Molecular dynamics simulations of the SARS-CoV-2 Spike protein and variants of concern: structural evidence for convergent adaptive evolution.

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 in silico experiments suggest that the evolution of the mutations favored the increased stability of Spike protein while potentially improving its interaction with the ACE-2 receptor, which in turn may indicate putative structural outcomes of the selection of these mutations in the convergent adaptive evolution as it has been observed for SARS-CoV-2.Communicated by Ramaswamy H. Sarma.

Epidemiological and clinical characteristics of monkeypox cases in Brazil in 2022: a cross-sectional study. / Características epidemiológicas e clínicas dos casos de monkeypox no Brasil em 2022: estudo transversal.

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.

Características epidemiológicas e clínicas dos casos de monkeypox no Brasil em 2022: estudo transversal / Características epidemiológicas y clínicas de los casos de viruela del mono en Brasil em 2022: un estudio transversal / Epidemiological and clinical characteristics of monkeypox cases in Brazil in 2022: a cross-sectional study

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.

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.

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.

Estimating the early impact of vaccination against COVID-19 on deaths among elderly people in Brazil: Analyses of routinely-collected data on vaccine coverage and mortality.

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 Saúde (São Paulo, Brazil) initiative.

A vigilância genômica do SARS-CoV-2 no Brasil na resposta à pandemia da COVID-19

Ao Editor, Diariamente, milhares de variantes do SARS-CoV-2 surgem no mundo, evidenciando o desafio de reforçar a capacidade de detecção oportuna com ampliação e fortalecimento da vigilância epidemiológica, vigilância laboratorial e comunicação rápida, com desenvolvimento de pesquisas em saúde que possam apoiar as medidas de prevenção e controle da pandemia da COVID-19. Ainda que não se conheçam todas as implicações das novas variantes da COVID-19 para o controle da doença, algumas mutações ou combinações podem fornecer ao vírus uma vantagem seletiva, que contribui para aumentar a transmissibilidade ou a capacidade de evadir a resposta imune do hospedeiro. No Brasil, até 10 de abril de 2021, foram registrados e confirmados 13 445 006 casos e 361 334 óbitos por COVID-19, com incidência acumulada de 6 397,9 por 100 mil habitantes e mortalidade de 157,2 por 100 mil habitantes. De acordo com a Organização Mundial da Saúde (OMS), o Brasil é o segundo país com maior número de casos e óbitos por COVID-19 no mundo. Entretanto, além da alta incidência e mortalidade pela doença encontradas no Brasil, o Sistema Único de Saúde (SUS) está sendo desafiado pela circulação de variantes de atenção do SARS-CoV-2 nos estados.

List of priority congenital anomalies for surveillance under the Brazilian Live Birth Information System. / Lista de anomalias congênitas prioritárias para vigilância no âmbito do Sistema de Informações sobre Nascidos Vivos do Brasil.

OBJECTIVE: To define the list of priority congenital anomalies for improving their recording on the Brazilian Live Birth Information System (Sinasc). METHODS: Based on the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10), international protocols and meetings with specialists, the list of priority anomalies was built considering two main criteria: being diagnosable at birth and having intervention available at different levels. The list was submitted for consideration by the Brazilian Medical Genetics and Genomics Society. RESULTS: The list comprised eight groups of congenital anomalies distributed according to the type of related anomaly, as well as the affected part of the body and its corresponding code in ICD-10 Chapter XVII. CONCLUSION: The list of priority congenital anomalies for notification provides a basis for improving case recording on Sinasc.

Short report: Introduction of chikungunya virus ECSA genotype into the Brazilian Midwest and its dispersion through the Americas.

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.

List of priority congenital anomalies for surveillance under the Brazilian Information System on Live Births / Lista de anomalías congénitas prioritarias para la vigilancia bajo el Sistema de Información sobre Nacimientos Vivos en Brasil / Lista de anomalias congênitas prioritárias para vigilância no âmbito do Sistema de Informações sobre Nascidos Vivos do Brasil

Objective: To define the list of priority congenital anomalies for improving the registration in the Brazilian Live Birth Information System (Sinasc). Methods: Based on International Classification of Diseases, Tenth Revision (ICD-10), internation protocols and meetings with specialists, the list of priority anomalies was built considering two main criteria: being diagnosable at birth and having intervention available at different levels. The list was submitted for consideration by the Brazilian Society of Medical Genetics and Genomics. Results: The list comprised eight groups of congenital anomalies distributed according to the type of anomaly related, as well as the affect body part, all of which were related to some code of chapter XVII of ICD-10. Conclusion: The list of priority congenital anomalies for notification provides subsidies for improving registration at Sinasc.

Objetivo: Definir a lista de anomalias congênitas prioritárias para o aprimoramento do registro no Sistema de Informações sobre Nascidos Vivos (Sinasc). Métodos: A partir da Décima Revisão da Classificação Estatística Internacional de Doenças e Problemas Relacionados à Saúde (CID-10), protocolos internacionais e reuniões com especialistas, a lista de anomalias prioritárias foi construída considerando-se dois critérios principais: ser diagnosticável ao nascimento; e possuir intervenção disponível em diferentes níveis. A lista foi submetida a apreciação da Sociedade Brasileira de Genética Médica e Genômica. Resultados: Compuseram a lista oito grupos de anomalias distribuídos de acordo com o tipo de anomalia relacionada, bem como a parte do corpo afetada e sua correspondência ao código do capítulo XVII da CID-10. Conclusão: A lista de anomalias congênitas prioritárias para notificação fornece subsídios para o aprimoramento do registro no Sinasc.

Lista de anomalias congênitas prioritárias para vigilância no âmbito do Sistema de Informações sobre Nascidos Vivos do Brasil / Lista de anomalías congénitas prioritarias para la vigilancia bajo el Sistema de Información sobre Nacidos Vivos en Brasil / List of priority congenital anomalies for surveillance under the Brazilian Live Birth Information System

Objetivo: Definir a lista de anomalias congênitas prioritárias para o aprimoramento do registro no Sistema de Informações sobre Nascidos Vivos (Sinasc). Métodos: A partir da Décima Revisão da Classificação Estatística Internacional de Doenças e Problemas Relacionados à Saúde (CID-10), protocolos internacionais e reuniões com especialistas, a lista de anomalias prioritárias foi construída considerando-se dois critérios principais: ser diagnosticável ao nascimento; e possuir intervenção disponível em diferentes níveis. A lista foi submetida a apreciação da Sociedade Brasileira de Genética Médica e Genômica. Resultados: Compuseram a lista oito grupos de anomalias congênitas distribuídos de acordo com o tipo de anomalia relacionada, bem como a parte do corpo afetada e sua correspondência ao código do capítulo XVII da CID-10. Conclusão: A lista de anomalias congênitas prioritárias para notificação fornece subsídios para o aprimoramento do registro no Sinasc.

Objetivo: Definir la lista de anomalías congénitas prioritarias para perfeccionar el registro en el Sistema de Información de Nacidos Vivos (Sinasc). Métodos: Con base en la Clasificación Internacional de Enfermedades, Décima Revisión (CIE-10), protocolos internacionales y reuniones con especialistas, la lista de anomalías prioritarias se construyó considerando dos criterios principales: ser diagnosticables al nacer y tener intervención disponible en diferentes niveles. La lista fue sometida a la consideración de la Sociedad Brasileña de Genética y Genómica Médica. Resultados: La lista comprendía ocho grupos de anomalías congénitas distribuidos según el tipo de anomalía relacionada, así como la parte del cuerpo afectada, todos ellos relacionados con algún código del capítulo XVII de la CIE-10. Conclusión: La lista de anomalías congénitas prioritarias para notificación proporciona subsidios para mejorar el registro en Sinasc.

Objective: To define the list of priority congenital anomalies for improving their recording on the Brazilian Live Birth Information System (Sinasc). Methods: Based on the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10), international protocols and meetings with specialists, the list of priority anomalies was built considering two main criteria: being diagnosable at birth and having intervention available at different levels. The list was submitted for consideration by the Brazilian Medical Genetics and Genomics Society. Results: The list comprised eight groups of congenital anomalies distributed according to the type of related anomaly, as well as the affected part of the body and its corresponding code in ICD-10 Chapter XVII. Conclusion: The list of priority congenital anomalies for notification provides a basis for improving case recording on Sinasc.

Single-Nucleotide Polymorphisms of the MSH2 and MLH1 Genes, Potential Molecular Markers for Susceptibility to the Development of Basal Cell Carcinoma in the Brazilian Population.

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 Paraíba 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 < 0.0001). The SNPs rs565410865 was also statistical significance between the genotypes of and the age group (p = 0.0027) and tumor location (p = 0,0191). The result suggests that SNPs rs2303425 and rs565410865 are associated with susceptibility to the development of BCC in the Brazilian population and may be considered as potential molecular markers for BCC.

Dideoxy single allele-specific PCR - DSASP new method to discrimination allelic

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 (χ2 = 9.7, P < 0.05). A comparative analysis of the data obtained from both methods did not differ significantly (χ2 = 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.

Main ion channels and receptors associated with visceral hypersensitivity in irritable bowel syndrome.

Irritable bowel syndrome (IBS) is a very frequent functional gastrointestinal disorder characterized by recurrent abdominal pain or discomfort and alteration of bowel habits. The IBS physiopathology is extremely complex. Visceral hypersensitivity plays an important role in the pathogenesis of abdominal pain in both in vitro and in vivo models of this functional disorder. In order to obtain a general view of the participation of the main ion channels and receptors regarding the visceral hypersensitivity in the IBS and to describe their chemical structure, a literature review was carried out. A bibliographical research in the following electronic databases: Pubmed and Virtual Library in Health (BVS) was fulfilled by using the search terms "ion channels" "or" "receptors" "and" "visceral hypersensitivity" "or" "visceral nociception" "and" "irritable bowel syndrome". Original and review articles were considered for data acquisition. The activation of the ATP ion-gated channels, voltage-gated sodium (Nav) and calcium (Cav) channels, as well as the activation of protease-activated receptors (PAR2), transient receptor potential vanilloide-1, serotonin, cannabinoids and cholecystokinin are involved in the genesis of visceral hypersensitivity in IBS. The involvement of ion channels and receptors concerning visceral hypersensitivity is noteworthy in IBS models.

Association study of SNPs of genes IFNGR1 (rs137854905), GSTT1 (rs71748309), and GSTP1 (rs1695) in gastric cancer development in samples of patient in the northern and northeastern Brazil.

Cancer is a multifactorial disease with a high mortality rate in Brazil and worldwide. Gastric cancer (GC) is considered the fourth type of malignancy more frequent in the population worldwide and the second leading cause of death. This work aimed to evaluate single nucleotide polymorphisms (SNPs) of IFNGR1, GSTT1, and GSTP1 genes samples in gastric cancer. We analyzed 60 samples of gastric cancer, 26 diffuse and 34 intestinal types, totaling 120 alleles for each SNP. The results were obtained by PCR and allele-specific PCR. Statistical analyzes performed using BioEstat 5.0 software, applying the Fisher's exact test and chi-square. Only the SNP gene GSTP1 (rs1695) were significantly associated with gastric cancer in the samples analyzed (χ(2) = 8.73, P < 0.05). Our results suggest that the GSTP1 gene SNP (rs1695) can be considered a risk factor associated with gastric carcinogenesis.