Physical activity alters the effect of genetic determinants of adiposity on hypertension among individuals of European ancestry in the UKB.

Hypertension is a leading risk factor for cardiovascular disease and is modulated by genetic variants. This study aimed to assess the effect of obesity genetic liability and physical activity on hypertension among European and African ancestry individuals within the UK Biobank (UKB). Participants were 230 115 individuals of European ancestry and 3239 individuals of African ancestry from UKB. Genetic liability for obesity were estimated using previously published data including genetic variants and effect sizes for body mass index (BMI), waist-hip ratio (WHR) and waist circumference (WC) using Plink software. The outcome was defined as stage 2 hypertension (systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥90 mmHg, or the use of anti-hypertensive medications). The association between obesity genetic liability and the outcome was assessed across categories of self-reported physical activity using logistic regression. Among European ancestry participants, there was up to a 1.2 greater odds of hypertension in individuals with high genetic liability and low physical activity compared to individuals with low genetic liability and high physical activity (p < 0.001). In individuals engaging in low levels of physical activity compared with moderate/high physical activity, the effect of BMI genetic liability on hypertension was greater (p interaction = 0.04). There was no evidence of an association between obesity genetic liability and hypertension in individuals of African ancestry in the whole sample or within separate physical activity groups (p > 0.05). This study suggests that higher physical activity levels are associated with lower odds of stage 2 hypertension among European ancestry individuals who carry high genetic liability for obesity. This cannot be inferred for individuals of African ancestry, possibly due to the low African ancestry sample size within the UKB.

Interrupting sitting acutely attenuates cardiometabolic risk markers in South Asian adults living with overweight and obesity.

PURPOSE: This study examined the acute effects of interrupting sitting with light-intensity walking on postprandial cardiometabolic risk markers in South Asian adults. METHODS: South Asians with overweight/obesity (n = 19; body mass index [BMI] > 23 kg·m-2) and normal-weight (n = 8; BMI 18.0-22.9 kg·m-2) aged 48.8 ± 5.6 years completed two, 5-h conditions: (1) prolonged sitting (SIT), and (2) interrupted sitting with 5-min bouts of light-intensity walking every 30-min (INT-SIT). Blood samples and resting expired air samples were collected throughout each condition. Statistical analyses were completed using linear mixed models. RESULTS: In participants with overweight/obesity, postprandial glucose, triglycerides (TAG) and metabolic load index (MLI) over time were lower, whereas resting substrate utilisation and resting energy expenditure (REE) were higher, in INT-SIT than SIT (all p ≤ 0.05). Compared with SIT (0.18 [95% CI 0.13, 0.22] kcal.min-1), INT-SIT (0.23 [95% CI 0.18, 0.27] kcal.min-1) increased postprandial REE iAUC in participants with overweight/obesity (p = 0.04, d = 0.51). Postprandial TAG concentrations over time were lower in INT-SIT versus SIT (p = 0.01, d = 30) in normal-weight participants, with no differences in any other outcomes for this sample group. CONCLUSION: These findings suggest that interrupting sitting with 5-min bouts of light walking every 30-min acutely attenuates cardiometabolic risk markers among South Asians living with overweight/obesity, whereas limited effects may be seen in individuals with normal-weight.

The implementation and impacts of the Comprehensive Care Standard in Australian acute care hospitals: a survey study.

BACKGROUND: Comprehensive care (CC) is becoming a widely acknowledged standard for modern healthcare as it has the potential to improve health service delivery impacting both patient-centred care and clinical outcomes. In 2019, the Australian Commission on Safety and Quality in Health Care mandated the implementation of the Comprehensive Care Standard (CCS). However, little is known about the implementation and impacts of the CCS in acute care hospitals. Our study aimed to explore care professionals' self-reported knowledge, experiences, and perceptions about the implementation and impacts of the CCS in Australian acute care hospitals. METHODS: An online survey using a cross-sectional design that included Australian doctors, nurses, and allied health professionals in acute care hospitals was distributed through our research team and organisation, healthcare organisations, and clinical networks using various methods, including websites, newsletters, emails, and social media platforms. The survey items covered self-reported knowledge of the CCS and confidence in performing CC, experiences in consumer involvement and CC plans, and perceptions of organisational support and impacts of CCS on patient care and health outcomes. Quantitative data were analysed using Rstudio, and qualitative data were analysed thematically using Nvivo. RESULTS: 864 responses were received and 649 were deemed valid responses. On average, care professionals self-reported a moderate level of knowledge of the CCS (median = 3/5) and a high level of confidence in performing CC (median = 4/5), but they self-reported receiving only a moderate level of organisational support (median = 3/5). Only 4% (n = 17) of respondents believed that all patients in their unit had CCS-compliant care plans, which was attributed to lack of knowledge, motivation, teamwork, and resources, documentation issues, system and process limitations, and environment-specific challenges. Most participants believed the CCS introduction improved many aspects of patient care and health outcomes, but also raised healthcare costs. CONCLUSION: Care professionals are confident in performing CC but need more organisational support. Further education and training, resources, multidisciplinary collaboration, and systems and processes that support CC are needed to improve the implementation of the CCS. Perceived increased costs may hinder the sustainability of the CCS. Future research is needed to examine the cost-effectiveness of the implementation of the CCS.

A new measure of exercise adherence: the ATEMPT (Adherence To Exercise for Musculoskeletal Pain Tool).

OBJECTIVES: This study aimed to (1) develop a new measure of adherence to exercise for musculoskeletal (MSK) pain (Adherence To Exercise for Musculoskeletal Pain Tool: ATEMPT) based on previously conceptualised domains of exercise adherence, (2) report the content and structural validity, internal consistency, test-retest reliability, and measurement error for the ATEMPT outcome measure in patients managed with exercise for MSK pain. METHODS: ATEMPT was created using statements describing adherence generated by patients, physiotherapists and researchers, with content validity established. Baseline and retest questionnaires were distributed to patients recommended exercise for MSK pain in 11 National Health Service physiotherapy clinics. Items demonstrating low response variation were removed and the following measurement properties assessed: structural validity, internal consistency, test-retest reliability and measurement error. RESULTS: Baseline and retest data were collected from 382 and 112 patients with MSK pain, respectively. Confirmatory factor analysis established that a single factor solution was the best fit according to Bayesian Information Criterion. The 6-item version of the measure (scored 6-30) demonstrated optimal internal consistency (Cronbach's Alpha 0.86, 95% CI 0.83 to 0.88) with acceptable levels of test-retest reliability (intraclass correlation coefficient 0.84, 95% CI 0.78 to 0.88) and measurement error (smallest detectable change 3.77, 95% CI 3.27 to 4.42) (SE of measurement 2.67, 95% CI 2.31 to 3.16). CONCLUSION: The 6-item ATEMPT was developed from the six domains of exercise adherence. It has adequate content and structural validity, internal consistency, test-retest reliability and measurement error in patients with MSK pain, but should undergo additional testing to establish the construct validity and responsiveness.

Towards inclusive healthcare: evaluating knowledge, confidence and awareness of LGBTQ + health among Internal Medicine Trainees in London.

BACKGROUND: Patients from the lesbian, gay, bisexual, transgender, queer plus (LGBTQ +) community face various health inequalities and report poor healthcare experiences. Little is known about how knowledgeable and confident UK doctors are around LGBTQ + health, and previous research demonstrates that UK medical schools rarely deliver teaching in this area. This research evaluated the level of knowledge, awareness and confidence of LGBTQ + health among Internal Medical Trainees (IMTs) in London. METHODS: London IMTs were invited to complete an online questionnaire evaluating knowledge, awareness and confidence in LGBTQ + health. Stratified analysis of results by demographics was performed. RESULTS: Three hundred and fifteen surveys were analysed from 796 eligible trainees (40%). Confidence in caring for LGBTQ + patients was variable. Confidence in discussing gender identity was lower than for sexual orientation. Knowledge of health issues affecting LGBTQ + patients varied. Most participants had never received training on LGBTQ + health at undergraduate (n = 201, 64%) or postgraduate level (n = 252, 80%), but the majority of participants felt that training would be useful (n = 233, 74%). Stratified analysis revealed that IMTs who received previous LGBTQ + teaching at undergraduate or postgraduate level were considerably more confident discussing sexual orientation with patients, compared to those who received no previous teaching. CONCLUSIONS: There is a clear need for education on LGBTQ + health, given the varied levels of knowledge and confidence identified. A significant majority of IMTs in London have never received teaching on LGBTQ + health, although there exists a strong desire for this. LGBTQ + health topics should be integrated into undergraduate and postgraduate training and examinations for IMTs. This would support IMTs in delivering high quality and inclusive care for all patients, particularly those of sexual orientation and gender identity minorities. There are relatively few published studies exploring competency in LGBTQ + health among doctors, and this is the first among UK Internal Medicine Trainees.

Breaking up sitting with short frequent or long infrequent physical activity breaks does not lead to compensatory changes in appetite, appetite-regulating hormones or energy intake.

The aim of this study was to determine the appetite-related responses to breaking up prolonged sitting with physical activity bouts differing in frequency and duration among adult females. Fourteen sedentary females aged 34 ± 13 years with a body mass index of 27.1 ± 6.3 kg/m2 (mean ± SD) took part in a randomised crossover trial with three, 7.5 h conditions: (1) uninterrupted sitting (SIT), (2) sitting with short frequent 2-min moderate-intensity walking breaks every 30 min (SHORT-BREAKS), and (3) sitting with longer duration, less frequent 10-min moderate-intensity walking breaks every 170-180 min (LONG-BREAKS). The intensity and total duration of physical activity was matched between the SHORT-BREAKS and LONG-BREAKS conditions. Linear mixed models were used to compare the outcomes between conditions with significance being accepted as p ≤ 0.05. There were no significant between-condition differences in hunger, satisfaction, prospective food consumption or overall appetite area under the curve (AUC) (all p ≥ 0.801). Absolute ad libitum energy intake and relative energy intake (REI) did not differ significantly between conditions (all p ≥ 0.420). Acylated ghrelin and total peptide YY incremental and total AUC did not differ significantly between conditions (all p ≥ 0.388). Yet, there was a medium effect size for the higher acylated ghrelin incremental AUC in SHORT-BREAKS versus SIT (d = 0.61); the reverse was seen for total AUC, which was lower in SHORT-BREAKS versus SIT (d = 0.69). These findings suggest that breaking up sitting does not lead to compensatory changes in appetite, appetite hormones or energy intake regardless of physical activity bout duration and frequency among adult females.

Spectroscopic evaluation of UVI-cement mineral interactions: ettringite and hydrotalcite.

Portland cement based grouts used for radioactive waste immobilization contain high replacement levels of supplementary cementitious materials, including blast-furnace slag and fly ash. The minerals formed upon hydration of these cements may have capacity for binding actinide elements present in radioactive waste. In this work, the minerals ettringite (Ca6Al2(SO4)3(OH)12·26H2O) and hydrotalcite (Mg6Al2(OH)16CO3·4H2O) were selected to investigate the importance of minor cement hydrate phases in sequestering and immobilizing UVI from radioactive waste streams. U LIII-edge X-ray absorption spectroscopy (XAS) was used to probe the UVI coordination environment in contact with these minerals. For the first time, solid-state 27Al magic angle spinning nuclear magnetic resonance (MAS-NMR) spectroscopy was applied to probe the Al coordination environment in these UVI-contacted minerals and make inferences on the UVI coordination, in conjunction with the X-ray spectroscopy analyses. The U LIII-edge XAS analysis of the UVI-contacted ettringite phases found them to be similar (>∼70%) to the uranyl oxyhydroxides present in a mixed becquerelite/metaschoepite mineral. Fitting of the EXAFS region, in combination with 27Al NMR analysis, indicated that a disordered Ca- or Al-bearing UVI secondary phase also formed. For the UVI-contacted hydrotalcite phases, the XAS and 27Al NMR data were interpreted as being similar to uranyl carbonate, that was likely Mg-containing.

Translation of the 27-gene immuno-oncology test (IO score) to predict outcomes in immune checkpoint inhibitor treated metastatic urothelial cancer patients.

BACKGROUND: The IO Score is a 27-gene immuno-oncology (IO) classifier that has previously predicted benefit to immune checkpoint inhibitor (ICI) therapy in triple negative breast cancer (TNBC) and non-small cell lung cancer (NSCLC). It generates both a continuous score and a binary result using a defined threshold that is conserved between breast and lung. Herein, we aimed to evaluate the IO Score's binary threshold in ICI-naïve TCGA bladder cancer patients (TCGA-BLCA) and assess its clinical utility in metastatic urothelial cancer (mUC) using the IMvigor210 clinical trial treated with the ICI, atezolizumab. METHODS: We identified a list of tumor immune microenvironment (TIME) related genes expressed across the TCGA breast, lung squamous and lung adenocarcinoma cohorts (TCGA-BRCA, TCGA-LUSQ, and TCGA-LUAD, 939 genes total) and then examined the expression of these 939 genes in TCGA-BLCA, to identify patients as having high inflammatory gene expression. Using this as a test of classification, we assessed the previously established threshold of IO Score. We then evaluated the IO Score with this threshold in the IMvigor210 cohort for its association with overall survival (OS). RESULTS: In TCGA-BLCA, IO Score positive patients had a strong concordance with high inflammatory gene expression (p < 0.0001). Given this concordance, we applied the IO Score to the ICI treated IMvigor210 patients. IO Score positive patients (40%) had a significant Cox proportional hazard ratio (HR) of 0.59 (95% CI 0.45-0.78 p < 0.001) for OS and improved median OS (15.6 versus 7.5 months) compared to IO Score negative patients. The IO Score remained significant in bivariate models combined with all other clinical factors and biomarkers, including PD-L1 protein expression and tumor mutational burden. CONCLUSION: The IMvigor210 results demonstrate the potential for the IO Score as a clinically useful biomarker in mUC. As this is the third tumor type assessed using the same algorithm and threshold, the IO Score may be a promising candidate as a tissue agnostic marker of ICI clinical benefit. The concordance between IO Score and inflammatory gene expression suggests that the classifier is capturing common features of the TIME across cancer types.

Acquired Acrodermatitis enteropathica - an unusual cause of vulva ulceration in a post-operative patient: a case report.

Acrodermatitis enteropathica (AE) is a rare disorder which can be congenital or acquired. The main features are peri-orificial dermatitis, gastrointestinal symptom in the form of diarrhoea, acral dermatitis and alopecia, among others. This report aims to highlight that AE is an important differential diagnosis to consider, when managing older patients with mucosal infections or ulcerations. Here, we present the case of a 68-year-old female with end-stage liver disease who presented with a right inter-trochanteric femoral fracture following a fall and was noted, on admission, to have non-healing mucosal ulcers.

Evaluating a multi-component intervention to reduce and break up office workers' sitting with sit-stand desks using the APEASE criteria.

OBJECTIVE: Sedentary workplace interventions have had success in reducing excessive sitting time in office workers, but barriers to implementation and uptake remain. This study formally assessed a theory-derived, sit-stand desk intervention using the APEASE (Acceptability, Practicability, Effectiveness, Affordability, Side-effects, Equity) criteria. METHODS: Thirteen adults (eight female, mean age 38 ± 10 years) from the treatment arm of a sedentary behaviour intervention participated in semi-structured interviews. Thematic codes were inductively assigned to data items followed by deductive charting using the APEASE criteria. RESULTS: The intervention was highly acceptable, practicable, safe to deploy, and helped workers reduce workplace sitting time, though individual preferences and workload mediated engagement. Affordability of sit-stand desks and Equity of access were potential barriers to uptake. CONCLUSIONS: Through the lens of the APEASE criteria, this theory-derived, multi-component sit-stand desk intervention showed acceptability, practicability and effectiveness in reducing and breaking up sedentary time at work with minimal side effects. Using this approach with further tailoring and personalisation may help workers achieve greater reductions in workplace sitting, though affordability and equity should be considered further.

A structural equation model of second language writing strategies and their influence on anxiety, proficiency, and perceived benefits with online writing.

Second language (L2) writing strategies are essential for successful learning outcomes in courses with a substantial writing component and this is especially true during emergency remote teaching (ERT) when online writing tasks help compensate for the missing offline communication. Online writing tasks are multimodal and interactive, and widely delivered through assignment modules, discussion forums, social media, and other online channels, yet little is known pertaining to L2 writing strategies and online writing beliefs. The current study investigates the types of L2 writing strategies students employed during ERT in the midst of Covid-19 and then used structural modeling to understand how strategies relate to online writing task perceptions, L2 writing anxiety, and L2 writing proficiency. The four L2 writing strategy categories are related to planning, monitoring, reviewing, and translating. Following a cross-sectional survey design, a total of 256 South Korean EFL students completed the study's questionnaire administered during their second semester of ERT. Overall, students reported using planning and monitoring strategies the most while using moderate levels of translation and review strategies. Translation strategies produced a significant positive relationship with L2 writing anxiety, indicating effort-avoidance behavior among apprehensive writers. Contrarily, planning and review strategies were positively associated with increased levels of perceived benefits with online writing tasks. When added to the model, the statistically significant correlations among monitoring category and outcome variables vanished, indicating a mediation effect. Along with addressing future directions in L2 writing strategy research in the post-Covid era, some pedagogical implications for the evolving application of translation strategies are discussed.

Video conferencing in the e-learning context: explaining learning outcome with the technology acceptance model.

This study uses the technology acceptance model (TAM) to help explain how the use of technology influences learning outcomes emanating from engagement with the Zoom video conference platform. To this end, structural equation modeling was used to analyze the relationships among the TAM variables in reference to Zoom taught during the Covid-19 pandemic. Following a cross-sectional research design, data were collected using Davis's TAM (1989) scales including perceived ease of use (PEoU), perceived usefulness (PU), behavioral intentions, and attitude from 321 South Korean university students attending their 10th week of English as a foreign language (EFL) conversational English classes. Results revealed that seven of the ten proposed hypotheses were confirmed, with path coefficients having small to large effect sizes. Most notably, PEoU with Zoom strongly affected PU and actual use. In addition, PU with Zoom predicted intentions to use Zoom in the future; however, it failed to influence perceived learning outcomes. While PU predicted future use, it did not influence actual use regarding how well students reported their current performance in their video conference course. PEoU with video conference tools was an influential antecedent to usefulness, attitude, and perceived learning outcome. Lastly, two notable instances of mediation through PU occurred. In consideration of findings, students and instructors should be well trained on the use and functionality of video conference software before its implementation in video conference classrooms.

Sedentary behaviour in the workplace: prevalence, health implications and interventions.

INTRODUCTION: This paper reviews the prevalence and health risks of excess sedentary behaviour in office workers, and the effectiveness of sedentary workplace interventions in a manner accessible to practitioners. SOURCES OF DATA: A narrative review of empirical studies obtained from PubMed and Web of Science. AREAS OF AGREEMENT: Office workers are highly sedentary, increasing their risk of health problems. Interventions using individual, organisational and environmental level strategies can be effective for reducing workplace sitting. AREAS OF CONTROVERSY: The effects of sedentary workplace interventions on health are inconsistent. This may be due to a lack of randomized controlled trials powered to detect changes in health outcomes. GROWING POINTS: Multicomponent interventions that use a combination of the strategies above may be the most effective for reducing sitting. AREAS TIMELY FOR DEVELOPING RESEARCH: Determining the long-term health and cost-effectiveness of sedentary workplace interventions is a priority to encourage employer buy-in for their implementation.

Convalescent plasma therapy for the treatment of patients with COVID-19: Assessment of methods available for antibody detection and their correlation with neutralising antibody levels.

INTRODUCTION: The lack of approved specific therapeutic agents to treat coronavirus disease (COVID-19) associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has led to the rapid implementation of convalescent plasma therapy (CPT) trials in many countries, including the United Kingdom. Effective CPT is likely to require high titres of neutralising antibody (nAb) in convalescent donations. Understanding the relationship between functional neutralising antibodies and antibody levels to specific SARS-CoV-2 proteins in scalable assays will be crucial for the success of a large-scale collection. We assessed whether neutralising antibody titres correlated with reactivity in a range of enzyme-linked immunosorbent assays (ELISA) targeting the spike (S) protein, the main target for human immune response. METHODS: Blood samples were collected from 52 individuals with a previous laboratory-confirmed SARS-CoV-2 infection. These were assayed for SARS-CoV-2 nAbs by microneutralisation and pseudo-type assays and for antibodies by four different ELISAs. Receiver operating characteristic (ROC) analysis was used to further identify sensitivity and specificity of selected assays to identify samples containing high nAb levels. RESULTS: All samples contained SARS-CoV-2 antibodies, whereas neutralising antibody titres of greater than 1:20 were detected in 43 samples (83% of those tested) and >1:100 in 22 samples (42%). The best correlations were observed with EUROimmun immunoglobulin G (IgG) reactivity (Spearman Rho correlation coefficient 0.88; p < 0.001). Based on ROC analysis, EUROimmun would detect 60% of samples with titres of >1:100 with 100% specificity using a reactivity index of 9.1 (13/22). DISCUSSION: Robust associations between nAb titres and reactivity in several ELISA-based antibody tests demonstrate their possible utility for scaled-up production of convalescent plasma containing potentially therapeutic levels of anti-SARS-CoV-2 nAbs.

Perceived influences on reducing prolonged sitting in police staff: a qualitative investigation using the Theoretical Domains Framework and COM-B model.

BACKGROUND: Workplace interventions have shown promise for reducing sitting in office workers. Police office staff remain an understudied population group that work within a disciplined organisation with distinctive work tasks around public safety, potentially affecting their capability, opportunity, and motivation to change sitting behaviour. This study aimed to assess the perceived influences on reducing workplace sitting in non-operational, desk-based police staff in order to derive theoretical determinants for behaviour change. METHODS: Ten police staff from a single police force in Bedfordshire, England [eight female; 39.5 ± 11.5 years] took part in face-to-face semi-structured interviews lasting 46 ± 11 min on average. Thematic analysis identified key themes which were then mapped onto the Theoretical Domains Framework (TDF) and linked to the Capability, Opportunity, Motivation-Behaviour (COM-B) model. RESULTS: Seven themes were identified: 'Work tasks are seated', 'Social norm is to sit', 'Belief in ability to regulate behaviour', 'Knowledge of health risks', 'Organisational support', 'Impact on productivity', and 'Perceived autonomy for sitting reduction'. CONCLUSIONS: Awareness of behaviour and health impacts (Capability), social and physical support to sit less (Opportunity), and habit formation techniques (Motivation) are recommended considerations in sitting reduction workplace interventions for police staff.

Impaired postprandial glucose and no improvement in other cardiometabolic responses or cognitive function by breaking up sitting with bodyweight resistance exercises: a randomised crossover trial.

The effects of breaking up sitting with resistance exercise on cardiometabolic health and cognitive function in young healthy adults are unknown. This study evaluated the acute effects of breaking up sitting with bodyweight resistance exercise on postprandial glucose, lipids, blood pressure and cognitive function. A randomised crossover design was used. Twelve normal-weight participants aged 25 ± 6 years took part in two, 5 h conditions: (1) uninterrupted sitting (SIT), and (2) sitting with 3 min of bodyweight resistance exercise breaks every 30 min (REX). Dietary intake was standardised across conditions. Linear mixed models were used to compare outcomes between conditions. Postprandial glucose was significantly higher in the REX condition than in SIT (incremental area under the curve 346.3 [95% confidence interval: 233.9, 458.7] and 256.9 [144.4, 369.3] mmol/L∙5 h, respectively, p = 0.045). Blood pressure, lipids and cognitive function outcomes were not different between conditions (p ≥ 0.05). This study suggests that breaking up sitting with bodyweight resistance exercise does not benefit cardiometabolic health or cognitive function acutely in young healthy adults. The longer-term effects of breaking up sitting with resistance exercise warrants investigation to appropriately inform public health guidelines.

Finding satisfaction: intrinsic motivation for synchronous and asynchronous communication in the online language learning context.

Intrinsic value is related to intrinsic motivation and influences learners' decisions to begin, continue, and return to learning tasks. In the context of a fully online foreign language English course, we used structural equation modeling to explore the motivation for asynchronous collaborative writing practice, motivation for video-synchronous speaking practice, course satisfaction, and the mediating effect course satisfaction has on behavioral intentions to use language learning technology. Cross-sectional survey results (n = 186) revealed that students who were motivated by asynchronous online collaborative writing were more likely to enjoy online learning in general when compared to students who reported motivation for video-synchronous online speaking practice. Moreover, the relationship between motivation for collaborative writing and behavioral intentions to use language learning technology was mediated by course satisfaction. A follow-up open-ended survey (n = 65) revealed that students held positive views for online second language writing and speaking practice overall but for distinctly different reasons. The findings are discussed in terms of their theoretical implications for modeling e-learning approaches with significance for promoting instructional training effectiveness and transformative learning.

The Siderophore Synthetase IucA of the Aerobactin Biosynthetic Pathway Uses an Ordered Mechanism.

Biosynthesis of the hydroxamate siderophore aerobactin requires the activity of four proteins encoded within the iuc operon. Recently, we biochemically reconstituted the biosynthetic pathway and structurally characterized IucA and IucC, two enzymes that sequentially couple N6-acetyl-N6-hydroxylysine to the primary carboxylates of citrate. IucA and IucC are members of a family of non-ribosomal peptide synthetase-independent siderophore (NIS) synthetases that are involved in the production of other siderophores, including desferrioxamine, achromobactin, and petrobactin. While structures of several members of this family were solved previously, there is limited mechanistic insight into the reaction catalyzed by NIS synthetases. Therefore, we performed a terreactant steady-state kinetic analysis and herein provide evidence for an ordered mechanism in which the chemistry is preceded by the formation of the quaternary complex. We further probed two regions of the active site with site-directed mutagenesis and identified several residues, including a conserved motif that is present on a dynamic loop, that are important for substrate binding and catalysis.

Immobilizing Pertechnetate in Ettringite via Sulfate Substitution.

Technetium-99 immobilization in low-temperature nuclear waste forms often relies on additives that reduce environmentally mobile pertechnetate (TcO4-) to insoluble Tc(IV) species. However, this is a short-lived solution unless reducing conditions are maintained over the hazardous life cycle of radioactive wastes (some ∼10,000 years). Considering recent experimental observations, this work explores how rapid formation of ettringite [Ca6Al2(SO4)3(OH)12·26(H2O)], a common mineral formed in cementitious waste forms, may be used to directly immobilize TcO4-. Results from ab initio molecular dynamics (AIMD) simulations and solid-phase characterization techniques, including synchrotron X-ray absorption, fluorescence, and diffraction methods, support successful incorporation of TcO4- into the ettringite crystal structure via sulfate substitution when synthesized by aqueous precipitation methods. One sulfate and one water are replaced with one TcO4- and one OH- during substitution, where Ca2+-coordinated water near the substitution site is deprotonated to form OH- for charge compensation upon TcO4- substitution. Furthermore, AIMD calculations support favorable TcO4- substitution at the SO42- site in ettringite rather than gypsum (CaSO4·2H2O, formed as a secondary mineral phase) by at least 0.76 eV at 298 K. These results are the first of their kind to suggest that ettringite may contribute to TcO4- immobilization and the overall lifetime performance of cementitious waste forms.

Acute effects of breaking up prolonged sedentary time on cardiovascular disease risk markers in adults with paraplegia.

Elevated levels of cardiovascular disease (CVD) risk markers are highly prevalent in people with a spinal cord injury (SCI). Breaking up prolonged sedentary time with short, regular bouts of physical activity can reduce postprandial glucose and lipid levels in able-bodied individuals. The effects in people with paraplegia are unknown. The study aims were to examine the acute postprandial glucose (primary aim), lipid, blood pressure, and psychological responses (secondary aims) to breaking up prolonged sedentary time in individuals with paraplegia. This was a randomized crossover design trial. Fourteen participants with paraplegia (age 51 ± 9 years, trunk fat mass 44.3 ± 7.7%) took part in the following two, 5.5-hour conditions: (1) uninterrupted sedentary time (SED), and (2) sedentary time interrupted with 2 minutes of moderate-intensity arm crank ergometer physical activity every 20 minutes (SED-ACT). Standardized breakfast and lunch test meals were consumed during each condition. The outcomes were compared between conditions using linear mixed models. Glucose area under the curve (AUC) was significantly lower during the lunch postprandial period in SED-ACT vs SED (incremental AUC 1.9 [95% CI 1.0, 2.7) and 3.0 [2.1, 3.9] mmol/L∙2.5 hour, respectively, P = .015, f = 0.34). There were no differences between conditions for the breakfast or total 5.5 hours postprandial periods (P > .05). Positive affect was higher in SED-ACT than SED (P = .001). Breaking up prolonged sedentary time acutely attenuates lunch postprandial glucose and improves positive affect in people with paraplegia. This may have clinical relevance for reducing CVD risk and improving psychological well-being in this population.