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

Saúde mental e funcionalidade psicossocial durante a pandemia da covid19 na população brasileira

Apesar dos grandes avanços na medicina, as doenças infecciosas continuam sendo uma das maiores ameaças ao bem-estar da humanidade. A epidemia do SARS-CoV-2 que atualmente acomete todos os continentes, é o maior surto de pneumonia atípica desde a síndrome respiratória aguda grave (SARS) em 2003. A quarentena de comunidades inteiras, fechamento de escolas e isolamento social, além de sentimentos negativos como por exemplo, frustação e tédio, insegurança, medo ao desconhecido e medo de infectar-se, falta de perspectiva, excesso de informações e perda financeira mudaram abruptamente a vida cotidiana, trazendo várias consequências físicas e mentais. A COVID-19 pode afetar as pessoas de maneiras diferentes, com base em alguns fatores sociodemográficos e de saúde. Enquanto algumas pessoas sofrem mais, outras são capazes de aceitar a situação e de se recuperar em um curto período de tempo. A pandemia do SARS-CoV-2 também trouxe grandes limitações à pesquisa, pois dificultou a ida a campo, diminuiu a possibilidade de incursões em contextos de pesquisa, principalmente nos serviços de saúde, afetando o uso de técnicas que utilizam a palavra, o olhar e a empatia. Assim, essa tese teve como objetivo verificar a prevalência e determinantes da saúde mental e funcionamento psicossocial na população brasileira e comparar tais desfechos entre trabalhadores que atuaram em diferentes locais de trabalho durante a pandemia da COVID19. No primeiro artigo intitulado “Mental health, functioning and quality of life between work in the office and work from home employees during first wave of COVID19 in Brazil” verificamos o impacto da pandemia da COVID19 na saúde mental de trabalhadores que ficaram em casa (home office) e dos que continuaram sua rotina, trabalhando fora de casa e concluímos que durante a pandemia houve um impacto negativo na saúde mental tanto nos que trabalharam em casa, como os que trabalhavam fora de casa, porém os que trabalhavam em casa foram menos afetados. No segundo artigo intitulado “Validity and reliability of the Digital Functioning Assessment Short Test (D-FAST) in the general population” validamos a escala FAST para a versão digital e auto-aplicada. Também foi realizada uma análise de cluster onde foi classificada a funcionalidade em três clusters (baixo, médio e alto funcionamento) da população brasileira durante a pandemia da COVID19. A versão digital da FAST apresentou fortes propriedades psicométricas na amostra da população geral, indicando que o instrumento mede um construto multidimensional de funcionamento, incentivando seu uso por pesquisadores e clínicos em sua prática. Assim, podemos concluir que problemas de saúde mental e mau funcionamento psicossocial podem ser uma marca deixada por esta pandemia.Although great advances in medicine, infectious diseases remain one of the greatest threats to the well-being of humanity. The SARS-CoV-2 epidemic, which currently affects all continents, is the largest outbreak of atypical pneumonia since severe acute respiratory syndrome (SARS) in 2003. The quarantine of entire communities, school closures and social isolation, in addition to negative feelings such as frustration and boredom, insecurity, fear of the unknown and fear of becoming infected, lack of perspective, excess of information and financial loss abruptly changed the everyday life, bringing various physical and mental consequences. COVID-19 can affect people in different ways, based on certain sociodemographic and health factors. While some people suffer more, others are able to accept the situation and recover in a short period. The SARSCoV- 2 pandemic also brought major limitations to research, as it made it difficult to go to the field, reduced the possibility of incursions into research contexts, especially in health services, affecting the use of techniques that use the word, the look and empathy. Thus, this thesis aimed to verify the prevalence and determinants of mental health and psychosocial functioning in the Brazilian population and to compare such outcomes among workers who worked in different workplaces during the COVID19 pandemic. In the first manuscript entitled “Mental health, functioning and quality of life between work in the office and work from home employees during first wave of COVID19 in Brazil” we verified the impact of the COVID19 pandemic on the mental health of workers in home office, and those who continued their routine, working at office, and we concluded that during the pandemic there was a negative impact on mental health both in those who worked at home and those who worked in office, but those who worked from home were less affected. In the second article entitled “Validity and reliability of the Digital Functioning Assessment Short Test (D-FAST) in the general population”, we validated the FAST scale for the digital and self-applied version. A cluster analysis was also performed, where functionality was classified into three clusters (low, medium and high functioning) of the Brazilian population during the COVID19 pandemic. The digital version of FAST showed strong psychometric properties in the general population sample, indicating that the instrument measures a multidimensional construct of functioning, encouraging its use by researchers and clinicians in their practice. Thus, we can conclude that mental health problems and psychosocial impairment may be a mark left by this pandemic

Efeitos de um breve protocolo de treinamento de respiração profunda sobre os sintomas de ansiedade em pacientes com transtorno bipolar

O Transtorno Bipolar (TB) é uma das doenças mais incapacitantes no mundo. É frequentemente acompanhado de comorbidades, tanto clínicas quanto psiquiátricas. Ansiedade é uma das comorbidades mais prevalente em TB, e o tratamento é difícil, pois as medicações podem induzir mania. Portanto, os métodos alternativos com potencial para melhorar sintomas ansiosos são muito importantes. Respiração profunda (RP) é uma técnica simples, que não necessita de grandes investimentos, não precisa de espaço específico. A respiração profunda tem grande potencial para o tratamento de transtornos psicológicos, porém a literatura ainda carece de avaliações dos benefícios e um protocolo definido de RP, com tempo de duração e frequência dos exercícios respiratórios. Essa dissertação tem como objetivo geral avaliar os efeitos de um protocolo de exercícios de respiração profunda em pacientes com Transtorno Bipolar. Os pacientes realizaram sete encontros, sendo três destes para avaliação (antes e após aplicação do protocolo e um mês após protocolo) e quatro para intervenção. Foi utilizado o programa estatístico R para compilação e análise dos dados. Vinte pacientes aceitaram participar do estudo e realizaram a avaliação pré-intervenção, porém quatorze pacientes completaram o protocolo, sendo que 3 desistiram devido a questões de logística e 3 foram excluídos do estudo por não atenderem todos os critérios de inclusão. As escalas HAM-A, BECK-A, HAM-D e YMRS tiveram diferenças significativas pré, pós-intervenção e follow-up. Os resultados indicam que o protocolo de Respiração Profunda é efetivo na redução dos níveis de ansiedade em pacientes com Transtorno Bipolar. O protocolo de Respiração Profunda não tem efeitos colaterais e pode ser aplicado para aliviar os sintomas de ansiedade em pacientes com Transtorno Bipolar.Bipolar Disorder (BD) is one of the most disabling diseases in the world. It is often accompanied by comorbidities, both clinical and psychiatric. Anxiety is one of the most prevalent comorbidities in BD, and treatment is difficult as medications can induce mania. Therefore, alternative methods with potential for improving anxiety symptoms are very important. Deep breathing (DB) is a simple technique that does not require large investments, does not need specific space. Deep breathing has great potential for the treatment of psychological disorders, but the literature still lacks benefits assessments and a defined DB protocol, with duration and frequency of breathing exercises. This project aims to evaluate the effects of a protocol of deep breathing exercises in patients with Bipolar Disorder. The patients performed seven meetings, three of which were for evaluation (before and after the application of the protocol and one day after the protocol) and four for the intervention. The statistical program R was used for data compilation and analysis. Twenty patients accepted to participate in the study and carried out the pre-intervention evaluation, but fourteen patients completed the protocol, three of whom gave up due to logistics issues and three were excluded from the study because they did not meet all the inclusion criteria. The HAM-A, BECK-A, HAM-D and YMRS scales had significant pre, post-intervention, and follow-up differences. The results indicate that the Deep Breathing protocol is effective in reducing anxiety levels in patients with Bipolar Disorder. The Deep Breathing protocol has no negative side effects and can be applied to alleviate anxiety symptoms in patients with Bipolar Disorder

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/

A 669Kb deletion in 17q23.2, encompassing TBX2 and TBX4 genes, in a girl with a moderate developmental delay without any other pertinent abnormality

Microdeletion of the 17q23.1-q23.2 region recently emerged as a syndrome (OMIM#613355) based in a small number of cases with a common phenotype including mild-to-moderate developmental delay, heart defects, microcephaly, postnatal grow retardation, and hand, foot, and limb abnormalities. All patients reported to date present mild to moderate developmental delay, in particular speech delay, and half of them hearing loss. The smallest overlapping region has approximately 2.2 Mb and includes the transcription factors TBX2 and TBX4 genes. These genes have been implicated in a number of developmental pathways, including those of the heart and limbs. The TBX4 gene is also associated with the autosomal dominant small patella syndrome (SPS, OMIM 147891). Here we report a 8 year-old girl with moderate developmental delay including learning disabilities. The test for Fragile X syndrome indicated an allele within the grey area (number of repeats ~50 CGG) inherited from her mother and probably not relevant. Affymetrix Cytoscan HD chromosome microarray analysis was performed and a 669 Kb interstitial deletion was detected at 17q23.2 region, encompassing only five OMIM genes: BCAS3, TBX2, TBX4, NACA2 and BRIP1. To our knowledge this is the smallest deletion described in this region. None of the genes present in the deleted region are known to be associated with developmental problems. We compare our patient with the other similar reported cases, in order to add some increased value to the phenotype-genotype correlation of deletions in this region.N/

Small Deletion of 143 Kb Encompassing Exon 2 of the AUTS2: Rise of a NewMicrodeletion Syndrome?

Abstract publicado em: Chromosome Res. 2015 Jun;23 Suppl 1:35-36. doi: 10.1007/s10577-015-9476-6.Chromosome microarray analysis is a powerful diagnostic tool and is being used as a first-line approach to detect chromosome imbalances associated with intellectual disability, dysmorphic features and congenital anomalies. This test enables the identification of new copy number variants (CNVs) and their association with new microdeletion/microduplication syndromes in patients previously without diagnosis. Here we report the case of a 17 year-old female with severe intellectual disability, absence of speech, microcephaly and congenital abnormalities with a previous normal karyotype performed at a younger age. Affymetrix CytoScan HD chromosome microarray analysis was performed detecting a 143 Kb deletion at the 7q11.22 breakpoint, encompassing exon 2 of AUTS2 gene: arr[hg19] 7q11.22(69238957- 69381975)×1. The AUTS2 gene has been recently implicated in neurodevelopment and is a candidate gene for numerous neurological disorders. Common clinical features described in patients with deletions in AUTS2 gene include intellectual disability, speech delay and microcephaly, among others. Thus, the CNV identified in our patient explains the phenotype observed. We compare our patient with other similar reported cases, adding additional value to the phenotypegenotype correlation of deletions in this region. The growing collection of new cases with similar phenotypes, and the observation of this deletion occurring frequently de novo, indicates this CNV as a possible new single gene microdeletion syndrome

ESTUDO/ANÁLISE DOCUMENTAL: UMA REVISÃO TEÓRICA E METODOLÓGICA

O presente estudo tem por objetivo descrever o tema dapesquisa/análise documental, em seus aspectos teóricos e metodológicos. Falada aproximação e distanciamento entre pesquisa documental e pesquisabibliográfica. Descreve os elementos que devem ser observados na da pesquisadocumental: contexto, autores, interesses, confiabilidade, natureza do texto,conceitos-chave. Feito a seleção primária dos documentos é realizada a análisedocumental em que se reúne o objeto do estudo (problema e objetivos) e osdocumentos selecionados refazendo uma análise observando os elementosmencionados. É um procedimento metodológico praticamente decisivo paraalgumas áreas, como humanas e sociais. Em muitas pesquisas, os documentossão a única fonte de informação. Também pode ser utilizado de forma associadaou complementar com outros procedimentos metodológicos

Identifying pathways between psychiatric symptoms and psychosocial functioning in the general population

The present study aims to identify pathways between psychiatric network symptoms and psychosocial functioning and their associated variables among functioning clusters in the general population. A cross-sectional web-based survey was administered in a total of 3,023 individuals in Brazil. The functioning clusters were derived by a previous study identifying three different groups based on the online Functioning Assessment Short Test. Networking analysis was fitted with all items of the Patient-Reported Outcomes Measurement Information System for depression and for anxiety (PROMIS) using the mixed graphical model. A decision tree model was used to identify the demographic and clinical characteristics of good and low functioning. A total of 926 (30.63%) subjects showed good functioning, 1,436 (47.50%) participants intermediate functioning, and 661 (21.86%) individuals low functioning. Anxiety and uneasy symptoms were the most important nodes for good and intermediate clusters but anxiety, feeling of failure, and depression were the most relevant symptoms for low functioning. The decision tree model was applied to identify variables capable to discriminate individuals with good and low functioning. The algorithm achieved balanced accuracy 0.75, sensitivity 0.87, specificity 0.63, positive predictive value 0.63 negative predictive value 0.87 (p<0.001), and an area under the curve of 0.83 (95%CI:0.79–0.86, p<0.01). Our results show that individuals who present psychological distress are more likely to experience poor functional status, suggesting that this subgroup should receive a more comprehensive psychiatric assessment and mental health care