Dementia-Inclusive Choices for Exercise Toolkit: Impact on the Knowledge, Perspectives, and Practices of Exercise Providers.

Physical activity improves the well-being of persons living with dementia but few exercise programs include them. The Dementia-Inclusive Choices for Exercise (DICE) toolkit aims to improve exercise providers' understanding of dementia and ability to support persons living with dementia in physical activity. We evaluated the co-designed DICE toolkit with exercise providers using a mixed-methods approach comprising pre/post questionnaires and interviews and reflection diaries. Among 16 participants, self-efficacy for exercise delivery to persons living with dementia and both knowledge and attitudes toward dementia significantly improved. Thematic analysis suggested participants (a) had a deeper understanding of the variability of dementia, (b) were planning for equitable access for persons living with dementia, (c) planned to promote social connection through exercise, and (d) were optimistic for future engagement with persons living with dementia. The DICE toolkit may improve exercise providers' knowledge and confidence to plan proactively to support persons living with dementia in programs and services.

The dementia-inclusive choices in exercise project: Using participatory action research to improve physical activity supports for persons with dementia.

Persons with dementia have the right to equal inclusion in rehabilitation, including physical activity. However, the perspectives of persons with dementia are rarely integrated into decision-making related to physical activity programming, services, and supports. Here, we describe the participatory action research (PAR) approach used to develop the Dementia-Inclusive Choices for Exercise (DICE) toolkit, which aims to increase the quality and number of physical activity opportunities available to persons with dementia. The DICE Research Team included persons with dementia, a family care partner, exercise professionals, community and dementia service providers, health care professionals, and researchers who worked to: 1) Engage/maintain the Research Team; 2) Set/navigate ways of engagement; 3) Understand barriers to physical activity; 4) Prioritize the audience and actions; 5) Develop the toolkit; 6) Conduct usability testing; and 7) Implement and evaluate. Guided by the Behaviour Change Wheel, and informed by interviews, focus groups, and existing research, our PAR Team chose to prioritize training exercise providers; exercise providers can enable exercise for persons with dementia if they understand common changes with dementia and how to support persons with dementia in exercise. The content and format of the toolkit was co-developed: drafted by our Research Team, adapted through a stakeholder workshop, and refined through iterative development and usability testing. The product of our PAR process, the DICE toolkit, includes videos meant to destigmatize dementia, training modules and a training manual for exercise providers, a physical activity handout for persons with dementia, and wallet cards to help persons with dementia communicate their abilities, needs, and preferences. Our usability study indicated that the toolkit could be used by exercise providers and may improve attitudes about dementia. Our vision is that our co-developed DICE toolkit will empower exercise providers to improve physical activity opportunities and support for persons with dementia.

Developing a Regional Strategy for Older Adults Living With Frailty: Recommendations From Patients, Family Caregivers and Health Care Providers.

Introduction: Health care organizations are increasingly recognizing the need to integrate the health care system to better care for older adults. We partnered with a local health centre to inform the development of a Regional Frail Senior Strategy for Southwestern Ontario, Canada. Methodology: Interviews were conducted with 12 older adults (65+, with chronic conditions) and family caregivers. 44 interviews were also completed with health care providers from across the region. To engage with a range of stakeholders on the strategy, four feedback fairs were hosted. Interviewees emphasized the importance of person and family-centred care, integration of health care services, issues of access, and further training and education for health care professionals. Findings and stakeholder feedback were synthesized into 14 recommendations. Discussion: The data and recommendations outlined in this paper informed the development of the frailty strategy for a region in Ontario. Participatory methods and stakeholder engagement identified pertinent themes related to enhancing care for older adults with frailty. Conclusion: The creation of a frailty strategy is imperative in recognizing and responding to the needs of older adults with complex conditions. Our approach may be relevant to other organizations and health systems interested in developing their own regional frailty strategies.

In Their Own Words: How COVID-19 Has Impacted the Well-Being of Persons Living with Dementia in the Community.

COVID-19 has had a devasting impact on older adults in Canada, including persons living with dementia. This intrinsic case study sought to understand the perceptions of persons living with dementia regarding how COVID-19 has impacted their well-being. Ten persons living with dementia participated in in-depth qualitative interviews about their experience with COVID-19. Using thematic analysis, four themes were identified: (1) expressing current and future concerns; (2) social connections and isolation; (3) adapting to change and resilience through engagement and hope; and (4) we're not all the same: reflecting individual experiences of the pandemic. Results highlight that while COVID-19 contributed to isolation, concerns, and frustrations, persons with dementia also demonstrated adaptation and resilience. This study reinforced that persons with dementia and their responses to challenges are unique. Therefore, interventions to support persons with dementia must also be individualized to each person's abilities and circumstances.

Evaluation of electrochemical properties of nanostructured metal oxide electrodes immersed in redox-inactive organic media.

This paper describes analysis of dropcast nanocrystalline and electrochemically deposited films of NiO and α-Fe2O3 as model metal oxide semiconductors immersed in redox-inactive organic electrolyte solutions using electrochemical impedance spectroscopy (EIS). Although the data reported here fit a circuit commonly used to model EIS data of metal oxide electrodes, which comprises an RC circuit nested inside a second RC circuit that is in series with a resistor, our interpretation of the physical meaning of these circuit elements differs from that applied to EIS measurements of metal oxide electrodes immersed in redox-active media. The data presented here are most consistent with an interpretation in which the nested RC circuit represents charge transfer between the metal oxide film and the underlying metal electrode, and the non-nested RC circuit represents the resistance and capacitance associated with formation of a charge-compensating double-layer at the exposed interface between the metal electrode and electrolyte solution. Applying this interpretation to analysis of EIS data collected for metal oxide films in organic media enables the impact of film morphology on electrochemical behavior to be distinguished from the effects of the intrinsic electronic structure of the metal oxide. This distinction is crucial to the evaluation of nanostructured metal oxide electrodes for electrochemical energy storage and electrocatalysis applications.

Physicochemical implications of surface alkylation of high-valent, Lindqvist-type polyoxovanadate-alkoxide clusters.

We report a rare example of the direct alkylation of the surface of a plenary polyoxometalate cluster by leveraging the increased nucleophilicity of vanadium oxide assemblies. Addition of methyl trifluoromethylsulfonate (MeOTf) to the parent polyoxovanadate cluster, [V6O13(TRIOLR)2]2- (TRIOL = tris(hydroxymethyl)methane; R = Me, NO2) results in functionalisation of one or two bridging oxide ligands of the cluster core to generate [V6O12(OMe)(TRIOLR)2]1- and [V6O11(OMe)2(TRIOLR)2]2-, respectively. Comparison of the electronic absorption spectra of the functionalised and unfunctionalised derivatives indicates the decreased overall charge of the complex results in a decrease in the energy required for ligand to metal charge transfer events to occur, while simultaneously mitigating the inductive effects imposed by the capping TRIOL ligand. Electrochemical analysis of the family of organofunctionalised polyoxovanadate clusters reveals the relationship of ligand environment and the redox properties of the cluster core: increased organofunctionalisation of the surface of the vanadium oxide assembly translates to anodic shifts in the reduction events of the Lindqvist ion. Overall, this work provides insight into the electronic effects induced upon atomically precise modifications to the surface structure of nanoscopic, redox-active metal oxide assemblies.

Innovation processes for ageing-related health technologies.

Innovative technologies offer potential benefits for the health and care needs of an ageing population, but the processes by which these innovations are developed and implemented are not well understood. As part of a Canadian research network focused on ageing and technology, we explored how technologies currently being developed to support older adults and their caregivers fare through the processes of innovation. We conducted a multiple case study focused on development of four technology products. Interviews were conducted with project members (n = 8) during site visits to the locations of the four cases, as well as with other key informants (n = 12). Directed coding, guided by the Accelerating Diffusion of Proven Technologies for Older Adults (ADOPT) model was used to analyse the data. Findings illustrate the complexities of innovation processes, including the challenges in developing a business case as well as benefits of a collaborative network.

Enabling health technology innovation in Canada: Barriers and facilitators in policy and regulatory processes.

OBJECTIVES: Health care innovation and technologies can improve patient outcomes, but policies and regulations established to protect the public interest may become barriers to improvement of health care delivery. We conducted a scoping review to identify policy and regulatory barriers to, and facilitators of, successful innovation and adoption of health technologies (excluding pharmaceutical and information technologies) in Canada. METHODS: The review followed Arksey and O'Malley's methodology to assess the breadth and depth of literature on this topic and drew upon published and grey literature from 2000-2016. Four reviewers independently screened citations for inclusion. RESULTS: Sixty- seven full- text documents were extracted to collect facilitators and barriers to health technology innovation and adoption. The extraction table was themed using content analysis, and reanalyzed, resulting in facilitators and barriers under six broad themes: development, assessment, implementation, Canadian policy context, partnerships and resources. CONCLUSION: This scoping review identified current barriers and highlights numerous facilitators to create a responsive regulatory and policy environment that encourages and supports effective co-creation of innovations to optimize patient and economic outcomes while emphasizing the importance of sustainability of health technologies.

The Chromatin Remodeler Isw1 Prevents CAG Repeat Expansions During Transcription in Saccharomyces cerevisiae.

CAG/CTG trinucleotide repeats are unstable sequences that are difficult to replicate, repair, and transcribe due to their structure-forming nature. CAG repeats strongly position nucleosomes; however, little is known about the chromatin remodeling needed to prevent repeat instability. In a Saccharomyces cerevisiae model system with CAG repeats carried on a YAC, we discovered that the chromatin remodeler Isw1 is required to prevent CAG repeat expansions during transcription. CAG repeat expansions in the absence of Isw1 were dependent on both transcription-coupled repair (TCR) and base-excision repair (BER). Furthermore, isw1∆ mutants are sensitive to methyl methanesulfonate (MMS) and exhibit synergistic MMS sensitivity when combined with BER or TCR pathway mutants. We conclude that CAG expansions in the isw1∆ mutant occur during a transcription-coupled excision repair process that involves both TCR and BER pathways. We observed increased RNA polymerase II (RNAPII) occupancy at the CAG repeat when transcription of the repeat was induced, but RNAPII binding did not change in isw1∆ mutants, ruling out a role for Isw1 remodeling in RNAPII progression. However, nucleosome occupancy over a transcribed CAG tract was altered in isw1∆ mutants. Based on the known role of Isw1 in the reestablishment of nucleosomal spacing after transcription, we suggest that a defect in this function allows DNA structures to form within repetitive DNA tracts, resulting in inappropriate excision repair and repeat-length changes. These results establish a new function for Isw1 in directly maintaining the chromatin structure at the CAG repeat, thereby limiting expansions that can occur during transcription-coupled excision repair.

Chromatin modifications and DNA repair: beyond double-strand breaks.

DNA repair must take place in the context of chromatin, and chromatin modifications and DNA repair are intimately linked. The study of double-strand break repair has revealed numerous histone modifications that occur after induction of a DSB, and modification of the repair factors themselves can also occur. In some cases the function of the modification is at least partially understood, but in many cases it is not yet clear. Although DSB repair is a crucial activity for cell survival, DSBs account for only a small percentage of the DNA lesions that occur over the lifetime of a cell. Repair of single-strand gaps, nicks, stalled forks, alternative DNA structures, and base lesions must also occur in a chromatin context. There is increasing evidence that these repair pathways are also regulated by histone modifications and chromatin remodeling. In this review, we will summarize the current state of knowledge of chromatin modifications that occur during non-DSB repair, highlighting similarities and differences to DSB repair as well as remaining questions.

Common sense: folk wisdom that ethnobiological and ethnomedical research cannot afford to ignore.

Common sense [CS], especially that of the non-scientist, can have predictive power to identify promising research avenues, as humans anywhere on Earth have always looked for causal links to understand, shape and control the world around them. CS is based on the experience of many individuals and is thus believed to hold some truths. Outcomes predicted by CS are compatible with observations made by whole populations and have survived tests conducted by a plethora of non-scientists. To explore our claim, we provide 4 examples of empirical insights (relevant to probably all ethnic groups on Earth) into causal phenomena predicted by CS: (i) "humans must have a sense of time", (ii) "at extreme latitudes, more people have the winter blues", (iii) "sleep is a cure for many ills" and (iv) "social networks affect health and disease". While CS is fallible, it should not be ignored by science - however improbable or self-evident the causal relationships predicted by CS may appear to be.

Chronomedicine: an old concept's fledging? A selective literature search.

Chronomedicine may be conceptualized as dealing with the prevention, causation, diagnosis, and treatment of diseases in humans with a particular focus on the role "time" [Greek: chrónos] plays in our physiology, endocrinology, metabolism and behavior at many organizational levels. While it has been used as a term and somewhat pursued as a discipline for decades, it appears that chronomedicine has captured a broader interest as a promising specialty only more recently. This commentary addresses roots of chronomedicine in the 1900s and perspectives for chronomedicine in the 21st century. Classical terms of chronobiology, e.g., Zeitgeber, melatonin and circadian, may be traced back to Aschoff, Lerner, and Halberg, respectively, but who actually coined the term "chronomedicine" and used it first in a publication remains unclear. Importantly, it could be(come) rather straightforward to transfer abundant insights gained from chronobiology to strategies in chronomedicine as animal models have been increasingly developed to understand human health and disease. Perspectively, chronomedicine should comprise "clinical chronomedicine" (individual-based) and "preventive chronomedicine" (population-based). Overall, due to the "maturing" of chronomedicine as a field, the near future might bring a section dedicated to chronomedicine in existing journals, or even a "Journal of Chronomedicine" as vectors of ideas and research.

What do we know 40 years after Nixon declared the 'war on cancer'? On the origin, prevention and treatment of cancer.

Evolutionary principles suggested by Darwin and Wallace some 150 years ago can provide insights into the origins of cancer. Moreover, they can form a basis for answering the question implicitly posed when Nixon declared the war on cancer in 1971: Can we actually 'cure' cancer? As explained lucidly by Greaves in 2001, necessary keys to evolution and thus for the origin of species, including ours, are changes of genes or mutations; but changes of genes are also necessary links in the causal chains which lead to cancer. In effect, cancer is therefore, according to Greaves, an 'evolutionary legacy'. Intriguingly, the realization that cancer is a consequence of changes in genes which are conditiones sine qua non for evolution suggests a mutation paradox on an evolutionary scale: in individuals, mutations may have devastating adverse health effects, including cancer. Populations, however, as a whole can be expected to benefit ultimately from changes of genes to better adapt to environmental challenges. On the basis of premises from evolution theory, it remains for us to interweave growing insights into evolutionary principles with realistic objectives for the primary prevention of and, where the latter fails, coexistence with cancer so that what we do for patients can become more of an art rather than a war.

A possible role of perinatal light in mood disorders and internal cancers: reconciliation of instability and latitude concepts.

Thought-provoking experimental evidence suggests that perinatal light exposure may imprint circadian clocks with lasting effects on the alignment and the stability of circadian rhythms later in life. Assuming that exposure to light early in life could determine the stability of an individual's circadian system later in life, the present hypothesis proposes that time of year and location of birth (i.e., season and latitude) and thus differential Zeitgeber strengths may be key contributors to a person's susceptibility of developing mood disorders like seasonal affective disorder (SAD) and common internal cancers such as those of breast and prostate. Consequently, when and where people are born might critically predispose them to both mood disorders and internal cancers, and may affect the onset and course of such illnesses. This paper develops a causal framework and presents suggestions for rigorous tests of the associated corollary and predictions. It does not escape our attention that links between the perinatal Zeitgeber strength of light and its effects on the stability of circadian systems later in life could have a role to play in affecting long-term health beyond cancer and mood disorders - mostly in adults but also in children.

The glucanosyltransferase Gas1 functions in transcriptional silencing.

Transcriptional silencing is a crucial process that is mediated through chromatin structure. The histone deacetylase Sir2 silences genomic regions that include telomeres, ribosomal DNA (rDNA) and the cryptic mating-type loci. Here, we report an unsuspected role for the enzyme Gas1 in locus-specific transcriptional silencing. GAS1 encodes a beta-1,3-glucanosyltransferase previously characterized for its role in cell wall biogenesis. In gas1 mutants, telomeric silencing is defective and rDNA silencing is enhanced. We show that the catalytic activity of Gas1 is required for normal silencing, and that Gas1's role in silencing is distinct from its role in cell wall biogenesis. Established hallmarks of silent chromatin, such as Sir2 and Sir3 binding, H4K16 deacetylation, and H3K56 deacetylation, appear unaffected in gas1 mutants. Thus, another event required for telomeric silencing must be influenced by GAS1. Because the catalytic activity of Gas1 is required for telomeric silencing, Gas1 localizes to the nuclear periphery, and Gas1 and Sir2 physically interact, we propose a model in which carbohydrate modification of chromatin components provides a new regulatory element that may be critical for chromatin function but which is virtually unexplored in the current landscape of chromatin analysis.