Host-directed therapies are emerging as a promising tool in the curing of difficult-to-treat infections, such as those caused by drug-resistant bacteria. In this study, we aim to test the potential ...activity of the FDA- and EMA-approved drugs cysteamine and cystamine against
. In human macrophages (differentiated THP-1 cells), these drugs restricted
growth similar to that achieved by amikacin. Here, we use the human ex vivo granuloma-like structures (GLS) model of infection with the
rough (MAB-R) and smooth (MAB-S) variants to study the activity of new therapies against
. We demonstrate that cysteamine and cystamine show a decrease in the number of total GLSs per well in the MAB-S and MAB-R infected human peripheral blood mononuclear cells (PBMCs). Furthermore, combined administration of cysteamine or cystamine with amikacin resulted in enhanced activity against the two
morpho variants compared to treatment with amikacin only. Treatment with cysteamine and cystamine was more effective in reducing GLS size and bacterial load during MAB-S infection compared with MAB-R infection. Moreover, treatment with these two drugs drastically quenched the exuberant proinflammatory response triggered by the MAB-R variant. These findings showing the activity of cysteamine and cystamine against the R and S
morphotypes support the use of these drugs as novel host-directed therapies against
infections.
Commercially available Interferon-γ release assays (IGRAs), including the last-generation QuantiFERON TB-Plus (QFT-Plus), are effective in aiding the diagnosis of tuberculosis (TB) infection but ...cannot distinguish latent TB subjects from active TB patients. The aim of this study was to prospectively evaluate the performance of an HBHA-based IGRA, combined with commercially available IGRAs, to assess their usefulness as a prognostic biomarkers and aid in the monitoring of TB treatment in children. Following clinical, microbiological, and radiological assessment, children younger than 18 years of age classified as either LTBI or active TB were tested at baseline and during treatment by the QuantiFERON TB-Plus (QFT) assay and an aliquot of whole-blood was stimulated with HBHA. Among the 655 children evaluated, 559 (85.3%) were classified as “Non TB”, 44 patients (6.7%) with active TB, and 52 (7.9%) with LTBI. The median HBHA-IGRA IFN-gamma responses were able to discriminate active TB from LTBI (0.13 IU/ml vs 1.995, (
p
< 0,0001), those with asymptomatic TB from those with symptomatic TB (1.01 IU/ml vs 0.115 IU/ml,
p
0.017), or more severe TB (p 0.022), and significantly raised during successful TB treatment (
p
< 0.0001). Conversely, CD4 + and CD8 + responses were similar in all groups of patients, although active TB patients had higher CD4 + responses and LTBI higher CD8 + responses.
Conclusion
: HBHA-based IGRA, combined with CD4 + and CD8 + responses assessed by commercially available IGRAs, is a useful support in the characterization of the TB spectrum in children and monitoring of TB-therapy.
What is Known:
• Current immune diagnostics are not able to discriminate active and latent Ttuberculosis, including the recently approved QFT-PLUS.
.
• New immunological assays with prognostic value are highly needed
.
What is New:
• HBHA-based IGRA, combined with CD4
+
and CD8
+
responses assessed by commercially available IGRAs, is a useful support for the differentiation of active and latent TB in children.
.
• HBHA-based IGRA, combined with CD4
+
and CD8
+
responses assessed by commercially available IGRAs, is a useful support in the monitoring of TBtherapy in children.
.
Background. The profile of cellular immunological responses of children across the spectrum of COVID-19, ranging from acute SARS-CoV-2 infection to full recovery or Long COVID, has not yet been fully ...investigated. Methods. We examined and compared cytokines in sera and cell subsets in peripheral blood mononuclear cells (B and regulatory T lymphocytes) collected from four distinct groups of children, distributed as follows: younger than 18 years of age with either acute SARS-CoV-2 infection (n = 49); fully recovered from COVID-19 (n = 32); with persistent symptoms (Long COVID, n = 51); and healthy controls (n = 9). Results. In the later stages after SARS-CoV-2 infection, the cohorts of children, both with recovered and persistent symptoms, showed skewed T and B subsets, with remarkable differences when compared with children at the onset of the infection and with controls. The frequencies of IgD+CD27− naïve B cells, IgD+IgM+ and CD27−IgM+CD38dim B cells were higher in children with recent infection than in those with an older history of disease (p < 0.0001 for all); similarly, the total and natural Tregs compartments were more represented in children at onset when compared with Long COVID (p < 0.0001 and p = 0.0005, respectively). Despite the heterogeneity, partially due to age, sex and infection incidence, the susceptibility of certain children to develop persistent symptoms after infection appeared to be associated with the imbalance of the adaptive immune response. Following up and comparing recovered versus Long COVID patients, we analyzed the role of circulating naïve and switched B and regulatory T lymphocytes in counteracting the evolution of the symptomatology emerged, finding an interesting correlation between the amount and ability to reconstitute the natural Tregs component with the persistence of symptoms (linear regression, p = 0.0026). Conclusions. In this study, we suggest that children affected by Long COVID may have a compromised ability to switch from the innate to the adaptive immune response, as supported by our data showing a contraction of naïve and switched B cell compartment and an unstable balance of regulatory T lymphocytes occurring in these children. However, further prospective immunological studies are needed to better clarify which factors (epigenetic, diet, environment, etc.) are involved in the impairment of the immunological mechanisms in the Long COVID patients.
Gesellschaftskritik von rechts hat Konjunktur: Rechtspopulistische Parteien und Bewegungen erklären sich derzeit in vielen Staaten zum Sprachrohr (angeblich) unterdrückter Meinungen. Nicht erst seit ...der Covid-19-Pandemie ist das Internet dabei zentraler Schauplatz der Auseinandersetzungen. Der These folgend, dass rechtsextreme Narrative inzwischen auch in gesamtgesellschaftlichen Debatten ausgemacht werden können, haben wir Videos der Social-Media-Plattform YouTube auf diese Narrative analysiert. Gemeinsamen Bezug bilden die jüngsten Ereignisse um die Regulierung von Abtreibung in Polen, wo im Oktober 2020 das geltende Abtreibungsrecht für verfassungswidrig erklärt wurde, und Argentinien, dessen Regierung Abtreibung am 30. Dezember 2020 legalisierte. Während im analysierten Diskursausschnitt Frauenrechte und eine liberale Abtreibungspolitik oft positive Bewertung finden, bieten diese Themen auch Anlass hitziger Debatten, die häufig in Beleidigung, Herabwürdigung oder Hass umschlagen. Sexismus, Misogynie und vor allem Antifeminismus können dabei als besonders geeignete Anknüpfungspunkte für rechtsextreme Inhalte identifiziert werden.
Gesellschaftskritik von rechts hat Konjunktur: Rechtspopulistische Parteien und Bewegungen erklären sich derzeit in vielen Staaten zum Sprachrohr (angeblich) unterdrückter Meinungen. Nicht erst seit ...der Covid-19-Pandemie ist das Internet dabei zentraler Schauplatz der Auseinandersetzungen. Der These folgend, dass rechtsextreme Narrative inzwischen auch in gesamtgesellschaftlichen Debatten ausgemacht werden können, haben wir Videos der Social-Media-Plattform YouTube auf diese Narrative analysiert. Gemeinsamen Bezug bilden die jüngsten Ereignisse um die Regulierung von Abtreibung in Polen, wo im Oktober 2020 das geltende Abtreibungsrecht für verfassungswidrig erklärt wurde, und Argentinien, dessen Regierung Abtreibung am 30. Dezember 2020 legalisierte. Während im analysierten Diskursausschnitt Frauenrechte und eine liberale Abtreibungspolitik oft positive Bewertung finden, bieten diese Themen auch Anlass hitziger Debatten, die häufig in Beleidigung, Herabwürdigung oder Hass umschlagen. Sexismus, Misogynie und vor allem Antifeminismus können dabei als besonders geeignete Anknüpfungspunkte für rechtsextreme Inhalte identifiziert werden.
A finales de 2017, una pareja de Austria comenzó a construir un asentamiento proyectado para albergar eventualmente hasta 20 000 habitantes en 16 kilómetros cuadrados del departamento de Caazapá, en ...Paraguay, al que llamaron El Paraíso Verde. La convocatoria, difundida en diversas páginas web y canales de YouTube, apuntaba a un ciudadano germanohablante desencantado de las políticas migratorias de la Unión Europea respecto a los refugiados y en búsqueda de una vida más < >. La llegada de la pandemia de covid-19 se usó para enfatizar la necesidad de emigrar. Paraguay ponía menos restricciones de circulación y la vacunación no era obligatoria. Desde entonces, la migración al país se ha intensificado. Este estudio responde a cómo se representan las desigualdades en tiempos de la pandemia en el marco de un proyecto de migración europea a Paraguay. Para responder esta pregunta, enmarco este tipo de migración en la llamada migración de estilo de vida (Benson y O'Reilly, 2009), que supone un grado de privilegio en los sujetos migrantes y se construye sobre imaginarios coloniales. Utilizando herramientas del análisis de discurso, muestro cómo los colonos de habla alemana tematizan las desigualdades en lo concerniente al sistema de salud paraguayo bajo un prisma colonial e inscrito en el movimiento new age llamado Anastasia, y lo contrasto con la visión que brindan los vecinos de la comunidad en comentarios de Facebook en un canal de noticias local, donde destacan que los migrantes extranjeros están protegidos por el poder político local, es decir, en un marco más amplio de corrupción estructural, y denuncian distintas formas de clientelismo.
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