Susceptibility loci CNVs with incomplete penetrance accurate diagnosis with uncertain prognosis

Chromosomal microarray analysis (CMA) is the first-tier test for developmental delay, autism spectrum disorders, and congenital abnormalities in postnatal diagnosis and for ultrasound abnormalities in prenatal diagnosis. The detection of variants with clinical significance by CMA, when compared to karyotype, can increase up to 10-20% in postnatal diagnosis and up to 5-18% in prenatal diagnosis. Nevertheless CMA also detects incomplete penetrance neuro-Susceptibility Loci Copy Number Variants (SL-CNV), which although having clinical significance have an uncertain prognosis. The aim of this study is to identify from the literature a set of SLCNV, and the corresponding penetrance for each variant, determining their occurrence in our cohort of postnatal samples ran between January 2012 and August 2018 and prenatal samples ran between January 2015 and August 2018. We have established a 21 SL-CNV set, and from a total of 835 postnatal samples and 317 prenatal samples we have identified 36 and 11 cases, respectively, with a variant in one of the 21 established SLCNV. The percentage of cases with a SL-CNV is relatively similar between postnatal samples (4.5%) and prenatal samples (3.5%), although the reason of referral for the two groups is not completely overlapping and also the total number of prenatal samples represents about half of the time span of the postnatal samples, which might have underestimated their occurrence. The estimated penetrance for each of the established SL-CNV present some inter-publication variability, especially concerning samples with different phenotypes. Nevertheless some variants show concordance. Estimating the penetrance for SL-CNV, and their clinical impact for the patient or carriers in the family, is a complex task. Only time, analysis of larger cohorts, and future knowledge of genotype-environment-phenotype interactions will overcome this difficulty, decreasing uncertainty for the around 4% of patients diagnosed by CMA.info:eu-repo/semantics/publishedVersio

Influence of muscle-tendon unit structure, function, and menstrual cycle phase in dancers’ physical performance

Flexibility and jump are crucial capabilities for dancers but reaching good performance in both is a challenge. Given that muscle-tendon stiffness (SMTU) might affect both these capabilities and that muscle structure and concentration of female hormones across the menstrual cycle may affect SMTU, this thesis aimed to determine the factors that might affect SMTU and, therefore, physical performance in female dancers, especially through the menstrual cycle. A piece of equipment to measure and train flexibility in highly flexible participants was developed and validated. Then, fifteen young adult dance students under oral contraception, eleven dance students without contraception and twenty non-dancers without contraception completed several laboratory-based tests. Participants underwent semitendinosus and rectus femoris ultrasound imaging, flexibility and vertical jump tests including electromyography, kinematics, and pain mixed-method assessment. Participants also provided serum/saliva samples on test days, including ovulatory, follicular and luteal phases. An intervention involving stretching the most flexible limb allowed evaluation of limb asymmetries and impact on function. Results showed no statistical structural and functional differences between dancers and non-dancers. Asymmetries in flexibility, but SMTU, between limbs, were found for all groups. Those asymmetries appear to not influence jump performance. Four-series of passive constant torque stretch was not sufficient to cause or increase any asymmetry or to affect SMTU. Stretching did not change jump height, muscle activation and kinematics of vertical jumps. Dancers presented irregular menstrual cycle with the change in hormone across the phases being associated with changes in key outcome variables. Thus, oestrogen and relaxin appear to be positively correlated to muscle laxity while progesterone is positively correlated to SMTU. This thesis’ results will provide data for the development of training strategies to improve performance and potentially decrease injuries in dancers. Additionally, contributing to research on hormonal factors in female performance and, therefore, women’s health

9q21.13q21.31 deletion in a patient with intellectual disability severe speech delay and and dysmorphic features a newly recognized microdeletion syndrome

The increased use of chromosomal microarray analysis has led to the identification of new microdeletion/microduplication syndromes, enabling better genotype-phenotype correlations. Interstitial deletions involving the long arm of chromosome 9 are rare but recently a microdeletion syndrome at 9q21.13 was suggested, with mental retardation, speech delay, epilepsy, autistic behaviour and moderate facial dysmorphism as the main characteristics. Here we present a male child with intellectual disability, severe speech delay, microcephaly and dysmorphic features carrying an interstitial deletion, detected by the Affymetrix Cytoscan HD microarray, of 6.56 Mb at 9q21.13q21.31 region encompassing 16 OMIM genes (arr[GRCh37] 9q21.13q21.31(76551542_83116342)x1). Among the genes in the deleted region the PRUNE2, PCSK5, RORB and TRPM6 genes are expressed in the nervous system and have been describe as being candidate genes to play a role in mental retardation or neurological disorders. Although the cohort of patients identified with deletions in this region is still small our patient phenotype partially overlaps the others described in the literature. The collection of more cases with deletion of the 9q21.13 region will help establishing a clear classification for this CNV, finding the real weight in the patient’s phenotype, delineating the genetic counseling for their families, and clearly establishing this microdeletion as a syndrome.N/

an index for the quality of crisis finance

The Global Financial Safety Net (GFSN) – the institutions and arrangements that provide short-term crisis finance – has turned into a highly complex, uncoordinated system of global, multilateral, and bilateral instruments. The present paper elaborates on a composite index of the GFSN to analyse its preparedness for shielding countries from financial crises. This first-of-its-kind index comprises six components that measure the vulnerability and resilience of individual countries to financial crises derived from economic and political economy financial crisis literature. We apply this index to data from 192 UN member countries we collected in the GFSN tracker for the period of the COVID-19 pandemic in terms of their asses to and use of the GFSN. This index, and the use of novel forms of graphical displaying, allow us to identify a hierarchy in the access to short-term liquidity by the GFSN. At the bottom, we find low-income countries with sole access to IMF standard conditional crisis finance, while we find at the top countries with access to bilateral currency swaps, especially those provided by the US Federal Reserve. Our analysis also reveals that first, the temporary reformed unconditional access of IMF crisis finance during the pandemic has temporarily improved those countries’ position in the GFSN hierarchy; second, bilateral swaps as crisis finance instruments reinforce the GFSN hierarchy. Since access to adequate emergency liquidity is decisive for a country’s financial crisis prevention capacity and the ability to engage in social cohesion and climate policy, we suggest to flatten the hierarchy by keeping access to IMF unconditional finance open beyond the COVID-19 crisis, expanding regional financial arrangements, and by coordinating GFSN elements, including currency swap providing central banks

SVInterpreter: A Comprehensive Topologically Associated Domain-Based Clinical Outcome Prediction Tool for Balanced and Unbalanced Structural Variants

With the advent of genomic sequencing, a number of balanced and unbalanced structural variants (SVs) can be detected per individual. Mainly due to incompleteness and the scattered nature of the available annotation data of the human genome, manual interpretation of the SV’s clinical significance is laborious and cumbersome. Since bioinformatic tools developed for this task are limited, a comprehensive tool to assist clinical outcome prediction of SVs is warranted. Herein, we present SVInterpreter, a free Web application, which analyzes both balanced and unbalanced SVs using topologically associated domains (TADs) as genome units. Among others, gene-associated data (as function and dosage sensitivity), phenotype similarity scores, and copy number variants (CNVs) scoring metrics are retrieved for an informed SV interpretation. For evaluation, we retrospectively applied SVInterpreter to 97 balanced (translocations and inversions) and 125 unbalanced (deletions, duplications, and insertions) previously published SVs, and 145 SVs identified from 20 clinical samples. Our results showed the ability of SVInterpreter to support the evaluation of SVs by (1) confirming more than half of the predictions of the original studies, (2) decreasing 40% of the variants of uncertain significance, and (3) indicating several potential position effect events. To our knowledge, SVInterpreter is the most comprehensive TAD-based tool to identify the possible disease-causing candidate genes and to assist prediction of the clinical outcome of SVs. SVInterpreter is available at http://dgrctools-insa.min-saude.pt/cgi-bin/SVInterpreter.py.This research was supported by national funds through FCT—Fundação para a Ciência e a Tecnologia, Research Grant HMSP-ICT/0016/2013 of the Harvard Medical School—Portugal Program in Translational Research and Informationinfo:eu-repo/semantics/publishedVersio

SVInterpreter: a web-based tool for structural variants inspection and identification of possible disease-causing candidate genes

Introduction: With the advent of genomic sequencing, the identification of structural variants (SVs) is no longer a challenge, being possible to detect an average of 5 K SVs by individual. Contrarily, the annotation of the genome is incomplete, and the data is scattered along different databases, making SV manual evaluation complicated and time-consuming. Also, the available tools are limited on their scope. Thus, to address the need of a comprehensive application to assist evaluation of clinical outcome of SVs, we developed Structural Variant Interpreter (SVInterpreter). Methods: SVInterpreter is a free Python-CGI developed Web application able to analyze SVs using Topologically Associated Domains as genome units, within which genome browsers data, medically actionable genes, virtual gene panels and HPO similarity results, among other information, is retrieved. Results: We started by re-analysing 220 published SVs, of which about 50% were previously classified as VUS. SVInterpreter corroborated the previous classification in about 84% of the SVs. In about 5% of the SVs, SVInterpreter gave indication of possible position effect, through phenotype similarity, disrupted chromatin loops or genome wide association studies. Then, we show the applicability of SVInterpreter on the clinical setting, by inspecting 15 cases analysed by chromosomal microarray or genome sequencing. Conclusions: To our knowledge, SVInterpreter is the most comprehensive TAD based tool to assist prediction of clinical outcome of SVs. Based on gathered information, identification of possible disease-causing candidate genes and SVs is easily achievable. SVInterpreter is available at http://dgrctools-insa.min-saude.pt/cgi-bin/SVInterpreter.pyinfo:eu-repo/semantics/publishedVersio

Analysis of bone mineral loss by dental panoramic radiography in men over 40 years old in the state of Roraima / Análise da perda mineral óssea por radiografia panorâmica dentária em homens com mais de 40 anos de idade no estado de Roraima

Background: The present study was conducted to understand the possible application of panoramic radiography as an alternative diagnostic measure for the detection of osteopenia and osteoporosis. Moreover, we surveyed to understand the oral hygiene of the participants.Materials and Methods: A questionnaire-based survey for self-assessment was done, followed by a detailed radiographic evaluation and Cortical Mandibular Index (ICM) and Mentonian Index (IM) recording. Later, statistical analyses were done for descriptive analysis and possible important factors responsible for the obtained ICM and IM values. Results: The obtained results suggested that for the present study population of 112 participants, and considered 25 parameters, age was a major factor (P 0.00456) along with the use of a personal toothbrush (P 0.01265), and exchange of a new toothbrush (P 0.0293). These factors were significantly influential on the ICM outcomes (P 0.06645) whereas the influence of the considered parameters was not significantly influential on IM results. Conclusion: The descriptive results suggested that osteopenia and osteoporosis were dominant among the patients as confirmed by the radiographic analysis. Hence, panoramic radiography can be an effective alternative in the diagnosis of osteoporosis. However, confirmation should be obtained from further large-scale studies on diverse populations with more contributing factors

A contribuição do Gnothi Seauton para a educação

O presente texto tem como objetivo adjuntar à máxima délfica gnothi seauton (conhece-te a ti mesmo) como auxílio para a educação contemporânea. Este preceito foi apresentado por Michel Foucault (2018) em um de seus cursos no Collège de France no ano de 1981-1982 intitulado como A hermenêutica do sujeito. Foucault utilizará como eixo de seu curso o diálogo socrático O primeiro Alcibíades (2016) para demonstrar a relação entre mestre e discípulo em uma ótica do cuidado de si.A educação nos dias atuais tem passado por momentos de incertezas, das quais professores e alunos se distanciam cada vez mais, este distanciamento por incrível que pareça, interfere no desenvolvimento dos alunos em sala de aula, sobretudo no ensino médio em que os adolescentes estão em momento de reconhecimento e busca pela própria identidade, a proposta é trazer este preceito para a contemporaneidade afim de reaproximar professores de alunos.O conhece-te a ti mesmo será, portanto, o fio condutor para encontrar o caminho dessa aproximação entre ambos, será por esta relação do cuidado de si que o reencontro consigo mesmo será possível dentro e fora da sala de aula. Para que isso seja possível, percorreremos tais caminhos; (i) entender o conceito de gnothi seauton e (ii) o cuidado de si como estratégia para a educação nos dias atuais

“Eu sou do tipo que não desisto”: a construção de narrativas para pensar antropologia e a epidemia do Zika em Pernambuco

As narrativas têm o poder de alinhavar, costurar e tecer histórias. Ao tecer uma história, os elementos que escolhemos para contá-la são colocados em uma ordem que faça sentido. A narrativa constitui-se como uma importante forma de comunicação, através da qual contamos sobre experiências e também aproximamos pessoas das experiências narradas. Pensando que as narrativas promovem e nos fazem compreender experiências, a proposta deste trabalho é contar sobre a epidemia de Zika no estado de Pernambuco através da ficcionalização de uma história, essa qual construída a partir de dados etnográficos. O  propósito é experimentar as possibilidades de afetação da narrativa dentro da antropologia da saúde por meio dessa história, que contará sobre os impactos da epidemia no cotidiano das mães e crianças que ainda sofrem suas consequências. A aposta é perceber como a composição de histórias que tiveram como fonte os dados de campo podem inspirar a reflexão antropológica, promovendo diferentes leituras e possibilidades interpretativas. Sem a intenção de cobrir de modo totalizante o fenômeno da epidemia, a pretensão aqui é antes valorizar narrativas em nuances pouco audíveis e potencialmente esquecíveis.