Plasmodium falciparum:Rosettes do not protect merozoites from invasion-inhibitory antibodies

Rosetting is a parasite adhesion phenotype associated with severe malaria in African children. Why parasites form rosettes is unknown, although enhanced invasion or immune evasion have been suggested as possible functions. Previous work showed that rosetting does not enhance parasite invasion under standard in vitro conditions. We hypothesised that rosetting might promote invasion in the presence of host invasion-inhibitory antibodies, by allowing merozoites direct entry into the erythrocytes in the rosette and so minimising exposure to plasma antibodies. We therefore investigated whether rosetting influences invasion in the presence of invasion-inhibitory antibodies to MSP-1. We found no difference in invasion rates between isogenic rosetting and non-rosetting lines from two parasite strains, R29 and TM284, in the presence of MSP-1 antibodies (P=0.62 and P=0.63, Student's t test, TM284 and R29, respectively). These results do not support the hypothesis that rosettes protect merozoites from inhibitory antibodies during invasion. The biological function of rosetting remains unknown

Human Plasmodium knowlesi Infection Detected by Rapid Diagnostic Tests for Malaria

We describe a PCR-confirmed case of Plasmodium knowlesi infection with a high parasitemia level and clinical signs of severe malaria in a migrant worker from Malaysian Borneo in the Netherlands. Investigations showed that commercially available rapid antigen tests for detection of human Plasmodium infections can detect P. knowlesi infections in humans

Inhaled corticosteroid use is associated with increased circulating tregulatory cells in children with asthma

BACKGROUND: T regulatory (Treg) cells are important in balancing immune responses and dysregulation of Treg cells has been implicated in the pathogenesis of multiple disease states including asthma. In this study, our primary aim was to determine Treg cell frequency in the peripheral blood of children with and without asthma. The secondary aim was to explore the association between Treg cell frequency with allergen sensitization, disease severity and medication use. METHODS: Peripheral blood mononuclear cells from healthy control subjects (N = 93) and asthmatic children of varying disease severity (N = 66) were characterized by multi-parameter flow cytometry. RESULTS: Our findings demonstrate that children with asthma had a significantly increased frequency of Treg cells compared to children without asthma. Using a multivariate model, increased Treg cell frequency in children with asthma was most directly associated with inhaled corticosteroid use, and not asthma severity, allergic sensitization, or atopic status of the asthma. CONCLUSION: We conclude that low dose, local airway administration of corticosteroids is sufficient to impact the frequency of Treg cells in the peripheral blood. These data highlight the importance of considering medication exposure when studying Treg cells and suggest inhaled corticosteroid use in asthmatics may improve disease control through increased Treg cell frequency

Mistral 7B

We introduce Mistral 7B v0.1, a 7-billion-parameter language model engineered for superior performance and efficiency. Mistral 7B outperforms Llama 2 13B across all evaluated benchmarks, and Llama 1 34B in reasoning, mathematics, and code generation. Our model leverages grouped-query attention (GQA) for faster inference, coupled with sliding window attention (SWA) to effectively handle sequences of arbitrary length with a reduced inference cost. We also provide a model fine-tuned to follow instructions, Mistral 7B -- Instruct, that surpasses the Llama 2 13B -- Chat model both on human and automated benchmarks. Our models are released under the Apache 2.0 license.Comment: Models and code are available at https://mistral.ai/news/announcing-mistral-7b

Serial cardiac biomarker assessment in adults with congenital heart disease hospitalized for decompensated heart failure

Background. Biomarkers are increasingly part of assessing and managing heart failure (HF) in adults with congenital heart disease (CHD). Objectives. To understand the response of cardiac biomarkers with therapy for acute decompensated heart failure (ADHF) and the relationship to prognosis after discharge in adults with CHD. Design. A prospective, observational cohort study with serial blood biomarker measurements. Settings. Single-center study in the inpatient setting with outpatient follow-up. Participants. Adults (≥18 years old) with CHD admitted with ADHF between August 1, 2019, and March 1, 2020. Exposure. We measured body mass, Kansas City Cardiomyopathy Questionnaire (KCCQ-12) score, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and high-sensitivity C-reactive protein (hsCRP) at enrollment, discharge, and 1st clinic follow-up visit; soluble suppression of tumorigenicity 2 (sST2) was measured at the first two time points. Measures. Univariate regression assessed the association between changes in weight, biomarkers, and changes in KCCQ-12 scores, between enrollment and discharge ( ) and between discharge and 1st clinical follow-up visit . Wilcoxon rank-sum tests assessed the association between change in biomarkers, KCCQ-12 scores, and the composite outcome of cardiovascular death or rehospitalization for ADHF. Results. A total of 26 patients were enrolled. The median age was 51.9 years [IQR: 38.8, 61.2], 13 (54.2%) were women, and median hospital stay was 6.5 days [IQR: 4.0, 15.0] with an associated weight loss of 2.8 ​kg [IQR -5.1, −1.7]. All three cardiac biomarkers decreased during hospitalization with diuresis while KCCQ-12 scores improved; a greater decrease in sST2 was associated with an improved KCCQ-12 symptom frequency (SF) subdomain score (p ​= ​0.012), but otherwise, there was no significant relationship between biomarkers and KCCQ-12 change. Change in hsCRP and NT-proBNP after discharge was not associated with the composite outcome (n ​= ​8, vs. n ​= ​16 who did not experience the outcome; Δ Post-discharge hsCRP +5.1 vs. −1.0 ​mg/l, p ​= ​0.061; NT-proBNP +785.0 vs. +130.0 ​pg/ml, p ​= ​0.220). Conclusions. Serial biomarker measurements respond to acute diuresis in adults with CHD hospitalized for ADHF. These results should motivate further research into the use of biomarkers to inform HF therapy in adults with CHD