Intracellular survival of Burkholderia cenocepacia in macrophages is associated with a delay in the maturation of bacteria-containing vacuoles

Strains of the Burkholderia cepacia complex (Bcc) are opportunistic bacteria that can cause life-threatening infections in patients with cystic fibrosis and chronic granulomatous disease. Previous work has shown that Bcc isolates can persist in membrane-bound vacuoles within amoeba and macrophages without bacterial replication, but the detailed mechanism of bacterial persistence is unknown. In this study, we have investigated the survival of the Burkholderia cenocepacia strain J2315 within RAW264.7 murine macrophages. Strain J2315 is a prototypic isolate of the widespread and transmissible ET12 clone. Unlike heat-inactivated bacteria, which reach lysosomes shortly after internalization, vacuoles containing live B. cenocepacia J2315 accumulate the late endosome/lysosome marker LAMP-1 and start fusing with lysosomal compartments only after 6 h post internalization. Using fluorescent fluid-phase probes, we also demonstrated that B. cenocepacia-containing vacuoles continued to interact with newly formed endosomes, and maintained a luminal pH of 6.4 +/- 0.12. In contrast, vacuoles containing heat-inactivated bacteria had an average pH of 4.8 +/- 0.03 and rapidly merged with lysosomes. Additional experiments using concanamycin A, a specific inhibitor of the vacuolar H+-ATPase, revealed that vacuoles containing live bacteria did not exclude the H+-ATPase. This mode of bacterial survival did not require type III secretion, as no differences were found between wild type and a type III secretion mutant strain. Collectively, our results suggest that intracellular B. cenocepacia cause a delay in the maturation of the phagosome, which may contribute to facilitate bacterial escape from the microbicidal activities of the host cell.

Obesity associated severe asthma represents a distinct clinical phenotype - Analysis of the British Thoracic Society Difficult Asthma Registry patient cohort according to body mass index

BACKGROUND: Obesity has emerged as a risk factor for the development of asthma and it may also influence asthma control and airways inflammation. However, the role of obesity in severe asthma remains unclear. OBJECTIVE: To explore the association between obesity (defined by BMI) and severe asthma. METHODS: Data from the National Registry for dedicated UK Difficult Asthma Services were used to compare patient demographics, disease characteristics and healthcare utilisation between three body mass index (BMI) categories (normal weight: 18.5 -24.99, overweight: 25 -29.99, obese: =30) in a well characterised group of severe asthmatic adults. RESULTS: The study population consisted of 666 severe asthmatics with a median BMI of 29.8 (interquartile range 22.5 -34.0). The obese group exhibited greater asthma medication requirements in terms of maintenance corticosteroid therapy (48.9% versus 40.4% and 34.5% in the overweight and normal weight groups, respectively), steroid burst therapy and short-acting ß2-agonist (SABA) use per day. Significant differences were seen with gastro-oesophageal reflux disease (GORD) (53.9% versus 48.1% and 39.7% in the overweight and normal weight groups, respectively) and proton pump inhibitor (PPI) use. Bone density scores were higher in the obese group, whilst pulmonary function testing revealed a reduced FVC and raised Kco. Serum IgE levels decreased with increasing BMI and the obese group were more likely to report eczema, but less likely to have a history of nasal polyps. CONCLUSIONS: Severe asthmatics display particular characteristics according to BMI that support the view that obesity associated severe asthma may represent a distinct clinical phenotype.1Royal Brompton Hospital, London, UK;2Department of Computing, Imperial College, UK3Airways Disease, National Heart & Lung Institute, Imperial College, UK;4Centre for infection and immunity, Queen's University of Belfast, UK;5University of Leicester, UK;6The University of Manchester and University Hospital of South Manchester, UK;7Birmingham Heartlands Hospital, University of Birmingham, UK;8Gartnavel General Hospital, University of Glasgow, UK;9Glasgow Royal Infirmary, Glasgow, UKCorrespondence: Dr Andrew N. Menzies-Gow, Royal Brompton Hospital, Fulham Road, London SW3 6HP.

Optical transmission of periodic annular apertures in metal film on high-refractive index substrate: The role of the nanopillar shape

The influence of annular aperture parameters on the optical transmission through arrays of coaxial apertures in a metal film on high refractive index substrates has been investigated experimentally and numerically. It is shown that the transmission resonances are related to plasmonic crystal effects rather than frequency cutoff behavior associated with annular apertures. The role of deviations from ideal aperture shape occurring during the fabrication process has also been studied. Annular aperture arrays are often considered in many applications for achieving high optical transmission through metal films and understanding of nanofabrication tolerances are important. (C) 2010 American Institute of Physics.

Cognitive maturation in preterm and term born adolescents

Background: Adolescence is a critical period of brain structural reorganisation and maturation of cognitive abilities. This relatively late developmental reorganisation may be altered in individuals who were born preterm.

Methods: We carried out longitudinal neuropsychological testing in 94 very preterm individuals (VPT; before 33 weeks' gestation) and 44 term born individuals at mean ages of 15.3 years ( adolescence) and 19.5 years (young adulthood).

Results: Full scale, verbal and performance IQ and phonological verbal fluency were significantly lower in the VPT group than the term group at both ages. Repeated measures ANOVA showed only one group by time point interaction for semantic verbal fluency (F= 10.25; df = 107; p = 0.002). Paired- sample t tests showed that semantic verbal fluency increased significantly in the term group over adolescence (t = -5.10; df = 42; p < 0.001), but did not increase in the VPT group (t = 0.141; df = 69; p = 0.889). For verbal IQ, there was a significant interaction between time point and sex (F = 4.48; df = 1; p = 0.036) with paired- sample t tests showing that verbal IQ decreased in males between adolescence and adulthood (t = 3.35; df = 71; p = 0.001), but did not change significantly in females (t = 0.20; df = 52; p = 0.845).

Conclusion: Decrements of intellectual functioning in VPT individuals persist into adulthood. Additionally, there is a deficit in the adolescent maturation of semantic verbal fluency in individuals born VPT.

Slower postnatal growth is associated with delayed cerebral cortical maturation in preterm newborns

Slower postnatal growth is an important predictor of adverse neurodevelopmental outcomes in infants born preterm. However, the relationship between postnatal growth and cortical development remains largely unknown. Therefore, we examined the association between neonatal growth and diffusion tensor imaging measures of microstructural cortical development in infants born very preterm. Participants were 95 neonates born between 24 and 32 weeks gestational age studied twice with diffusion tensor imaging: scan 1 at a median of 32.1 weeks (interquartile range, 30.4 to 33.6) and scan 2 at a median of 40.3 weeks (interquartile range, 38.7 to 42.7). Fractional anisotropy and eigenvalues were recorded from 15 anatomically defined cortical regions. Weight, head circumference, and length were recorded at birth and at the time of each scan. Growth between scans was examined in relation to diffusion tensor imaging measures at scans 1 and 2, accounting for gestational age, birth weight, sex, postmenstrual age, known brain injury (white matter injury, intraventricular hemorrhage, and cerebellar hemorrhage), and neonatal illness (patent ductus arteriosus, days intubated, infection, and necrotizing enterocolitis). Impaired weight, length, and head growth were associated with delayed microstructural development of the cortical gray matter (fractional anisotropy: P <0.001), but not white matter (fractional anisotropy: P = 0.529), after accounting for prenatal growth, neonatal illness, and brain injury. Avoiding growth impairment during neonatal care may allow cortical development to proceed optimally and, ultimately, may provide an opportunity to reduce neurological disabilities related to preterm birth.

The impact of body mass index on maternal and neonatal outcomes: a retrospective study in a UK obstetric population, 2004-2011

Objective: To assess the prevalence of overweight and obesity, and the impact of body mass index (BMI) on maternal and neonatal outcomes, in a UK obstetric population.
Design: Retrospective study.
Setting: A tertiary referral unit in Northern Ireland.
Population: A total of 30 298 singleton pregnancies over an 8-year period, 2004–2011.
Methods: Women were categorised according to World Health Organization classification: underweight (BMI < 18.50 kg/m2); normal weight (BMI 18.50–24.99 kg/m2; reference group); overweight (BMI 25.00–29.99 kg/m2); obese class I (BMI 30.00–34.99 kg/m2); obese class II (BMI 35–39.99 kg/m2); and obese class III (BMI = 40 kg/m2). Maternal and neonatal outcomes were examined using logistic regression, adjusted for confounding variables.
Main outcome measures: Maternal and neonatal outcomes.
Results: Compared with women of normal weight, women who were overweight or obese class I were at significantly increased risk of hypertensive disorders of pregnancy (OR 1.9, 99% CI 1.7–2.3; OR 3.5, 99% CI 2.9–4.2); gestational diabetes mellitus (OR 1.7, 99% CI 1.3–2.3; OR 3.7, 99% CI 2.8–5.0); induction of labour (OR 1.2, 99% CI 1.1–1.3; OR 1.3, 99% CI 1.2–1.5); caesarean section (OR 1.4, 99% CI 1.3–1.5; OR 1.8, 99% CI 1.6–2.0); postpartum haemorrhage (OR 1.4, 99% CI 1.3–1.5; OR 1.8, 1.6–2.0); and macrosomia (OR 1.5, 99% CI 1.3–1.6; OR 1.9, 99% CI 1.6–2.2), with the risks increasing for obese classes II and III. Women in obese class III were at increased risk of preterm delivery (OR 1.6, 99% CI 1.1–2.5), stillbirth (OR 3.0, 99% CI 1.0–9.3), postnatal stay > 5 days (OR 2.1, 99% CI 1.5–3.1), and infant requiring admission to a neonatal unit (OR 1.6, 99% CI 1.0–2.6).
Conclusions: By categorising women into overweight and obesity subclassifications (classes I –III), this study clearly demonstrates an increasing risk of adverse outcomes across BMI categories, with women who are overweight also at significant risk.
Keywords Body mass index, maternal and neonatal outcomes,obesity, pregnancy

Economic globalization, inequality and body mass index:a cross-national analysis of 127 countries

This article investigates to what extent the worldwide increase in body mass index (BMI) has been affected by economic globalization and inequality. We used time-series and longitudinal cross-national analysis of 127 countries from 1980 to 2008. Data on mean adult BMI were obtained from the Global Burden of Metabolic Risk Factors of Chronic Diseases Collaborating Group. Globalization was measured using the Swiss Economic Institute (KOF) index of economic globalization. Economic inequality between countries was measured with the mean difference in gross domestic product per capita purchasing power parity in international dollars. Economic inequality within countries was measured using the Gini index from the Standardized World Income Inequality Database. Other covariates including poverty, population size, urban population, openness to trade and foreign direct investment were taken from the World Development Indicators (WDI) database. Time-series regression analyses showed that the global increase in BMI is positively associated with both the index of economic globalization and inequality between countries, after adjustment for covariates. Longitudinal panel data analyses showed that the association between economic globalization and BMI is robust after controlling for all covariates and using different estimators. The association between economic inequality within countries and BMI, however, was significant only among high-income nations. More research is needed to study the pathways between economic globalization and BMI. These findings, however, contribute to explaining how contemporary globalization can be reformed to promote better health and control the global obesity epidemic. © 2013 Copyright Taylor and Francis Group, LLC.

Nonparametric Estimation of Data Dimensionality Prior to Data Compression: the case of the Human Development Index

In many applications in applied statistics researchers reduce the complexity of a data set by combining a group of variables into a single measure using factor analysis or an index number. We argue that such compression loses information if the data actually has high dimensionality. We advocate the use of a non-parametric estimator, commonly used in physics (the Takens estimator), to estimate the correlation dimension of the data prior to compression. The advantage of this approach over traditional linear data compression approaches is that the data does not have to be linearized. Applying our ideas to the United Nations Human Development Index we find that the four variables that are used in its construction have dimension three and the index loses information.

Effect of cataract extraction on the Glaucoma Progression Index (GPI) in glaucoma patients

PURPOSE: To determine the effect of cataract extraction on the glaucoma progression index (GPI) in glaucoma patients with coexisting cataract.

PATIENTS AND METHODS: This is a retrospective noncomparative study. Consecutive eligible patients with glaucoma who underwent phacoemulsification alone or in combination with augmented trabeculectomy were included. All patients had Swedish Interactive Threshold Algorithm-standard 24-2 visual fields within 10 months of surgery. Exclusion criteria included other ocular morbidity, intraoperative complications, and perimetric reliability indices greater than 33%. Comparison was made between the immediate visual fields before and after surgery. The main outcome measure was the change in GPI. Changes in the pattern standard deviation (PSD) and mean deviation (MD) were also assessed. Comparison of means was performed with the paired t test.

RESULTS: Thirty-three eyes of 33 patients (all Whites) were analyzed. The mean age at surgery was 77.0+/-8.7 years. Visual field tests were performed 3.3+/-3.0 months SD before surgery and 5.4+/-2.6 months after surgery. There was a statistically significant increase in the GPI after cataract surgery (from 71.5+/-18.5% to 74.6+/-17.1%; P=0.02). The improvement in MD was also statistically significant (from -11.8+/-5.3 to -10.2+/-5.3 dB; P <0.01), but the change in PSD did not reach statistical significance.

CONCLUSIONS: Uncomplicated cataract extraction resulted in a statistically significant improvement in the 24-2 Swedish Interactive Threshold Algorithm-standard GPI and MD, but not in PSD. Both the MD and the GPI may be influenced by lens opacities, which could make detection of glaucoma visual field progression more difficult for clinicians in glaucoma patients with concurrent cataract.

Perimetric progression in open angle glaucoma and the Visual Field Index (VFI)

PURPOSE: To evaluate the changes in the Visual Field Index (VFI) in eyes with perimetric glaucomatous progression, and to compare these against stable glaucoma patients.

PATIENTS AND METHODS: Consecutive patients with open angle glaucoma with a minimum of 6 reliable visual fields and 2 years of follow-up were identified. Perimetric progression was assessed by 4 masked glaucoma experts from different units, and classified into 3 categories: "definite progression," "suspected progression," or "no progression." This was compared with the Glaucoma Progression Analysis (GPA) II and VFI linear regression analysis, where progression was defined as a negative slope with significance of <5%.

RESULTS: Three hundred ninety-seven visual fields from 51 eyes of 39 patients were assessed. The mean number of visual fields was 7.8 (SD 1.1) per eye, and the mean follow-up duration was 63.7 (SD 13.4) months. The mean VFI linear regression slope showed an overall statistically significant difference (P<0.001, analysis of variance) for each category of progression. Using expert consensus opinion as the reference standard, both VFI analysis and GPA II had high specificity (0.93 and 0.90, respectively), but relatively low sensitivity (0.45 and 0.41, respectively).

CONCLUSIONS: The mean VFI regression slope in our cohort of eyes without perimetric progression showed a statistically significant difference compared with those with suspected and definite progression. VFI analysis and GPA II both had similarly high specificity but low sensitivity when compared with expert consensus opinion.