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Based on personal experience over several years, we carried out a comparative analysis of two different European health systems, in Portugal and France, from a perspective comparing occupational medicine and use of telemedicine in a postpandemic context. This analysis addressed four aspects: Health System; Occupational Medicine; Telemedicine/Telework; and Future and Suggestions. The study employed searches and review of recent articles, guidelines, and recommendations from the authorities responsible for regulation (Medical Doctors Order, Labor Legislation, and Medical Collegiate Recommendations) and analysis of some statistical indicators from recent studies. Three tables on Occupational Health and Medicine present some relevant data and facilitate comparisons. Despite the difficulties of comparison, given the basic differences between these two systems (Beveridge vs. Bismark), it can be concluded that there is a greater acceptance of judicious use of teleconsultation in France (from 15 to 35%). This includes its use by occupational nurses, in the context of the "Visite de Information et Prevention", with good acceptance among employers and employees. There are still some difficulties to be resolved concerning security, conducting biometrics, and objective examinations. We expect that these issues will be overcome with improved biosensing, adequate training, and proper regulation. Given the shortage of occupational physicians and the customary overrunning of legal deadlines, we believe that these possibilities and suggestions should be explored and adopted by the specialty's Collegiates. Certain recommendations to this effect are made.
Com base na experiência pessoal de vários anos, foi realizada uma análise comparativa de dois sistemas de saúde europeus diferentes, de Portugal e da França, em uma perspectiva direcionada a uma comparação da medicina do trabalho e a utilização da telemedicina no contexto pós-pandêmico, em que ela se normalizou. Esta análise comparativa incide em quatro aspectos: sistema de saúde; medicina do trabalho; telemedicina/teletrabalho; e futuro e sugestões. Foram incluídas pesquisa e revisão documental de vários artigos recentes, normativas e recomendações das autoridades responsáveis pela tutela (Recomendações Colegiais, Ordem dos Médicos, Código do Trabalho), e foram feitas comparações de alguns indicadores estatísticos e estudos recentes. Três tabelas sobre a saúde, a medicina do trabalho e a telemedicina apresentam alguns dados relevantes e facilitam a comparação. Apesar da comparação difícil dadas as diferenças de base dos dois sistemas (modelo Beveridge versus Bismarck), parece ser possível concluir que existe uma maior abertura para a utilização criteriosa da teleconsulta na França (entre 15 e 35%), incluindo o seu uso por enfermeiras no contexto da visite d'information et de prévention, com uma boa aceitação pelos empregadores e trabalhadores. Ainda existem dificuldades por resolver, nomeadamente sobre a segurança e as dificuldades na sua utilização ou na realização da biometria ou exame objetivo. Por meio de melhorias no biosensing e de uma formação adequada, essas questões serão ultrapassadas. Dada a falta de médicos do trabalho e a habitual dilação dos prazos legais, essa possibilidade e as sugestões deveriam ser exploradas e enquadradas pelo Colégio da especialidade. Realizam-se algumas sugestões nesse sentido.
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The Piper genus, known for its pharmacological potential, comprises 2,263 species primarily found in tropical regions. Despite recent advancements in pain therapies, the demand for more effective and well-tolerated analgesics and anti-inflammatories, particularly for chronic pain, remains. This study assessed the effects of essential oils from Piper caldense, Piper mosenii, and Piper mikanianum on nociceptive behavior induced by formalin and capsaicin, as well as their anti-inflammatory impact induced by carrageenan, using adult zebrafish models. Results indicated non-toxic essential oils with antinociceptive properties in both neurogenic and inflammatory phases of formalin-induced nociception through interaction with the TRPA1 receptor. Additionally, P. mosenii essential oil also blocked the nociceptive effect of capsaicin, a TRPV1 receptor agonist. Furthermore, essential oils from P. caldense and P. mikanianum exhibited significant anti-inflammatory effects by reducing carrageenan-induced abdominal edema. These findings highlight the pharmacological potential of Piper's essential oils as antinociceptive and anti-inflammatory agents.
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Aceites Volátiles , Piper , Animales , Carragenina/efectos adversos , Pez Cebra , Aceites Volátiles/farmacología , Aceites Volátiles/uso terapéutico , Capsaicina , Analgésicos/farmacología , Analgésicos/uso terapéutico , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Extractos Vegetales/farmacología , Formaldehído/efectos adversos , Edema/inducido químicamente , Edema/tratamiento farmacológicoRESUMEN
The rebound-competent viral reservoir, composed of a virus that is able to persist during antiretroviral therapy (ART) and mediate reactivation of systemic viral replication and rebound viremia after ART interruption (ATI), remains the biggest obstacle to treating HIV infection. A better understanding of the cellular and tissue origins and the dynamics of viral populations that initiate rebound upon ATI could help develop therapeutic strategies for reducing the rebound-competent viral reservoir. In this study, barcoded simian immunodeficiency virus (SIV), SIVmac239M, was used to infect rhesus macaques to enable monitoring of viral barcode clonotypes contributing to virus detectable in plasma after ATI. Blood and tissues from secondary lymphoid organs (spleen, mesenteric lymph nodes, and inguinal lymph nodes) and from the colon, ileum, lung, liver, and brain were analyzed using viral barcode sequencing, intact proviral DNA assay, single-cell RNA sequencing, and combined CODEX and RNAscope in situ hybridization. Four of seven animals had viral barcodes detectable by deep sequencing of plasma at necropsy, although plasma viral RNA remained below 22 copies per milliliter. Among the tissues studied, mesenteric lymph nodes, inguinal lymph nodes, and spleen contained viral barcodes detected in plasma. CD4+ T cells were the main cell type harboring viral RNA after ATI. Furthermore, T cell zones in lymphoid tissues showed higher viral RNA abundance than B cell zones for most animals. These findings are consistent with lymphoid tissues contributing to the virus present in plasma early after ATI.
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Infecciones por VIH , Síndrome de Inmunodeficiencia Adquirida del Simio , Virus de la Inmunodeficiencia de los Simios , Animales , Virus de la Inmunodeficiencia de los Simios/genética , Macaca mulatta , Infecciones por VIH/tratamiento farmacológico , Antirretrovirales/uso terapéutico , Antirretrovirales/farmacología , Tejido Linfoide , Replicación Viral , ARN Viral , Carga Viral , Linfocitos T CD4-PositivosRESUMEN
The rebound-competent viral reservoir (RCVR), comprised of virus that is able to persist during antiretroviral therapy (ART) and mediate reactivation of systemic viral replication and rebound viremia after antiretroviral therapy interruption (ATI), remains the biggest obstacle to the eradication of HIV infection. A better understanding of the cellular and tissue origins and the dynamics of viral populations that initiate rebound upon ATI could help develop targeted therapeutic strategies for reducing the RCVR. In this study, barcoded SIVmac239M was used to infect rhesus macaques to enable monitoring of viral barcode clonotypes contributing to virus detectable in plasma after ATI. Blood, lymphoid tissues (LTs, spleen, mesenteric and inguinal lymph nodes), and non-lymphoid tissues (NLTs, colon, ileum, lung, liver, and brain) were analyzed using viral barcode sequencing, intact proviral DNA assay, single-cell RNA sequencing, and combined CODEX/RNAscope/ in situ hybridization. Four of seven animals had viral barcodes detectable by deep sequencing of plasma at necropsy although plasma viral RNA remained < 22 copies/mL. Among the tissues studied, mesenteric and inguinal lymph nodes, and spleen contained viral barcodes detected in plasma, and trended to have higher cell-associated viral loads, higher intact provirus levels, and greater diversity of viral barcodes. CD4+ T cells were the main cell type harboring viral RNA (vRNA) after ATI. Further, T cell zones in LTs showed higher vRNA levels than B cell zones for most animals. These findings are consistent with LTs contributing to virus present in plasma early after ATI. One Sentence Summary: The reemerging of SIV clonotypes at early post-ATI are likely from the secondary lymphoid tissues.
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Essential oils extracted from many plant species have different biological activities, among which microbial activity stands out. Species of the genus Piper have antimicrobial potential against different species of bacteria and fungi. In this sense, the present study aimed to determine the chemical composition of the essential oil from the leaves of Piper gaudichaudianum (EOPG), as well as to investigate their antimicrobial activity and their modulatory effect on the Norfloxacin resistance in the Staphylococcus aureus SA1199B strain overproducer of the NorA efflux pump. Furthermore, their inhibitory activities on the biofilm formation as well as on the cellular differentiation of C. albicans were evaluated. Gas chromatography analysis identified 24 compounds, such as hydrocarbon sesquiterpenes (54.8%) and oxygenated sesquiterpenes (28.5%). To investigate the antimicrobial potential of EOPG against S. aureus, E. coli, and C. albicans, a microdilution assay was performed, and no intrinsic antimicrobial activity was observed. On the other hand, the oil potentiated the activity of Norfloxacin against the SA1199B strain, indicating that EOPG could be used in association with Norfloxacin against S. aureus strains resistant to this antibiotic. EOPG also inhibited S. aureus biofilm formation, as evidenced by the crystal violet assay. In the dimorphism assay, EOPG was able to inhibit the cell differentiation process in C. albicans. Results indicate that EOPG could be used in association with Norfloxacin in the treatment of infections caused by resistant S. aureus strains overproducing the NorA efflux pump. Furthermore, its ability to inhibit the formation of hyphae by C. albicans suggests that EOPG could also be applied in the prevention and/or treatment of fungal infections.
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The advent of quantum computing threatens blockchain protocols and networks because they utilize non-quantum resistant cryptographic algorithms. When quantum computers become robust enough to run Shor's algorithm on a large scale, the most used asymmetric algorithms, utilized for digital signatures and message encryption, such as RSA, (EC)DSA, and (EC)DH, will be no longer secure. Quantum computers will be able to break them within a short period of time. Similarly, Grover's algorithm concedes a quadratic advantage for mining blocks in certain consensus protocols such as proof of work. Today, there are hundreds of billions of dollars denominated in cryptocurrencies and other digital assets that rely on blockchain ledgers as well as thousands of blockchain-based applications storing value in blockchain networks. Cryptocurrencies and blockchain-based applications require solutions that guarantee quantum resistance in order to preserve the integrity of data and assets in these public and immutable ledgers. The quantum threat and some potential solutions are well understood and presented in the literature. However, most proposals are theoretical, require large QKD networks, or propose new quantum-resistant blockchain networks to be built from scratch. Our work, which is presented in this paper, is pioneer in proposing an end-to-end framework for post-quantum blockchain networks that can be applied to existing blockchain to achieve quantum-resistance. We have developed an open-source implementation in an Ethereum-based (i.e., EVM compatible) network that can be extended to other existing blockchains. For the implementation we have (i) used quantum entropy to generate post-quantum key pairs, (ii) established post-quantum TLS connections and X.509 certificates to secure the exchange of information between blockchain nodes over the internet without needing a large QKD network, (iii) introduced a post-quantum second signature in transactions using Falcon-512 post-quantum keys, and (iv) developed the first on-chain verification of post-quantum signatures using three different mechanisms that are compared and analyzed: Solidity smart-contracts run by the validators for each transaction, modified EVM Opcode, and precompiled smart contracts.
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Trans-Caryophyllene (TC), a sesquiterpene, with proven biological activities, which in this work was tested alone, encapsulated in liposomes and associated with Fluconazole in vitro in an attempt to enhance the effect of the drug. Liposomes were characterized from vesicle size, polydispersity index, and Zeta potential, and imaging by scanning electron microscopy. Antifungal assays were performed against Candida albicans, Candida tropicalis and Candida krusei by microdilution to determine the IC50 values and the viability curve. The Minimum Fungicidal Concentration (MFC) was performed by subcultivation in solid medium and the inhibitory effect of the association of TC and Fluconazole and tests to verify morphological changes was performed in micro-cultivation chambers based on concentrations on microdilution plates. The corresponding IC50 data of the substances ranged from 34.4 to 65249 µg/mL, considerably high values compared to the control (Fluconazole). The MFC of all compounds showing fungistatic effect. The performance of the compounds on the cell viability curve was similar in all tested strains, as they showed no antifungal potential when compared to the control (FCZ), when associated with FCZ they showed no significant antifungal activity. The free and liposomal TC also managed to restrict 100% of the fungal dimorphism, in both concentrations, against C. albicans, and against C. tropicalis the isolated TC did not show a significant inhibitory effect; however, against the C. krusei strain inhibited 100% in filamentous growth in both concentrations, which is statistically relevant. The liposomes were homogeneous, with vesicles with diameters of 185.46 nm for the control and 143.8 nm for the liposomal TC, and a surface charge potential of - 42.6 mV. By scanning microscopy, the spherical shapes of the vesicles were verified.
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Fluconazol , Liposomas , Fluconazol/farmacología , Candida , Antifúngicos/farmacología , Candida albicans , Pruebas de Sensibilidad MicrobianaRESUMEN
Coronavirus disease (COVID-19) has the virus that causes the SARS-CoV-2 severe acute respiratory syndrome, which has reached a pandemic proportion, with thousands of deaths worldwide already registered. It has no standardized effective clinical treatment, arousing the urgent need for the discovery of bioactive compounds for the treatment of symptoms of COVID-19. In this context, the present study aimed to evaluate the influence of seasonality on the yield and chemical composition of the essential oils of Piper cernuum and Piper rivinoides as well as to evaluate the anti-SARS-CoV-2 potential of the major components of each oil by molecular docking and quantum chemical calculation (Density Functional Theory method), being possible indicate that the winter and autumn periods, the seasons of the year where it is possible to obtain the highest percentage of Piper cernuum and Piper rivinoides oils, respectively. Regarding the anti-SARS-Cov-2 potential, the present work showed that the dihydroagarofuran present in Piper cernuum, presented a strong interaction with amino acid residues from Mpro, presenting a potential similar to Remdesivir, a drug for clinical use. Regarding methyltransferase, dihydroagarofuran (Piper cernuum) and myristicin (Piper rivinoids) showed better affinity, with important interactions at the active site of the inhibitor Sinefugin, suggesting a potential inhibitory effect of the heterodimer methyltransferase complex NSP16-NSP10 SARS Cov-2. Molecular docking and molecular dynamics studies represent an initial step, being indicative for future in vitro studies of dihydroagarofuran and myristicin, as possible pharmacological tools for COVID-19.Communicated by Ramaswamy H. Sarma.
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COVID-19 , Aceites Volátiles , Piper , Humanos , Simulación del Acoplamiento Molecular , SARS-CoV-2/metabolismo , Metiltransferasas/química , Estaciones del Año , Teoría Funcional de la Densidad , Aceites Volátiles/farmacología , Aceites Volátiles/química , Piper/química , Simulación de Dinámica Molecular , Inhibidores de ProteasasRESUMEN
The gut is a major reservoir in HIV-infected individuals on antiretroviral therapy (ART) and in long-term non-progressors (LTNPs). Whether ART reduces gut infection and reservoirs in LTNPs is unknown. Herein, SIV-infected LTNP Rhesus macaques were treated with short- or long-term ART, and SIV envelope gp120 sequences obtained from single genome amplification were analyzed before and after ART in peripheral blood and the intestine. Although ART does not eliminate SIV in these LTNPs, a longer ART period dramatically reduces SIV infection in the gut. This study highlights the importance of long-term ART in LTNPs to minimize gut infection and prolong remission.
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Infecciones por VIH , Síndrome de Inmunodeficiencia Adquirida del Simio , Virus de la Inmunodeficiencia de los Simios , Animales , Síndrome de Inmunodeficiencia Adquirida del Simio/tratamiento farmacológico , Virus de la Inmunodeficiencia de los Simios/genética , Macaca mulatta , Infecciones por VIH/tratamiento farmacológico , Antirretrovirales/uso terapéuticoRESUMEN
Introdução: Estudantes universitários da área de saúde apresentam uma rotina que exacerba inadequações no estilo de vida e sono, as quais contribuem para um estado de inflamação crônica de baixo grau. Objetivo: investigar se há associação entre o consumo de uma dieta pró-inflamatória e a qualidade do sono de estudantes universitários. Materiais e métodos: Estudo transversal, com amostra de conveniência que incluiu 102 universitários, com 18 ou mais anos de idade, recrutados entre março de 2019 e março de 2020, matriculados em cursos de Nutrição de universidades públicas e privadas da cidade de Fortaleza. A qualidade do sono foi avaliada por meio da escala Pittsburgh Sleep Quality Index (PSQI) ou Índice de Qualidade do Sono de Pittsburgh, validado no Brasil (PSQI-BR). O consumo alimentar foi investigado a partir de um questionário de frequência alimentar. Foi determinado o Padrão Empírico de Inflamação da Dieta (EDIP-SP), validado para o Brasil, o qual quantifica ingestão de carnes processadas, verduras, legumes, frutas, arroz e feijão. Também foi determinada a presença de inflamação crônica por meio dos marcadores proteína C-reativa e Relação Neutrófilo/Linfócito. Resultados: A alimentação consumida é, em média, anti-inflamatória (-1,57 ± 0,69). Apenas 1,96% dos avaliados tinha boa qualidade do sono; 75,49% apresentavam distúrbio do sono. Não houve associação entre o EDIP-SP e os marcadores inflamatórios investigados, nem com a qualidade do sono. Discussão: A maioria dos estudantes apresentou má qualidade do sono e dieta anti-inflamatória. Esta homogeneidade pode ter determinado a ausência de associação e correlações. Conclusões: Os estudantes universitários avaliados têm má qualidade do sono, mas ingerem dieta anti-inflamatória, sem associação entre estas duas variáveis(AU)
Introduction: University students in the health area have a routine that exacerbates inadequacies in lifestyle and sleep, which contribute to a state of chronic low-grade inflammation. Objective: to evaluate whether there is an association between the consumption of pro-inflammatory diet and the sleep quality of university students. Material and Methods: Cross-sectional study, with a convenience sample that included 102 university students, aged 18 or over, recruited between March 2019 and March 2020, enrolled in Nutrition courses at public and private universities in the Fortaleza city. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI), validated in Brazil (PSQI-BR). Food consumption was investigated using a food frequency questionnaire, and the Empirical Dietary Inflammation Pattern (EDIP-SP), validated by Brazil. The EDIP-SP quantifies the intake of processed meats, vegetables, fruits, rice and beans. The presence of inflammation was also determined through the markers C-reactive protein and Neutrophil/ Lymphocyte Ratio. Results: The food consumed is, on average, anti-inflammatory (-1.57 ± 0.69). Only 1.96% of those evaluated had good sleep quality; 75.49% had a sleep disorder. There was no association between EDIPSP and the inflammatory markers investigated, nor with sleep quality. Discussion: Most students had poor sleep quality and anti-inflammatory diet. This homogeneity may have determined the absence of association and correlations. Conclusions: The evaluated university students have poor sleep quality, but eat an antiinflammatory diet, with no association between these two variables(AU)
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Humanos , Masculino , Femenino , Adolescente , Adulto , Trastornos del Sueño-Vigilia , Dieta , Ingestión de Alimentos , Inflamación , Estilo de Vida , Peso CorporalRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first reported in Wuhan, China in December 2019 and caused a global pandemic resulting in millions of deaths and tens of millions of patients positive tests. While studies have shown a D614G mutation in the viral spike protein are more transmissible, the effects of this and other mutations on the host response, especially at the cellular level, are yet to be fully elucidated. In this experiment we infected normal human bronchial epithelial (NHBE) cells with the Washington (D614) strain or the New York (G614) strains of SARS-CoV-2. We generated RNA sequencing data at 6, 12, and 24 hours post-infection (hpi) to improve our understanding of how the intracellular host response differs between infections with these two strains. We analyzed these data with a bioinformatics pipeline that identifies differentially expressed genes (DEGs), enriched Gene Ontology (GO) terms and dysregulated signaling pathways. We detected over 2,000 DEGs, over 600 GO terms, and 29 affected pathways between the two infections. Many of these entities play a role in immune signaling and response. A comparison between strains and time points showed a higher similarity between matched time points than across different time points with the same strain in DEGs and affected pathways, but found more similarity between strains across different time points when looking at GO terms. A comparison of the affected pathways showed that the 24hpi samples of the New York strain were more similar to the 12hpi samples of the Washington strain, with a large number of pathways related to translation being inhibited in both strains. These results suggest that the various mutations contained in the genome of these two viral isolates may cause distinct effects on the host transcriptional response in infected host cells, especially relating to how quickly translation is dysregulated after infection. This comparison of the intracellular host response to infection with these two SARS-CoV-2 isolates suggest that some of the mechanisms associated with more severe disease from these viruses could include virus replication, metal ion usage, host translation shutoff, host transcript stability, and immune inhibition.
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COVID-19 , SARS-CoV-2 , Humanos , New York , SARS-CoV-2/genética , Glicoproteína de la Espiga del Coronavirus/genética , Proteínas Virales , WashingtónRESUMEN
Boron Neutron Capture Therapy (BNCT) is a promising binary disease-targeted therapy, as neutrons preferentially kill cells labeled with boron (10B), which makes it a precision medicine treatment modality that provides a therapeutic effect exclusively on patient-specific tumor spread. Contrary to what is usual in radiotherapy, BNCT proposes cell-tailored treatment planning rather than to the tumor mass. The success of BNCT depends mainly on the sufficient spatial biodistribution of 10B located around or within neoplastic cells to produce a high-dose gradient between the tumor and healthy tissue. However, it is not yet possible to precisely determine the concentration of 10B in a specific tissue in real-time using non-invasive methods. Critical issues remain to be resolved if BNCT is to become a valuable, minimally invasive, and efficient treatment. In addition, functional imaging technologies, such as PET, can be applied to determine biological information that can be used for the combined-modality radiotherapy protocol for each specific patient. Regardless, not only imaging methods but also proteomics and gene expression methods will facilitate BNCT becoming a modality of personalized medicine. This work provides an overview of the fundamental principles, recent advances, and future directions of BNCT as cell-targeted cancer therapy for personalized radiation treatment.
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BACKGROUND: Gold nanoparticles (AuNP) may be useful in precision radiotherapy and disease monitoring as theragnostic agents. In diagnostics, they can be detected by computerized tomography (CT) because of their higher atomic number. AuNP may also improve the treatment results in radiotherapy due to a higher cross-section, locally improving the physically absorbed dose. METHODS: Key parameters values involved in the use of AuNP were imposed to be optimal in the clinical scenario. Mass concentration of AuNP as an efficient contrast agent in clinical CT was found and implemented in a Monte Carlo simulation method for dose calculation under different proposed therapeutic beams. The radiosensitization effect was determined in irradiated cells with AuNP. RESULTS: an AuNP concentration was found for a proper contrast level and enhanced therapeutic effect under a beam typically used for image-guided therapy and monitoring. This lower energetic proposed beam showed potential use for treatment monitoring in addition to absorbed dose enhancement and higher radiosensitization at the cellular level. CONCLUSION: the results obtained show the use of AuNP concentration around 20 mg Au·mL-1 as an efficient tool for diagnosis, treatment planning, and monitoring treatment. Simultaneously, the delivered prescription dose provides a higher radiobiological effect on the cancer cell for achieving precision radiotherapy.
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Ru/Rh asymmetric plaques for ophthalmic brachytherapy have special geometric designs with a cutout intended to prevent irradiation of critical ocular structures proximal to the tumor. In this work, we present new geometric models for PENELOPE+PenEasy Monte Carlo simulations of these applicators, differing from the vendor-reported geometry, that better match their real geometry to assess their dosimetric impact. Simulation results were benchmarked to experimental dosimetric data from radiochromic film measurements, data provided by the manufacturer in the calibration certificates, and other experimental results published in the literature, obtaining, in all cases, better agreement with the modified geometries. The clinical impact of the new geometric models was evaluated by simulating real clinical cases using patient-specific eye models. The cases calculated using the modified geometries presented higher doses to the critical structures proximal to the cutout region. The modified geometric models presented in this work provide a more accurate representation of the asymmetric plaques, greatly improving the agreement between Monte Carlo calculations and experimental measurements. Lack of consideration of accurate geometric models has been shown to be translated into notable increases in dose to organs at risk in clinical cases.
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The purpose of this work is to present useful recommendations for the use of [18F]FDG-PET/CT imaging in radiotherapy planning and monitoring under different versions of EARL accreditation for harmonization of PET devices. A proof-of-concept experiment designed on an anthropomorphic phantom was carried out to establish the most suitable interpolation methods of the PET images in the different steps of the planning procedure. Based on PET/CT images obtained by using these optimal interpolations for the old EARL accreditation (EARL1) and for the new one (EARL2), the treatment plannings of representative actual clinical cases were calculated, and the clinical implications of the resulting differences were analyzed. As expected, EARL2 provided smaller volumes with higher resolution than EARL1. The increase in the size of the reconstructed volumes with EARL1 accreditation caused high doses in the organs at risk and in the regions adjacent to the target volumes. EARL2 accreditation allowed an improvement in the accuracy of the PET imaging precision, allowing more personalized radiotherapy. This work provides recommendations for those centers that intend to benefit from the new accreditation, EARL2, and can help build confidence of those that must continue working under the EARL1 accreditation.
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Fluorodesoxiglucosa F18 , Tomografía Computarizada por Tomografía de Emisión de Positrones , Fantasmas de Imagen , Tomografía de Emisión de Positrones/métodosRESUMEN
Background: Chikungunya virus (CHIKV) is a mosquito-borne pathogen, within the Alphavirus genus of the Togaviridae family, that causes ~1.1 million human infections annually. CHIKV uses Aedes albopictus and Aedes aegypti mosquitoes as insect vectors. Human infections can develop arthralgia and myalgia, which results in debilitating pain for weeks, months, and even years after acute infection. No therapeutic treatments or vaccines currently exist for many alphaviruses, including CHIKV. Targeting the phagocytosis of CHIKV by macrophages after mosquito transmission plays an important role in early productive viral infection in humans, and could reduce viral replication and/or symptoms. Methods: To better characterize the transcriptional response of macrophages during early infection, we generated RNA-sequencing data from a CHIKV-infected human macrophage cell line at eight or 24 hours post-infection (hpi), together with mock-infected controls. We then calculated differential gene expression, enriched functional annotations, modulated intracellular signaling pathways, and predicted therapeutic drugs from these sequencing data. Results: We observed 234 pathways were significantly affected 24 hpi, resulting in six potential pharmaceutical treatments to modulate the affected pathways. A subset of significant pathways at 24 hpi includes AGE-RAGE, Fc epsilon RI, Chronic myeloid leukemia, Fc gamma R-mediated phagocytosis, and Ras signaling. We found that the MAPK1 and MAPK3 proteins are shared among this subset of pathways and that Telmisartan and Dasatinib are strong candidates for repurposed small molecule therapeutics that target human processes. The results of our analysis can be further characterized in the wet lab to contribute to the development of host-based prophylactics and therapeutics.
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Aedes , Fiebre Chikungunya , Virus Chikungunya , Animales , Humanos , Virus Chikungunya/genética , Mosquitos Vectores , Fiebre Chikungunya/tratamiento farmacológico , Línea Celular , MacrófagosRESUMEN
The central nervous system (CNS) HIV reservoir is an obstacle to achieving an HIV cure. The basal ganglia harbor a higher frequency of SIV than other brain regions in the SIV-infected rhesus macaques of Chinese-origin (chRMs) even on suppressive combination antiretroviral therapy (ART). Since residual HIV/SIV reservoir is associated with inflammation, we characterized the neuroinflammation by gene expression and systemic levels of inflammatory molecules in healthy controls and SIV-infected chRMs with or without ART. CCL2, IL-6, and IFN-γ were significantly reduced in the cerebrospinal fluid (CSF) of animals receiving ART. Moreover, there was a correlation between levels of CCL2 in plasma and CSF, suggesting the potential use of plasma CCL2 as a neuroinflammation biomarker. With higher SIV frequency, the basal ganglia of untreated SIV-infected chRMs showed an upregulation of secreted phosphoprotein 1 (SPP1), which could be an indicator of ongoing neuroinflammation. While ART greatly reduced neuroinflammation in general, proinflammatory genes, such as IL-9, were still significantly upregulated. These results expand our understanding of neuroinflammation and signaling in SIV-infected chRMs on ART, an excellent model to study HIV/SIV persistence in the CNS.
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Terapia Antirretroviral Altamente Activa , Macaca mulatta/virología , Enfermedades Neuroinflamatorias/genética , Enfermedades Neuroinflamatorias/metabolismo , Síndrome de Inmunodeficiencia Adquirida del Simio/genética , Síndrome de Inmunodeficiencia Adquirida del Simio/metabolismo , Virus de la Inmunodeficiencia de los Simios , Transcriptoma , Animales , Encéfalo , Sistema Nervioso Central , Quimiocinas/metabolismo , China , Citocinas/metabolismo , Modelos Animales de Enfermedad , Expresión Génica , Perfilación de la Expresión Génica , VIH , Infecciones por VIH/sangre , Infecciones por VIH/genética , Infecciones por VIH/metabolismo , Virus de la Influenza A , Síndrome de Inmunodeficiencia Adquirida del Simio/sangre , Síndrome de Inmunodeficiencia Adquirida del Simio/inmunologíaRESUMEN
A retrospective study of poxvirus infections diagnosed in cattle from Goiás state (GO), Brazil, from 2010 to 2018, was performed. All cases have been investigated by the GO Official Veterinary Service (Agrodefesa), from which technical forms and protocols of veterinary diagnosis laboratories were reviewed. In most cases, samples of oral or cutaneous tissues and/or swabs were submitted for virological diagnosis by polymerase chain reaction (PCR) and/or virus isolation. Thirty seven outbreaks/cases of vesicular disease were notified in cattle of 25 counties; in 33 cases the animals presented lesions clinically compatible with poxviruses. The etiology of 25 out of 33 outbreaks/cases was confirmed as poxviruses by PCR and/or viral isolation: 13 as bovine vaccinia virus (VACV), six as pseudocowpox virus (PCPV), five as bovine papular stomatitis virus (BPSV) and one coinfection (VACV and an Orf virus-like parapoxvirus). The laboratory confirmed that cases occurred mainly in dairy cattle (19/25) and during the dry season (22/25). In adult cattle, gross changes were observed mainly in the teats and udder and included vesicles, ulcers, crusts, papules and scars and varied of type, severity and affected region, depending on the poxvirus species. In calves, the main lesions were ulcers in the mouth and muzzle. Zoonotic lesions compatible with poxvirus infections were observed for all diagnosed poxviruses, affecting especially the hands of milkers and other farm workers. Our data demonstrate the sanitary and economic relevance of these diseases and the wide circulation of different poxviruses in cattle from GO.
Foi realizado um estudo retrospectivo das infecções por poxvírus diagnosticadas em bovinos do estado de Goiás (GO), entre 2010 e 2018. Todos os casos foram investigados pela Agência Goiana de Defesa Agropecuária (Agrodefesa). Foram revisados formulários técnicos e protocolos de laboratórios de diagnóstico veterinário. Na maioria dos casos, amostras de tecidos orais ou cutâneos e/ou swabs foram encaminhadas para diagnóstico virológico. Foram notificados 37 surtos/casos de doença vesicular em bovinos em 25 municípios; em 33 casos os animais apresentavam lesões clinicamente compatíveis com poxvírus. A etiologia de 25 de 33 surtos/casos foi confirmada como poxvírus por PCR e/ou isolamento viral: 13 como vírus vaccínia (VACV), seis como vírus pseudocowpox (PCPV), cinco como vírus da estomatite papular bovina (BPSV) e um caso de coinfecção (VACV e um parapoxvírus semelhante ao Orf vírus). Os casos confirmados laboratorialmente ocorreram principalmente em bovinos leiteiros (19/25) e durante a estação seca (22/25). Em bovinos adultos, alterações macroscópicas foram observadas principalmente nas tetas e úbere e incluíram vesículas, úlceras, crostas, pápulas e cicatrizes e variaram quanto ao tipo, gravidade e região afetada, dependendo da espécie do poxvírus. Em bezerros, as principais lesões foram úlceras na boca e focinho. Lesões zoonóticas compatíveis com infecção por poxvírus foram observadas em todas as poxviroses diagnosticadas, afetando principalmente as mãos dos ordenhadores e outros trabalhadores rurais. Nossos dados demonstram a relevância sanitária e econômica dessas doenças e a ampla circulação de diferentes poxvírus em bovinos de GO.
Asunto(s)
Humanos , Animales , Bovinos , Infecciones por Poxviridae/diagnóstico , Infecciones por Poxviridae/epidemiología , Infecciones por Poxviridae/patología , Parapoxvirus/aislamiento & purificación , Virus Vaccinia/aislamiento & purificación , Virus de la Seudoviruela de las Vacas/aislamiento & purificación , Coinfección/veterinaria , Zoonosis ViralesRESUMEN
A retrospective study of poxvirus infections diagnosed in cattle from Goiás state (GO), Brazil, from 2010 to 2018, was performed. All cases have been investigated by the GO Official Veterinary Service (Agrodefesa), from which technical forms and protocols of veterinary diagnosis laboratories were reviewed. In most cases, samples of oral or cutaneous tissues and/or swabs were submitted for virological diagnosis by polymerase chain reaction (PCR) and/or virus isolation. Thirty seven outbreaks/cases of vesicular disease were notified in cattle of 25 counties; in 33 cases the animals presented lesions clinically compatible with poxviruses. The etiology of 25 out of 33 outbreaks/cases was confirmed as poxviruses by PCR and/or viral isolation: 13 as bovine vaccinia virus (VACV), six as pseudocowpox virus (PCPV), five as bovine papular stomatitis virus (BPSV) and one coinfection (VACV and an Orf virus-like parapoxvirus). The laboratory confirmed that cases occurred mainly in dairy cattle (19/25) and during the dry season (22/25). In adult cattle, gross changes were observed mainly in the teats and udder and included vesicles, ulcers, crusts, papules and scars and varied of type, severity and affected region, depending on the poxvirus species. In calves, the main lesions were ulcers in the mouth and muzzle. Zoonotic lesions compatible with poxvirus infections were observed for all diagnosed poxviruses, affecting especially the hands of milkers and other farm workers. Our data demonstrate the sanitary and economic relevance of these diseases and the wide circulation of different poxviruses in cattle from GO.(AU)
Foi realizado um estudo retrospectivo das infecções por poxvírus diagnosticadas em bovinos do estado de Goiás (GO), entre 2010 e 2018. Todos os casos foram investigados pela Agência Goiana de Defesa Agropecuária (Agrodefesa). Foram revisados formulários técnicos e protocolos de laboratórios de diagnóstico veterinário. Na maioria dos casos, amostras de tecidos orais ou cutâneos e/ou swabs foram encaminhadas para diagnóstico virológico. Foram notificados 37 surtos/casos de doença vesicular em bovinos em 25 municípios; em 33 casos os animais apresentavam lesões clinicamente compatíveis com poxvírus. A etiologia de 25 de 33 surtos/casos foi confirmada como poxvírus por PCR e/ou isolamento viral: 13 como vírus vaccínia (VACV), seis como vírus pseudocowpox (PCPV), cinco como vírus da estomatite papular bovina (BPSV) e um caso de coinfecção (VACV e um parapoxvírus semelhante ao Orf vírus). Os casos confirmados laboratorialmente ocorreram principalmente em bovinos leiteiros (19/25) e durante a estação seca (22/25). Em bovinos adultos, alterações macroscópicas foram observadas principalmente nas tetas e úbere e incluíram vesículas, úlceras, crostas, pápulas e cicatrizes e variaram quanto ao tipo, gravidade e região afetada, dependendo da espécie do poxvírus. Em bezerros, as principais lesões foram úlceras na boca e focinho. Lesões zoonóticas compatíveis com infecção por poxvírus foram observadas em todas as poxviroses diagnosticadas, afetando principalmente as mãos dos ordenhadores e outros trabalhadores rurais. Nossos dados demonstram a relevância sanitária e econômica dessas doenças e a ampla circulação de diferentes poxvírus em bovinos de GO.(AU)
Asunto(s)
Humanos , Animales , Bovinos , Virus Vaccinia/aislamiento & purificación , Parapoxvirus/aislamiento & purificación , Virus de la Seudoviruela de las Vacas/aislamiento & purificación , Infecciones por Poxviridae/diagnóstico , Infecciones por Poxviridae/patología , Infecciones por Poxviridae/epidemiología , Coinfección/veterinaria , Zoonosis ViralesRESUMEN
The present study aimed to evaluate the spatial distribution and risk factors for infection by Toxoplasma gondii in sheep in the state of Goiás, located in the central-western region of Brazil. Through the immunofluorescence antibody test (IFAT), the seroprevalence of anti-T. gondii antibodies was analyzed in 1000 blood serum samples obtained from sheep in all macro and micro regions of the state of Goiás. Data related to sex, age of the animals, size of the farm, type of farm, water source, veterinary assistance, replacement of the herd, presence of domestic cats, presence of wild cats and presence of other wild animals were obtained at the sampling time. The differences between the seroprevalences obtained in relation to the variables analyzed were estimated using Pearson's chi-square test (χ2). The odds ratio (OR) values for each risk factor evaluated were statistically analyzed with a confidence interval of 95%. Positivity for IgG anti-T. gondii was observed (titer ≥64) in 34.3% (343/1000) of the samples, which ranged from 26.9% (31/115) to 44.2% (53/120) and from 21.8 (12/55) to 55.2% (16 / 29), respectively in the analyzed mesoregions and microregions. In all investigated regions of the State of Goiás, serum-reactive animals were detected with the age of the animals, the source of water, the form of replacement of the herd and the presence of domestic cats and wild animals risk factors statistically associated with the occurrence of T. gondii in animals.