Effects of volunteering over six months on loneliness, social and mental health outcomes among older adults: The HEAL-HOA Dual Randomized Controlled Trial.

OBJECTIVE: To determine the beneficial effects of volunteering as lay counselor via telephone on own loneliness, social network engagement, perceived social support, stress, anxiety, and depressive symptoms among Chinese older adults in Hong Kong during the COVID-19 pandemic. DESIGN, SETTING, INTERVENTION, AND PARTICIPANTS: "Helping Alleviate Loneliness in Hong Kong Older Adults" (HEAL-HOA), a dual randomized controlled trial, was implemented to test effects of telephone-based psychosocial interventions delivered by older-adult volunteers for low-income lonely older adults. To evaluate the effects of volunteering on loneliness, we randomized 375 individuals ages 50-70 into a volunteering condition versus an active control (psychoeducation with social gatherings). Following a 6-week training, participants in the volunteering condition, delivered tele-interventions to older intervention recipients. MEASUREMENT: The primary outcome was loneliness measured with the UCLA Loneliness Scale. Secondary outcomes were loneliness measured with the De Jong Gierveld Scale (DJG), social network engagement, perceived social support, perceived stress, anxiety, and depressive symptoms. Assessments were completed before training (baseline) and immediately after the 6-month volunteering period. RESULTS: Results from linear mixed models show significant positive effects of volunteering (significant interactions of condition × time) on both measures of loneliness (dppc2 = -0.41 ULCA Loneliness score, dppc2 = -0.70 total DJG score), social network engagement, stress and depressive symptoms as compared to control participants. CONCLUSIONS: The HEAL-HOA trial demonstrates beneficial effects of volunteer-delivered tele-interventions on decreasing loneliness on the volunteer interventionists themselves. Communicating these benefits for volunteers may attract more older adults into volunteering. This effective tele-based volunteer program is scalable for wider implementation. SUMMARY: This RCT tested effects of volunteering on loneliness in Hong Kong during the COVID-19-pandemic. Three hundred seventy-five individuals ages 50-70 were randomized into volunteering (delivering tele-interventions against loneliness) versus an active control condition. After 6 months, volunteers compared to controls, showed benefits on loneliness, social network engagement, stress and depressive symptoms. A program engaging lonely older adults in loneliness intervention delivery has beneficial effects on volunteers themselves and could be a scalable solution for our loneliness epidemic.

'Who tells me when to stay active or to leave?' age differences in and predictors of endorsement of prescriptive views of aging.

OBJECTIVES: Prescriptive views of aging (PVoA) are normative age-based expectations about age-appropriate behavior for older adults, e.g. that they should stay fit/active (active aging norms) but also behave altruistically toward younger generations (altruistic disengagement norms). We aimed at examining age differences in endorsement of active aging and altruistic disengagement and investigated predictors of endorsement. METHOD: In the AGEISM Germany survey, a representative sample of N = 1,915 German participants was recruited, covering a wide age range (Mage=56.57 years, 16-96 years). Cross-sectional data was collected via computer-assisted telephone interviews. RESULTS: Active aging was more strongly endorsed than altruistic disengagement. Endorsement of both PVoA was higher in older age groups - even more pronounced for altruistic disengagement. Endorsement of both norms was positively associated with positive age stereotypes. Furthermore, active aging was predicted by age centrality whereas altruistic disengagement was predicted by negative age stereotypes. Age was still a robust predictor of PVoA even after entering additional predictors. CONCLUSION: Although associated, prescriptive age norms (i.e. beliefs how older people should behave) and descriptive age norms (i.e. beliefs about how older adults and the aging process are like) represent partly independent belief systems, highlighting the importance to assess & further investigate predictors and consequences of PVoA, which become more prevalent with age.

The use of EQ-5D-5L as a patient-reported outcome measure in evaluating community rehabilitation services in Alberta, Canada.

BACKGROUND: The purpose of this study was to describe the characteristics and health-related quality of life (HRQL) of patients accessing community rehabilitation services in Alberta, Canada, using routinely collected EQ-5D-5L data, and explore factors associated with the impact of these services. METHODS: A retrospective, longitudinal, observational design was used. Patients completed the EQ-5D-5L and demographic questions at intake and end of rehabilitation care. Change in EQ-5D-5L dimensions from intake until end of rehabilitation was examined using the Pareto Classification of Health Change. Change scores were calculated for the EQ-5D-5L index, VAS, and total sum scores. Change groups in the EQ-5D-5L index and VAS scores, were defined by minimally important differences of 0.04 and 7.0, respectively. One level change was considered important for the total sum score. Effect size of the change in index, VAS, and total sum scores was also examined. Chi-squared tests were conducted to examine whether change in EQ-5D-5L varied by age, gender, region, and having anxiety/depression at intake. RESULTS: Three service programs were examined; pulmonary rehabilitation (n = 542), group-based community exercise (n = 463), and physiotherapy for bone and joint care (n = 391). At intake, HRQL in all programs was lower than that of the general Alberta population norms and improved by end of rehabilitation. The mean (SD) change in index, VAS, and total sum scores were 0.02 (0.13), 6.0 (18.3), and - 0.5 (2.4) in pulmonary rehabilitation, 0.06 (0.13), 6.6 (18.7), - 1.2 (2.4) in community exercise, and 0.13 (0.16), 1.2 (0.9), and - 2.8 (2.8) in physiotherapy, respectively. Based on change of the index score, 24% deteriorated, 38% improved, and 38% had no change in pulmonary rehabilitation; 17% deteriorated, 51% improved, and 32% had no change in community exercise; 5% deteriorated, 72% improved, and 23% had no change in physiotherapy. Similar trends were seen in the VAS and total sum scores. Older age, urban region, and having anxiety/depression at intake were associated with positive change in EQ-5D-5L. CONCLUSIONS: The results of this study are intended to inform program/service level decisions by describing the characteristics and HRQL of patients accessing community rehabilitation, as well as the predictors of change in health status, which will help direct future program growth and service changes.

Fear of Falling Carries Over into Overprotection in Old Age: A Cross-Lagged Panel Analysis.

Fear of falling might result in overprotection by one's social environment. In turn, feeling dependent could increase fear of falling. However, the association between fear of falling and perceived overprotection and its temporal order is unknown. This longitudinal study explores this potential mutual longitudinal association. This study presents secondary analyses from a larger trial. We tested the association between fear of falling and perceived overprotection in a cross-lagged path model controlled for falls, health-related quality of life, age, gender, and trial condition. N = 310 participants (M = 70 years, range: 64-92) completed self-reports at Time 1, 7 (Time 2), and 11 weeks (Time 3) after baseline assessment. We found a positive association from fear of falling to perceived overprotection (ß = .12, 95% CI[0.02, 0.21], p = .02; ß = .10; [0.01, 0.18], p = .03). The reversed cross-lagged paths were not significant. Findings suggest higher fear of falling translates into perceived overprotection, which may in turn increase loss of independence in old age.

Expression and purification of a cleavable recombinant fortilin from Escherichia coli for structure activity studies.

Complications related to atherosclerosis account for approximately 1 in 4 deaths in the United States and treatment has focused on lowering serum LDL-cholesterol levels with statins. However, approximately 50% of those diagnosed with atherosclerosis have blood cholesterol levels within normal parameters. Human fortilin is an anti-apoptotic protein and a factor in macrophage-mediated atherosclerosis and is hypothesized to protect inflammatory macrophages from apoptosis, leading to subsequent cardiac pathogenesis. Fortilin is unique because it provides a novel drug target for atherosclerosis that goes beyond lowering cholesterol and utilization of a solution nuclear magnetic resonance (NMR) spectroscopy, structure-based drug discovery approach requires milligram quantities of pure, bioactive, recombinant fortilin. Here, we designed expression constructs with different affinity tags and protease cleavage sites to find optimal conditions to obtain the quantity and purity of protein necessary for structure activity relationship studies. Plasmids encoding fortilin with maltose binding protein (MBP), 6-histidine (6His) and glutathione-S-transferase (GST), N- terminal affinity tags were expressed and purified from Escherichia coli (E. coli). Cleavage sites with tobacco etch virus (TEV) protease and human rhinovirus (HRV) 3C protease were assessed. Despite high levels of expression of soluble protein, the fusion constructs were resistant to proteinases without the inclusion of amino acids between the cleavage site and N-terminus. We surveyed constructs with increasing lengths of glycine/serine (GGS) linkers between the cleavage site and fortilin and found that inclusion of at least one GGS insert led to successful protease cleavage and pure fortilin with conserved binding to calcium as measured by NMR.

Participatory Action Research-Dadirri-Ganma, using Yarning: methodology co-design with Aboriginal community members.

BACKGROUND: Appropriate choice of research design is essential to rightly understand the research problem and derive optimal solutions. The Comorbidity Action in the North project sought to better meet the needs of local people affected by drug, alcohol and mental health comorbidity. The aim of the study focused on the needs of Aboriginal peoples and on developing a truly representative research process. A methodology evolved that best suited working with members of a marginalised Aboriginal community. This paper discusses the process of co-design of a Western methodology (participatory action research) in conjunction with the Indigenous methodologies Dadirri and Ganma. This co-design enabled an international PhD student to work respectfully with Aboriginal community members and Elders, health professionals and consumers, and non-Indigenous service providers in a drug and alcohol and mental health comorbidity project in Adelaide, South Australia. METHODS: The PhD student, Aboriginal Elder mentor, Aboriginal Working Party, and supervisors (the research team) sought to co-design a methodology and applied it to address the following challenges: the PhD student was an international student with no existing relationship with local Aboriginal community members; many Aboriginal people deeply distrust Western research due to past poor practices and a lack of implementation of findings into practice; Aboriginal people often remain unheard, unacknowledged and unrecognised in research projects; drug and alcohol and mental health comorbidity experiences are often distressing for Aboriginal community members and their families; attempts to access comorbidity care often result in limited or no access; and Aboriginal community members experience acts of racism and discrimination as health professionals and consumers of health and support services. The research team considered deeply how knowledge is shared, interpreted, owned and controlled, by whom and how, within research, co-morbidity care and community settings. The PhD student was supported to co-design a methodology that was equitable, democratic, liberating and life-enhancing, with real potential to develop feasible solutions. RESULTS: The resulting combined Participatory Action Research (PAR)-Dadirri-Ganma methodology sought to create a bridge across Western and Aboriginal knowledges, understanding and experiences. Foundation pillars of this bridge were mentoring of the PhD student by senior Elders, who explained and demonstrated the critical importance of Yarning (consulting) and Indigenous methodologies of Dadirri (deep listening) and Ganma (two-way knowledge sharing), and discussions among all involved about the principles of Western PAR. CONCLUSIONS: Concepts within this paper are shared from the perspective of the PhD student with the permission and support of local Elders and Working Group members. The intention is to share what was learned for the benefit of other students, research projects and community members who are beginning a similar journey.

HuR biological function involves RRM3-mediated dimerization and RNA binding by all three RRMs.

HuR/ELAVL1 is an RNA-binding protein involved in differentiation and stress response that acts primarily by stabilizing messenger RNA (mRNA) targets. HuR comprises three RNA recognition motifs (RRMs) where the structure and RNA binding of RRM3 and of full-length HuR remain poorly understood. Here, we report crystal structures of RRM3 free and bound to cognate RNAs. Our structural, NMR and biochemical data show that RRM3 mediates canonical RNA interactions and reveal molecular details of a dimerization interface localized on the α-helical face of RRM3. NMR and SAXS analyses indicate that the three RRMs in full-length HuR are flexibly connected in the absence of RNA, while they adopt a more compact arrangement when bound to RNA. Based on these data and crystal structures of tandem RRM1,2-RNA and our RRM3-RNA complexes, we present a structural model of RNA recognition involving all three RRM domains of full-length HuR. Mutational analysis demonstrates that RRM3 dimerization and RNA binding is required for functional activity of full-length HuR in vitro and to regulate target mRNAs levels in human cells, thus providing a fine-tuning for HuR activity in vivo.

Benefits of volunteering on psychological well-being in older adulthood: evidence from a randomized controlled trial.

Objectives: Long-term volunteering has been associated with better physical, mental, and cognitive health in correlational studies. Few studies, however, have examined the longitudinal benefits of volunteering with randomized experimental designs (e.g., intervention studies). Even fewer studies have examined whether such benefits can be shown after short-term volunteering. To fill this gap, we conducted four 1-hour volunteering intervention sessions to promote volunteering among a group of older adults with limited volunteering experience and examined the impact of volunteering on depressive symptoms, meaning in life, general self-efficacy, and perceived autonomy.Methods: A total of 384 participants aged 50-96 years were assigned at random to either an intervention group to promote volunteering behaviors or an active control group to promote physical activity. The participants' monthly volunteering minutes, depressive symptoms, meaning in life, general self-efficacy and perceived autonomy were measured at baseline and six weeks, three months, and six months after the intervention.Results: Being in the volunteering intervention condition was not directly associated with depressive symptoms, meaning in life, general self-efficacy, or perceived autonomy at the 6-week, 3-month, or 6-month follow-ups after the intervention. However, there was an indirect effect of the intervention on depressive symptoms: participants in the intervention group, who had increased their volunteering at the 3-month follow-up, reported fewer depressive symptoms at the 6-month follow-up.Discussion: Our randomized controlled trial suggests that short-term volunteering does not reliably lead to short-term changes in psychosocial health measures as correlational studies would suggest. Efforts need to be made to encourage older adults to maintain long-term volunteering.

Self-Efficacy for Physical Activity-A Question of Item Framing and Age?

Older adults process and remember positive information relatively better than negative information, compared with younger adults; this is known as the positivity effect. This study examined whether older adults compared with younger adults also respond differently to positively and negatively framed questionnaire items. Participants (N = 275; age = 18-81 years) were randomly assigned to a positively or negatively framed version of a self-efficacy for physical activity questionnaire. Self-efficacy, physical activity intentions, and planned physical activity in the following week were regressed on experimental group and age, controlling for baseline physical activity and covariates. A significant Age × Frame interaction showed that item framing made a difference in planned physical activity for the oldest age group (+350 min compared with the youngest group). This study provides initial support for the positivity effect in item framing on physical activity plans, but not on intentions or self-efficacy. Item framing should be taken into consideration for accurate measurement, but could also be a simple intervention approach.

Center of Biomedical Research Excellence in Matrix Biology: Building Research Infrastructure, Supporting Young Researchers, and Fostering Collaboration.

The Center of Biomedical Research Excellence in Matrix Biology strives to improve our understanding of extracellular matrix at molecular, cellular, tissue, and organismal levels to generate new knowledge about pathophysiology, normal development, and regenerative medicine. The primary goals of the Center are to i) support junior investigators, ii) enhance the productivity of established scientists, iii) facilitate collaboration between both junior and established researchers, and iv) build biomedical research infrastructure that will support research relevant to cell-matrix interactions in disease progression, tissue repair and regeneration, and v) provide access to instrumentation and technical support. A Pilot Project program provides funding to investigators who propose applying their expertise to matrix biology questions. Support from the National Institute of General Medical Sciences at the National Institutes of Health that established the Center of Biomedical Research Excellence in Matrix Biology has significantly enhanced the infrastructure and the capabilities of researchers at Boise State University, leading to new approaches that address disease diagnosis, prevention, and treatment. New multidisciplinary collaborations have been formed with investigators who may not have previously considered how their biomedical research programs addressed fundamental and applied questions involving the extracellular matrix. Collaborations with the broader matrix biology community are encouraged.

Strategies to support culturally safe health and wellbeing evaluations in Indigenous settings in Australia and New Zealand: a concept mapping study.

BACKGROUND: In recent decades, financial investment has been made in health-related programs and services to overcome inequities and improve Indigenous people's wellbeing in Australia and New Zealand. Despite policies aiming to 'close the gap', limited evaluation evidence has informed evidence-based policy and practice. Indigenous leaders have called for evaluation stakeholders to align their practices with Indigenous approaches. METHODS: This study aimed to strengthen culturally safe evaluation practice in Indigenous settings by engaging evaluation stakeholders, in both countries, in a participatory concept mapping study. Concept maps for each country were generated from multi-dimensional scaling and hierarchical cluster analysis. RESULTS: The 12-cluster Australia map identifies four cluster regions: An Evaluation Approach that Honours Community; Respect and Reciprocity; Core Heart of the Evaluation; and Cultural Integrity of the Evaluation. The 11-cluster New Zealand map identifies four cluster regions: Authentic Evaluation Practice; Building Maori Evaluation Expertise; Integrity in Maori Evaluation; and Putting Community First. Both maps highlight the importance of cultural integrity in evaluation. Differences include the distinctiveness of the 'Respecting Language Protocols' concept in the Australia map in contrast to language being embedded within the cluster of 'Knowing Yourself as an Evaluator in a Maori Evaluation Context' in the New Zealand map. Participant ratings highlight the importance of all clusters with some relatively more difficult to achieve, in practice. Notably, the 'Funding Responsive to Community Needs and Priorities' and 'Translating Evaluation Findings to Benefit Community' clusters were rated the least achievable, in Australia. The 'Conduct of the Evaluation' and the 'Prioritising Maori Interests' clusters were rated as least achievable in New Zealand. In both countries, clusters of strategies related to commissioning were deemed least achievable. CONCLUSIONS: The results suggest that the commissioning of evaluation is crucial as it sets the stage for whether evaluations: reflect Indigenous interests, are planned in ways that align with Indigenous ways of working and are translated to benefit Indigenous communities Identified strategies align with health promotion principles and relational accountability values of Indigenous approaches to research. These findings may be relevant to the commissioning and conduct of Indigenous health program evaluations in developed nations.

Study protocol of a multi-center RCT testing a social-cognitive intervention to promote volunteering in older adults against an active control.

BACKGROUND: Volunteering could be a win-win opportunity for older adults: Links between volunteering and societal improvements as well as older adults' own health and longevity are found in several observational studies. RCTs to increase volunteering in older adults are however sparse, leaving the question of causality unanswered. This study protocol describes a theory-based social-cognitive intervention with multiple behavior change techniques to increase volunteering among community-dwelling older adults in Hong Kong. METHODS: In a parallel group, two-arm, randomized controlled trial, an initial N = 360 are assigned to receive either the volunteering intervention or the active control intervention (parallel content targeting physical activity). The primarily outcome measure is self-reported volunteering minutes per month at baseline, six weeks, three months and six months after the intervention. Participants in the treatment group are expected to increase their weekly volunteering minutes over time as compared to participants in the control group. Possible active ingredients of the intervention as well as mental and physical health outcomes of increased volunteering are investigated by means of mediation analyses. DISCUSSION: Like many industrialized nations, Hong Kong faces a rapid demographic change. An effective psychological intervention to encourage retirees to engage in formal volunteering would alleviate some of the societal challenges a growing proportion of older adults entails. TRIAL REGISTRATION: Primary Registry and Trial Identifying Number ChiCTR-IIC-17010349 , secondary CCRB trial number CUHK_CCRB00543, registration date 2016/12/28.

Ribbon α-Conotoxin KTM Exhibits Potent Inhibition of Nicotinic Acetylcholine Receptors.

KTM is a 16 amino acid peptide with the sequence WCCSYPGCYWSSSKWC. Here, we present the nuclear magnetic resonance (NMR) structure and bioactivity of this rationally designed α-conotoxin (α-CTx) that demonstrates potent inhibition of rat α3ß2-nicotinic acetylcholine receptors (rα3ß2-nAChRs). Two bioassays were used to test the efficacy of KTM. First, a qualitative PC12 cell-based assay confirmed that KTM acts as a nAChR antagonist. Second, bioactivity evaluation by two-electrode voltage clamp electrophysiology was used to measure the inhibition of rα3ß2-nAChRs by KTM (IC50 = 0.19 ± 0.02 nM), and inhibition of the same nAChR isoform by α-CTx MII (IC50 = 0.35 ± 0.8 nM). The three-dimensional structure of KTM was determined by NMR spectroscopy, and the final set of 20 structures derived from 32 distance restraints, four dihedral angle constraints, and two disulfide bond constraints overlapped with a mean global backbone root-mean-square deviation (RMSD) of 1.7 ± 0.5 Å. The structure of KTM did not adopt the disulfide fold of α-CTx MII for which it was designed, but instead adopted a flexible ribbon backbone and disulfide connectivity of C2-C16 and C3-C8 with an estimated 12.5% α-helical content. In contrast, α-CTx MII, which has a native fold of C2-C8 and C3-C16, has an estimated 38.1% α-helical secondary structure. KTM is the first reported instance of a Framework I (CC-C-C) α-CTx with ribbon connectivity to display sub-nanomolar inhibitory potency of rα3ß2-nAChR subtypes.

CO2-fixing one-carbon metabolism in a cellulose-degrading bacterium Clostridium thermocellum.

Clostridium thermocellum can ferment cellulosic biomass to formate and other end products, including CO2 This organism lacks formate dehydrogenase (Fdh), which catalyzes the reduction of CO2 to formate. However, feeding the bacterium 13C-bicarbonate and cellobiose followed by NMR analysis showed the production of 13C-formate in C. thermocellum culture, indicating the presence of an uncharacterized pathway capable of converting CO2 to formate. Combining genomic and experimental data, we demonstrated that the conversion of CO2 to formate serves as a CO2 entry point into the reductive one-carbon (C1) metabolism, and internalizes CO2 via two biochemical reactions: the reversed pyruvate:ferredoxin oxidoreductase (rPFOR), which incorporates CO2 using acetyl-CoA as a substrate and generates pyruvate, and pyruvate-formate lyase (PFL) converting pyruvate to formate and acetyl-CoA. We analyzed the labeling patterns of proteinogenic amino acids in individual deletions of all five putative PFOR mutants and in a PFL deletion mutant. We identified two enzymes acting as rPFOR, confirmed the dual activities of rPFOR and PFL crucial for CO2 uptake, and provided physical evidence of a distinct in vivo "rPFOR-PFL shunt" to reduce CO2 to formate while circumventing the lack of Fdh. Such a pathway precedes CO2 fixation via the reductive C1 metabolic pathway in C. thermocellum These findings demonstrated the metabolic versatility of C. thermocellum, which is thought of as primarily a cellulosic heterotroph but is shown here to be endowed with the ability to fix CO2 as well.

Recognition of the 3' splice site RNA by the U2AF heterodimer involves a dynamic population shift.

An essential early step in the assembly of human spliceosomes onto pre-mRNA involves the recognition of regulatory RNA cis elements in the 3' splice site by the U2 auxiliary factor (U2AF). The large (U2AF65) and small (U2AF35) subunits of the U2AF heterodimer contact the polypyrimidine tract (Py-tract) and the AG-dinucleotide, respectively. The tandem RNA recognition motif domains (RRM1,2) of U2AF65 adopt closed/inactive and open/active conformations in the free form and when bound to bona fide Py-tract RNA ligands. To investigate the molecular mechanism and dynamics of 3' splice site recognition by U2AF65 and the role of U2AF35 in the U2AF heterodimer, we have combined single-pair FRET and NMR experiments. In the absence of RNA, the RRM1,2 domain arrangement is highly dynamic on a submillisecond time scale, switching between closed and open conformations. The addition of Py-tract RNA ligands with increasing binding affinity (strength) gradually shifts the equilibrium toward an open conformation. Notably, the protein-RNA complex is rigid in the presence of a strong Py-tract but exhibits internal motion with weak Py-tracts. Surprisingly, the presence of U2AF35, whose UHM domain interacts with U2AF65 RRM1, increases the population of the open arrangement of U2AF65 RRM1,2 in the absence and presence of a weak Py-tract. These data indicate that the U2AF heterodimer promotes spliceosome assembly by a dynamic population shift toward the open conformation of U2AF65 to facilitate the recognition of weak Py-tracts at the 3' splice site. The structure and RNA binding of the heterodimer was unaffected by cancer-linked myelodysplastic syndrome mutants.

Data-driven process to improve VA surgical flow.

Purpose During years 2014-2016, Veterans Health Administration National Surgery Office conducted a surgical flow improvement initiative (SFII) to assist low-performing surgery programs to improve their operating room efficiency (ORE). The initiative was co-sponsored by VHA National Surgery Office and VHA Office of Systems Redesign and Improvement. The paper aims to discuss this issue. Design/methodology/approach An SFII algorithm, based on first-time-start (FTS), cancellation rate (CR), lag time (LT) and OR utilization, assigned an ORE performance Level (1-low to 4-high) to each VA Medical Center (VAMC). In total, 15 VAMCs with low-performance surgery programs participated in SFII to assess the current state of their surgical flow processes and used redesign methods to focus on improvement objectives. Findings At the end of the project, 14 VSAs, 40 RPIWs, 45 "90-day projects" and 73 Just-Do-It's were completed with 65 percent (158/243) improvement actions and 86 percent sites improving/sustaining all four ORE metrics. There was a statistically significant difference in improvement across the three stages (baseline, improvement, sustain) for FTS (45.6-68.7 percent; F=44.74; p<0.000); CR (16.1-9.5 percent; F=34.46; p<0.000); LT (63.1-36.3 percent; F=92.00; p<0.000); OR utilization (43.4-57.7 percent; F=6.92; p<0.001) and VAMC level (1.7-3.65; F=80.11; p<0.000). The majority developed "fair to excellent" sustainment (91 percent) and spread (82 percent) plans. The projected annual estimated return-on-investment was $27,949,966. Originality/value The SFII successfully leveraged a small number of faculty, coaches, and industrial engineers to produce significant improvement in ORE across a large national integrated health care network. This strategy can serve healthcare leaders in managing complex healthcare issues in their facilities.

Effects of Fluorophore Attachment on Protein Conformation and Dynamics Studied by spFRET and NMR Spectroscopy.

Fluorescence-based techniques are widely used to study biomolecular conformations, intra- and intermolecular interactions, and conformational dynamics of macromolecules. Especially for fluorescence-based single-molecule experiments, the choice of the fluorophore and labeling position are highly important. In this work, we studied the biophysical and structural effects that are associated with the conjugation of fluorophores to cysteines in the splicing factor U2AF65 by using single pair Förster resonance energy transfer (FRET) and nuclear magnetic resonance (NMR) spectroscopy. It is shown that certain acceptor fluorophores are advantageous depending on the experiments performed. The effects of dye attachment on the protein conformation were characterized using heteronuclear NMR experiments. The presence of hydrophobic and aromatic moieties in the fluorophores can significantly affect the conformation of the conjugated protein, presumably by transient interactions with the protein surface. Guidelines are provided for carefully choosing fluorophores, considering their photophysical properties and chemical features for the design of FRET experiments, and for minimizing artifacts.

Who benefits from a dietary online intervention? Evidence from Italy, Spain and Greece.

OBJECTIVE: The traditional Mediterranean diet includes high consumption of fruits, vegetables, olive oil, legumes, cereals and nuts, moderate to high intake of fish and dairy products, and low consumption of meat products. Intervention effects to improve adoption of this diet may vary in terms of individuals' motivational or volitional prerequisites. In the context of a three-country research collaboration, intervention effects on these psychological constructs for increasing adoption of the Mediterranean diet were examined. DESIGN: An intervention was conducted to improve Mediterranean diet consumption with a two-month follow-up. Linear multiple-level models examined which psychological constructs (outcome expectancies, planning, action control and stage of change) were associated with changes in diet scores. SETTING: Web-based intervention in Italy, Spain and Greece. SUBJECTS: Adults (n 454; mean age 42·2 (sd 10·4) years, range 18-65 years; n 112 at follow-up). RESULTS: Analyses yielded an overall increase in the Mediterranean diet scores. Moreover, there were interactions between time and all four psychological constructs on these changes. Participants with lower levels of baseline outcome expectancies, planning, action control and stage of change were found to show steeper slopes, thus greater behavioural adoption, than those who started out with higher levels. CONCLUSIONS: The intervention produced overall improvements in Mediterranean diet consumption, with outcome expectancies, planning, action control and stage of change operating as moderators, indicating that those with lower motivational or volitional prerequisites gained more from the online intervention. Individual differences in participants' readiness for change need to be taken into account to gauge who would benefit most from the given treatment.

Phosphorylation releases constraints to domain motion in ERK2.

Protein motions control enzyme catalysis through mechanisms that are incompletely understood. Here NMR (13)C relaxation dispersion experiments were used to monitor changes in side-chain motions that occur in response to activation by phosphorylation of the MAP kinase ERK2. NMR data for the methyl side chains on Ile, Leu, and Val residues showed changes in conformational exchange dynamics in the microsecond-to-millisecond time regime between the different activity states of ERK2. In inactive, unphosphorylated ERK2, localized conformational exchange was observed among methyl side chains, with little evidence for coupling between residues. Upon dual phosphorylation by MAP kinase kinase 1, the dynamics of assigned methyls in ERK2 were altered throughout the conserved kinase core, including many residues in the catalytic pocket. The majority of residues in active ERK2 fit to a single conformational exchange process, with kex ≈ 300 s(-1) (kAB ≈ 240 s(-1)/kBA ≈ 60 s(-1)) and pA/pB ≈ 20%/80%, suggesting global domain motions involving interconversion between two states. A mutant of ERK2, engineered to enhance conformational mobility at the hinge region linking the N- and C-terminal domains, also induced two-state conformational exchange throughout the kinase core, with exchange properties of kex ≈ 500 s(-1) (kAB ≈ 15 s(-1)/kBA ≈ 485 s(-1)) and pA/pB ≈ 97%/3%. Thus, phosphorylation and activation of ERK2 lead to a dramatic shift in conformational exchange dynamics, likely through release of constraints at the hinge.

Translating good intentions into physical activity: older adults with low prospective memory ability profit from planning.

Prospective memory (PM) is the ability to remember to perform an intended action in the future and is necessary for regular physical activity (PA). For older adults with declining PM, planning strategies may help them to act upon their intentions. This study investigates PM as a moderator in a mediation process: intention predicting PA via planning. A mediated moderation was estimated with longitudinal data of older adults (M = 70 years). Intentions (T1) predicted PA (T3) via action and coping planning (T2). PM was included as moderator on the planning-PA association. Both planning strategies were significant partial mediators (action planning: b = 0.17, 95 % CI [0.10, 0.29]; coping planning: b = 0.08, 95 % CI [0.02, 0.18]). For individuals with lower PM, the indirect effect via coping planning was stronger than with higher PM (b = 0.06, 95 % CI [0.01, 0.16]). Action planning is important for PA in old age regardless of PM performance, whereas older adults with lower PM benefitted most from coping planning. Intervention studies for older adults should consider training PM and promote planning skills.