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Background: Hospital-acquired infection (HAI) is an increasing cause of neonatal morbidity/mortality in low-income settings. Hospital staff behaviours (e.g., hand hygiene) are key contributors to HAI. Understanding the drivers of these can inform interventions to improve infection prevention and control (IPC).Aim: To explore barriers/facilitators to IPC in a neonatal unit in Harare, Zimbabwe.Methods: Interviews were conducted with 15 staff members of neonatal and maternity units alongside ethnographic observations. The interview guide and data analysis were informed by the COM-B (Capability, Opportunity, Motivation-Behaviour) model and explored individual, socio-cultural, and organizational barriers/facilitators to IPC. Potential interventions were identified using the Behaviour-Change Wheel.Findings: Enablers within Capability included awareness of IPC, and within Motivation beliefs that IPC was crucial to one's role, and concerns about consequences of poor IPC. Staff were optimistic that IPC could improve, contingent upon resource availability (Opportunity). Barriers included: limited knowledge of guidelines, no formal feedback on performance (Capability), lack of resources (Opportunity), often leading to improvization and poor habit formation. Further barriers included the unit's hierarchy, e.g., low engagement of cleaners and mothers in IPC, and staff witnessing implementation of poor practices by other team members (Opportunity). Potential interventions could include role-modelling, engaging mothers and staff across cadres, audit and feedback and flexible protocols (adaptable to water/handrub availability).Conclusions: Most barriers to IPC fell within Opportunity, whilst most enablers fell under Capability and Motivation. Theory-based investigation provides the basis for systematically identifying and developing interventions to address barriers and enablers to IPC in low-income settings. [ABSTRACT FROM AUTHOR]

This study aimed to determine whether there are seasonal changes in the performance of QuantiFERON-TB Gold In-Tube (QFT-GIT) assays, an interferon-gamma release assay widely used for the diagnosis of tuberculosis infection. Results of 31,932 QFT-GIT assays performed at a large independent, accredited diagnostic service provider in London, UK over a 4.5-year-period were analysed. The proportion of positive results was significantly lower in autumn (14.8%) than in spring (16.0%; p = 0.0366) and summer (17.5%; p < 0.0001), but similar to winter (15.2%; p = 0.4711). The proportion of indeterminate results was significantly higher in autumn (8.2%) than in spring (6.2%; p < 0.0001), summer (4.8%; p < 0.0001), and winter (6.2%; p < 0.0001). The highest proportions of indeterminate results were observed in October (8.4%) and November (8.8%), the lowest in June (4.5%). Our data show that significant seasonal variation occurs in the performance of QFT-GIT assays in a temperate climate setting. Potential underlying mechanisms, including host and environmental factors, are discussed. [ABSTRACT FROM AUTHOR]

Summary From the use of antiretroviral therapy to prevent mother-to-child transmission to the possibility of HIV cure hinted at by the Mississippi baby experience, paediatric HIV infection has been pivotal to our understanding of HIV pathogenesis and management. Daily medication and indefinite antiretroviral therapy is recommended for children infected with HIV. Maintenance of life-long adherence is difficult and the incidence of triple-class virological failure after initiation of antiretroviral therapy increases with time. This challenge shows the urgent need to define novel strategies to provide long-term viral suppression that will allow safe interruption of antiretroviral therapy without viral rebound and any associated complications. HIV-infected babies treated within a few days of birth have a unique combination of a very small pool of integrated viruses, a very high proportion of relatively HIV resistant naive T cells, and an unparalleled capacity to regenerate an immune repertoire. These features make this group the optimum model population to investigate the potential efficacy of immune-based therapies. If successful, these investigations could change the way we manage HIV infection. [ABSTRACT FROM AUTHOR]

Background Nosocomial outbreaks of viral etiology are costly and can have a major impact on patient care. Many viruses are known to persist in the inanimate environment and may pose a risk to patients and health care workers. We investigate the frequency of environmental contamination with common health care-associated viruses and explore the use of torque-teno virus as a marker of environmental contamination. Methods Environmental screening for a variety of clinically relevant viruses was carried out over 3 months in a UK pediatric hospital using air sampling and surface swabbing. Swabs were tested for the presence of virus nucleic acid by quantitative polymerase chain reactions. Results Viral nucleic acid was found on surfaces and in the air throughout the screening period, with adenovirus DNA being the most frequent. Door handles were frequently contaminated. Torque-teno virus was also found at numerous sites. Conclusion Evidence of environmental contamination with viral pathogens is present in health care environments and may be indicative of an infectious virus being present. Screening for viruses should be included in infection control strategies. Torque-teno virus may provide a better marker of contamination and reduce time and cost of screening for individual viruses. [ABSTRACT FROM AUTHOR]

Abstract: Background/Purpose: After a change in national policy, central venous catheter (CVC) antisepsis with chlorhexidine was introduced in our hospital. Our aim was to evaluate whether this change reduced the rate of infection seen during parenteral nutrition (PN) in infants requiring gastrointestinal surgery. Methods: Two groups of consecutive infants were compared: control, 98 infants who had CVC antisepsis with 70% isopropanol alone, and chlorhexidine, 112 infants who had CVC antisepsis with 2% chlorhexidine in 70% isopropanol. Incidence rates of sepsis (blood cultures taken) and septicemia (blood cultures positive) were compared by Poisson regression. Results: Seventy-one percent of infants experienced clinically suspected sepsis. The incidence of septicemia was 32%. The incidence rate ratio for sepsis was 0.72 (95% confidence interval, 0.61-0.84) for the chlorhexidine group vs control (P < .0005). The incidence rate ratio for septicemia was 0.49 (95% confidence interval, 0.36-0.67; P < .0005); that is, over a given period of PN, patients had half the rate of positive blood cultures after the introduction of chlorhexidine antisepsis compared with before. Conclusion: (1) The incidence of sepsis and septicemia among surgical infants on PN for gastrointestinal anomalies is high. (2) Chlorhexidine CVC antisepsis has significantly reduced this incidence, and we advocate its use in this group of patients. [Copyright &y& Elsevier]

Abstract: Glutamine may have benefits during neonatal sepsis, but its effects on systemic inflammation are unknown. Our aim was to determine whether glutamine affects inflammation in neonatal endotoxemia. Eleven-day rat pups were given intraperitoneal injections of saline (control; C), endotoxin (300 μg/g Escherichia coli lipopolysaccharide) (E), saline with glutamine (2 mmol/g; G), or endotoxin with glutamine (EG). Animals were killed after 2 or 6 hours. Plasma glutamine (mmol/L) was measured enzymatically, and both tumor necrosis factor α (pg/mL) and interleukin 10 (IL-10) were measured by enzyme-linked immunosorbent assay. Results, expressed as mean ± SEM, were analyzed by analysis of variance. Endotoxemia caused a rapid significant decrease in plasma glutamine at 2 hours (C, 0.73 ± 0.06; E, 0.32 ± 0.07; mean difference, 0.41 [95% confidence interval {CI, 0.17-0.64}]; P < .001), which was prevented by intraperitoneal glutamine (EG, 0.59 ± 0.04; mean difference vs E, 0.27 mmol/L [95% CI, 0.03-0.50]; P < .05), indicating glutamine absorption, whereas CG animals had a plasma glutamine of 0.82 ± 0.07. Tumor necrosis factor α was greatly increased by 2-hour endotoxemia (C, 27 ± 7; E, 2247 ± 43; mean difference, 2220 pg/mL [95% CI, 2012-2429]; P < .001), and this increase was partly prevented by glutamine (EG, 1991 ± 91; P < .05 vs E; mean difference, 256; 95% CI, 47-465; P < .05). The effect of glutamine was more pronounced at 6 hours (C, 32 ± 27; E, 799 ± 193; EG, 219 ± 75, C vs E mean difference, 767; 95% CI, 346-1188; P < .001; E vs EG mean difference, 580; 95% CI, 159-1001; P < .01). The IL-10 levels were also greatly increased by 2-hour endotoxemia (C = 55 ± 21, E = 2429 ± 58, EG = 1989 ± 177; C vs E mean difference, 2374; 95% CI, 2740-2008; P < .001; E vs EG mean difference, 440; 95% CI, 74-807; P < .05). Glutamine administration partially prevents the sepsis-induced fall in plasma glutamine levels and reduces the concentration of both proinflammatory and antiinflammatory cytokines. [Copyright &y& Elsevier]

Abstract: The response of the developing immune system to HIV infection is complex and involves many innate and adaptive components. In almost all cases, the immune response is insufficient to eradicate the virus, and infection eventually results in a gradual decline of CD4 cells from both memory and naïve cell compartments. This can be quantitatively reversed by the institution of highly active antiretroviral therapy (HAART). Immune reconstitution of CD4T cells following HAART in children is characterised by a sustained increase of naïve T cells, a pattern of immune reconstitution that differs from that seen in adults. This, and other differences between HIV infection in children and adults, indicates that it cannot be assumed that the therapeutic approach used in adults will be optimal for HIV-infected children. The future of paediatric HIV infection is dependent on a greater understanding of the kinetics of CD4 depletion and reconstitution. [Copyright &y& Elsevier]

Abstract: Background/Purpose: P-selectin promotes adherence of leukocytes to the endothelium in inflammatory processes. The aim of this study was to investigate the expression of P-selectin and its role in the development of inflammation in neonates with necrotizing enterocolitis (NEC). Methods: Twenty-nine intestinal specimens from 13 neonates with NEC and 7 control neonates with congenital gastrointestinal abnormalities were studied. Histologic damage, immunohistochemical expression of P-selectin, and polymorphonuclear cell infiltrate were graded blindly. Mann-Whitney U and Spearman rank tests were used to compare grades. Results: Expression of P-selectin was increased in NEC compared with controls in both medium-sized vessels (P = .03) and in the microcirculation (P = .03). P-selectin expression on medium-sized vessels correlated with the degree of histologic injury (P = .02, r = 0.425). P-selectin expression was greatest in areas of active inflammation but markedly lower in necrotic areas. The degree of polymorphonuclear cell infiltration strongly correlated with P-selectin expression on both medium-sized vessels (P = .004, r = 0.513) and the microcirculation (P = .001, r = 0.578). Conclusions: Expression of P-selectin is increased in medium-sized vessels and in the microcirculation in intestinal specimens of neonates with NEC compared with neonatal controls. Expression of P-selectin is associated with the recruitment of polymorphonuclear cells and the severity of histologic injury, although P-selectin expression is lost in necrotic tissue. [Copyright &y& Elsevier]

Abstract: We performed a randomized controlled trial to compare the inflammatory and immune responses to Nissen fundoplication in infants and children undergoing either open or laparoscopic surgery. Methods: Forty children undergoing Nissen fundoplication were randomized to laparoscopy or open surgery using minimization with respect to age, neurologic status, and operating surgeon. Intraoperative and postoperative analgesias were standardized. Inflammatory markers (plasma malondialdehyde, nitrate plus nitrite level, and cytokines) and monocyte class II major histocompatibility complex expression were measured preoperatively, at end of surgery, 4, 24, and 48 hours postoperatively. Postoperative changes were compared between open and laparoscopic groups. Results: There were no significant changes in circulating malondialdehyde, nitrates plus/ nitrite, interleukin-10, or tumor necrosis factor α in the postoperative period in either group. Interleukin-1 receptor antagonist (IL-1rA) and IL-6 were significantly increased in both groups, with a tendency for greater elevation of IL-1rA in the open group. Monocyte major histocompatibility complex expression fell significantly in both groups; however, this fall appeared to be slightly more marked in the open group. Conclusions: The postoperative cytokine response is similar in children undergoing open and laparoscopic Nissen fundoplication. This trial indicates that laparoscopy may partly reduce postoperative immune suppression. [Copyright &y& Elsevier]

Adenovirus infections within the hematopoietic stem cell transplantation setting can lead to high rates of mortality and hospital-acquired cases have been associated with environmental reservoirs. To establish both location and levels of environmental adenovirus contamination, 48 cubicles containing 794 surfaces were screened postterminal clean over a 4-year period. After initial cleaning 23% of these sites had detectable adenovirus. These data were then used to develop and implement a cleaning standard algorithm for terminal cleaning that was implemented to ensure cubicles were adenovirus-free before the next patient admission. [ABSTRACT FROM AUTHOR]

The differentiation of IL-10-producing regulatory B cells (Bregs) in response to gut-microbiota-derived signals supports the maintenance of tolerance. However, whether microbiota-derived metabolites can modulate Breg suppressive function remains unknown. Here, we demonstrate that rheumatoid arthritis (RA) patients and arthritic mice have a reduction in microbial-derived short-chain fatty acids (SCFAs) compared to healthy controls and that in mice, supplementation with the SCFA butyrate reduces arthritis severity. Butyrate supplementation suppresses arthritis in a Breg-dependent manner by increasing the level of the serotonin-derived metabolite 5-Hydroxyindole-3-acetic acid (5-HIAA), which activates the aryl-hydrocarbon receptor (AhR), a newly discovered transcriptional marker for Breg function. Thus, butyrate supplementation via AhR activation controls a molecular program that supports Breg function while inhibiting germinal center (GC) B cell and plasmablast differentiation. Our study demonstrates that butyrate supplementation may serve as a viable therapy for the amelioration of systemic autoimmune disorders. • Stool butyrate levels are reduced in patients with RA compared to healthy controls • Supplementation with butyrate suppresses arthritis severity in a mouse model • Suppression of arthritis by butyrate supplementation depends upon AhR+Bregs • Butyrate increases serotonin-derived 5-HIAA, which directly activates AhR+Bregs The environmental signals that influence Breg function are not yet fully defined. Here, Rosser et al. demonstrate that the short-chain fatty acid butyrate supports Breg function by increasing the level of the serotonin-derived metabolite 5-Hydroxyindole-3-acetic acid (5-HIAA). 5-HIAA, in turn, activates the aryl-hydrocarbon receptor, a newly discovered transcriptional regulator for Bregs. [ABSTRACT FROM AUTHOR]

The role of environment in the spread of nosocomial infection has been acknowledged. One way to control the spread of infection is to control and monitor patient environments to prevent transmission. Studies applying the suggested aerobic colony count standards to monitor environmental contamination were undertaken over an 18-month period at both a London pediatric hospital and in adult intensive care units. The resulting data demonstrate that a large proportion of sites screened for bacterial contamination would fail if using the criteria suggested by previous authors—particularly those sites closest to patients—suggesting a new standard might be required. [ABSTRACT FROM AUTHOR]

Handwashing is one of the most important means of reducing the spread of infection. In this study, we investigated how sink location and visibility influences handwashing and microbial contamination detected on clinical sinks in 3 pediatric intensive care units. We conclude that the visibility of sinks directly impacts on handwashing frequency and duration and also impacts on levels of bacterial contamination on and around the sink area. [ABSTRACT FROM AUTHOR]

Background Emerging evidence supports the role of cell-derived microparticles (MPs) in the pathophysiology of acute coronary syndrome (ACS). Objectives To explore the relationship between coronary and systemic MP levels, investigate the correlation between MPs, inflammatory markers and Troponin T in patients with ACS. Methods Thirty seven patients with ACS scheduled for percutaneous coronary interventions (PCI) were studied. Eleven patients with stable angina (SA) were included as a control group. AnnexinV + MPs (AnV + MPs) and activated platelet-monocyte aggregates (PMA) from right atrium (RA) and culprit coronary artery (CO) distal to culprit lesion were measured using flow cytometry. High sensitivity C-reactive protein (CRP), Interleukin - 6 (IL-6), tumour necrosis factor – α (TNF-α), serum amyloid A (SAA) and Troponin T were assayed. Results Total and cell specific AnV + MP expression were higher in the ACS group in both the CO and RA, with greater levels detected in the CO. Platelet activation showed positive correlation with Troponin-T and platelet MP in both CO and RA of the ACS group (r = 0.4 for both; p = 0.04 & p = 0.03 respectively). Inflammatory markers levels did not differ between the ACS and SA patients. Conclusions Elevated coronary and systemic MP levels and positive correlation of platelet activation with Troponin-T and platelet MPs suggest a pathogenic role for MPs in ACS. [ABSTRACT FROM AUTHOR]

Background: WHO 2013 guidelines recommend universal treatment for HIV-infected children younger than 5 years. No paediatric trials have compared nucleoside reverse-transcriptase inhibitors (NRTIs) in first-line antiretroviral therapy (ART) in Africa, where most HIV-infected children live. We aimed to compare stavudine, zidovudine, or abacavir as dual or triple fixed-dose-combination paediatric tablets with lamivudine and nevirapine or efavirenz.Methods: In this open-label, parallel-group, randomised trial (CHAPAS-3), we enrolled children from one centre in Zambia and three in Uganda who were previously untreated (ART naive) or on stavudine for more than 2 years with viral load less than 50 copies per mL (ART experienced). Computer-generated randomisation tables were incorporated securely within the database. The primary endpoint was grade 2-4 clinical or grade 3/4 laboratory adverse events. Analysis was intention to treat. This trial is registered with the ISRCTN Registry number, 69078957.Findings: Between Nov 8, 2010, and Dec 28, 2011, 480 children were randomised: 156 to stavudine, 159 to zidovudine, and 165 to abacavir. After two were excluded due to randomisation error, 156 children were analysed in the stavudine group, 158 in the zidovudine group, and 164 in the abacavir group, and followed for median 2·3 years (5% lost to follow-up). 365 (76%) were ART naive (median age 2·6 years vs 6·2 years in ART experienced). 917 grade 2-4 clinical or grade 3/4 laboratory adverse events (835 clinical [634 grade 2]; 40 laboratory) occurred in 104 (67%) children on stavudine, 103 (65%) on zidovudine, and 105 (64%), on abacavir (p=0·63; zidovudine vs stavudine: hazard ratio [HR] 0·99 [95% CI 0·75-1·29]; abacavir vs stavudine: HR 0·88 [0·67-1·15]). At 48 weeks, 98 (85%), 81 (80%) and 95 (81%) ART-naive children in the stavudine, zidovudine, and abacavir groups, respectively, had viral load less than 400 copies per mL (p=0·58); most ART-experienced children maintained suppression (p=1·00).Interpretation: All NRTIs had low toxicity and good clinical, immunological, and virological responses. Clinical and subclinical lipodystrophy was not noted in those younger than 5 years and anaemia was no more frequent with zidovudine than with the other drugs. Absence of hypersensitivity reactions, superior resistance profile and once-daily dosing favours abacavir for African children, supporting WHO 2013 guidelines.Funding: European Developing Countries Clinical Trials Partnership. [ABSTRACT FROM AUTHOR]

The objective was to characterise cervical leukocyte populations and inflammatory mediators associated with term and recurrent spontaneous preterm birth (SPTB) in pregnant women with a history of SPTB. A prospective observational study was undertaken on 120 women with a history of SPTB. A cytobrush was used to sample cells from the cervix at 12–25 weeks’ gestation. Cells were enumerated and characterised by flow cytometry. Cytokines and chemokines were also measured. Participants were then grouped according to delivery at term (>36 + 6 weeks), late SPTB (34–36 + 6 weeks) or early SPTB (<34 weeks). Differences in leukocyte sub-populations, cytokine and chemokine levels were compared with outcome. Cervical leukocytes comprised up to 60% of the host-derived cells. Most of these (90–100%) were polymorphonuclear cells (PMN). Most of the remaining cells were mucosal macrophages expressing CD68 and CD103 in addition to markers shared with blood-borne monocytes. Failure to detect cervical macrophages in at least 250,000 cervical epithelial cells was a feature of women who experienced early SPTB (6 out of 6 cases, 95% CI 61–100%) compared with 34% (30 out of 88 cases, 95% CI 25–43%, P < 0.001) of women delivering after 34 weeks. CCL2 (MCP-1) was also low in SPTB before 34 weeks and levels above 75 ng/g and/or the presence of macrophages increased the specificity for birth after 34 weeks from 66% to 82% (55 out of 67 cases, 95% CI 73–91%). Absence of cervical macrophages and low CCL2 may be features of pregnancies at risk of early SPTB. [ABSTRACT FROM AUTHOR]

Summary Background Early antiretroviral therapy (ART) and virological suppression can affect evolving antibody responses to HIV infection. We aimed to assess frequency and predictors of seronegativity in infants starting early ART. Methods We compared HIV antibody results between two of three treatment groups of the Children with HIV Early Antiretroviral Therapy (CHER) trial, done from July, 2005, until July, 2011, in which infants with HIV infection aged 5·7–12·0 weeks with a percentage of CD4-positive T lymphocytes of at least 25% were randomly assigned to immediate ART for 96 weeks (ART-96W) or deferred ART until clinical or immunological progression (ART-Def). We measured antibody from all available stored samples for ART-96W and ART-Def at trial week 84 using three assays: fourth-generation enzyme immunoassay HIV antigen–antibody combination, HIV-1 and HIV-2 rapid antibody test, and quantitative anti-gp120 IgG ELISA. We also assessed odds of seropositivity with respect to age of ART initiation and cumulative viral load. The CHER trial was registered with ClinicalTrials.gov , number NCT00102960 . Findings The median age of the infants from when samples were taken (184 samples from 268 infants) was 92 weeks (IQR 90·6–93·4). More specimens from the ART-96W group were seronegative than from the ART-Def group by enzyme immunoassay (ART-96W 49 [46%] of 107 vs ART-Def eight [11%] of 75; p<0·0001) and rapid antibody test (54 [53%] of 101 vs eight [11%] of 74; p<0·0001). Median anti-gp120 IgG concentration was lower in the ART-96W group (230 μg/μL [IQR 133–13 129]) than in the ART-Def group (6870 μg/μL [1706–53 645]; p<0·0001). If ART was started between 12 and 24 weeks of age, odds of seropositivity were increased 13·7 times (95% CI 3·1–60·2; p=0·001) compared with starting it between 0 and 12 weeks. All children starting ART aged older than 24 weeks were seropositive. Cumulative viral load to week 84 correlated with anti-gp120 IgG concentrations (coefficient 0·54; p<0·0001) and increased odds of seropositivity (odds ratio 1·59 [95% CI 1·1–2·3]) adjusted for ART initiation age. Interpretation About half of children starting ART before 12 weeks of age were HIV seronegative by almost 2 years of age. HIV antibody tests cannot be used to reconfirm HIV diagnosis in children starting early ART. Long-term effects of seronegativity need further study. Clear guidelines are needed for retesting alongside improved diagnostic tests. Funding Wellcome Trust, Medical Research Council, and National Institutes of Health. [ABSTRACT FROM AUTHOR]

Objective HDL functionality has been shown to be impaired in inflammatory conditions, including coronary artery disease. The present study aims to determine the impact of low grade and acute inflammation on HDL function and structure. Approach and results i) The endothelial protective effects of HDL were compared between 26 periodontal patients and 26 age and sex matched controls by measuring paraoxonase activity in serum and nitric oxide bioavailability and superoxide production in endothelial cells. Paraoxonase activity and nitric oxide bioavailability were reduced, while superoxide production was increased (p < 0.01) in periodontal patients compared to controls. ii) HDL function, including cholesterol efflux and vascular cell adhesion molecule-1 expression, was subsequently measured in the periodontal patients following an inflammatory stimulus. There was an acute deterioration in HDL's endothelial protective function, without change in cholesterol efflux, after 24 h (p < 0.01 for all). These functional changes tracked increases of inflammatory markers and altered HDL composition. Finally, HDL function returned to baseline levels after resolution of inflammation. Conclusion This study demonstrates that even minor alterations in systemic inflammation can impair the endothelial protective effects of HDL. These functional changes were independent of cholesterol efflux and were associated with remodeling of the HDL proteome. All measures of HDL's endothelial protective functions recovered with resolution of inflammation. These findings suggest that HDL dysfunction may represent a novel mechanism linking inflammation with progression of atheroma. [ABSTRACT FROM AUTHOR]

Abstract: It has been hypothesised that post-mortem translocation, the migration of micro-organisms from mucosal surfaces into the body after death, leads to microbial overgrowth in post-mortem samples, which is more frequently polymicrobial and which would be detected more frequently with increased post-mortem interval (PMI) from death to autopsy. This study aimed to evaluate the association between PMI and bacteriological yield in post-mortem examinations of sudden unexpected deaths in infancy (SUDI). A retrospective review of all microbiological findings from >500 SUDI autopsies (7–365 days of age) was performed as part of a larger review of >1500 paediatric autopsies over a 10-year period, 1996–2005. All autopsies were carried out in a single specialist centre by a small number of paediatric pathologists. For the 507 SUDI included in the analysis, there were 2079 samples collected for bacteriological culture. The median PMI was 2 days. The proportion of positive cultures decreased from 83% for samples taken within 24h of death, to 67% when taken five or more days after death (chi-square for linear trend=19.99, P <0.0001). Polymicrobial cultures decreased from 61% to 46% (chi-square for linear trend=12.88, P =0.0003), and cultures taken two or more days after death yielded significantly fewer isolates per sample than cultures taken less than 2 days after death (Mann–Whitney U-test, P =0.009). The findings of this study demonstrate that a PMI of several days’ duration is neither associated with an increased frequency of positive cultures nor with an increased frequency of mixed-growth episodes as was hypothesised to occur with post-mortem translocation. Indeed, the opposite trend is observed, suggesting that a longer PMI may result in death of micro-organisms. However, these data do not allow assessment of the possibility of significant post-mortem translocation occurring within the first few hours after death. Whilst the interpretation of positive microbiological cultures in SUDI post-mortems remains difficult, a PMI of several days’ duration is not associated with an increased risk of post-mortem translocation and routine microbiological sampling is recommended in all SUDI autopsies, even when there is a PMI of several days. [Copyright &y& Elsevier]

Abstract: Objective: To assess the influence of mannose-binding lectin (MBL) genotype on endothelial function in the presence and absence of infection in childhood. Methods: We studied 2176 children aged 10 years drawn from the Avon Longitudinal Study of Parents and Children. Endothelial function was assessed by flow mediated dilatation (FMD). Exon 1 and promoter polymorphisms in the MBL gene were determined by heteroduplexing procedures. Children were classified as AA (wild type) AO (heterozygotes) and OO (homozygotes). Results: During the vascular assessment, 544 children presented with current or recent (<2 weeks) infection (INF). FMD was reduced in the INF group compared to controls (10% reduction in FMD, p <0.001). MBL genotype was not associated with FMD in controls, although a relationship with the degree of impairment during INF was observed (8.0%, 7.6% and 26.6% lower FMD compared to controls for groups AA, AO, OO respectively, p <0.05). After multivariate analysis, OO was associated with reduced FMD in the INF group (odds ratio 2.95 [1.33, 6.52], p <0.001). Conclusion: Homozygosity for MBL variant alleles is associated with greater impairment in FMD during infection in childhood. This suggests a gene-environment interaction operating in early life that may have relevance for the initiation and progression of atherosclerosis. [Copyright &y& Elsevier]

Host-pathogen interactions that allow Helicobacter pylori to survive and persist in the stomach of susceptible individuals remain unclear. Human β-defensins (hBDs), epithelial-derived antimicrobial peptides are critical components of host-defense at mucosal surfaces. The role of H. pylori-mediated NF-κB and epidermal growth factor receptor (EGFR) activation on β-defensin expression was investigated. Transient transfection studies utilizing β-defensin promoter constructs were conducted in gastric cells with contribution of individual signaling events evaluated by the addition of specific inhibitors, small interference nucleotide-binding oligomerization domain 1 (NOD 1) RNA or plasmids encoding Vaccinia virus proteins that interrupt interleukin-1 and Toll-like receptor signaling. The role of individual MAPK pathways was further delineated in HEK-293 cells expressing conditional MAPK mutants. We found hBD2 expression exclusively dependent on the presence of the bacterial cag pathogenicity island, with NOD1 a critical host sensor, Impairment of murine β-defensin 4 (an orthologue of hBD2) expression in NOD1-deficient mice 7-days post-infection further confirmed the role of this cytoplasmic pattern-recognition receptor in eliciting host innate immunity. In contrast to hBD2, hBD3 expression was NOD1-independent but EGFR and ERK pathway-dependent. Importantly, Toll-like receptor signaling was not implicated in H. pylori-mediated hBD2 and hBD3 gene expression. The divergent signaling events governing hBD2 and hBD3 expression suggest temporal functional variation, such that hBD2 may contribute to antimicrobial barrier function during the inflammatory phase with hBD3 playing a greater role during the repair, wound healing phase of infection. [ABSTRACT FROM AUTHOR]