Elbow conditions: research priorities setting in partnership with the James Lind Alliance.

OBJECTIVE: To undertake a UK-based James Lind Alliance (JLA) Priority Setting Partnership for elbow conditions and be representative of the views of patients, carers and healthcare professionals (HCPs). SETTING: This was a national collaborative study organised through the British Elbow and Shoulder Society. PARTICIPANTS: Adult patients, carers and HCPs who have managed or experienced elbow conditions, their carers and HCPs in the UK involved in managing of elbow conditions. METHODS: The rigorous JLA priority setting methodology was followed. Electronic and paper scoping surveys were distributed to identify potential research priority questions (RPQs). Initial responses were reviewed and a literature search was performed to cross-check categorised questions. Those questions already sufficiently answered were excluded and the remaining questions were ranked in a second survey according to priority for future elbow conditions research. Using the JLA methodology, responses from HCP and patients were combined to create a list of the top 18 questions. These were further reviewed in a dedicated multistakeholder workshop where the top 10 RPQs were agreed by consensus. RESULTS: The process was completed over 24 months. The initial survey resulted in 467 questions from 165 respondents (73% HCPs and 27% patients/carers). These questions were reviewed and combined into 46 summary topics comprising: tendinopathy, distal biceps pathology, arthritis, stiffness, trauma, arthroplasty and cubital tunnel syndrome. The second (interim prioritisation) survey had 250 respondents (72% HCP and 28% patients/carers). The top 18 ranked questions from this survey were taken to the final workshop where a consensus was reached on the top 10 RPQs. CONCLUSIONS: The top 10 RPQs highlight areas of importance that currently lack sufficient evidence to guide diagnosis, treatment and rehabilitation of elbow conditions. This collaborative process will guide researchers and funders regarding the topics that should receive most future attention and benefit patients and HCPs.

Development and evaluation of time-resolved fluorescent immunochromatographic assay for quantitative detection of SARS-CoV-2 spike antigen.

BACKGROUND: The spread of COVID-19 worldwide caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has necessitated efficient, sensitive diagnostic methods to identify infected people. We report on the development of a rapid 15-minute time-resolved fluorescent (TRF) lateral flow immunochromatographic assay for the quantitative detection of the SARS-CoV-2 spike protein receptor-binding domain (S1-RBD). OBJECTIVES: Our objective was to develop an efficient method of detecting SARS-CoV-2 within 15 min of sample collection. METHODS: We constructed and evaluated a portable, disposable lateral flow device, which detected the S1-RBD protein directly in nasopharyngeal swab samples. The device emits a fluorescent signal in the presence of S1-RBD, which can be captured by an automated TRF instrument. RESULTS: The TRF lateral flow assay signal was linear from 0 to 20 ng/ml and demonstrated high accuracy and reproducibility. When evaluated with clinical nasopharyngeal swabs, the assay was performed at >80% sensitivity, >84% specificity, and > 82% accuracy for detection of the S1-RBD antigen. CONCLUSION: The new S1-RBD antigen test is a rapid (15 min), sensitive, and specific assay that requires minimal sample preparation. Critically, the assay correlated closely with PCR-based methodology in nasopharyngeal swab samples, showing that the detected S1-RBD antigen levels correlate with SARS-CoV-2 virus load. Therefore, the new TRF lateral flow test for S1-RBD has potential application in point-of-care settings.

Reducing Loneliness Among Aging Adults: The Roles of Personal Voice Assistants and Anthropomorphic Interactions.

The perception of feeling lonely is an influential factor in determining quality of life among aging adults. As the US Census Bureau projects that the number of Americans ages 65 and older will double by 2060, reducing loneliness is imperative. Personal voice assistants (PVAs) such as Amazon's Echo offer the ease-of-use of voice control with a friendly, helpful artificial intelligence. This study aimed to understand the influence of a PVA on loneliness reduction among adults of advanced ages, i.e., 75+, and explore anthropomorphism as a potential underlying mechanism. Participants (N = 16) ages 75 or older used an Amazon Echo PVA for 8 weeks in an independent living facility in the Midwest. Surveys were used to collect information about perceived loneliness, and PVA interaction data was recorded and analyzed. Participants consistently exceeded the required daily interactions. As hypothesized, after the first 4 weeks of the intervention, aging adults reported significantly lower loneliness (baseline mean = 2.22, SD = 0.42; week 4 mean = 1.99, SD = 0.45, Z = -2.45, and p = 0.01). Four dominant anthropomorphic themes emerged after thematic analysis of the entire 8 weeks' PVA interaction data (Cohen's Kappa = 0.92): (1) greetings (user-initiated, friendly phrases); (2) comments/questions (user-initiated, second-person pronoun), (3) polite interactions (user-initiated, direct-name friendly requests), (4) reaction (user response to Alexa). Relational greetings predicted loneliness reductions in the first 4 weeks and baseline loneliness predicted relational greetings with the PVA during the entire 8 weeks, suggesting that anthropomorphization of PVAs may play a role in mitigating loneliness in aging adults.

The spike-ACE2 binding assay: An in vitro platform for evaluating vaccination efficacy and for screening SARS-CoV-2 inhibitors and neutralizing antibodies.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 has become a worldwide pandemic, and there is a pressing need for the rapid development of novel therapeutic strategies. SARS-CoV-2 viral entry is mediated by interaction between the receptor binding domain (RBD) of the SARS-CoV-2 Spike protein and host cellular receptor, human angiotensin converting enzyme 2 (ACE2). The lack of a high throughput screening (HTS) platform for candidate drug screening means that no targeted COVID-19 treatments have been developed to date. To overcome this limitation, we developed a novel, rapid, simple, and HTS binding assay platform to screen potential inhibitors of the RBD-ACE2 complex. Three "neutralizing" mouse monoclonal antibodies capable of blocking the RBD-ACE2 interaction were identified using our binding assay and pseudovirus neutralization assay followed by further validation with the Focus Reduction Neutralization Test (FRNT), which analyzes the neutralization capacity of samples in the presence of live SARS-CoV-2. Furthermore, the consistency of our binding assay and FRNT results (R2 = 0.68) was demonstrated by patients' serum, of which were COVID-19 positive (n = 34) and COVID-19 negative (n = 76). Several small molecules selected for their potential to inhibit the Spike-ACE2 complex in silico were also confirmed with the binding assay. In addition, we have evaluated vaccine efficacy using binding assay platform and validated through pseudovirus neutralization assay. The correlation between binding assay & psuedovirus assay of the post vaccinated serum showed well correlated (R2 = 0.09) Moreover, our binding assay platform successfully validated different Spike RBD mutants. These results indicate that our binding assay can be used as a platform for in vitro screening of small molecules and monoclonal antibodies, and high-throughput assessment of antibody levels after vaccination. When conducting drug screening, computer virtual screening lacks actual basis, construction of pseudoviruses is relatively complicated, and even FRNT requires a P3 laboratory. There are few methods to determine the competitiveness of the target drug and SRBD or ACE2. Our binding assay can fill this gap and accelerate the process and efficiency of COVID-19 drug screening.