Inhibition of the SREBP pathway prevents SARS-CoV-2 replication and inflammasome activation.

SARS-CoV-2 induces major cellular lipid rearrangements, exploiting the host's metabolic pathways to replicate. Sterol regulatory element binding proteins (SREBPs) are a family of transcription factors that control lipid metabolism. SREBP1 is associated with the regulation of fatty acids, whereas SREBP2 controls cholesterol metabolism, and both isoforms are associated with lipid droplet (LD) biogenesis. Here, we evaluated the effect of SREBP in a SARS-CoV-2-infected lung epithelial cell line (Calu-3). We showed that SARS-CoV-2 infection induced the activation of SREBP1 and SREBP2 and LD accumulation. Genetic knockdown of both SREBPs and pharmacological inhibition with the dual SREBP activation inhibitor fatostatin promote the inhibition of SARS-CoV-2 replication, cell death, and LD formation in Calu-3 cells. In addition, we demonstrated that SARS-CoV-2 induced inflammasome-dependent cell death by pyroptosis and release of IL-1ß and IL-18, with activation of caspase-1, cleavage of gasdermin D1, was also reduced by SREBP inhibition. Collectively, our findings help to elucidate that SREBPs are crucial host factors required for viral replication and pathogenesis. These results indicate that SREBP is a host target for the development of antiviral strategies.

Analysis of the anthropometric measurements of the smile using 3D stereophotogrammetry / Análise das medidas antropométricas do sorriso utilizando a estereofotogrametria 3D

3D stereophotogrammetry makes the analysis of facial soft tissues possible, and has the potential to contribute to human identification processes. Nowadays, the images available through social networks are composed of a significant amount of smile photos, making techniques such as 3D stereophotogrammetry relevant. The objective of the present study was to quantitatively analyze the anthropometric measurements of the smile through 3D stereophotogrammetry, including area, angular, and linear measurements. Anatomical landmarks were used to make possible the area, angular, and linear measurements. The sample consisted of 25 volunteers, 13 female and 12 male, both in the 19-25 age group, resulting in a mean age of 22.31.9 and 23.31.5, respectively. The anatomical landmarks were marked on the face of the volunteers using a black eyeliner, and the photographs were taken using the 3D stereophotogrammetry technique (Vectra H1, Canfield, NY, USA), being 3 photographs with a spontaneous smile and 3 at rest, right lateral, left lateral and frontal of each. Among the results of the comparison between genders and the photo/smile relation of the statistical analysis, variables such as the mentolabial angle and the vermilion height of the upper lip showed significant p-values of 0.046 and 0.014, respectively. It can be concluded that anthropometric measurements of three-dimensional smile images can be performed with the use of 3D stereophotogrammetry, with the purpose of contributing to facial identification methods

A estereofotogrametria 3D possibilita a análise dos tecidos moles faciais e tem o potencial de contribuir para os processos de identificação humana. Atualmente, as imagens disponíveis nas redes sociais são compostas por uma quantidade significativa de fotos de sorrisos, tornando relevante técnicas como a estereofotogrametria 3D. O objetivo do presente estudo foi analisar quantitativamente as medidas antropométricas do sorriso por meio da estereofotogrametria 3D, incluindo medidas de área, angulares e lineares. Referenciais anatômicos foram utilizados para possibilitar as medidas de área, angulares e lineares. A amostra foi composta por 25 voluntários, sendo 13 do sexo feminino e 12 do sexo masculino, ambos na faixa etária de 19 a 25 anos, resultando em média de idade de 22,3±1,9 e 23,3±1,5, respectivamente. Os referenciais anatômicos foram marcados na face dos voluntários com delineador preto e as fotografias foram realizadas pela técnica de estereofotogrametria 3D (Vectra H1, Canfield, NY, EUA), sendo 3 fotografias com sorriso espontâneo e 3 em repouso, direita lateral, esquerda lateral e frontal de cada um. Dentre os resultados da comparação entre gêneros e relação foto/sorriso da análise estatística, variáveis como o ângulo mentolabial e a altura do vermelhão do lábio superior apresentaram valores de p significativos de 0,046 e 0,014, respectivamente. Pode-se concluir que medidas antropométricas de imagens tridimensionais do sorriso podem ser realizadas com o uso da estereofotogrametria 3D, com a finalidade de contribuir com os métodos de identificação facial

Advanced clinical parameters: A complementary hydroxyurea adherence evaluation in sickle cell anemia treatment.

OBJECTIVES: Given the complex pathology of sickle cell anemia (SCA) and low adherence to hydroxyurea (HU) treatment, there is a need to seek parameters that identify recent changes in patient status. The advanced clinical parameters (ACPs) allow an early analysis of hematopoiesis. We aimed to draw the demographic profile of non-adherent SCA patients and to verify the use of ACPs as a measure of HU treatment adherence. METHOD: In a cross-sectional study, we divided 83 SCA subjects treated with HU into Children (<12 years old) and adolescents/adults (≥12 years old). Their hemogram with the ACPs, electronic medical charts and pharmacy claim data were analyzed. RESULTS: Non-adherent ≥12 years old patients had significantly increased WBC, absolute neutrophil, lymphocyte, monocyte, and basophil counts, RBC, RET, RDW, and PLT, and significantly decreased MCV and MCH. Subjects in the adolescent/adult group with IG† ≥0.035 cells/mm3 had the RR for non-adherence increased by 4.6 times (p = .014), and the systemic immune inflammation index (SII) of non-adherent patients was also significantly higher (p = .042). CONCLUSION: IG† presents clinical utility in early identification of non-adherence to HU, especially when combined with other parameters, suggesting the evaluation of ACPs in laboratory routine, as they can be easily implemented.

Long-term monitoring of drug consumption patterns during the COVID-19 pandemic in a small-sized community in Brazil through wastewater-based epidemiology.

The abuse of legal and illegal drugs is a global public health problem, also affecting the social and economic well-being of the population. Thus, there is a significant interest in monitoring drug consumption. Relevant epidemiological information on lifestyle habits can be obtained from the chemical analysis of urban wastewater. In this work, passive sampling using polar organic chemical integrative samplers (POCIS) was used to quantify licit and illicit drugs biomarkers in wastewater for the application of wastewater-based epidemiology (WBE). In this WBE study, a small urban community of approximately 1179 inhabitants was monitored from 18 March 2020 to 3 March 2021, covering the mobility restriction and flexibilization periods of the COVID-19 pandemic in Brazil. Consumption was estimated for amphetamine, caffeine, cocaine, MDMA, methamphetamine, nicotine, and THC. The highest estimated consumption among illicit drugs was for THC (2369 ± 1037 mg day-1 1000 inh-1) followed by cocaine (353 ± 192 mg day-1 1000 inh-1). There was a negative correlation between consumption of caffeine, cocaine, MDMA, nicotine, and THC with human mobility, expressed by cellular phone mobility reports (P-value = 0.0094, 0.0019, 0.0080, 0.0009, and 0.0133, respectively). Our study is the first long-term drug consumption evaluation during the COVID-19 pandemic, with continuous sampling for almost a whole year. The observed reduction in consumption of both licit and illicit drugs is probably associated with stay-at-home orders and reduced access, which can be due to the closure of commercial facilities during some time of the evaluated period, smaller drug supply, and reduced income of the population due to the shutdown of companies and unemployment. The assay described in this study can be used as a complementary and cost-effective tool to the long-term monitoring of drug use biomarkers in wastewater, a relevant epidemiological strategy currently limited to short collection times.

The Relevance of Ultrastructural Studies of Metastatic Cells from Women with Breast Cancer History.

The interaction between cancer cells and the surrounding microenvironment is determinant for metastasis success. In this study, the ultrastructural relevance of cells in the malignant pleural effusion (MPE) of women with breast cancer history was investigated. In MPE, it is possible to observe single cells and clusters. Women whose MPE presents carcinomas in aggregates have a better prognosis when compared to cases in which metastatic single cells are found. Samples were collected via fine-needle aspiration puncture (US-FNA). Subsequent to the material preparation and ultrathin cuts, they were observed using light and transmission electron microscopy (LM/TEM). LM and TEM images served as a basis for the creation of a digital sculpture using ZBrush® software. Clusters exhibited structural stability, en route vesicles allowing exocytosis of electron-dense fibrous elements, and cytoplasmic protrusions contributing to migratory and invasive skills. Single cells presented different necrotic phenotypes and many displayed leukocyte-like characteristics. Cluster cooperative relationships seem to be related to a long-term permanence in MPE. The absence of a collaborative network presumably triggers a more aggressive behavior of single cells. Its putative fusion with leukocytes can maximize the efficiency for transendothelial migration, increasing chances of metastatic success and, unfortunately, reducing survival of women with recidivism.

Situação clínico-epidemiológica da sífilis gestacional em anápolis-go: uma análise retrospectiva / Situación clínica y epidemiológica de la sífilis gestacional en anápolis-go: un análisis retrospectivo / Clinical-epidemiological situation of gestational syphilis in anápolis-go: a retrospective analysis

RESUMO Objetivo: descrever a situação clínica e epidemiológica da sífilis gestacional em Anápolis, Goiás, Brasil, entre os anos de 2012 e 2018. Método: estudo epidemiológico, descritivo e transversal de natureza quantitativa. Como instrumento de coleta, foram utilizados dados da ficha de notificação da sífilis gestacional cadastradas no Departamento de Vigilância Epidemiológica. Para análise estatística, foi utilizado o teste qui-quadrado com nível de significância 5% (p<0,05). Resultados: evidenciou-se aumento dos casos de sífilis gestacional. A assistência foi oferecida a 522 pacientes, entre 19 e 29 anos (58,1%), com etnia parda (69,1%) e com ensino médio incompleto (24,5%); predominou a sífilis primária (30,8%) e alto índice de não tratamento do parceiro (57,1%). Conclusão: dentro do período estudado, houve aumento dos casos de sífilis gestacional e não tratamento do parceiro. Este estudo poderá contribuir para o planejamento de ações de prevenção primária e secundária, visando diminuir a incidência da doença e suas consequências.

RESUMEN Objetivo: describir la situación clínica y epidemiológica de la sífilis gestacional en Anápolis, Goiás, Brasil, entre los años 2012 y 2018. Método: estudio descriptivo y transversal de carácter cuantitativo. Se utilizaron como instrumento de recogida los datos de la ficha de notificación de sífilis gestacional registrada en el Departamento de Vigilancia Epidemiológica. Para el análisis estadístico se utilizó la prueba de chi-cuadrado con un nivel de significación del 5% (p<0,05). Resultados: se evidenció un aumento de los casos de sífilis gestacional. La asistencia se ofreció a 522 mujeres, con edades comprendidas entre los 19 y los 29 años (58,1%), de etnia parda (69,1%) y con estudios secundarios incompletos (24,5%); predominó la sífilis latente (58,1%), seguida de la sífilis primaria (30,8%) y un alto índice de no tratamiento de la pareja (57,1%). Conclusión: dentro del período estudiado, hubo un aumento de los casos de sífilis gestacional y no tratamiento de la pareja. Este estudio puede contribuir a la planificación de acciones de prevención primaria y secundaria, con el objetivo de disminuir la incidencia de la enfermedad y sus consecuencias.

ABSTRACT Objective: to describe the clinical and epidemiological situation of gestational syphilis in Anápolis, Goiás, Brazil, between the years 2012 to 2018. Method: descriptive, cross-sectional study of a quantitative nature. As a collection instrument, data from the gestational syphilis notification form registered in the Epidemiological Surveillance Department were used. For statistical analysis, the chi-square test was used, with a 5% significance level (p<0.05). Results: an increase in gestational syphilis cases was evidenced. Care was offered to 522 women, aged between 19 and 29 years (58.1%), with brown ethnicity (69.1%) and incomplete high school education (24.5%); latent syphilis predominated (58.1%), followed by primary syphilis (30.8%) and a high rate of non-treatment of the partner (57.1%). Conclusion: within the period studied, there was an increase in cases of gestational syphilis and non-treatment of the partner. This study may contribute to the planning of primary and secondary prevention actions, aiming to decrease the incidence of the disease and its consequences.

Prospective cohort of AIDS patients screened for cryptococcal antigenaemia, pre-emptively treated and followed in Brazil.

BACKGROUND: Cryptococcal meningitis has a high morbidity and mortality among AIDS population. Cryptococcal antigen (CrAg) detection is considered an independent predictor for meningitis and death. Since 2011, the World Health Organization recommends CrAg screening for people living with HIV/AIDS (PLHAs) with CD4 counts <100-200 cells/µl. Its implementation is still limited in low-middle-income countries. We aimed to estimate the prevalence and predictors of CrAg positivity in PLHAs. We also evaluated outcomes among those who were CrAg-positive. METHODS: Prospective cohort conducted at an infectious diseases hospital, in Brazil. Adults with CD4 <200 cells/µl, without previous cryptococcal disease and regardless of symptoms, were enrolled from 2015 to 2018. CrAg tests were performed by LFA. Lumbar puncture was done in CrAg+ individuals and pre-emptive therapy was offered for those without meningitis. RESULTS: Of 214 individuals recruited, 88% were antiretroviral experienced, of which only 11.6% with viral suppression. Overall, CrAg prevalence was 7.9% (95% CI, 4.7-12.4). In CD4 ≤100 cells/µl group it was 7.5% (95% CI, 4.1-12.6) and 9.1% (95% CI, 3.4-19.0) in the group with CD4 101 to 199 cells/µl (p = 0.17). Prevalence in asymptomatic subjects was 5.3% (95% CI, 1.4-13.1). One among 17 CrAg+ participants had documented meningoencephalitis and no subclinical meningitis was detected. Adherence to pre-emptive treatment was 68.7% (11/16). There were no statistically significant differences in sociodemographic, clinical or laboratory characteristics to predict CrAg positivity. No case of cryptococcal disease was diagnosed among CrAg + subjects, followed by a median of 12 months. CONCLUSIONS: CrAg screening for severely immunosuppressed PLHAs in Brazil yielded a prevalence of 7.9%. No difference was found in the prevalence of CrAg stratified by CD4 values (CD4 <100 versus CD4 101-199 cells/µl). No clinical nor laboratory factors predicted CrAg positivity, corroborating the need for the implementation of universal CrAg screening for PLHAs with CD4 <200 cells/µl in similar settings.

Exame colpocitológico: perfil epidemiológico em uma Estratégia Saúde da Família / Papanicolaou test: epidemiological profile in a Family Health Strategy

Objetivo: verificar a freqüência de alterações sugestivas de Câncer do Colo do Útero, de agosto de 2013 até agosto 2014, através da avaliação dos resultados dos exames de Papanicolau, registrados nos livros de acompanhamento de mulheres no controle do Câncer do Colo do Útero, realizados em mulheres a partir da adolescência até a senescência. Casuística e Métodos: estudo transversal realizado a partir de dados coletados na Estratégia Saúde da Família Vila Mutirão, pertencente à Região Noroeste da Cidade de Goiânia ­ Goiás ­Brasil. Resultados: Dentre os dados analisados das 747 pacientes, 644 (86,21%) não apresentaram indícios ou constatações de Câncer do Colo do Útero, 70 (9,38%) não apresentaram dados. Ainda, 33 (4,4) apresentaram algum tipo de lesão sugestiva pré-cancerígena, pré-cancerígena propriamente dita ou cancerígena, sendo que destas, 18 (2,40%) evidenciaram lesão sugestiva pré-cancerígena, 15 (2,00%) lesão pré-cancerígena, nenhuma (0%) apresentou lesões cancerígenas. Conclusão: neste estudo avaliou-se a frequência de alterações, sendo mínima a prevalência de lesões precursoras ou sugestivas de câncer do colo do útero. Verificaram-se também associações semelhantes sobre os fatores de risco relacionados ao câncer do colo do útero (idade e escolaridade)

Objective: To verify the frequency of changes suggestive of cervical cancer, from August 2013 to August 2014, by evaluating the results of the Pap smears, recorded in the books accompanying women in the control of cervical cancer, performed in women - from adolescence to senescence. Methods: a cross - sectional study based on data collected in the Vila Mutirão Family Health Strategy, belonging to the Northwest Region of the City of Goiânia - Goiás - Brazil. Results: Among the 747 patients analyzed, 644 (86.21%) had no evidence or findings of cervical cancer, 70 (9.38%) did not present data. Still, 33 (4,4) presented some pre-cancerous, pre-cancerous or carcinogenic suggestive lesion, of which 18 (2.40%) showed suggestive precancerous lesion, 15 (2.00%) precancerous lesion, none (0%) presented carcinogenic lesions. Conclusion: this study evaluated the frequency of alterations, with minimal prevalence of cervical or cervical cancer precursor lesions. Similar associations were also found on risk factors related to cervical cancer (age and schooling)

Quando indicar marcapasso na TAVI? / When to indicate a pacemaker in TAVI?

O implante por cateter de prótese valvar aórtica (TAVI) constitui um marco na cardiologia moderna, sendo uma alternativa terapêutica fundamental para os pacientes inoperáveis ou com risco intermediário para cirurgia de troca valvar aórtica...

O perfil epidemiológico e o desempenho da GAL-3 e CK-19 em lesões foliculares e suspeitas para malignidade da tireoide / The epidemiological profile and the performance of GAL-3 and CK-19 in follicular lesions and suspicious for malignancy of the thyroid

Objetivos: Analisar dados epidemiológicos de pacientes submetidos à PAAF, classificados como lesões foliculares (classe IV) e suspeitos para malignidade (classe V) pelo Sistema Bethesda para Laudos Citopatológicos da Tireoide e avaliar o desempenho do painel imunocitoquímico com os marcadores CK-19, Galectina-3 e HBME-1 no diagnóstico destes pacientes. Metodologia: Estudo retrospectivo transversal, que analisou 24 laudos anatomopatológicos do Centro de Patologia de Curitiba, entre 2011 e 2014, classificados como classe IV e V do Sistema Bethesda, cujas lâminas foram avaliadas pela imunocitoquímica, usando-se os marcadores CK-19, GAL-3 e HBME-1. Resultados: 83,3% dos pacientes eram mulheres, com idade média de 45,7 anos. O tamanho médio das lesões foi 12,5mm, localizadas 56,5% no lobo D. O painel de marcadores apresentou sensibilidade 100%, especificidade 90,5% e eficácia 95,5% para as lesões avaliadas. Conclusão: A imunocitoquímica demostrou-se um exame pré-operatório eficaz para diferenciação de lesões foliculares e suspeitas para malignidade do carcinoma papilífero da tireoide

Objectives: To analyze epidemiological data of patients who undergone FNA that was classified as follicular lesions (Class IV) and suspicious for malignancy (Class V) by the Bethesda System for Reporting Thyroid Cytopathology and evaluate the performance of immunocytochemical panel with markers CK-19, Galectin-3 and HBME-1 in these patients. Methodology: This is a cross-sectional retrospective study. It was analyzed 24 pathological between 2011 and 2014, from the Curitiba Pathology Center, classified as Class IV and V in the Bethesda System for Reporting Thyroid Cytopathology, which slides were stained with immunocytochemistry using the markers: CK19 GAL-13 and HBME-1. Results: In this study 83.3% of the patients were women with a mean age of 45.7 years. The average size of the nodules was 12.5mm and 56.5% was located in the right lobe. Regarding the diagnosis of follicular lesions and suspicious for malignancy, the sensitivity of the exam with the standard biological markers used was 100%, specificity 90,5% and efficacy 95.5%. Conclusion: The immunocytochemistry demonstrated to be an effective pre-operative exam for differentiation of follicular lesions and suspicious for malignancy of papillary thyroid carcinoma

O perfil epidemiológico e o desempenho da GAL-3 e CK-19 em lesões foliculares e suspeitas para malignidade da tireoide / The epidemiological profile and the performance of GAL-3 and CK-19 in follicular lesions and suspicious for malignancy of the thyroid

Objetivos: Analisar dados epidemiológicos de pacientes submetidos à PAAF, classificados como lesões foliculares (classe IV) e suspeitos para malignidade (classe V) pelo Sistema Bethesda para Laudos Citopatológicos da Tireoide e avaliar o desempenho do painel imunocitoquímico com os marcadores CK-19, Galectina-3 e HBME-1 no diagnóstico destes pacientes. Metodologia: Estudo retrospectivo transversal, que analisou 24 laudos anatomopatológicos do Centro de Patologia de Curitiba, entre 2011 e 2014, classificados como classe IV e V do Sistema Bethesda, cujas lâminas foram avaliadas pela imunocitoquímica, usando-se os marcadores CK-19, GAL-3 e HBME-1. Resultados: 83,3% dos pacientes eram mulheres, com idade média de 45,7 anos. O tamanho médio das lesões foi 12,5mm, localizadas 56,5% no lobo D. O painel de marcadores apresentou sensibilidade 100%, especificidade 90,5% e eficácia 95,5% para as lesões avaliadas. Conclusão: A imunocitoquímica demostrou-se um exame pré-operatório eficaz para diferenciação de lesões foliculares e suspeitas para malignidade do carcinoma papilífero da tireoide

Objectives: To analyze epidemiological data of patients who undergone FNA that was classified as follicular lesions (Class IV) and suspicious for malignancy (Class V) by the Bethesda System for Reporting Thyroid Cytopathology and evaluate the performance of immunocytochemical panel with markers CK-19, Galectin-3 and HBME-1 in these patients. Methodology: This is a cross-sectional retrospective study. It was analyzed 24 pathological between 2011 and 2014, from the Curitiba Pathology Center, classified as Class IV and V in the Bethesda System for Reporting Thyroid Cytopathology, which slides were stained with immunocytochemistry using the markers: CK19 GAL-13 and HBME-1. Results: In this study 83.3% of the patients were women with a mean age of 45.7 years. The average size of the nodules was 12.5mm and 56.5% was located in the right lobe. Regarding the diagnosis of follicular lesions and suspicious for malignancy, the sensitivity of the exam with the standard biological markers used was 100%, specificity 90,5% and efficacy 95.5%. Conclusion: The immunocytochemistry demonstrated to be an effective pre-operative exam for differentiation of follicular lesions and suspicious for malignancy of papillary thyroid carcinoma

Colour evaluation of a phycobiliprotein-rich extract obtained from Nostoc PCC9205 in acidic solutions and yogurt.

BACKGROUND: Phycobiliproteins are coloured proteins produced by cyanobacteria, which have several applications because of their colour properties. However, there is no available information about the colour stability of phycobiliproteins from Nostoc sp. in food systems. The aim of this work was to study the colour stability of a purple-coloured phycobiliprotein-rich extract from the cyanobacterium Nostoc PCC9205 in acidic solutions and yogurt. RESULTS: Variations of pH for Nostoc PCC9205 extract have shown stability for the L* (lightness) and a* (redness) indexes in the range 1.0-7.0. The b* index (blueness), however, increased at pH values below 4.0, indicating loss of the blue colour. The Nostoc PCC9205 extract was used as colorant in yogurt (pH 4.17) stored for 60 days. Instrumental colour analysis showed no changes for the L* and a* indexes during storage, whereas the b* index changed after 20 days of storage. A multiple comparison test showed colour instability after 20 days of storage. A hedonic scale test performed on the 60th day of storage showed acceptability of the product. CONCLUSIONS: The red component of the phycobiliprotein-rich extract from Nostoc PCC9205 presented an improved stability in acidic media and yogurt compared with the blue component of this extract.