospitalização de uma criança implica sempre situações de mudança e stress na vida da criança e dos pais alterando a dinâmica familiar. Este estudo aborda as necessidades dos pais na hospitalização da criança, e tem como finalidade perceber a importância, a satisfação e a independência dos pais perante a necessidade de confiar e a necessidade de sentir que confiam em si. O estudo incidiu sobre uma amostra de 184 pais/acompanhantes de crianças hospitalizadas, provenientes de 4 hospitais. Trata-se de um estudo descritivo e exploratório, no qual se utilizou como instrumento de colheita de dados o questionário das necessidades dos pais (NPQ-Needs of Parents Questionaire) e procedeu-se ao tratamento dos dados através do SPSS. Os resultados obtidos mostram que os pais das crianças hospitalizadas se encontram mais satisfeitos quanto maior a importância atribuída pelos mesmos à necessidade de sentir que confiam em si. Constatamos ainda que os pais destacam a importância e satisfação em ambas as necessidades abordadas. A idade da criança influencia a perceção dos pais em relação à independência, na necessidade de confiar e na de que confiem em si, pois quanto mais jovem é a criança mais os pais acham que o hospital os deve ajudar a superar as necessidades. No número de internamentos, os pais das crianças com menor número de internamentos acham que o hospital os deveria ajudar a superar as necessidades percecionadas em ambas as necessidades, e consideram muito importante que os profissionais confiem em si. Afim de melhorar a confiança deve-se trabalhar em parceria com os pais e dar muita importância à comunicação, à empatia, à escuta - áreas fundamentais da enfermagem, para deteção precoce das necessidades sentidas pelos pais nem sempre verbalizadas. Este trabalho contribui para aumentar o conhecimento sobre as necessidades dos pais das crianças hospitalizadas, pensamos que seria interessante conhecer a perspetiva das crianças sobre as suas necessidades durante a hospitalização.

The hospitalization of a child often leads to routine changes and stress situations to the child and parents, modifying the family habit. The present study addresses the needs of parents in the child's hospitalization, and aim to realize the importance, satisfaction and independence from parents to the need of trust and the need of feel that you trust. The sampling variables of the study were based on 184 parents of hospitalized children answers, coming from four hospitals. This is a descriptive study, in which was used the Needs of Parents Questionnaire (NPQ-Needs of Parents Questionnaire) as a tool to collect the data. All the data was processed on SPSS. The results show that the parents of hospitalized children are more satisfied as more importance are given by them to the need of feel that you trust. Also, the parents point more prominence to importance and satisfaction in both needs mention in this study. The child's age influence the parent's perception towards independency, for the need of trust and trust each other, because younger the child is more the parents feel that the hospital should help to overcome their needs. Concerning to the number of hospitalizations, parents of children with fewer hospitalizations think the hospital should help overcome the needs perceived in both needs, and consider it very important that professionals trust itself. In order to improve confidence, the hospital should work in partnership with parents and give much importance to communication, empathy, listening - key areas of nursing, for early detection of needs experienced by parents who do not always verbalize. This work contributes to raise knowledge about the needs of parents of hospitalized children, we think it will be very interesting to identify the children's needs during hospitalization.

Fetoscopic endotracheal occlusion for severe isolated diaphragmatic hernia: initial experience from a single clinic in Brazil.

OBJECTIVE: To report on the initial experience in a single Brazilian university clinic of the use of fetoscopic endotracheal occlusion (FETO) to treat severe isolated congenital diaphragmatic hernia (CDH). METHODS: The inclusion criteria for FETO for this prospective study were isolated CDH and intrathoracic herniation of the liver, as well as the lung area to head circumference ratio (LHR) <1.0. The main variables evaluated were LHR and observed to expected (o/e) LHR before and after FETO, gestational age (GA) at FETO, reversal of tracheal occlusion (TO), and birth and discharge of a living child from the hospital. RESULTS: Among 8 isolated left-sided CDH cases with normal karyotypes, the median LHR and o/e LHR before FETO were 0.7 (range: 0.6-0.9) and 0.27 (range: 0.22-0.32), respectively. The median LHR and o/e LHR after FETO were 1.2 (range: 0.9-1.8) and 0.45 (0.31-0.67), respectively. The median GA at FETO, reversal of TO and birth were 26.8 (range: 26-29), 32.5 (range: 31.0-34.0) and 37 weeks (range: 35-37), respectively. Neonatal survival at the time of hospital discharge was 50% (4/8). CONCLUSION: FETO is feasible at our institution and may help to improve postnatal survival of children with severe CDH in developing countries.

Interstitial deletion of 7q31.32 → q33 secondary to a paracentric inversion of a maternal chromosome 7.

Carriers of paracentric inversions (PAIs) are usually asymptomatic. However, such inversions may lead to the formation of recombinant gametes and then to an abnormal gestation. Here we report a girl with a 7q31.32 → q33 deletion secondary to a maternal PAI of chromosome 7. This finding was confirmed through FISH and whole-genome array-CGH analyses. The deficiency of the chromosome 7 observed in our patient was never described before and we did not find any known gene localized within the deficient segment that could be related to her findings of hypoplastic iliac bones, hypoplastic labia minora and postaxial polydactyly. This case highlights the fact that rare viable recombinants can be developed from PAIs, an issue that must be discussed in the genetic counseling.

Gestão do conhecimento usando data mining: estudo de caso na Universidade Federal de Lavras / Knowledge management using data mining: a case study of the Federal University of Lavras

A gestão do conhecimento abrange toda a forma de gerar, armazenar, distribuir e utilizar o conhecimento, tornando necessária a utilização de tecnologias de informação para facilitar esse processo, devido ao grande aumento no volume de dados. A descoberta de conhecimento em banco de dados é uma metodologia que tenta solucionar esse problema e o data mining é uma técnica que faz parte dessa metodologia. Este artigo desenvolve, aplica e analisa uma ferramenta de data mining, para extrair conhecimento referente à produção científica das pessoas envolvidas com a pesquisa na Universidade Federal de Lavras. A metodologia utilizada envolveu a pesquisa bibliográfica, a pesquisa documental e o método do estudo de caso. As limitações encontradas na análise dos resultados indicam que ainda é preciso padronizar o modo do preenchimento dos currículos Lattes para refinar as análises e, com isso, estabelecer indicadores. A contribuição foi gerar um banco de dados estruturado, que faz parte de um processo maior de desenvolvimento de indicadores de ciência e tecnologia, para auxiliar na elaboração de novas políticas de gestão científica e tecnológica e aperfeiçoamento do sistema de ensino superior brasileiro.

O trabalho da mulher / The work of women

A autora faz uma análise dos desafios encontrados pela mulher que trabalha, fazendo um paralelo sobre o trabalho feminino em geral. Foram revistas as conquistas alcançadas pela mulher, ao longo da história e suas lutas até a criação da legislação trabalhista feminina. São analisadas as características da mão de obra feminina, os efeitos do trabalho, as razões do absenteísmo feminino, os riscos a que é submetida no trabalho, a gravidez e a problemática do mercado de trabalho para a mulher. A autora conclui que, apesar dos avanços, as leis são desrespeitadas impunemente, a discriminação sexual ainda é motivo de preocupação e que a mulher, para se impor na sociedade, deve lutar pelo efetivo cumprimento de seus direitos básicos de trabalho e cidadania.