Overexpression of the autism candidate gene Cyfip1 pathologically enhances olivo-cerebellar signaling in mice.

Cyfip1, the gene encoding cytoplasmic FMR1 interacting protein 1, has been of interest as an autism candidate gene for years. A potential role in autism spectrum disorder (ASD) is suggested by its location on human chromosome 15q11-13, an instable region that gives rise to a variety of copy number variations associated with syndromic autism. In addition, the CYFIP1 protein acts as a binding partner to Fragile X Messenger Ribonucleoprotein (FMRP) in the regulation of translation initiation. Mutation of FMR1, the gene encoding FMRP, causes Fragile X syndrome, another form of syndromic autism. Here, in mice overexpressing CYFIP1, we study response properties of cerebellar Purkinje cells to activity of the climbing fiber input that originates from the inferior olive and provides an instructive signal in sensorimotor input analysis and plasticity. We find that CYFIP1 overexpression results in enhanced localization of the synaptic organizer neurexin 1 (NRXN1) at climbing fiber synaptic input sites on Purkinje cell primary dendrites and concomitant enhanced climbing fiber synaptic transmission (CF-EPSCs) measured using whole-cell patch-clamp recordings from Purkinje cells in vitro. Moreover, using two-photon measurements of GCaMP6f-encoded climbing fiber signals in Purkinje cells of intact mice, we observe enhanced responses to air puff stimuli applied to the whisker field. These findings resemble our previous phenotypic observations in a mouse model for the human 15q11-13 duplication, which does not extend to the Cyfip1 locus. Thus, our study demonstrates that CYFIP1 overexpression shares a limited set of olivo-cerebellar phenotypes as those resulting from an increased number of copies of non-overlapping genes located on chromosome 15q11-13.

Vaccine Mismatches, Viral Circulation, and Clinical Severity Patterns of Influenza B Victoria and Yamagata Infections in Brazil over the Decade 2010-2020: A Statistical and Phylogeny-Trait Analyses.

Worldwide, infections by influenza viruses are considered a major public health challenge. In this study, influenza B vaccine mismatches and clinical aspects of Victoria and Yamagata infections in Brazil were assessed. Clinical samples were collected from patients suspected of influenza infection. In addition, sociodemographic, clinical, and epidemiological information were collected by the epidemiological surveillance teams. Influenza B lineages were determined by real-time RT-PCR and/or Sanger sequencing. In addition, putative phylogeny−trait associations were assessed by using the BaTS program after phylogenetic reconstruction by a Bayesian Markov Chain Monte Carlo method (BEAST software package). Over 2010−2020, B/Victoria and B/Yamagata-like lineages co-circulated in almost all seasonal epidemics, with B/Victoria predominance in most years. Vaccine mismatches between circulating viruses and the trivalent vaccine strains occurred in five of the eleven seasons (45.5%). No significant differences were identified in clinical presentation or disease severity caused by both strains, but subjects infected by B/Victoria-like viruses were significantly younger than their B/Yamagata-like counterparts (16.7 vs. 31.4 years, p < 0.001). This study contributes to a better understanding of the circulation patterns and clinical outcomes of B/Victoria- and B/Yamagata-like lineages in Brazil and advocate for the inclusion of a quadrivalent vaccine in the scope of the Brazilian National Immunization Program.

Demographic, socioeconomic and epidemiological aspects of COVID-19 in the Cunha Canal Sub-Basin Region, Rio de Janeiro / Aspectos demográficos, socioeconômicos e epidemiológicos da COVID-19 na Região da Sub-Bacia do Canal do Cunha, Rio de Janeiro

The objective of this study was to analyze the COVID-19 incidence of and mortality in a population from a territorial area with a predominance of neighborhoods with slum areas (subnormal settlements), and its relationship with contextual variables. We analyzed 36 neighborhoods of the Canal do Cunha Sub-basin that presented 30,008 deaths by COVID-19 until February 5, 2021. Cumulative incidence, cumulative mortality, and cumulative lethality rates were considered as dependent variables. Contextual variables included patient neighborhood; proportion of ASN by neighborhoods, percentage of black and brown people, age group; income ratio, and sanitation indices. The variables were analyzed descriptively, bivariately by Spearman correlation, and Moran's spatial statistics were performed. The Complexo do Alemão, Mangueira, and Maré neighborhoods had the highest proportions of cases and deaths from COVI-19. The percentage of infection in the 20 to 29, 30 to 39, and 40 to 49 age groups were 13.6%, 21.5%, and 20.1%, respectively. In the 70 to 79 age group was 7.3% of the total COVID-19 cases, and 26.7% deaths and 34.2% lethality rate. When added the records of black and brown people with those without records for color/race there was significant positive moderate correlation between the cumulative incidence rate and mortality rate (rho = 0.383; p=0.048 and rho= 0.3176; p= 0.0106). The global and local Moran's spatial statistical evaluation allowed to verify intermediate and medium priority areas that need to strengthen the surveillance and control system of COVID-19. The epidemiological situation of an area with a high percentage of slum areas showed that mortality by COVID-19 in black and brown people is related to demographic aspects and that there is low notification of cases and deaths attributed to COVID-19 in residents of areas with slums.

Objetivo desse estudo foi analisar a incidência e mortalidade por COVID-19 em população de área territorial com predominância de bairros com áreas de favelas (aglomerados subnormais), e sua relação com variáveis contextuais. Foram analisados 36 bairros da Sub-bacia do Canal do Cunha que apresentaram 30.008 óbitos por COVID-19 até o dia 05 de fevereiro de 2021. Considerou-se como variáveis dependentes as taxas de incidência acumulada, mortalidade acumulada e letalidade acumulada. Entre as variáveis contextuais, foram incluídas bairro do paciente; proporção de ASN por bairros, percentual de pretos e pardos, faixa etária; razão de renda, e índices de saneamento. As variáveis foram analisadas de forma descritiva, bivariada pela correlação de Spearman e utilizado a estatística espacial de Moran. Os bairros Complexo do Alemão, Mangueira e Maré foram que apresentaram as maiores proporções de casos e óbitos por COVI-19. O percentual de infecção nas faixas de 20 a 29 anos, 30 a 39 anos e 40 a 49 anos foram de 13,6%, 21.5% e 20,1%, respectivamente. Na faixa etária entre 70 e 79 anos foi 7,3% do total de casos de COVID-19, e 26,7%  de óbitos e 34,2% taxa de letalidade. Quando somado os registros de pessoas pretas e parda com os sem registro para cor/raça houve correlação moderada positiva significativa entre a taxa de incidência acumulada e a taxa de mortalidade  (rho = 0,383; p=0,048 e rho= 0,3176; p=0,0106). A avaliação estatística espacial global e local de Moran permitiu verificar áreas de prioridade intermediárias e médias que necessitam reforçar o sistema de vigilância e controle da COVID-19. A situação epidemiológica de área com grande percentual de áreas favelas mostrou que a mortalidade por COVID-19 em pessoas pretas e pardas está relacionada a aspectos demográficos e que ocorre baixa notificação de casos e de óbitos atribuídas ao COVID-19 em moradores de áreas com favelas.

Aspectos demográficos, socioeconômicos e epidemiológicos da COVID-19 na Região da Sub-Bacia do Canal do Cunha, Rio de Janeiro / Demographic, socioeconomic and epidemiological aspects of COVID-19 in theCunha Canal Sub-Basin Region, Rio de Janeiro

Objetivo desse estudo foi analisar a incidência e mortalidade por COVID-19 em população de área territorial com predominância de bairros com áreas de favelas (aglomerados subnormais), e sua relação com variáveis contextuais. Foram analisados 36 bairros da Sub-bacia do Canal do Cunha que apresentaram 30.008 óbitos por COVID-19 até o dia 05 de fevereiro de 2021. Considerou-se como variáveis dependentes as taxas de incidência acumulada, mortalidade acumulada e letalidade acumulada. Entre as variáveis contextuais, foram incluídas bairro do paciente; proporção de ASN por bairros, percentual de pretos e pardos, faixa etária; razão de renda, e índices de saneamento. As variáveis foram analisadas de forma descritiva, bivariada pela correlação de Spearmane utilizadoa estatística espacial de Moran. Os bairros Complexo do Alemão, Mangueira e Maré foram que apresentaram as maiores proporções de casos e óbitos por COVI-19. O percentual de infecção nas faixas de 20 a 29 anos, 30 a 39 anos e 40 a 49 anos foram de 13,6%, 21.5% e 20,1%, respectivamente. Na faixa etária entre 70 e 79 anos foi 7,3% do total de casos de COVID-19, e 26,7% de óbitos e 34,2% taxa de letalidade. Quando somado os registros de pessoas pretas e parda com os sem registro para cor/raça houve correlaçãomoderada positiva significativa entre a taxa de incidência acumulada e a taxa de mortalidade (rho = 0,383; p=0,048 e rho= 0,3176; p=0,0106). A avaliação estatística espacial global e local de Moran permitiu verificar áreas de prioridade intermediárias e médias que necessitam reforçar o sistema de vigilância e controle da COVID-19. A situação epidemiológica de área com grande percentual de áreas favelas mostrou que a mortalidade por COVID-19 em pessoas pretas e pardas está relacionada a aspectos demográficos e que ocorre baixa notificação de casos e de óbitos atribuídas ao COVID-19 em moradores de áreas com favelas.