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

Exploiting bacterial DNA gyrase as a drug target: current state and perspectives

DNA gyrase is a type II topoisomerase that can introduce negative supercoils into DNA at the expense of ATP hydrolysis. It is essential in all bacteria but absent from higher eukaryotes, making it an attractive target for antibacterials. The fluoroquinolones are examples of very successful gyrase-targeted drugs, but the rise in bacterial resistance to these agents means that we not only need to seek new compounds, but also new modes of inhibition of this enzyme. We review known gyrase-specific drugs and toxins and assess the prospects for developing new antibacterials targeted to this enzyme

Reasons for admission in asylum-seeking and non-asylum-seeking patients in a paediatric tertiary care centre.

BACKGROUND: In the last decade an increasing number of asylum-seeking children arrived in Europe and local healthcare systems have been challenged to adapt to their health needs. The aim of this study was to compare the spectrum of disease and management of asylum-seeking and non-asylum-seeking children requiring hospital admission. METHODS: This was a retrospective cohort study including health data from recently arrived asylum-seeking and non-asylum-seeking children admitted between January 2016 and December 2017. Data were collected using electronic administrative and medical records. RESULTS: Of 11,794 admissions of 9407 patients, 149 (1%) were asylum-seeking and 11,645 (99%) from non-asylum-seeking children. In asylum-seeking children the median age was 4 years (interquartile range [IQR] 0–13) with 61% males and in non-asylum-seeking children 4 years (IQR 0–11) years with 56% males. Respiratory infections accounted for 17–19% of admissions in both groups. Rare infectious diseases were more frequent in asylum-seeking children (15 vs 7%; difference in proportions 0.08, 95% confidence interval [CI] 0.02–0.14; p <0.001,). Injuries were more frequent in non-asylum-seeking children (22 vs 13%; difference in proportions 0.09, 95% CI 0.04–0.014; p <0.01). Admissions for mental health disorders were infrequent but more common in asylum-seeking children (6 vs 3%; difference in proportions 0.03, 95% CI −0.01 – 0.07; p = 0.02) Prescription of analgesics was lower in asylum-seeking than non-asylum-seeking children (3.4 vs 6.5 accounting units per admission). Antibiotic prescription was comparable in both groups. CONCLUSION: Asylum-seeking children represent a small number of total admissions. Age distribution and main reason for admission being diseases of the respiratory system were comparable in asylum-seeking and non-asylum-seeking children. Rare infections and mental health disorders are important diseases in asylum-seeking children and require special attention and training of staff working with paediatric asylum seekers

Asylum-Seeking Children with Medical Complexity and Rare Diseases in a Tertiary Hospital in Switzerland.

The aim of this study was to assess the characteristics of asylum-seeking children with medical complexity visiting a tertiary care hospital in Switzerland, detailing their underlying medical conditions and management. Asylum-seeking patients with frequent visits between January 2016 and December 2017 were identified using administrative and electronic health records. Of 462 patients, 19 (4%) fulfilled the inclusion criteria with 811 (45%) visits. The age of the 19 patients ranged from 0 to 16.7 years (median of 7 years) with two main age groups identified:  12 years. Nine (47%) patients originated from Syria. A total of 34/811(4%) visits were hospital admissions, 66/811 (8%) emergency department visits and 320/811(39%) outpatient department visits. In children < 2 years genetic diseases (5/8; 63%) and nutritional problems (6/8; 75%) were most common; in adolescents, orthopedic diseases (4/8; 50%) and mental health problems (4/8; 50%). Asylum-seeking children with medical complexity represent a small but important group of patients requiring frequent medical consultations. The high proportion of young patients with genetic diseases and severe nutritional problems suggests that new strategies are required in the management of this specific group of asylum-seeking children. This could be achieved by improved co-ordination between hospital and non-hospital care exploring options for integrated care