Helicobacter pylori infection in asymptomatic children: comparison of diagnostic tests

Background. Childhood is known to be a major risk period for acquiring Helicobacter pylori infection. Studies of the epidemiology of H. pylori infection depend on the validity of the diagnostic tools used to detect the infection in the pediatric setting. This study aims to conduct a combination of diagnostic tests on the same children, evaluate the sensitivity and the specificity of IgG antibody testing compared with the ¹³C‐urea breath test, and examine the variability in the prevalence of H. pylori infection in asymptomatic children based on the use of different diagnostic tests. Methods. ¹³C‐urea breath test (¹³C‐UBT), whole blood FlexSure (systemic antibodies), and OraSure (salivary antibodies) tests were conducted on 287 asymptomatic children (151 boys, 136 girls; ages 2–18 years). The three tests were conducted on each child during the same day. The prevalence was calculated using each test independently. Results. H. pylori infection was detected in 32%, 22%, or 18% of the studied children, based on UBT, OraSure, or FlexSure, respectively. A total of 103 children tested positive for any one test (92 on UBT, 8 on FlexSure, 3 on OraSure), giving a prevalence of 35% based on the “parallel” method. Only 39 children tested positive in all three tests, giving a prevalence of 14% based on the “serial” method. Using the UBT as the gold standard, the sensitivity of FlexSure and OraSure were 48% and 65%, respectively, and the specificity of both tests was greater than 95%. When we applied the parallel method, the sensitivity and specificity of the combined antibody tests (FlexSure+OraSure) compared to the UBT were 71% and 95%, respectively. Conclusions. Among asymptomatic children, there is a wide variation in the prevalence of H. pylori infection based on the diagnostic test used. The study shows that antibody assays are less suitable than the UBT. However, under certain conditions, the IgG assays (combined systemic, salivary, or both) are less expensive alternative tools to the UBT for epidemiological studies in children.     

Natural environments,ancestral diets,and microbial ecology: is there a modern “paleo-deficit disorder”? Part I

Famed microbiologist René J. Dubos (1901–1982) was an early pioneer in the developmental origins of health and disease (DOHaD) construct. In the 1960s, he conducted groundbreaking experimental research concerning the ways in which early-life experience with nutrition, microbiota, stress, and other environmental variables could influence later-life health outcomes. He also wrote extensively on potential health consequences of a progressive loss of contact with natural environments (now referred to as green or blue space), arguing that Paleolithic experiences have created needs, particularly in the mental realm, that might not be met in the context of rapid global urbanization. He posited that humans would certainly adapt to modern urban landscapes and high technology, but there might be a toll to be paid in the form of higher psychological distress (symptoms of anxiety and depression) and diminished quality of life. In particular, there might be an erosion of humanness, exemplified by declines in altruism/empathy. Here in the first of a two-part review, we examine contemporary research related to natural environments and question to what extent Dubos might have been correct in some of his 50-year-old assertions.

“Human beings can almost certainly survive and multiply in the polluted cage of technological civilization, but we may sacrifice much of our humanness in adapting to such conditions…The maintenance of biological and mental health requires that technological societies provide in some form the biological freedom enjoyed by our Paleolithic ancestors”.Dr René Dubos, Invited Editorial, Life Magazine, 1970 [1].

     

Impacts of Climate Change on the Timing of the Production Season of Maple Syrup in Eastern Canada

Maple syrup production is an important economic activity in north-eastern North-America. The beginning and length of the production season is linked to daily variation in temperature. There are increasing concerns about the potential impact of climatic change on this industry. Here, we used weekly data of syrup yield for the 1999–2011 period from 121 maple stands in 11 regions of Québec (Canada) to predict how the period of production may be impacted by climate warming. The date at which the production begins is highly variable between years with an average range of 36 days among the regions. However, the average start date for a given region, which ranged from Julian day 65 to 83, was highly predictable (r² = 0.88) using the average temperature from January to April (T_J-A). A logistic model predicting the weekly presence or absence of production was also developed. Using the inputs of 77 future climate scenarios issued from global models, projections of future production timing were made based on average T_J-A and on the logistic model. The projections of both approaches were in very good agreement and suggest that the sap season will be displaced to occur 15–19 days earlier on average in the 2080–2100 period. The data also show that the displacement in time will not be accompanied by a greater between years variability in the beginning of the season. However, in the southern part of Québec, very short periods of syrup production due to unfavourable conditions in the spring will occur more frequently in the future although their absolute frequencies will remain low.     

Detection of Innate Immune Response Modulating Impurities in Therapeutic Proteins

Therapeutic proteins can contain multiple impurities, some of which are variants of the product, while others are derived from the cell substrate and the manufacturing process. Such impurities, even when present at trace levels, have the potential to activate innate immune cells in peripheral blood or embedded in tissues causing expression of cytokines and chemokines, increasing antigen uptake, facilitating processing and presentation by antigen presenting cells, and fostering product immunogenicity. Currently, while products are tested for host cell protein content, assays to control innate immune response modulating impurities (IIRMIs) in products are focused mainly on endotoxin and nucleic acids, however, depending on the cell substrate and the manufacturing process, numerous other IIRMI could be present. In these studies we assess two approaches that allow for the detection of a broader subset of IIRMIs. In the first, we use commercial cell lines transfected with Toll like receptors (TLR) to detect receptor-specific agonists. This method is sensitive to trace levels of IIRMI and provides information of the type of IIRMIs present but is limited by the availability of stably transfected cell lines and requires pre-existing knowledge of the IIRMIs likely to be present in the product. Alternatively, the use of a combination of macrophage cell lines of human and mouse origin allows for the detection of a broader spectrum of impurities, but does not identify the source of the activation. Importantly, for either system the lower limit of detection (LLOD) of impurities was similar to that of PBMC and it was not modified by the therapeutic protein tested, even in settings where the product had inherent immune modulatory properties. Together these data indicate that a cell-based assay approach could be used to screen products for the presence of IIRMIs and inform immunogenicity risk assessments, particularly in the context of comparability exercises.     

IL-4Rα-Dependent Alternative Activation of Macrophages Is Not Decisive for Mycobacterium tuberculosis Pathology and Bacterial Burden in Mice

Classical activation of macrophages (caMph or M1) is crucial for host protection against Mycobacterium tuberculosis (Mtb) infection. Evidence suggests that IL-4/IL-13 alternatively activated macrophages (aaMph or M2) are exploited by Mtb to divert microbicidal functions of caMph. To define the functions of M2 macrophages during tuberculosis (TB), we infected mice deficient for IL-4 receptor α on macrophages (LysM^creIL-4Rα^-/lox) with Mtb. We show that absence of IL-4Rα on macrophages does not play a major role during infection with Mtb H37Rv, or the clinical Beijing strain HN878. This was demonstrated by similar mortality, bacterial burden, histopathology and T cell proliferation between infected wild-type (WT) and LysM^creIL-4Rα^-/lox mice. Interestingly, we observed no differences in the lung expression of inducible nitric oxide synthase (iNOS) and Arginase 1 (Arg1), well-established markers for M1/M2 macrophages among the Mtb-infected groups. Kinetic expression studies of IL-4/IL-13 activated bone marrow-derived macrophages (BMDM) infected with HN878, followed by gene set enrichment analysis, revealed that the MyD88 and IL-6, IL-10, G-CSF pathways are significantly enriched, but not the IL-4Rα driven pathway. Together, these results suggest that IL-4Rα-macrophages do not play a central role in TB disease progression.     

Alterations in mitochondrial dynamics with age‐related Sirtuin1/Sirtuin3 deficiency impair cardiomyocyte contractility

Sirtuin1 (SIRT1) and Sirtuin3 (SIRT3) protects cardiac function against ischemia/reperfusion (I/R) injury. Mitochondria are critical in response to myocardial I/R injury as disturbance of mitochondrial dynamics contributes to cardiac dysfunction. It is hypothesized that SIRT1 and SIRT3 are critical components to maintaining mitochondria homeostasis especially mitochondrial dynamics to exert cardioprotective actions under I/R stress. The results demonstrated that deficiency of SIRT1 and SIRT3 in aged (24–26 months) mice hearts led to the exacerbated cardiac dysfunction in terms of cardiac systolic dysfunction, cardiomyocytes contractile defection, and abnormal cardiomyocyte calcium flux during I/R stress. Moreover, the deletion of SIRT1 or SIRT3 in young (4–6 months) mice hearts impair cardiomyocyte contractility and shows aging‐like cardiac dysfunction upon I/R stress, indicating the crucial role of SIRT1 and SIRT3 in protecting myocardial contractility from I/R injury. The biochemical and seahorse analysis showed that the deficiency of SIRT1/SIRT3 leads to the inactivation of AMPK and alterations in mitochondrial oxidative phosphorylation (OXPHOS) that causes impaired mitochondrial respiration in response to I/R stress. Furthermore, the remodeling of the mitochondria network goes together with hypoxic stress, and mitochondria undergo the processes of fusion with the increasing elongated branches during hypoxia. The transmission electron microscope data showed that cardiac SIRT1/SIRT3 deficiency in aging alters mitochondrial morphology characterized by the impairment of mitochondria fusion under I/R stress. Thus, the age‐related deficiency of SIRT1/SIRT3 in the heart affects mitochondrial dynamics and respiration function that resulting in the impaired contractile function of cardiomyocytes in response to I/R.