Handheld Point-of-Care Lactate Measurement at Admission Predicts Mortality in Ugandan Children Hospitalized with Pneumonia: A Prospective Cohort Study.

Globally, pneumonia is the leading cause of death among children younger than 5 years old, with most deaths occurring in low-income countries. Rapid bedside tools to assist practitioners to accurately triage and risk-stratify these patients may improve clinical care and patient outcomes. We conducted a prospective cohort study of children with pneumonia admitted to two Ugandan hospitals to examine the predictive value of a single point-of-care lactate measurement using a commercially available handheld device, the Lactate Scout Analyzer. One hundred and fifty-five children were included, 90 (58%) male, with a median (interquartile range [IQR]) age of 11 (1.4-20) months. One hundred and twenty-five (81%) patients had chest indrawing, 133 (86%) were hypoxemic, and 75 (68%) had a chest x-ray abnormality. In-hospital mortality was 22/155 (14%). Median (IQR) admission lactate level was 2.4 (1.8-3.6) mmol/L among children who survived versus 7.2 (2.6-9.7) mmol/L among those who died (P < 0.001). Lactate was a better prognostic marker of mortality (area under receiver operator characteristic 0.76, 95% confidence interval: 0.69-0.87, P ≤ 0.001), than any single clinical sign or composite clinical risk score. Lactate level at admission of < 2.0, 2.0-4.0, and > 4.0 mmol/L accurately risk-stratified children, with 5-day mortality of 2%, 11% and 26%, respectively (P < 0.001). Slow lactate clearance also predicted subsequent mortality in children with repeated lactate measurements. Hand-held lactate measurement is a clinically informative and convenient tool in low-resource settings for triage and risk stratification of pediatric pneumonia.

Is maternal education a social vaccine for childhood malaria infection? A cross-sectional study from war-torn Democratic Republic of Congo.

In zones of violent conflict in the tropics, social disruption leads to elevated child mortality, of which malaria is the leading cause. Understanding the social determinants of malaria transmission may be helpful to optimize malaria control efforts. We conducted a cross-sectional study of healthy children aged 2 months to 5 years attending well-child and/or immunization visits in the Democratic Republic of Congo (DRC). Six hundred and forty-seven children were tested for malaria antigenemia by rapid diagnostic test and the accompanying parent or legal guardian simultaneously completed a survey questionnaire related to demographics, socioeconomic status, maternal education, as well as bednet use and recent febrile illness. We examined the associations between variables using multivariable logistic regression analysis, chi-squared statistic, Fisher's exact test, and Spearman's rank correlation, as appropriate. One hundred and twenty-three out of the 647 (19%) children in the study tested positive for malaria. Higher levels of maternal education were associated with a lower risk of malaria in their children. The prevalence of malaria in children of mothers with no education, primary school, and beyond primary was 41/138 (30%), 41/241 (17%), and 39/262 (15%), respectively (p = 0.001). In a multivariable logistic regression model adjusting for the effect of a child's age and study site, the following remained significant predictors of malaria antigenemia: maternal education, number of children under five per household, and HIV serostatus. Higher maternal education, through several putative causal pathways, was associated with lower malaria prevalence among children in the DRC. Our findings suggest that maternal education might be an effective 'social vaccine' against malaria in the DRC and globally.

Obesity-induced lysine acetylation increases cardiac fatty acid oxidation and impairs insulin signalling.

AIMS: Lysine acetylation is a novel post-translational pathway that regulates the activities of enzymes involved in both fatty acid and glucose metabolism. We examined whether lysine acetylation controls heart glucose and fatty acid oxidation in high-fat diet (HFD) obese and SIRT3 knockout (KO) mice. METHODS AND RESULTS: C57BL/6 mice were placed on either a HFD (60% fat) or a low-fat diet (LFD; 4% fat) for 16 or 18 weeks. Cardiac fatty acid oxidation rates were significantly increased in HFD vs. LFD mice (845 ± 76 vs. 551 ± 87 nmol/g dry wt min, P < 0.05). Activities of the fatty acid oxidation enzymes, long-chain acyl-CoA dehydrogenase (LCAD), and ß-hydroxyacyl-CoA dehydrogenase (ß-HAD) were increased in hearts from HFD vs. LFD mice, and were associated with LCAD and ß-HAD hyperacetylation. Cardiac protein hyperacetylation in HFD-fed mice was associated with a decrease in SIRT3 expression, while expression of the mitochondrial acetylase, general control of amino acid synthesis 5 (GCN5)-like 1 (GCN5L1), did not change. Interestingly, SIRT3 deletion in mice also led to an increase in cardiac fatty acid oxidation compared with wild-type (WT) mice (422 ± 29 vs. 291 ± 17 nmol/g dry wt min, P < 0.05). Cardiac lysine acetylation was increased in SIRT3 KO mice compared with WT mice, including increased acetylation and activity of LCAD and ß-HAD. Although the HFD and SIRT3 deletion decreased glucose oxidation, pyruvate dehydrogenase acetylation was unaltered. However, the HFD did increase Akt acetylation, while decreasing its phosphorylation and activity. CONCLUSION: We conclude that increased cardiac fatty acid oxidation in response to high-fat feeding is controlled, in part, via the down-regulation of SIRT3 and concomitant increased acetylation of mitochondrial ß-oxidation enzymes.

Chemical similarity between historical and novel host plants promotes range and host expansion of the mountain pine beetle in a naïve host ecosystem.

Host plant secondary chemistry can have cascading impacts on host and range expansion of herbivorous insect populations. We investigated the role of host secondary compounds on pheromone production by the mountain pine beetle (Dendroctonus ponderosae) (MPB) and beetle attraction in response to a historical (lodgepole pine, Pinus contorta var. latifolia) and a novel (jack pine, Pinus banksiana) hosts, as pheromones regulate the host colonization process. Beetles emit the same pheromones from both hosts, but more trans-verbenol, the primary aggregation pheromone, was emitted by female beetles on the novel host. The phloem of the novel host contains more α-pinene, a secondary compound that is the precursor for trans-verbenol production in beetle, than the historical host. Beetle-induced emission of 3-carene, another secondary compound found in both hosts, was also higher from the novel host. Field tests showed that the addition of 3-carene to the pheromone mixture mimicking the aggregation pheromones produced from the two host species increased beetle capture. We conclude that chemical similarity between historical and novel hosts has facilitated host expansion of MPB in jack pine forests through the exploitation of common host secondary compounds for pheromone production and aggregation on the hosts. Furthermore, broods emerging from the novel host were larger in terms of body size.