Association between genotypic diversity and biofilm production in group B Streptococcus

Background: Group B Streptococcus (GBS) is a leading cause of sepsis and meningitis and an important factor in premature and stillbirths. Biofilm production has been suggested to be important for GBS pathogenesis alongside many other elements, including phylogenetic lineage and virulence factors, such as pili and capsule type. A complete understanding of the confluence of these components, however, is lacking. To identify associations between biofilm phenotype, pilus profile and lineage, 293 strains from asymptomatic carriers, invasive disease cases, and bovine mastitis cases, were assessed for biofilm production using an in vitro assay. Results: Multilocus sequence type (ST) profile, pilus island profile, and isolate source were associated with biofilm production. Strains from invasive disease cases and/or belonging to the ST-17 and ST-19 lineages were significantly more likely to form weak biofilms, whereas strains producing strong biofilms were recovered more frequently from individuals with asymptomatic colonization. Conclusions: These data suggest that biofilm production is a lineage-specific trait in GBS and may promote colonization of strains representing lineages other than STs 17 and 19. The findings herein also demonstrate that biofilms must be considered in the treatment of pregnant women, particularly for women with heavy GBS colonization

Air Pollution and Childhood Respiratory Allergies in the United States

BackgroundChildhood respiratory allergies, which contribute to missed school days and other activity limitations, have increased in recent years, possibly due to environmental factors.ObjectiveIn this study we examined whether air pollutants are associated with childhood respiratory allergies in the United States.MethodsFor the approximately 70,000 children from the 1999-2005 National Health Interview Survey eligible for this study, we assigned between 40,000 and 60,000 ambient pollution monitoring data from the U.S. Environmental Protection Agency, depending on the pollutant. We used monitors within 20 miles of the child's residential block group. We used logistic regression models, fit with methods for complex surveys, to examine the associations between the reporting of respiratory allergy or hay fever and annual average exposure to particulate matter < or = 2.5 microm in diameter (PM2.5), PM < or = 10 microm in diameter, sulfur dioxide, and nitrogen dioxide and summer exposure to ozone, controlling for demographic and geographic factors.ResultsIncreased respiratory allergy/hay fever was associated with increased summer O3 levels [adjusted odds ratio (AOR) per 10 ppb = 1.20; 95% confidence interval (CI), 1.15-1.26] and increased PM2.5 (AOR per 10 microg/m3 = 1.23; 95% CI, 1.10-1.38). These associations persisted after stratification by urban-rural status, inclusion of multiple pollutants, and definition of exposures by differing exposure radii. No associations between the other pollutants and the reporting respiratory allergy/hay fever were apparent.ConclusionsThese results provide evidence of adverse health for children living in areas with chronic exposure to higher levels of O3 and PM2.5 compared with children with lower exposures

Fine Particulate Matter (PM(2.5)) Air Pollution and Selected Causes of Postneonatal Infant Mortality in California

Studies suggest that airborne particulate matter (PM) may be associated with postneonatal infant mortality, particularly with respiratory causes and sudden infant death syndrome (SIDS). To further explore this issue, we examined the relationship between long-term exposure to fine PM air pollution and postneonatal infant mortality in California. We linked monitoring data for PM ≤2.5 μm in aerodynamic diameter (PM(2.5)) to infants born in California in 1999 and 2000 using maternal addresses for mothers who lived within 5 miles of a PM(2.5) monitor. We matched each postneonatal infant death to four infants surviving to 1 year of age, by birth weight category and date of birth (within 2 weeks). For each matched set, we calculated exposure as the average PM(2.5) concentration over the period of life for the infant who died. We used conditional logistic regression to estimate the odds of postneonatal all-cause, respiratory-related, SIDS, and external-cause (a control category) mortality by exposure to PM(2.5), controlling for the matched sets and maternal demographic factors. We matched 788 postneonatal infant deaths to 3,089 infant survivors, with 51 and 120 postneonatal deaths due to respiratory causes and SIDS, respectively. We found an adjusted odds ratio for a 10−μg/m(3) increase in PM(2.5) of 1.07 [95% confidence interval (CI), 0.93–1.24] for overall postneonatal mortality, 2.13 (95% CI, 1.12–4.05) for respiratory-related postneonatal mortality, 0.82 (95% CI, 0.55–1.23) for SIDS, and 0.83 (95% CI, 0.50–1.39) for external causes. The California findings add further evidence of a PM air pollution effect on respiratory-related postneonatal infant mortality

Comparison of Quarterly and Yearly Calibration Data for Propensity Score Adjusted Web Survey Estimates

While web surveys have become increasingly popular as a method of data collection, there is concern that estimates obtained from web surveys may not reflect the target population of interest. Web survey estimates can be calibrated to existing national surveys using a propensity score adjustment, although requirements for the size and collection timeline of the reference data set have not been investigated. We evaluate health outcomes estimates from the National Center for Health Statistics’ Research and Development web survey. In our study, the 2016 National Health Interview Survey as well as its quarterly subsets are considered as reference datasets for the web data. It is demonstrated that the calibrated health estimates overall vary little when using the quarterly or yearly data, suggesting that there is flexibility in selecting the reference dataset. This finding has many practical implications for constructing reference data, including the reduced cost and burden of a smaller sample size and a more flexible timeline

Chronic IL9 and IL-13 Exposure Leads to an Altered Differentiation of Ciliated Cells in a Well-Differentiated Paediatric Bronchial Epithelial Cell Model

Asthma is a chronic inflammatory disease characterised by airways remodelling. In mouse models IL-9 and IL-13 have been implicated in airways remodelling including mucus hypersecretion and goblet cell hyperplasia. Their role, especially that of IL-9, has been much less studied in authentic human ex vivo models of the bronchial epithelium from normal and asthmatic children. We assessed the effects of IL-9, IL-13 and an IL-9/IL-13 combination, during differentiation of bronchial epithelial cells from normal (n = 6) and asthmatic (n = 8) children. Cultures were analysed for morphological markers and factors associated with altered differentiation (MUC5AC, SPDEF and MMP-7). IL-9, IL-9/IL-13 combination and IL-13 stimulated bronchial epithelial cells from normal children had fewer ciliated cells [14.8% (SD 8.9), p = 0.048, 12.4 (SD 6.1), p = 0.016 and 7.3% (SD 6.6), p = 0.031] respectively compared with unstimulated [(21.4% (SD 9.6)]. IL-9 stimulation had no effect on goblet cell number in either group whereas IL-9/IL-13 combination and IL-13 significantly increased goblet cell number [24.8% (SD 8.8), p = 0.02), 32.9% (SD 8.6), p = 0.007] compared with unstimulated normal bronchial cells [(18.6% (SD 6.2)]. All stimulations increased MUC5AC mRNA in bronchial epithelial cells from normal children and increased MUC5AC mucin secretion. MMP-7 localisation was dysregulated in normal bronchial epithelium stimulated with Th2 cytokines which resembled the unstimulated bronchial epithelium of asthmatic children. All stimulations resulted in a significant reduction in transepithelial electrical resistance values over time suggesting a role in altered tight junction formation. We conclude that IL-9 does not increase goblet cell numbers in bronchial epithelial cell cultures from normal or asthmatic children. IL-9 and IL-13 alone and in combination, reduce ciliated cell numbers and transepithelial electrical resistance during differentiation of normal epithelium, which clinically could inhibit mucociliary clearance and drive an altered repair mechanism. This suggests an alternative role for IL-9 in airways remodelling and reaffirms IL-9 as a potential therapeutic target

B-Type Natriuretic Peptide in Pregnant Women With Heart Disease

ObjectivesThe objectives of this study were to examine: 1) B-type natriuretic peptide (BNP) response to pregnancy in women with heart disease; and 2) the relationship between BNP levels and adverse maternal cardiac events during pregnancy.BackgroundPregnancy imposes a hemodynamic stress on the heart. BNP might be a useful biomarker to assess the ability of the heart to adapt to the hemodynamic load of pregnancy.MethodsThis was a prospective study of women with structural heart disease seen at our center. Serial clinical data and plasma BNP measurements were obtained during the first trimester, third trimester, and after delivery (>6 weeks).ResultsSeventy-eight pregnant women were studied; 66 women with heart disease (age 31 ± 5 years), and 12 healthy women (age 33 ± 5 years). During pregnancy, the median peak BNP level was higher in women with heart disease compared with control subjects (median 79, interquartile range 51 to 152 pg/ml vs. median 35, interquartile range 21 to 43 pg/ml, p < 0.001). In women with heart disease, those with subaortic ventricular dysfunction had higher BNP levels (p = 0.03). A BNP >100 pg/ml was measured in all women with events during pregnancy (n = 8). Sixteen women had increased BNP levels during pregnancy but did not have clinical events. None of the women with BNP ≤100 pg/ml had events. BNP ≤100 pg/ml had a negative predictive value of 100% for identifying events during pregnancy.ConclusionsMany pregnant women with heart disease have increased BNP levels during pregnancy. Incorporating serial BNP levels in into clinical practice can be helpful, specifically in adjudicating suspected adverse cardiac events during pregnancy

Leptin fails to blunt the lipopolysaccharide-induced activation of the hypothalamic-pituitary-adrenal axis in rats

Copyright @ 2013 The authors. This work is licensed under a Creative Commons Attribution 3.0 Unported License.Obesity is a risk factor for sepsis morbidity and mortality, whereas the hypothalamic-pituitary-adrenal (HPA) axis plays a protective role in the body's defence against sepsis. Sepsis induces a profound systemic immune response and cytokines serve as excellent markers for sepsis as they act as mediators of the immune response. Evidence suggests that the adipokine leptin may play a pathogenic role in sepsis. Mouse endotoxaemic models present with elevated leptin levels and exogenously added leptin increased mortality whereas human septic patients have elevated circulating levels of the soluble leptin receptor (Ob-Re). Evidence suggests that leptin can inhibit the regulation of the HPA axis. Thus, leptin may suppress the HPA axis, impairing its protective role in sepsis.We hypothesised that leptin would attenuate the HPA axis response to sepsis.We investigated the direct effects of an i.p. injection of 2 mg/kg leptin on the HPA axis response to intraperitoneally injected 25 μg/kg lipopolysaccharide (LPS) in the male Wistar rat. We found that LPS potently activated the HPA axis, as shown by significantly increased plasma stress hormones, ACTH and corticosterone, and increased plasma interleukin 1β (IL1β) levels, 2 h after administration. Pre-treatment with leptin, 2 h before LPS administration, did not influence the HPA axis response to LPS. In turn, LPS did not affect plasma leptin levels. Our findings suggest that leptin does not influence HPA function or IL1b secretion in a rat model of LPS-induced sepsis, and thus that leptin is unlikely to be involved in the acute-phase endocrine response to bacterial infection in rats.The section is funded by grants from the MRC, BBSRC, NIHR and an Integrative Mammalian Biology (IMB) Capacity Building Award, and by a FP7-HEALTH-2009-241592 EuroCHIP grant and is supported by the NIHR Imperial Biomedical Research Centre Funding Scheme. This work is supported by a BBSRC Doctoral Training-Strategic Skills Award grant (BB/F017340/1)