CD28 between tolerance and autoimmunity: The side effects of animal models [version 1; referees: 2 approved]

Regulation of immune responses is critical for ensuring pathogen clearance and for preventing reaction against self-antigens. Failure or breakdown of immunological tolerance results in autoimmunity. CD28 is an important co-stimulatory receptor expressed on T cells that, upon specific ligand binding, delivers signals essential for full T-cell activation and for the development and homeostasis of suppressive regulatory T cells. Many in vivo mouse models have been used for understanding the role of CD28 in the maintenance of immune homeostasis, thus leading to the development of CD28 signaling modulators that have been approved for the treatment of some autoimmune diseases. Despite all of this progress, a deeper understanding of the differences between the mouse and human receptor is required to allow a safe translation of pre-clinical studies in efficient therapies. In this review, we discuss the role of CD28 in tolerance and autoimmunity and the clinical efficacy of drugs that block or enhance CD28 signaling, by highlighting the success and failure of pre-clinical studies, when translated to humans

Land-use change and carbon stocks: regional assessment of sugarcane areas in Brazil.

Abstract: In agricultural product Life Cycle Assessment (LCA), emissions or removals of carbon (C) from land-use change can highly affect the global warming. The aim of this study was to evaluate the impacts of biomass C values and stock change factors on land use change (LUC) emissions in areas of sugarcane expansion in Brazil. In this study, we used stratified random sample in order to estimate changes in land cover through geotechnologies and associated C stocks from literature data. For that, the total area was stratified by three criteria: soil type, % of native vegetation in 1998 and age of sugarcane plantation in 2018. The sample size represented 12.8% of the studied area (172,000 ha). To this end, a matrix of primary combinations was combined with spatial data such as land cover in 1998, soil types, biomes and Köppen climate classification. Estimates of C stock changes in soil and biomass were calculated the Stock-Difference Method, according to IPCC Guidelines and specialized literature. Respecting the uncertainties, this approach allowed to have an estimate of C balance in sugarcane fields at the regional level in Brazil. Three main recommendations: (i) values of FMG> 1.0 (FMG, stock change factor for management regime), should be used for sugarcane, but future research ratification is necessary; (ii) biomass C values of sugarcane biomass above 5 tonnes C ha-1 should be used, especially when sugarcane is harvested without burning; and (iii) as there is still no relationship between level of pasture degradation and C content in soil, biomass C values and pasture FMG should be carefully chosen in pasture conversion to sugarcane

LCA applied to perennial cropping systems: a review focused on the farm stage

International audienc

Use of ‘Pharmaceutical services’ Medical Subject Headings (MeSH) in articles assessing pharmacists' interventions

Background: Medical Subject Headings (MeSH) thesaurus contribute towards efficient searching of biomedical information. However, insufficient coverage of specific fields and inaccuracies in the indexing of articles can lead to bias during literature retrieval. Objectives: This meta-research study aimed to assess the use of ‘Pharmaceutical Services’ MeSH terms in studies evaluating the effect of pharmacists' interventions. Methods: An updated systematic search (Jan-2022) to gather meta-analyses comparing pharmacists' interventions vs. other forms of care was performed. All MeSH terms allocated to the MEDLINE record of each primary study included in the selected meta-analyses were systematically extracted. Terms from the ‘Pharmaceutical Services’ branch, including its descendants, as well as other 26 pharmacy-specific MeSH terms, were identified. The assignment of these terms as a ‘Major MeSH’ was also evaluated. Descriptive statistics and social network analyses to evaluate the co-occurrence of the MeSH terms in the articles were conducted. Sensitivity analyses including only meta-analyses with declared objectives mentioning the words ‘pharmacist’ or ‘pharmacy’ were performed (SPSS v.24.0). Results: Overall, 138 meta-analyses including 2012 primary articles were evaluated. A median of 15 [IQR 12–18] MeSH terms were assigned per article with a slight positive time-trend (Spearman rho = 0.193; p < 0.001). Only 36.6% (n = 736/2012) and 58.1% (n = 338/1099) of studies were indexed with one MeSH term from the ‘Pharmaceutical Services’ branch in the overall and sensitivity analyses, respectively. In <20% of cases, these terms were a ‘Major MeSH’. The pharmacy-specific term ‘Pharmacists’ was the most frequently used, yet in only 27.8% and 47.7% of articles in the original and sensitivity analyses, respectively. Social networks showed a weak association between pharmacy-specific and ‘Pharmaceutical services’ branch MeSH terms. Conclusions: The availability of a ‘Pharmaceutical services’ branch hierarchic tree and further pharmacy-specific MeSH terms incorporated into the MeSH thesaurus in the past years is not related to the accurate indexing of articles.info:eu-repo/semantics/publishedVersio

Effect of Head-Down Tilt Bedrest (10 Days) on Lymphocyte Reactivity

Immunological responses of six healthy males to 10 days of headdown tilt bedrest (HDT) were assessed. Lymphocyte responsiveness was severely reduced immediately before, during, and immediately after the HDT, even though the lymphocyte numbers did not change. By contrast, delayed-type hypersensitivity was not affected. No dramatic changes were found in WBC counts and lymphocyte subpopulations, with the only exception of natural killer (NK) cells which transiently decreased immediatley after HDT. Plasma cortisol levels were elevated above normal immediately before and during the HDT. The data suggest that the mitogenic response of lymphocytes was affected by psychological and fluid shift stress. These results are compared with data obtained during and after spaceflight. We conclude that the stress of HDT induces changes in immunological responsiveness that are strikingly similar to those arising from the stress of spaceflight