An ATP-binding cassette-type cysteine transporter in Campylobacter jejuni inferred from the structure of an extracytoplasmic solute receptor protein

Campylobacter jejuni is a Gram-negative food-borne pathogen associated with gastroenteritis in humans as well as cases of the autoimmune disease Guillain Barre syndrome. C. jejuni is asaccharolytic because it lacks an active glycolytic pathway for the use of sugars as a carbon source. This suggests an increased reliance on amino acids as nutrients and indeed the genome sequence of this organism indicates the presence of a number of amino acid uptake systems. Cj0982, also known as CjaA, is a putative extracytoplasmic solute receptor for one such uptake system as well as a major surface antigen and vaccine candidate. The crystal structure of Cj0982 reveals a two-domain protein with density in the enclosed cavity between the domains that clearly defines the presence of a bound cysteine ligand. Fluorescence titration experiments were used to demonstrate that Cj0982 binds cysteine tightly and specifically with a K-d of similar to 10(-7) M consistent with a role as a receptor for a high- affinity transporter. These data imply that Cj0982 is the binding protein component of an ABC-type cysteine transporter system and that cysteine uptake is important in the physiology of C. jejuni

Citizen science to improve patient and public involvement in GUideline Implementation in oral health and DEntistry (the GUIDE platform)

Background: Citizen science is a way to democratise science by involving groups of citizens in the research process. Clinical guidelines are used to improve practice, but their implementation can be limited. Involving patients and the public can enhance guideline implementation, but there is uncertainty about the best approaches to achieve this. Citizen science is a potential way to involve patients and the public in improving clinical guideline implementation. We aimed to explore the application of citizen science methods to involve patients and the public in the dissemination and implementation of clinical guidelines in oral health and dentistry. Methods: We developed GUIDE (GUideline Implementation in oral health and DEntistry), a citizen science online platform, using a participatory approach with researchers, oral health professionals, guideline developers and citizens. Recruitment was conducted exclusively online. The platform focused on prespecified challenges related to oral health assessment guidelines, and asked citizens to generate ideas, as well as vote and comment on other citizens' ideas to improve those challenges. Citizens also shared their views via surveys and two online synchronous group meetings. Data were collected on participant's demographics, platform engagement and experience of taking part. The most promising idea category was identified by an advisory group based on engagement, feasibility and relevance. We presented quantitative data using descriptive statistics and analysed qualitative data using inductive and deductive thematic analysis. Results: The platform was open for 6 months and we recruited 189 citizens, from which over 90 citizens actively engaged with the platform. Most citizens were over 34 years (64%), female (58%) and had a university degree (50%). They generated 128 ideas, 146 comments and 248 votes. The challenge that led to most engagement was related to prevention and oral health self-care. To take this challenge forward, citizens generated a further 36 ideas to improve a pre-existing National Health Service oral care prevention leaflet. Citizens discussed motivations to take part in the platform (understanding, values, self-care), reasons to stay engaged (communication and feedback, outputs and impact, and relevance of topics discussed) and suggestions to improve future platforms. Conclusion: Citizen science is an effective approach to generate and prioritise ideas from a group of citizens to improve oral health and dental services. Prevention and oral health self-care were of particular interest to citizens. More research is needed to ensure recruitment of a diverse group of citizens and to improve retention in citizen science projects. Patient or Public Contribution: This project was inherently conducted with the input of public partners (citizen scientists) in all key aspects of its conduct and interpretation. In addition, two public partners were part of the research team and contributed to the design of the project, as well as key decisions related to its conduct, analysis, interpretation and dissemination and are co-authors of this manuscript.</p

Function of hyperekplexia-causing alpha(1)R271Q/L glycine receptors is restored by shifting the affected residue out of the allosteric signaling pathway

BACKGROUND AND PURPOSE Glycine receptor a1 subunit R271Q and R271L (a1R271Q/L) mutations cause the neuromotor disorder, hereditary hyperekplexia. Studies suggest that the 271 residue is located within the allosteric signalling pathway linking the agonist binding site to the channel gate. The present study aimed to investigate a possible mechanism for restoring the function of the a1R271Q/L glycine receptor

Citizen science to improve patient and public involvement in GUideline Implementation in oral health and DEntistry (the GUIDE platform)

BackgroundCitizen science is a way to democratise science by involving groups of citizens in the research process. Clinical guidelines are used to improve practice, but their implementation can be limited. Involving patients and the public can enhance guideline implementation, but there is uncertainty about the best approaches to achieve this. Citizen science is a potential way to involve patients and the public in improving clinical guideline implementation. We aimed to explore the application of citizen science methods to involve patients and the public in the dissemination and implementation of clinical guidelines in oral health and dentistry.MethodsWe developed GUIDE (GUideline Implementation in oral health and DEntistry), a citizen science online platform, using a participatory approach with researchers, oral health professionals, guideline developers and citizens. Recruitment was conducted exclusively online. The platform focused on prespecified challenges related to oral health assessment guidelines, and asked citizens to generate ideas, as well as vote and comment on other citizens' ideas to improve those challenges. Citizens also shared their views via surveys and two online synchronous group meetings. Data were collected on participant's demographics, platform engagement and experience of taking part. The most promising idea category was identified by an advisory group based on engagement, feasibility and relevance. We presented quantitative data using descriptive statistics and analysed qualitative data using inductive and deductive thematic analysis.ResultsThe platform was open for 6 months and we recruited 189 citizens, from which over 90 citizens actively engaged with the platform. Most citizens were over 34 years (64%), female (58%) and had a university degree (50%). They generated 128 ideas, 146 comments and 248 votes. The challenge that led to most engagement was related to prevention and oral health self-care. To take this challenge forward, citizens generated a further 36 ideas to improve a pre-existing National Health Service oral care prevention leaflet. Citizens discussed motivations to take part in the platform (understanding, values, self-care), reasons to stay engaged (communication and feedback, outputs and impact, and relevance of topics discussed) and suggestions to improve future platforms.ConclusionCitizen science is an effective approach to generate and prioritise ideas from a group of citizens to improve oral health and dental services. Prevention and oral health self-care were of particular interest to citizens. More research is needed to ensure recruitment of a diverse group of citizens and to improve retention in citizen science projects

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Benthic megafauna of the western Clarion-Clipperton Zone, Pacific Ocean

There is a growing interest in the exploitation of deep-sea mineral deposits, particularly on the abyssal seafloor of the central Pacific Clarion-Clipperton Zone (CCZ), which is rich in polymetallic nodules. In order to effectively manage potential exploitation activities, a thorough understanding of the biodiversity, community structure, species ranges, connectivity, and ecosystem functions across a range of scales is needed. The benthic megafauna plays an important role in the functioning of deep-sea ecosystems and represents an important component of the biodiversity. While megafaunal surveys using video and still images have provided insight into CCZ biodiversity, the collection of faunal samples is needed to confirm species identifications to accurately estimate species richness and species ranges, but faunal collections are very rarely carried out. Using a Remotely Operated Vehicle, 55 specimens of benthic megafauna were collected from seamounts and abyssal plains in three Areas of Particular Environmental Interest (APEI 1, APEI 4, and APEI 7) at 3100–5100 m depth in the western CCZ. Using both morphological and molecular evidence, 48 different morphotypes belonging to five phyla were found, only nine referrable to known species, and 39 species potentially new to science. This work highlights the need for detailed taxonomic studies incorporating genetic data, not only within the CCZ, but in other bathyal, abyssal, and hadal regions, as representative genetic reference libraries that could facilitate the generation of species inventories

The effect of autonomy, training opportunities, age and salaries on job satisfaction in the South East Asian retail petroleum industry

South East Asian petroleum retailers are under considerable pressure to improve service quality by reducing turnover. An empirical methodology from this industry determined the extent to which job characteristics, training opportunities, age and salary influenced the level of job satisfaction, an indicator of turnover. Responses are reported on a random sample of 165 site employees (a 68% response rate) of a Singaporean retail petroleum firm. A restricted multivariate regression model of autonomy and training opportunities explained the majority (35.4%) of the variability of job satisfaction. Age did not moderate these relationships, except for employees >21 years of age, who reported enhanced job satisfaction with additional salary. Human Capital theory, Life Cycle theory and Job Enrichment theory are invoked and explored in the context of these findings in the South East Asian retail petroleum industry. In the South East Asian retail petroleum industry, jobs providing employees with the opportunity to undertake a variety of tasks that enhanced the experienced meaningfulness of work are likely to promote job satisfaction, reduce turnover and increase the quality of service