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As a developing region, Latin America faces unique cancer control and prevention challenges, which are intensified when considering rare cancers, including sarcomas. Sarcomas are a group of malignancies that arise in the connective tissues of the body-such as muscle, fat, nerves, blood vessels, and bones-accounting for a diverse range of tumours that, although rare, require specialized attention. Sarcoma care and research in Latin America require a comprehensive approach that includes deeper epidemiologic knowledge, diagnostic capacity building, access to innovative treatments, increased patient advocacy, and strengthening of clinical research capacity. This article will review current challenges and opportunities for treating patients with sarcoma in Latin America and outline a pathway toward improvement for regional collaborative groups.
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PURPOSE: Mutations of the KIT gene are the molecular hallmark of most GI stromal tumors (GISTs). Imatinib has revolutionized GIST treatment. Adjuvant imatinib for 3 years is the standard of care for high-risk resected GIST. However, the GIST molecular biologic profile has found different responses to this approach. Despite this, genetic testing at diagnosis is not a routine and empirical adjuvant imatinib remains the rule. Barriers to genetic profiling include concerns about the cost and utility of testing. This analysis aims to determine whether targeted genetic testing reduces costs as an ancillary tool for a limited-resource scenario instead of adjuvant empirical imatinib in patients with resected high-risk GIST. METHODS: The cost evaluation analysis of molecular testing for GIST was based on the Cost of Preventing an Event (COPE), considering the Number Needed to Treat and the costs of each test compared with the cost of 3-year empirical adjuvant imatinib and real treatment costs (median number of cycles) from the public and private Brazilian Healthcare System's perspective. The analysis compared the costs of the molecular tests (broad next-generation sequencing [NGS], GS Infinity DNA/RNA assay, and targeted NGS: GS Focus GIST and the Fleury GIST Tumor DNA sequencing panel), costs of drug acquisition, considering discounts (imatinib mesylate and Glivec), and the costs of supportive care. RESULTS: In both scenarios, public and private, regardless of the use of imatinib or Glivec, tailoring adjuvant treatment reduced costs, irrespective of the number of cycles. The only exception was the combination of the broad NGS test and imatinib in the Public Healthcare System. CONCLUSION: The molecularly tailored adjuvant imatinib reduced costs considering the COPE of available NGS tests for both the public and private Brazilian health care systems.
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Antineoplásicos , Tumores do Estroma Gastrointestinal , Humanos , Mesilato de Imatinib/uso terapêutico , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/genética , Antineoplásicos/uso terapêutico , Brasil , Quimioterapia Adjuvante , Testes GenéticosRESUMO
As zoonoses representam 75% das doenças emergentes. Estas doenças são uma ameaça permanente à saúde e bem-estar humanos, e têm o potencial de se tornar cada vez mais frequentes devido à degradação de habitats, alteração de utilização das terras, e aumento da mobilidade global de pessoas, animais e produtos animais. O objetivo deste estudo foi investigar o impacto de dez zoonoses (brucelose, cisticercose, equinococose, leishmaniose, leptospirose, doença de Lyme, raiva, toxoplasmose, triquinelose e febre do Nilo Ocidental) nos internamentos em hospitais do Serviço Nacional de Saúde português entre 2002 e 2016.(AU)
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Zoonoses/epidemiologia , Hospitalização/estatística & dados numéricos , Portugal , Raiva/epidemiologia , Triquinelose/epidemiologia , Febre do Nilo Ocidental/epidemiologia , Brucelose/epidemiologia , Cisticercose/epidemiologia , Doença de Lyme/epidemiologia , Leishmaniose/epidemiologia , Toxoplasmose/epidemiologia , Estudos Retrospectivos , Equinococose/epidemiologia , Leptospirose/epidemiologiaRESUMO
BACKGROUND: The anti-COVID-19 vaccines are new, and we should be alert of potential adverse effects of them. AIMS OF THE STUDY: To report a case of a large hemorrhagic stroke 5 days after ChAdOx1 nCoV-19 vaccination. METHODS: Clinical, imaging, and laboratory data of a patient with stroke admitted to our emergency department. RESULTS: A woman, 57 years old, took the first dose of the ChAdOx1 nCoV-19 vaccine and shortly thereafter presented mild systemic symptoms and started on aspirin. On day 5, she had a sudden onset of sweating and paleness, which has followed by left hemiparesis, vomiting, and somnolence. Computed tomography showed a large right deep frontal lobe parenchymal hematoma with the inundation of the entire ventricular system. Platelets count, fibrinogen, prothrombin time, and D-dimer were normal. Digital subtraction angiography did not show any signs of thrombosis or aneurysms in brain circulation. CONCLUSIONS: Clinicians should be aware of cerebrovascular adverse effects of ChAdOx1 nCoV-19, including out-of-context of vaccine-induced immune thrombotic thrombocytopenia.
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COVID-19 , ChAdOx1 nCoV-19/efeitos adversos , Acidente Vascular Cerebral Hemorrágico , Trombocitopenia , Vacinas contra COVID-19 , Feminino , Humanos , Pessoa de Meia-Idade , VacinaçãoRESUMO
Manganese porphyrins are well-known protectors against the deleterious effects of pro-oxidant species such as superoxide ions and hydrogen peroxide. The present study investigated the antioxidant cytochrome c-like activities of Mn(III)TMPyP [meso-tetrakis (4-N-methyl pyridinium) porphyrin] against superoxide ion and hydrogen peroxide that remained unexplored for this porphyrin. The association of TMPyP with a model of the inner mitochondrial membrane, cardiolipin (CL)-containing liposomes, shifted +30 mV vs. NHE (normal hydrogen electrode) redox potential of the Mn(II)/Mn(III) redox couple. In CL-containing liposomes, Mn(III)TMPyP was reduced by superoxide ions and recycled by Fe(III)cytochrome c to the oxidized form. Similarly, isolated rat liver mitoplasts added to a sample of Mn(II)TMPyP promoted immediate porphyrin reoxidation by electron transfer to the respiratory chain. These results show that Mn(III)TMPyP can act as an additional pool of Fe(III)cytochrome c capable of transferring electrons that escape from the IV complex back into the respiratory chain. Unlike Fe(II)cytochrome c, Mn(II)TMPyP was not efficient for hydrogen peroxide clearance. Therefore, by reducing cytochrome c, Mn(II)TMPyP can indirectly contribute to hydrogen peroxide elimination.
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Antioxidantes/química , Citocromos c/química , Mitocôndrias Hepáticas/enzimologia , Membranas Mitocondriais/enzimologia , Porfirinas/química , Animais , Ratos , Ratos WistarRESUMO
Monitoring of the suspended sediment concentration (SSC) is important for the analysis of morphological processes in watersheds and rivers, river habitats, and human activities associated with river management. Acoustic Doppler current profilers (ADCP) are used for measurements of flow and velocity in rivers through acoustic waves, which can also be converted into sediment concentrations. In this context, the objective is to verify the applicability of the use of ADCPs (Sontek YSI, model M9 River Surveyor) as an alternative for SSC estimates, this being a recent application of the equipment, mainly in rivers in the Amazon region rich in sediments in suspension. Thus, the Gartner method was used, calibrating its equation with the concentrations obtained by the point sampling method, collected with a bottle of Van Dorn in the Guamá River, Amazon, Brazil. The method used to obtain the SSC with data measured via ADCP resulted in a satisfactory estimate of the concentrations. The correlations between the measured and estimated sediment concentrations had R2 = 0.6827 for point sampling method and R2 = 0.8103 for vertically averaged SSC. These satisfactory results demonstrate the potential of using ADCP to estimate sediments suspended in Amazon basin.
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Sedimentos Geológicos , Rios , Acústica , Brasil , Monitoramento Ambiental , HumanosRESUMO
The present study aimed to investigate the influence of albumin structure and gold speciation on the synthesis of gold nanoparticles (GNPs). The strategy of synthesis was the addition of HAuCl4 solutions at different pH values (3-12) to solutions of human and bovine serum albumins (HSA and BSA) at the same corresponding pH values. Different pH values influence the GNP synthesis due to gold speciation. Besides the inherent effect of pH on the native structure of albumins, the use N-ethylmaleimide (NEM)-treated and heat-denaturated forms of HSA and BSA provided additional insights about the influence of protein structure, net charge, and thiol group approachability on the GNP synthesis. NEM treatment, heating, and the extreme values of pH promoted loss of the native albumin structure. The formation of GNPs indicated by the appearance of surface plasmon resonance (SPR) bands became detectable from 15 days of the synthesis processes that were carried out with native, NEM-treated and heat-denaturated forms of HSA and BSA, exclusively at pH 6 and 7. After 2 months of incubation, SPR band was also detected for all synthesis carried out at pH 8.0. The mean values of the hydrodynamic radius (RH) were 24 and 34 nm for GNPs synthesized with native HSA and BSA, respectively. X-ray diffraction (XRD) revealed crystallites of 13 nm. RH, XRD, and zeta potential values were consistent with GNP capping by the albumins. However, the GNPs produced with NEM-treated and heat-denaturated albumins exhibited loss of protein capping by lowering the ionic strength. This result suggests a significant contribution of non-electrostatic interactions of albumins with the GNP surface, in these conditions. The denaturation of proteins exposes hydrophobic groups to the solvent, and these groups could interact with the gold surface. In these conditions, the thiol blockage or oxidation, the latter probably favored upon heating, impaired the formation of a stable capping by thiol coordination with the gold surface. Therefore, the cysteine side chain of albumins is important for the colloidal stabilization of GNPs rather than as the reducing agent for the synthesis. Despite the presence of more reactive gold species at more acidic pH values, i.e., below 6.0, in these conditions the loss of native albumin structure impaired GNP synthesis. Alkaline pH values (9-12) combined the unfavorable conditions of denaturated protein structure with less reactive gold species. Therefore, an optimal condition for the synthesis of GNPs using serum albumins involves more reactive gold salt species combined with a reducing and negatively charged form of the protein, all favored at pH 6-7.
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Thioredoxins are multifunctional oxidoreductase proteins implicated in the antioxidant cellular apparatus and oxidative stress. They are involved in several pathologies and are promising anticancer targets. Identification of noncatalytic binding sites is of great interest for designing new allosteric inhibitors of thioredoxin. In a recent work, we predicted normal mode motions of human thioredoxin 1 and identified two major putative hydrophobic binding sites. In this work we investigated noncovalent interactions of human thioredoxin 1 with three phenotiazinic drugs acting as prooxidant compounds by using molecular docking and circular dichroism spectrometry to probe ligand binding into the previously predicted allosteric hydrophobic pockets. Our in silico and CD spectrometry experiments suggested one preferred allosteric binding site involving helix 3 and adopting the best druggable conformation identified by NMA. The CD spectra showed binding of thioridazine into thioredoxin 1 and suggested partial helix unfolding, which most probably concerns helix 3. Taken together, these data support the strategy to design thioredoxin inhibitors targeting a druggable allosteric binding site.
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Sítio Alostérico , Fenotiazinas/farmacologia , Tiorredoxinas/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Simulação de Acoplamento Molecular , Fenotiazinas/química , Ligação Proteica , Tiorredoxinas/químicaRESUMO
Os resíduos sólidos dos serviços de saúde (RSSS) oferecem risco potencial para saúde pública e meio ambiente perante um gerenciamento inadequado. Objetivou-se verificar aspectos do manejo interno dos RSSS do município paraense de Marituba. Através da aplicação de questionários e visitas de campo, realizou-se um estudo descritivo, observacional em treze estabelecimentos de saúde. O volume total de resíduos gerados era de cerca de 13.000kg/semana. Havia limitações nas diversas etapas do manejo interno, como a realização de tratamento interno somente num local, o armazenamento externo, que ocorria em quatro instituições e de maneira precária, entre outros. Também, havia conformidades como acondicionamento em sacos e recipientes adequados, segregação dos resíduos comuns. De modo geral, as normas federais não eram atendidas e o gerenciamento de RSSS dos estabelecimentos de saúde necessita de adequação na realização de todas as etapas do manejo, para controlar e diminuir os riscos e reduzir a quantidade de resíduos.
Medical wastes offer a potential risk to public health and the environment before an inadequate management. This study aims to verify aspects of internal handling of medical wastes in the city of Marituba, Pará State. By means of questionnaires and field visits, a descriptive and observational study was performed in 13 health establishments in the city. The total volume of generated medical wastes was about 13,000kg/week. There were deficiencies in many stages of the internal handling, for example the internal treatment that was performed in only one of the establishments, external storage made in 4 establishments and in precarious ways, among many others. Also, there were conformities as packing in adequate bags and containers as well as common waste separation. In general way, the federal norms were not accomplished and management of medical wastes in health establishments needs adequacy in every stage of the handling in order to control and reduce risks, decreasing the quantity of residues.
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Eliminação de Resíduos de Serviços de Saúde/normas , Brasil , Saúde da População UrbanaRESUMO
Medical wastes offer a potential risk to public health and the environment before an inadequate management. This study aims to verify aspects of internal handling of medical wastes in the city of Marituba, Pará State. By means of questionnaires and field visits, a descriptive and observational study was performed in 13 health establishments in the city. The total volume of generated medical wastes was about 13,000 kg/week. There were deficiencies in many stages of the internal handling, for example the internal treatment that was performed in only one of the establishments, external storage made in 4 establishments and in precarious ways, among many others. Also, there were conformities as packing in adequate bags and containers as well as common waste separation. In general way, the federal norms were not accomplished and management of medical wastes in health establishments needs adequacy in every stage of the handling in order to control and reduce risks, decreasing the quantity of residues.
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Eliminação de Resíduos de Serviços de Saúde/normas , Brasil , Saúde da População UrbanaRESUMO
O propósito deste estudo foi de apresentar uma avaliação não somente do método de expansão palatina, evidenciando os principais trabalhos, como também das possíveis alterações que poderão ocorrer no complexo dento facial dos indivíduos submetidos a esse tratamento, com o intuito de proporcionar aos ortodontistas uma visão geral desse importante meio auxiliar de tratamento, demonstrando as vantagens e desvantagens da aplicação clínica da expansão rápida do palato com o aparelho expansor Hyrax. Pode-se ainda constatar que a expansão palatina está indicada para tratamento de mordida cruzada esquelética, mordida cruzada posterior de grande magnitude, mordida cruzada total e atresia maxilar acompanhada de atresia do arco dentário inferior. Verificou-se também que a expansão rápida da maxila está indicada, em detrimento dos procedimentos de expansão lenta, sempre que se tenciona atingir o efeito ortopédico para o reposicionamento espacial da maxila e o ganho de tecido ósseo, dependendo do estágio de desenvolvimento oclusal