RESUMO

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by selective dopaminergic loss. Non dopaminergic neurotransmitters such as glutamate are also involved in PD progression. NMDA receptor/postsynaptic density protein 95 (PSD-95)/neuronal nitric oxide synthase (nNOS) activation is involved in neuronal excitability in PD. Here, we are focusing on the evaluating these post-synaptic protein levels in the 6-OHDA model of PD. Adult male C57BL/6 mice subjected to unilateral striatal injury with 6-OHDA were assessed at 1-, 2-, or 4-weeks post-lesion. Animals were subjected to an apomorphine-induced rotation test followed by the analysis of protein content, synaptic structure, and NOx production. All biochemical analysis was performed comparing the control versus lesioned sides of the same animal. 6-OHDA mice exhibited contralateral rotation activity, difficulties in coordinating movements, and changes in Iba-1 and glial fibrillary acidic protein (GFAP) expression during the whole period. At one week of survival, the mice showed a shift in NMDA composition, favoring the GluN2A subunit and increased PSD95 and nNOS expression and NOx formation. After two-weeks, a decrease in the total number of synapses was observed in the lesioned side. However, the number of excitatory synapses was increased with a higher content of GluN1 subunit and PSD95. After four weeks, NMDA receptor subunits restored to control levels. Interestingly, NOx formation in the serum increased. This study reveals, for the first time, the temporal course of behavioral deficits and glutamatergic synaptic plasticity through NMDAr subunit shift. Together, these data demonstrate that dopamine depletion leads to a fine adaptive response over time, which can be used for further studies of therapeutic management adjustments with the progression of PD.

RESUMO

BACKGROUND: Primary Health Care (PHC) is essential for effective, efficient, and more equitable health systems for all people, including those living with HIV/AIDS. This study evaluated the impact of the exposure to one of the largest community-based PHC programs in the world, the Brazilian Family Health Strategy (FHS), on AIDS incidence and mortality. METHODS AND FINDINGS: A retrospective cohort study carried out in Brazil from January 1, 2007 to December 31, 2015. We conducted an impact evaluation using a cohort of 3,435,068 ≥13 years low-income individuals who were members of the 100 Million Brazilians Cohort, linked to AIDS diagnoses and deaths registries. We evaluated the impact of FHS on AIDS incidence and mortality and compared outcomes between residents of municipalities with low or no FHS coverage (unexposed) with those in municipalities with 100% FHS coverage (exposed). We used multivariable Poisson regressions adjusted for all relevant municipal and individual-level demographic, socioeconomic, and contextual variables, and weighted with inverse probability of treatment weighting (IPTW). We also estimated the FHS impact by sex and age and performed a wide range of sensitivity and triangulation analyses; 100% FHS coverage was associated with lower AIDS incidence (rate ratio [RR]: 0.76, 95% CI: 0.68 to 0.84) and mortality (RR: 0.68, 95%CI: 0.56 to 0.82). FHS impact was similar between men and women, but was larger in people aged ≥35 years old both for incidence (RR: 0.62, 95% CI: 0.53 to 0.72) and mortality (RR: 0.56, 95% CI: 0.43 to 0.72). The absence of important confounding variables (e.g., sexual behavior) is a key limitation of this study. CONCLUSIONS: AIDS should be an avoidable outcome for most people living with HIV today and our study shows that FHS coverage could significantly reduce AIDS incidence and mortality among low-income populations in Brazil. Universal access to comprehensive healthcare through community-based PHC programs should be promoted to achieve the Sustainable Development Goals of ending AIDS by 2030.

Assuntos

Síndrome da Imunodeficiência Adquirida , Atenção Primária à Saúde , Humanos , Brasil/epidemiologia , Masculino , Feminino , Incidência , Adulto , Síndrome da Imunodeficiência Adquirida/mortalidade , Síndrome da Imunodeficiência Adquirida/epidemiologia , Estudos Retrospectivos , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Estudos de Coortes , População da América do Sul

RESUMO

Objetivo: Avaliar o risco de Lesão por Pressão em pessoas acamadas assistidas pela Estratégia Saúde da Família. Método: Estudo transversal, com abordagem quantitativa, realizado com 62 pacientes. A coleta de dados sucedeu-se por meio de questionário semiestruturado com dados sociodemográficos, clínicos e a avaliação do risco de Lesão por Pressão por meio da Escala de Braden. Os dados foram analisados pelo softwareestatístico Statistical Package for Social Science, versão 20.0. Resultados: Prevaleceram os pacientes do sexo feminino (61,3 %), cor branca (43,5%), viúvos (35,5%), aposentados (66,1%) e não alfabetizados (62,9%). O principal motivo de estar acamado foi devido a sequelas do Acidente Vascular Encefálico (35,5%). Evidenciou-se prevalência de risco muito alto em 59,7% das pessoas acamadas. Conclusão: O risco para Lesão por Pressão foi elevado, e a identificação dos fatores de risco é necessária e pode contribuir para estratégias preventivas ou redutoras deste agravo. (AU)

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Objective: To assess the risk of pressure ulcers in bedridden individuals assisted by the Family Health Strategy. Method: A cross-sectional study employing a quantitative approach was conducted with 62 patients. Data collection was performed through a semi-structured questionnaire, encompassing sociodemographic and clinical data, as well as the assessment of pressure ulcer risk using the Braden Scale. Data were analyzed using the Statistical Package for the Social Sciences software, version 20.0. Results: Female patients (61.3%), Caucasians (43.5%), widows (35.5%), married individuals (66.1%), and those with no formal education (62.9%) predominated. The primary reason for being bedridden was sequelae from a stroke (35.5%). A prevalence of very high risk was observed in 59.7% of bedridden individuals. Conclusion: The risk of pressure ulcers was high, emphasizing the necessity of identifying risk factors to inform preventive or mitigating strategies for this condition. (AU)

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Objetivo: Evaluar el riesgo de Úlceras por Presión en personas encamadas atendidas por la Estrategia Salud de la Familia. Método: Se realizó un estudio transversal con enfoque cuantitativo con 62 pacientes. La recolección de datos se realizó a través de un cuestionario semiestructurado con datos sociodemográficos y clínicos, así como la evaluación del riesgo de úlceras por presión utilizando la Escala de Braden. Los datos fueron analizados utilizando el softwareStatistical Package for Social Science, versión 20.0. Resultados: Predominaron pacientes de sexo femenino (61,3%), raza blanca (43,5%), viudas (35,5%), jubiladas (66,1%) y analfabetas (62,9%). El principal motivo de encamación fue por las secuelas de un accidente cerebrovascular (35,5%). Hubo una prevalencia de riesgo muy alta en el 59,7% de las personas encamadas. Conclusión: El riesgo de úlceras por presión fue alto, y la identificación de los factores de riesgo es necesaria y puede contribuir a estrategias preventivas o reductoras de esta condición. (AU)

Assuntos

Humanos , Adulto , Úlcera por Pressão , Estratégias de Saúde Nacionais

RESUMO

Objetivo: Verificar a autoeficácia no uso de preservativo de estudantes do curso de graduação em enfermagem de uma Universidade Pública Federal no interior de Minas Gerais. Métodos: Estudo observacional, transversal e descritivo com abordagem quantitativa, realizado com discentes de graduação em enfermagem. Utilizou-se um instrumento sociodemográfico e a Escala de Autoeficácia no Uso de Preservativos. Resultados: Participaram 148 estudantes, predominando na faixa etária de 18 a 25 anos (74,3%), de cor branca (52,7%), gênero feminino (82,4%) e heterossexuais (77,7%). Dos 117 (79,1%) com vida sexual ativa, 53 (45,3%) usam preservativo e 51 (43,6%) usam pílula ou injeção. Observou-se alta pontuação na autoeficácia no uso de preservativo. Houve diferenças significativas nas dimensões Habilidade, Assertividade e escore total da escala entre os que têm e os que não têm vida sexual ativa. Conclusão: Os estudantes mostraram ter conhecimento satisfatório sobre a autoeficácia do uso de preservativos, apesar da baixa adesão. Isso ressalta a importância de estratégias educativas focadas na prática efetiva e consistente do uso de preservativos para prevenção de Infecções Sexualmente Transmissíveis. (AU)

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Objective: Verify self-efficacy in condom use among undergraduate nursing students at a Federal Public University in the interior of Minas Gerais. Methods: This was an observational, cross-sectional, and descriptive study with a quantitative approach, conducted with undergraduate nursing students. Data were collected using a sociodemographic instrument and the Condom Use SelfEfficacy Scale. Results: A total of 148 students participated, predominantly aged 18 to 25 years (74.3%), identifying as white (52.7%), female (82.4%), and heterosexual (77.7%). Of the 117 students (79.1%) who were sexually active, 53 (45.3%) reported using condoms and 51 (43.6%) used pills or injections. High scores in condom use self-efficacy were observed. Significant differences were noted in the Skill, Assertiveness, and total score dimensions of the scale between sexually active and inactive students. Conclusion: The students demonstrated satisfactory knowledge regarding the self-efficacy of condom use, despite low adherence rates. This underscores the importance of educational strategies focused on effective and consistent condom use practices for the prevention of Sexually Transmitted Infections. (AU)

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Objetivo: Verificar la autoeficacia en el uso del preservativo entre estudiantes de enfermería de una Universidad Pública Federal del interior de Minas Gerais. Métodos: Estudio observacional, transversal y descriptivo con enfoque cuantitativo, realizado con estudiantes de grado en enfermería. Se utilizó un instrumento sociodemográfico y la Escala de Autoeficacia en el Uso de Preservativos. Resultados: Participaron 148 estudiantes, predominando en el rango de edad de 18 a 25 años (74,3%), de raza blanca (52,7%), género femenino (82,4%) y heterosexuales (77,7%). De los 117 (79,1%) con vida sexual activa, 53 (45,3%) usan preservativo y 51 (43,6%) usan píldora o inyección. Se observó un alto puntaje en la autoeficacia en el uso de preservativos. Hubo diferencias significativas en las dimensiones Habilidad, Asertividad y puntuación total de la escala entre los que tienen y no tienen vida sexual activa. Conclusión: Los estudiantes mostraron tener un conocimiento satisfactorio sobre la autoeficacia del uso de preservativos, apesar de la baja adhesión. Esto resalta la importancia de estrategias educativas enfocadas en la práctica efectiva y consistente del uso de preservativos para la prevención de Infecciones Sexualmente Transmisibles. (AU)

Assuntos

Infecções Sexualmente Transmissíveis , Autoeficácia , Planejamento Familiar , Minorias Sexuais e de Gênero

RESUMO

OBJECTIVE: To evaluate the antimicrobial activity of Brazilian honeys against oral microorganisms. DESIGN: Organic honeys (OH-1 to OH-8) were diluted (%-w/v) and sterilized by filtration. Antimicrobial activity was defined by determining MIC and CBM against oral Streptococcus. The component responsible for the antimicrobial action was defined by a catalase assay. Antibiofilm activity was evaluated against the monospecies biofilm of Streptococcus mutans  (ATCC 700610). RESULTS: OHs showed antimicrobial activity principally OH-1, OH-2, OH-3, and OH-7 with MIC values ​​ranging between 10 and 25%. The mechanism of action occurs mainly by hydrogen peroxide produced by honey enzymes. OH-1, OH-2, and OH-7 showed total biofilm destruction at low concentrations. CONCLUSION: Brazilian honeys have promising antimicrobial and antibiofilm activity with the potential to control oral microbiota.

Assuntos

Antibacterianos , Biofilmes , Mel , Testes de Sensibilidade Microbiana , Boca , Biofilmes/efeitos dos fármacos , Mel/análise , Brasil , Boca/microbiologia , Antibacterianos/farmacologia , Streptococcus mutans/efeitos dos fármacos , Streptococcus mutans/fisiologia , Humanos , Streptococcus/efeitos dos fármacos , Streptococcus/fisiologia

RESUMO

Zika virus (ZIKV) infections during pregnancy can result in Congenital Zika Syndrome (CZS), a range of severe neurological outcomes in fetuses that primarily occur during early gestational stages possibly due to placental damage. Although some placentas can maintain ZIKV persistence for weeks or months after the initial infection and diagnosis, the impact of this viral persistence is still unknown. Here, we aimed to investigate the immunological repercussion of ZIKV persistence in term placentas. As such, term placentas from 64 pregnant women diagnosed with Zika in different gestational periods were analyzed by ZIKV RT-qPCR, examination of decidua and placental villous histopathology, and expression of inflammation-related genes and IFNL1-4. Subsequently, we explored primary cultures of term decidual Extravillous Trophoblasts (EVTs) and Term Chorionic Villi (TCV) explants, as in vitro models to access the immunological consequences of placental ZIKV infection. Placenta from CZS cases presented low IFNL1-4 expression, evidencing the critical protective role of theses cytokines in the clinical outcome. Term placentas cleared for ZIKV showed increased levels of IFNL1, 3, and 4, whether viral persistence was related with a proinflammatory profile. Conversely, upon ZIKV persistence placentas with decidual inflammation showed high IFNL1-4 levels. In vitro experiments showed that term EVTs are more permissive, and secreted higher levels of IFN-α2 and IFN-λ1 compared to TCV explants. The results suggest that, upon ZIKV persistence, the maternal-skewed decidua contributes to placental inflammatory and antiviral signature, through chronic deciduitis and IFNL upregulation. Although further studies are needed to elucidate the mechanisms underlying the decidual responses against ZIKV. Hence, this study presents unique insights and valuable in vitro models for evaluating the immunological landscape of placentas upon ZIKV persistence.

RESUMO

BACKGROUND: In Chagas disease (CD), a neglected tropical disease caused by the parasite Trypanosoma cruzi, the development of mental disorders such as anxiety, depression, and memory loss may be underpinned by social, psychological, and biological stressors. Here, we investigated biological factors underlying behavioral changes in a preclinical model of CD. METHODOLOGY/PRINCIPAL FINDINGS: In T. cruzi-infected C57BL/6 mice, a kinetic study (5 to 150 days postinfection, dpi) using standardized methods revealed a sequential onset of behavioral changes: reduced innate compulsive behavior, followed by anxiety and depressive-like behavior, ending with progressive memory impairments. Hence, T. cruzi-infected mice were treated (120 to 150 dpi) with 10 mg/Kg/day of the selective serotonin reuptake inhibitor fluoxetine (Fx), an antidepressant that favors neuroplasticity. Fx therapy reversed the innate compulsive behavior loss, anxiety, and depressive-like behavior while preventing or reversing memory deficits. Biochemical, histological, and parasitological analyses of the brain tissue showed increased levels of the neurotransmitters GABA/glutamate and lipid peroxidation products and decreased expression of brain-derived neurotrophic factor in the absence of neuroinflammation at 150 dpi. Fx therapy ameliorated the neurochemical changes and reduced parasite load in the brain tissue. Next, using the human U-87 MG astroglioma cell line, we found no direct effect of Fx on parasite load. Crucially, serotonin/5-HT (Ser/5-HT) promoted parasite uptake, an effect increased by prior stimulation with IFNγ and TNF but abrogated by Fx. Also, Fx blocked the cytokine-driven Ser/5-HT-promoted increase of nitric oxide and glutamate levels in infected cells. CONCLUSION/SIGNIFICANCE: We bring the first evidence of a sequential onset of behavioral changes in T. cruzi-infected mice. Fx therapy improves behavioral and biological changes and parasite control in the brain tissue. Moreover, in the central nervous system, cytokine-driven Ser/5-HT consumption may favor parasite persistence, disrupting neurotransmitter balance and promoting a neurotoxic environment likely contributing to behavioral and cognitive disorders.

Assuntos

Astrócitos , Doença de Chagas , Fluoxetina , Camundongos Endogâmicos C57BL , Serotonina , Trypanosoma cruzi , Animais , Fluoxetina/farmacologia , Fluoxetina/uso terapêutico , Doença de Chagas/tratamento farmacológico , Doença de Chagas/psicologia , Trypanosoma cruzi/efeitos dos fármacos , Trypanosoma cruzi/fisiologia , Serotonina/metabolismo , Camundongos , Astrócitos/efeitos dos fármacos , Modelos Animais de Doenças , Encéfalo/efeitos dos fármacos , Encéfalo/parasitologia , Encéfalo/metabolismo , Comportamento Animal/efeitos dos fármacos , Masculino , Humanos , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Cognição/efeitos dos fármacos , Depressão/tratamento farmacológico , Carga Parasitária , Ansiedade/tratamento farmacológico

RESUMO

Background: Conditional Cash Transfers (CCT) are the world's most widely implemented interventions for poverty alleviation. Still, there is no solid evidence of the CCT effects on the reduction of the burden of Tuberculosis (TB) in marginalized and extremely vulnerable populations. We estimated the effect of the Bolsa Família Program (BFP), the largest CCT in the world, on TB incidence, mortality, and case-fatality rate using a nationwide cohort of 54.5 million individuals during a 12-year period in Brazil. Methods: We selected low-income individuals who entered in the 100 Million Brazilians Cohort and were linked to nationwide TB registries between 2004 to 2015, and compared BFP beneficiaries and non-beneficiaries using a quasi-experimental impact evaluation design. We employed inverse probability of treatment weighting (IPTW) multivariable Poisson regressions, adjusted for all relevant socioeconomic, demographic, and healthcare confounding variables - at individual and municipal level. Subsequently, we evaluated BFP effects for different subpopulations according to ethnoracial factors, wealth levels, sex, and age. We also performed several sensitivity and triangulation analyses to verify the robustness of the estimates. Findings: Exposure to BFP was associated with a large reduction in TB incidence in the low-income individuals under study (adjusted rate ratio [aRR]:0.59;95%CI:0.58-0.60) and mortality (aRR:0.69;95%CI:0.65-0.73). The strongest BFP effect was observed in Indigenous people both for TB incidence (aRR:0.37;95%CI:0.32-0.42), and mortality-aRR:0.35;95%CI:0.20-0.62), and in Black and Pardo people (Incidence-aRR:0.58;95%CI:0.57-0.59; Mortality -aRR:0.69;95%CI:0,64-0,73). BFP effects showed a clear gradient according to wealth levels and were considerably stronger among the extremely poor individuals for TB incidence (aRR:0.49, 95%CI:0.49-0.50) and mortality (aRR:0.60;95%CI:0.55-0.65). The BFP effects on case-fatality rates were also positive, however without statistical significance. Interpretation: CCT can strongly reduce TB incidence and mortality in extremely poor, Indigenous, Black and Pardo populations, and could significantly contribute to achieving the End TB Strategy targets and the TB-related Sustainable Development Goals.

RESUMO

The relationships between race, education, wealth, their intersections and AIDS morbidity/mortality were analyzed in retrospective cohort of 28.3 million individuals followed for 9 years (2007-2015). Together with several sensitivity analyses, a wide range of interactions on additive and multiplicative scales were estimated. Race, education, and wealth were each strongly associated with all of the AIDS-related outcomes, and the magnitude of the associations increased as intersections were included. A significantly higher risk of illness (aRR: 3.07, 95%CI:2.67-3.53) and death (aRR: 4.96, 95%CI:3.99-6.16) from AIDS was observed at the intersection of Black race, lower educational attainment, and less wealth. A higher case-fatality rate (aRR: 1.62, 95%CI:1.18-2.21) was also seen for the same intersectional group. Historically oppressed groups lying at the intersections of race, education, and wealth, had a considerably higher risk of illness and death from AIDS. AIDS-related interventions will require the implementation of comprehensive intersectoral policies that follow an intersectionality perspective.

RESUMO

Tumor necrosis factor (TNF) and interferon-gamma (IFNγ) are important inflammatory mediators in the development of cytokine storm syndrome (CSS). Single nucleotide polymorphisms (SNPs) regulate the expression of these cytokines, making host genetics a key factor in the prognosis of COVID-19. In this study, we investigated the associations of the TNF -308G/A and IFNG +874T/A polymorphisms with COVID-19. We analyzed the frequencies of the two polymorphisms in the control groups (CG: TNF -308G/A, n = 497; IFNG +874T/A, n = 397), a group of patients with COVID-19 (CoV, n = 222) and among the subgroups of patients with nonsevere (n = 150) and severe (n = 72) COVID-19. We found no significant difference between the genotypic and allelic frequencies of TNF -308G/A in the groups analyzed; however, both the frequencies of the high expression genotype (TT) (CoV: 13.51% vs. CG: 6.30%; p = 0.003) and the *T allele (CoV: 33.56% vs. CG: 24. 81%; p = 0.001) of the IFNG +874T/A polymorphism were higher in the COVID-19 group than in the control group, with no differences between the subgroups of patients with nonsevere and severe COVID-19. The *T allele of IFNG +874T/A (rs2430561) is associated with susceptibility to symptomatic COVID-19. These SNPs provided valuables clues about the potential mechanism involved in the susceptibility to developing symptomatic COVID-19.

Assuntos

COVID-19 , Predisposição Genética para Doença , Genótipo , Interferon gama , SARS-CoV-2 , Feminino , Humanos , Masculino , Alelos , COVID-19/genética , COVID-19/virologia , Síndrome da Liberação de Citocina/genética , Frequência do Gene , Interferon gama/genética , Polimorfismo de Nucleotídeo Único , SARS-CoV-2/patogenicidade , Fator de Necrose Tumoral alfa/genética

RESUMO

The re-emergence of yellow fever (YF) urged new mass vaccination campaigns and, in 2017, the World Health Organization approved the use of the fractional dose (FD) of the YF vaccine due to stock shortage. In an observational cross-sectional investigation, we have assessed viremia, antibodies, soluble mediators and effector and memory T and B-cells induced by primary vaccination of volunteers with FD and standard dose (SD). Similar viremia and levels of antibodies and soluble markers were induced early after immunization. However, a faster decrease in the latter was observed after SD. The FD led to a sustained expansion of helper T-cells and an increased expression of activation markers on T-cells early after vaccination. Although with different kinetics, expansion of plasma cells was induced upon SD and FD immunization. Integrative analysis reveals that FD induces a more complex network involving follicular helper T cells and B-cells than SD. Our findings substantiate that FD can replace SD inducing robust correlates of protective immune response against YF.

RESUMO

Living with extremely low-income is an important risk factor for HIV/AIDS and can be mitigated by conditional cash transfers. Using a cohort of 22.7 million low-income individuals during 9 years, we evaluated the effects of the world's largest conditional cash transfer, the Programa Bolsa Família, on HIV/AIDS-related outcomes. Exposure to Programa Bolsa Família was associated with reduced AIDS incidence by 41% (RR:0.59; 95%CI:0.57-0.61), mortality by 39% (RR:0.61; 95%CI:0.57-0.64), and case fatality rates by 25% (RR:0.75; 95%CI:0.66-0.85) in the cohort, and Programa Bolsa Família effects were considerably stronger among individuals of extremely low-income [reduction of 55% for incidence (RR:0.45, 95% CI:0.42-0.47), 54% mortality (RR:0.46, 95% CI:0.42-0.49), and 37% case-fatality (RR:0.63, 95% CI:0.51 -0.76)], decreasing gradually until having no effect in individuals with higher incomes. Similar effects were observed on HIV notification. Programa Bolsa Família impact was also stronger among women and adolescents. Several sensitivity and triangulation analyses demonstrated the robustness of the results. Conditional cash transfers can significantly reduce AIDS morbidity and mortality in extremely vulnerable populations and should be considered an essential intervention to achieve AIDS-related sustainable development goals by 2030.

Assuntos

Síndrome da Imunodeficiência Adquirida , População da América do Sul , Adolescente , Humanos , Feminino , Estudos de Coortes , Síndrome da Imunodeficiência Adquirida/epidemiologia , Síndrome da Imunodeficiência Adquirida/prevenção & controle , Renda , Pobreza , Brasil/epidemiologia

RESUMO

OBJECTIVE: Assess the level of measles vaccine-induced neutralizing antibodies against the D8 genotype and the persistence of humoral and cell-mediated immunity in children who received their first dose of the measles, mumps, and rubella vaccine eight years previously. METHODS: Measles-specific IgG and neutralizing antibodies were determined in serum using ELISA and plaque reduction neutralization test, respectively. Cellular response was evaluated from peripheral blood mononuclear cells (PBMC). IFN-γ-secreting cells, memory B and T cells, and immunological mediators were assayed by ELISpot, flow cytometry, and multiplex liquid microarray assay, respectively. RESULTS: Antibody concentrations declined over time; however, the vaccine-induced neutralizing antibodies' effect against D8 and vaccinal genotypes persisted. PBMC stimulated with the vaccine virus exhibited specific IFN- γ-measles-secreting responses in most participants. Participants with high levels of neutralizing antibodies showed a higher proportion of activated B cells compared to participants with low levels of neutralizing antibodies, while proportions of memory CD4+ and CD8+ T cells were similar between these groups. PBMC supernatant cytokine levels showed a significant difference between stimulated and non-stimulated conditions for IL-2, TNF-α, IL-10, and CXCL10. CONCLUSION: Despite the decline in antibody concentrations over time, the participants still demonstrated neutralizing capacity against the measles D8 genotype five to eight years after the second dose of the measles, mumps, and rubella vaccine. Additionally, most of the enrolled children exhibited cell-mediated immunity responses to measles virus stimulation.

Assuntos

Sarampo , Caxumba , Rubéola (Sarampo Alemão) , Criança , Humanos , Caxumba/prevenção & controle , Leucócitos Mononucleares , Vacina contra Sarampo-Caxumba-Rubéola , Brasil , Anticorpos Antivirais , Anticorpos Neutralizantes , Vacina contra Sarampo , Imunidade Celular , Rubéola (Sarampo Alemão)/prevenção & controle

RESUMO

The cGAS-STING pathway appears to contribute to dysregulated inflammation during coronavirus disease 2019 (COVID-19); however, inflammatory factors related to long COVID are still being investigated. In the present study, we evaluated the association of cGAS and STING gene expression levels and plasma IFN-α, TNF-α and IL-6 levels with COVID-19 severity in acute infection and long COVID, based on analysis of blood samples from 148 individuals, 87 with acute COVID-19 and 61 in the post-COVID-19 period. Quantification of gene expression was performed by real-time PCR, and cytokine levels were quantified by ELISA and flow cytometry. In acute COVID-19, cGAS, STING, IFN-α, TNF-α, and IL-6 levels were higher in patients with severe disease than in those with nonsevere manifestations (p < 0.05). Long COVID was associated with elevated cGAS, STING and IFN-α levels (p < 0.05). Activation of the cGAS-STING pathway may contribute to an intense systemic inflammatory state in severe COVID-19 and, after infection resolution, induce an autoinflammatory disease in some tissues, resulting in long COVID.

Assuntos

COVID-19 , Síndrome de COVID-19 Pós-Aguda , Humanos , Interferon-alfa , Interleucina-6 , Nucleotidiltransferases/genética , Nucleotidiltransferases/metabolismo , Transdução de Sinais/genética , Fator de Necrose Tumoral alfa/genética

RESUMO

In Brazil, the COVID-19 burden was substantial, and risk factors associated with higher in-hospital mortality rates have been extensively studied. However, information on short-term all-cause mortality and the factors associated with death in patients who survived the hospitalization period of acute SARS-CoV-2 infection is limited. We analyzed the six-month post-hospitalization mortality rate and possible risk factors of COVID-19 patients in a single center in Brazil. This is a retrospective cohort study focused on a six-month follow-up. The exclusion criteria were death during hospitalization, transference to another hospital, and age under 18. We collected data from the charts of all hospitalized patients from March 2020 to December 2020 with a positive RT-PCR test for SARS-CoV-2, resulting in a sample size of 106 patients. The main outcome was death after hospitalization, whereas comorbidities and demographics were evaluated as risk factors. The crude post-hospitalization death rate was 16%. The first 30 days of follow-up had the highest mortality rate. In a Cox regression model for post-hospitalization mortality, previous chronic kidney disease (HR, 4.06, 95%CI 1.46 - 11.30) and longer hospital stay (HR 1.01, 95%CI 1.00 - 1.02) were the only factors statistically associated with death. In conclusion, a high six-month all-cause mortality was observed. Within the six-month follow-up, a higher risk of death was observed for patients who had prior CKD and longer hospital stay. These findings highlight the importance of more intensive medical surveillance during this period.

Assuntos

COVID-19 , Insuficiência Renal Crônica , Humanos , Alta do Paciente , Assistência ao Convalescente , Estudos Retrospectivos , SARS-CoV-2

RESUMO

OBJECTIVE: This study aimed to assess the effect of titanium dioxide (TiO2) and silver (Ag) nanoparticles dispersed in glycerol or water, serving as optical clearing agents nanocolloids (OCAs-NC), for improving optical coherence tomography (OCT) images and highlighting incipient lesions in ex vivo human teeth. MATERIALS AND METHODS: Twelve human teeth with incipient lesions were divided into seven groups according to the OCA-NC; they were subjected to G1 (air), G2 (glycerol), G3 (TiO2 0.1%), G4 (TiO2 0.01%), G5 (TiO2 0.001%), G6 (AgNO3 10%), and G7 (AgNO3 100%). The OCA-NC was applied to the occlusal surface, and two-dimensional images of the specimens were analyzed using OCT (930 nm central wavelength; 100 nm bandwidth; 5 mW output power; axial resolution of 7/5.3 µm in water and air, respectively; lateral resolution of 8 µm; and light penetration depth of 1.6 mm inside the sample). RESULTS: The findings demonstrated that the utilization of OCAs-NC containing metallic or dielectric nanoparticles (AgNO3 and TiO2) led to improved differentiation between sound and demineralized enamel on occlusal surfaces. Additionally, it enhanced the depth of image penetration when analyzing this hard tissue with OCT. CLINICAL RELEVANCE: In the current context of minimally invasive dentistry, the use of OCAs-NC in conjunction with OCT can provide clinicians with early diagnosis, allowing for the determination of less/more invasive therapies and consequently halting the disease before cavitation of dental tissues occurs.

Assuntos

Cárie Dentária , Nanopartículas , Humanos , Suscetibilidade à Cárie Dentária , Glicerol , Tomografia de Coerência Óptica , Cárie Dentária/diagnóstico por imagem , Água

RESUMO

Dengue virus (DENV) is one of the most important and widespread arthropod-borne viruses, causing millions of infections over the years. Considering its epidemiological importance, efforts have been directed towards understanding various aspects of DENV biology, which have been facilitated by the development of different molecular strategies for engineering viral genomes, such as reverse genetics approaches. Reverse genetic systems are a powerful tool for investigating virus-host interaction, for vaccine development, and for high-throughput screening of antiviral compounds. However, stable manipulation of DENV genomes is a major molecular challenge, especially when using conventional cloning systems. To circumvent this issue, we describe a simple and efficient yeast-based reverse genetics system to recover infectious DENV clones.

Assuntos

Vírus da Dengue , Dengue , Humanos , Vírus da Dengue/genética , Genética Reversa , Ensaios de Triagem em Larga Escala , Genoma Viral , Dengue/genética , Replicação Viral/genética

RESUMO

Abstract The aim of the present study was to examine the relationships between gender, sense of coherence (SOC), social support, perception of academic environment and mental health of dental students during the coronavirus disease 2019 (COVID-19) pandemic. A longitudinal study involving 65 undergraduates enrolled from the first to sixth semesters in the bachelor dental course of Universidade Federal Fluminense, Brazil, was conducted. Baseline data (2018) included age, gender, SOC, social support, stress control and perception of education environment. Depression, anxiety and stress were assessed at baseline (response rate: 93%) and two-year follow-up (2020; response rate: 37%). Structural Equation Modelling was used to test the relationships between independent variables and depression, anxiety and stress during COVID-19 pandemic. Lower social support (β = -0.15), lower stress control (β = -0.20) and lower SOC (β = -0.39) were directly linked to higher depression (β = 0.22). Female gender (β = 0.22), worse perception of educational environment (β = -0.24) and lower SOC (β = -0.57) directly predicted higher anxiety. Female gender (β = 0.18), lower stress control (β = -0.21), and lower SOC (β = -0.46) directly predicted higher stress. The link between gender and both depression and stress, was mediated by stress control. Social support was indirectly linked to depression and stress via SOC. Perception of educational environment mediated the link between SOC and anxiety. Mental health of dental students during COVID-19 pandemic was influenced by demographic characteristics, perception of educational environment, social support and SOC through both direct and indirect pathways.

RESUMO

Resumen: El objetivo de este trabajo fue evaluar los factores explicativos de la respuesta inmune humoral en adultos mayores de establecimientos de estancia prolongada de Buenos Aires, Argentina, hasta 180 días post vacunación. Se utilizó un diseño de cohorte abierta, prospectiva, multicéntrica, con voluntarios que recibieron dos dosis de vacunas Sputnik V, Sinopharm o AZD1222. Se analizaron muestras de plasma en los tiempos 0, 21 días post primera dosis, 21 días post segunda dosis, 120 y 180 días post primera dosis. Se ajustaron modelos lineales marginales y aditivos generalizados mixtos para evaluar el comportamiento de la concentración de anticuerpos IgG anti-Spike en el tiempo según grupo de exposición (naïve/no-naïve) y vacuna. Las covariables analizadas fueron: ocurrencia de brote de COVID-19 en establecimientos de estancia prolongada y comorbilidades. Se incluyeron en el análisis 773 participantes con una mediana de edad de 83 años (RIQ: 76-89). Al final del estudio, los niveles de anticuerpos del grupo naïve: Sinopharm fueron significativamente menores que el resto de los grupos (p < 0,05); los del no-naïve: Sinopharm resultaron similares a los naïve que recibieron AZD1222 (p = 0,945) o Sputnik V (p = 1). Los participantes expuestos a brotes en establecimientos de estancia prolongada presentaron niveles de anticuerpos significativamente mayores, independientemente del grupo de exposición y la vacuna (p < 0,001). Concluimos que la exposición previa a COVID-19, el tipo de vacuna y la pertenencia a un establecimiento de estancia prolongada con antecedente de brote son factores a considerar frente a futuros eventos epidémicos con dinámicas de transmisión y mecanismos inmunológicos similares al COVID-19, en poblaciones similares a la analizada en este trabajo.

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Abstract: This study evaluated the explanatory factors of humoral immune response in older adults admitted to long-term care institutions in Buenos Aires, Argentina, up to 180 days after vaccination. An open-label, prospective, multicenter cohort study was conducted with volunteers who received two doses of the Sputnik V, Sinopharm, or AZD1222 vaccines. Plasma samples were analyzed at 0 and 21 days after the first dose, 21 days after the second dose, and 120 and 180 days after the first dose. Marginal linear models and generalized additives mixed models were adjusted to determine the behavior of anti-spike IgG antibody concentration over time according to exposure group (naïve/no-naïve) and vaccine. Occurrence of an outbreak of COVID-19 in long-term care institutions and comorbidities were the covariates analyzed. A total of 773 participants were included, with a mean age of 83 years (IQR: 76-89). Results showed that antibody levels in the naïve: Sinopharm group were significantly lower to the other groups (p < 0.05). Antibody levels in the no-naïve: Sinopharm group were similar to those in the naïve group who received AZD1222 (p = 0.945) or Sputnik V (p = 1). Participants exposed to outbreaks in long-term care institutions had significantly higher antibody levels, regardless of exposure group and vaccine (p < 0.001). In conclusion, previous exposure to COVID-19, type of vaccine, and admittance into a long-term care institution with a history of outbreaks are factors to be considered in future epidemic events with transmission dynamics and immunological mechanisms similar to COVID-19, in populations similar to the one analyzed.

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Resumo: Este estudo teve como objetivo avaliar os fatores explicativos da resposta imune humoral em idosos em instituições de longa permanência em Buenos Aires, Argentina, até 180 dias após a vacinação. Foi realizado um estudo de coorte aberto, prospectivo e multicêntrico, com voluntários que receberam duas doses das vacinas Sputnik V, Sinopharm ou AZD1222. As amostras de plasma foram analisadas nos tempos 0, 21 dias após a primeira dose, 21 dias após a segunda dose, 120 e 180 dias após a primeira dose. Os modelos lineares marginais e os aditivos generalizados mistos foram ajustados para determinar o comportamento da concentração de anticorpos IgG anti-Spike ao longo do tempo de acordo com o grupo de exposição (naïve/no-naïve) e vacina. As covariáveis analisadas foram ocorrência de pico de COVID-19 nas instituições de longa permanência e comorbidades. Foram incluídos 773 participantes, com média de idade de 83 anos (IIQ: 76-89). Os resultados apontaram níveis de anticorpos do grupo naïve: Sinopharm significativamente mais baixos do que os outros grupos (p < 0,05); e as variáveis do grupo no-naïve: Sinopharm foram semelhantes à do grupo naïve que recebeu AZD1222 (p = 0,945) ou Sputnik V (p = 1). Os participantes expostos a picos nas instituições de longa permanência apresentaram níveis de anticorpos significativamente maiores, independentemente do grupo de exposição e da vacina (p < 0,001). Conclui-se que a exposição prévia à COVID-19, tipo de vacina e adesão a uma instituição de longa permanência com histórico de pico são fatores a serem considerados em futuros eventos epidêmicos com dinâmica de transmissão e mecanismos imunológicos semelhantes à COVID-19, em populações semelhantes à analisada neste trabalho.

RESUMO

RESUMO Este artigo, orientado pelo referencial teórico foucaultiano, tem por objetivo analisar quais sujeitos emergem nos enunciados que compõem o texto oficial da Política Nacional de Saúde LGBT brasileira. Enxerga tal política pública de saúde como um artefato pedagógico incrementado pelo dispositivo da sexualidade, objetivando formas de vida e orientando o sujeito a dinamizar uma pedagogia de constituição de si com a finalidade de se fazer visível - tornar-se sujeito de direitos - frente às normas pautadas pelo Estado para controle de corpos-sexualidades. Reafirmamos que essa política de saúde é uma conquista oriunda de lutas pró-democráticas travadas pela comunidade LGBT ao longo de 40 anos, dentre outros movimentos. Todavia, podemos observar uma matriz biopolítica que a perpassa, elencando quais corpos devem ser assistidos pelo Estado; muitos deles indecifráveis e que escapam, pois suas performances na sociedade e as denominações às quais adotam para si não correspondem às regras de captura identitária nela postuladas.

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ABSTRACT This article, guided by the Foucauldian theoretical framework, aims to analyze which subjects emerge in the statements that make up the official text of the Brazilian National LGBT Health Policy, seeing such public health policy as a pedagogical artifact enhanced by the device of sexuality: aiming at forms of life , guiding the subject to stimulate a pedagogy of self-constitution with the purpose of making themselves visible - becoming a subject of rights - in the face of the norms set by the State for controlling bodies-sexualities. Finally, we reaffirm that this health policy is an achievement arising from pro-democratic struggles waged by the LGBT community over 40 years, among other movements. However, we can observe a biopolitical matrix that permeates it, listing which bodies should be assisted by the State; many of these are indecipherable and escape, because their performances in society and the names they adopt for themselves do not correspond to the rules of identity capture postulated in it.