Comparative Analysis of Fecal Microbiota in Infants with and without Eczema

Eczema is a chronic form of childhood disorder that is gaining in prevalence in affluent societies. Previous studies hypothesized that the development of eczema is correlated with changes in microbial profile and composition of early life endemic microbiota, but contradictory conclusions were obtained, possibly due to the lack of minimization of apparent non-health related confounders (e.g., age, antibiotic consumption, diet and mode of delivery). In this study, we recruited seven caesarean-delivered and total formula-fed infants, and comparatively examined the early-life endemic microbiota in these infants with and without eczema. Using 16S pyrosequencing, infants' fecal microbiota were observed to comprise Proteobacteria, Firmicutes, Actinobacteria and Bacteroidetes as the four main phyla, and the presence and absence of specific populations within these four phyla are primarily mediated by ageing. Quantitative analysis of bacterial targets on a larger sample size (n = 36 at 1, 3, and 12 months of age) revealed that the abundances of Bifidobacterium and Enterobacteriaceae were different among caesarean-delivered infants with and without eczema, and the bacterial targets may be potential biomarkers that can correlate to the health status of these infants. Our overall findings suggest that the minimization of possible confounders is essential prior to comparative evaluation and correlation of fecal microbiota to health status, and that stool samples collected from caesarean-delivered infants at less than 1 year of age may represent a good cohort to study for potential biomarkers that can distinguish infants with eczema from those without. These findings would greatly facilitate future efforts in understanding the possible pathogenesis behind certain bacterial targets, and may lead to a timely intervention that reduces the occurrence of early life eczema and possibly allergic disorders in later life

Metabolomics to unveil and understand phenotypic diversity between pathogen populations

Visceral leishmaniasis is caused by a parasite called Leishmania donovani, which every year infects about half a million people and claims several thousand lives. Existing treatments are now becoming less effective due to the emergence of drug resistance. Improving our understanding of the mechanisms used by the parasite to adapt to drugs and achieve resistance is crucial for developing future treatment strategies. Unfortunately, the biological mechanism whereby Leishmania acquires drug resistance is poorly understood. Recent years have brought new technologies with the potential to increase greatly our understanding of drug resistance mechanisms. The latest mass spectrometry techniques allow the metabolome of parasites to be studied rapidly and in great detail. We have applied this approach to determine the metabolome of drug-sensitive and drug-resistant parasites isolated from patients with leishmaniasis. The data show that there are wholesale differences between the isolates and that the membrane composition has been drastically modified in drug-resistant parasites compared with drug-sensitive parasites. Our findings demonstrate that untargeted metabolomics has great potential to identify major metabolic differences between closely related parasite strains and thus should find many applications in distinguishing parasite phenotypes of clinical relevance

A dimensioning and tolerancing methodology for concurrent engineering applications I: problem representation

This paper is the first of two which present a methodology for determining the dimensional specifications of all the component parts and sub-assemblies of a product according to their dimensional requirements. To achieve this goal, two major steps are followed, each of which is described in a paper. In the first paper, all relationships necessary for finding the values of dimensions and tolerances are represented in a matrix form, known as a Dimensional Requirements/Dimensions (DR/D) matrix. In the second paper, the values of individual dimensions and tolerances are determined by applying a comprehensive solution strategy to satisfy all the relationships represented in the DR/D matrix. The methodology is interactive and suitable for use in a concurrent engineering (CE) environment. The graphical tool presented in this paper will assist a CE team in visualizing the overall D&T problem and foreseeing the ramifications of decisions regarding the selection of dimensions and tolerances. This will assist the CE team to systematically determine all the controllable variables, such as dimensions, tolerances, and manufacturing processes

A dimensioning and tolerancing methodology for concurrent engineering applications II: comprehensive solution strategy

Dimensioning and tolerancing (D&T) is a multidisciplinary problem which requires the fulfillment of a large number of dimensional requirements. However, almost all of the currently available D&T tools are only intended for use by the designer. In addition, they typically provide solutions for the requirements one at time. This paper presents a methodology for determining the dimensional specifications of the component parts and sub-assemblies of a product by satisfying all of its requirements. The comprehensive solution strategy presented here includes: a strategy for separating D&T problems into groups, the determination of an optimum solution order for coupled functional equations, a generic tolerance allocation strategy, and strategies for solving different types of D&T problems. A number of commonly used cost minimization strategies, such as the use of standard parts, preferred sizes, preferred fits, and preferred tolerances, have also been incorporated into the proposed methodology. The methodology is interactive and intended for use in a concurrent engineering environment by members of a product development team

The web-based ASSO-food frequency questionnaire for adolescents: relative and absolute reproducibility assessment

Background: A new food frequency questionnaire (FFQ) has been recently developed within the Italian Adolescents and Surveillance System for the Obesity prevention (ASSO) Project; it was found to be appropriate for ranking adolescents in food and nutrient levels of intake. The aim of this study was to assess the relative and absolute reproducibility of the ASSO-FFQ for 24 food groups, energy and 52 nutrients. Methods: A test-retest study was performed on two ASSO-FFQs administered one month apart of each other to 185 adolescents, aged 14–17 and attending secondary schools in Palermo (Italy). Wilcoxon test assessed differences in median daily intakes between the two FFQs. Agreement was evaluated by quintiles comparison and weighted kappa. Intraclass Correlation Coefficients (ICC) and Bland-Altman method assessed the relative and absolute reliability respectively. Results: Significant difference (p < 0.05) in median intakes was found only for bread substitutes, savoury food, water, soft drinks, carbohydrates and sugar. The subjects classified into the same or adjacent quintiles for food groups ranged from 62% (white bread) to 91% (soft drinks); for energy and nutrients from 64% (polyunsaturated fatty acids) to 90% (ethanol). Mean values of weighted kappa were 0.47 and 0.48, respectively for food groups and nutrients. Fair to good ICC values (>0.40) were assessed for thirteen food groups, energy and forty-three nutrients. Limits of Agreement were narrow for almost all food groups and all nutrients. Conclusions: The ASSO-FFQ is a reliable instrument for estimating food groups, energy and nutrients intake in adolescents

The chemopreventive polyphenol Curcumin prevents hematogenous breast cancer metastases in immunodeficient mice

Dissemination of metastatic cells probably occurs long before diagnosis of the primary tumor. Metastasis during early phases of carcinogenesis in high risk patients is therefore a potential prevention target. The plant polyphenol Curcumin has been proposed for dietary prevention of cancer. We therefore examined its effects on the human breast cancer cell line MDA-MB-231 in vitro and in a mouse metastasis model. Curcumin strongly induces apoptosis in MDA- MB- 231 cells in correlation with reduced activation of the survival pathway NF kappa B, as a consequence of diminished I kappa B and p65 phosphorylation. Curcumin also reduces the expression of major matrix metalloproteinases (MMPs) due to reduced NF kappa B activity and transcriptional downregulation of AP-1. NF kappa B/p65 silencing is sufficient to downregulate c-jun and MMP expression. Reduced NF kappa B/AP-1 activity and MMP expression lead to diminished invasion through a reconstituted basement membrane and to a significantly lower number of lung metastases in immunodeficient mice after intercardiac injection of 231 cells (p=0.0035). 68% of Curcumin treated but only 17% of untreated animals showed no or very few lung metastases, most likely as a consequence of down-regulation of NF kappa B/AP-1 dependent MMP expression and direct apoptotic effects on circulating tumor cells but not on established metastases. Dietary chemoprevention of metastases appears therefore feasible. Copyright (c) 2007 S. Karger AG, Basel

The frontline antibiotic vancomycin induces a zinc starvation response in bacteria by binding to Zn(II).

Vancomycin is a front-line antibiotic used for the treatment of nosocomial infections, particularly those caused by methicillin-resistant Staphylococcus aureus. Despite its clinical importance the global effects of vancomycin exposure on bacterial physiology are poorly understood. In a previous transcriptomic analysis we identified a number of Zur regulon genes which were highly but transiently up-regulated by vancomycin in Streptomyces coelicolor. Here, we show that vancomycin also induces similar zinc homeostasis systems in a range of other bacteria and demonstrate that vancomycin binds to Zn(II) in vitro. This implies that vancomycin treatment sequesters zinc from bacterial cells thereby triggering a Zur-dependent zinc starvation response. The Kd value of the binding between vancomycin and Zn(II) was calculated using a novel fluorometric assay, and NMR was used to identify the binding site. These findings highlight a new biologically relevant aspect of the chemical property of vancomycin as a zinc chelator.This work was supported by funding from the Royal Society, UK (516002.K5877/ROG), the Medical Research Council, UK (G0700141). A.Z. was supported from the Said foundation and Cambridge Trust.This is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/srep1960

Salicylic acid-based organic dyes acting as the photosensitizer for solar cells

A D-π-A metal-free organic dye, featuring salicylic acid as a novel acceptor/anchoring unit, has been designed, synthesized and applied to dye-sensitized solar cell. The detailed photophysical, electrochemical, photovoltaic and sensitizing properties of the organic dye were investigated, in addition to the computational studies of the dye and dye-(TiO2)6 system. A solar cell device using this new organic dye as a sensitizer produced a solar to electric power conversion efficiency (PCE) of 3.49% (J(sc) = 6.69 mAcm-2, V(oc) = 0.74 V and ff = 0.70) under 100 mWcm(-2) simulated AM 1.5 G solar irradiation, demonstrating that the salicylic acid-based organic dye is a suitable alternative to currently used organometallic dye

Health-related quality of life among general practice patients with differing chronic diseases in Germany: Cross sectional survey

Background This study was carried out to compare the HRQoL of patients in general practice with differing chronic diseases with the HRQoL of patients without chronic conditions, to evaluate the HRQoL of general practice patients in Germany compared with the HRQoL of the general population, and to explore the influence of different chronic diseases on patients HRQoL, independently of the effects of multiple confounding variables. Methods A cross-sectional questionnaire survey including the SF-36, the EQ-5D and demographic questions was conducted in 20 general practices in Germany. 1009 consecutive patients aged 15–89 participated. The SF-36 scale scores of general practice patients with differing chronic diseases were compared with those of patients without chronic conditions. Differences in the SF-36 scale/summary scores and proportions in the EQ-5D dimensions between patients and the general population were analyzed. Independent effects of chronic conditions and demographic variables on the HRQoL were analyzed using multivariable linear regression and polynomial regression models. Results The HRQoL for general practice patients with differing chronic diseases tended to show more physical than mental health impairments compared with the reference group of patients without. Patients in general practice in Germany had considerably lower SF-36 scores than the general population (P < 0.001 for all) and showed significantly higher proportions of problems in all EQ-5D dimensions except for the self-care dimension (P < 0.001 for all). The mean EQ VAS for general practice patients was lower than that for the general population (69.2 versus 77.4, P < 0.001). The HRQoL for general practice patients in Germany seemed to be more strongly affected by diseases like depression, back pain, OA of the knee, and cancer than by hypertension and diabetes. Conclusion General practice patients with differing chronic diseases in Germany had impaired quality of life, especially in terms of physical health. The independent impacts on the HRQoL were different depending on the type of chronic disease. Findings from this study might help health professionals to concern more influential diseases in primary care from the patient´s perspective

Consumer perceptions of co-branding alliances: Organizational dissimilarity signals and brand fit

This study explores how consumers evaluate co-branding alliances between dissimilar partner firms. Customers are well aware that different firms are behind a co-branded product and observe the partner firms’ characteristics. Drawing on signaling theory, we assert that consumers use organizational characteristics as signals in their assessment of brand fit and for their purchasing decisions. Some organizational signals are beyond the control of the co-branding partners or at least they cannot alter them on short notice. We use a quasi-experimental design and test how co-branding partner dissimilarity affects brand fit perception. The results show that co-branding partner dissimilarity in terms of firm size, industry scope, and country-of-origin image negatively affects brand fit perception. Firm age dissimilarity does not exert significant influence. Because brand fit generally fosters a benevolent consumer attitude towards a co-branding alliance, the findings suggest that high partner dissimilarity may reduce overall co-branding alliance performance