Circulating Pneumolysin Is a Potent Inducer of Cardiac Injury during Pneumococcal Infection

Streptococcus pneumoniae accounts for more deaths worldwide than any other single pathogen through diverse disease manifestations including pneumonia, sepsis and meningitis. Life-threatening acute cardiac complications are more common in pneumococcal infection compared to other bacterial infections. Distinctively, these arise despite effective antibiotic therapy. Here, we describe a novel mechanism of myocardial injury, which is triggered and sustained by circulating pneumolysin (PLY). Using a mouse model of invasive pneumococcal disease (IPD), we demonstrate that wild type PLY-expressing pneumococci but not PLY-deficient mutants induced elevation of circulating cardiac troponins (cTns), well-recognized biomarkers of cardiac injury. Furthermore, elevated cTn levels linearly correlated with pneumococcal blood counts (r=0.688, p=0.001) and levels were significantly higher in non-surviving than in surviving mice. These cTn levels were significantly reduced by administration of PLY-sequestering liposomes. Intravenous injection of purified PLY, but not a non-pore forming mutant (PdB), induced substantial increase in cardiac troponins to suggest that the pore-forming activity of circulating PLY is essential for myocardial injury in vivo. Purified PLY and PLY-expressing pneumococci also caused myocardial inflammatory changes but apoptosis was not detected. Exposure of cultured cardiomyocytes to PLY-expressing pneumococci caused dose-dependent cardiomyocyte contractile dysfunction and death, which was exacerbated by further PLY release following antibiotic treatment. We found that high PLY doses induced extensive cardiomyocyte lysis, but more interestingly, sub-lytic PLY concentrations triggered profound calcium influx and overload with subsequent membrane depolarization and progressive reduction in intracellular calcium transient amplitude, a key determinant of contractile force. This was coupled to activation of signalling pathways commonly associated with cardiac dysfunction in clinical and experimental sepsis and ultimately resulted in depressed cardiomyocyte contractile performance along with rhythm disturbance. Our study proposes a detailed molecular mechanism of pneumococcal toxin-induced cardiac injury and highlights the major translational potential of targeting circulating PLY to protect against cardiac complications during pneumococcal infections

Food Insecurity and Childhood Obesity: A Systematic Review

BACKGROUND AND OBJECTIVES: Addressing food insecurity while promoting healthy body weights among children is a major public health challenge. Our objective is to examine longitudinal associations between food insecurity and obesity in US children aged 1 to 19 years. METHODS: Sources for this research include PubMed, CINAHL, and Scopus databases (January 2000 to February 2022). We included English language studies that examined food insecurity as a predictor of obesity or increased weight gain. We excluded studies outside the United States and those that only considered the unadjusted relationship between food security and obesity. Characteristics extracted included study design, demographics, methods of food security assessment, and anthropometric outcomes. RESULTS: Literature searches identified 2272 articles; 13 met our inclusion criteria. Five studies investigated the relationship between food insecurity and obesity directly, whereas 12 examined its relationship with body mass index or body mass index z-score. Three studies assessed multiple outcomes. Overall, evidence of associations between food insecurity and obesity was mixed. There is evidence for possible associations between food insecurity and obesity or greater weight gain in early childhood, for girls, and for children experiencing food insecurity at multiple time points. Heterogeneity in study methods limited comparison across studies. CONCLUSIONS: Evidence is stronger for associations between food insecurity and obesity among specific subgroups than for children overall. Deeper understanding of the nuances of this relationship is critically needed to effectively intervene against childhood obesity

Divergência genética em cultivares de morangueiro, baseada em caracteres morfoagronômicos

Os caracteres morfoagronômicos são tradicionalmente usados na caracterização de cultivares e no estudo da divergência genética, contribuindo na definição de estratégias para o melhoramento genético. Este trabalho teve por objetivo avaliar a divergência genética por meio de caracteres morfoagronômicos de 11 cultivares de morangueiro (Aromas, Camarosa, Camino Real, Campinas, Diamante, Dover, Oso Grande, Sweet Charlie, Toyonoka, Tudla e Ventana), nas condições climáticas da região Centro-Sul do Paraná. Foram analisados 29 caracteres morfoagronômicos relacionados com a planta, folha, flor, fruto e aquênios do morangueiro. As similaridades genéticas foram calculadas por meio de análise multivariada e, os cultivares, agrupados com base na matriz de similaridade genética, usando-se UPGMA. Dentre os 29 caracteres morfoagronômicos avaliados, oito apresentaram diferenças não significativas (p < 0,05). A similaridade média foi de 38%, variando de 19 (aromas e camino real) a 62% (Camino Real e Camarosa; Aromas e Sweet Charlie). O dendrograma alocou os cultivares em quatro grupos, contudo, essa divisão não foi coerente com a origem e genealogia dos cultivares. O cultivar Tudla apresenta elevado potencial "per se" para utilização em programas de melhoramento. O cruzamento mais promissor com base nos caracteres morfoagronômicos é entre os cultivares Camarosa e Campinas

Going, going, gone: the effects of aid policies on graduation at three large public institutions

This paper exploits uniquely detailed data and cross-institution variation in aid for three large public universities to identify the effects of aid on the probability of college graduation. The results indicate that need-based and merit-based aid both increase graduation rates at large public institutions, but primarily through the types of students that ‘select’ these institutions. Merit-based aid facilitates an institution attracting students who have higher observed academic ability that raises the probability of graduation. Need-based aid enables an institution to attract students with non-academic attributes such as social and cultural networks that, while often unobserved, improve graduation success. Broadly, our results suggest that recent aid policy that has moved away from need-based aid for low-income students (reducing their ability to find the best institutional match) and toward merit-based aid (that alters the distribution of high ability students across colleges) could foster stagnant graduation rates even with rising enrollment rates that have been observed over the last three decades. Copyright Springer Science+Business Media, LLP 2006Higher education policy, Economics of education, Financial aid, College enrollment, College completion,