Cofactor Selectivity in Methylmalonyl Coenzyme A Mutase, a Model Cobamide-Dependent Enzyme.

Cobamides, a uniquely diverse family of enzyme cofactors related to vitamin B12, are produced exclusively by bacteria and archaea but used in all domains of life. While it is widely accepted that cobamide-dependent organisms require specific cobamides for their metabolism, the biochemical mechanisms that make cobamides functionally distinct are largely unknown. Here, we examine the effects of cobamide structural variation on a model cobamide-dependent enzyme, methylmalonyl coenzyme A (CoA) mutase (MCM). The in vitro binding affinity of MCM for cobamides can be dramatically influenced by small changes in the structure of the lower ligand of the cobamide, and binding selectivity differs between bacterial orthologs of MCM. In contrast, variations in the lower ligand have minor effects on MCM catalysis. Bacterial growth assays demonstrate that cobamide requirements of MCM in vitro largely correlate with in vivo cobamide dependence. This result underscores the importance of enzyme selectivity in the cobamide-dependent physiology of bacteria.IMPORTANCE Cobamides, including vitamin B12, are enzyme cofactors used by organisms in all domains of life. Cobamides are structurally diverse, and microbial growth and metabolism vary based on cobamide structure. Understanding cobamide preference in microorganisms is important given that cobamides are widely used and appear to mediate microbial interactions in host-associated and aquatic environments. Until now, the biochemical basis for cobamide preferences was largely unknown. In this study, we analyzed the effects of the structural diversity of cobamides on a model cobamide-dependent enzyme, methylmalonyl-CoA mutase (MCM). We found that very small changes in cobamide structure could dramatically affect the binding affinity of cobamides to MCM. Strikingly, cobamide-dependent growth of a model bacterium, Sinorhizobium meliloti, largely correlated with the cofactor binding selectivity of S. meliloti MCM, emphasizing the importance of cobamide-dependent enzyme selectivity in bacterial growth and cobamide-mediated microbial interactions

Comparison of government and non-government alcohol and other drug (AOD) treatment service delivery for the lesbian, gay, bisexual, and transgender (LGBT) community

Background: Lesbian, gay, bisexual, and transgender (LGBT) populations are more likely to misuse alcohol and other drugs (AOD), compared to the general population. However, LGBT engagement with AOD treatment is often precluded by insensitivity and misunderstanding of LGBT issues. These treatment barriers may be a consequence of either worker attitudes, organizational factors or a combination of both. Few studies have compared service context as an impediment to AOD treatment. Objectives: This pilot study sought to examine and compare staff attitudes, knowledge and awareness of LGBT issues in two state-wide AOD services within Australia. One organization was a government service, whilst the other was faith based. Methods: A cross-sectional study of a convenience sample (N = 130) of workers employed in a state-wide government AOD service (n = 65), and a state-wide non-government service (n = 65) was conducted. Participants self-completed a questionnaire comprising tools previously used to assess staff attitudes, knowledge and awareness of LGBT issues. Results: Few significant differences in attitudes and awareness of LGBT issues between government and non-government respondents were found. Nearly all respondents were supportive of LGBT persons irrespective of organizational context, with a small number of negative views. Although most respondents demonstrated awareness of organizational policies and practices relating to LGBT clients, many were “unsure” or “neutral” of what these might be. Conclusion: It is confirming that the majority of staff report supportive attitudes towards LGBT clients. Findings suggest that organizations need to continue to take leadership to strengthen organizational training and capacity to deliver LGBT friendly AOD treatment practices

Роль корпоративной культуры в системе мотивации труда

OBJECTIVES: Multimorbidity is common in the older population, but the impact of combinations of chronic conditions on disability and quality of life (QoL) is not well known. This analysis explores the effect of specific combinations of chronic diseases on disability, QoL and self-rated health (SRH). DESIGN: We used data from two population representative cross-sectional studies, the Northern Ireland Health and Social Wellbeing Survey (NIHSWS) 2005 and the Survey of Lifestyle, Attitudes and Nutrition (SLAN) 2007 (conducted in the Republic of Ireland). SETTING: Randomly selected community-living participants were interviewed at home. PARTICIPANTS: A total of 6159 participants aged 50 years and older were included in the analysis. OUTCOME MEASURES: Chronic conditions were classified as cardiovascular disease, chronic pain, diabetes or respiratory disease. Interaction terms estimated by logistic regression were used to examine the effects of multiple chronic conditions on disability, SRH and QoL. RESULTS: Each chronic condition group was correlated with each of the others after adjusting for sociodemographic factors. Those from Northern Ireland were more likely to report a limitation in daily activities (45%) compared to those from the Republic of Ireland (21%). Each condition had an independent effect on disability, SRH and QoL, and those with multiple chronic conditions reported the worst outcomes. However, there were no statistically significant positive interactions between chronic condition groups with respect to any outcome. CONCLUSIONS: Chronic conditions affect individuals largely independent of each other with respect to their effect on disability, SRH and QoL. However, a significant proportion of the population aged 50 years and over across the island of Ireland lives with multimorbidity, and this group is at the highest risk of disability, poor SRH and poor QoL

Impaired Orthostatic Blood Pressure Recovery is associated with Unexplained and Injurious Falls

Background/Objectives: Cardiovascular disorders are recognised as important modifiable risk factors for falls. However the association between falls and orthostatic hypotension (OH) remains ambivalent, particularly because of poor measurement methods of previous studies. Our goal was to determine for the first time to what extent OH (and variants) are risk factors for incident falls, unexplained falls (UF), injurious falls (IF) and syncope using dynamic blood pressure (BP) measurements in a population study. Design: Nationally Representative Longitudinal Cohort Study - The Irish Longitudinal Study on Ageing (TILDA) – wave 1 (2009-2011) with 2 year follow-up at wave 2 (2012-2013). Setting: Community dwelling adults. Participants: 4127 participants were randomly sampled from the population of older adults aged ≥50 years resident in Ireland. Measurements: Continuous BP recordings measured during active stands were analysed. OH and variants (initial OH and impaired orthostatic BP stabilisation OH(40)) were defined using dynamic BP measurements. Associations with the number of falls, UF, IF and syncope reported two years later were assessed using negative binomial and modified Poisson regression. Results: Participants had a mean age 61.5(8.2) years (54.2% female). OH(40) was associated with increased relative risk of UF (RR:1.52 95%CI:1.03-2.26). OH was associated with all-cause falls (IRR:1.40 95%CI:1.01-1.96), UF(RR:1.81 95%CI:1.06-3.09), and IF(RR:1.58 95%CI:1.12-2.24). IOH was not associated with any outcome. Conclusion: With the exception of initial orthostatic hypotension, beat-to-beat measures of impaired orthostatic BP recovery (delayed or incomplete stabilisation) are independent risk factors for future falls, unexplained falls, and injurious falls

British Association of Paediatric Surgeons International Affairs Committee: A report of international fellowships

Objective This paper describes the fellowship programme of the International Affairs Committee of the British Association of Paediatric Surgeons.Patients and methods The selection of low-income and middle-income country (LMIC) fellows from 2005 to 2016, their funding, experience, and current roles are described. Qualitative and quantitative analysis was performed. Results Thirty-eight trainees from 21 LMIC were awarded fellowships over the 11-year period. Thirty-two have completed the fellowship at time of writing, all are now in consultant positions. Obtaining a visa was the single most cited barrier to starting the fellowship. Twenty completed the questionnaire. Hundred percent felt the  fellowship had contributed to personal development and 71% had altered clinical practice subsequent to their experience. Thirty-three percent have gained research opportunities.Conclusion This evaluation supports LMIC-high-income country partnerships and highlights the benefits of fellowships to both the individual surgeon, their department and patient population.  Keywords: BAPS, fellowship, low- and middle-income country, partnershi

Quarterly Report (QR8)

Comprehensive report on the progress of the StratusLab project in Q8

Periodic Report (PR1)

Comprehensive report of the first year of the StratusLab project

The ENHANCES study--Enhancing Head and Neck Cancer patients' Experiences of Survivorship: study protocol for a randomized controlled trial

Background Few cancers pose greater challenges than head and neck (H&N) cancer. Residual effects following treatment include body image changes, pain, fatigue and difficulties with appetite, swallowing and speech. Depression is a common comorbidity. There is limited evidence about ways to assist patients to achieve optimal adjustment after completion of treatment. In this study, we aim to examine the effectiveness and feasibility of a model of survivorship care to improve the quality of life of patients who have completed treatment for H&N cancer. Methods This is a preliminary study in which 120 patients will be recruited. A prospective randomised controlled trial of the H&N Cancer Survivor Self-management Care Plan (HNCP) involving pre- and post-intervention assessments will be used. Consecutive patients who have completed a defined treatment protocol for H&N cancer will be recruited from two large cancer services and randomly allocated to one of three study arms: (1) usual care, (2) information in the form of a written resource or (3) the HNCP delivered by an oncology nurse who has participated in manual-based training and skill development in patient self-management support. The trained nurses will meet patients in a face-to-face interview lasting up to 60 minutes to develop an individualised HNCP, based on principles of chronic disease self-management. Participants will be assessed at baseline, 3 and 6 months. The primary outcome measure is quality of life. The secondary outcome measures include mood, self-efficacy and health-care utilisation. The feasibility of implementing this intervention in routine clinical care will be assessed through semistructured interviews with participating nurses, managers and administrators. Interviews with patients who received the HNCP will explore their perceptions of the HNCP, including factors that assisted them in achieving behavioural change. Discussion In this study, we aim to improve the quality of life of a patient population with unique needs by means of a tailored self-management care plan developed upon completion of treatment. Delivery of the intervention by trained oncology nurses is likely to be acceptable to patients and, if successful, will be a model of care that can be implemented for diverse patient populations

Quarterly Report (QR4)

In the fourth quarter, two beta releases of the StratusLab cloud distribution were made and deployed on the project's reference cloud infrastructure. The v1.0 production release is expected just after the close of Q4 due to the scheduling of the project's development sprints. The project continues to operate a production grid service over the StratusLab cloud distribution, demonstrating its functionality and stability. The project has also demonstrated the deployment of a grid site with the Claudia service manager with some autoscaling features