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The yellow fever (YF) vaccine is one of the safest and most effective vaccines currently available. Still, its administration in people living with HIV (PLWH) is limited due to safety concerns and a lack of consensus regarding decreased immunogenicity and long-lasting protection for this population. The mechanisms associated with impaired YF vaccine immunogenicity in PLWH are not fully understood, but the general immune deregulation during HIV infection may play an important role. To assess if HIV infection impacts YF vaccine immunogenicity and if markers of immune deregulation could predict lower immunogenicity, we evaluated the association of YF neutralization antibody (NAb) titers with the pre-vaccination frequency of activated and exhausted T cells, levels of pro-inflammatory cytokines, and frequency of T cells, B cells, and monocyte subsets in PLWH and HIV-negative controls. We observed impaired YF vaccine immunogenicity in PLWH with lower titers of YF-NAbs 30 days after vaccination, mainly in individuals with CD4 count <350 cells/mm3. At the baseline, those individuals were characterized by having a higher frequency of activated and exhausted T cells and tissue-like memory B cells. Elevated levels of those markers were also observed in individuals with CD4 count between 500 and 350 cells/mm3. We observed a negative correlation between the pre-vaccination level of CD8+ T cell exhaustion and CD4+ T cell activation with YF-NAb titers at D365 and the pre-vaccination level of IP-10 with YF-NAb titers at D30 and D365. Our results emphasize the impact of immune activation, exhaustion, and inflammation in YF vaccine immunogenicity in PLWH.
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OBJECTIVE: To verify the effect of foot reflexology on the electrical muscle activity of the lateral and medial gastrocnemius muscle, and to examine the distribution, plantar pressure, and body sway in patients with type 2 diabetes mellitus. METHODS: This pilot randomized controlled trial enrolled 17 volunteers who were clinically diagnosed with diabetes mellitus. The sample was assigned to one of two groups: the control group (CG, n = 7), who received information on foot care and health, and the intervention group (IG, n = 10), who received the application of foot reflexology on specific areas of the feet, for 10 consecutive days. There was blinding of the evaluator and the therapist. Surface electromyography (EMG) was used to assess the electrical activity of the medial and lateral gastrocnemius muscles in maximum voluntary isometric contraction (MVIC) and isotonic contraction (IC); baropodometry and stabilometry were used to analyze unloading, plantar weight distribution, and body sway. RESULTS: There was a statistically significant difference for the variables of maximum peak electrical activity of the left medial gastrocnemius (p = 0.03; effect size = 0.87 and power = 0.81) and left lateral gastrocnemius muscles (p = 0.04, effect size = 0.70 and power = 0.66) respectively, in the intragroup IC, and median frequency of the left medial gastrocnemius muscle in the intragroup MVIC (p = 0.03; effect size = 0.64 and power = 0.59), and in the variables intergroups of the total area on the right side (p = 0.04; effect size = 1.03 and power = 0.50) and forefoot area on the left side (p = 0.02; effect size = 0.51 and power = 0.16). CONCLUSIONS: We conclude that foot reflexology influenced some variables of the intergroup plantar distribution and intragroup EMG in the sample studied. There is a need for a placebo group, a larger sample and a follow-up to strengthen the findings of these experiments.
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Diabetes Mellitus Tipo 2 , Manipulações Musculoesqueléticas , Humanos , Projetos Piloto , Pé/fisiologia , Eletromiografia , Músculo Esquelético/fisiologiaRESUMO
5-Azacitidine has been used before stem cell transplantation in juvenile myelomonocytic leukaemia (JMML) patients. Recently, we have described immunophenotypic features in JMML at diagnosis. Here, our aim was to examine the changes in the immunophenotypic features during azacitidine treatment, correlating it with clinical response. Patients treated with 5-azacitidine were evaluated at diagnosis and after three and six cycles of medication. Among 32 patients entering the study, 28 patients were examined after three cycles and 25 patients after six. Patients showed a reduction in CD34/CD117+ cells: median 3.35% at diagnosis, 2.8% after three cycles and 1.63% after six. B-cell progenitors were decreased at diagnosis and decreased after treatment. Monocytes decreased: 11.91% to 6.4% and 4.18% respectively. Complete response was associated with increase in classical monocytes. T lymphocytes, reduced at diagnosis, increased in patients responding to 5-azacitidine. Immunophenotypic aberrancies including expression of CD7 in myeloid progenitors remained after treatment. This feature was associated with a worse response to treatment, as well as presence of NF1. Immunophenotyping was feasible in all patients. Clinical response was associated with a decrease of myeloid progenitors and monocytes and a rise in T lymphocytes although phenotypic aberrancies persisted. The largest effect was observed after three cycles.
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Leucemia Mielomonocítica Juvenil , Antígenos CD34 , Azacitidina/uso terapêutico , Humanos , Imunofenotipagem , Contagem de LinfócitosRESUMO
Fear extinction (FExt) is used to treat patients with posttraumatic stress disorder (PTSD). However, fear related to traumatic events can be persistent and return even after successful extinction. The neurochemical control of extinction seems to be performed by several neurotransmitters, including dopamine (DA), through D1 and D2 receptors. Recently, we showed that intranasally applied DA (IN-DA) facilitated the FExt, but the mechanisms by which it promoted this effect are still unknown. This study focused on investigating whether these effects are mediated by the action of DA on D2-like receptors since these receptors seem to be related to neurochemical and molecular changes underlying extinction. Also, we investigated whether IN-DA treatment would affect conditioned fear-induced antinociception (Fear-IA). Rats treated with IN-DA (1 mg/kg) twenty-five minutes after sulpiride (SUL; 40 mg/kg, i.p., D2-antagonist) were subjected to the extinction of contextual fear. IN-DA applied before the extinction session induced the FExt and prevented Fear-IA. These effects were impaired by pre-treatment with SUL, suggesting that the IN-DA effects are mediated by DA on D2-like receptors. SUL per se also facilitated the FExt but did not affect Fear-IA. These data suggest IN-DA as a promising pharmacological tool to supplement the psychotherapy of patients suffering from PTSD.
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Condicionamento Psicológico/fisiologia , Antagonistas dos Receptores de Dopamina D2/farmacologia , Dopamina/farmacologia , Extinção Psicológica/fisiologia , Medo/fisiologia , Receptores de Dopamina D2/fisiologia , Sulpirida/farmacologia , Administração Intranasal , Animais , Condicionamento Psicológico/efeitos dos fármacos , Dopaminérgicos/farmacologia , Extinção Psicológica/efeitos dos fármacos , Masculino , Ratos , Sulpirida/antagonistas & inibidoresRESUMO
Resumo: Introdução: Como o tromboembolismo venoso (TEV) é uma das principais causas de mortes evitáveis em pacientes hospitalizados, é importante a criação de medidas para sua prevenção e seu tratamento. Porém, para a profilaxia de qualidade, a educação e o envolvimento dos pacientes são necessários, e uma das ferramentas para facilitar as atividades educativas em saúde são as tecnologias educacionais. Objetivo: Este estudo teve como objetivos construir e validar um aplicativo móvel sobre orientações para prevenção de TEV em pacientes hospitalizados durante a internação e após a alta hospitalar. Método: Trata-se de um estudo metodológico composto por duas fases (construção e validação), divididas em nove etapas. A fase de validação foi realizada com 11 juízes especialistas e 30 representantes do público-alvo. Utilizaram-se quatro instrumentos de coletas de dados: Suitability Assessment of Materials (SAM), Instrumento de Validação de Conteúdo Educativo em Saúde (IVCES), Instrumento de Avaliação para o Público-alvo e System Usability Scale (SUS), todos interpretados mediante avaliação específica. Resultado: Entre os juízes especialistas, a média da pontuação do SAM foi 89,4%, e a do IVCES, 93,8%. Em relação à opinião do público-alvo, a média de concordância no primeiro instrumento de coleta de dados foi 95%, e a do SUS, 79,5 pontos. Conclusão: O aplicativo móvel foi considerado válido mediante a metodologia aplicada por juízes especialistas e público-alvo.
Abstract: Introduction: Venous thromboembolism (TEV) is one of the main causes of preventable deaths in hospitalized patients. Therefore, it is important to create methods for its prevention and treatment. However, for quality prophylaxis, it is necessary to educate and involve patients, and one of the tools to facilitate educational activities in health is educational technologies. Objective: To build and validate a mobile application on guidelines for preventing TEV in hospitalized patients during hospitalization and after discharge from hospital. Methods: Methodological study consisting of two phases (construction and validation), divided into nine steps. The validation phase was carried out with 11 expert judges and 30 representatives of the target audience. Four data collection instruments were used: Suitability Assessment of Materials (SAM), Health Educational Content Validation Instrument (IVCES), Target Audience Assessment Instrument and System Usability Scale (SUS), all interpreted by specific evaluation. Results: Among the expert judges, the average score for the SAM was 89.4% and for the IVCES, 93.8%. In relation to the opinion of the target audience, the average agreement score in the first data collection instrument was 95% and for the SUS, 79.5 points. Conclusion: The mobile application was considered valid according to the methodology applied by the expert judges and target audience.
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The diagnosis of juvenile myelomonocytic leukaemia (JMML) is based on clinical, laboratory and molecular features but immunophenotyping [multiparametric flow cytometry (MFC)] has not been used routinely. In the present study, we describe the flow cytometric features at diagnosis with special attention to the distribution of monocytic subsets and the relation between MFC and molecular subgroups. MFC was performed with an eight-colour platform based on Euroflow. We studied 33 JMML cases. CD34+ /CD117+ /CD13+ cells >2% was found in 25 cases, and 51·5% presented an aberrant expression of CD7. A decrease of CD34+ /CD19+ /CD10+ cells was seen in eight cases and in four they were absent. The granulocytic population had a decreased side scatter in 29 cases. Bone marrow monocytic precursors were increased in 28 patients, with a decrease in classical monocytes (median 80·7%) and increase in CD16+ (intermediate and non-classical). A more pronounced increase in myeloid CD34+ cells was seen in patients with Neurofibromatosis type 1 (NF1) and tyrosine-protein phosphatase non-receptor type 11 (PTPN11), with aberrant CD7 expression in four of six and 10/12 patients respectively. Thus, JMML shows an immunophenotypic profile similar to myelodysplastic syndromes, and a different monocyte subset distribution when compared with chronic MML. MFC proved to be an important diagnostic tool that can help in differential diagnosis with other clonal diseases with monocytosis.
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Imunofenotipagem , Leucemia Mielomonocítica Juvenil/diagnóstico , Antígenos CD/análise , Antígenos CD/genética , Antígenos CD/imunologia , Medula Óssea/imunologia , Medula Óssea/patologia , Pré-Escolar , Feminino , Regulação Neoplásica da Expressão Gênica , Granulócitos/imunologia , Granulócitos/patologia , Humanos , Lactente , Leucemia Mielomonocítica Juvenil/genética , Leucemia Mielomonocítica Juvenil/imunologia , MasculinoRESUMO
The notion of superstitious behavior can provide a basic background for understanding such notions as illusions and beliefs. The present study investigated the social mechanism of the transmission of superstitious behavior in an experiment that utilized participant replacement. The sample was composed of a total of 38 participants. Participants performed a task on a computer: they could click a colored rectangle using the mouse. When the rectangle was in a particular color, the participants received points independently of their behavior (variable time schedule). When the color of the rectangle was changed, no points were presented (extinction). Under an Individual Exposure condition, ten participants worked alone on the task. Other participants were exposed to the same experimental task under a Social Exposure condition, in which each participant first learned by observation and then worked on the task in a participant replacement (chain) procedure. The first participant in each chain in the Social Exposure condition was a confederate who worked on the task "superstitiously," clicking the rectangle when points were presented. Superstitious responding was transmitted because of the behavior of the confederate. This also influenced estimates of personal control. These findings suggest that social learning can facilitate the acquisition and maintenance of superstitious behavior and the illusion of control. Our data also suggest that superstitious behavior and the illusion of control may involve similar learning principles.
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Abstract The notion of superstitious behavior can provide a basic background for understanding such notions as illusions and beliefs. The present study investigated the social mechanism of the transmission of superstitious behavior in an experiment that utilized participant replacement. The sample was composed of a total of 38 participants. Participants performed a task on a computer: they could click a colored rectangle using the mouse. When the rectangle was in a particular color, the participants received points independently of their behavior (variable time schedule). When the color of the rectangle was changed, no points were presented (extinction). Under an Individual Exposure condition, ten participants worked alone on the task. Other participants were exposed to the same experimental task under a Social Exposure condition, in which each participant first learned by observation and then worked on the task in a participant replacement (chain) procedure. The first participant in each chain in the Social Exposure condition was a confederate who worked on the task "superstitiously," clicking the rectangle when points were presented. Superstitious responding was transmitted because of the behavior of the confederate. This also influenced estimates of personal control. These findings suggest that social learning can facilitate the acquisition and maintenance of superstitious behavior and the illusion of control. Our data also suggest that superstitious behavior and the illusion of control may involve similar learning principles.
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Humanos , Adolescente , Adulto , Superstições/psicologia , Aprendizado Social , Pesquisa ComportamentalRESUMO
Very little is known about the immunomodulatory potential of secondary metabolites isolated from marine microorganisms. In the present study, we characterized pyrenocine A, which is produced by the marine-derived fungus Penicillium paxilli Ma(G)K and possesses anti-inflammatory activity. Pyrenocine A was able to suppress, both pretreatment and posttreatment, the LPS-induced activation of macrophages via the inhibition of nitrite production and the synthesis of inflammatory cytokines and PGE2. Pyrenocine A also exhibited anti-inflammatory effects on the expression of receptors directly related to cell migration (Mac-1) as well as costimulatory molecules involved in lymphocyte activation (B7.1). Nitrite production was inhibited by pyrenocine A in macrophages stimulated with CpG but not Poly I:C, suggesting that pyrenocine A acts through the MyD88-dependent intracellular signaling pathway. Moreover, pyrenocine A is also able to inhibit the expression of genes related to NF κ B-mediated signal transduction on macrophages stimulated by LPS. Our results indicate that pyrenocine A has promissory anti-inflammatory properties and additional experiments are necessary to confirm this finding in vivo model.