Relationship between breastfeeding and asthma prevalence in young children exposed to adverse childhood experiences

Objective: To investigate if duration of supplemental breastfeeding is associated with a lower asthma risk and whether adverse childhood experiences (ACEs) early in life influence this relationship in children ages 3 to 5 years. Methods: Data were from the 2011–2012 National Survey of Children's Health, a nationally representative cross-sectional survey. Modified Poisson regression models were used to estimate incident risk ratios (IRR) for lifetime and current asthma in young children aged 3 to 5 years (n = 15,642). We tested for effect measure modification using stratified analyses. Results: Exclusive breastfeeding for at least 6 months or supplemental breastfeeding for children ≥12 months significantly reduced the risk of lifetime asthma prevalence compared to never breastfed children (IRR 0.64; 95% CI: 0.46–0.88, p = 0.007; and IRR 0.68; 95% CI: 0.47–0.99, p = 0.044, respectively), adjusted for covariates. In stratified analyses, breastfeeding reduced the risk of lifetime asthma for children who experienced 1 ACE but not for children who experienced 2 or more ACEs. Conclusion: Exclusive breastfeeding for at least 6 months, with and without supplementation, appears to prevent asthma or delay its onset. The protective effect of breastfeeding was attenuated among children who experienced more than 2 ACEs. The known harmful effects that ACEs have on children's health may outweigh the benefits of breastfeeding in reducing the risk of a child developing asthma. Understanding how specific time periods in a child's life may be most affected by exposure to early life adversities, along with the protective effect of breastfeeding against asthma, are important areas of further study.     

An EU-wide approach to HTA: An irrelevant development or an opportunity not to be missed?

An EU-wide cooperation on HTA has been proposed recently by the European Commission, focusing on relative effectiveness assessment (REA) for pharmaceuticals and medical devices. This cooperation is operationalised through a proposal for a regulation. While a good step in the right direction, this HTA cooperation framework needs to be more explicit and pragmatic about clinical value definition, what constitutes quality of evidence, how real-world evidence is handled, whether the same assessment requirements will apply for medical devices as they do for pharmaceuticals, and how to safeguard consistency in REA interpretation. If demand-rather than supply-driven, this initiative can deliver wider benefits: Europe can improve its power in global drug design and development, while Member States will have at their disposal more resources to assess performance of interventions in their healthcare systems.

     

Germ-line mutations, DNA damage, and global hypermethylation in mice exposed to particulate air pollution in an urban/industrial location

Particulate air pollution is widespread, yet we have little understanding of the long-term health implications associated with exposure. We investigated DNA damage, mutation, and methylation in gametes of male mice exposed to particulate air pollution in an industrial/urban environment. C57BL/CBA mice were exposed in situ to ambient air near two integrated steel mills and a major highway, alongside control mice breathing high-efficiency air particulate (HEPA) filtered ambient air. PCR analysis of an expanded simple tandem repeat (ESTR) locus revealed a 1.6-fold increase in sperm mutation frequency in mice exposed to ambient air for 10 wks, followed by a 6-wk break, compared with HEPA-filtered air, indicating that mutations were induced in spermatogonial stem cells. DNA collected after 3 or 10 wks of exposure did not exhibit increased mutation frequency. Bulky DNA adducts were below the detection threshold in testes samples, suggesting that DNA reactive chemicals do not reach the germ line and cause ESTR mutation. In contrast, DNA strand breaks were elevated at 3 and 10 wks, possibly resulting from oxidative stress arising from exposure to particles and associated airborne pollutants. Sperm DNA was hypermethylated in mice breathing ambient relative to HEPA-filtered air and this change persisted following removal from the environmental exposure. Increased germ-line DNA mutation frequencies may cause population-level changes in genetic composition and disease. Changes in methylation can have widespread repercussions for chromatin structure, gene expression and genome stability. Potential health effects warrant extensive further investigation.     

Statins and their increased risk of inducing diabetes

Introduction: Statins are evidence-based drugs to prevent cardiovascular (CV) disease. However, their benefits have been disputed by a statin-related increased risk of new onset diabetes (NOD) in randomized controlled trials and meta-analyses.

Areas covered: This review provides an update based on recent outstanding evidence on the statin effect on the risk of diabetes. It also describes mechanisms potentially explaining adverse effects of statins on glucose homeostasis. PubMed was searched for original articles and reviews published from January 2010 (inclusive) to May 2015 (inclusive), which include the Search terms statins, diabetes, glucose, and insulin. NOD risk seems to be more relevant with high-intensity rather than with low-intensity statin treatment. Also, this risk is particularly increased in patients at risk for the development of diabetes. It appears that statins adversely affect glucose homeostasis in parallel with their 3-hydroxy-3-methylglutaryl-coenzyme A inhibition capacity. It was suggested that lipophilic statins are more diabetogenic than the hydrophilic ones. Mechanisms explaining statin diabetogeneicity include impaired insulin secretion by pancreatic β cells together with increased insulin resistance of various tissues.

Expert opinion: The CV outcome benefits from statin use outweigh the diabetes menace. However, patients at risk for the development of diabetes should be prescribed statins with caution.     

Remodeling of myocyte gap junctions in arrhythmogenic right ventricular cardiomyopathy due to a deletion in plakoglobin (Naxos disease).

OBJECTIVES: We tested the hypothesis that defective interactions between adhesion junctions and the cytoskeleton caused by the plakoglobin mutation in Naxos disease lead to remodeling of gap junctions and altered expression of the major gap junction protein, connexin43. BACKGROUND: Naxos disease, a recessive form of arrhythmogenic right ventricular cardiomyopathy, is associated with a high incidence of arrhythmias and sudden cardiac death. Naxos disease is caused by a mutation in plakoglobin, a protein that links cell-cell adhesion molecules to the cytoskeleton. METHODS: Myocardial expression of connexin43 and other intercellular junction proteins was characterized in 4 patients with Naxos disease. Immunohistochemistry was performed in all 4 patients, and immunoblotting and electron microscopy were performed in 1 patient who died in childhood before overt arrhythmogenic right ventricular cardiomyopathy had developed. RESULTS: Connexin43 expression at intercellular junctions was reduced significantly in both right and left ventricles in all patients with Naxos disease. Electron microscopy revealed smaller and fewer gap junctions interconnecting ventricular myocytes. Mutant plakoglobin was expressed but failed to localize normally at intercellular junctions. Localization of N-cadherin, alpha- and beta-catenins, plakophilin-2, desmoplakin-1, and desmocollin-2 at intercalated disks appeared normal. CONCLUSIONS: Remodeling of gap junctions occurs early in Naxos disease, presumably because of abnormal linkage between mechanical junctions and the cytoskeleton. Gap junction remodeling may produce a coupling defect which, combined with the subsequent development of pathologic changes in myocardium, could contribute to a highly arrhythmogenic substrate and enhance the risk of sudden death in Naxos disease.     

Interleukin-18 Antagonism Improved Histopathological Conditions of Malaria Infection in Mice

Background: Interleukin 18 (IL-18) exerts pleiotropic roles in many inflammatory-related diseases including parasitic infection. Previous studies have demonstrated the promising therapeutic potential of modulating IL-18 bioactivity in various pathological conditions. However, its involvement during malaria infection has yet to be established. In this study, we demonstrated the effect of modulating IL-18 on the histopathological conditions of malaria infected mice. Methods: Plasmodium berghei ANKA infection in male ICR mice was used as a model for malaria infection. Modulation of IL-18 release was carried out by treatment of malarial mice with recombinant mouse IL-18 (rmIL-18) and recombinant mouse IL-18 Fc chimera (rmIL-18Fc) intravenously. Histopathological study and analysis were performed on major organs including brain, liver, spleen, lungs and kidney. Results: Treatment with rmIL-18Fc resulted in significant improvements on the histopathological conditions of the organs in malaria-infected mice. Conclusion: IL-18 is an important mediator of malaria pathogenesis and targeting IL-18 could prove beneficial in malaria-infected host.Key Words: Malaria, Interleukin-18, Plasmodium berghei, Histopathology