Search

The Spike protein's structure of the SARS-CoV-2 provides a unique opportunity to consider perturbations at the atomic level. We used the cryo-electron microscopy structure of the open conformation of the Spike protein to assess the impact of the mutations observed in the variants of concern at the molecular level. Molecular dynamics were subsequently performed with both the wt and the mutated forms to compare the flexibility and variation data for each residue of the three-dimensional fluctuations in the region associated with each alpha carbon. Additionally, protein-protein docking was used to investigate the interaction of each mutated profile with the ACE-2 receptor. After the molecular dynamics, the results show that the mutations increased the stability of the trimeric protein, with greater stability observed in the Gamma variant harboring the 10 characteristic mutations. The results of molecular dynamics, as shown by RMSF demonstrated for the residues that comprise the binding domain receptor (RBD), exhibited a reduction in flexibility, which was more pronounced in the Gamma variant. Finally, protein-protein docking experiments revealed an increase in the number of hydrophobic interactions and hydrogen bonds in the Gamma variant against the ACE-2 receptor, as opposed to the other variants. Taken together, these

to describe epidemiological and clinical characteristics of monkeypox (MPX) in Brazil, from the identification of the first case, on June 7, 2022, to Epidemiological Week (EW) 39, ending on October 1, 2022.this was a descriptive study of cases notified to the Ministry of Health; trends were analyzed based on the number of confirmed and probable cases per EW; the cases were also described according to demographic and clinical variables.out of 31,513 notifications, 23.8% were confirmed; 91.8% were male; 70.6% were cis men; and median age was 32 years. Fever (58.0%), adenomegaly (42.4%), headache (39.9%) and rash (37.0%) were the most frequent symptoms; 27.5% reported being immunosuppressed, 34.6% were living with HIV and 10.5% had a sexually transmitted infection; three deaths were recorded.the MPX case profile was similar to that of other countries; surveillance actions must be strengthened to control the outbreak.descrever características epidemiológicas e clínicas da monkeypox (MPX) no Brasil desde a identificação do primeiro caso, em 7 de junho de 2022, até a semana epidemiológica (SE) 39, encerrada em 1º de outubro de 2022.estudo descritivo dos casos notificados ao Ministério da Saúde; as tendências foram analisadas sobre o número de casos confirmados e prováveis, por SE; os casos foram descritos segundo variáveis demográficas e variáveis clínicas.das 33.513 notificações, 23,8% foram confirmadas, 91,8% eram do sexo masculino e 70,6% de homens cis com idade mediana de 32 anos; febre (58,0%), adenomegalia (42,4%), cefaleia (39,9%) e erupções (37,0%) foram os sintomas mais frequentes; 27,5% declararam ser imunossuprimidos, 34,6% viviam com HIV e 10,5% possuíam infecção sexualmente transmissível; três óbitos foram registrados.o perfil de casos de MPX foi semelhante ao de outros países; ações de vigilância devem ser reforçadas para o controle do surto.Describir las características epidemiológicas y clínicas de la viruela del mono (MPX) en Brasil, desde la identificación del primer caso, el 7 de junio de 2022, hasta la semana epidemiológica (SE) 39, finalizando el 1° de octubre de 2022.Las tendencias de los casos notificados al Ministerio de Salud se analizaron como el número de casos notificados confirmados y probables, por SE. Los casos se describieron según variables demográficas y clínicas.se confirmaron 33.513 notificaciones un 23,8%; 91,8% del sexo masculino; un 70,6% de hombres cis; con edad promedio de 32 años. Fiebre (58,0%), adenomegalia (42,4%), cefalea (39,9%) y exantema (37,0%) fueron los síntomas más frecuentes. Un 27,5% declaró estar inmunodeprimido, 34,6% vivía con VIH y 10,5% tenía alguna infección de transmisión sexual. Se registraron 3 muertes.El perfil de los casos MPX fue similar al de otros países. Se deben reforzar las acciones de vigilancia para controlar el brote.

Resumo Objetivo: descrever características epidemiológicas e clínicas da monkeypox (MPX) no Brasil desde a identificação do primeiro caso, em 7 de junho de 2022, até a semana epidemiológica (SE) 39, encerrada em 1º de outubro de 2022. Métodos: estudo descritivo dos casos notificados ao Ministério da Saúde; as tendências foram analisadas sobre o número de casos confirmados e prováveis, por SE; os casos foram descritos segundo variáveis demográficas e variáveis clínicas. Resultados: das 33.513 notificações, 23,8% foram confirmadas, 91,8% eram do sexo masculino e 70,6% de homens cis com idade mediana de 32 anos; febre (58,0%), adenomegalia (42,4%), cefaleia (39,9%) e erupções (37,0%) foram os sintomas mais frequentes; 27,5% declararam ser imunossuprimidos, 34,6% viviam com HIV e 10,5% possuíam infecção sexualmente transmissível; três óbitos foram registrados. Conclusão: o perfil de casos de MPX foi semelhante ao de outros países; ações de vigilância devem ser reforçadas para o controle do surto. Resumen Objetivo: Describir las características epidemiológicas y clínicas de la viruela del mono (MPX) en Brasil, desde la identificación del primer caso, el 7 de junio de 2022, hasta la semana epidemiológica (SE) 39, finalizando el 1° de octubre de 2022. Métodos: Las tendencias de los casos notificados al Ministerio de Salud se analizaron como el número de casos notificados confirmados y probables, por SE. Los casos se describieron según variables demográficas y clínicas. Resultados: se confirmaron 33.513 notificaciones un 23,8%; 91,8% del sexo masculino; un 70,6% de hombres cis; con edad promedio de 32 años. Fiebre (58,0%), adenomegalia (42,4%), cefalea (39,9%) y exantema (37,0%) fueron los síntomas más frecuentes. Un 27,5% declaró estar inmunodeprimido, 34,6% vivía con VIH y 10,5% tenía alguna infección de transmisión sexual. Se registraron 3 muertes. Conclusión: El perfil de los casos MPX fue similar al de otros países. Se deben reforzar las acciones de vigilancia para controlar el brote. Abstract Objective: to describe epidemiological and clinical characteristics of monkeypox (MPX) in Brazil, from the identification of the first case, on June 7, 2022, to Epidemiological Week (EW) 39, ending on October 1, 2022. Methods: this was a descriptive study of cases notified to the Ministry of Health; trends were analyzed based on the number of confirmed and probable cases per EW; the cases were also described according to demographic and clinical variables. Results: out of 31,513 notifications, 23.8% were confirmed; 91.8% were male; 70.6% were cis men; and median age was 32 years. Fever (58.0%), adenomegaly (42.4%), headache (39.9%) and rash (37.0%) were the most frequent symptoms; 27.5% reported being immunosuppressed, 34.6% were living with HIV and 10.5% had a sexually transmitted infection; three deaths were recorded. Conclusion: the MPX case profile was similar to that of other countries; surveillance actions must be strengthened to control the outbreak.

Background: Vaccination against COVID-19 in Brazil started in January 2021, with health workers and the elderly as the priority groups. We assessed whether there was an impact of vaccinations on the mortality of elderly individuals in a context of wide transmission of the SARS-CoV-2 gamma (P.1) variant. Methods: By May 15, 2021, 238,414 COVID-19 deaths had been reported to the Brazilian Mortality Information System. Denominators for mortality rates were calculated by correcting population estimates for all-cause deaths reported in 2020. Proportionate mortality at ages 70-79 and 80+ years relative to deaths at all ages were calculated for deaths due to COVID-19 and to other causes, as were COVID-19 mortality rate ratios relative to individuals aged 0-69 years. Vaccine coverage data were obtained from the Ministry of Health. All results were tabulated by epidemiological weeks 1-19, 2021. Findings: The proportion of all COVID-19 deaths at ages 80+ years was over 25% in weeks 1-6 and declined rapidly to 12.4% in week 19, whereas proportionate COVID-19 mortality for individuals aged 70-79 years started to decline by week 15. Trends in proportionate mortality due to other causes remained stable. Mortality rates were over 13 times higher in the 80+ years age group compared to that of 0-69 year olds up to week 6, and declined to 5.0 times in week 19. Vaccination coverage (first dose) of 90% was reached by week 9 for individuals aged 80+ years and by week 13 for those aged 70-79 years. Coronavac accounted for 65.4% and AstraZeneca for 29.8% of all doses administered in weeks 1-4, compared to 36.5% and 53.3% in weeks 15-19, respectively. Interpretation: Rapid scaling up of vaccination coverage among elderly Brazilians was associated with important declines in relative mortality compared to younger individuals, in a setting where the gamma variant predominates. Had mortality rates among the elderly remained proportionate to what was observed up to week 6, an estimated additional 43,802 COVID-related deaths would have been expected up to week 19. Funding: CGV and AJDB are funded by the Todos pela Saude (Sao Paulo, Brazil) initiative.

BackgroundVaccination against COVID-19 in Brazil started in January 2021, with health workers and the elderly as the priority groups. We assessed whether there was an impact of vaccinations on the mortality of elderly individuals in a context of wide transmission of the SARS-CoV-2 gamma (P.1) variant.MethodsBy May 27, 2021, 147238,414 COVID-19 deaths had been reported to the Brazilian Mortality Information System. Denominators for mortality rates were calculated by correcting population estimates for all-cause deaths reported in 2020. Proportionate mortality at ages 70-79 and 80+ years relative to deaths at all ages were calculated for deaths due to COVID-19 and to other causes, as were COVID-19 mortality rate ratios relative to individuals aged 0-69 years. Vaccine coverage data were obtained from the Ministry of Health. All results were tabulated by epidemiological weeks 1-19, 2021.FindingsThe proportion of all COVID-19 deaths at ages 80+ years was over 25% in weeks 1-6 and declined rapidly to 12.4% in week 19, whereas proportionate COVID-19 mortality for individuals aged 70-79 years started to decline by week 15. Trends in proportionate mortality due to other causes remained stable. Mortality rates were over 13 times higher in the 80+ years age group compared to that of 0-69 year olds up to week 6, and declined to 5.0 times in week 19. Vaccination coverage (first dose) of 90% was reached by week 9 for individuals aged 80+ years and by week 13 for those aged 70-79 years. Coronavac accounted for 65.4% and AstraZeneca for 29.8% of all doses administered in weeks 1-4, compared to 36.5% and 53.3% in weeks 15-19, respectively.InterpretationRapid scaling up of vaccination coverage among elderly Brazilians was associated with important declines in relative mortality compared to younger individuals, in a setting where the gamma variant predominates. Had mortality rates among the elderly remained proportionate to what was observed up to week 6, an estimated additional 43,802 COVID-related deaths would have been expected up to week 19.

The COVID-19 pandemic in Brazil has demonstrated an important public health impact, as has been observed in the world. In Brazil, the Amazon Region contributed with a large number of cases of COVID-19, especially in the beginning of the circulation of SARS-CoV-2 in the country. Thus, we describe the epidemiological profile of COVID-19 and the genetic diversity of SARS-CoV-2 strains circulating in the Amazon Region. We observe an extensive spread of virus in this Brazilian site. The data on sex, age and symptoms presented by the investigated individuals were similar to what has been observed worldwide. The genomic analysis of the viruses revealed important amino acid changes, including the D614G and the I33T in Spike and ORF6 proteins, respectively. The latter found in strains originating in Brazil. The phylogenetic analyzes demonstrated the circulation of the lineages B.1 and B.1.1, whose circulation in Brazil has already been previous reported. Our data reveals molecular epidemiology of SARS-CoV-2 in the Amazon Region. These findings also reinforce the importance of continuous genomic surveillance this virus with the aim of providing accurate and updated data to understand and map the transmission network of this agent in order to subsidize operational decisions in public health.

BackgroundBrazil has experienced a large dengue virus (DENV) epidemic in 2019, highlighting a continual struggle with effective control and public health preparedness. Brazil is a world leader in real-time genomic surveillance of arboviruses, although such technology and expertise remains inaccessible for the vast majority of local researchers and public health workers. In 2019, we led field and classroom initiatives for the genomic surveillance of DENV in Brazil.MethodsOxford Nanopore MinION technology was used for sequencing, focusing on generating DENV1 and DENV2 complete genomes. Using phylogenetic and epidemiological approaches conducted in real-time during a training program and subsequently through online channels, we explored the recent spatio-temporal evolution and spread of these viruses in Brazil.FindingsIn the years following the Zika virus epidemic (2017-2018) reporting was at an all-time low, and significant increases in reported cases and deaths in 2019 did not reflect a higher case fatality ratio. Estimated transmission potential and reporting of other arboviruses suggests that neither arboviral reporting saturation nor climatic factors can easily explain the post-Zika period and resurgence in 2019 (respectively). Phylogenetic analysis revealed complex patterns of transmission, with lineage co-circulation and replacement, in which the North and the Southeast acted as sources of dispersion to other regions. We identified two lineages within the already reported DENV2 BR-4 clade, for which the effective reproduction number had seasonal signatures alike reported cases, with a temporal increase towards 2019 mirroring the large epidemic that year.InterpretationWe describe the recent evolution and diffusion of DENV1 and DENV2 in Brazil. Importantly, the surveillance outputs and training initiative here described serve as proof-of-concept of the potential of portable sequencing for both research and local capacity building in the area of genomic surveillance of arboviruses.FundingDecit, SCTIE, BrMoH, CNPq, CAPES, EU Horizon 2020 through ZIKAlliance and STARBIOS2.

Ao Editor, Diariamente, milhares de variantes do SARS-CoV-2 surgem no mundo, evidenciando o desafio de reforcar a capacidade de deteccao oportuna com ampliacao e fortalecimento da vigilância epidemiologica, vigilância laboratorial e comunicacao rapida, com desenvolvimento de pesquisas em saude que possam apoiar as medidas de prevencao e controle da pandemia da COVID-19. Ainda que nao se conhecam todas as implicacoes das novas variantes da COVID-19 para o controle da doenca, algumas mutacoes ou combinacoes podem fornecer ao virus uma vantagem seletiva, que contribui para aumentar a transmissibilidade ou a capacidade de evadir a resposta imune do hospedeiro. No Brasil, ate 10 de abril de 2021, foram registrados e confirmados 13 445 006 casos e 361 334 obitos por COVID-19, com incidencia acumulada de 6 397,9 por 100 mil habitantes e mortalidade de 157,2 por 100 mil habitantes. De acordo com a Organizacao Mundial da Saude (OMS), o Brasil e o segundo pais com maior numero de casos e obitos por COVID-19 no mundo. Entretanto, alem da alta incidencia e mortalidade pela doenca encontradas no Brasil, o Sistema Unico de Saude (SUS) esta sendo desafiado pela circulacao de variantes de atencao do SARS-CoV-2 nos estados.

Since introduction into Brazil in 2014, chikungunya virus (CHIKV) has presented sustained transmission, although much is unknown about its circulation in the midwestern states. Here, we analyze 24 novel partial and near complete CHIKV genomes from Cuiaba, an urban metropolis located in the Brazilian midwestern state of Mato Grosso (MT). Nanopore technology was used for sequencing CHIKV complete genomes. Phylogenetic and epidemiological approaches were used to explore the recent spatio-temporal evolution and spread of the CHIKV-ECSA genotype in Midwest Brazil as well as in the Americas. Epidemiological data revealed a reduction in the number of reported cases over 2018–2020, likely as a consequence of a gradual accumulation of herd-immunity. Phylogeographic reconstructions revealed that at least two independent introductions of the ECSA lineage occurred in MT from a dispersion event originating in the northeastern region and suggest that the midwestern Brazilian region appears to have acted as a source of virus transmission towards Paraguay, a bordering South American country. Our results show a complex dynamic of transmission between epidemic seasons and suggest a possible role of Brazil as a source for international dispersion of the CHIKV-ECSA genotype to other countries in the Americas., Author summary Since its introduction into Brazil in 2014, chikungunya virus (CHIKV) has presented sustained transmission, although much is unknown about its circulation in the midwestern states. Here, using a combined strategy of a mobile sequencing mission through this region, with genomic and epidemiological analysis we generated 24 novel partial and near complete CHIKV genome sequences by means of portable nanopore sequencing of chikungunya virus isolates obtained directly from clinical samples. Our findings reinforce that continued genomic surveillance strategies are needed to assist in the monitoring and understanding of arbovirus epidemics, which might help to attenuate public health impact of infectious diseases.

Gastric cancer (GC) is a multifactorial disease with a high mortality rate in Brazil and worldwide. This work aimed to evaluate single nucleotide polymorphisms (SNP) rs1695, in the Glutathione S-Transferase Pi (GSTP1) gene in GC samples by comparative analysis Specific PCR - ASP and Dideoxy Single Allele-Specific PCR - DSASP methods. The DSASP is the proposed new method for allelic discrimination. This work analyzed 60 GC samples, 26 diffuse and 34 intestinal types. The SNP rs1695 of the GSTP1 gene was significantly associated with GC analyzed by DSASP method (χ 2 = 9.7, P < 0.05). A comparative analysis of the data obtained from both methods did not differ significantly (χ 2 = 0.08, P > 0.05). These results suggest that the SNP rs1695 of the GSTP1 gene was a risk factor associated with gastric carcinogens is and the DSASP method was a new successfully low-cost strategy to study allelic discrimination.

Basal cell carcinoma - BCC is considered a multifactorial neoplasm involving genetic, epigenetic and environmental factors. Where UVB radiation is considered the main physical agent involved in BCC carcinogenesis. The Brazil and state of Paraiba are exposed to high levels of UVB rays. The mismatch repair - MMR is important DNA repair mechanisms to maintain replication fidelity. Therefore, single nucleotide polymorphisms (SNPs) in genes encoding proteins involved in MMR may be potential molecular markers of susceptibility to BCC. The objective of this study was to evaluate and describe for the first time the SNPs rs560246973, rs2303425 and rs565410865 and risk of developing BCC. The present study analyzed 100 samples of paraffin-embedded tissue from patients with histopathological diagnosis of BCC and 100 control samples. The results were obtained by genotyping method, Dideoxy Unique Allele Specific - PCR (DSASP). The SNPs rs2303425 were not associated with Basal Cell Carcinoma. However, the SNPs rs560246973 and rs565410865 was shown to be associated with the development of BCC when compared to control samples (P

O câncer é uma doença potencialmente letal. Os tumores se desenvolvem em células que estão se dividindo. Sua iniciação ou progressão está associada com o acúmulo de alterações genéticas. Essas alterações podem ser aberrações cromossômicas, mutações, polimorfismos e modificações epigenéticas. O câncer se desenvolve quando mecanismos de defesa do organismo sofrem alterações. Os tumores do sistema nervoso representam aproximadamente 2% de todos os tipos de câncer. O papel central do sistema nervoso e as conseqüências funcionais da perda de neurônios podem explicar a severidade dos tumores cerebrais. A formação dos tumores do cérebro humano é um processo complexo, envolvendo um acúmulo de alterações genéticas. Os genes supressores de tumor estão envolvidos na formação de tumores. Sua perda, inativação ou disfunção leva a célula a se dividir desordenadamente, surgindo assim tumores e neoplasias no local onde elas ocorrem. O objetivo deste trabalho foi fazer uma triagem de ocorrência de polimorfismos conformacionais no gene supressor de tumor PTEN em 50 amostras de tumores de Sistema Nervoso. Nenhuma alteração mutacional foi encontrada. Nossos resultados se assemelham aos da literatura em relação à ausência de alterações no gene PTEN em tumores benignos; em relação aos glioblastomas, a literatura cita uma alta freqüência de alterações no gene PTEN, mas não encontramos nenhuma alteração nas 9 amostras estudadas. Outro mecanismo como por exemplo a metilação da região promotora, poderia estar envolvido na inativação desse gene nos tumores analisados. Cancer is a potentially lethal illness. Tumors develop in cells that are dividing. Its initiation or progression is associated with the accumulation of genetic alterations. These alterations can be chromosome aberrations, mutations, polimorphisms and epigenetic modifications. The cancer develops when mechanisms of defence of the organism are altered. The tumors of the nervous system represent approximately 2% of all the types of cancer. The central role of the nervous system and the functional consequences of the loss of neurons can explain the severity of the cerebral tumors. The formation of the tumors of the human brain is a complex process, involving an accumulation of genetic alterations. The tumor suppressor genes are involved in the formation of tumors. If there is a loss, inactivation or disfunction, the cell will divide disorderly, and tumors and other neoplasias will appear in the place where they occur. The objective of this work was to make a selection of the occurrence of conformacional polymorphisms in the tumor suppresor gene PTEN in 50 samples of tumors of Nervous System. No mutacional alteration was found. Our results if are similar to the ones of the literature in relation to the absence of alterations in gene PTEN in benign tumors; in relation to glioblastomas, literature cites a high frequency of alterations in gene PTEN, but we did not find any alteration in the 9 studied samples. Another mechanism as, for example, the metilation of the promoterl region, could be involved in the inativação of this gene in the analyzed tumors.