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Objective: to evaluate the immune response to the SARS-CoV-2 vaccines in adults with immune-mediated rheumatic diseases (IMRDs) in comparison to healthy individuals, observed 1-20 weeks following the fourth vaccine dose. Additionally, to evaluate the impact of immunosuppressive therapies, vaccination schedules, the time interval between vaccination and sample collection on the vaccine's immune response. Methods: We designed a longitudinal observational study conducted at the rheumatology department of Hospital de Copiapó. Neutralizing antibodies (Nabs) titers against the Wuhan and Omicron variant were analyzed between 1-20 weeks after administration of the fourth dose of the SARS-CoV-2 vaccine to 341 participants (218 IMRD patients and 123 healthy controls). 218 IMRD patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), systemic vasculitis (VS) and systemic scleroderma (SS) were analyzed. Results: Performing a comparison between the variants, Wuhan vs Omicron, we noticed that there were significant differences (p<0.05) in the level of the ID50, both for healthy controls and for patients with IMRDs. The humoral response of patients with IMRDs is significantly lower compared to healthy controls for the Omicron variant of SARS-CoV-2 (p = 0.0015). The humoral response of patients with IMRDs decreases significantly when the time interval between vaccination and sample collection is greater than 35 days. This difference was observed in the response, both for the Wuhan variant and for the Omicron variant. Conclusion: The IMRDs patients, the humoral response variation in the SARS-CoV-2 vaccine depends on doses and type of vaccine administered, the humoral response times and the treatment that these patients are receiving.
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Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Imunização Secundária , Doenças Reumáticas , SARS-CoV-2 , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/administração & dosagem , Anticorpos Neutralizantes/sangue , Anticorpos Neutralizantes/imunologia , Doenças Reumáticas/imunologia , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Adulto , Idoso , Estudos Longitudinais , VacinaçãoRESUMO
The essential yeast protein GPN-loop GTPase 1 (Npa3) plays a critical role in RNA polymerase II (RNAPII) assembly and subsequent nuclear import. We previously identified a synthetic lethal interaction between a mutant lacking the carboxy-terminal 106-amino acid tail of Npa3 (npa3ΔC) and a bud27Δ mutant. As the prefoldin-like Bud27 protein participates in ribosome biogenesis and translation, we hypothesized that Npa3 may also regulate these biological processes. We investigated this proposal by using Saccharomyces cerevisiae strains episomally expressing either wild-type Npa3 or hypomorphic mutants (Npa3ΔC, Npa3K16R, and Npa3G70A). The Npa3ΔC mutant fully supports RNAPII nuclear localization and activity. However, the Npa3K16R and Npa3G70A mutants only partially mediate RNAPII nuclear targeting and exhibit a higher reduction in Npa3 function. Cell proliferation in these strains displayed an increased sensitivity to protein synthesis inhibitors hygromycin B and geneticin/G418 (npa3G70A > npa3K16R > npa3ΔC > NPA3 cells) but not to transcriptional elongation inhibitors 6-azauracil, mycophenolic acid or 1,10-phenanthroline. In all three mutant strains, the increase in sensitivity to both aminoglycoside antibiotics was totally rescued by expressing NPA3. Protein synthesis, visualized by quantifying puromycin incorporation into nascent-polypeptide chains, was markedly more sensitive to hygromycin B inhibition in npa3ΔC, npa3K16R, and npa3G70A than NPA3 cells. Notably, high-copy expression of the TIF11 gene, that encodes the eukaryotic translation initiation factor 1A (eIF1A) protein, completely suppressed both phenotypes (of reduced basal cell growth and increased sensitivity to hygromycin B) in npa3ΔC cells but not npa3K16R or npa3G70A cells. We conclude that Npa3 plays a critical RNAPII-independent and previously unrecognized role in translation initiation.
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Fator de Iniciação 1 em Eucariotos , Higromicina B , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Núcleo Celular/metabolismo , Núcleo Celular/genética , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo , Higromicina B/farmacologia , Biossíntese de Proteínas/efeitos dos fármacos , Inibidores da Síntese de Proteínas/farmacologia , RNA Polimerase II/genética , RNA Polimerase II/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/crescimento & desenvolvimento , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas Monoméricas de Ligação ao GTP/genética , Proteínas Monoméricas de Ligação ao GTP/metabolismoRESUMO
Edible films elaborated from macromolecules, like carbohydrates, proteins, and lipids, must protect and maintain the integrity of foods during their handling, storage, and transportation. In this work, the effect of the concentration of zein (1-2% w/v), sodium alginate (1.5-2% w/v), and glycerol (2-4% w/v) on edible films physicochemical properties was evaluated. The Zein-Alginate-Glycerol interaction was evidenced by the FTIR analysis, the high permeability to water vapor and contact angles less than 90° of the polymer matrices formed. The film made with 2% zein, 1.5% sodium alginate and 4% glycerol preserved the quality of the chili pepper during 15 days of storage at 20 °C, the edible films allowed 3 more days of shelf life for weight loss and 10 more days for firmness. Edible films could be used in chili peppers that are destined for industrial processing, and before use, remove the film with a simple wash. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01393-z.
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In Chagas disease, the mechanisms involved in cardiac damage are an active field of study. The factors underlying the evolution of lesions following infection by Trypanosoma cruzi and, in some cases, the persistence of its antigens and the host response, with the ensuing development of clinically observable cardiac damage, are analyzed in this review.
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Over the last decades, the challenges in survival models have been changing considerably and full probabilistic modeling is crucial in many medical applications. Motivated from a new biological interpretation of cancer metastasis, we introduce a general method for obtaining more flexible cure rate models. The proposal model extended the promotion time cure rate model. Furthermore, it includes several well-known models as special cases and defines many new special models. We derive several properties of the hazard function for the proposed model and establish mathematical relationships with the promotion time cure rate model. We consider a frequentist approach to perform inferences, and the maximum likelihood method is employed to estimate the model parameters. Simulation studies are conducted to evaluate its performance with a discussion of the obtained results. A real dataset from population-based study of incident cases of melanoma diagnosed in the state of São Paulo, Brazil, is discussed in detail.
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Melanoma , Modelos Estatísticos , Humanos , Funções Verossimilhança , Análise de Sobrevida , Distribuição de Poisson , Brasil , Melanoma/terapiaRESUMO
Extracts of Hibiscus sabdariffa L. (commonly called Rosselle or "Jamaica flower" in Mexico) have been shown to have antibiotic and antivirulence properties in several bacteria. Here, an organic extract of H. sabdariffa L. is shown to inhibit motility in Salmonella enterica serovars Typhi and Typhimurium. The compound responsible for this effect was purified and found to be the hibiscus acid. When tested, this compound also inhibited motility and reduced the secretion of both flagellin and type III secretion effectors. Purified hibiscus acid was not toxic in tissue-cultured eukaryotic cells, and it was able to reduce the invasion of Salmonella Typhimurium in epithelial cells. Initial steps to understand its mode of action showed it might affect membrane proton balance.
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Antibacterianos/farmacologia , Citratos/farmacologia , Flagelos/fisiologia , Flores/química , Hibiscus/química , Extratos Vegetais/farmacologia , Salmonella enterica/efeitos dos fármacos , Flagelos/efeitos dos fármacosRESUMO
In this article, we discuss an extension of the classical negative binomial cure rate model with piecewise exponential distribution of the time to event for concurrent causes, which enables the modeling of monotonic and non-monotonic hazard functions (ie, the shape of the hazard function is not assumed as in traditional parametric models). This approach produces a flexible cure rate model, depending on the choice of time partition. We discuss local influence on this negative binomial power piecewise exponential model. We report on Monte Carlo simulation studies and application of the model to real melanoma and leukemia datasets.
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Melanoma , Modelos Estatísticos , Simulação por Computador , Humanos , Melanoma/diagnóstico , Melanoma/terapia , Método de Monte Carlo , Análise de SobrevidaRESUMO
Although disasters threaten all people who experience them, they do not affect all members of society in the same way. Its effects are not solely restricted to the economic sphere; they also affect the physical and mental health of those who suffer from them, having a particular impact on women and limiting their life chances. The aim of this study was to examine the impact the 2010 Haiti earthquake had on the seropositivity of female survivors. METHOD: Using data from the Demographic and Health Survey, this study examines the impact of the 2010 Haiti earthquake on gender relations associated with the probability of being HIV positive through the differences-in-differences strategy. RESULTS: A differential of four percentage points is observed in the probability of HIV seropositivity between men and women, favoring men. Additionally, it is observed that the probability of seropositivity intensifies when the cohabitation household is headed by a woman. CONCLUSION: Disasters are not indifferent to the gender of the people affected. In the second decade of the 21st century, the conclusions obtained show, once again, the need for incorporating the gender perspective into the management of natural hazards in the field of health. This is the case of the differential exposure to HIV after the earthquake in Haiti.
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Desastres , Terremotos , Infecções por HIV , Feminino , Infecções por HIV/epidemiologia , Haiti/epidemiologia , Humanos , Masculino , SobreviventesRESUMO
Cardiopathy is a common, irreversible manifestation of the chronic phase of Chagas disease; however, there is controversy as to how the causes for progression from the acute to the chronic phase are defined. In this work, the presence of the parasite is correlated with the occurrence of cell infiltration and fibrosis in cardiac tissues, as well as IgG detection and disease progression in a murine model. Fifty CD1 mice were infected intraperitoneally with Trypanosoma cruzi, while 30 control were administered with saline solution. Parasitemia levels were determined, and IgG titers were quantified by ELISA. At different times, randomly selected mice were euthanized, and the heart was recovered. Cardiac tissue slides were stained with HE and Masson trichrome stain. A significant increase in parasitemia levels was observed after 15 days post-infection (dpi), with a maximum of 4.1 × 106 parasites on 33 dpi, ending on 43 dpi; amastigote nests were observed on 15-62 dpi. Histological analysis revealed lymphocytic infiltration and fibrotic lesions from 8 dpi until the end of the study, on 100 dpi. The presence of plasma cells in the myocardium observed on 40-60 dpi, accompanied by seropositivity to ELISA on 40-100 dpi, was regarded as the hallmark of the transition phase. Meanwhile, the chronic phase, characterized by the absence of amastigotes, presence of cell infiltration, fibrotic lesions, and seropositivity, started on 62 dpi. A strong correlation between parasitemia and the presence of amastigote nests was found (r 2 = 0.930), while correlation between the presence of fibrosis and of amastigote nests was weak (r 2 = 0.306), and that between fibrosis and lymphocyte infiltration on 100 dpi was strong (r 2 = 0.899). The murine model is suitable to study Chagas disease, since it can reproduce the chronic and acute phases of the human disease. The acute phase was determined to occur on 1-60 dpi, while the chronic phase starts on 62 dpi, and fibrotic damage is a consequence of the continuous inflammatory infiltration; on the other hand, fibrosis was determined to start on the acute phase, being more apparent in the chronic phase, when Chagas disease-related cardiopathy is induced.
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INTRODUCTION: Macular hemorrhages result in a sudden and profound loss of vision. The primary treatment modalities include observation, intravitreal injection of antiangiogenic drugs, neodymium-doped yttrium aluminum garnet hialoidotomy, intravitreal injection of gas with or without tissue plasminogen activator, as monotherapy or combined with surgery. In this paper, we report four cases of macular hemorrhages of different causes treated with different approaches, and we review the literature in this regard. CASE PRESENTATION: All four patients presented different causes of macular hemorrhage. The first case had a preretinal hemorrhage due to a Valsalva retinopathy and was treated with surgery. Case 2 had a multilevel macular hemorrhage due to a rupture of a retinal arteriolar macroaneurysm and was treated with pneumatic displacement, laser, and intravitreal ranibizumab. Case 3 presented an extensive subretinal hemorrhage due to a choroidal rupture after high-energy ocular trauma that was also successfully treated with surgery. The last case was a preretinal hemorrhage due to diabetic retinopathy managed with neodymium-doped yttrium aluminum garnet laser. Different treatment approaches were successfully performed in all cases with good outcomes. CONCLUSION: There is an extensive range of options available for the management of macular hemorrhages, and the best option depends on the characteristics of each particular case. Proper and timely management of these diseases can achieve an excellent visual outcome, especially if the location of the hemorrhage is preretinal.
INTRODUCCIÓN: Las hemorragias maculares producen una pérdida de la visión súbita y profunda. Las principales modalidades de tratamiento incluyen observación, inyección intravítrea de fármacos antiangiogénicos, hialoidotomía con láser neodymium-doped yttrium aluminium garnet, inyección intravítrea de gas y/o activador de plasminógeno tisular, en monoterapia o combinadas con cirugía. En el presente trabajo reportamos cuatro casos de hemorragias maculares de distintas causas, tratadas con diferentes abordajes, y realizamos una revisión de la literatura al respecto. PRESENTACIÓN DE CASOS: Los cuatro pacientes mostrados presentaron diferentes causas de hemorragias maculares. El primer caso tuvo una hemorragia prerretiniana debido a retinopatía de Valsalva y fue tratado con cirugía, el Caso 2 tuvo una hemorragia macular multinivel debido a una rotura de un macroaneurisma arteriolar retiniano y fue manejado con desplazamiento neumático, láser y ranibizumab intravítreo, el Caso 3 presentó una hemorragia subretiniana extensa debido a rotura coroidea posterior a un trauma ocular cerrado de alta energía y fue tratado exitosamente con cirugía. El último caso presentó una hemorragia prerretiniana debido a retinopatía diabética, manejada con láser neodymium-doped yttrium aluminium garnet. Los diferentes tratamientos fueron realizados exitosamente con buenos resultados. CONCLUSIÓN: Existen amplias opciones disponibles para el manejo de las hemorragias maculares y la mejor opción depende de las características de cada caso en particular. El manejo apropiado y oportuno de éstas puede lograr un resultado visual bueno, especialmente si la localización de la hemorragia es prerretiniana.