167,374 research outputs found

    T4 apoptosis in the acute phase of SARS-CoV-2 infection predicts long COVID

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    BackgroundAs about 10% of patients with COVID-19 present sequelae, it is important to better understand the physiopathology of so-called long COVID.MethodTo this aim, we recruited 29 patients hospitalized for SARS-CoV-2 infection and, by Luminex®, quantified 19 soluble factors in their plasma and in the supernatant of their peripheral blood mononuclear cells, including inflammatory and anti-inflammatory cytokines and chemokines, Th1/Th2/Th17 cytokines, and endothelium activation markers. We also measured their T4, T8 and NK differentiation, activation, exhaustion and senescence, T cell apoptosis, and monocyte subpopulations by flow cytometry. We compared these markers between participants who developed long COVID or not one year later.ResultsNone of these markers was predictive for sequelae, except programmed T4 cell death. T4 lymphocytes from participants who later presented long COVID were more apoptotic in culture than those of sequelae-free participants at Month 12 (36.9 ± 14.7 vs. 24.2 ± 9.0%, p = 0.016).ConclusionsOur observation raises the hypothesis that T4 cell death during the acute phase of SARS-CoV-2 infection might pave the way for long COVID. Mechanistically, T4 lymphopenia might favor phenomena that could cause sequelae, including SARS-CoV-2 persistence, reactivation of other viruses, autoimmunity and immune dysregulation. In this scenario, inhibiting T cell apoptosis, for instance, by caspase inhibitors, could prevent long COVID

    Hypersensibilité aux venins d’hyménoptères : le point en 2023 [Hymenoptera venom allergy: what's new in 2023]

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    Hymenoptera venom allergy is a central thematic in allergology. The recent limitation in the obtention of certain venom products has forced Swiss centers to adapt their diagnostic and therapeutical approaches. In this review, we will discuss diagnostics tools using recombinants serologies, recent recommendations for the screening of indolent systemic mastocytosis and the different immunotherapy protocols available for venom desensitization using aqueous and aluminum hydroxide-adsorbed purified venoms

    Table_6_Impaired macrophage and memory T-cell responses to Bacillus Calmette-Guerin nonpolar lipid extract.docx

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    IntroductionThe attenuation of BCG has led to the loss of not only immunogenic proteins but also lipid antigens.MethodsThus, we compared the macrophage and T-cell responses to nonpolar lipid extracts harvested from BCG and Mycobacterium tuberculosis (Mtb) to better understand the role of BCG lipids in the already known diminished responses of the vaccine strain.ResultsRelative to Mtb, nonpolar lipid extract from BCG presented a reduced capacity to trigger the expression of the genes encoding TNF, IL-1b, IL-6 and IL-10 in RAW 264.7 macrophages. Immunophenotyping of PBMCs isolated from healthy individuals revealed that lipids from both BCG and Mtb were able to induce an increased frequency of CD4+ and CD8+ T cells, but only the lipid extract from Mtb enhanced the frequency of CD4-CD8-double-negative, γσ+, CD4+HLA-DR+, and γσ+HLA-DR+ T cells relative to the nonstimulated control. Interestingly, only the Mtb lipid extract was able to increase the frequency of CD4+ memory (CD45RO+) T cells, whereas the BCG lipid extract induced a diminished frequency of CD4+ central memory (CD45RO+CCR7-) T cells after 48 h of culture compared to Mtb.DiscussionThese findings show that the nonpolar lipids of the BCG bacilli presented diminished ability to trigger both proinflammatory and memory responses and suggest a potential use of Mtb lipids as adjuvants to increase the BCG vaccine efficacy.</p

    Cost effectiveness of two online interventions supporting self-care for eczema for parents/carers and young people

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    Objective: to estimate the cost-effectiveness of online behavioural interventions (EczemaCareOnline.org.uk) designed to support eczema self-care management for parents/carers and young people from an NHS perspective.Methods: two within-trial economic evaluations, using regression-based approaches, adjusting for baseline and pre-specified confounder variables, were undertaken alongside two independent, pragmatic, parallel group, unmasked randomised controlled trials, recruiting through primary care. Trial 1 recruited 340 parents/carers of children aged 0-12 years and Trial 2 337 young people aged 13-25 years with eczema scored ≥5 on Patient-Oriented Eczema Measure (POEM). Participants were randomised (1:1) to online intervention plus usual care or usual care alone. Resource use, collected via medical notes review, was valued using published unit costs in UK £Sterling 2021. Quality-of-life was elicited using proxy CHU-9D in Trial 1 and self-report EQ-5D-5L in Trial 2. Results: the intervention was dominant (cost saving and more effective) with a high probability of cost-effectiveness (&gt;68%) in most analyses. The exception was the complete case cost-utility analysis for Trial 1 (omitting participants with children aged &lt;2), with adjusted incremental cost savings of -£34.15 (95% CI -104.54 to 36.24) and incremental QALYs of -0.003 (95% CI -0.021 to 0.015) producing an incremental cost per QALY of £12,466. In the secondary combined (Trials 1 and 2) cost-effectiveness analysis the adjusted incremental cost was -£20.35 (95% CI -55.41 to 14.70), with incremental success (≥2-point change on POEM) of 10.3% (95% CI 2.3% to 18.1%).Conclusion: the free at point of use online eczema self-management intervention was low cost to run and cost-effective.<br/

    Phase-3 trial of recombinant human alkaline phosphatase for patients with sepsis-associated acute kidney injury (REVIVAL)

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    Purpose: Ilofotase alfa is a human recombinant alkaline phosphatase with reno-protective effects that showed improved survival and reduced Major Adverse Kidney Events by 90 days (MAKE90) in sepsis-associated acute kidney injury (SA-AKI) patients. REVIVAL, was a phase-3 trial conducted to confirm its efficacy and safety. Methods: In this international double-blinded randomized-controlled trial, SA-AKI patients were enrolled < 72 h on vasopressor and < 24 h of AKI. The primary endpoint was 28-day all-cause mortality. The main secondary endpoint was MAKE90, other secondary endpoints were (i) days alive and free of organ support through day 28, (ii) days alive and out of the intensive care unit (ICU) through day 28, and (iii) time to death through day 90. Prior to unblinding, the statistical analysis plan was amended, including an updated MAKE90 definition. Results: Six hundred fifty patients were treated and analyzed for safety; and 649 for efficacy data (ilofotase alfa n = 330; placebo n = 319). The observed mortality rates in the ilofotase alfa and placebo groups were 27.9% and 27.9% at 28 days, and 33.9% and 34.8% at 90 days. The trial was stopped for futility on the primary endpoint. The observed proportion of patients with MAKE90A and MAKE90B were 56.7% and 37.4% in the ilofotase alfa group vs. 64.6% and 42.8% in the placebo group. Median [interquartile range (IQR)] days alive and free of organ support were 17 [0–24] and 14 [0–24], number of days alive and discharged from the ICU through day 28 were 15 [0–22] and 10 [0–22] in the ilofotase alfa and placebo groups, respectively. Adverse events were reported in 67.9% and 75% patients in the ilofotase and placebo group. Conclusion: Among critically ill patients with SA-AKI, ilofotase alfa did not improve day 28 survival. There may, however, be reduced MAKE90 events. No safety concerns were identified

    2019 Height-Diameter Allometry Data for Palm Species on the Barro Colorado Island 50-ha Plot

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    Please cite this dataset asRamos, Pablo, Paulino Villareal, and Helene C. Muller-Landau. 2024. 2019 Height-Diameter Allometry Data for Palm Species on the Barro Colorado Island 50-ha Plot. Smithsonian Figshare. https://doi.org.10.25573/data.25021787Objective:Collect height allometry data for BCI palm species to enable improved estimation of palm biomass stocks and fluxes using palm-specific biomass allometry equations including height such as those of Goodman et al. 2013 Forest Ecology and Management. Particular interest in heights of Socratea exorrhiza, given that this species grows in diameter as well as height.Where: 50 ha plot on Barro Colorado Island, Panama.How: Measurements were taken with a Nikon forestry laser rangefinder using the sine method (Larjavaara & Muller-Landau, 2013).Data processingHCM manually combined the 3 original data files (morepalmhtform.xlsx, moresocrex.xlsx, otherpalms2015.xlsx) into one file, combineAllPalmHeights2019.xlsx, that just had rows with data. There were problems with number formats for hom and altura columns – many of them were somehow misformatted as d.m dates, so had to be manually reentered. Also converted comments regarding the height of raices or sancos to a new column Altura sancos o raices. When there were comments on flores or frutas, changed values of flores or frutas, respectively, columns from blank to “si”. In cases where there was a comment “nada” or “no encontrado”, I changed status2019 to “DN” and moved that comment to the Notas column. Status2019 was changed to “A” for all cases with new data. Personas, frutas, and flores were standardized in terms of what types of entries were present.Additional information:Comments that were on the bottom of the spreadsheet of “morepalmhtform.xlsx”:nota Altura mínimo base hoja, Altura máxima tronc, Altura maximo hojas en el caso de de Bachman’s donde algunos tallos crecen con ángulo pronunciado y no permite medir el largo del tronco directamente hemos puesto la medida de la distancia horizontal en metros ejem 5.6- 4.8 el 4.8 es desde la base hasta donde llega la altura de manara horizontal. La idea es calcular la hipotenusa para saber el largo del troncoColumna dist base: es la distancia desde la base del tallo inclianado hasta donde el tallo empieza los 90 gradosAuthor contributionsHelene C. Muller-Landau selected the trees, designed the methods, processed the data, and drafted the metadata. Pablo Ramos and Paulino Villareal collected the field data. Under the “Personas” column, R = Ramos, V = Villareal, E = Equipo = Ramos + Villareal.Literature CitedCondit, R., R. Perez, S. Aguilar, S. Lao, R. Foster, and S. P. Hubbell. 2019. Complete data from the Barro Colorado 50-ha plot: 423617 trees, 35 years, 2019 version. https://doi.org/10.15146/5xcp-0d46Goodman, R. C., O. L. Phillips, D. del Castillo Torres, L. Freitas, S. Tapia Cortese, A. Monteagudo, and T. R. Baker. 2013. Amazon palm biomass and allometry. Forest Ecology and Management, 310: 994-1004. https://doi.org/10.1016/j.foreco.2013.09.045Larjavaara, M., and H. C. Muller-Landau. 2013. Measuring tree height: a quantitative comparison of two common field methods in a moist tropical forest. Methods in Ecology and Evolution. https://doi.org/10.1111/2041-210X.12071Muller-Landau, H. C. 2023. Combined Band Dendrometer Protocol Used by ForestGEO in Panama. Smithsonian Tropical Research Institute. Smithsonian Figshare. https://doi.org/10.25573/data.20010176</p

    USP22 lentiviral shRNA vectors.

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    The Ubiquitin Specific Peptidase 22 (USP22), a component of the Spt-Ada-Gcn5 Acetyltransferase (SAGA) histone modifying complex, is overexpressed in multiple human cancers, but how USP22 impacts tumorigenesis is not clear. We reported previously that Usp22 loss in mice impacts execution of several signaling pathways driven by growth factor receptors such as erythroblastic oncogene B b2 (ERBB2). To determine whether changes in USP22 expression affects ERBB2-driven tumorigenesis, we introduced conditional overexpression or deletion alleles of Usp22 into mice bearing the Mouse mammary tumor virus-Neu-Ires-Cre (MMTV-NIC) transgene, which drives both rat ERBB2/NEU expression and Cre recombinase activity from the MMTV promoter resulting in mammary tumor formation. We found that USP22 overexpression in mammary glands did not further enhance primary tumorigenesis in MMTV-NIC female mice, but increased lung metastases were observed. However, deletion of Usp22 significantly decreased tumor burden and increased survival of MMTV-NIC mice. These effects were associated with markedly decreased levels of both Erbb2 mRNA and protein, indicating Usp22 loss impacts MMTV promoter activity. Usp22 loss had no impact on ERBB2 expression in other settings, including MCF10A cells bearing a Cytomegalovirus (CMV)—driven ERBB2 transgene or in human epidermal growth factor receptor 2 (HER2)+ human SKBR3 and HCC1953 cells. Decreased activity of the MMTV promoter in MMTV-NIC mice correlated with decreased expression of known regulatory factors, including the glucocorticoid receptor (GR), the progesterone receptor (PR), and the chromatin remodeling factor Brahma-related gene-1 (BRG1). Together our findings indicate that increased expression of USP22 does not augment the activity of an activated ERBB2/NEU transgene but impacts of Usp22 loss on tumorigenesis cannot be assessed in this model due to unexpected effects on MMTV-driven Erbb2/Neu expression.</div
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