Concerted functions of<i> Streptococcus gordonii</i> surface proteins PadA and Hsa mediate activation of human platelets and interactions with extracellular matrix

A range of Streptococcus bacteria are able to interact with blood platelets to form a thrombus (clot). Streptococcus gordonii is ubiquitous within the human oral cavity and amongst the common pathogens isolated from subjects with infective endocarditis. Two cell surface proteins, Hsa and Platelet adherence protein A (PadA), in S. gordonii mediate adherence and activation of platelets. In this study, we demonstrate that PadA binds activated platelets and that an NGR (Asparagine-Glycine-Arginine) motif within a 657 amino acid residue N-terminal fragment of PadA is responsible for this, together with two other integrin-like recognition motifs RGT and AGD. PadA also acts in concert with Hsa to mediate binding of S. gordonii to cellular fibronectin and vitronectin, and to promote formation of biofilms. Evidence is presented that PadA and Hsa are each reliant on the other\u27s active presentation on the bacterial cell surface, suggesting cooperativity in functions impacting both colonization and pathogenesis

An exploration of stakeholders’ perceptions of the barriers to clinical use of Assistive Technologies in services for upper-limb stroke rehabilitation

Introduction Half of all patients commencing stroke rehabilitation have marked impairment of the hemiplegic arm, with only 14% regaining useful function. Assistive technologies (ATs) have been developed and evaluated yet currently reach only a fraction of patients. The NIHR funded a five year research programme to generate understanding necessary to develop cost-effective stroke services in upper-limb rehabilitation. This stage aims to understand the potential advantages and disadvantages to the clinical use of ATs, and the needs and priorities of stakeholders. Method Participants include people with a stroke (n=40), their carers (n=20), health care professionals (n= 40), budget holders (n=15) and service commissioners (n=15). An interactive exhibition was held at the University of Southampton in October 2009 where stakeholders tested a range of ATs. Focus groups with each stakeholder group will be conducted within three months of the exhibition to discuss personal involvement in AT use, and positive and negative views on the AT presented. Results Results will be categorised in terms of barriers and facilitators to the use of upper-limb technologies addressing issues such as user comfort and acceptability, cost-benefit, evidence of effect and funding provision. Conclusion Getting research implemented in practice is challenging. This novel approach explores the barriers to using new technologies from the perspective of all key stakeholders. These findings will be combined with those of a national survey, and systematic review to inform a clinical trial resulting in a recommended care pathway for upper-limb rehabilitation

Transcriptome analysis of <i>Streptococcus gordonii </i>Challis DL1 indicates a role for the biofilm-associated <i>fruRBA </i>operon in response to <i>Candida albicans</i>

Multiple levels of interkingdom signaling have been implicated in maintaining the ecological balance between Candida albicans and commensal streptococci to assure a state of oral health. To better understand the molecular mechanisms involved in the initial streptococcal response to the presence of C. albicans that can initiate oral surface colonization and biofilm formation, hypha-forming cells were incubated with Streptococcus gordonii cells for 30 minutes to assess the streptococcal transcriptome response. A genome wide microarray analysis and quantitative PCR validation of S. gordonii transcripts identified a number of genes, the majority of which were involved in metabolic functions that were differentially expressed in the presence of hyphae. The fruR, fruB and fruA genes encoding the transcriptional regulator, fructose-1-phosphate kinase, and fructose-specific permease, respectively, of the phosphoenolpyruvate-dependent fructose phosphotransferase system, were consistently up-regulated. An S. gordonii mutant in which these genes were deleted by allelic replacement, formed an architecturally-distinct, less robust biofilm with C. albicans than did parental strain cells. Complementing the mutant with plasmid borne fruR, fruB and fruA genes caused phenotype reversion, indicating that the genes in this operon played a role in dual species biofilm formation. This genome wide analysis of the S. gordonii transcriptional response to C. albicans has identified several genes that have potential roles in interkingdom signaling and responses

In vivo model for microbial invasion of tooth root dentinal tubules

ABSTRACT Objective Bacterial penetration of dentinal tubules via exposed dentine can lead to root caries and promote infections of the pulp and root canal system. The aim of this work was to develop a new experimental model for studying bacterial invasion of dentinal tubules within the human oral cavity. Material and Methods Sections of human root dentine were mounted into lower oral appliances that were worn by four human subjects for 15 d. Roots were then fixed, sectioned, stained and examined microscopically for evidence of bacterial invasion. Levels of invasion were expressed as Tubule Invasion Factor (TIF). DNA was extracted from root samples, subjected to polymerase chain reaction amplification of 16S rRNA genes, and invading bacteria were identified by comparison of sequences with GenBank database. Results All root dentine samples with patent tubules showed evidence of bacterial cell invasion (TIF value range from 5.7 to 9.0) to depths of 200 mm or more. A spectrum of Gram-positive and Gram-negative cell morphotypes were visualized, and molecular typing identified species of Granulicatella, Streptococcus, Klebsiella, Enterobacter, Acinetobacter, and Pseudomonas as dentinal tubule residents. Conclusion A novel in vivo model is described, which provides for human root dentine to be efficiently infected by oral microorganisms. A range of bacteria were able to initially invade dentinal tubules within exposed dentine. The model will be useful for testing the effectiveness of antiseptics, irrigants, and potential tubule occluding agents in preventing bacterial invasion of dentine

What is a return to work after stroke?: 12 month work outcomes in a feasibility trial

Background: Return to work (RTW) is an outcome in determining the effectiveness of rehabilitation post-stroke. However, stroke survivors (SS) may return to different roles with altered work status. Income, hours, responsibilities and job-satisfaction may be reduced. SS may be dissatisfied if unable to resume apriori work status; alternatively adjusted work status may be viewed positively if perceived as a way of reducing the risk of another stroke. The purpose of this study was to explore what is meant by RTW. Method: Information about the nature of RTW (job type, hours, roles, responsibilities) was extracted from 3, 6 and 12 month follow-up postal questionnaires in 46 SS participants in a feasibility randomised controlled trial investigating effectiveness of a vocational rehabilitation intervention. Results/Findings: Participants took a mean 90 (SD:70, range 7-227) days to RTW. 19/46 reported working at 12 months. In 17 who supplied complete data, 7(41%) reported reduced working hours. Participants incurred a mean wage loss of 44% against pre-stroke earnings. 10/17(59%) participants were in the same job with the same employer and 6(35%) were working in different/modified jobs (1 missing:). 10/17(59%) had work-place adjustments. 18/46 (39%) participants were happy with their work situation. Discussion: Participants experienced marked changes in work status post-stroke, with implications for job-satisfaction, financial security and quality of life. Research into psychological adjustment following altered vocational status in SS is warranted. Conclusion: RTW is a complex outcome and may not translate to a return to pre-stroke vocational status. It is important to consider what constitutes a RTW following stroke

Population Testing for Cancer Predisposing BRCA1/BRCA2 Mutations in the Ashkenazi-Jewish Community: A Randomized Controlled Trial

Technological advances raise the possibility of systematic population-based genetic testing for cancer-predisposing mutations, but it is uncertain whether benefits outweigh disadvantages. We directly compared the psychological/quality-of-life consequences of such an approach to family history (FH)-based testing

Beliefs About Medication and Uptake of Preventive Therapy in Women at Increased Risk of Breast Cancer: Results From a Multicenter Prospective Study

Introduction Uptake of preventive therapies for breast cancer is low. We examined whether women at increased risk of breast cancer can be categorized into groups with similar medication beliefs, and whether belief group membership was prospectively associated with uptake of preventive therapy. Patients and Methods Women (n = 732) attending an appointment to discuss breast cancer risk were approached; 408 (55.7%) completed the Beliefs About Medicines and the Perceived Sensitivity to Medicines questionnaires. Uptake of tamoxifen at 3 months was reported in 258 (63.2%). The optimal number of belief groups were identified using latent profile analysis. Results Uptake of tamoxifen was 14.7% (38/258). One in 5 women (19.4%; 78/402) reported a strong need for tamoxifen. The model fit statistics supported a 2-group model. Both groups held weak beliefs about their need for tamoxifen for current and future health. Group 2 (38%; 154/406 of the sample) reported stronger concerns about tamoxifen and medicines in general, and stronger perceived sensitivity to the negative effects of medicines compared with group 1 (62%; 252/406). Women with low necessity and lower concerns (group 1) were more likely to initiate tamoxifen (18.3%; 33/180) than those with low necessity and higher concerns (group 2) (6.4%; 5/78). After adjusting for demographic and clinical factors, the odds ratio was 3.37 (95% confidence interval, 1.08-10.51; P = .036). Conclusion Uptake of breast cancer preventive therapy was low. A subgroup of women reported low need for preventive therapy and strong medication concerns. These women were less likely to initiate tamoxifen. Medication beliefs are targets for supporting informed decision-making

In vivo model for microbial invasion of tooth root dentinal tubules

Objective Bacterial penetration of dentinal tubules via exposed dentine can lead to root caries and promote infections of the pulp and root canal system. The aim of this work was to develop a new experimental model for studying bacterial invasion of dentinal tubules within the human oral cavity. Material and Methods Sections of human root dentine were mounted into lower oral appliances that were worn by four human subjects for 15 d. Roots were then fixed, sectioned, stained and examined microscopically for evidence of bacterial invasion. Levels of invasion were expressed as Tubule Invasion Factor (TIF). DNA was extracted from root samples, subjected to polymerase chain reaction amplification of 16S rRNA genes, and invading bacteria were identified by comparison of sequences with GenBank database. Results All root dentine samples with patent tubules showed evidence of bacterial cell invasion (TIF value range from 5.7 to 9.0) to depths of 200 mm or more. A spectrum of Gram-positive and Gram-negative cell morphotypes were visualized, and molecular typing identified species of Granulicatella, Streptococcus, Klebsiella, Enterobacter, Acinetobacter, and Pseudomonas as dentinal tubule residents. Conclusion A novel in vivo model is described, which provides for human root dentine to be efficiently infected by oral microorganisms. A range of bacteria were able to initially invade dentinal tubules within exposed dentine. The model will be useful for testing the effectiveness of antiseptics, irrigants, and potential tubule occluding agents in preventing bacterial invasion of dentine

Meaningful health outcomes for paediatric neurodisability: stakeholder prioritisation and appropriateness of patient reported outcome measures

BACKGROUND: Health services are increasingly focused on measuring and monitoring outcomes, particularly those that reflect patients' priorities. To be meaningful, outcomes measured should be valued by patients and carers, be consistent with what health professionals seek to achieve, and be robust in terms of measurement properties. The aim of this study was (i) to seek a shared vision between families and clinicians regarding key aspects of health as outcomes, beyond mortality and morbidity, for children with neurodisability, and (ii) to appraise which multidimensional patient reported outcome measures (PROMs) could be used to assess salient health domains. METHODS: Relevant outcomes were identified from (i) qualitative research with children and young people with neurodisability and parent carers, (ii) Delphi survey with health professionals, and (iii) systematic review of PROMs. The International Classification of Functioning Disability and Health provided a common language to code aspects of health. A subset of stakeholders participated in a prioritisation meeting incorporating a Q-sorting task to discuss and rank aspects of health. RESULTS: A total of 33 pertinent aspects of health were identified. Fifteen stakeholders from the qualitative and Delphi studies participated in the prioritisation meeting: 3 young people, 5 parent carers, and 7 health professionals. Aspects of health that emerged as more important for families and targets for health professionals were: communication, emotional wellbeing, pain, sleep, mobility, self-care, independence, mental health, community and social life, behaviour, toileting and safety. Whilst available PROMs measure many aspects of health in the ICF, no single PROM captures all the key domains prioritised as for children and young people with neurodisability. The paucity of scales for assessing communication was notable. CONCLUSIONS: We propose a core suite of key outcome domains for children with neurodisability that could be used in evaluative research, audit and as health service performance indicators. Future work could appraise domain-specific PROMs for these aspects of health; a single measure assessing the key aspects of health that could be applied across paediatric neurodisability remains to be developed