The potential of physical activity and technology interventions to reduce anxiety in older adults

Background: Older adults have low levels of mental health literacy relating to anxiety, which may explain why they delay or do not seek help. Emerging evidence supports effectiveness of lifestyle interventions, including physical activity (PA), in reducing anxiety. The COVID-19 pandemic has highlighted technology's potential to facilitate healthcare provision. We explored older adults’ understanding of anxiety, perspectives on whether PA interventions could reduce anxiety, and whether technology could facilitate this. Methods: The INDIGO trial evaluated a PA intervention for participants aged 60 years and above, at risk of cognitive decline, and not meeting PA guidelines at baseline. Twenty-nine trial completers attended follow-up semi-structured qualitative interviews. Results: Thematic analysis revealed participants’ diverse understanding of anxiety with some relating anxiety to worry, uncertainty and fear, as well as physical manifestations and feeling out of control, while others found the concept confusing. Participants generally thought that PA interventions could reduce anxiety through “mindful” and/or “physiological” processes. Views about technology were more polarised, possibly reflecting a “digital divide”. Participants expressed that technology could help with information provision, health monitoring and motivation. Participants were open to using wearable activity monitors, online platforms and portable devices. Limitations: Participants had completed a PA intervention trial, had relatively high education levels and interviews were only conducted in English. Conclusions: Results highlight the importance of providing more information and education about anxiety to older adults to increase understanding and help-seeking. Findings also support likely acceptability of PA interventions for anxiety, with the option of technology as a facilitator

Physical Activity for Cognitive Health: A Model for Intervention Design for People Experiencing Cognitive Concerns and Symptoms of Depression or Anxiety

Background: People experiencing cognitive concerns and symptoms of depression or anxiety are at risk for Alzheimer's disease and dementia. We know physical activity can benefit cognition but understanding how to best support engagement is an ongoing challenge. Evidence-based conceptual models of factors underpinning physical activity engagement in target populations can inform intervention tailoring to address this challenge. Objective: This study (part of a pragmatic physical activity implementation trial) aimed to develop a specified model of physical activity engagement in people experiencing depressive or anxiety symptoms and cognitive concerns, to enable optimized dementia risk reduction intervention tailoring. Methods: We employed a qualitative design, triangulating data from three sources: semi-structured individual interviews with people experiencing cognitive concerns and mild to moderate depressive or anxiety symptoms; review of published evidence; and the Capability, Opportunity and Motivation system of behavior, an existing behavioral science model. Findings were integrated to develop a contextualized model of mechanisms of action for optimizing engagement. Results: Twenty-one participants were interviewed, and 24 relevant papers included. Convergent and complementary themes extended understanding of intervention needs. Findings highlighted emotional regulation, capacities to enact intentions despite barriers, and confidence in existing skills as areas of population-specific need that have not previously been emphasized. The final model provides specificity, directionality, and linked approaches for intervention tailoring. Conclusion: This study demonstrated that people experiencing cognitive concerns and symptoms of depression or anxiety require different interventions to improve physical activity engagement. This novel model can enable more precise intervention tailoring, and, ultimately, benefits for a key at-risk population

Retention and Mentoring (RAM) Initiative

National and local surveys (e.g., COACHE, 2010; VCU Great Place Initiative, 2013) suggest that a primary reason for workplace dissatisfaction among faculty and staff is lack of adequate mentorship. Evidence also suggests that mentoring programs improve recruitment and retention of underrepresented faculty and staff (e.g., Daley, Wingard, & Reznik, 2006). VCU and VCU Health currently have decentralized and isolated mentoring programs across campuses: a centralized mentoring program accessible to all employees does not exist to address faculty and staff professional development and networking needs. Our project sought to fill this gap. Specifically, we proposed to develop an online database designed to match mentors with mentees based on multiple criteria. Our goal was to address faculty and staff mentoring and professional development needs as a means to build a culture of connection to promote retention of employees

The 2018 Otto Aufranc Award: How does genome-wide variation affect osteolysis risk after THA?

BACKGROUND: Periprosthetic osteolysis resulting in aseptic loosening is a leading cause of THA revision. Individuals vary in their susceptibility to osteolysis and heritable factors may contribute to this variation. However, the overall contribution that such variation makes to osteolysis risk is unknown. QUESTIONS/PURPOSES: We conducted two genome-wide association studies to (1) identify genetic risk loci associated with susceptibility to osteolysis; and (2) identify genetic risk loci associated with time to prosthesis revision for osteolysis. METHODS: The Norway cohort comprised 2624 patients after THA recruited from the Norwegian Arthroplasty Registry, of whom 779 had undergone revision surgery for osteolysis. The UK cohort included 890 patients previously recruited from hospitals in the north of England, 317 who either had radiographic evidence of and/or had undergone revision surgery for osteolysis. All participants had received a fully cemented or hybrid THA using a small-diameter metal or ceramic-on-conventional polyethylene bearing. Osteolysis susceptibility case-control analyses and quantitative trait analyses for time to prosthesis revision (a proxy measure of the speed of osteolysis onset) in those patients with osteolysis were undertaken in each cohort separately after genome-wide genotyping. Finally, a meta-analysis of the two independent cohort association analysis results was undertaken. RESULTS: Genome-wide association analysis identified four independent suggestive genetic signals for osteolysis case-control status in the Norwegian cohort and 11 in the UK cohort (p ≤ 5 x 10). After meta-analysis, five independent genetic signals showed a suggestive association with osteolysis case-control status at p ≤ 5 x 10 with the strongest comprising 18 correlated variants on chromosome 7 (lead signal rs850092, p = 1.13 x 10). Genome-wide quantitative trait analysis in cases only showed a total of five and nine independent genetic signals for time to revision at p ≤ 5 x 10, respectively. After meta-analysis, 11 independent genetic signals showed suggestive evidence of an association with time to revision at p ≤ 5 x 10 with the largest association block comprising 174 correlated variants in chromosome 15 (lead signal rs10507055, p = 1.40 x 10). CONCLUSIONS: We explored the heritable biology of osteolysis at the whole genome level and identify several genetic loci that associate with susceptibility to osteolysis or with premature revision surgery. However, further studies are required to determine a causal association between the identified signals and osteolysis and their functional role in the disease. CLINICAL RELEVANCE: The identification of novel genetic risk loci for osteolysis enables new investigative avenues for clinical biomarker discovery and therapeutic intervention in this disease

Combined bezafibrate, medroxyprogesterone acetate and valproic acid treatment inhibits osteosarcoma cell growth without adversely affecting normal mesenchymal stem cells.

This document is the Accepted Manuscript version of a published work that appeared in final form in Bioscience Reports. To access the final edited and published work see http://dx.doi.org/10.1042/BSR20202505Drug repurposing is a cost effective means of targeting new therapies for cancer. We have examined the effects of the repurposed drugs, bezafibrate, medroxyprogesterone acetate and valproic acid on human osteosarcoma cells, i.e., SAOS2 and MG63 compared with their normal cell counterparts, i.e. mesenchymal stem/stromal cells (MSCs). Cell growth, viability and migration were measured by biochemical assay and live cell imaging, whilst levels of lipid-synthesising enzymes were measured by immunoblotting cell extracts. These drug treatments inhibited the growth and survival of SAOS2 and MG63 cells most effectively when used in combination (termed V-BAP). In contrast, V-BAP treated MSCs remained viable with only moderately reduced cell proliferation. V-BAP treatment also inhibited migratory cell phenotypes. MG63 and SAOS2 cells expressed much greater levels of fatty acid synthase and stearoyl CoA desaturase 1 than MSCs, but these elevated enzyme levels significantly decreased in the V-BAP treated osteosarcoma cells prior to cell death. Hence, we have identified a repurposed drug combination that selectively inhibits the growth and survival of human osteosarcoma cells in association with altered lipid metabolism without adversely affecting their non-transformed cell counterparts

Spatiotemporal coordination of cell division and growth during organ morphogenesis

A developing plant organ exhibits complex spatiotemporal patterns of growth, cell division, cell size, cell shape, and organ shape. Explaining these patterns presents a challenge because of their dynamics and cross-correlations, which can make it difficult to disentangle causes from effects. To address these problems, we used live imaging to determine the spatiotemporal patterns of leaf growth and division in different genetic and tissue contexts. In the simplifying background of the speechless (spch) mutant, which lacks stomatal lineages, the epidermal cell layer exhibits defined patterns of division, cell size, cell shape, and growth along the proximodistal and mediolateral axes. The patterns and correlations are distinctive from those observed in the connected subepidermal layer and also different from the epidermal layer of wild type. Through computational modelling we show that the results can be accounted for by a dual control model in which spatiotemporal control operates on both growth and cell division, with cross-connections between them. The interactions between resulting growth and division patterns lead to a dynamic distributions of cell sizes and shapes within a deforming leaf. By modulating parameters of the model, we illustrate how phenotypes with correlated changes in cell size, cell number, and organ size may be generated. The model thus provides an integrated view of growth and division that can act as a framework for further experimental study

A manganese photosensitive tricarbonyl molecule [Mn(CO)3(tpa-κ(3)N)]Br enhances antibiotic efficacy in a multi-drug-resistant Escherichia coli

Carbon monoxide-releasing molecules (CORMs) are a promising class of new antimicrobials, with multiple modes of action that are distinct from those of standard antibiotics. The relentless increase in antimicrobial resistance, exacerbated by a lack of new antibiotics, necessitates a better understanding of how such novel agents act and might be used synergistically with established antibiotics. This work aimed to understand the mechanism(s) underlying synergy between a manganese-based photoactivated carbon monoxide-releasing molecule (PhotoCORM), [Mn(CO)3(tpa-κ(3)N)]Br [tpa=tris(2-pyridylmethyl)amine], and various classes of antibiotics in their activities towards Escherichia coli EC958, a multi-drug-resistant uropathogen. The title compound acts synergistically with polymyxins [polymyxin B and colistin (polymyxin E)] by damaging the bacterial cytoplasmic membrane. [Mn(CO)3(tpa-κ(3)N)]Br also potentiates the action of doxycycline, resulting in reduced expression of tetA, which encodes a tetracycline efflux pump. We show that, like tetracyclines, the breakdown products of [Mn(CO)3(tpa-κ(3)N)]Br activation chelate iron and trigger an iron starvation response, which we propose to be a further basis for the synergies observed. Conversely, media supplemented with excess iron abrogated the inhibition of growth by doxycycline and the title compound. In conclusion, multiple factors contribute to the ability of this PhotoCORM to increase the efficacy of antibiotics in the polymyxin and tetracycline families. We propose that light-activated carbon monoxide release is not the sole basis of the antimicrobial activities of [Mn(CO)3(tpa-κ(3)N)]Br

Lifetime risk and genetic predisposition to post-traumatic OA of the knee in the UK Biobank

Objective Acute knee injury is associated with post-traumatic OA (PTOA). Very little is known about the genome-wide associations of PTOA when compared with idiopathic OA (iOA). Our objective was to describe the development of knee OA after knee injury and its genetic associations in UK Biobank (UKB). Design Clinically significant structural knee injuries in those <=50 years were identified from electronic health record and self-reported data in 502,409 UKB participants. Time-to-first knee OA code was compared in injured cases and age-/sex-matched non-injured controls using Cox Proportional Hazards models. A time-to-OA genome-wide association study (GWAS) sought evidence for PTOA risk variants 6 months-20 years following injury. Evidence for associations of two iOA polygenic risk scores (PRS) was sought. Results Of 4233 knee injury cases, 1896 (44.8%) were female (mean age at injury 34.1 years [SD10.4]). Over a median of 30.2 (IQR19.5-45.4) years, 1096 (25.9%) of injured cases developed knee OA. The overall hazards ratio (HR) for knee OA after injury was 1.81[1.70,1.93],P=8.9x10-74. Female sex and increasing age at injury were associated with knee OA following injury (HR1.15[1.02,1.30];1.07[1,07,1.07] respectively). OA risk was highest in the first 5 years after injury (HR3.26[2.67,3.98]), persisting for 40 years. In 3074 knee injury cases included in the time-to-OA GWAS, no variants reached genome-wide significance. iOA PRS was not associated with time-to-OA (HR 0.43[0.02,8.41]). Conclusions Increasing age at injury and female sex appear to be associated with future development of PTOA in UKB, the risk of which was greatest in the 5 years after injury. Further international efforts towards a better-powered meta-analysis will definitively elucidate genetic similarities and differences of PTOA and iOA