Burkholderia Hep_Hag autotransporter (BuHA) proteins elicit a strong antibody response during experimental glanders but not human melioidosis

Background The bacterial biothreat agents Burkholderia mallei and Burkholderia pseudomallei are the cause of glanders and melioidosis, respectively. Genomic and epidemiological studies have shown that B. mallei is a recently emerged, host restricted clone of B. pseudomallei. Results Using bacteriophage-mediated immunoscreening we identified genes expressed in vivo during experimental equine glanders infection. A family of immunodominant antigens were identified that share protein domain architectures with hemagglutinins and invasins. These have been designated Burkholderia Hep_Hag autotransporter (BuHA) proteins. A total of 110/207 positive clones (53%) of a B. mallei expression library screened with sera from two infected horses belonged to this family. This contrasted with 6/189 positive clones (3%) of a B. pseudomallei expression library screened with serum from 21 patients with culture-proven melioidosis. Conclusion Members of the BuHA proteins are found in other Gram-negative bacteria and have been shown to have important roles related to virulence. Compared with other bacterial species, the genomes of both B. mallei and B. pseudomallei contain a relative abundance of this family of proteins. The domain structures of these proteins suggest that they function as multimeric surface proteins that modulate interactions of the cell with the host and environment. Their effect on the cellular immune response to B. mallei and their potential as diagnostics for glanders requires further study

Premature mortality in refractory partial epilepsy: does surgical treatment make a difference?

Background: Epilepsy carries an increased risk of premature death. For some people with intractable focal epilepsy, surgery offers hope for a seizure-free life. The authors aimed to see whether epilepsy surgery influenced mortality in people with intractable epilepsy. Methods: The authors audited survival status in two cohorts (those who had surgery and those who had presurgical assessment but did not have surgery). Results: There were 40 known deaths in the non-surgical group (3365 person years of follow-up) and 19 in the surgical group (3905 person-years of follow-up). Non-operated patients were 2.4 times (95% CI 1.4 to 4.2) as likely to die as those who had surgery. They were 4.5 times (95% CI 1.9 to 10.9) as likely to die a probable epilepsy-related death. In the surgical group, those with ongoing seizures 1 year after surgery were 4.0 (95% CI 1.2 to 13.7) times as likely to die as those who were seizure-free or who had only simple partial seizures. Time-dependent Cox analysis showed that the yearly outcome group did not significantly affect mortality (HR 1.3, 95% CI 0.9 to 1.8). Conclusion: Successful epilepsy surgery was associated with a reduced risk of premature mortality, compared with those with refractory focal epilepsy who did not have surgical treatment. To some extent, the reduced mortality is likely to be conferred by inducing freedom from seizures. It is not certain whether better survival is attributable only to surgery, as treatment decisions were not randomised, and there may be inherent differences between the groups.<br/

'We capture their comments before we leave the station': Service user involvement in the delivery of Appropriate Adult Schemes

The concept of participation is now widely accepted in healthcare and social services, but is less apparent in the delivery of services for vulnerable people who encounter the Criminal Justice System and its associated agencies (Buck et al, 2020). This article considers the extent to which children and ‘vulnerable’ adults who have been detained in police custody are currently able to actively participate in the design and delivery of Appropriate Adult Schemes. This paper draws together responses from 43 services in England and Wales concerning levels of service user engagement to ascertain the current level of participation, and to make recommendations for the future. The paper applies Forbat, et al.'s (2009) models of service user involvement to conceptualise ideological drivers which underpin the Appropriate Adult Scheme's commitment to involvement. The data reveal that while there is a genuine desire to improve service user participation, that institutional, financial, and attitudinal barriers mean that participation either does not occur or is at a very cursory level

Whole egg consumption and cortical bone in healthy children

Eggs contain bioactive compounds thought to benefit pediatric bone. This cross-sectional study shows a positive link between childhood egg intake and radius cortical bone. If randomized trials confirm our findings, incorporating eggs into children's diets could have a significant impact in preventing childhood fractures and reducing the risk of osteoporosis. INTRODUCTION: This study examined the relationships between egg consumption and cortical bone in children. METHODS: The cross-sectional study design included 294 9-13-year-old black and white males and females. Three-day diet records determined daily egg consumption. Peripheral quantitative computed tomography measured radius and tibia cortical bone. Body composition and biomarkers of bone turnover were assessed using dual-energy X-ray absorptiometry and ELISA, respectively. RESULTS: Egg intake was positively correlated with radius and tibia cortical bone mineral content (Ct.BMC), total bone area, cortical area, cortical thickness, periosteal circumference, and polar strength strain index in unadjusted models (r = 0.144-0.224, all P < 0.050). After adjusting for differences in race, sex, maturation, fat-free soft tissue mass (FFST), and protein intakes, tibia relationships were nullified; however, egg intake remained positively correlated with radius Ct.BMC (r = 0.138, P = 0.031). Egg intake positively correlated with total body bone mineral density, BMC, and bone area in the unadjusted models only (r = 0.119-0.224; all P < 0.050). After adjusting for covariates, egg intake was a positive predictor of radius FFST (β = 0.113, P < 0.050) and FFST was a positive predictor of Ct.BMC (β = 0.556, P < 0.050) in path analyses. There was a direct influence of egg on radius Ct.BMC (β = 0.099, P = 0.035), even after adjusting for the mediator, FFST (β = 0.137, P = 0.020). Egg intake was positively correlated with osteocalcin in both the unadjusted (P = 0.005) and adjusted (P = 0.049) models. CONCLUSION: If the positive influence of eggs on Ct.BMC observed in this study is confirmed through future randomized controlled trials, whole eggs may represent a viable strategy to promote pediatric bone development and prevent fractures

Community outbreaks of group A Streptococcus revealed by genome sequencing

The frequent occurrence of disease outbreaks in humans caused by group A Streptococcus (GAS) is an on-going public health threat. Conventional bacterial typing methods lack the discriminatory power to confidently confirm or refute outbreaks in hospital and community settings. Microbial whole genome sequencing (WGS) provides a potential solution to this, but, there has been limited population-based surveillance with accompanying sequence data. We performed retrospective genomic surveillance of 93 clinical GAS isolates from individuals in a defined geographic region. Detailed clinical information was obtained for closely related clusters of isolates. Genomic sequence data was contextualised through comparison with international data. We identified 18 different emm genotypes within our bacterial population, and revealed both highly diverse and closely related isolates. This high level of diversity was maintained even in the context of international sequence data. We also identified two emm1 clusters, and one emm3 cluster, of closely-related isolates that differed only by 1 to 4 single nucleotide polymorphisms. Analysis of clinical information identified no healthcare associated contact between patients, indicating cryptic community transmission. Our findings suggest that genomic surveillance of GAS would increase detection of transmission and highlight opportunities for intervention

Prevalence and characterization of human mecC methicillin-resistant Staphylococcus aureus isolates in England

Objectives: There are limited data available on the epidemiology and prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in the human population that encode the recently described mecA homologue, mecC. To address this knowledge gap we undertook a prospective prevalence study in England to determine the prevalence of mecC among MRSA isolates.&lt;p&gt;&lt;/p&gt; Patients and methods: Three hundred and thirty-five sequential MRSA isolates from individual patients were collected from each of six clinical microbiology laboratories in England during 2011–12. These were tested by PCR or genome sequencing to differentiate those encoding mecA and mecC. mecC-positive isolates were further characterized by multilocus sequence typing, spa typing, antimicrobial susceptibility profile and detection of PBP2a using commercially available kits.&lt;p&gt;&lt;/p&gt; Results: Nine out of the 2010 MRSA isolates tested were mecC positive, indicating a prevalence among MRSA in England of 0.45% (95% CI 0.24%–0.85%). The remainder were mecA positive. Eight out of these nine mecC MRSA isolates belonged to clonal complex 130, the other being sequence type 425. Resistance to non-β-lactam antibiotics was rare among these mecC MRSA isolates and all were phenotypically identified as MRSA using oxacillin and cefoxitin according to BSAC disc diffusion methodology. However, all nine mecC isolates gave a negative result using three different commercial PBP2a detection assays. Conclusions: mecC MRSA are currently rare among MRSA isolated from humans in England and this study provides an important baseline prevalence rate to monitor future changes, which may be important given the increasing prevalence of mecC MRSA reported in Denmark.&lt;p&gt;&lt;/p&gt

Soluble silicon patterns and templates:calcium phosphate nanocrystal deposition in collagen type 1

Patterned mineralisation is a feature of many hard-tissues. The impressive mechanical properties exhibited by such tissues can be, in part, attributed to the patterned deposition of mineral within the organic matrix. Although not thermodynamically favourable, the deposition of calcium phosphate based mineral within collagen fibres occurs in vivo in bone and dentine. As a consequence, numerous researchers have investigated how matrix proteins may be conditioned to enable patterned mineral deposition to recapitulate the structures found in nature. In this study, we have demonstrated that this patterned mineralisation of collagen type I may be induced simply by the pretreatment of the collagen with orthosilicic acid (OSA). The OSA treatment of the collagen resulted in a structural change to the collagen fibres, modifying fibril diameter and changing the kinetics of fibre formation. NMR demonstrated that the OSA preferentially located to the termini of the procollagen fibrils, thereby templating the formation of apatitic calcium phosphate crystals within the collagen fibrils (as shown using TEM, EDX and SAED). This work demonstrates how simple inorganic ions can have potent effects on structuring biological precipitates and suggests why trace quantities of silicon ions are essential to the formation of healthy hard tissues

pH dependent binding in de novo hetero bimetallic coiled coils

Herein the first example of a bimetallic coiled coil featuring a lanthanide binding site is reported, opening opportunities to exploit the attractive NMR and photophysical properties of the lanthanides in multi metallo protein design. In our efforts to fully characterise the system we identified for the first time that lanthanide binding to such sites is pH dependent, with optimal binding at neutral pH, and that the double AsnAsp site is more versatile in this regard than the single Asp site. Our second site featured the structural HgCys3 site, the chemistry of which was essentially unaltered by the presence of the lanthanide site. In fact, both metal binding sites within the hetero bimetallic coiled coil displayed the same properties as their mononuclear single binding site controls, and operated independently of each other. Finally, pH can be used as an external trigger to control the binding of Hg(II) and Tb(III) to the two distinct sites within this coiled coil, and offers the opportunity to “activate” metal binding sites within complex multi metallo and multi-functional designs

Constraining the expansion rate of the Universe using low-redshift ellipticals as cosmic chronometers

We present a new methodology to determine the expansion history of the Universe analyzing the spectral properties of early type galaxies (ETG). We found that for these galaxies the 4000\AA break is a spectral feature that correlates with the relative ages of ETGs. In this paper we describe the method, explore its robustness using theoretical synthetic stellar population models, and apply it using a SDSS sample of $\sim$14 000 ETGs. Our motivation to look for a new technique has been to minimise the dependence of the cosmic chronometer method on systematic errors. In particular, as a test of our method, we derive the value of the Hubble constant $H_0 = 72.6 \pm 2.8$ (stat) $\pm2.3$ (syst) (68% confidence), which is not only fully compatible with the value derived from the Hubble key project, but also with a comparable error budget. Using the SDSS, we also derive, assuming w=constant, a value for the dark energy equation of state parameter $w = -1 \pm 0.2$ (stat) $\pm0.3$ (syst). Given the fact that the SDSS ETG sample only reaches $z \sim 0.3$, this result shows the potential of the method. In future papers we will present results using the high-redshift universe, to yield a determination of H(z) up to $z \sim 1$.Comment: 25 pages, 17 figures, JCAP accepte