Microindentation of fresh soft biological tissue: A rapid tissue sectioning and mounting protocol.

Microindentation of fresh biological tissues is necessary for the creation of 3D biomimetic models that accurately represent the native extracellular matrix microenvironment. However, tissue must first be precisely sectioned into slices. Challenges exist in the preparation of fresh tissue slices, as they can tear easily and must be processed rapidly in order to mitigate tissue degradation. In this study, we propose an optimised mounting condition for microindentation and demonstrate that embedding tissue in a mixture of 2.5% agarose and 1.5% gelatin is the most favourable method of tissue slice mounting for microindentation. This protocol allows for rapid processing of fresh biological tissue and is applicable to a variety of tissue types.

A qualitative evidence synthesis (QES) exploring the barriers and facilitators to screening in emergency departments using the theoretical domains framework.

BACKGROUND: Validated screening tools can be utilised to detect early disease processes and risk factors for disease and adverse outcomes. Consequently, identifying individuals in need of early intervention and targeted assessment can be achieved through the implementation of screening in the ED. Successful implementation can be impacted by a lack of resources and ineffective integration of screening into the clinical workflow. Tailored implementation processes and staff training, which are contextually specific to the ED setting, are facilitators to effective implementation. This review will assist in the identification of barriers and facilitators to screening in the ED using a QES to underpin implementation processes. Healthcare workers engage in screening in the ED routinely. Consequently, this review focused on synthesizing the experience of healthcare workers (HCWs) who are involved in this process. This synthesis is informed by a QES protocol published by the lead author in 2021 (Barry et al., HRB Open Res 3:50, 2021). METHODOLOGY: A comprehensive literature search, inclusive of grey literature sources, was undertaken. Initially, an a priori framework of themes was formed to facilitate the interpretation and organisation of search results. A context specific conceptual model was then formulated using "Best fit" framework synthesis which further assisted in the interpretation of data that was extracted from relevant studies. Dual blind screening of search results was undertaken using RAYYAN as a platform. Thirty studies were identified that met the inclusion criteria. Dual appraisal of full text articles was undertaken using CASP, GRADE CERQual assessed confidence of findings and data extraction was performed by two reviewers collaboratively. FINDINGS: This is the first known synthesis of qualitative research on HCW's experiences of screening in the ED. Predominantly, the findings illustrate that staff experience screening in the ED as a complex challenging process. The barriers and facilitators identified can be broadly categorised under preconditions to screen, motivations to screen and knowledge and skills to screen. Competing interests in the ED, environmental stressors such as overcrowding and an organisational culture that resists screening were clear barriers. Adequate resources and tailored education to underpin the screening process were clear facilitators. TRIAL REGISTRATION: PROSPERO: CRD42020188712 05/07/20.

Clinical research stakeholders' experiences of clinical research during COVID-19: a qualitative study.

BACKGROUND: The COVID-19 pandemic created a complex high-risk clinical research environment with clinical research activities significantly impacted. Clinical research stakeholders adapted rapidly to new clinical practices; PPE, infection control policies, all while engaging with a more unwell patient demographic. The aim of this study is to explore the experiences of conducting clinical research during COVID-19 with clinical research stakeholders. METHODS: This qualitative study of semi-structured interviews conducted with clinical research stakeholders in an acute Hospital setting across a variety of disciplines; Consultant Geriatrician, Clinical Research Nurse, Occupational Therapy, Physiotherapy. Interviews were fully transcribed prior to reflexive thematic analysis. NVivo software was used to support data management and analysis. RESULTS: Three main themes were produced; (1) The challenging COVID-19 clinical research landscape, (2) COVID-19 clinical research communication barriers, and (3) Adaptations and learnings from clinical research during COVID-19. CONCLUSIONS: This study explored the experiences of conducting clinical research during COVID-19 with clinical research stakeholders examining challenges faced and adaptations required. The findings inform, equip and support clinical research stakeholders in the event of future adverse public health events.

On the association between circulating biomarkers and atherosclerotic calcification in a cohort of arterial disease participants.

BACKGROUND AND AIMS: Atherosclerotic calcification is a powerful predictor of cardiovascular disease. This study aims to determine whether circulating levels of a local/systemic calcification inhibitor or a marker of bone formation correlate with measures of coronary or extracoronary calcification. METHODS AND RESULTS: Clinical computed tomography (CT) was performed on 64 arterial disease participants undergoing carotid and lower extremity endarterectomy. Coronary artery calcium (CAC) scores and volumes were acquired from the CT scans (n = 42). CAC scores and volumes were used to derive CAC density scores. Micro-CT was performed on excised carotid (n = 36) and lower extremity (n = 31) plaques to quantify the volume and volume fraction of extracoronary calcification. Circulating levels of dephospho-uncarboxylated Matrix Gla Protein (dp-ucMGP), fetuin-A, carboxylated and uncarboxylated osteocalcin (ucOC) were quantified using commercial immunoassays. Carotid participant CAC density scores were moderately negatively correlated with plasma dp-ucMGP (rs = -0.592, P = 0.008). A weak negative association was found between CAC scores and %ucOC for all participants (rs = -0.335, P = 0.040). Another weak negative correlation was observed between fetuin-A and the volume of calcification within excised carotid specimens (rs = -0.366, P = 0.031). Despite substantial differences in coronary and extracoronary calcium measurements, the levels of circulating biomarkers did not vary significantly between carotid and lower extremity subgroups. CONCLUSION: Correlations identified between circulating biomarkers and measures of coronary and extracoronary calcium were not consistent among participant subgroups. Further research is required to determine the association between circulating biomarkers, coronary and extracoronary calcium.