400 research outputs found

    Capsular profiling of the Cronobacter genus and the association of specific Cronobacter sakazakii and C. malonaticus capsule types with neonatal meningitis and necrotizing enterocolitis

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    Background: Cronobacter sakazakii and C. malonaticus can cause serious diseases especially in infants where they are associated with rare but fatal neonatal infections such as meningitis and necrotising enterocolitis. Methods: This study used 104 whole genome sequenced strains, covering all seven species in the genus, to analyse capsule associated clusters of genes involved in the biosynthesis of the O-antigen, colanic acid, bacterial cellulose, enterobacterial common antigen (ECA), and a previously uncharacterised K-antigen. Results: Phylogeny of the gnd and galF genes flanking the O-antigen region enabled the defining of 38 subgroups which are potential serotypes. Two variants of the colanic acid synthesis gene cluster (CA1 and CA2) were found which differed with the absence of galE in CA2. Cellulose (bcs genes) were present in all species, but were absent in C. sakazakii sequence type (ST) 13 and clonal complex (CC) 100 strains. The ECA locus was found in all strains. The K-antigen capsular polysaccharide Region 1 (kpsEDCS) and Region 3 (kpsMT) genes were found in all Cronobacter strains. The highly variable Region 2 genes were assigned to 2 homology groups (K1 and K2). C. sakazakii and C. malonaticus isolates with capsular type [K2:CA2:Cell+] were associated with neonatal meningitis and necrotizing enterocolitis. Other capsular types were less associated with clinical infections. Conclusion: This study proposes a new capsular typing scheme which identifies a possible important virulence trait associated with severe neonatal infections. The various capsular polysaccharide structures warrant further investigation as they could be relevant to macrophage survival, desiccation resistance, environmental survival, and biofilm formation in the hospital environment, including neonatal enteral feeding tubes

    The Early Prevention of Obesity in CHildren (EPOCH) Collaboration - an Individual Patient Data Prospective Meta-Analysis

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    BackgroundEfforts to prevent the development of overweight and obesity have increasingly focused early in the life course as we recognise that both metabolic and behavioural patterns are often established within the first few years of life. Randomised controlled trials (RCTs) of interventions are even more powerful when, with forethought, they are synthesised into an individual patient data (IPD) prospective meta-analysis (PMA). An IPD PMA is a unique research design where several trials are identified for inclusion in an analysis before any of the individual trial results become known and the data are provided for each randomised patient. This methodology minimises the publication and selection bias often associated with a retrospective meta-analysis by allowing hypotheses, analysis methods and selection criteria to be specified a priori.Methods/DesignThe Early Prevention of Obesity in CHildren (EPOCH) Collaboration was formed in 2009. The main objective of the EPOCH Collaboration is to determine if early intervention for childhood obesity impacts on body mass index (BMI) z scores at age 18-24 months. Additional research questions will focus on whether early intervention has an impact on children\u27s dietary quality, TV viewing time, duration of breastfeeding and parenting styles. This protocol includes the hypotheses, inclusion criteria and outcome measures to be used in the IPD PMA. The sample size of the combined dataset at final outcome assessment (approximately 1800 infants) will allow greater precision when exploring differences in the effect of early intervention with respect to pre-specified participant- and intervention-level characteristics.DiscussionFinalisation of the data collection procedures and analysis plans will be complete by the end of 2010. Data collection and analysis will occur during 2011-2012 and results should be available by 2013.<br /

    Onset dynamics of type A botulinum neurotoxin-induced paralysis

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    Experimental studies have demonstrated that botulinum neurotoxin serotype A (BoNT/A) causes flaccid paralysis by a multi-step mechanism. Following its binding to specific receptors at peripheral cholinergic nerve endings, BoNT/A is internalized by receptor-mediated endocytosis. Subsequently its zinc-dependent catalytic domain translocates into the neuroplasm where it cleaves a vesicle-docking protein, SNAP-25, to block neurally evoked cholinergic neurotransmission. We tested the hypothesis that mathematical models having a minimal number of reactions and reactants can simulate published data concerning the onset of paralysis of skeletal muscles induced by BoNT/A at the isolated rat neuromuscular junction (NMJ) and in other systems. Experimental data from several laboratories were simulated with two different models that were represented by sets of coupled, first-order differential equations. In this study, the 3-step sequential model developed by Simpson (J Pharmacol Exp Ther 212:16–21,1980) was used to estimate upper limits of the times during which anti-toxins and other impermeable inhibitors of BoNT/A can exert an effect. The experimentally determined binding reaction rate was verified to be consistent with published estimates for the rate constants for BoNT/A binding to and dissociating from its receptors. Because this 3-step model was not designed to reproduce temporal changes in paralysis with different toxin concentrations, a new BoNT/A species and rate (kS) were added at the beginning of the reaction sequence to create a 4-step scheme. This unbound initial species is transformed at a rate determined by kS to a free species that is capable of binding. By systematically adjusting the values of kS, the 4-step model simulated the rapid decline in NMJ function (kS ≥0.01), the less rapid onset of paralysis in mice following i.m. injections (kS = 0.001), and the slow onset of the therapeutic effects of BoNT/A (kS < 0.001) in man. This minimal modeling approach was not only verified by simulating experimental results, it helped to quantitatively define the time available for an inhibitor to have some effect (tinhib) and the relation between this time and the rate of paralysis onset. The 4-step model predicted that as the rate of paralysis becomes slower, the estimated upper limits of (tinhib) for impermeable inhibitors become longer. More generally, this modeling approach may be useful in studying the kinetics of other toxins or viruses that invade host cells by similar mechanisms, e.g., receptor-mediated endocytosis

    Scaling properties of protein family phylogenies

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    One of the classical questions in evolutionary biology is how evolutionary processes are coupled at the gene and species level. With this motivation, we compare the topological properties (mainly the depth scaling, as a characterization of balance) of a large set of protein phylogenies with a set of species phylogenies. The comparative analysis shows that both sets of phylogenies share remarkably similar scaling behavior, suggesting the universality of branching rules and of the evolutionary processes that drive biological diversification from gene to species level. In order to explain such generality, we propose a simple model which allows us to estimate the proportion of evolvability/robustness needed to approximate the scaling behavior observed in the phylogenies, highlighting the relevance of the robustness of a biological system (species or protein) in the scaling properties of the phylogenetic trees. Thus, the rules that govern the incapability of a biological system to diversify are equally relevant both at the gene and at the species level.Comment: Replaced with final published versio

    Broad MICA/B expression in the small bowel mucosa: a link between cellular stress and celiac disease

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    The MICA/B genes (MHC class I chain related genes A and B) encode for non conventional class I HLA molecules which have no role in antigen presentation. MICA/B are up-regulated by different stress conditions such as heat-shock, oxidative stress, neoplasic transformation and viral infection. Particularly, MICA/B are expressed in enterocytes where they can mediate enterocyte apoptosis when recognised by the activating NKG2D receptor present on intraepithelial lymphocytes. This mechanism was suggested to play a major pathogenic role in active celiac disease (CD). Due to the importance of MICA/B in CD pathogenesis we studied their expression in duodenal tissue from CD patients. By immunofluorescence confocal microscopy and flow cytometry we established that MICA/B was mainly intracellularly located in enterocytes. In addition, we identified MICA/B+ T cells in both the intraepithelial and lamina propria compartments. We also found MICA/B+ B cells, plasma cells and some macrophages in the lamina propria. The pattern of MICA/B staining in mucosal tissue in severe enteropathy was similar to that found in in vitro models of cellular stress. In such models, MICA/B were located in stress granules that are associated to the oxidative and ER stress response observed in active CD enteropathy. Our results suggest that expression of MICA/B in the intestinal mucosa of CD patients is linked to disregulation of mucosa homeostasis in which the stress response plays an active role.Fil: Allegretti, Yessica Lorena. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bondar, Constanza María. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Guzmán, Luciana. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Cueto Rua, Eduardo. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de la Plata; ArgentinaFil: Chopita, Nestor. Provincia de Buenos Aires. Hospital Interzonal General de Agudos Gral. San Martin; ArgentinaFil: Fuertes, Mercedes Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Zwirner, Norberto Walter. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Microbiología; ArgentinaFil: Chirdo, Fernando Gabriel. Universidad Nacional de la Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biologicas. Laboratorio de Investigaciones del Sistema Inmune; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

    Maternal feeding practices and fussy eating in toddlerhood: A discordant twin analysis

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    Background: Parental feeding practices are thought to play a causal role in shaping a child's fussiness; however, a child-responsive model suggests that feeding practices may develop in response to a child's emerging appetitive characteristics. We used a novel twin study design to test the hypothesis that mothers vary their feeding practices for twin children who differ in their 'food fussiness', in support of a child-responsive model. Methods: Participants were mothers and their 16 month old twin children (n=2026) from Gemini, a British twin birth cohort of children born in 2007. Standardized psychometric measures of maternal 'pressure to eat', 'restriction' and 'instrumental feeding', as well as child 'food fussiness', were completed by mothers. Within-family analyses examined if twin-pair differences in 'food fussiness' were associated with differences in feeding practices using linear regression models. In a subset of twins (n=247 pairs) who were the most discordant (highest quartile) on 'food fussiness' (difference score≥.50), Paired Samples T-test were used to explore the magnitude of differences in feeding practices between twins. Between-family analyses used Complex Samples General Linear Models to examine associations between feeding practices and 'food fussiness'. Results: Within-pair differences in 'food fussiness' were associated with differential 'pressure to eat' and 'instrumental feeding' (ps<.001), but not with 'restriction'. In the subset of twins most discordant on 'food fussiness', mothers used more pressure (p<.001) and food rewards (p<.05) with the fussier twin. Between-family analyses indicated that 'pressure to eat' and 'instrumental feeding' were positively associated with 'food fussiness', while 'restriction' was negatively associated with 'food fussiness' (ps<.001). Conclusions: Mothers appear to subtly adjust their feeding practices according to their perceptions of their toddler's emerging fussy eating behavior. Specifically, the fussier toddler is pressured more than their less fussy co-twin, and is more likely to be offered food rewards. Guiding parents on how to respond to fussy eating may be an important aspect of promoting feeding practices that encourage food acceptance

    The relationship between appetite and food preferences in British and Australian children

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    Background: Appetitive traits and food preferences are key determinants of children’s eating patterns but it is unclear how these behaviours relate to one another. This study explores relationships between appetitive traits and preferences for fruits and vegetables, and energy dense, nutrient poor (noncore) foods in two distinct samples of Australian and British preschool children. Methods: This study reports secondary analyses of data from families participating in the British GEMINI cohort study (n = 1044) and the control arm of the Australian NOURISH RCT (n = 167). Food preferences were assessed by parent-completed questionnaire when children were aged 3–4 years and grouped into three categories; vegetables, fruits and noncore foods. Appetitive traits; enjoyment of food, food responsiveness, satiety responsiveness, slowness in eating, and food fussiness were measured using the Children’s Eating Behaviour Questionnaire when children were 16 months (GEMINI) or 3–4 years (NOURISH). Relationships between appetitive traits and food preferences were explored using adjusted linear regression analyses that controlled for demographic and anthropometric covariates. Results: Vegetable liking was positively associated with enjoyment of food (GEMINI; β = 0.20 ± 0.03, p < 0.001, NOURISH; β = 0.43 ± 0.07, p < 0.001) and negatively related to satiety responsiveness (GEMINI; β = -0.19 ± 0.03, p < 0.001, NOURISH; β = -0.34 ± 0.08, p < 0.001), slowness in eating (GEMINI; β = -0.10 ± 0.03, p = 0.002, NOURISH; β = -0.30 ± 0.08, p < 0.001) and food fussiness (GEMINI; β = −0.30 ± 0.03, p < 0.001, NOURISH; β = -0.60 ± 0.06, p < 0.001). Fruit liking was positively associated with enjoyment of food (GEMINI; β = 0.18 ± 0.03, p < 0.001, NOURISH; β = 0.36 ± 0.08, p < 0.001), and negatively associated with satiety responsiveness (GEMINI; β = −0.13 ± 0.03, p < 0.001, NOURISH; β = −0.24 ± 0.08, p = 0.003), food fussiness (GEMINI; β = -0.26 ± 0.03, p < 0.001, NOURISH; β = −0.51 ± 0.07, p < 0.001) and slowness in eating (GEMINI only; β = -0.09 ± 0.03, p = 0.005). Food responsiveness was unrelated to liking for fruits or vegetables in either sample but was positively associated with noncore food preference (GEMINI; β = 0.10 ± 0.03, p = 0.001, NOURISH; β = 0.21 ± 0.08, p = 0.010). Conclusion: Appetitive traits linked with lower obesity risk were related to lower liking for fruits and vegetables, while food responsiveness, a trait linked with greater risk of overweight, was uniquely associated with higher liking for noncore foods

    Mechanical properties of β-HMX

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    Background: For a full understanding of the mechanical properties of a material, it is essential to understand the defect structures and associated properties and microhardness indentation is a technique that can aid this understanding. Results: The Vickers hardness on (010), {011} and {110} faces lay in the range of 304-363 MPa. The Knoop Hardnesses on the same faces lay in the range 314-482 MPa. From etching of three indented surfaces, the preferred slip planes have been identified as (001) and (101). For a dislocation glide, the most likely configuration for dislocation movement on the (001) planes is (001) [100] (|b| = 0.65 nm) and for the (101) plane as (101) 101~(|b| = 1.084 nm) although (101) [010] (|b| = 1.105 nm) is possible. Tensile testing showed that at a stress value of 2.3 MPa primary twinning occurred and grew with increasing stress. When the stress was relaxed, the twins decreased in size, but did not disappear. The twinning shear strain was calculated to be 0.353 for the (101) twin plane. Conclusions: HMX is considered to be brittle, compared to other secondary explosives. Comparing HMX with a range of organic solids, the values for hardness numbers are similar to those of other brittle systems. Under the conditions developed beneath a pyramidal indenter, dislocation slip plays a major part in accommodating the local deformation stresses. © 2015 Gallagher et al.; licensee Springer

    Evolution of vaccination rates after the implementation of a free systematic pneumococcal vaccination in Catalonian older adults: 4-years follow-up

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    BACKGROUND: The systematic vaccination with 23-valent polysaccharide pneumococcal vaccine (PPV) was introduced as a strategic objective of health for all the people over 65 in Catalonia in 1999. We analysed the evolution of the pneumococcal vaccination rates from 2000 to 2003. METHODS: We conducted a retrospective population-based study including all the individuals 65 years or older assigned to 8 Primary Care Centres (PCCs) in Tarragona (Catalonia, Spain), who figured in the administrative population databases on 31 December 2003 (n = 10,410 persons). We assessed whether every person had received PPV during the last four years (2000 to 2003) or whether they had received it before January 2000. Data sources were the computerised clinical records of the 8 participating PCCs, which included adult vaccination registries and diagnoses coded of International Classification of Diseases 9(th )Review RESULTS: The overall vaccination uptake increased to 38.6% at the end of 2000. Global accumulated coverages increased more slowly the following years: 44.4% in 2001, 50.9% in 2002, and 53.1% at the end of 2003. Vaccine uptake varied significantly according to age (46.7% in people 65–74 years-old, 60.9% in people 75 years or more; p < 0.001) and number of diseases or risk factors (DRFs) for pneumonia (47.1% vaccinated in people without DRFs, 56.8% in patients with one DRF, and 62.2% in patients with two or more DRFs; p < 0.001). The highest coverages were observed among those patients with: diabetes (65.9%), active neoplasia (64.8%), history of stroke (63.7%), and chronic lung disease (63.5%). The lowest uptake was observed among smokers (48.7%). DISCUSSION: The pneumococcal vaccination coverage increased quickly after the introduction of the recommendation for free vaccination in all the elderly people (with and without risk factors), but two years after the improvement the coverage became stable and increased slowly
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