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BACKGROUND: Identifying mosquito vectors is crucial for controlling diseases. Automated identification studies using the convolutional neural network (CNN) have been conducted for some urban mosquito vectors but not yet for sylvatic mosquito vectors that transmit the yellow fever. We evaluated the ability of the AlexNet CNN to identify four mosquito species: Aedes serratus, Aedes scapularis, Haemagogus leucocelaenus and Sabethes albiprivus and whether there is variation in AlexNet's ability to classify mosquitoes based on pictures of four different body regions. METHODS: The specimens were photographed using a cell phone connected to a stereoscope. Photographs were taken of the full-body, pronotum and lateral view of the thorax, which were pre-processed to train the AlexNet algorithm. The evaluation was based on the confusion matrix, the accuracy (ten pseudo-replicates) and the confidence interval for each experiment. RESULTS: Our study found that the AlexNet can accurately identify mosquito pictures of the genus Aedes, Sabethes and Haemagogus with over 90% accuracy. Furthermore, the algorithm performance did not change according to the body regions submitted. It is worth noting that the state of preservation of the mosquitoes, which were often damaged, may have affected the network's ability to differentiate between these species and thus accuracy rates could have been even higher. CONCLUSIONS: Our results support the idea of applying CNNs for artificial intelligence (AI)-driven identification of mosquito vectors of tropical diseases. This approach can potentially be used in the surveillance of yellow fever vectors by health services and the population as well.
Assuntos
Aedes , Mosquitos Vetores , Redes Neurais de Computação , Febre Amarela , Animais , Mosquitos Vetores/classificação , Febre Amarela/transmissão , Aedes/classificação , Aedes/fisiologia , Algoritmos , Processamento de Imagem Assistida por Computador/métodos , Culicidae/classificação , Inteligência ArtificialRESUMO
BACKGROUND: Domiciliation by Triatoma sordida is a public health concern in South America. This study aimed to evaluate the morphometric changes in the domestic and peridomestic populations of T. sordida. METHODS: Specimen hemelytra were mounted, digitized, and processed for geometric morphometric analyses. RESULTS: The specimens captured in houses were smaller than those captured in peridomiciles. A large size reduction effect was observed in female peridomicile populations compared with female house populations. CONCLUSIONS: T. sordida house populations were smaller than peridomestic populations. Wing geometric morphometry can be used as a tool to indicate T. sordida domiciliation.
Assuntos
Insetos Vetores , Triatoma , Asas de Animais , Triatoma/anatomia & histologia , Triatoma/classificação , Animais , Feminino , Masculino , Asas de Animais/anatomia & histologia , Insetos Vetores/anatomia & histologia , Insetos Vetores/classificação , Doença de Chagas/transmissão , HumanosRESUMO
PURPOSE: To assess the association between tumor-infiltrating lymphocytes (TILs) in ductal carcinoma in situ (DCIS) samples and disease recurrence. METHODS: This retrospective cohort study included women aged 18 years and older who underwent treatment between January 2007 and December 2020. Male patients, individuals diagnosed with invasive or microinvasive disease based on anatomopathological examination of surgical specimens, and those with a personal history of any other cancers were excluded. Additionally, the presence of "touching TILs" (lymphocytes in direct contact with tumor cells) and periductal desmoplasia were evaluated as complementary methods to represent the immunological microenvironment. The primary outcome was relapse-free survival based on TIL quantification adjusted for potential confounders. Pathologists assessed TILs in the sample with the highest tumor representation and quantified them as a percentage. Survival was evaluated using KaplanâMeier curves, log-rank tests, and Cox regression models. RESULTS: A total of 191 patients met the eligibility criteria. The mean follow-up duration was 77.2 months, with a recurrence rate of 9.2%. Patients with TILs ≥ 17% had a greater risk of recurrence (HR 2.97, 95% CI 1.17-7.51; p = 0.02). Additionally, focal necrosis (HR 6.4, 95% CI 1.39-34.71; p = 0.018) or comedonecrosis (HR 4.53, 95% CI 1.34-15.28; p = 0.015) were associated with increased recurrence risk. According to the multivariate model, comedonecrosis and TILs ≥ 17% were significantly associated with recurrence (p = 0.034 and p = 0.035, respectively). Regarding the evaluations of "touching TILs" and periductal desmoplasia, no statistical significance was found when assessing their association with disease recurrence. CONCLUSION: In our cohort, a high percentage of TILs (≥ 17%) and the presence of comedonecrosis were independently associated with DCIS recurrence.
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Deforestation and high human mobility due to mining activities have been key to the increase in malaria cases in the Americas. Here, we review the epidemiological and control aspects of malaria in the Amazon mining areas. Epidemiological evidence shows: 1) a positive correlation between illegal mining activity and malaria incidence, mostly in the Amazon region; 2) most Brazilian miners are males aged 15-29 years who move between states and even countries; 3) miners do not fear the disease and rely on medical care, diagnosis, and medication when they become ill; 4) illegal mining has emerged as the most reported anthropogenic activity within indigenous lands and is identified as a major cause of malaria outbreaks among indigenous people in the Amazon; and 5) because mining is largely illegal, most areas are not covered by any healthcare facilities or activities, leading to little assistance in the diagnosis and treatment of malaria. Our review identified five strategies for reducing the malaria incidence in areas with mining activities: 1) reviewing legislation to control deforestation and mining expansion, particularly in indigenous lands; 2) strengthening malaria surveillance by expanding the network of community health agents to support rapid diagnosis and treatment; 3) reinforcing vector control strategies, such as the use of insecticide-treated nets; 4) integrating deforestation alerts into the national malaria control program; and 5) implementing multi-sectoral activities and providing prompt assistance to indigenous populations. With this roadmap, we can expect a decrease in malaria incidence in the Amazonian mining areas in the future.
Assuntos
Malária , Mineração , Humanos , Brasil/epidemiologia , Malária/epidemiologia , Malária/transmissão , Malária/prevenção & controle , Incidência , Masculino , Conservação dos Recursos Naturais , AnimaisRESUMO
Aim: Methylation of LDLR, PCSK9 and LDLRAP1 CpG sites was assessed in patients with familial hypercholesterolemia (FH). Methods: DNA methylation of was analyzed by pyrosequencing in 131 FH patients and 23 normolipidemic (NL) subjects.Results: LDLR, PCSK9 and LDLRP1 methylation was similar between FH patients positive (MD) and negative (non-MD) for pathogenic variants in FH-related genes. LDLR and PCSK9 methylation was higher in MD and non-MD groups than NL subjects (p < 0.05). LDLR, PCSK9 and LDLRAP1 methylation profiles were associated with clinical manifestations and cardiovascular events in FH patients (p < 0.05).Conclusion: Differential methylation of LDLR, PCSK9 and LDLRAP1 is associated with hypercholesterolemia and cardiovascular events. This methylation profile maybe useful as a biomarker and contribute to the management of FH.
[Box: see text].
Assuntos
Metilação de DNA , Hiperlipoproteinemia Tipo II , Proteína Associada a Proteínas Relacionadas a Receptor de LDL , Pró-Proteína Convertase 9 , Receptores de LDL , Humanos , Pró-Proteína Convertase 9/genética , Receptores de LDL/genética , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Proteína Associada a Proteínas Relacionadas a Receptor de LDL/genética , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/etiologia , Ilhas de CpG , Proteínas Adaptadoras de Transdução de SinalRESUMO
OBJECTIVES: This study explored the association of deleterious variants in pharmacodynamics (PD) genes with statin response and adverse effects in patients with familial hypercholesterolemia (FH) and analyzed their potential effects on protein structure and stability. METHODS: Clinical and laboratory data were obtained from 144 adult FH patients treated with statins. A panel of 32 PD genes was analyzed by exon-targeted gene sequencing. Deleterious variants were identified using prediction algorithms and their structural effects were analyzed by molecular modeling studies. RESULTS: A total of 102 variants were predicted as deleterious (83 missense, 8 stop-gain, 4 frameshift, 1 indel, 6 splicing). The variants ABCA1 rs769705621 (indel), LPA rs41267807 (p.Tyr2023Cys) and KIF6 rs20455 (p.Trp719Arg) were associated with reduced low-density lipoprotein cholesterol (LDLc) response to statins, and the LPL rs1801177 (p.Asp36Asn) with increased LDLc response (P < 0.05). LPA rs3124784 (p.Arg2016Cys) was predicted to increase statin response (P = 0.022), and ABCA1 rs769705621 to increase the risk of statin-related adverse events (SRAE) (P = 0.027). LPA p.Arg2016Cys and LPL p.Asn36Asp maintained interactions with solvent, LPA p.Tyr2023Cys reduced intramolecular interaction with Gln1987, and KIF6 p.Trp719Arg did not affect intramolecular interactions. DDMut analysis showed that LPA p.Arg2016Cys and p.Tyr2023Cys and LPL p.Asp36Asn caused energetically favorable changes, and KIF6 p.Trp719Arg resulted in unfavorable energetic changes, affecting protein stability. CONCLUSION: Deleterious variants in ABCA1, LPA, LPL and KIF6 are associated with variability in LDLc response to statins, and ABCA1 rs769705621 is associated with SRAE risk in FH patients. Molecular modeling studies suggest that LPA p.Tyr2023Cys and KIF6 p.Trp719Arg disturb protein conformational structure and stability.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Inibidores de Hidroximetilglutaril-CoA Redutases , Transportador 1 de Cassete de Ligação de ATP , Hiperlipoproteinemia Tipo II , Lipase LipoproteicaRESUMO
AIM: Methylation of LDLR, PCSK9 and LDLRAP1 CpG sites was assessed in patients with familial hypercholesterolemia (FH). METHODS: DNA methylation of was analyzed by pyrosequencing in 131 FH patients and 23 normolipidemic (NL) subjects. RESULTS: LDLR, PCSK9 and LDLRP1 methylation was similar between FH patients positive (MD) and negative (non-MD) for pathogenic variants in FH-related genes. LDLR and PCSK9 methylation was higher in MD and non-MD groups than NL subjects (p < 0.05). LDLR, PCSK9 and LDLRAP1 methylation profiles were associated with clinical manifestations and cardiovascular events in FH patients (p < 0.05). CONCLUSION: Differential methylation of LDLR, PCSK9 and LDLRAP1 is associated with hypercholesterolemia and cardiovascular events. This methylation profile maybe useful as a biomarker and contribute to the management of FH.
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Amblyomma ticks are vectors of both Rickettsia rickettsii and R. parkeri in the Americas, where capybaras (Hydrochoerus hydrochaeris) are the main hosts in urban areas, thus contributing to the transmission of spotted fever. Herein, we studied: (i) the seasonal dynamics and abundance of ticks in areas where capybaras live, (ii) the effect of environmental variables on tick abundance, and (iii) the presence of Rickettsia-infected ticks. Between September 2021 and September 2022, we sampled ticks using cloth-dragging at 194 sites on the shore of Lake Paranoá in Brasília, Brazil. We measured environmental data (season, vegetation type, canopy density, temperature, humidity, and presence or vestige of capybara) at each site. Nymphs and adults were morphologically identified to the species level, and a selected tick sample including larvae was subjected to genotypic identification. We investigated Rickettsia-infected ticks by PCR (gltA, htrA, ompB, and ompA genes) and associations between tick abundance and environmental variables using Generalized Linear Models. A total of 30,334 ticks (96% larvae) were captured. Ticks were identified as Amblyomma, with A. sculptum comprising 97% of the adult/nymphs. Genotype identification of a larval sample confirmed that 95% belonged to A. dubitatum. Seasonal variables showed significant effects on tick abundance. Most larvae and nymphs were captured during the early dry season, while the adults were more abundant during the wet season. Vegetation variables and the presence of capybaras showed no association with tick abundance. Rickettsia parkeri group and R. bellii were identified in A. dubitatum, while A. sculptum presented R. bellii. We conclude that: (i) Amblyomma ticks are widely distributed in Lake Paranoá throughout the year, especially larvae at the dry season, (ii) the abundance of Amblyomma ticks is explained more by climatic factors than by vegetation or presence of capybaras, and (iii) A. dubitatum ticks are potential vectors of R. parkeri in Brasília.
Assuntos
Amblyomma , Rickettsia , Estações do Ano , Animais , Rickettsia/genética , Rickettsia/isolamento & purificação , Brasil , Amblyomma/microbiologia , Ninfa/microbiologia , Larva/microbiologia , Infecções por Rickettsia/transmissão , Infecções por Rickettsia/microbiologia , Vetores Aracnídeos/microbiologia , Roedores/microbiologia , Roedores/parasitologia , Meio AmbienteRESUMO
OBJECTIVES: This study explored the association of deleterious variants in pharmacodynamics (PD) genes with statin response and adverse effects in patients with familial hypercholesterolemia (FH) and analyzed their potential effects on protein structure and stability. METHODS: Clinical and laboratory data were obtained from 144 adult FH patients treated with statins. A panel of 32 PD genes was analyzed by exon-targeted gene sequencing. Deleterious variants were identified using prediction algorithms and their structural effects were analyzed by molecular modeling studies. RESULTS: A total of 102 variants were predicted as deleterious (83 missense, 8 stop-gain, 4 frameshift, 1 indel, 6 splicing). The variants ABCA1 rs769705621 (indel), LPA rs41267807 (p.Tyr2023Cys) and KIF6 rs20455 (p.Trp719Arg) were associated with reduced low-density lipoprotein cholesterol (LDLc) response to statins, and the LPL rs1801177 (p.Asp36Asn) with increased LDLc response (Pâ <â 0.05). LPA rs3124784 (p.Arg2016Cys) was predicted to increase statin response (Pâ =â 0.022), and ABCA1 rs769705621 to increase the risk of statin-related adverse events (SRAE) (Pâ =â 0.027). LPA p.Arg2016Cys and LPL p.Asn36Asp maintained interactions with solvent, LPA p.Tyr2023Cys reduced intramolecular interaction with Gln1987, and KIF6 p.Trp719Arg did not affect intramolecular interactions. DDMut analysis showed that LPA p.Arg2016Cys and p.Tyr2023Cys and LPL p.Asp36Asn caused energetically favorable changes, and KIF6 p.Trp719Arg resulted in unfavorable energetic changes, affecting protein stability. CONCLUSION: Deleterious variants in ABCA1, LPA, LPL and KIF6 are associated with variability in LDLc response to statins, and ABCA1 rs769705621 is associated with SRAE risk in FH patients. Molecular modeling studies suggest that LPA p.Tyr2023Cys and KIF6 p.Trp719Arg disturb protein conformational structure and stability.
Assuntos
Transportador 1 de Cassete de Ligação de ATP , Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipoproteinemia Tipo II , Cinesinas , Lipase Lipoproteica , Humanos , Cinesinas/genética , Masculino , Feminino , Pessoa de Meia-Idade , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Transportador 1 de Cassete de Ligação de ATP/genética , Lipase Lipoproteica/genética , Adulto , Estabilidade Proteica , LDL-Colesterol/sangue , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Currently, sea turtle habitats are being altered by climate change and human activities, with habitat loss posing an urgent threat to Indian sea turtles. Thus, the objective of this study is to analyze the dynamic shoreline alterations and their impacts on Olive Ridley Sea Turtle (ORT) nesting sites in Gahirmatha Marine Wildlife Sanctuary from 1990 to 2022. Landsat satellite images served as input datasets to assess dynamic shoreline changes. This study assessed shoreline alterations and their rates across 929 transects divided into four zones using the Digital Shoreline Analysis System (DSAS) software. The results revealed a significant 14-km northward shift in the nesting site due to substantial coastal erosion, threatening the turtles' Arribada. This study underscores the need for conservation efforts to preserve nesting environments amidst changing coastal landscapes, offering novel insights into the interaction between coastal processes and marine turtle nesting behaviors.
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Conservação dos Recursos Naturais , Ecossistema , Comportamento de Nidação , Tartarugas , Animais , Tartarugas/fisiologia , Índia , Monitoramento Ambiental , Mudança ClimáticaRESUMO
Familial Hypercholesterolemia (FH) is a genetic disorder associated with premature atherosclerosis and increased risk of cardiovascular diseases. LDLR deleterious mutations are associated with FH, however the role of some missense variants in FH pathogenicity remains to be elucidated. This study explored the predictive impact of LDLR missense variants on protein structure and investigated their functional effects on LDLR expression in HepG2 cells transfected with CRISPR/Cas9 constructs. FH (n = 287) and non-FH patients (n = 45) were selected, and lipid profile was obtained from medical records. LDLR variants were identified using an exon-targeted gene sequencing strategy, considering its cost-effective to increase accuracy in the identification step of the most likely FH-related variants in a less laborious process. LDLR variants were selected based on conflicting pathogenicity results found in Clinvar, in silico prediction tools, affected LDLR domains, and less common variants considering minor allele frequency < 0.05. Molecular modeling studies were used to predict the effects of LDLR missense variants on protein structure. Recombinant LDLR variants were constructed using CRISPR/Cas9 system and were used to transfect HepG2 cells. Functional assays in transfected cells were performed to assess LDLR expression using flow cytometry and western blotting, and LDLR activity using flow cytometry and confocal microscopy. The variants rs121908039 (c.551G>A, p.C184Y), rs879254797 (c.1118G>A, p.G373D), rs28941776 (c.1646G>A, p.G549D), rs750518671 (c.2389G>C, p.V797L), rs5928 (c.2441G>A, p.R814Q) and rs137853964 (c.2479G>A, p.V827I) were selected for molecular docking analysis. The p.C184Y exhibited a favorable energy change for protein stability due to its interaction with EGF-A/EGF-B regions; p.G373D and p.G549D displayed intermediate energy changes; and p.R814Q and p.V827I showed smaller energy changes. The results of functional assays showed that p.G373D, p.V797L and p.R814Q reduced LDLR expression and activity (p < 0.05). Microscopic analysis of the p.V797L and p.G373D variants revealed altered lipid localization and accumulation in transfected HepG2 cells. Carriers of p.G549D, p.V797L and p.R814Q had higher LDL cholesterol levels than non-FH group, and (p < 0.05). p.G373D and p.G549D were associated with clinical manifestations of FH. In conclusion, the p.C184Y, p.G373D, p.G549D and p.R814Q variants alter protein stability and intramolecular interactions, while p.V797L has a minimal impact on protein stability, and p.V827I has no significant intramolecular interactions. p.G373D, p.V767L and p.R814Q are associated with impaired LDLR expression and activity.
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Hiperlipoproteinemia Tipo II , Western BlottingRESUMO
ABSTRACT Deforestation and high human mobility due to mining activities have been key to the increase in malaria cases in the Americas. Here, we review the epidemiological and control aspects of malaria in the Amazon mining areas. Epidemiological evidence shows: 1) a positive correlation between illegal mining activity and malaria incidence, mostly in the Amazon region; 2) most Brazilian miners are males aged 15-29 years who move between states and even countries; 3) miners do not fear the disease and rely on medical care, diagnosis, and medication when they become ill; 4) illegal mining has emerged as the most reported anthropogenic activity within indigenous lands and is identified as a major cause of malaria outbreaks among indigenous people in the Amazon; and 5) because mining is largely illegal, most areas are not covered by any healthcare facilities or activities, leading to little assistance in the diagnosis and treatment of malaria. Our review identified five strategies for reducing the malaria incidence in areas with mining activities: 1) reviewing legislation to control deforestation and mining expansion, particularly in indigenous lands; 2) strengthening malaria surveillance by expanding the network of community health agents to support rapid diagnosis and treatment; 3) reinforcing vector control strategies, such as the use of insecticide-treated nets; 4) integrating deforestation alerts into the national malaria control program; and 5) implementing multi-sectoral activities and providing prompt assistance to indigenous populations. With this roadmap, we can expect a decrease in malaria incidence in the Amazonian mining areas in the future.
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ABSTRACT Background: Domiciliation by Triatoma sordida is a public health concern in South America. This study aimed to evaluate the morphometric changes in the domestic and peridomestic populations of T. sordida. Methods: Specimen hemelytra were mounted, digitized, and processed for geometric morphometric analyses. Results: The specimens captured in houses were smaller than those captured in peridomiciles. A large size reduction effect was observed in female peridomicile populations compared with female house populations. Conclusions: T. sordida house populations were smaller than peridomestic populations. Wing geometric morphometry can be used as a tool to indicate T. sordida domiciliation.
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A pandemia do novo coronavírus colocou em alerta os sistemas de saúde, estabelecendo sentimentos de instabilidade e de medo. O trabalho é e importante pilar para o traçado de políticas públicas. Objetivo: analisar a contaminação pelo COVID-19 em profissionais de hospital de referência no Pará. Metodologia: Trata-se de estudo retrospectivo, quantitativo, observacional, com aplicação de série temporal no período de março de 2020 a março de 2022. Foram incluídos todos os servidores atuantes durante a pandemia, que apresentaram atestados médicos com diagnóstico de COVID, e/ou testagem positiva, ou atestados por suspeita de contaminação. O perfil de servidores foi analisado, explorando as variáveis sexo, idade, convivência ou não com parceiros, grau de escolaridade, cargo e setor; juntamente com a incidência de casos confirmados e incidência total (suspeitos e confirmados). Resultados: O total de afastamentos do trabalho devido ao diagnóstico de COVID-19 foi de 1.420 casos, mais 839 casos suspeitos; sendo que 173 trabalhadores apresentaram reincidência. A incidência foi maior nos meses de maio de 2020, março de 2021 e janeiro de 2022. Houve predominância do sexo feminino e da categoria de enfermagem. Setores administrativos e financeiros apresentaram maior porcentagem de contaminados durante a pandemia (73,40%), proporcionalmente ao quantitativo de servidores atuantes na lotação. Entretanto, foram servidores da assistência direta ao paciente que apresentaram maior porcentagem de reinfecção. Conclusão: Foi possível visualizar três ondas na distribuição temporal dos casos de COVID-19, com destaque para elevação nos primeiros meses de 2022. O declínio no diagnóstico de casos novos no hospital estudado após dois anos de pandemia pode representar esforços individuais e coletivos em resistir às dificuldades da conjuntura. É importante observar o comportamento da pandemia em distintas regiões do Brasil para atualização de estratégias de enfrentamento como um todo.
The new coronavirus pandemic has put health systems on alert, establishing feelings of instability and fear. Working is an important pillar for the design of public policies. Objective: to analyze the contamination by COVID-19 in professionals of a reference hospital in Para's State. Methodology: This is a retrospective, quantitative, observational study, with the application of a time series from March 2020 to March 2022. All civil servants working during the pandemic, who presented medical certificates with a diagnosis of COVID, and/or or positive test, or attestations for suspected contamination. The servants' profile was analyzed, exploring the variables sex, age, living or not with partners, education level, position and sector; along with the incidence of confirmed cases and total incidence (suspected and confirmed). Results: The total number of absences from work due to the diagnosis of COVID-19 was 1,420 cases, plus 839 suspected cases; 173 workers presented recurrence. The incidence was higher in the months of May 2020, March 2021 and January 2022. There was a predominance of females and the nursing category. Administrative and financial sectors had a higher percentage of people infected during the pandemic (73.40%), proportionally to the number of servers working in the capacity. However, it was direct patient care workers who had the highest percentage of reinfection. Conclusion: It was possible to visualize three waves in the temporal distribution of COVID-19 cases, with emphasis on an increase in the first months of 2022. The decline in the diagnosis of new cases in the hospital studied after two years of the pandemic may represent individual and collective efforts to resist to the difficulties of the situation. It is important to observe the behavior of the pandemic in different regions of Brazil to update coping strategies in a general scenery.
La nueva pandemia de coronavirus ha puesto en alerta a los sistemas de salud, estableciendo sentimientos de inestabilidad y miedo. El trabajo es un pilar importante para el diseño de políticas públicas. Objetivo: analizar la contaminación por COVID-19 en profesionales de un hospital de referencia en el Estado de Pará. Metodología: Se trata de un estudio retrospectivo, cuantitativo, observacional, con la aplicación de una serie de tiempo de marzo de 2020 a marzo de 2022. Todos los funcionarios que trabajaron durante la pandemia, que presentaron certificados médicos con diagnóstico de COVID, y/o o test positivo, o atestados por sospecha de contaminación. Se analizó el perfil de los funcionarios, explorando las variables sexo, edad, convivencia o no con la pareja, nivel de escolaridad, cargo y sector; junto con la incidencia de casos confirmados y la incidencia total (sospechosos y confirmados). Resultados: El número total de bajas laborales por diagnóstico de COVID-19 fue de 1.420 casos, más 839 casos sospechosos; 173 trabajadores presentaron recurrencia. La incidencia fue mayor en los meses de mayo de 2020, marzo de 2021 y enero de 2022. Hubo predominio del sexo femenino y de la categoría de enfermería. Los sectores administrativo y financiero presentaron mayor porcentaje de infectados durante la pandemia (73,40%), proporcionalmente al número de servidores que trabajaban en esa función. Sin embargo, fueron los trabajadores de atención directa al paciente los que presentaron el mayor porcentaje de reinfección. Conclusiones: Fue posible visualizar tres olas en la distribución temporal de los casos de COVID-19, destacándose un aumento en los primeros meses de 2022. La disminución en el diagnóstico de nuevos casos en el hospital estudiado después de dos años de pandemia puede representar esfuerzos individuales y colectivos para resistir a las dificultades de la situación. Es importante observar el comportamiento de la pandemia en diferentes regiones de Brasil para actualizar las estrategias de afrontamiento en un escenario general.
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Humanos , Masculino , Feminino , Pessoal de Saúde/estatística & dados numéricos , COVID-19/epidemiologia , Hospitais/estatística & dados numéricos , Estudos Retrospectivos , Saúde Ocupacional , Transmissão de Doença Infecciosa , Pandemias/estatística & dados numéricos , Empregados do Governo , Reinfecção/epidemiologia , Pesquisa sobre Serviços de SaúdeRESUMO
Background: Recent data suggest that breast-conserving surgery (BCS) may positively impact overall survival (OS) in early breast cancer. However, the role of BCS in locally advanced breast cancer (LABC) following neoadjuvant therapy (NAT) remains uncertain. Methods: We conducted a retrospective cohort study involving 530 LABC patients who underwent surgery after NAT between 2010 and 2015. Outcomes examined included OS, distant recurrence rates (DRR), and loco-regional recurrence rates (LRRs). Results: Among the 927 breast cancer patients who received NAT, 530 were eligible for our study. Of these, 24.6% underwent BCS, while 75.4% underwent mastectomy (MS). The median follow-up duration was 79 months. BCS patients exhibited a higher pathological complete response (PCR) rate compared to those who underwent MS (22.3% vs. 10%, p < 0.001). The 6-year OS rates for BCS and MS were 81.5% and 62%, respectively (p < 0.000). In multivariate OS analysis, MS was associated with worse outcomes (OR 1.678; 95% CI 1.069-2.635; p = 0.024), as was body mass index (BMI) (OR 1.031; 95% CI 1.006-1.058; p = 0.017), and stage IIIB or IIIC (OR 2.450; 95% CI 1.561-3.846; p < 0.000). Conversely, PCR (OR 0.42; 95% CI 0.220-0.801; p = 0.008) was associated with improved survival. DRR was significantly lower in BCS (15.4%) compared to MS (36.8%) (OR 0.298; 95% CI 0.177-0.504). LRRs were comparable between BCS (9.2%) and MS (9.5%) (OR 0.693; 95% CI 0.347-1.383). Conclusion: Our findings suggest that BCS is oncologically safe, even for patients with large lesions, and is associated with superior OS rates compared to MS. Additionally, lower BMI, lower pretreatment stage, and achieving PCR were associated with improved survival outcomes.
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Familial hypercholesterolemia (FH) is a disorder of lipid metabolism that causes elevated low-density lipoprotein cholesterol (LDL-c) and increased premature atherosclerosis risk. Statins inhibit endogenous cholesterol biosynthesis, which reduces LDL-c plasma levels and prevent from cardiovascular events. This study aimed to explore the effects of statin treatment on serum lipidomic profile and to identify biomarkers of response in subjects with FH. Seventeen adult FH patients underwent a 6-week washout followed by 4-week treatment with atorvastatin (80 mg/day) or rosuvastatin (40 mg/day). LDL-c response was considered good (4070 % reduction, n = 9) or poor (333 % reduction, n = 8). Serum lipidomic profile was analyzed by ultra-high-performance liquid chromatography combined with electrospray ionization tandem time-of-flight mass spectrometry, and data were analyzed using MetaboAnalyst v5.0. Lipidomic analysis identified 353 lipids grouped into 16 classes. Statin treatment reduced drastically 8 of 13 lipid classes, generating a characteristic lipidomic profile with a significant contribution of phosphatidylinositols (PI) 16:0/18:2, 18:0/18:1 and 18:0/18:2; and triacylglycerols (TAG) 18:2x2/18:3, 18:1/18:2/18:3, 16:1/18:2x2, 16:1/18:2/18:3 and 16:1/18:2/Arachidonic acid (p-adjusted <0.05). Biomarker analysis implemented in MetaboAnalyst subsequently identified PI 16:1/18:0, 16:0/18:2 and 18:0/18:2 as predictors of statin response with and receiver operating characteristic (ROC) areas under the curve of 0.98, 0.94 and 0.91, respectively. In conclusion, statins extensively modulate the overall serum lipid composition of FH individuals and these findings suggest that phosphatidyl-inositol molecules are potential predictive biomarkers of statin response.
Assuntos
Biomarcadores , Hiperlipoproteinemia Tipo II , Fosfatidilinositóis , Inibidores de Hidroximetilglutaril-CoA Redutases , LipidômicaRESUMO
Familial hypercholesterolemia (FH) is a disorder of lipid metabolism that causes elevated low-density lipoprotein cholesterol (LDL-c) and increased premature atherosclerosis risk. Statins inhibit endogenous cholesterol biosynthesis, which reduces LDL-c plasma levels and prevent from cardiovascular events. This study aimed to explore the effects of statin treatment on serum lipidomic profile and to identify biomarkers of response in subjects with FH. Seventeen adult FH patients underwent a 6-week washout followed by 4-week treatment with atorvastatin (80 mg/day) or rosuvastatin (40 mg/day). LDL-c response was considered good (40-70 % reduction, n = 9) or poor (3-33 % reduction, n = 8). Serum lipidomic profile was analyzed by ultra-high-performance liquid chromatography combined with electrospray ionization tandem time-of-flight mass spectrometry, and data were analyzed using MetaboAnalyst v5.0. Lipidomic analysis identified 353 lipids grouped into 16 classes. Statin treatment reduced drastically 8 of 13 lipid classes, generating a characteristic lipidomic profile with a significant contribution of phosphatidylinositols (PI) 16:0/18:2, 18:0/18:1 and 18:0/18:2; and triacylglycerols (TAG) 18:2x2/18:3, 18:1/18:2/18:3, 16:1/18:2x2, 16:1/18:2/18:3 and 16:1/18:2/Arachidonic acid (p-adjusted <0.05). Biomarker analysis implemented in MetaboAnalyst subsequently identified PI 16:1/18:0, 16:0/18:2 and 18:0/18:2 as predictors of statin response with and receiver operating characteristic (ROC) areas under the curve of 0.98, 0.94 and 0.91, respectively. In conclusion, statins extensively modulate the overall serum lipid composition of FH individuals and these findings suggest that phosphatidyl-inositol molecules are potential predictive biomarkers of statin response.
Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipoproteinemia Tipo II , Adulto , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , LDL-Colesterol , Lipidômica , Hiperlipoproteinemia Tipo II/tratamento farmacológico , Colesterol , BiomarcadoresRESUMO
The effects of the toxic dinoflagellate Alexandrium catenella were investigated on growth, survival, and histopathology in larvae and spat of the Tehuelche scallop Aequipecten tehuelchus from Patagonia, Argentina. The study consisted of laboratory incubations of scallop larvae/spat with A. catenella, using environmentally realistic abundances of the dinoflagellate. Survival, growth, and histopathological effects were documented for scallop larvae/spat before, during, and after 7-day-long exposure to A. catenella. The scallops were grouped in flasks containing 0 (control), 20, 200, and 2000 cells mL-1 of A. catenella. The presence of A. catenella induced reduced larvae survival after 24 h, whereas a clear effect was observed after 3 days (survival of control larvae 95%, 72, and 79% for 20 and 200 cells mL-1, respectively, and 43% for 2000 cells mL-1). The growth rates of the control larvae and those exposed to 20 mL-1 cells were significantly different from zero. Histopathological effects (melanization, loss of connective tissue, necrosis, and inflammatory responses) were observed in spat exposed to A. catenella. These effects were more pronounced at the highest dinoflagellate concentration. Blooms of A. catenella frequently coincide with the reproductive season of A. tehuelchus, thus there is a need to further study the relationship between harmful algal blooms and the effect on scallops' natural populations in the region.
Assuntos
Dinoflagellida , Pectinidae , Animais , Dinoflagellida/fisiologia , Proliferação Nociva de Algas , Alimentos Marinhos , Argentina , LarvaRESUMO
BACKGROUND: Familial hypercholesterolemia (FH) is caused by pathogenic variants in low-density lipoprotein (LDL) receptor (LDLR) or its associated genes, including apolipoprotein B (APOB), proprotein convertase subtilisin/kexin type 9 (PCSK9), and LDLR adaptor protein 1 (LDLRAP1). However, approximately 40% of the FH patients clinically diagnosed (based on FH phenotypes) may not carry a causal variant in a FH-related gene. Variants located at 3' untranslated region (UTR) of FH-related genes could elucidate mechanisms involved in FH pathogenesis. This study used a computational approach to assess the effects of 3'UTR variants in FH-related genes on miRNAs molecular interactions and to explore the association of these variants with molecular diagnosis of FH. METHODS AND RESULTS: Exons and regulatory regions of FH-related genes were sequenced in 83 FH patients using an exon-target gene sequencing strategy. In silico prediction tools were used to study the effects of 3´UTR variants on interactions between miRNAs and target mRNAs. Pathogenic variants in FH-related genes (molecular diagnosis) were detected in 44.6% FH patients. Among 59 3'UTR variants identified, LDLR rs5742911 and PCSK9 rs17111557 were associated with molecular diagnosis of FH, whereas LDLR rs7258146 and rs7254521 and LDLRAP1 rs397860393 had an opposite effect (p < 0.05). 3´UTR variants in LDLR (rs5742911, rs7258146, rs7254521) and PCSK9 (rs17111557) disrupt interactions with several miRNAs, and more stable bindings were found with LDLR (miR-4435, miR-509-3 and miR-502) and PCSK9 (miR-4796). CONCLUSION: LDLR and PCSK9 3´UTR variants disturb miRNA:mRNA interactions that could affect gene expression and are potentially associated with molecular diagnosis of FH.
Assuntos
Hiperlipoproteinemia Tipo II , MicroRNAs , Humanos , Pró-Proteína Convertase 9/genética , Regiões 3' não Traduzidas/genética , MicroRNAs/genética , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/diagnóstico , Receptores de LDL/genética , MutaçãoRESUMO
The neglected parasitosis giardiasis is one of the most common intestinal infections worldwide, affecting mainly infants and young children. Giardia duodenalis may disturb the local microbiome, leading to intestinal ecosystem disorders, and altering different processes in the host, such as the immune response. Nevertheless, the alterations promoted by G. duodenalis on the human gut microbiome have not been thoroughly investigated. Here, we characterized the gut microbiota of G. duodenalis-infected children and determine the main alterations promoted by the parasite. To do so, fecal samples of 26 infected and four uninfected children aged 2 to 6 years old were processed for High Efficiency Microarray analysis, in order to describe their bacterial and viral profiles. Then, we quantified the total bacterial population by qPCR and assessed fecal calprotectin levels, which are closely related with gut inflammation. A total of 286 bacteria's species and 17 viruses' strains were identified. Our results revealed no statistically significant differences between G. duodenalis positive and negative groups in the taxa's phyla and families. However, bacterial species diversity was increased in children infected with G. duodenalis (p < 0.05), while the total number of bacteria was decreased (p < 0.05). Considering the virome analysis, 17 different strains were identified, 88% being bacteriophages. The correlation analysis revealed an important disruption in the balance of DNA virus and bacteria within the intestinal microbiota of Giardia-positive children. Our findings constitute the first description of the gut virome of Giardia-infected children and suggest that G. duodenalis infection exerts a modulatory effect on the gut microbiome, promoting local inflammation and altering the equilibrium of the parasite-microbiota-host triad. This highlights the importance of considering polymicrobial associations and understanding the broader context of giardiasis. Overall, our study provides new insights into the complex interactions between intestinal parasites and the microbiota, which may have implications for the development of novel therapeutic interventions in the future.