Measuring the association between the opening of a new multi-national restaurant with young people's eating behaviours.

Out-of-home eating (takeaway, take-out and fast-foods) is associated with intakes of higher energy and fat, and lower intakes of micronutrients, and is associated with excess weight gain. In 2017, a unique opportunity arose to measure the association between the opening of a new multi-national fast-food restaurant (McDonald's) and consumption of fast-food on young people aged 11-16. This study uses a repeated cross-sectional design to explore group level change over time with respect to out-of-home eating behaviours of young people. Two secondary schools in Redcar and Cleveland agreed to participate and facilitated the completion of a questionnaire on their pupils eating behaviours at three timepoints a) prior to the new restaurant opening, b) three months post-opening and c) nine months post opening. Reported frequency of visits to McDonald's showed a statistically significant increase in visits between 3 and 9 months of the restaurant opening. This research asks and explores the question of whether the introduction of a new multi-national fast-food restaurant influences eating habits of young people attending schools near the new outlet.

An analysis of food and beverage advertising on bus shelters in a deprived area of Northern England.

OBJECTIVE: To quantify the extent of food and beverage advertising on bus shelters in a deprived area of the UK, to identify the healthfulness of advertised products, and any differences by level of deprivation. The study also sought to assess the creative strategies used and extent of appeal to young people. DESIGN: Images of bus shelter advertisements were collected via in person photography (in 2019) and Google Street View (photos recorded in 2018). Food and beverage advertisements were grouped into one of seventeen food categories and classified as healthy/less healthy using the UK Nutrient Profile Model. The deprivation level of the advertisement location was identified using the UK Index of Multiple Deprivation. SETTING: Middlesbrough and Redcar and Cleveland in South Teesside. PARTICIPANTS: N/A. RESULTS: Eight hundred and thirty-two advertisements were identified, almost half (48·9 %) of which were for foods or beverages. Of food and non-alcoholic beverage adverts, 35·1 % were less healthy. Most food advertisements (98·9 %) used at least one of the persuasive creative strategies. Food advertisements were found to be of appeal to children under 18 years of age (71·9 %). No differences in healthiness of advertised foods were found by level of deprivation. CONCLUSIONS: Food advertising is extensive on bus shelters in parts of the UK, and a substantial proportion of this advertising is classified as less healthy and would not be permitted to be advertised around television programming for children. Bus shelter advertising should be considered part of the UK policy deliberations around restricting less healthy food marketing exposure.

Traumatic Stress, Chronic Ethanol Exposure, or the Combination, Alter Cannabinoid System Components in Reward and Limbic Regions of the Mouse Brain.

The cannabinoid system is independently affected by stress and chronic ethanol exposure. However, the extent to which co-occurrence of traumatic stress and chronic ethanol exposure modulates the cannabinoid system remains unclear. We examined levels of cannabinoid system components, anandamide, 2-arachidonoylglycerol, fatty acid amide hydrolase, and monoacylglycerol lipase after mouse single-prolonged stress (mSPS) or non-mSPS (Control) exposure, with chronic intermittent ethanol (CIE) vapor or without CIE vapor (Air) across several brain regions using ultra-high-performance liquid chromatography tandem mass spectrometry or immunoblotting. Compared to mSPS-Air mice, anandamide and 2-arachidonoylglycerol levels in the anterior striatum were increased in mSPS-CIE mice. In the dorsal hippocampus, anandamide content was increased in Control-CIE mice compared to Control-Air, mSPS-Air, or mSPS-CIE mice. Finally, amygdalar anandamide content was increased in Control-CIE mice compared to Control-Air, or mSPS-CIE mice, but the anandamide content was decreased in mSPS-CIE compared to mSPS-Air mice. Based on these data we conclude that the effects of combined traumatic stress and chronic ethanol exposure on the cannabinoid system in reward pathway regions are driven by CIE exposure and that traumatic stress affects the cannabinoid components in limbic regions, warranting future investigation of neurotherapeutic treatment to attenuate these effects.

Feasibility and acceptability of a Takeaway Masterclass aimed at encouraging healthier cooking practices and menu options in takeaway food outlets.

OBJECTIVE: To evaluate the feasibility and acceptability of the Takeaway Masterclass, a three-hour training session delivered to staff of independent takeaway food outlets that promoted healthy cooking practices and menu options. DESIGN: A mixed-methods study design. All participating food outlets provided progress feedback at 6 weeks post-intervention. Baseline and 6-week post-intervention observational and self-reported data were collected in half of participating takeaway food outlets. SETTING: North East England. PARTICIPANTS: Independent takeaway food outlet owners and managers. RESULTS: Staff from eighteen (10 % of invited) takeaway food outlets attended the training; attendance did not appear to be associated with the level of deprivation of food outlet location. Changes made by staff that required minimal effort or cost to the business were the most likely to be implemented and sustained. Less popular changes included using products that are difficult (or expensive) to source from suppliers, or changes perceived to be unpopular with customers. CONCLUSION: The Takeaway Masterclass appears to be a feasible and acceptable intervention for improving cooking practices and menu options in takeaway food outlets for those who attended the training. Further work is required to increase participation and retention and explore effectiveness, paying particular attention to minimising adverse inequality effects.

A Pedometer-Based Physically Active Learning Intervention: The Importance of Using Preintervention Physical Activity Categories to Assess Effectiveness.

PURPOSE: To assess physical activity outcomes of a pedometer-based physically active learning (PAL) intervention in primary school children. METHODS: Six paired schools were randomly allocated to either a 6-week teacher-led pedometer-based physically active learning intervention or a control (n = 154, female = 60%, age = 9.9 [0.3] y). Accelerometers assessed total daily sedentary time, light physical activity (LPA), and moderate-to-vigorous physical activity (MVPA). Preintervention mean daily MVPA minutes grouped participants as Low Active (<45 min/d) and High Active (≥45 min/d). RESULTS: From the final sample size, the intervention (n = 52) significantly improved LPA versus control (n = 31, P = .04), by reducing sedentary time. More intervention (+10%) than control (+3%) pupils met the 60 minutes per day guidelines. In both intervention subgroups, pupils spent less time in LPA (P < .05) versus control. The greatest nonsignificant increase was found in the Low Active pupils MVPA levels. CONCLUSIONS: Improvements in LPA were statistically significant in the intervention versus control group. In subgroup analysis, Low Active pupils in the intervention showed the greatest beneficial effects and the Most Active pupils may have replaced MVPA and sedentary time with LPA. The intervention group housed clusters of pupils showing variable responsiveness, justifying routine examination of subgroup variability in future studies.

A bivalent typhoid live vector vaccine expressing both chromosome- and plasmid-encoded Yersinia pestis antigens fully protects against murine lethal pulmonary plague infection.

Live attenuated bacteria hold great promise as multivalent mucosal vaccines against a variety of pathogens. A major challenge of this approach has been the successful delivery of sufficient amounts of vaccine antigens to adequately prime the immune system without overattenuating the live vaccine. Here we used a live attenuated Salmonella enterica serovar Typhi strain to create a bivalent mucosal plague vaccine that produces both the protective F1 capsular antigen of Yersinia pestis and the LcrV protein required for secretion of virulence effector proteins. To reduce the metabolic burden associated with the coexpression of F1 and LcrV within the live vector, we balanced expression of both antigens by combining plasmid-based expression of F1 with chromosomal expression of LcrV from three independent loci. The immunogenicity and protective efficacy of this novel vaccine were assessed in mice by using a heterologous prime-boost immunization strategy and compared to those of a conventional strain in which F1 and LcrV were expressed from a single low-copy-number plasmid. The serum antibody responses to lipopolysaccharide (LPS) induced by the optimized bivalent vaccine were indistinguishable from those elicited by the parent strain, suggesting an adequate immunogenic capacity maintained through preservation of bacterial fitness; in contrast, LPS titers were 10-fold lower in mice immunized with the conventional vaccine strain. Importantly, mice receiving the optimized bivalent vaccine were fully protected against lethal pulmonary challenge. These results demonstrate the feasibility of distributing foreign antigen expression across both chromosomal and plasmid locations within a single vaccine organism for induction of protective immunity.

Does brief telephone support improve engagement with a web-based weight management intervention? Randomized controlled trial.

BACKGROUND: Recent reviews suggest Web-based interventions are promising approaches for weight management but they identify difficulties with suboptimal usage. The literature suggests that offering some degree of human support to website users may boost usage and outcomes. OBJECTIVE: We disseminated the POWeR ("Positive Online Weight Reduction") Web-based weight management intervention in a community setting. POWeR consisted of weekly online sessions that emphasized self-monitoring, goal-setting, and cognitive/behavioral strategies. Our primary outcome was intervention usage and we investigated whether this was enhanced by the addition of brief telephone coaching. We also explored group differences in short-term self-reported weight loss. METHODS: Participants were recruited using a range of methods including targeted mailouts, advertisements in the local press, notices on organizational websites, and social media. A total of 786 adults were randomized at an individual level through an online procedure to (1) POWeR only (n=264), (2) POWeR plus coaching (n=247), or (3) a waiting list control group (n=275). Those in the POWeR plus coaching arm were contacted at approximately 7 and 28 days after randomization for short coaching telephone calls aimed at promoting continued usage of the website. Website usage was tracked automatically. Weight was assessed by online self-report. RESULTS: Of the 511 participants allocated to the two intervention groups, the median number of POWeR sessions completed was just one (IQR 0-2 for POWeR only, IQR 0-3 for POWeR plus coach). Nonetheless, a substantial minority completed at least the core three sessions of POWeR: 47 participants (17.8%, 47/264) in the POWeR-only arm and 64 participants (25.9%, 64/247) in the POWeR plus coaching arm. Participants in the POWeR plus coaching group persisted with the intervention for longer and were 1.61 times more likely to complete the core three sessions than the POWeR-only group (χ(2) 1=4.93; OR 1.61, 95% CI 1.06-2.47; n=511). An intention-to-treat analysis showed between-group differences in weight loss (F2,782=12.421, P<.001). Both intervention groups reported more weight loss than the waiting list control group. Weight loss was slightly, but not significantly, greater in the POWeR plus coaching group. A large proportion of participants assigned to POWeR plus coaching refused phone calls or were not contactable (57.9%, 143/247). Exploratory analyses identified health and sociodemographic differences between those who did and did not engage in coaching when it was made available to them. Users who engaged with coaching used the intervention more and lost more weight than those who did not. CONCLUSIONS: In common with most Web-based intervention studies, usage of POWeR was suboptimal overall. However, our findings suggest that supplementing Web-based weight management with brief human support could improve usage and outcomes in those who take it up. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN): 98176068; http://www.controlled-trials.com/ISRCTN98176068 (Archived by WebCite at http://www.webcitation.org/6OKRjM2oy).

A cross-sectional survey study exploring provision and delivery of expanded community tier 2 behavioural weight management services in England.

Guidelines recommend provision of local behavioural weight management (tier 2) programmes for adults living with overweight and obesity. Following the publication of the UK Government's publication 'Tackling Obesity: empowering adults and children to live healthier lives' in July 2021, Government invested around £30 million of additional funding to support the expansion of local authority commissioned tier 2 provision for adults living with excess weight. We conducted a cross-sectional survey study to scope the types of services available, to whom they were made available, and barriers and facilitators to service delivery. An e-survey was disseminated to local authority commissioned tier 2 service providers in England from September to October 2022. Through a combination of closed and open (qualitative) questions, the survey collected data on referral routes, participant eligibility criteria, service content and format, and challenges and enablers to service delivery. Quantitative data were analysed descriptively whilst thematic content analysis was applied to qualitative data. We received 52 responses (estimated response rate = 59%) representing all nine England regions and 89 unique local authorities. Most services were multi-component (84.3%), were 12 weeks duration (78.0%), were group-based (90.0%), were primarily delivered in-person (86.0%), and were free to participants (90.2%). Five responses indicated provision of support for other health and wellbeing issues, for example, mental health, assistance with debt. To improve future WMS service commissioning and delivery, WMS providers need to be allowed adequate time and resource to properly prepare for service delivery. Referral systems and criteria should be made clear and straightforward to both referrers and service users, and strategies to manage surplus referrals should be explored.

A mixed method evaluation of a theory based intervention to reduce sedentary behaviour in contact centres- the stand up for health stepped wedge feasibility study.

INTRODUCTION: Contact centres have higher levels of sedentary behaviour than other office-based workplaces. Stand Up for Health (SUH) is a theory-based intervention developed using the 6SQuID framework to reduce sedentary behaviour in contact centre workers. The aim of this study was to test acceptability and feasibility of implementing SUH in UK contact centres. METHODS: The study was conducted in 2020-2022 (pre COVID and during lockdown) and used a stepped-wedge cluster randomised trial design including a process evaluation. The intervention included working with contact centre managers to develop and implement a customised action plan aligning with SUH's theory of change. Workplace sedentary time, measured using activPAL™ devices, was the primary outcome. Secondary outcomes included productivity, mental wellbeing, musculoskeletal health and physical activity. Empirical estimates of between-centre standard deviation and within-centre standard deviation of outcomes from pre-lockdown data were calculated to inform sample size calculations for future trials. The process evaluation adopted the RE-AIM framework to understand acceptability and feasibility of implementing the intervention. Interviews and focus groups were conducted with contact centre employees and managers, and activity preferences were collected using a questionnaire. RESULTS: A total of 11 contact centres participated: 155 employees from 6 centres in the pre-lockdown data collection, and 54 employees from 5 centres post-lockdown. Interviews and focus groups were conducted with 33 employees and managers, and 96 participants completed an intervention activity preference questionnaire. Overall, the intervention was perceived as acceptable and feasible to deliver. Most centres implemented several intervention activities aligned with SUH's theory of change and over 50% of staff participated in at least one activity (pre-lockdown period). Perceived benefits including reduced sedentary behaviour, increased physical activity, and improved staff morale and mood were reported by contact centre employees and managers. CONCLUSIONS: SUH demonstrates potential as an appealing and acceptable intervention, impacting several wellbeing outcomes. TRIAL REGISTRATION: The trial has been registered on the ISRCTNdatabase: http://www.isrctn.com/ISRCTN11580369.

Accelerated large-scale multiple sequence alignment.

BACKGROUND: Multiple sequence alignment (MSA) is a fundamental analysis method used in bioinformatics and many comparative genomic applications. Prior MSA acceleration attempts with reconfigurable computing have only addressed the first stage of progressive alignment and consequently exhibit performance limitations according to Amdahl's Law. This work is the first known to accelerate the third stage of progressive alignment on reconfigurable hardware. RESULTS: We reduce subgroups of aligned sequences into discrete profiles before they are pairwise aligned on the accelerator. Using an FPGA accelerator, an overall speedup of up to 150 has been demonstrated on a large data set when compared to a 2.4 GHz Core2 processor. CONCLUSIONS: Our parallel algorithm and architecture accelerates large-scale MSA with reconfigurable computing and allows researchers to solve the larger problems that confront biologists today. Program source is available from http://dna.cs.byu.edu/msa/.

Mucosally delivered Salmonella typhi expressing the Yersinia pestis F1 antigen elicits mucosal and systemic immunity early in life and primes the neonatal immune system for a vigorous anamnestic response to parenteral F1 boost.

Neonates respond poorly to conventional vaccines. This has been attributed, in part, to the immaturity of neonatal dendritic cells that lack full capacity for Ag presentation and T cell stimulation. We engineered an attenuated Salmonella Typhi strain to express and export the F1 Ag of Y. pestis (S. Typhi(F1)) and investigated its immunogenicity early in life using a heterologous prime-boost regimen. Newborn mice primed intranasally with a single dose of S. Typhi(F1) elicited mucosal Ab- and IFN-gamma-secreting cells 1 wk after immunization. They also developed a potent and fast anamnestic response to a subsequent parenteral boost with F1-alum, which surpassed those of mice primed and boosted with S. Typhi(F1) or F1-alum. Neonatal priming with S. Typhi(F1), as opposed to priming with F1-alum, resulted in a more balanced IgG2a/IgG1 profile, enhanced avidity maturation and stimulation of B memory cells, and strong Th1-type cell-mediated immunity. S. Typhi(F1) enhanced the activation and maturation of neonatal CD11c+ dendritic cells, shown by increased expression of CD80, CD86, CD40, and MHC-II cell surface markers and production of proinflammatory cytokines IL-12, TNF-alpha, IL-6, and MCP-1. S. Typhi(F1)-stimulated neonatal DC had improved capacity for Ag presentation and T cell stimulation in vitro and induced F1-specific CD4+ and CD8+ T cell responses when adoptively transferred to newborn mice. Mucosal immunization with S. Typhi expressing a foreign Ag effectively primes the neonatal immune system for potent, fast, and broader responses to a parenteral Ag boost. Such a strategy can prevent infectious diseases, including those considered biowarfare threats, early in life.

Chronic Intermittent Ethanol Exposure Increases Ethanol Consumption Following Traumatic Stress Exposure in Mice.

Individuals with post-traumatic stress disorder (PTSD) often use alcohol to cope with their distress. This aberrant use of alcohol often develops into alcohol use disorder (AUD) leading to high rates of PTSD-AUD co-occurrence. Individuals with comorbid PTSD-AUD have more intense alcohol cravings and increased relapse rates during withdrawal than those with AUD alone. Also, individuals with PTSD or AUD alone often show similar psychological behaviors, such as impulsivity and anhedonia. Extensive clinical studies on the behavioral effects of PTSD-AUD comorbidity, namely alcohol use, have been performed. However, these effects have not been well studied or mechanistically explored in animal models. Therefore, the present study evaluated the effects of traumatic stress comorbid with alcohol exposures on ethanol intake, impulsivity, and anhedonia in mice. Adult male C57Bl/6 mice were first exposed to either mouse single-prolonged stress (mSPS), an animal model that has been validated for characteristics akin to PTSD symptoms, or control conditions. Baseline two-bottle choice ethanol consumption and preference tests were conducted after a 7-day isolation period, as part of the mSPS exposure. Next, mice were exposed to air or chronic intermittent ethanol (CIE), a vapor-induced ethanol dependence and withdrawal model, for 4 weeks. Two-bottle choice ethanol drinking was used to measure dependence-induced ethanol consumption and preference during periods intervening CIE cycles. The novelty suppressed feeding (NSF) test was used to evaluate impulsivity and anhedonia behaviors 48 h after mSPS and/or repeated CIE exposure. Results showed that, compared to control conditions, mSPS did not affect baseline ethanol consumption and preference. However, mSPS-CIE mice increased Post-CIE ethanol consumption compared to Control-Air mice. Mice exposed to mSPS had a shorter latency to feed during the NSF, whereas CIE-exposed mice consumed less palatable food reward in their home cage after the NSF. These results demonstrate that mice exposed to both mSPS and CIE are more vulnerable to ethanol withdrawal effects, and those exposed to mSPS have increased impulsivity, while CIE exposure increases anhedonia. Future studies to examine the relationship between behavioral outcomes and the molecular mechanisms in the brain after PTSD-AUD are warranted.

Design, rationale and analysis plan for the Stand Up for Health trial in contact centres: a stepped wedge feasibility study.

BACKGROUND: Contact centres are one of the most sedentary workplaces, with employees spending a very high proportion of their working day sitting down. About a quarter of contact centre staff regularly experience musculoskeletal health problems due to high levels of sedentary behaviour, including lower back pain. There have been no previous randomised studies specifically aiming to reduce sedentary behaviour in contact centre staff. To address this gap, the Stand Up for Health (SUH) study aims to test the feasibility and acceptability of a complex theory-based intervention to reduce sedentary behaviour in contact centres. METHODS: The Stand Up for Health study has a stepped wedge cluster randomised trial design, which is a pragmatic design whereby clusters (contact centres) are randomised to time points at which they will begin to receive the intervention. All contact centre staff have the opportunity to experience the intervention. To minimise the resource burden in this feasibility study, data collection is not continuous, but undertaken on a selective number of occasions, so the stepped wedge design is "incomplete". Eleven contact centres in England and Scotland have been recruited, and the sample size is approximately 27 per centre (270 in total). The statistical analysis will predominantly focus on assessing feasibility, including the calculation of recruitment rates and rates of attrition. Exploratory analysis will be performed to compare objectively measured sedentary time in the workplace (measured using an activPAL™ device) between intervention and control conditions using a linear mixed effects regression model. DISCUSSION: To our knowledge, this is the first stepped wedge feasibility study conducted in call centres. The rationale and justification of our novel staircase stepped wedge design has been presented, and we hope that by presenting our study design and statistical analysis plan, it will contribute to the literature on stepped wedge trials, and in particular feasibility stepped wedge trials. The findings of the study will also help inform whether this is a suitable design for other settings where data collection is challenging. TRIAL REGISTRATION: The trial has been registered on the ISRCTN database: http://www.isrctn.com/ISRCTN11580369.

Community-based prehabilitation before elective major surgery: the PREP-WELL quality improvement project.

Optimising health and well-being before elective major surgery via prehabilitation initiatives is important for good postoperative outcomes. In a busy tertiary centre in North East England, the lack of a formal prehabilitation service meant that opportunities were being missed to optimise patients for surgery. This quality improvement project aimed to implement and evaluate a community-based prehabilitation service for people awaiting elective major surgery: PREP-WELL. A multidisciplinary, cross-sector team introduced PREP-WELL in January 2018. PREP-WELL provided comprehensive assessment and management of perioperative risk factors in the weeks before surgery. During a 12-month pilot, patients were referred from five surgical specialties at James Cook University Hospital. Data were collected on participant characteristics, behavioural and health outcomes, intervention acceptability and costs, and process-related factors. By December 2018, 159 referrals had been received, with 75 patients (47%) agreeing to participate. Most participants opted for a supervised programme (72%) and were awaiting vascular (43%) or orthopaedic (35%) surgery. Median programme duration was 8 weeks. The service was delivered as intended with participants providing positive feedback. Health-related quality of life (HRQoL; EuroQol 5D (EQ-5D) utility) and functional capacity (6 min walk distance) increased on average from service entry to exit, with mean (95% CI) changes of 0.108 (-0.023 to 0.240) and 35 m (-5 to 76 m), respectively. Further increases in EQ5D utility were observed at 3 months post surgery. Substantially more participants were achieving recommended physical activity levels at exit and 3 months post surgery compared with at entry. The mean cost of the intervention was £405 per patient; £52 per week. The service was successfully implemented within existing preoperative pathways. Most participants were very satisfied and improved their risk profile preoperatively. Funding has been obtained to support service development and expansion for at least 2 more years. During this period, alternative pathways will be developed to facilitate wider access and greater uptake.

Repeated stress exposure in mid-adolescence attenuates behavioral, noradrenergic, and epigenetic effects of trauma-like stress in early adult male rats.

Stress in adolescence can regulate vulnerability to traumatic stress in adulthood through region-specific epigenetic activity and catecholamine levels. We hypothesized that stress in adolescence would increase adult trauma vulnerability by impairing extinction-retention, a deficit in PTSD, by (1) altering class IIa histone deacetylases (HDACs), which integrate effects of stress on gene expression, and (2) enhancing norepinephrine in brain regions regulating cognitive effects of trauma. We investigated the effects of adolescent-stress on adult vulnerability to severe stress using the single-prolonged stress (SPS) model in male rats. Rats were exposed to either (1) adolescent-stress (33-35 postnatal days) then SPS (58-60 postnatal days; n = 14), or (2) no adolescent-stress and SPS (58-60 postnatal days; n = 14), or (3) unstressed conditions (n = 8). We then measured extinction-retention, norepinephrine, HDAC4, and HDAC5. As expected, SPS exposure induced an extinction-retention deficit. Adolescent-stress prior to SPS eliminated this deficit, suggesting adolescent-stress conferred resiliency to adult severe stress. Adolescent-stress also conferred region-specific resilience to norepinephrine changes. HDAC4 and HDAC5 were down-regulated following SPS, and these changes were also modulated by adolescent-stress. Regulation of HDAC levels was consistent with the pattern of cognitive effects of SPS; only animals exposed to SPS without adolescent-stress exhibited reduced HDAC4 and HDAC5 in the prelimbic cortex, hippocampus, and striatum. Thus, HDAC regulation caused by severe stress in adulthood interacts with stress history such that seemingly conflicting reports describing effects of adolescent stress on adult PTSD vulnerability may stem in part from dynamic HDAC changes following trauma that are shaped by adolescent stress history.

Age-related murine hippocampal CA1 laminae oxidative stress measured in vivo by QUEnch-assiSTed (QUEST) MRI: impact of isoflurane anesthesia.

Age-related impairments in spatial learning and memory often precede non-familial neurodegenerative disease. Ex vivo studies suggest that physiologic age-related oxidative stress in hippocampus area CA1 may contribute to prodromal spatial disorientation and to morbidity. Yet, conventional blood or cerebrospinal fluid assays appear insufficient for early detection or management of oxidative stress within CA1 sub-regions in vivo. Here, we address this biomarker problem using a non-invasive MRI index of CA1 laminae oxidative stress based on reduction in R1 (= 1/T1) after anti-oxidant administration. An R1 reduction reflects quenching of continuous and excessive production of endogenous paramagnetic free radicals. Careful motion-correction image acquisition, and avoiding repeated exposure to isoflurane, facilitates detection of hippocampus CA1 laminae oxidative stress with QUEnch-assiSTed (QUEST) MRI. Intriguingly, age- and isoflurane-related oxidative stress is localized to the stratum lacunosum of the CA1 region. Our data raise the possibility of using QUEST MRI and FDA-approved anti-oxidants to remediate spatial disorientation and later neurodegeneration with age in animals and humans.

YscP and YscU switch the substrate specificity of the Yersinia type III secretion system by regulating export of the inner rod protein YscI.

Pathogenic yersiniae utilize a type III secretion system to inject antihost factors, called Yops, directly into the cytosol of eukaryotic cells. The Yops are injected via a needle-like structure, comprising the YscF protein, on the bacterial surface. While the needle is being assembled, Yops cannot be secreted. YscP and YscU switch the substrate specificity of the secretion system to enable Yop export once the needle attains its proper length. Here, we demonstrate that the inner rod protein YscI plays a critical role in substrate specificity switching. We show that YscI is secreted by the type III secretion system and that YscI secretion by a yscP mutant is abnormally elevated. Furthermore, we show that mutations in the cytoplasmic domain of YscU reduce YscI secretion by the yscP null strain. We also demonstrate that mutants expressing one of three forms of YscI (those with mutations Q84A, L87A, and L96A) secrete substantial amounts of Yops yet exhibit severe defects in needle formation. In the absence of YscP, mutants with the same changes in YscI assemble needles but are unable to secrete Yops. Together, these results suggest that the formation of the inner rod, not the needle, is critical for substrate specificity switching and that YscP and YscU exert their effects on substrate export by controlling the secretion of YscI.

Influencing organisational change in the NHS: lessons learned from workplace wellness initiatives in practice.

This article presents a discussion of the key issues in influencing organisational change in NHS settings, in the development of workplace wellness interventions to improve employee health and wellbeing. To tackle poor public health and associated rising healthcare costs, there must be a focus on the root cause of many preventable diseases - unhealthy lifestyle choices. Workplace wellness initiatives are now an important prevention strategy adopted by socially responsible organisations to target the health and wellbeing of working age adults. Lessons learned from initiatives in secondary care suggest that effective implementation requires change in organisational 'health culture', through a combination of education, behaviour change intervention, needs-based facilities, and services and strategies for developing supportive and health-promoting work environments. Most of all, employers must demonstrate a commitment to health and wellness that is fully integrated with their mission, values and long-term vision, paving the way for sustainable lifestyle changes. Evaluation systems must be in place to measure the impact and outcomes of wellness schemes.

Comparing usage of a web and app stress management intervention: An observational study.

Choices in the design and delivery of digital health behaviour interventions may have a direct influence on subsequent usage and engagement. Few studies have been able to make direct, detailed comparisons of differences in usage between interventions that are delivered via web or app. This study compared the usage of two versions of a digital stress management intervention, one delivered via a website (Healthy Paths) and the other delivered via an app (Healthy Mind). Design modifications were introduced within Healthy Mind to take account of reported differences in how individuals engage with websites compared to apps and mobile phones. Data were collected as part of an observational study nested within a broader exploratory trial of Healthy Mind. Objective usage of Healthy Paths and Healthy Mind were automatically recorded, including frequency and duration of logins, access to specific components within the intervention and order of page/screen visits. Usage was compared for a two week period following initial registration. In total, 381 participants completed the registration process for Healthy Paths (web) and 162 participants completed the registration process for Healthy Mind (app). App users logged in twice as often (Mdn = 2.00) as web users (Mdn = 1.00), U = 13,059.50, p ≤ 0.001, but spent half as much time (Mdn = 5.23 min) on the intervention compared to web users (Mdn = 10.52 min), U = 19,740.00, p ≤ 0.001. Visual exploration of usage patterns over time revealed that a significantly higher proportion of app users (n = 126, 82.35%) accessed both types of support available within the intervention (i.e. awareness and change-focused tools) compared to web users (n = 92, 40.17%), χ2(1, n = 382) = 66.60, p < 0.001. This study suggests that the digital platform used to deliver an intervention (i.e. web versus app) and specific design choices (e.g. navigation, length and volume of content) may be associated with differences in how the intervention content is used. Broad summative usage data (e.g. total time spent on the intervention) may mask important differences in how an intervention is used by different user groups if it is not complemented by more fine-grained analyses of usage patterns over time. TRIAL REGISTRATION NUMBER: ISRCTN67177737.