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    ABSTRACT: Umbilical vessel catheterisation is a common intervention in neonatal care. Many complications are recognised, some of which are life-threatening. We report the case of a term neonate who was compromised at birth following antepartum haemorrhage with evidence of multiorgan ischaemic injury. Following resuscitation and umbilical vessel catheterisation, she developed pneumoperitoneum. At laparotomy, a patent vitellointestinal duct was identified and resected. Intestinal perforation was found in the duct wall, most plausibly explained by the unintentional catheterisation of the duct via the umbilicus. Learning to recognise umbilical cord anomalies, such as patent vitellointestinal duct, can be simple and could prevent potentially serious complications.
    Case Reports 11/2013; 2013(nov27_1).
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    ABSTRACT: Infants within neonatal intensive care units can receive multiple medically essential painful procedures a day. How they respond to these stimuli, how best to alleviate the negative effects, and the long-term consequences for the infant are all significant questions that have yet to be fully answered. In recent years several studies have examined cortical responses to noxious stimuli in the neonate through the use of near-infrared spectroscopy (NIRS) and electroencephalography (EEG). These investigations dispel any notion that the newborn infant does not process noxious stimuli at a cortical level and open the way for future research. In this Viewpoint article we review these studies and discuss key clinical challenges which may be elucidated with the use of these techniques. Conclusion: Simultaneously measuring the changes that are evoked in behaviour, physiology and the cortex following noxious events will provide the best approach to understanding the neonate's experience of pain. This article is protected by copyright. All rights reserved.
    Acta Paediatrica 11/2013;
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    ABSTRACT: Background:Concern about the risk of leukaemia in children living near nuclear power plants (NPPs) persists. Previous British analyses have been area based and consequently thought to be less effective than case-control studies.Methods:Cases of childhood leukaemia and non-Hodgkin lymphoma (LNHL) born and diagnosed in Great Britain between 1962 and 2007, with matched cancer-free controls, were analysed by logistic regression to estimate the risk of residential proximity at birth and diagnosis to the nearest NPP, adjusting for relevant variables.Results:For 9821 children with LNHL under the age of 5 years, the estimated extra risk associated with residential proximity to an NPP at birth was negative-interpolated Odds Ratio (OR) at 5 km was 0.86 (0.49-1.52). The comparison of 10 618 children with LNHL under five with 16 760 similarly aged children with other cancers also gave a negative estimate of the extra risk of residential proximity at diagnosis-interpolated OR at 5 km was 0.86 (0.62-1.18).Conclusion:Our results show little evidence of an increase in risk of LNHL to children aged under 5 years from living in the vicinity of an NPP. Risk estimates are incompatible with comparable ones published in a recent German case-control study.British Journal of Cancer advance online publication, 12 September 2013; doi:10.1038/bjc.2013.560 www.bjcancer.com.
    British Journal of Cancer 09/2013;
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    ABSTRACT: Recent studies in the SIV-macaque model of HIV infection suggest that Nef-specific CD8+ T-cell responses may mediate highly effective immune control of viraemia. In HIV infection Nef recognition dominates in acute infection, but in large cohort studies of chronically infected subjects, breadth of T cell responses to Nef has not been correlated with significant viraemic control. Improved disease outcomes have instead been associated with targeting Gag and, in some cases, Pol. However analyses of the breadth of Nef-specific T cell responses have been confounded by the extreme immunogenicity and multiple epitope overlap within the central regions of Nef, making discrimination of distinct responses impossible via IFN-gamma ELISPOT assays. Thus an alternative approach to assess Nef as an immune target is needed. Here, we show in a cohort of >700 individuals with chronic C-clade infection that >50% of HLA-B-selected polymorphisms within Nef are associated with a predicted fitness cost to the virus, and that HLA-B alleles that successfully drive selection within Nef are those linked with lower viral loads. Furthermore, the specific CD8+ T cell epitopes that are restricted by protective HLA Class I alleles correspond substantially to effective SIV-specific epitopes in Nef. Distinguishing such individual HIV-specific responses within Nef requires specific peptide-MHC I tetramers. Overall, these data suggest that CD8+ T cell targeting of certain specific Nef epitopes contributes to HIV suppression. These data suggest that a re-evaluation of the potential use of Nef in HIV T-cell vaccine candidates would be justified.
    PLoS ONE 09/2013; 8(9):e73117.
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    ABSTRACT: Lipopolysaccharide O-antigens are the basis of serotyping schemes for Gram negative bacteria and help to determine the nature of host-bacterial interactions. Haemophilus parainfluenzae is a normal commensal of humans but is also an occasional pathogen. The prevalence, diversity and biosynthesis of O-antigens were investigated in this species for the first time. 18/18 commensal H. parainfluenzae isolates contain a O-antigen biosynthesis gene cluster flanked by glnA and pepB, the same position as the hmg locus for tetrasaccharide biosynthesis in Haemophilus influenzae. The O-antigen loci show diverse restriction digest patterns but fall into two main groups: (1) those encoding enzymes for the synthesis and transfer of FucNAc4N in addition to the Wzy-dependent mechanism of O-antigen synthesis and transport and (2) those encoding galactofuranose synthesis/transfer enzymes and an ABC transporter. The other glycosyltransferase genes differ between isolates. Three H. parainfluenzae isolates fell outside these groups and are predicted to synthesise O-antigens containing ribitol phosphate or deoxytalose. Isolates using the ABC transporter system encode a putative O-antigen ligase, required for the synthesis of O-antigen-containing LPS glycoforms, at a separate genomic location. The presence of an O-antigen contributes significantly to H. parainfluenzae resistance to the killing effect of human serum in vitro. The discovery of O-antigens in H. parainfluenzae is striking, as its close relative H. influenzae lacks this cell surface component.
    International journal of medical microbiology: IJMM 08/2013;
  • The Lancet 08/2013; 382(9890):369-70.
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    ABSTRACT: The first meningococcal vaccine with the potential to provide broad coverage against serogroup B disease has recently been approved for use in Europe. This vaccine, multi-component serogroup B vaccine (4CMenB), contains recombinant proteins and outer membrane vesicles, and has been extensively studied in clinical trials involving over 7500 adults, children and infants. As well as demonstrating immunogenicity against a range of serogroup B meningococcal strains, these trials have also demonstrated relatively high rates of fever following infant immunization. This article will summarize the vaccine composition, clinical trials and suggested schedules of this vaccine, with specific attention to immunogenicity, reactogenicity, safety, potential coverage and optimal implementation of this vaccine.
    Expert Review of Vaccines 08/2013; 12(8):837-58.
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    ABSTRACT: HLA-B*57 is strongly associated with immune control of HIV and delayed AIDS progression. The closely-related, but less protective, HLA-B*58:01 presents similar epitopes, but HLA-B*58:01(+) individuals do not generate CD8(+) T-cells targeting the KF11-Gag epitope linked with low viraemia. Here we show that HLA-B*58:01 binds and presents KF11 peptide, but HIV infected HLA-B*58:01(+) cells fail to process KF11. This unexpected finding demonstrates that immunodominance patterns can be influenced by intracellular events independent of HLA binding motifs.
    Journal of Virology 07/2013;
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    ABSTRACT: The Vi capsular polysaccharide (ViPS) protects Salmonella enterica subspecies enterica serotype Typhi (S.Typhi) in vivo by multiple mechanisms. Recent microbiological reports from typhoid endemic countries suggest that acapsulate S.Typhi may occur in nature and contribute to clinical typhoid fever that is indistinguishable from disease caused by capsulate strains. The prevalence and genetic basis of ViPS-negative S.Typhi isolates in children from Kathmandu, Nepal, were tested in 68 isolates. Although 5.9% of isolates tested negative for capsular expression by slide agglutination tests, a novel multiplex PCR assay and individual PCR analyses demonstrated the presence of all 14 genes responsible for the synthesis, transportation and regulation of the ViPS. These data suggest that phenotypically acapsulate S.Typhi may not have a genetic basis for the same.
    Journal of Tropical Pediatrics 04/2013;
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    ABSTRACT: A quadrivalent meningococcal vaccine conjugated to CRM197 (MenACWY-CRM197) is immunogenic in young infants. We assessed the memory B-cell and antibody responses after a primary and booster course of MenACWY-CRM197 in children. At 5 months of age, following primary immunisation, serogroup-specific memory B-cells were detectable in fewer than 25% of children, although protective antibody titres (hSBA≥4) were detectable in 69% of children against serogroup A and more than 95% against the other serogroups. At 12 months, before booster immunisation the percentages with hSBA≥4 were 5% for serogroup A, and between 44 and 70% for the other serogroups. One month after booster immunisation with MenACWY-CRM197 over 50% of children had detectable memory B-cells, and 91% had hSBA≥4 against serogroup A and more than 99% against the other serogroups. These data show that few antigen-specific anticapsular memory B-cells can be detected after two-doses priming with MenACWY-CRM197. For MenC and CRM197, the antigens with the highest number of B-cells at 5 months, there was a definite (p≤0.02) but weak correlation with antibody persistence at 12 months. Although previous studies suggest that measuring memory B-cell responses after priming immunisations in infancy can be used to predict antibody persistence and memory responses, this may not be suitable for all antigens in young children.
    Vaccine 04/2013;
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