Search

Background: Gastroschisis, a congenital anomaly involving a defect in the fetal abdominal wall, has increased in prevalence in many countries, but the aetiology is uncertain. We tested the hypothesis that high maternal alcohol consumption and poor diet in the first trimester are risk factors in a case-control study in the UK (1 July 2007 to 28 February 2010). Methods: Gastroschisis cases and three controls per case (matched for maternal age) were identified at 18- to 20-week routine anomaly screening ultrasound scan (USS). Interviews were carried out during the antenatal period (median 24 weeks' gestation) using a piloted questionnaire. Conditional logistic regression was used to describe the associations between exposure variables and gastroschisis, adjusted for known confounding variables. Results: The response rate was 73% for cases (n = 91) and 70% for controls (n = 217). High consumption of fruits and vegetables during the first trimester (aOR 0.2; 95% CI 0.04-0.6), taking folic acid for at least 6 weeks during the first trimester (aOR 0.3; 95% CI 0.1-0.7) and increasing body fat percentage of total maternal body weight (aOR 0.9; 95% CI 0.8-0.9 per 1% increase) were independently associated with reduced risk. Cigarette smoking (aOR 2.7; 95% CI 1.1-6.8) was an independent risk factor. Conclusion: We report for the first time that higher intake of fruits and vegetables during the first trimester, longer duration of folic acid supplementation and higher body fat percentage are associated with reduced risk of fetal gastroschisis, independent of cigarette smoking. The increased risk of cigarette smoking is greatest in older women and in high socio-economic groups. [ABSTRACT FROM AUTHOR]

The worldwide incidence of malignant melanoma has been increasing during the past decade and is a public health concern because this disease accounts for up to 90% of deaths from cutaneous malignancies. It remains a devastating disease with few therapeutic options once in an advanced stage. Current methods of detection, prognostication, and monitoring of melanoma focus on clinical, morphologic, and histopathologic characteristics of measurable tumor. Although this information provides some insight into disease behavior and outcome, melanoma is still an unpredictable disease. Significant effort has been put into finding an informative serologic biomarker. However, the marker remains elusive, and investigations continue. Using the PubMed database, we reviewed the published literature on serologic melanoma biomarkers and present a synopsis of the extensive investigations that have been performed thus far, provide some insight into why most have failed to become incorporated into routine clinical use, and present an overview of innovative methods currently being explored. [ABSTRACT FROM AUTHOR]

AIM: To determine whether local politicians influence the distribution of traffic calming measures. METHODS: Longitudinal ecological study in two UK cities. Local political constituencies were categorized by representation by members of the cabinet structure as a marker of influence. The density of traffic calming features per political area, adjusted for the historical pattern of road injuries, was compared between cabinet represented and non-represented areas. RESULTS: Traffic calming density was significantly associated with cabinet representation status, adjusted for historical collision risk (risk ratio 2.77, 95% confidence interval 1.37 to 5.61). CONCLUSION: These results support the hypothesis that senior local politicians are effective advocates for enhancing safety in their areas. [ABSTRACT FROM AUTHOR]

This report details the development and use of a population based emergency room surveillance system in the UK. Despite some difficulties in accessing high quality data the system has stimulated a considerable number of research and intervention projects. While surveillance systems with high quality data collection and coding parameters remain the gold standard, imperfect systems, particularly if population based, can play a substantial part in stimulating injury prevention initiatives. [ABSTRACT FROM AUTHOR]

The role of physicians in public health practice has been widely debated. To help identify the distinctive contribution of public health medicine, we reviewed recommended competencies in the UK and USA and debated these with members of the Welsh Affairs Committee of the UK Faculty of Public Health Medicine. We concluded that none of the lists of competencies published to date adequately defined a distinct medical specialty. We have distinguished public health medicine expertise from related public health competencies and other general competencies needed for the effective practice of public health medicine. We discuss the implications of this proposed scheme for training and recruitment. [ABSTRACT FROM AUTHOR]

The Welsh Paediatric Surveillance Unit was established in 1994 to monitor the incidence and prevalence of a number of uncommon disorders of childhood in Wales. Its work complements that of the British Paediatric Surveillance Unit. Information from consultant paediatricians is obtained by means of a monthly card return system; return rate is over 90%. [ABSTRACT FROM AUTHOR]

Background: Dental plaque biofilms are the causative agents of caries, gingivitis and periodontitis. Both mechanical and chemical strategies are used in routine oral hygiene strategies to reduce plaque build-up. If allowed to mature biofilms can create anoxic microenvironments leading to communities which harbor pathogenic Gram-negative anaerobes. When subjected to high velocity fluid jets and sprays biofilms can be fluidized which disrupts the biofilm structure and allows the more efficient delivery of antimicrobial agents., Methods: To investigate how such jets may disrupt anoxic niches in the biofilm, we used planar optodes to measure the dissolved oxygen (DO) concentration at the base of in-vitro biofilms grown from human saliva and dental plaque. These biofilms were subject to "shooting" treatments with a commercial high velocity microspray (HVM) device., Results: HVM treatment resulted in removal of much of the biofilm and a concurrent rapid shift from anoxic to oxic conditions at the base of the surrounding biofilm. We also assessed the impact of HVM treatment on the microbial community by tracking 7 target species by qPCR. There was a general reduction in copy numbers of the universal 16S RNA by approximately 95%, and changes of individual species in the target region ranged from approximately 1 to 4 log reductions., Conclusion: We concluded that high velocity microsprays removed a sufficient amount of biofilm to disrupt the anoxic region at the biofilm-surface interface.

Background/objectives: Interplay between the Hedgehog (HH) and epidermal growth factor receptor (EGFR) pathways modulating the outcome of their signaling activity have been reported in various cancers including pancreatic ductal adenocarcinoma (PDAC). Therefore, simultaneous targeting of these pathways may be clinically beneficial. This Phase I study combined HH and EGFR inhibition in metastatic PDAC patients., Methods: Combined effects of HH and EGFR inhibition using Vismodegib and Erlotinib with or without gemcitabine in metastatic solid tumors were assessed by CT. Another cohort of patients with metastatic PDAC was evaluated by FDG-PET and tumor biopsies-derived biomarkers., Results: Treatment was well tolerated with the maximum tolerated dose cohort experiencing no grade 4 toxicities though 25% experienced grade 3 adverse effects. Recommended phase II dose of Vismodegib and Erlotinib were each 150 mg daily. No tumor responses were observed although 16 patients achieved stable disease for 2-7 cycles. Paired biopsy analysis before and after first cycle of therapy in PDAC patients showed reduced GLI1 mRNA, phospho-GLI1 and associated HH target genes in all cases. However, only half of the cases showed reduced levels of desmoplasia or changes in fibroblast markers. Most patients had decreased phospho-EGFR levels., Conclusions: Vismodegib and Erlotinib combination was well-tolerated although overall outcome in patients with metastatic PDAC was not significantly impacted by combination treatment. Biomarker analysis suggests direct targets inhibition without significantly affecting the stromal compartment. These findings conflict with pre-clinical mouse models, and thus warrant further investigation into how upstream inhibition of these pathways is circumvented in PDAC., Competing Interests: Declaration of competing interest The authors declared no conflicts with this submission., (Copyright © 2019. Published by Elsevier B.V.)

A comparative proteomic analysis was utilized to evaluate similarities and differences in membrane samples derived from the cariogenic bacterium Streptococcus mutans, including the wild-type strain and four mutants devoid of protein translocation machinery components, specifically ∆ffh, ∆yidC1, ∆yidC2, or ∆ffh/yidC1. The purpose of this work was to determine the extent to which the encoded proteins operate individually or in concert with one another and to identify the potential substrates of the respective pathways. Ffh is the principal protein component of the signal recognition particle (SRP), while yidC1 and yidC2 are dual paralogs encoding members of the YidC/Oxa/Alb family of membrane-localized chaperone insertases. Our results suggest that the co-translational SRP pathway works in concert with either YidC1 or YidC2 specifically, or with no preference for paralog, in the insertion of most membrane-localized substrates. A few instances were identified in which the SRP pathway alone, or one of the YidCs alone, appeared to be most relevant. These data shed light on underlying reasons for differing phenotypic consequences of ffh, yidC1 or yidC2 deletion. Our data further suggest that many membrane proteins present in a ∆yidC2 background may be non-functional, that ∆yidC1 is better able to adapt physiologically to the loss of this paralog, that shared phenotypic properties of ∆ffh and ∆yidC2 mutants can stem from impacts on different proteins, and that independent binding to ribosomal proteins is not a primary functional activity of YidC2. Lastly, genomic mutations accumulate in a ∆yidC2 background coincident with phenotypic reversion, including an apparent W138R suppressor mutation within yidC1., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Intrinsically disordered stress proteins have been shown to act as chaperones, protecting proteins from damage caused by stresses such as freezing and thawing. Dehydration proteins (dehydrins) are intrinsically disordered stress proteins that are found in almost all land plants. They consist of a variable number of the short, semi-conserved, Y-, S-, and K-segments, with longer stretches of poorly conserved sequences in between. Previous studies have provided conflicting views on the details of the dehydrin cryoprotective mechanism of enzymes. Experiments with polyethylene glycol (PEG) have shown that PEG cryoprotective efficiency is the same as dehydrins of the same hydrodynamic radius, suggesting that the protein's disordered and polar nature is important, rather than the specific order of the residues. To further elucidate the mechanism, we created scrambled variants of the wild grape dehydrins K 2 and YSK 2 and tested their ability to protect lactate dehydrogenase and yeast frataxin homolog-1 from freeze/thaw damage. The results show that for preventing aggregation, it is the sequence composition and the size of the dehydrin that is the most important factor in protection, while for freeze/thaw damage causing loss of secondary structure, it is the sequence composition that is most significant., (© 2019 The Protein Society.)

As a major etiological agent of human dental caries, Streptococcus mutans resides primarily in biofilms that form on the tooth surfaces, also known as dental plaque. In addition to caries, S. mutans is responsible for cases of infective endocarditis with a subset of strains being indirectly implicated with the onset of additional extraoral pathologies. During the past 4 decades, functional studies of S. mutans have focused on understanding the molecular mechanisms the organism employs to form robust biofilms on tooth surfaces, to rapidly metabolize a wide variety of carbohydrates obtained from the host diet, and to survive numerous (and frequent) environmental challenges encountered in oral biofilms. In these areas of research, S. mutans has served as a model organism for ground-breaking new discoveries that have, at times, challenged long-standing dogmas based on bacterial paradigms such as Escherichia coli and Bacillus subtilis . In addition to sections dedicated to carbohydrate metabolism, biofilm formation, and stress responses, this article discusses newer developments in S. mutans biology research, namely, how S. mutans interspecies and cross-kingdom interactions dictate the development and pathogenic potential of oral biofilms and how next-generation sequencing technologies have led to a much better understanding of the physiology and diversity of S. mutans as a species.

Proper envelope biogenesis of Streptococcus mutans , a biofilm-forming and dental caries-causing oral pathogen, requires two paralogs ( yidC1 and yidC2 ) of the universally conserved YidC/Oxa1/Alb3 family of membrane integral chaperones and insertases. The deletion of either paralog attenuates virulence in vivo , but the mechanisms of disruption remain unclear. Here, we determined whether the deletion of yidC affects cell surface properties, extracellular glucan production, and/or the structural organization of the exopolysaccharide (EPS) matrix and biophysical properties of S. mutans biofilm. Compared to the wild type, the Δ yidC 2 mutant lacked staining with fluorescent vancomycin at the division septum, while the Δ yidC1 mutant resembled the wild type. Additionally, the deletion of either yidC1 or yidC2 resulted in less insoluble glucan synthesis but produced more soluble glucans, especially at early and mid-exponential-growth phases. Alteration of glucan synthesis by both mutants yielded biofilms with less dry weight and insoluble EPS. In particular, the deletion of yidC2 resulted in a significant reduction in biofilm biomass and pronounced defects in the spatial organization of the EPS matrix, thus modifying the three-dimensional (3D) biofilm architecture. The defective biofilm harbored smaller bacterial clusters with high cell density and less surrounding EPS than those of the wild type, which was stiffer in compression yet more susceptible to removal by shear. Together, our results indicate that the elimination of either yidC paralog results in changes to the cell envelope and glucan production that ultimately disrupts biofilm development and EPS matrix structure/composition, thereby altering the physical properties of the biofilms and facilitating their removal. YidC proteins, therefore, represent potential therapeutic targets for cariogenic biofilm control. IMPORTANCE YidC proteins are membrane-localized chaperone insertases that are universally conserved in all bacteria and are traditionally studied in the context of membrane protein insertion and assembly. Both YidC paralogs of the cariogenic pathogen Streptococcus mutans are required for proper envelope biogenesis and full virulence, indicating that these proteins may also contribute to optimal biofilm formation in streptococci. Here, we show that the deletion of either yidC results in changes to the structure and physical properties of the EPS matrix produced by S. mutans , ultimately impairing optimal biofilm development, diminishing its mechanical stability, and facilitating its removal. Importantly, the universal conservation of bacterial yidC orthologs, combined with our findings, provide a rationale for YidC as a possible drug target for antibiofilm therapies., (Copyright © 2018 American Society for Microbiology.)

Bacteria belonging to the genus Streptococcus are the first inhabitants of the oral cavity, which can be acquired right after birth and thus play an important role in the assembly of the oral microbiota. In this article, we discuss the different oral environments inhabited by streptococci and the species that occupy each niche. Special attention is given to the taxonomy of Streptococcus , because this genus is now divided into eight distinct groups, and oral species are found in six of them. Oral streptococci produce an arsenal of adhesive molecules that allow them to efficiently colonize different tissues in the mouth. Also, they have a remarkable ability to metabolize carbohydrates via fermentation, thereby generating acids as byproducts. Excessive acidification of the oral environment by aciduric species such as Streptococcus mutans is directly associated with the development of dental caries. However, less acid-tolerant species such as Streptococcus salivarius and Streptococcus gordonii produce large amounts of alkali, displaying an important role in the acid-base physiology of the oral cavity. Another important characteristic of certain oral streptococci is their ability to generate hydrogen peroxide that can inhibit the growth of S. mutans . Thus, oral streptococci can also be beneficial to the host by producing molecules that are inhibitory to pathogenic species. Lastly, commensal and pathogenic streptococci residing in the oral cavity can eventually gain access to the bloodstream and cause systemic infections such as infective endocarditis.

Streptococcus mutans strongly influences the development of pathogenic biofilms associated with dental caries. Our understanding of S. mutans behaviour in biofilms is based on a few well-characterized laboratory strains; however, individual isolates vary widely in genome content and virulence-associated phenotypes, such as biofilm formation and environmental stress sensitivity. Using an ecological biofilm model, we assessed the impact of co-cultivation of several S. mutans isolates with Streptococcus oralis and Actinomyces naeslundii on biofilm composition following exposure to sucrose. The laboratory reference strain S. mutans UA159 and clinical isolates Smu44 (most aciduric), Smu56 (altered biofilm formation) and Smu81 (more sensitive to oxidative stress) were used. Our data revealed S. mutans isolates varied in their ability to compete and become dominant in the biofilm after the addition of sucrose, and this difference correlated with sensitivity to H 2 O 2 produced by S. oralis. Smu81 was particularly sensitive to H 2 O 2 and could not compete with S. oralis in mixed-species biofilm, despite forming robust biofilms on its own. Thus, diminished oxidative stress tolerance in S. mutans isolates can impair their ability to compete in complex biofilms, even in the presence of sucrose, which could influence the progression of a healthy biofilm community to one capable of causing disease., (© 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.)

The ability of certain oral biofilm bacteria to moderate pH through arginine metabolism by the arginine deiminase system (ADS) is a deterrent to the development of dental caries. Here, we characterize a novel Streptococcus strain, designated strain A12, isolated from supragingival dental plaque of a caries-free individual. A12 not only expressed the ADS pathway at high levels under a variety of conditions but also effectively inhibited growth and two intercellular signaling pathways of the dental caries pathogen Streptococcus mutans. A12 produced copious amounts of H2O2 via the pyruvate oxidase enzyme that were sufficient to arrest the growth of S. mutans. A12 also produced a protease similar to challisin (Sgc) of Streptococcus gordonii that was able to block the competence-stimulating peptide (CSP)-ComDE signaling system, which is essential for bacteriocin production by S. mutans. Wild-type A12, but not an sgc mutant derivative, could protect the sensitive indicator strain Streptococcus sanguinis SK150 from killing by the bacteriocins of S. mutans. A12, but not S. gordonii, could also block the XIP (comX-inducing peptide) signaling pathway, which is the proximal regulator of genetic competence in S. mutans, but Sgc was not required for this activity. The complete genome sequence of A12 was determined, and phylogenomic analyses compared A12 to streptococcal reference genomes. A12 was most similar to Streptococcus australis and Streptococcus parasanguinis but sufficiently different that it may represent a new species. A12-like organisms may play crucial roles in the promotion of stable, health-associated oral biofilm communities by moderating plaque pH and interfering with the growth and virulence of caries pathogens., (Copyright © 2016, American Society for Microbiology. All Rights Reserved.)

A unique 373 bp region (igr66) between grpE and dnaK of Streptococcus mutans lacks a promoter but is required for optimal production of DnaK. Northern blotting using probes specific to hrcA, igr66 or dnaK revealed multiple transcripts produced from the dnaK operon and 5'-RACE mapped 5' termini of multiple dnaK transcripts within igr66. One product mapped to a predicted 5'-SL (stem-loop) and two others mapped just 5' to Shine-Dalgarno (SD)-like sequences located immediately upstream to dnaK and to a predicted SL 120 bp upstream of the dnaK start codon (3'-SL). A collection of cat reporter-gene strains containing mutant derivatives of igr66 were engineered. Chloramphenicol acetyltransferase (CAT) activity varied greatly between strains, but there were no correlative changes in cat mRNA levels. Interestingly, mutations introduced into the SD-like sequences 5' to the 3'-SL resulted in an 83-98% decrease in CAT activity. Markerless point mutations introduced upstream of dnaK in the SD-like sequences impaired growth at elevated temperatures and resulted in up to a 40% decrease in DnaK protein after heat shock. Collectively, these results indicate processing within igr66 enhances translation in a temperature dependent manner via non-canonical ribosome binding sites positioned >120 bp upstream of dnaK., (© 2015 John Wiley & Sons Ltd.)

Objectives: We examined the role of social cohesion as a component of vulnerability and resilience to the psychological distress of flooding., Methods: A survey collected data from 2238 individuals living in flood-affected areas of England (South Yorkshire and Worcestershire) in 2007. We used Bayesian structural equation modeling to assess factors relating to the latent variables of resilience (years in area, family nearby, and social cohesion) and vulnerability (disruption of essential services, flood risk, and previous flood experience)., Results: Flooding was strongly associated with poor mental health; however, resilience factors (associated with the ability to cope with natural disasters), but not vulnerability, were strongly associated with a reduction in psychological distress., Conclusions: Resilience and social cohesion were important influences on the risk of developing poor mental health following flooding. Increasing resilience of communities by strengthening social cohesion through measures that increase civic participation and changing land use should be considered as potentially inexpensive and effective defenses against avoidable mental harm that will result from increased climate instability.

Streptococcus mutans displays complex regulation of genetic competence, with ComX controlling late competence gene transcription. The rcrRPQ operon has been shown to link oxidative stress tolerance, (p)ppGpp metabolism and competence in S. mutans. Importantly, an rcrR polar (ΔrcrR-P) mutant is hyper-transformable, but an rcrR non-polar (ΔrcrR-NP) mutant cannot be transformed. Transcriptome comparisons of the rcrR mutants using RNA-Seq and quantitative real-time polymerase chain reaction revealed little expression in the 5' region of comX in ΔrcrR-NP, but high level expression in the 3' region. Northern blotting with comX probes revealed two distinct transcripts in the ΔrcrR-P and ΔrcrR-NP strains, and 5' Rapid Amplification of cDNA Ends mapped the 5' terminus of the shorter transcript to nt +140 of the comX structural gene, where a unique 69-aa open reading frame, termed XrpA, was encoded in a different reading frame than ComX. Two single-nucleotide substitution mutants (comX::T162C; comX::T210A) were introduced to disrupt XrpA without affecting the sequence of ComX. When the mutations were in the ΔrcrR-NP genetic background, ComX production and transformation were restored. Overexpression of xrpA led to impaired growth in aerobic conditions and decreased transformability. These results reveal an unprecedented mechanism for competence regulation and stress tolerance by a gene product encoded within the comX gene that appears unique to S. mutans., (© 2015 John Wiley & Sons Ltd.)

The genus Streptococcus comprises important pathogens that have a severe impact on human health and are responsible for substantial economic losses to agriculture. Here, we utilize 46 Streptococcus genome sequences (44 species), including eight species sequenced here, to provide the first genomic level insight into the evolutionary history and genetic basis underlying the functional diversity of all major groups of this genus. Gene gain/loss analysis revealed a dynamic pattern of genome evolution characterized by an initial period of gene gain followed by a period of loss, as the major groups within the genus diversified. This was followed by a period of genome expansion associated with the origins of the present extant species. The pattern is concordant with an emerging view that genomes evolve through a dynamic process of expansion and streamlining. A large proportion of the pan-genome has experienced lateral gene transfer (LGT) with causative factors, such as relatedness and shared environment, operating over different evolutionary scales. Multiple gene ontology terms were significantly enriched for each group, and mapping terms onto the phylogeny showed that those corresponding to genes born on branches leading to the major groups represented approximately one-fifth of those enriched. Furthermore, despite the extensive LGT, several biochemical characteristics have been retained since group formation, suggesting genomic cohesiveness through time, and that these characteristics may be fundamental to each group. For example, proteolysis: mitis group; urea metabolism: salivarius group; carbohydrate metabolism: pyogenic group; and transcription regulation: bovis group.

A cohort comprising residents of a housing regeneration and health programme was created from routinely collected data using a system which allows us to anonymously link housing data to individuals and their health. The regeneration programme incorporating four rolling work packages runs from 2009 to 2014. The main intervention cohort we describe here contains the 18 312 residents of 9051 residences at baseline. The cohort will be followed continuously through routine health data (demographics, mortality, hospital admissions and general practitioner records including prescriptions) with periodic updates of housing regeneration intervention data. Here, we describe the baseline data for the primary health outcomes of emergency hospital admissions for cardiovascular and respiratory conditions and injuries for those aged ≥60 years. We will compare the health of residents within the homes before and after the housing regeneration work has taken place, and we will calculate the change in health service costs with use of hospital and General Practitioners (GP) services. We will also use a difference in differences approach to assess changes in comparison with comparator cohorts. These data will be accessible at the end of the study period in 2016. Further information about this study can be obtained from Ronan Lyons; r.a.lyons@swansea.ac.uk.

Objective: The incidence of gastroschisis, a congenital anomaly where the infant abdominal wall is defective and intestines protrude from the abdominal cavity, is increasing in many countries. The role of maternal stress in some adverse birth outcomes is now well established. We tested the hypothesis that major stressful life events in the first trimester are risk factors for gastroschisis, and social support protective, in a case-control study in the United Kingdom., Methods: Gastroschisis cases and three controls per case (matched for maternal age) were identified at routine 18-20 week fetal anomaly ultrasound scan, in 2007-2010. Face to face questionnaire interviews were carried out during the antenatal period (median 24 weeks gestation) asking about serious stressful events and social support in the first trimester. Data were analysed using conditional logistic regression., Results: Two or more stressful life events in the first trimester (adjusted OR 4.9; 95% CI 1.2-19.4), and moving address in the first trimester (aOR 4.9; 95% CI 1.7-13.9) were strongly associated with risk of gastroschisis, independent of behavioural risk factors including smoking, alcohol, and poor diet. Perceived availability of social support was not associated with reduced risk of gastroschisis (aOR 0.8; 95% CI 0.2-3.1)., Conclusions: Stressful maternal life events in the first trimester of pregnancy including change of address were strongly associated with a substantial increase in the risk of gastroschisis, independent of stress related high risk behaviours such as smoking, alcohol consumption and poor diet. This suggests that stress pathways are involved in the aetiology of gastroschisis.

High coverage, whole genome shotgun (WGS) sequencing of 57 geographically- and genetically-diverse isolates of Streptococcus mutans from individuals of known dental caries status was recently completed. Of the 57 sequenced strains, fifteen isolates, were selected based primarily on differences in gene content and phenotypic characteristics known to affect virulence and compared with the reference strain UA159. A high degree of variability in these properties was observed between strains, with a broad spectrum of sensitivities to low pH, oxidative stress (air and paraquat) and exposure to competence stimulating peptide (CSP). Significant differences in autolytic behavior and in biofilm development in glucose or sucrose were also observed. Natural genetic competence varied among isolates, and this was correlated to the presence or absence of competence genes, comCDE and comX, and to bacteriocins. In general strains that lacked the ability to become competent possessed fewer genes for bacteriocins and immunity proteins or contained polymorphic variants of these genes. WGS sequence analysis of the pan-genome revealed, for the first time, components of a Type VII secretion system in several S. mutans strains, as well as two putative ORFs that encode possible collagen binding proteins located upstream of the cnm gene, which is associated with host cell invasiveness. The virulence of these particular strains was assessed in a wax-worm model. This is the first study to combine a comprehensive analysis of key virulence-related phenotypes with extensive genomic analysis of a pathogen that evolved closely with humans. Our analysis highlights the phenotypic diversity of S. mutans isolates and indicates that the species has evolved a variety of adaptive strategies to persist in the human oral cavity and, when conditions are favorable, to initiate disease.

Crashes involving young drivers (YD) cause significant morbidity and mortality in Great Britain (GB). Graduated Driver Licensing (GDL) is used in some countries to address this. This study assessed potential casualty and cost savings of possible GDL programmes in GB. Police road crash data were analysed to identify YD crashes at night or while carrying passengers. These data were then used to estimate the potential effects of GDL. 314,561 casualties and 3469 fatalities occurred in YD crashes. 25.1% of YD crashes occurred between 9 pm and 6 am and 24.4% occurred with a 15- to 24-year old passenger in the car. A 'strict' form of GDL in GB (night time restriction 9 pm-6 am, no 15-24 year old passengers) with 50% compliance would prevent 114 deaths and 872 serious casualties each year. The estimated value of prevention is £424M pa. A 'less strict' form of GDL (night time restriction 10 pm-5 am, maximum of one 15-19 year old passenger) with 50% compliance would prevent 81 deaths and 538 serious injuries. The estimated value of prevention is £273M pa. Implementing GDL in GB could save significant numbers of lives. Public health organisations have a duty to advocate for such legislation.

Recent rapid advances in "-omics" technologies have yielded new insights into the interaction of the oral microbiome with its host. Associations of species that are usually considered to be acid-tolerant with caries have been confirmed, while some recognized as health-associated are often present in greater proportions in the absence of caries. In addition, some newly identified bacteria have been suggested as potential contributors to the caries process. In spite of this progress, two major challenges remain. The first is that there is a great deal of heterogeneity in the phenotypic capabilities of individual species of oral bacteria. The second is that the most abundant taxa in oral biofilms display remarkable phenotypic plasticity, i.e., the bacteria associated most strongly with health or with caries can morph rapidly in response to alterations in environmental pH, carbohydrate availability and source, and oxygen tension and redox environment. However, new technologic advances coupled with "old-fashioned microbiology" are starting to erode the barriers to a more complete understanding of oral biofilm physiology and ecology, and in doing so are beginning to provide insights for the creation of novel cost-effective caries control therapies.

Introduction of pneumococcal polysaccharide (PPV23) and conjugate vaccine (PCV7) programmes were expected to change the epidemiology of invasive pneumococcal disease (IPD) and pneumonia in the UK. We describe the epidemiology of IPD and hospitalization with pneumonia using high-quality surveillance data over an 8-year period, 2002-2009. Although PPV23 uptake increased from 49% to 70% and PCV7 uptake reached 98% by 2009, the overall incidence of IPD increased from 11.8/100 000 to 16.4/100 000 (P=0.13), and the incidence of hospitalization with pneumonia increased from 143/100 000 to 207/100 000 (P<0.001). Although a reduction in the proportion of IPD caused by PCV7 serotypes was observed, concurrent increases in PPV23 and non-vaccine serotype IPD contributed to an increased IPD burden overall. Marked inequalities in the geographical distribution of disease were observed. Existing vaccination programmes have, so far, not been sufficient to address an increasing burden of pneumococcal disease in our locality.

The cariogenic bacterium Streptococcus mutans has two paralogues of the YidC/Oxa1/Alb3 family of membrane protein insertases/chaperones. Disruption of yidC2 results in loss of genetic competence, decreased membrane-associated ATPase activity and stress sensitivity (acid, osmotic and oxidative). Elimination of yidC1 has less severe effects, with little observable effect on growth or stress sensitivity. To examine the respective roles of YidC1 and YidC2, a conditional expression system was developed allowing simultaneous elimination of both endogenous YidCs. The function of the YidC C-terminal tails was also investigated and a chimeric YidC1 protein appended with the C terminus of YidC2 enabled YidC1 to complement a ΔyidC2 mutant for stress tolerance, ATP hydrolysis activity and extracellular glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity. Elimination of yidC1 or yidC2 affected levels of extracellular proteins, including GtfB, GtfC and adhesin P1 (AgI/II, PAc), which were increased without YidC1 but decreased in the absence of YidC2. Both yidC1 and yidC2 were shown to contribute to S. mutans biofilm formation and to cariogenicity in a rat model. Collectively, these results provide evidence that YidC1 and YidC2 contribute to cell surface biogenesis and protein secretion in S. mutans and that differences in stress sensitivity between the ΔyidC1 and ΔyidC2 mutants stem from a functional difference in the C-termini of these two proteins.

Little is known about the risk of tuberculosis transmission from children. We reviewed the published literature on the transmission of tuberculosis during outbreaks involving children 3 to 11 years of age and report that transmission rates among close contacts in school outbreaks are on average higher (weighted average 69.8% vs. 39.3%) if the index case is a child than an adult.

Aims: Investigating the distribution and origin of Cryptosporidium species in a water catchment affected by destocking and restocking of livestock as a result of a foot and mouth disease epidemic., Methods and Results: Surface water, livestock and wildlife samples were screened for Cryptosporidium and oocysts characterised by sequencing SSU rRNA and COWP loci, and fragment analysis of ML1, ML2 and GP60 microsatellite loci. Oocyst concentrations in water samples (0-20.29 per 10 l) were related to rainfall events, amount of rainfall and topography. There was no detectable impact from catchment restocking. Cryptosporidium spp. found in water were indicative of livestock (Cryptosporidium andersoni and Cryptosporidium parvum) and wildlife (novel genotypes) sources. However, C. andersoni was not found in any animals sampled. Calf infections were age related; C. parvum was significantly more common in younger animals (<4 weeks old). Older calves shared Cryptosporidium bovis, Cryptosporidium ryanae and C. parvum. Wildlife shed C. parvum, Cryptosporidium ubiquitum, muskrat genotype II and deer genotype., Conclusions: Several factors affect the occurrence of Cryptosporidium within a catchment. In addition to farmed and wild animal hosts, topography and rainfall patterns are particularly important., Significance and Impact of the Study: These factors must be considered when undertaking risk-based water safety plans., (© 2011 The Authors. Journal of Applied Microbiology © 2011 The Society for Applied Microbiology.)

Background: The summer of 2007 was the wettest in the UK since records began in 1914 and resulted in severe flooding in several regions. We carried out a health impact assessment using population-based surveys to assess the prevalence of and risk factors for the psychosocial consequences of this flooding in the United Kingdom., Methods: Surveys were conducted in two regions using postal, online, telephone questionnaires and face-to-face interviews. Exposure variables included the presence of flood water in the home, evacuation and disruption to essential services (incident management variables), perceived impact of the floods on finances, house values and perceived health concerns. Validated tools were used to assess psychosocial outcome (mental health symptoms): psychological distress (GHQ-12), anxiety (GAD-7), depression (PHQ-9) and probable post-traumatic stress disorder (PTSD checklist-shortform). Multivariable logistic regression was used to describe the association between water level in the home, psychological exposure variables and incident management variables, and each mental health symptom, adjusted for age, sex, presence of an existing medical condition, employment status, area and data collection method., Results: The prevalence of all mental health symptoms was two to five-fold higher among individuals affected by flood water in the home. People who perceived negative impact on finances were more likely to report psychological distress (OR 2.5, 1.8-3.4), probable anxiety (OR 1.8, 1.3-2.7) probable depression (OR 2.0, 1.3-2.9) and probable PTSD (OR 3.2, 2.0-5.2). Disruption to essential services increased adverse psychological outcomes by two to three-fold. Evacuation was associated with some increase in psychological distress but not significantly for the other three measures., Conclusion: The psychosocial and mental health impact of flooding is a growing public health concern and improved strategies for minimising disruption to essential services and financial worries need to be built in to emergency preparedness and response systems. Public Health Agencies should address the underlying predictors of adverse psychosocial and mental health when providing information and advice to people who are or are likely to be affected by flooding.

We hypothesized that different types of residential heating would be associated with different levels of indoor carbon monoxide (CO) and further that this might result in a differential in the concentration of cyclic 3':5' guanosine monophosphate (cGMP) in blood platelets in exposed residents. Individuals, who were recruited from homes using different fuel for heating, donated a venous blood sample in the winter and in the summer. In the winter the median blood platelet cGMP value for the group using liquid propane gas (LPG) was 65% higher than for the group using piped natural gas for heating (p <0.001). Also in the group using LPG, the median concentration of cGMP in the winter was 39% higher than the summer median (p < 0.003). The mean indoor concentrations of CO were measured over a period of 1 week during the winter and were <1 ppm. We conclude that observed differences were associated with emissions from different types of heating but that CO exposure alone is too low to explain these.

YidC/Oxa/Alb3 family proteins catalyze the insertion of integral membrane proteins in bacteria, mitochondria, and chloroplasts, respectively. Unlike gram-negative organisms, gram-positive bacteria express 2 paralogs of this family, YidC1/SpoIIIJ and YidC2/YgjG. In Streptococcus mutans, deletion of yidC2 results in a stress-sensitive phenotype similar to that of mutants lacking the signal recognition particle (SRP) protein translocation pathway, while deletion of yidC1 has a less severe phenotype. In contrast to eukaryotes and gram-negative bacteria, SRP-deficient mutants are viable in S. mutans; however, double SRP-yidC2 mutants are severely compromised. Thus, YidC2 may enable loss of the SRP by playing an independent but overlapping role in cotranslational protein insertion into the membrane. This is reminiscent of the situation in mitochondria that lack an SRP pathway and where Oxa1 facilitates cotranslational membrane protein insertion by binding directly to translation-active ribosomes. Here, we show that OXA1 complements a lack of yidC2 in S. mutans. YidC2 also functions reciprocally in oxa1-deficient Saccharomyces cerevisiae mutants and mediates the cotranslational insertion of mitochondrial translation products into the inner membrane. YidC2, like Oxa1, contains a positively charged C-terminal extension and associates with translating ribosomes. Our results are consistent with a gene-duplication event in gram-positive bacteria that enabled the specialization of a YidC isoform that mediates cotranslational activity independent of an SRP pathway.

Catering businesses continue to be the most common setting for foodborne disease outbreaks. In a study of catering businesses in England and Wales, operational practices relating to the supply, preparation, and service of food in 88 businesses associated with outbreaks were compared with those practices at 88 control businesses. Operational practices did not differ significantly between case and control businesses but larger small medium-size enterprise (SME) businesses were more likely to be associated with foodborne disease outbreaks than were micro-SME businesses. Businesses associated with outbreaks of Salmonella infection were less likely to use local or national suppliers but instead used regional suppliers, especially for eggs. This practice was the only significantly independent operational practice associated with outbreaks of Salmonella infection. Regional egg suppliers also were more likely to be used by businesses associated with outbreaks attributed to food vehicles containing eggs. Businesses associated with egg-associated outbreaks were less likely to use eggs produced under an approved quality assurance scheme, suggesting that the underlying risk associated with using regional suppliers may relate to the use of contaminated eggs.

Oxa/YidC/Alb family proteins are chaperones involved in membrane protein insertion and assembly. Streptococcus mutans has two YidC paralogs. Elimination of yidC2, but not yidC1, results in stress sensitivity with decreased membrane-associated F(1)F(o) ATPase activity and an inability to initiate growth at low pH or high salt concentrations (A. Hasona, P. J. Crowley, C. M. Levesque, R. W. Mair, D. G. Cvitkovitch, A. S. Bleiweis, and L. J. Brady, Proc. Natl. Acad. Sci. USA 102:17466-17471, 2005). We now show that Escherichia coli YidC complements for acid tolerance, and partially for salt tolerance, in S. mutans lacking yidC2 and that S. mutans YidC1 or YidC2 complements growth in liquid medium, restores the proton motive force, and functions to assemble the F(1)F(o) ATPase in a previously engineered E. coli YidC depletion strain (J. C. Samuelson, M. Chen, F. Jiang, I. Moller, M. Wiedmann, A. Kuhn, G. J. Phillips, and R. E. Dalbey, Nature 406:637-641, 2000). Both YidC1 and YidC2 also promote membrane insertion of known YidC substrates in E. coli; however, complete membrane integrity is not fully replicated, as evidenced by induction of phage shock protein A. While both function to rescue E. coli growth in broth, a different result is observed on agar plates: growth of the YidC depletion strain is largely restored by 247YidC2, a hybrid S. mutans YidC2 fused to the YidC targeting region, but not by a similar chimera, 247YidC1, nor by YidC1 or YidC2. Simultaneous expression of YidC1 and YidC2 improves complementation on plates. This study demonstrates functional redundancy between YidC orthologs in gram-negative and gram-positive organisms but also highlights differences in their activity depending on growth conditions and species background, suggesting that the complete functional spectrum of each is optimized for the specific bacteria and environment in which they reside.

Despite structured enforcement of food hygiene requirements known to prevent foodborne disease outbreaks, catering businesses continue to be the most common setting for outbreaks in the United Kingdom. In a matched case control study of catering businesses, 148 businesses associated with outbreaks were compared with 148 control businesses. Hazard analysis critical control point systems and/or formal food hygiene training qualifications were not protective. Food hygiene inspection scores were not useful in predicting which catering businesses were associated with outbreaks. Businesses associated with outbreaks were more likely to be larger small and medium-sized enterprises (SMEs) or to serve Chinese cuisine and less likely to have the owner or manager working in the kitchen, but when size of the SME was taken into account these two differences were no longer significant. In larger businesses, case businesses were more likely to be hotels and were more commonly associated with viral foodborne outbreaks, but there was no explanation within the data for this association.

Background: It is not clear whether associations between respiratory symptoms and indoor mould are causal. A randomised controlled trial was conducted to see whether asthma improves when indoor mould is removed., Methods: Houses of patients with asthma were randomly allocated into two groups. In one group, indoor mould was removed, fungicide was applied and a fan was installed in the loft. In the control group, intervention was delayed for 12 months. Questionnaires were administered and peak expiratory flow rate was measured at baseline, 6 months and 12 months., Results: Eighty-one houses were allocated to the intervention group and 83 to the control group; 95 participants in 68 intervention houses and 87 in 63 control houses supplied follow-up information. Peak expiratory flow rate variability declined in both groups, with no significant differences between them. At 6 months, significantly more of the intervention group showed a net improvement in wheeze affecting activities (difference between groups 25%, 95% CI 3% to 47%; p = 0.028), perceived improvement of breathing (52%, 95% CI 30% to 74%; p<0.0001) and perceived reduction in medication (59%, 95% CI 35% to 81%; p<0.0001). By 12 months the intervention group showed significantly greater reductions than the controls in preventer and reliever use, and more improvement in rhinitis (24%, 95% CI 9% to 39%; p = 0.001) and rhinoconjunctivitis (20%, 95% CI 5% to 36%; p = 0.009)., Conclusions: Although there was no objective evidence of benefit, symptoms of asthma and rhinitis improved and medication use declined following removal of indoor mould. It is unlikely that this was entirely a placebo effect.

Background: In recent years, awareness of the risks of chemical and poison exposure has increased, and a number of highly publicized terrorist events have heightened community fears. In particular, there is concern surrounding the potential risk of a covert release, which underpins the need to develop robust methods of population surveillance., Aims and Methods: This article outlines the proceedings of a working group and focuses on the need for greater international cooperation and understanding of existing toxicological surveillance systems in a variety of countries. Poison control centers have well-established local networks and experienced staff, which make them well-placed to detect chemical and poison release. This needs further development to ensure timely detection of signals, which might be better achieved by robust international networks and consistent use of data collection tools. We illustrate some of the strengths and weaknesses of existing surveillance methods, and present a position statement on the minimum dataset required by future surveillance systems., Conclusions: Poison control centers provide a useful platform for developing surveillance activity. Having proposed a number of common aims and objectives, it is hoped that these consensus statements will inform decision makers and stimulate discussion of how international toxicological surveillance programs might best be developed.

Background: Rates of injuries may occur more frequently in different types of homes., Methods: Retrospective population-based cohort study utilizing three linked databases: a population register, an architectural assessment of homes in the area, and an emergency department-based injury surveillance system., Results: Over 58,000 homes were classified into 94 different types according to age, size, and built form. Among the 112,248 inhabitants, there were 18,044 emergency department attendances for treatment of an injury suffered in the home. Adjusted odds ratio of injuries for residents of purpose-built apartments was substantially elevated for all injuries (2.07; 95% confidence interval [CI]=1.87-2.30) and poisoning episodes (5.6; 95% CI=3.8-8.3)., Conclusions: Residents of apartment buildings have substantially higher injury rates. Additional research is required to investigate the contribution of environmental hazards and behavioral factors underlying these high rates.

Concern that living near a particular landfill site in Wales caused increased risk of births with congenital malformations led us to examine whether residents living close to 24 landfill sites in Wales experienced increased rates of congenital anomalies after the landfills opened compared with before they opened. We carried out a small-area study in which expected rates of congenital anomalies in births to mothers living within 2 km of the sites, before and after opening of the sites, were estimated from a logistic regression model fitted to all births in residents living at least 4 km away from these sites and hence not likely to be subject to contamination from a landfill, adjusting for hospital catchment area, year of birth, sex, maternal age, and socioeconomic deprivation score. We investigated all births from 1983 through 1997 with at least one recorded congenital anomaly [International Classification of Diseases, Ninth Revision (ICD-9), codes 7400-7599; International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10), codes Q000-Q999]. The ratio of the observed to expected rates of congenital anomalies before landfills opened was 0.87 [95% confidence interval (CI), 0.75-1.00], and this increased to 1.21 (95% CI, 1.04-1.40) after opening, giving a standardized risk ratio of 1.39 (95% CI, 1.12-1.72). Enhanced congenital malformation surveillance data collected from 1998 through 2000 showed a standardized risk ratio of 1.04 (95% CI, 0.88-1.21). Causal inferences are difficult because of possible biases from incomplete case ascertainment, lack of data on individual-level exposures, and other socioeconomic and lifestyle factors that may confound a relationship with area of residence. However, the increase in risk after the sites opened requires continued enhanced surveillance of congenital anomalies, and site-specific chemical exposure studies. Key words: congenital malformations, epidemiology, landfill, small-area health statistics.

Objectives: To determine whether area wide traffic calming distribution reflects known inequalities in child pedestrian injury rates. To determine whether traffic calming is associated with changes in childhood pedestrian injury rates., Design: Small area ecological study, longitudinal analysis of injury rates with cross sectional analysis of traffic calming and method of travel to school., Settings: Two cities in the United Kingdom., Participants: 4-16 year old children between 1992 and 2000., Main Outcome Measures: Area wide traffic calming distribution by area deprivation status and changes in injury rate/1000., Results: The most deprived fourth of city A had 4.8 times (95% CI 3.71 to 6.22) the number of traffic calming features per 1000 population compared with the most affluent fourth. Injury rates among the most deprived dropped from 9.42 to 5.07 from 1992-94 to 1998-2000 (95% CI for change 2.82 to 5.91). In city B, the traffic calming ratio of the most to least deprived fourth was 1.88 (95% CI 1.46 to 2.42); injury rates in the deprived areas dropped from 8.92 to 7.46 (95% CI for change -0.84 to 3.77). Similar proportions of 9-12 year olds walked to school in both cities., Conclusions: Area wide traffic calming is associated with absolute reductions in child pedestrian injury rates and reductions in relative inequalities in child pedestrian injury rates.