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Platelets contribute to inflammation however, the role of platelet activation during the pathophysiological response to invasive bacterial infection and sepsis is not clear. Herein, we have investigated platelet activation in a mouse model of invasive Streptococcus pyogenes infection at 5, 12, and 18 hours post infection and correlated this to parameters of infection. The platelet population in ex-vivo blood samples showed no increased integrin activation or surface presentation of CD62P, however platelet-neutrophil complex formation and plasma levels of CD62P were increased during bacterial dissemination and the progression of sepsis, indicating that platelet activation had occurred in vivo. Platelet-neutrophil complex formation was the most discriminatory marker of platelet activation. Platelet-neutrophil complexes were increased above baseline levels during early sepsis but decreased to significantly lower levels than baseline during late sepsis. The removal of these complexes from the circulation coincided with a significant increase in organ damage and the accumulation of platelets in the liver sinusoids, suggesting that platelet activation in the circulation precedes accumulation of platelets in damaged organs. The results demonstrate that monitoring platelet activation using complementary methods may provide prognostic information during the pathogenesis of invasive S. pyogenes infection.

Platelets are rapidly responsive sentinel cells that patrol the bloodstream and contribute to the host response to infection. Platelets have been reported to form heterotypic aggregates with leukocytes and may modulate their function. Here, we have investigated platelet-neutrophil complex formation and neutrophil function in response to distinct agonists. The endogenous platelet activator thrombin gave rise to platelet-dependent neutrophil activation, resulting in enhanced phagocytosis and bacterial killing. Streptococcus pyogenes is an important causative agent of severe infectious disease, which can manifest as sepsis and septic shock. M1 protein from S. pyogenes also mediated platelet-neutrophil complex formation; however, these neutrophils were dysfunctional and exhibited diminished chemotactic ability and bacterial killing. This reveals an important agonist-dependent neutrophil dysfunction during platelet-neutrophil complex formation and highlights the role of platelets during the immune response to streptococcal infection.

Background By 2025, adult obesity prevalence is projected to increase in 44 of 53 of European-region countries. Childhood obesity tracks directly onto adult obesity, and children of low socioeconomic position families are at disproportionately higher risk of being obese compared with their more affluent peers. A previous review of research from developed countries identified factors mediating this relationship. This systematic review updates and extends those findings specifically within the context of Ireland and the United Kingdom. Objective The aim of this systematic review is to summarise peer-reviewed research completed in Ireland and the United Kingdom between 2011–2021 examining mediators of socioeconomic differentials in adiposity outcomes for youth. Design An electronic search of four databases, Ovid MEDLINE, Embase, Web of Science and EBSCOhost was conducted. Quantitative studies, published in the English language, examining mediators of socioeconomic differentials in adiposity outcomes in youth, and conducted in Ireland and the United Kingdom between 2011–2021 were included. An appraisal of study quality was completed. The systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results Following screening, a total of 23 papers were eligible for inclusion. Results indicate socioeconomic differentials for Ireland and the United Kingdom follow similar patterns to other developed countries and have similar mediating factors including early life and parent-level factors. However, this review identified additional factors that mediate the relationship, namely access to green space and favorable neighborhood conditions. Identifying these factors present further opportunities for potential interventions and confirm the requirement for tailored and appropriate research and interventions for Ireland and the United Kingdom. Conclusion This review identified several modifiable factors that should be considered when planning interventions aimed at reducing socioeconomic differentials in adiposity among youth in Ireland and the United Kingdom. Support was found for interventions to be made as early as possible in an at-risk child’s life, with the prenatal and preschool periods considered the most efficacious. Results were equivocal about the role of physical activity in the risk of childhood overweight and obesity. While multi-country analyses provide excellent overviews, country- or area-specific research may produce more nuanced, and potentially more powerful findings, which can help better inform policy responses and interventions.