Self-Assembled Recombinant Elastin and Globular Protein Vesicles with Tunable Properties for Diverse Applications.

Vesicles are self-assembled structures comprised of a membrane-like exterior surrounding a hollow lumen with applications in drug delivery, artificial cells, and micro-bioreactors. Lipid or polymer vesicles are the most common and are made of lipids or polymers, respectively. They are highly useful structures for many applications but it can be challenging to decorate them with proteins or encapsulate proteins in them, owing to the use of organic solvent in their formation and the large size of proteins relative to lipid or polymer molecules. By utilization of recombinant fusion proteins to make vesicles, specific protein domains can be directly incorporated while also imparting tunability and stability. Protein vesicle assembly relies on the design and use of self-assembling amphiphilic proteins. A specific protein vesicle platform made in purely aqueous conditions of a globular, functional protein fused to a glutamate-rich leucine zipper (ZE) and a thermoresponsive elastin-like polypeptide (ELP) fused to an arginine-rich leucine zipper (ZR) is discussed here. The hydrophobic conformational change of the ELP above its transition temperature drives assembly, and strong ZE/ZR binding enables incorporation of the desired functional protein. Mixing the soluble proteins on ice induces zipper binding, and then warming above the ELP transition temperature (Tt) triggers the transition to and growth of protein-rich coacervates and, finally, reorganization of proteins into vesicles. Vesicle size is tunable based on salt concentration, rate of heating, protein concentration, size of the globular protein, molar ratio of the proteins, and the ELP sequence. Increasing the salt concentration decreases vesicle size by decreasing the Tt, resulting in a shorter coacervation transition stage. Likewise, directly changing the heating rate also changes this time and increasing protein concentration increases coalescence. Increasing globular protein size decreases the size of the vesicle due to steric hindrance. By changing the ELP sequence, which consists of (VPGXG)n, through the guest residue (X) or number of repeats (n), Tt is changed, affecting size. Additionally, the chemical nature of X variation has endowed vesicles with stimuli responsiveness and stability at physiological conditions.Protein vesicles have been used for biocatalysis, biomacromolecular drug delivery, and vaccine applications. Photo-cross-linkable vesicles were used to deliver small molecule cargo to cancer cells in vitro and antigen to immune cells in vivo. pH-responsive vesicles effectively delivered functional protein cargo, including cytochrome C, to the cytosol of cancer cells in vitro, using hydrophobic ion pairing to improve cargo distribution in the vesicles and release. The globular protein used to make the vesicles can be varied to achieve different functions. For example, enzyme vesicles exhibit biocatalysis, and antigen vesicles induce antibody and cellular immune responses after vaccination in mice. Collectively, the development and engineering of the protein vesicle platform has employed amphiphilic self-assembly strategies and rational protein engineering to control physical, chemical, and biological properties for biotechnology and nanomedicine applications.

Rational design of elastin-like polypeptide fusion proteins to tune self-assembly and properties of protein vesicles.

Protein vesicles made from bioactive proteins have potential value in drug delivery, biocatalysis, and as artificial cells. As the proteins are produced recombinantly, the ability to precisely tune the protein sequence provides control not possible with polymeric vesicles. The tunability and biocompatibility motivated this work to develop protein vesicles using rationally designed protein building blocks to investigate how protein sequence influences vesicle self-assembly and properties. We have reported an elastin-like polypeptide (ELP) fused to an arginine-rich leucine zipper (ZR) and functional, globular proteins fused to a glutamate-rich leucine zipper (ZE) that self-assemble into protein vesicles when warmed from 4 to 25 °C due to the hydrophobic transition of ELP. Previously, we demonstrated the ability to tune vesicle properties by changing protein and salt concentration, ZE : ZR ratio, and warming rate. However, there is a limit to the properties that can be achieved via assembly conditions. In order to access a wider range of vesicle diameter and stability profiles, this work investigated how modifiying the hydrophobicity and length of the ELP sequence influenced self-assembly and the final properties of protein vesicles using mCherry as a model globular protein. The results showed that both transition temperature and diameter of protein vesicles were inversely correlated to the ELP guest residue hydrophobicity and the number of ELP pentapeptide repeats. Additionally, sequence manipulation enabled assembly of vesicles with properties not accessible by changes to assembly conditions. For example, introduction of tyrosine at 5 guest residue positions in ELP enabled formation of nanoscale vesicles stable at physiological salt concentration. This work yields design guidelines for modifying the ELP sequence to manipulate protein vesicle transition temperature, size and stability to achieve desired properties for particular biofunctional applications.

Systematic review of self-management interventions for older adults with cancer.

AIM: The purpose of this systematic review was to determine the effectiveness of self-management interventions for older adults with cancer and to determine the effective components of said interventions. METHODS: We conducted a systematic review of self-management interventions for older adults (65+) with cancer guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. We conducted an exhaustive search of the following databases: Ageline, AMED, ASSIA, CINAHL, Cochrane, Embase, Medline, PsychINFO, and Sociological Abstracts. We assessed for quality using the Cochrane Risk of Bias tool and Down & Black for quasi-experimental studies, with data synthesized in a narrative and tabular format. RESULTS: Sixteen thousand nine hundred and eight-five titles and abstracts were screened, subsequently 452 full-text papers were reviewed by two independent reviewers, of which 13 full-text papers were included in the final review. All self-management interventions included in this review measured Quality of Life; other outcomes included mood, self-care activity, supportive care needs, self-advocacy, pain intensity, and analgesic intake; only one intervention measured frailty. Effective interventions were delivered by a multidisciplinary teams (n = 4), nurses (n = 3), and mental health professionals (n = 1). Self-management core skills most commonly targeted included: problem solving; behavioural self-monitoring and tailoring; and settings goals and action planning. CONCLUSIONS: Global calls to action argue for increased emphasize on self-management but presently, few interventions exist that explicitly target the self-management needs of older adults with cancer. Future work should focus on explicit pathways to support older adults and their caregivers to prepare for and engage in cancer self-management processes and behaviours.

Providing Medical Information to Older Adults in a Web-Based Environment: Systematic Review.

BACKGROUND: Cancer is a disease that predominantly affects older adults, and several organizations recommend the completion of a geriatric assessment to help with cancer treatment decision-making. Owing to a shortage of geriatric teams and the vast number of older adults diagnosed with cancer each year, a web-based geriatric assessment may improve access to geriatric assessment for older adults. We systematically reviewed the literature to obtain the latest evidence for the design of our web-based geriatric assessment tool Comprehensive Health Assessment for My Plan. OBJECTIVE: This review aimed to probe the following questions: what is the impact of providing health test results to older adults in a web-based environment without the presence of a health care provider for patient-centered outcomes, including satisfaction, perceived harm, empowerment, quality of life, and health care use (eg, hospitalization, physician visits, emergency room visits, and costs), and what recommendations do older adults and developers have for designing future apps or websites for older adults? METHODS: This systematic review was guided by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analysis) statement. Studies were limited to publications in English that examined a web-based tool that provided test results to older adults (aged ≥65 years) without the presence of a health care provider. A health sciences librarian performed the search on November 29, 2019, on the following electronic databases: MEDLINE, Embase, CINAHL, PsycINFO, and the Cochrane Library. The quality of the included studies was assessed using the Mixed Methods Appraisal Tool Version 2018. The findings are summarized narratively and in tabular format. RESULTS: A total of 26,898 titles and abstracts were screened by 2 independent reviewers, of which 94 studies were selected for a full-text review, and 9 studies were included in this review. There were only 2 randomized controlled trials of high quality that explored the effects of receiving health care results on the web via eHealth tools for older adults or provided evidence-based recommendations for designing such tools. Older adults were generally satisfied with receiving screening results via eHealth tools, and several studies suggested that receiving health screening results electronically improved participants' quality of life. However, user interfaces that were not designed with older adults in mind and older adults' lack of confidence in navigating eHealth tools proved challenging to eHealth uptake and use. All 9 studies included in this systematic review made recommendations on how to design eHealth tools that are intuitive and useful for older adults. CONCLUSIONS: eHealth tools should incorporate specific elements to ensure usability for older adults. However, more research is required to fully elucidate the impact of receiving screening and results via eHealth tools without the presence of a health care provider for patient-centered outcomes in this target population.

Flipping it online: re-imagining teaching search skills for knowledge syntheses.

Introduction: This program description outlines our approach to re-developing our three-part series for graduate students on comprehensive searching for knowledge syntheses from in-person to online delivery using a flipped classroom model. The re-development coincided with our library's response to COVID-19. Description: This series followed a flipped classroom model where participants completed asynchronous modules built on Articulate Rise 360 before attending a synchronous session. Each week of content covered unique learning objectives. Pre- and post-class self-assessments were used to examine students' understanding of the materials. Outcomes: 152 unique participants registered for the series across two offerings in summer 2020. We observed high engagement with pre-work modules and active participation during synchronous sessions. Discussion: We found the flipped classroom approach to work well for our users in an online environment. Moving forward, we intend to continue with our re-developed online workshop series with minor modifications, in addition to in-person instruction.

Pedagogical practices that influence professional identity formation in baccalaureate nursing education: A scoping review.

OBJECTIVES: The purpose of this review was to identify pedagogical practices that contribute to professional identity formation in undergraduate nursing education and to map the components of professional identity described within these practices. DESIGN: A scoping review using a six-stage methodological framework was used to capture a range of evidence describing how professional identity has been conceptualized and integrated into nursing curriculum. DATA SOURCES: Databases searched included: Ovid MEDLINE: Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Ovid MEDLINE® Daily and Ovid MEDLINE® 1946-Present, EBSCO CINAHL (1981 to present), OVID PsycINFO (1806 to Present), ProQuest ERIC, ASSIA, and Sociological Abstracts. Additional studies were identified by scanning the reference lists of relevant articles. REVIEW METHODS: The study team collaboratively designed the data charting table and two coauthors independently screened the studies using Covidence software. Qualitative content analysis was used to categorize learning outcomes into five components of professional identity that were associated with pedagogical practices identified in the studies. RESULTS: A total of 114 peer-reviewed journal articles were initially charted. Articles were categorized as intervention studies (46, 40%), perspective studies (40, 35%), theoretical papers (17, 15%), or reviews (11, 10%). To ensure feasibility in collating and reporting the results, the review focused on the 46 empirical intervention studies that described associations between pedagogical practices and professional identity formation learning outcomes for students. CONCLUSIONS: This scoping review illustrates the range of contexts in which nursing students learn, the multidimensional nature of identity formation, as well as the breadth of pedagogical practices and learning outcomes that guide course design. The results can be used to inform future curriculum planning and to identify focused research questions to extend our understanding of evidence-based teaching practices supporting professional identity formation.

Protocol for a systematic review of self-management interventions for older adults living with cancer.

BACKGROUND: Cancer predominates in adults over age 65. Cancer treatments are known to create physical and psychosocial challenges, which may be amplified for older adults with cancer. Learning and applying self-management behaviours and skills during treatment with cancer can help to manage/recover health and improve quality of life. In many other chronic illnesses, self-management interventions are known to improve health outcomes and lower healthcare costs. The purpose of this systematic review is to determine the effectiveness of self-management interventions for older adults with cancer on physical, psychosocial, and health system-related outcomes. METHODS: We are conducting a systematic review of self-management interventions for older adults (65+) diagnosed with cancer (solid tumour or haematological) in the active treatment phase of cancer. This systematic review is guided by the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. Studies are limited to experimental or quasi-experimental methods published in English, French, German, or Dutch. A search strategy was designed with a Health Sciences librarian and performed using the following electronic databases: Ageline, AMED, ASSIA, Cinahl, Cochrane, Embase, Medline, PsychINFO, and Sociological Abstracts. Approximately 14,000 titles and abstracts are being electronically screened by a minimum of 2 reviewers, with relevant studies to be screened for full text. The final sample of included studies will be assessed for quality using the Cochrane Risk of Bias tool and Down and Black for quasi-experimental studies, with data synthesized in a narrative and tabular format. DISCUSSION: This systematic review will expand the knowledge base of interventions supporting self-management for older adults with cancer. This study will inform future intervention development by identifying gaps and strengths in effective self-management interventions targeting the needs of older adults receiving active treatment for cancer. SYSTEMATIC REVIEW REGISTRATION: PROPERO registry ID# CRD42019134113.

Identifying and understanding the health and social care needs of older adults with multiple chronic conditions and their caregivers: a scoping review.

BACKGROUND: As the population is aging, the number of persons living with multiple chronic conditions (MCC) is expected to increase. This review seeks to answer two research questions from the perspectives of older adults with MCC, their caregivers and their health care providers (HCPs): 1) What are the health and social care needs of community-dwelling older adults with MCC and their caregivers? and 2) How do social and structural determinants of health impact these health and social care needs? METHODS: We conducted a scoping review guided by a refinement of the Arksey & O'Malley framework. Articles were included if participants were 55 years or older and have at least two chronic conditions. We searched 7 electronic databases. The data were summarized using thematic analysis. RESULTS: Thirty-six studies were included in this review: 28 studies included participants with MCC; 12 studies included HCPs; 5 studies included caregivers. The quality of the studies ranged from moderate to good. Five main areas of needs were identified: need for information; coordination of services and supports; preventive, maintenance and restorative strategies; training for older adults, caregivers and HCPs to help manage the older adults' complex conditions; and the need for person-centred approaches. Structural and social determinants of health such as socioeconomic status, education and access influenced the needs of older adults with MCC. CONCLUSION: The review highlights that most of the needs of older adults with MCC focus on lack of access to information and coordination of care. The main structural and social determinants that influenced older adults' needs were their level of education/health literacy and their socioeconomic status.

Identifying and understanding the health and social care needs of older adults with multiple chronic conditions and their caregivers: a protocol for a scoping review.

INTRODUCTION: People are living longer; however, they are not necessarily experiencing good health and well-being as they age. Many older adults live with multiple chronic conditions (MCC), and complex health issues, which adversely affect their day-to-day functioning and overall quality of life. As a result, they frequently rely on the support of friend and/or family caregivers. Caregivers of older adults with MCC often face challenges to their own well-being and also require support. Currently, not enough is known about the health and social care needs of older adults with MCC and the needs of their caregivers or how best to identify and meet these needs. This study will examine and synthesise the literature on the needs of older adults with MCC and those of their caregivers, and identify gaps in evidence and directions for further research. METHODS AND ANALYSIS: We will conduct a scoping review of the peer-reviewed and grey literature using the updated Arksey and O'Malley framework. The literature will be identified using a multidatabase and grey literature search strategy developed by a health sciences librarian. Papers, reports and other materials addressing the health and social care needs of older adults and their friend/family caregivers will be included. Search results will be screened, independently, by two reviewers, and data will be abstracted from included literature and charted in duplicate. ETHICS AND DISSEMINATION: This scoping review does not require ethics approval. We anticipate that study findings will inform novel strategies for identifying and ascertaining the health and social care needs of older adults living with MCC and those of their caregivers. Working with knowledge-user members of our team, we will prepare materials and presentations to disseminate findings to relevant stakeholder and end-user groups at local, national and international levels. We will also publish our findings in a peer-reviewed journal.