Virtual reality after stroke: Identifying important characteristics when designing experiences to improve engagement in upper limb rehabilitation.

Objective: Virtual reality (VR) has been used to improve upper limb function after stroke but there is little to guide product developers in building experiences that engage users in the sustained, repetitive training required. This research sought to understand the characteristics of VR scenarios best suited to engaging someone with a stroke during recovery to achieve therapeutic outcomes. Methods: Five creative immersive VR scenarios were designed by an experienced VR content creator containing unique combinations of VR characteristics. The usefulness of the scenarios was reviewed by expert clinicians experienced in stroke rehabilitation. Following this review, seven stroke survivors participated in each experience and reported on their engagement and motivation. Outcome measures were the User Satisfaction Evaluation Questionnaire and the modified Intrinsic Motivation Inventory. Semi-structured interviews were conducted with five participants following their immersive VR experience and analysed thematically. Results: Expert clinicians reported potential therapeutic value in the immersive VR scenarios by providing opportunities for repeated and graded practice of upper limb movements. Stroke survivors reported varied levels of enjoyment and engagement for each scenario. They recommended changes to the experiences, primarily relating to the tailoring of the scenarios to match varied upper limb capacities. Conclusion: This study highlights the characteristics of immersive VR scenarios that are important in sustaining motivation and providing high-repetition task-specific movement experiences. Differences in the experience and preferences of stroke participants regarding the characteristics of immersive VR experiences indicate that a variety of experiences are necessary to engage and sustain participation in an immersive VR-related therapy programme.

Designing an occupation-based group intervention for adult inpatient rehabilitation: Partnering with clinicians and patients using a nominal group technique design.

INTRODUCTION: Occupation-based interventions use engagement in a person's daily activities to achieve change. There is growing research into the use of occupation-based group interventions in the inpatient rehabilitation setting. It remains unclear whether occupation-based groups offer comparable outcomes to occupation-based interventions delivered individually; this research will precede a clinical trial aimed at comparing these two approaches for improving occupational performance outcomes. This study details the process of co-designing the intervention. Partnering with clinicians and patients in the design of healthcare interventions can promote patient-centred care, enhance uptake, and improve applicability and sustainability of the intervention to that setting. METHODS: A modified nominal group technique (NGT) design was applied to facilitate two meetings and an electronic survey with an expert panel of clinicians and patients. Twelve participants (n = 4 occupational therapists, n = 1 registered nurse, n = 1 physiotherapist, n = 1 occupational therapy assistant, n = 1 occupational therapy manager, and n = 4 patients) were purposively recruited. A modified approach to the technique's four stages was used: silent generation, round robin, clarification, and voting. Consensus was set at >50%. Qualitative data from group discussions were analysed thematically. FINDINGS: All participants agreed the intervention should include patient-centred, goal-directed, practice of daily activities, including breakfast and lunch preparation, domestic tasks, and laundry. Other components that were agreed included where the groups could run, group size, eligibility criteria, and frequency. Key themes from clinicians included needing a goal-directed intervention, focused on progressing towards hospital discharge; time and resource requirements were also discussed. Patients emphasised the importance of building social connections, opportunity to engage in meaningful activity, and the importance of linking participation to patient goals. CONCLUSION: Through collaboration with clinicians and patients, an occupation-based group intervention considering the available evidence, alongside clinical, experiential, and contextual sources of knowledge was developed; this resulted in an evidence-based, patient-centred, and contextually relevant intervention.

Occupation-based interventions to improve occupational performance and participation in the hospital setting: a systematic review.

PURPOSE: To critically review the evidence for occupation-based interventions in improving occupational performance and participation outcomes in the hospital setting. METHODS: Five databases were searched from 2000-2022. Peer-reviewed studies of any design investigating the impact of occupation-based interventions in the hospital setting were included. Methodological quality was assessed using the appropriate tool for each study design. Following data extraction, a narrative synthesis was conducted. RESULTS: Thirty-three studies comprising of 26 experimental, five non-experimental, and two mixed methods studies were included (n = 1646 participants). Results indicate good evidence to support occupation-based interventions to improve occupational performance and participation outcomes in inpatient rehabilitation; it is unclear whether they are more effective than any control/alternative intervention. Research in the acute and mental health hospital settings were scarcer. Understanding the benefits of occupation-based interventions was enhanced through qualitative results including improving independence and confidence to discharge home, increasing motivation for therapy, connecting with others, and peer-based learning. CONCLUSIONS: Heterogeneity and methodological weaknesses across existing studies limits the conclusions that can be drawn on the impact of occupation-based interventions in the hospital setting. More rigorous research should be conducted with better reporting of intervention design and the use of robust measures of occupational performance.Implications For RehabilitationThe use of occupation-based interventions should be considered to improve occupational performance and participation outcomes in the hospital setting.There is good evidence to support the impact of occupation-based interventions on improving occupational performance and participation outcomes in the inpatient rehabilitation setting; evidence in the acute and mental health settings is scarcer.Occupation-based interventions are valued by both patients and clinicians for their impact on patient outcomes and the patient experience.

Statistical Shape and Bone Property Models of Clinical Populations as the Foundation for Biomechanical Surgical Planning: Application to Shoulder Arthroplasty.

This work developed, validated, and compared statistical shape, statistical intensity, and statistical shape and intensity models (SSMs, SIMs, SSIMs) of scapulae from a clinical population. SSMs efficiently describe bone shape variation while SIMs describe bone material property variation, and SSIM's combine description of both variables. This work establishes these models' efficacy and whether they can be used in surgical planning. Models were developed using shoulder arthroplasty data of patients with bone erosion, which is challenging to treat and would benefit from improved surgical planning. Models were created using previously validated nonrigid registration and material property assignment processes that were optimized for scapula characteristics. The models were assessed using standard metrics, anatomical measurements, and correlation analyses. The SSM and SIM specificity and generalization error metrics were 3.4 mm and <1 mm and 184 HU and 156 HU, respectively. The SSIM did not achieve the same level of performance as the SSM and SIM in this study (e.g., shape generalization: SSIM-2.2 mm versus SSM-<1 mm). Anatomical correlation analysis showed that the SSM more effectively and efficiently described shape variation compared to the SSIM. The SSM and SIM modes of variation were not strongly correlated (e.g., rmax = 0.56 for modes explaining ≤2.1% of variance). The SSIM is outperformed by the SSM and SIM and the latter two are not strongly correlated; therefore, using the SSM and SIM in conjunction will generate synthetic bone models with realistic characteristics and thus can be used for biomechanical surgical planning applications.

Pragmatic mAb lead molecule engineering from a developability perspective.

As the number of antibody drugs being approved and marketed increases, our knowledge of what makes potential drug candidates a successful product has increased tremendously. One of the critical parameters that have become clear in the field is the importance of mAb "developability." Efforts are being increasingly focused on simultaneously selecting molecules that exhibit both desirable biological potencies and manufacturability attributes. In the current study mutations to improve the developability profile of a problematic antibody that inconsistently precipitates in a batch scale-dependent fashion using a standard platform purification process are described. Initial bioinformatic analysis showed the molecule has no obvious sequence or structural liabilities that might lead it to precipitate. Subsequent analysis of the molecule revealed the presence of two unusual positively charged mutations on the light chain at the interface of VH and VL domains, which were hypothesized to be the primary contributor to molecule precipitation during process development. To investigate this hypothesis, straightforward reversion to the germline of these residues was carried out. The resulting mutants have improved expression titers and recovered stability within a forced precipitation assay, without any change to biological activity. Given the time pressures of drug development in industry, process optimization of the lead molecule was carried out in parallel to the "retrospective" mutagenesis approach. Bespoke process optimization for large-scale manufacturing was successful. However, we propose that such context-dependent sequence liabilities should be included in the arsenal of in silico developability screening early in development; particularly since this specific issue can be efficiently mitigated without the requirement for extensive screening of lead molecule variants.

The obesity paradigm and the role of health services in obesity prevention: a grounded theory approach.

BACKGROUND: Health services have a clear role in the treatment of obesity and diseases linked to obesity but a less well-established role in prevention, particularly in hospital and community-based health services. METHODS: The aim of this research was to examine whether and how hospital and community-based health services incorporate adult obesity prevention into policy and practice. The case study setting was an Australian based health service. Grounded theory informed all aspects of the research including participant recruitment, data collection and data analysis. A systems approach guided the analysis of diverse perspectives, relationships and interconnections within the study context. RESULTS: The prevailing paradigm within the health service is that obesity is a matter of choice. This dominant perspective combined with a disease focused medical model overly simplifies the complex issue of obesity and reinforces the paradigm which treats obesity as a matter of individual responsibility. A focus on individual change hinders health services from playing an effective role in obesity prevention and leads to unintended consequences, including increasing stigma. CONCLUSIONS: Health service responses to obesity and its prevention compound the negative elements associated with obesity for individuals and are ineffective in creating positive change at individual or a societal level. An alternative systems-level approach is needed to align health service responses with contemporary approaches that address obesity prevention as a complex problem.

Obesity prevention and the role of hospital and community-based health services: a scoping review.

BACKGROUND: Control of obesity is an important priority to reduce the burden of chronic disease. Clinical guidelines focus on the role of primary healthcare in obesity prevention. The purpose of this scoping review is to examine what the published literature indicates about the role of hospital and community based health services in adult obesity prevention in order to map the evidence and identify gaps in existing research. METHODS: Databases were searched for articles published in English between 2006 and 2016 and screened against inclusion and exclusion criteria. Further papers were highlighted through a manual search of the reference lists. Included papers evaluated interventions aimed at preventing overweight and obesity in adults that were implemented within and/or by hospital and community health services; were an empirical description of obesity prevention within a health setting or reported health staff perceptions of obesity and obesity prevention. RESULTS: The evidence supports screening for obesity of all healthcare patients, combined with referral to appropriate intervention services but indicates that health professionals do not typically adopt this practice. As well as practical issues such as time and resourcing, implementation is impacted by health professionals' views about the causes of obesity and doubts about the benefits of the health sector intervening once someone is already obese. As well as lacking confidence or knowledge about how to integrate prevention into clinical care, health professional judgements about who might benefit from prevention and negative views about effectiveness of prevention hinder the implementation of practice guidelines. This is compounded by an often prevailing view that preventing obesity is a matter of personal responsibility and choice. CONCLUSIONS: This review highlights that whilst a population health approach is important to address the complexity of obesity, it is important that the remit of health services is extended beyond medical treatment to incorporate obesity prevention through screening and referral. Further research into the role of health services in obesity prevention should take a systems approach to examine how health service structures, policy and practice interrelationships, and service delivery boundaries, processes and perspectives impact on changing models of care.

Application of Imaging Flow Cytometry for the Characterization of Intracellular Attributes in Chinese Hamster Ovary Cell Lines at the Single-Cell Level.

Biopharmaceutical manufacturing using Chinese hamster ovary (CHO) cells requires the generation of high-producing clonal cell lines. During cell line development, cell cloning using fluorescence-activated cell sorting (FACS) has the potential to combine isolation of single cells with sorting based on specific cellular attributes that correlate with productivity and/or growth, identifying cell lines with desirable phenotypes for manufacturing. This study describes the application of imaging flow cytometry (IFC) to characterize recombinant cell lines at the single-cell level to identify cell attributes predictive of productivity. IFC assays are developed to quantify the organelle content and recombinant heavy-chain (HC) and light-chain (LC) polypeptide as well as messenger RNA (mRNA) amounts in single cells. The assays are then validated against orthogonal standard flow cytometry, western blot, and quantitative reverse transcription polymerase chain reaction (qRT-PCR) methods. The authors describe how these IFC assays may be used in cell line development and show how cellular properties can be correlated with productivity at the single-cell level, allowing the isolation of such cells during the cloning process. From the analysis, HC polypeptide and mRNA are found to be predictive of productivity early in the culture; however, specific organelle content did not show any correlation with productivity.

Advanced allied health assistants: an emerging workforce.

OBJECTIVE: Nationally and internationally there is work underway to continue to advance the scope of practice of allied health assistants (AHA). The advanced role requires additional training and competency development, as well as significant clinical experience. To build on the evidence relating to advanced scope AHAs, ACT Health undertook a project to explore the potential for the development of the local AHA workforce. This paper provides an overview of the project. METHODS: The potential for advanced AHAs in the Australian Capital Territory (ACT) was assessed using literature reviews, consultation with other services working with advanced AHAs and interviews with local allied health managers and assistants. RESULTS: A role for advanced AHAs within the ACT workforce was recommended, along with the need to further develop the AHA governance structure and AHA training packages and to undertake more research into the AHA workforce. CONCLUSION: AHAs make a positive contribution to the delivery of effective, responsive, consumer-focused healthcare. The advanced AHA role provides further opportunities to enhance the flexibility of allied health services while also providing a career structure for this growing workforce.

Role, implementation, and effectiveness of advanced allied health assistants: a systematic review.

BACKGROUND: The purpose of this systematic review was to determine the effectiveness and implementation of advanced allied health assistant roles. METHODS: A systematic search of seven databases and Google Scholar was conducted to identify studies published in English peer-reviewed journals from 2003 to 2013 and reporting on the effectiveness and implementation of advanced allied health assistant (A/AHA) roles. Reference lists were also screened to identify additional studies, and the authors' personal collections of studies were searched. Studies were allocated to the National Health and Medical Research Council hierarchy of evidence, and appraisal of higher-level studies (III-1 and above) conducted using the Centre for Evidence Based Medicine Systematic Review Critical Appraisal Sheet for included systematic reviews or the PEDro scale for level II and III-1 studies. Data regarding country, A/AHA title, disciplines, competencies, tasks, level of autonomy, clients, training, and issues regarding the implementation of these roles were extracted, as were outcomes used and key findings for studies investigating their effectiveness. RESULTS: Fifty-three studies were included, and most because they reported background information rather than investigating A/AHA roles, this representing low-level information. A/AHAs work in a range of disciplines, with a variety of client groups, and in a number of different settings. Little was reported regarding the training available for A/AHAs. Four studies investigated the effectiveness of these roles, finding that they were generally well accepted by clients, and provided more therapy time. Issues in integrating these new roles into existing health systems were also reported. CONCLUSION: A/AHA roles are being implemented in a range of settings, and appear to be effective in terms of process measures and stakeholder perceptions. Few studies have investigated these roles, indicating a need for research to be conducted in this area to enable policy-makers to consider the value of these positions and how they can best be utilized.

Selective ß2-adrenoreceptor stimulation attenuates myocardial cell death and preserves cardiac function after ischemia-reperfusion injury.

OBJECTIVE: ß(2)-adrenoreceptor activation has been shown to protect cardiac myocytes from cell death. We hypothesized that acute ß(2)-adrenoreceptor stimulation, using arformoterol (ARF), would attenuate myocardial ischemia/reperfusion (R) injury via NO synthase activation and cause a subsequent increase in NO bioavailability. METHODS AND RESULTS: Male C57BL/6J and endothelial NO synthase (eNOS) knockout mice were subjected to 45 minutes of myocardial ischemia and 24 hours of R. ARF or vehicle was administered 5 minutes before R. Serum troponin-I was measured, and infarct size per area-at-risk was evaluated at 24 hours of R. Echocardiography was performed at baseline and 2 weeks after R. Myocardial cAMP, protein kinase A, eNOS/Akt phosphorylation status, and NO metabolite levels were assayed. ARF (1 µg/kg) reduced infarct size per area-at-risk by 53.1% (P<0.001 versus vehicle) and significantly reduced troponin-I levels (P<0.001 versus vehicle). Ejection fraction was significantly preserved in ARF-treated hearts compared with vehicle hearts at 2 weeks of R. Serum cAMP and nuclear protein kinase A C-α increased 5 and 15 minutes after ARF injection, respectively (P<0.01). ARF increased Akt phosphorylation at Thr(308) (P<0.001) and Ser(473) (P<0.01), and eNOS phosphorylation at Ser(1177) (P<0.01). ARF treatment increased heart nitrosothiol levels (P<0.001) at 15 min after injection. ARF failed to reduce infarct size in eNOS(-/-) mice. CONCLUSIONS: Our results indicate that ß(2)-adrenoreceptor stimulation activates cAMP, protein kinase A, Akt, and eNOS and augments NO bioavailability. Activation of this prosurvival signaling pathway attenuates myocardial cell death and preserves cardiac function after ischemia/reperfusion.

Seasonal cutaneous sarcoidosis: a photo-induced variant.

Sarcoidosis is a multisystem granulomatous disease, with cutaneous involvement in up to 35% of cases. Owing to its heterogeneous clinical presentation, sarcoidosis is often referred to as the 'great imitator' of dermatological disease. A rare variant of photosensitive cutaneous sarcoidosis has been infrequently reported in the literature. We describe an unusual case of recurrent, photo-distributed cutaneous sarcoidosis presenting only during the summer months.

Analysis of the role of COP9 Signalosome (CSN) subunits in K562; the first link between CSN and autophagy.

BACKGROUND: The COP9/signalosome (CSN) is a highly conserved eight subunit complex that, by deneddylating cullins in cullin-based E3 ubiquitin ligases, regulates protein degradation. Although studied in model human cell lines such as HeLa, very little is known about the role of the CSN in haemopoietic cells. RESULTS: Greater than 95% knockdown of the non-catalytic subunit CSN2 and the deneddylating subunit CSN5 of the CSN was achieved in the human myeloid progenitor cell line K562. CSN2 knockdown led to a reduction of both CSN5 protein and mRNA whilst CSN5 knockdown had little effect on CSN2. Both knockdowns inhibited CSN deneddylase function as demonstrated by accumulation of neddylated Cul1. Furthermore, both knockdowns resulted in the sequential loss of Skp2, Cdc4 and beta-TrCP F-box proteins. These proteins were rescued by the proteasome inhibitor MG132, indicating the autocatalytic degradation of F-box proteins upon loss of CSN2 or CSN5. Interestingly, altered F-box protein gene expression was also observed in CSN2 and CSN5 knockdowns, suggesting a potential role of the CSN in regulating F-box protein transcription.Loss of either CSN subunit dramatically reduced cell growth but resulted in distinct patterns of cell death. CSN5 knockdown caused mitotic defects, G2/M arrest and apoptotic cell death. CSN2 knockdown resulted in non-apoptotic cell death associated with accumulation of both the autophagy marker LC3-II and autophagic vacuoles. Treatment of vector control K562 cells with the autophagy inhibitors 3-methyladenine and bafilomycin A1 recapitulated the growth kinetics, vacuolar morphology and LC3-II accumulation of CSN2 knockdown cells indicating that the cellular phenotype of CSN2 cells arises from autophagy inhibition. Finally, loss of CSN2 was associated with the formation of a CSN5 containing subcomplex. CONCLUSION: We conclude that CSN2 is required for CSN integrity and the stability of individual CSN subunits, and postulate that CSN2 loss results in a phenotype distinct from that of cells lacking CSN5 possibly as a consequence of altered CSN5 activity within a resultant CSN subcomplex. Our data present the first evidence for the sequential loss of F-box proteins upon CSN manipulation and are the first to identify a potential link between CSN function and autophagy.

The aldo-keto reductase AKR1C3 contributes to 7,12-dimethylbenz(a)anthracene-3,4-dihydrodiol mediated oxidative DNA damage in myeloid cells: implications for leukemogenesis.

The aldo-keto reductase AKR1C3, has been shown to regulate myelopoiesis via its ability to metabolise prostaglandin D2 (PGD2). Other studies have demonstrated the oxidative activation of polycyclic aromatic hydrocarbon (PAH) procarcinogens by AKR1C3 in cell-free systems. This is the first study that addresses whether AKR1C3 mediates carcinogen activation within intact living cells following manipulation of AKR1C3 by molecular intervention. Quantitative RT-PCR identified AKR1C3 as the predominant AKR1C isoform expressed in acute myeloid leukemia (AML). Exposure of K562 and KG1a myeloid cell lines to the known AKR1C3 substrate 7,12-dimethylbenz(a)anthracene-3,4-dihydrodiol (7,12-DMBA-3,4-diol) resulted in both single strand DNA breaks and oxidative DNA damage as measured using conventional and FPG-modified comet assays respectively. PGD2-keto reductase activity was shown to be correlated with relative AKR1C3 expression and together with quantitative real time PCR was used to validate the RNAi-knockdown of AKR1C3 in K562 cells. Knockdown of AKR1C3 did not alter single strand DNA breaks following 7,12-DMBA-3,4-diol exposure but significantly decreased oxidative DNA damage. A similar interrelationship between AKR1C3 activity and 7,12-DMBA-3,4-diol mediated oxidative DNA damage but not single strand breaks was observed in KG1a cells. Finally, AKR1C3 knockdown also resulted in spontaneous erythroid differentiation of K562 cells. Since K562 cells are a model of AML blast crisis of chronic myeloid leukemia (CML) the data presented here identify AKR1C3 as a novel mediator of carcinogen-induced initiation of leukemia, as a novel regulator of erythroid differentiation and paradoxically as a potential new target in the treatment of CML.