Layperson-Delivered Telephone-Based Behavioral Activation Among Low-Income Older Adults During the COVID-19 Pandemic: The HEAL-HOA Randomized Clinical Trial.

Importance: Older adults are particularly vulnerable to loneliness and its physical and psychosocial sequelae, but scalable interventions are lacking, especially during disasters such as pandemics. Objective: To compare the effects of layperson-delivered, telephone-based behavioral activation and mindfulness interventions vs telephone-based befriending on loneliness among at-risk older adults. Design, Setting, and Participants: This assessor-blinded, 3-arm randomized clinical trial screened Chinese older adults through household visits and community referrals from April 1, 2021, to April 30, 2023, in Hong Kong. Eligible participants (≥65 years of age) who were lonely, digitally excluded, living alone, and living below the poverty line and provided consent to participate were randomized into behavioral activation, mindfulness, and befriending groups. Assessments were conducted at baseline, 1 month, and 3 months. Intervention: As part of the Helping Alleviate Loneliness in Hong Kong Older Adults (HEAL-HOA) dual randomized clinical trial, 148 older laypersons were trained to deliver a twice-weekly 30-minute intervention via telephone for 4 weeks. Main Outcomes and Measures: The primary outcome was loneliness measured by the UCLA Loneliness Scale (range, 20-80) and the De Jong Gierveld Loneliness Scale (range, 0-6), with higher scores on both scales indicating greater loneliness. Secondary outcomes were depression, perceived stress, life satisfaction, psychological well-being, sleep quality, perceived social support, and social network. Results: A total of 1151 participants (mean [SD] age, 76.6 [7.8] years; 843 [73.2%] female) were randomized to the behavioral activation (n = 335), mindfulness (n = 460) or befriending (n = 356) group. Most were widowed or divorced (932 [81.0%]), had primary education or below (782 [67.9%]), and had 3 or more chronic diseases (505 [43.9%]). Following intention-to-treat principles, linear mixed-effects regression model analyses showed that loneliness measured by the UCLA Loneliness Scale was significantly reduced in the behavioral activation group (mean difference [MD], -1.96 [95% CI, -3.16 to -0.77] points; P < .001]) and in the mindfulness group (MD, -1.49 [95% CI, -2.60 to -0.37] points; P = .004) at 3 months compared with befriending. Loneliness measured by the De Jong Gierveld Loneliness Scale was not significantly reduced at 3 months in the behavioral activation group (MD, -0.06 [95% CI, -0.26 to 0.13] points; P > .99]) but was in the mindfulness group (MD, 0.22 [95% CI, 0.03 to 0.40] points; P = .01) at 3 months compared with befriending. In the behavioral activation and mindfulness groups, sleep quality improved compared with befriending, but perceived stress increased. Psychological well-being and perceived social support improved in the behavioral activation group. No statistically significant between-group differences were observed in depression, life satisfaction, or social network. Conclusion and Relevance: In this randomized clinical trial, scalable psychosocial interventions delivered remotely by older laypersons appeared promising in reducing later life loneliness and addressing the pressing mental health challenges faced by aging populations and professional geriatric mental health workforce shortages. Further research should explore ways to maximize the clinical relevance and cost-effectiveness of these interventions. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2300072909.

Falls prevention is more than just promoting physical health: evaluation of the group-based, out-patient prevention program 'Staying safe and active in old age - falls prevention'.

Introduction: The aim of this study was to evaluate the German falls prevention program 'Staying safe and active in old age - falls prevention', which is already established in practice. Methods: The single-arm intervention study consisted of two time points, 6 months apart, to evaluate the multifactorial falls prevention program (n = 125 at Time 2). We observed the groups and their trainers and assessed which behavior change techniques (BCTs) were used. According to our evaluation framework, changes in the following three domains were assessed: (a) fall-related variables (i.e. number of falls, fear of falling), (b) physical functioning (i.e. performance-based gait speed, coordination, self-reported leg strength, balance, as well as habitual execution of the exercises), and (c) psychosocial functioning (i.e. quality of life, activities of daily living, mobility, and loneliness). Linear mixed models were used to determine changes in each variable. Results: Demonstration of behavior was the most frequently used BCT. The program showed significant benefits for fear of falling, balance, coordination, habitual execution, and loneliness over time (Cohen's d between -0.59 and 1.73). Number of falls, gait speed, coordination (dual task), activities of daily living, and quality of life were maintained (Cohen's d between -0.26 and 0.30), whereas leg strength and mobility decreased significantly at Time 2 (Cohen's d = -0.55 and -0.36). Discussion: Group-based falls prevention programs may facilitate social integration among older adults and may also enhance and maintain physical functioning in old age.Trial registration: German Clinical Trials Register identifier: DRKS00012321.

'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.

Study protocol of the 'HEAL-HOA' dual randomized controlled trial: Testing the effects of volunteering on loneliness, social, and mental health in older adults.

Background: Interventions to reduce loneliness in older adults usually do not show sustained effects. One potential way to combat loneliness is to offer meaningful social activities. Volunteering has been suggested as one such activity - however, its effects on loneliness remain to be tested in randomized controlled trials (RCT). Methods: This planned Dual-RCT aims to recruit older adults experiencing loneliness, with subsequent randomization to either a volunteering condition (6 weeks of training before delivering one of three tele-based loneliness interventions to older intervention recipients twice a week for 6 months) or to an active control condition (psycho-education with social gatherings for six months). Power analyses require the recruitment of N = 256 older adults to detect differences between the volunteering and the active control condition (128 in each) on the primary outcome of loneliness (UCLA Loneliness Scale). Secondary outcomes comprise social network engagement, perceived social support, anxiety and depressive symptoms, self-rated health, cognitive health, perceived stress, sleep quality, and diurnal cortisol (1/3 of the sample). The main analyses will comprise condition (volunteering vs. no-volunteering) × time (baseline, 6-, 12-, 18-, 24-months follow-ups) interactions to test the effects of volunteering on loneliness and secondary outcomes. Effects are expected to be mediated via frequency, time and involvement in volunteering. Discussion: If our trial can show that volunteers delivering one of the three telephone-based interventions to lonely intervention recipients benefit from volunteer work themselves, this might encourage more older adults to volunteer, helping to solve some of the societal issues involved with rapid demographic changes.

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.

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.

Backbone 1H, 13C and 15N assignments of the apo-acyl carrier protein (ACP1) of Pseudomonas aeruginosa.

The N-acyl-L-homoserine lactone (AHL) quorum sensing regulates virulence in the opportunistic pathogen, Pseudomonas aeruginosa. The LasI and RhlI AHL synthases use acyl carrier protein substrates to synthesize, respectively, the 3-oxododecanoyl-L-homoserine lactone (3-oxoC12-HSL) and butyryl-L-homoserine lactone (C4-HSL) QS signals for this bacterium. Although P. aeruginosa genome contains three open reading frames to encode three acyl carrier proteins, namely the ACP1, ACP2 and ACP3, microarray and gene replacement studies show that only the ACP1 carrier protein is under quorum sensing regulation. In this study, we isotopically enriched one of the acyl carrier proteins, ACP1 from P. aeruginosa and describe the backbone resonance assignments for this protein to delineate the structural and molecular basis of ACP1 recognition in P. aeruginosa AHL quorum sensing signal synthesis.

1H, 13C and 15N backbone and sidechain assignment of the Burkholderia mallei acyl carrier protein.

Acyl carrier proteins (ACPs) are universally conserved proteins amongst different species and are involved in fatty acid synthesis. Bacteria utilize ACPs as acyl carriers and donors for the synthesis of products such as endotoxins or acyl homoserine lactones (AHLs), which are used in quorum sensing mechanisms. In this study, wehave expressed isotopically labeled holo-ACP from Burkholderia mallei in Escherichia coli to assign 100% of non-proline backbone amide (HN) resonances, 95.5% of aliphatic carbon resonances and 98.6% of aliphatic hydrogen sidechain resonances.

Associations Between Implicit and Explicit Condom Use Measures With Condom Use Barriers: Relationships Make A Difference.

OBJECTIVE: The association between explicit and implicit psychological measures might be affected by the similarity of the assessment method and by the overlap of the components of the constructs being assessed. This study examined the association between condom use barriers and explicit and implicit measurements of condom use and the moderating role of sexual intercourse in these associations. DESIGN: This was a cross sectional correlational study. An analysis of baseline data from a randomized controlled trial including 149 university students was included. MAIN MEASURES: These included a questionnaire assessing condom use barriers, an implicit condom use test (a structured semi-projective test), and an explicit condom use question. Hierarchical regressions and correlations were examined in the full sample and by groups of participants with and without sexual intercourse. RESULTS: In those without sexual intercourse, all barriers sub-scales were significantly and negatively correlated with implicit condom use and unrelated to explicit condom use. In contrast, among those engaged in sexual intercourse, barriers were significantly and negatively correlated with the explicit condom use measure, and only barriers concerning partner and motivation correlated with implicit condom use tendencies. CONCLUSION: Having a sexual partner plays a major role in the relations between barriers and implicit and explicit condom use measures. The pattern of the results is discussed in relation to cognitive and social factors.

Carrier protein mediated cargo sensing in quorum signal synthases.

Acyl-homoserine lactone synthases make specific AHL quorum sensing signals to aid virulence in Gram-negative bacteria. Here, we use solution NMR spectroscopy to demonstrate that the carrier protein-enzyme interface accurately reveals substrate recognition mechanisms in two quorum signal synthases.

Understanding and overcoming challenges in times of personal or global crisis-Editorial on the Special Issue on Loneliness and Health.

The ever-present interest in loneliness has increased during the last decade. Although loneliness is generally not as prevalent as other topics and not among the top 5 most read papers in the journal Applied Psychology: Health and Well-Being, it is closely connected to topics therein, such as well-being and health. Conceptualizing loneliness as indicator of risk, it may function as a cue for action. Accordingly, understanding loneliness, its development, prevalence, effects, and how to support individuals to prevent or overcome loneliness is key and the main aim of this special issue. Therefore, theories and models are reviewed in this paper and synthesized together with other aspects relating to the field of loneliness research and intervention. Accordingly, we propose an agenda including key determinants (e.g., risk groups), how to proceed (various research methods), intervention components (e.g., behavior change techniques, SDGs), and how to perform dissemination (open science practices, co-creative approaches, etc.). The original studies in this special issue provide stimulating examples. Moreover, the commentaries give new insights and inspiring ideas. Overall, this special issue aims to give readers a lens with which to re-examine their own research, enable innovation, and empower addressing loneliness and its interconnection synergistically.

What do older adults think about when formulating implementation intentions for physical activity? Evidence from a qualitative study.

OBJECTIVES: Physical activity is an important health behaviour especially for older adults. Forming implementation intentions is an effective strategy to implement physical activity in daily life for young and middle-aged adults. However, evidence for older adults is inconclusive. This study explored the thoughts of older adults about implementation intentions and potential barriers and facilitators while formulating them. METHODS: Three samples of older adults from the United Kingdom (n = 8), Germany (n = 9) and Switzerland (n = 17) were prompted to think aloud while formulating implementation intentions to be more physically active. After the task, semi-structured interviews were conducted. Data were analysed thematically. RESULTS: Participants expressed pre-established thoughts about implementation intentions (e.g. they feel too restrictive). During the formulation of implementation intentions, several barriers to creating them were reported (e.g. problems with finding cues due to absence of recurring daily routines), but participants also mentioned that forming implementation intentions acted as a facilitator for physical activity (e.g. cues as useful reminders to be active, task itself triggering self-reflection about physical activity). After the task, participants reflected on circumstances that decrease the likelihood of enacting implementation intentions (e.g. spontaneous alternative activities, weather, health-related barriers, Covid-19-related barriers), which triggered spontaneous coping planning. CONCLUSIONS: The results on barriers and facilitators of implementation intentions and physical activity from older adults' perspectives provide starting points for improving instructions for older adults on how to create implementation intentions for physical activity. Future studies are needed to investigate whether the findings extend to implementation intentions for other behaviours.

Perceived Physical Functioning and Gait Speed as Mediators in the Association Between Fear of Falling and Quality of Life in Old Age.

Preserving Quality of Life (QoL) in old age gains in importance, but Fear of Falling (FoF) considerably limits QoL. The aim of our study was to understand how physical mediators may translate FoF to QoL. At Time 1, FoF, subjective leg strength, balance, QoL, and objective gait speed were assessed. QoL was reassessed after 6 months, at Time 2 (n = 125). A sequential mediation analysis examined whether the relationship between FoF and QoL could be mediated by leg strength, balance, and gait speed. FoF was directly associated with QoL (ß = -.27; 95% CI [-0.007, -0.001]) as well as indirectly via leg strength, balance, and gait speed (specific sequential indirect effect: ß = -.03; 95% CI [-0.06, -0.001]; R2 = .40 in QoL; controlled for age, QoL at Time 1). An intervention approach could be to address FoF and foster physical functioning and gait speed to maintain QoL.

What makes implementation intentions (in)effective for physical activity among older adults?

OBJECTIVES: For most populations, implementation intentions (IIs) facilitate physical activity (PA). However, for older adults, previous studies found mixed evidence for the effectiveness of this behaviour change technique. To examine which characteristics of IIs predict successful enactment, the content of older participants' IIs formed within a self-regulatory intervention to prompt PA was analysed. DESIGN: A sample of N = 126 German speaking adults aged 64 and older formed up to six IIs for PA and reported their enactment 5 weeks later. METHODS: Controlling for age and sex, multilevel models tested associations between characteristics of IIs (e.g., chronological rank of II, hetero- and homogeneity, specificity, presence of certain cues) and enactment. RESULTS: Significantly related to enactment were: the chronological rank of an II (first IIs superior to last IIs), greater heterogeneity in activities, greater specificity of when-cues, and greater use of pre-existing routines. CONCLUSIONS: Participants were more likely to enact their IIs 5 weeks later if they planned different (heterogeneous) activities, created IIs with more specific when-cues (e.g., on Monday at 9 am), and in particular a routine (e.g., after breakfast). They also enacted the first three IIs (chronological rank of II) more often than the last three IIs. Future experimental studies should test whether providing instructions to create IIs based on the above significant characteristics lead to more effective health behaviour change among older adults.

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.

Implementation of EQ-5D-5L as a routine outcome measure in Community Outpatient and Specialized Rehabilitation Services.

Rehabilitation is a person-centred approach that optimizes functioning to reduce impairments in individuals with illness, injury or disability. Patient-reported outcome measures (PROMs) have a role in rehabilitation to inform clinical practice, enhance patient-centered care, support health services programming, direct performance measurement, and contribute to quality improvement. A Canadian provincial health system implemented a Rehabilitation Model of Care that provides a real-world perspective on the adoption of a standardized PROM, the EuroQol EQ-5D-5L, in the community rehabilitation setting. This article will provide an overview of PROMs implementation in the community rehabilitation context, and discuss key facilitators and challenges to implementation within the 18 early adopter sites and with the spread and scale to 152 urban and rural sites. A change management approach, contextualized local coaching and strong leadership support were facilitators in the initial phases of implementation. Adequate resources and infrastructure from technological platforms for electronic data capture and visualization were assets in addition to clinical teams that had existing strong quality improvement cultures to collect PROMS in existing workflows. Challenges to implementation include the clinical relevance of the PROM, difficulty with contextualization to suit diverse clinical and programmatic teams, and the need for further knowledge sharing activities to build readiness for adoption. The implementation of PROMs in community rehabilitation has added value at the clinical (micro), programmatic (meso) and health system level (macro). Clinically, it has promoted the importance of incorporating the patients' voice into outcome measurement. At the program level, the cultivation of a data informed learning community was fostered as teams make improvements and use data to inform future program growth or service changes. Finally, at the health system level, data visualization promotes transparency and accountability with performance across the province and the standardized use of the EQ-5D-5L provides a consistent language to promote measurement throughout the health system.

Bioactive recombinant human oncostatin M for NMR-based screening in drug discovery.

Oncostatin M (OSM) is a pleiotropic, interleukin-6 family inflammatory cytokine that plays an important role in inflammatory diseases, including inflammatory bowel disease, rheumatoid arthritis, and cancer progression and metastasis. Recently, elevated OSM levels have been found in the serum of COVID-19 patients in intensive care units. Multiple anti-OSM therapeutics have been investigated, but to date no OSM small molecule inhibitors are clinically available. To pursue a high-throughput screening and structure-based drug discovery strategy to design a small molecule inhibitor of OSM, milligram quantities of highly pure, bioactive OSM are required. Here, we developed a reliable protocol to produce highly pure unlabeled and isotope enriched OSM from E. coli for biochemical and NMR studies. High yields (ca. 10 mg/L culture) were obtained in rich and minimal defined media cultures. Purified OSM was characterized by mass spectrometry and circular dichroism. The bioactivity was confirmed by induction of OSM/OSM receptor signaling through STAT3 phosphorylation in human breast cancer cells. Optimized buffer conditions yielded 1H, 15N HSQC NMR spectra with intense, well-dispersed peaks. Titration of 15N OSM with a small molecule inhibitor showed chemical shift perturbations for several key residues with a binding affinity of 12.2 ± 3.9 µM. These results demonstrate the value of bioactive recombinant human OSM for NMR-based small molecule screening.

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.

Repurposing Drugs to Treat Heart and Brain Illness.

Drug development is a complicated, slow and expensive process with high failure rates. One strategy to mitigate these factors is to recycle existing drugs with viable safety profiles and have gained Food and Drug Administration approval following extensive clinical trials. Cardiovascular and neurodegenerative diseases are difficult to treat, and there exist few effective therapeutics, necessitating the development of new, more efficacious drugs. Recent scientific studies have led to a mechanistic understanding of heart and brain disease progression, which has led researchers to assess myriad drugs for their potential as pharmacological treatments for these ailments. The focus of this review is to survey strategies for the selection of drug repurposing candidates and provide representative case studies where drug repurposing strategies were used to discover therapeutics for cardiovascular and neurodegenerative diseases, with a focus on anti-inflammatory processes where new drug alternatives are needed.