Expression and function of calcium-activated potassium channels following in-stent restenosis in a porcine coronary artery model

AbstractIn-stent restenosis (ISR) occurs due to proliferation and migration of smooth muscle cells from media to intima resulting in re-narrowing of the vessel lumen. This study aims to investigate changes in the three main KCa channels in response to stent implantation in porcine coronary arteries as their expression and function in ISR is yet to be defined. Twenty-eight days after stent implantation, immunofluorescent labelling with anti-desmin and anti-vWF confirm the presence of both endothelial and smooth muscle cells within the neointimal layer. Using real-time PCR, significant increase in the SK3 and IKCa and BKCa channel mRNA was observed within this layer alone. Western blot analysis confirms the expression of KCa channels in neointima. Although expression of BKCa was increased in the neointima in comparison with medial region of the artery, microelectrode recordings showed that the function of this channel was unchanged. However, the presence of functional BKCa in both medial and intimal cells suggests that smooth muscle cells migration may contribute to neointimal hyperplasia.Functional analysis using 1-EBIO and Bradykinin produced hyperpolarization of neointimal but not medial myocytes, which indicated the expression of functional endothelial SK3 and IKCa in the former and not in the latter. The expression of IKCa and SK3 within the neointimal layer suggested that some degree of recovery of both endothelial as well as smooth muscle regeneration had occurred. Future development of selective modulators of IKCa and SK3 channels may decrease the progression of ISR and improve coronary vascular function after stent placement, and is an area for future investigation

Resilient health care: a systematic review of conceptualisations, study methods and factors that develop resilience

Background Traditional approaches to safety management in health care have focused primarily on counting errors and understanding how things go wrong. Resilient Health Care (RHC) provides an alternative complementary perspective of learning from incidents and understanding how, most of the time, work is safe. The aim of this review was to identify how RHC is conceptualised, described and interpreted in the published literature, to describe the methods used to study RHC, and to identify factors that develop RHC. Methods Electronic searches of PubMed, Scopus and Cochrane databases were performed to identify relevant peer-reviewed studies, and a hand search undertaken for studies published in books that explained how RHC as a concept has been interpreted, what methods have been used to study it, and what factors have been important to its development. Studies were evaluated independently by two researchers. Data was synthesised using a thematic approach. Results Thirty-six studies were included; they shared similar descriptions of RHC which was the ability to adjust its functioning prior to, during, or following events and thereby sustain required operations under both expected and unexpected conditions. Qualitative methods were mainly used to study RHC. Two types of data sources have been used: direct (e.g. focus groups and surveys) and indirect (e.g. observations and simulations) data sources. Most of the tools for studying RHC were developed based on predefined resilient constructs and have been categorised into three categories: performance variability and Work As Done, cornerstone capabilities for resilience, and integration with other safety management paradigms. Tools for studying RHC currently exist but have yet to be fully implemented. Effective team relationships, trade-offs and health care ‘resilience’ training of health care professionals were factors used to develop RHC. Conclusions Although there was consistency in the conceptualisation of RHC, methods used to study and the factors used to develop it, several questions remain to be answered before a gold standard strategy for studying RHC can confidently be identified. These include operationalising RHC assessment methods in multi-level and diverse settings and developing, testing and evaluating interventions to address the wider safety implications of RHC amidst organisational and institutional change

Seeking consultation for urinary incontinence:Behaviours and barriers among Jordanian women

INTRODUCTION: The rates of seeking consultation for urinary incontinence (UI) and the barriers against consultations vary among countries and study populations and are influenced by various factors such as embarrassment, perception of illness, resources and culture.OBJECTIVES: To study healthcare-seeking behaviours and barriers among Jordanian women.METHODS: Between 1 March 2020 and 15 April 2020, we conducted a cross-sectional online survey among women 18 years of age or more who have UI and have access to the internet. We collected women's characteristics, UI types, severity, bother, seeking consultation behaviours and barriers. Logistic regression analyses were used to study the variables associated with seeking consultation.RESULTS: The data of 1454 women with a mean age (SD) of 41.5 (11.5) years were analysed. Mixed UI was the most common type (56.3%), while 43.8% of the participants sought consultation, and 33.8% waited 1 year before seeking consultation. The most common barriers were embarrassment (52.2%), considering UI as a normal occurrence with ageing (41.5%), and limited expectations of improvement from treatment (42.0%). The most common barriers vary according to UI type. Embarrassment was the most commonly reported barrier by women with mixed UI (29.4%), UI as normal with ageing was mostly considered by women with stress UI (11.5%) and treatment for UI is going to be expensive was expressed by women with mixed UI (19.4%). Seeking consultation decreased among women with more educational achievement (adjusted odds ratio [aOR]: 0.62; 95% confidence interval [CI]: 0.44-0.87) with university graduates doing so less than women with high school or less educational achievement. Additionally, seeking consultation was more among women who were aware of a family member with UI (aOR: 1.44; 95% CI: 1.03-2.01) compared to women who were not. Also, multiparous women (aOR: 1.8; 95% CI: 1.19-2.77) sought consultation more than nulliparous women. Seeking a consultation was more among women who were bothered by the impact of UI on various daily activities, namely, household activities (aOR: 1.42; 95% CI: 0.85-2.37), prayers (aOR: 1.7; 95% CI: 1.07-2.71) and sex life (aOR: 2.48; 95% CI: 1.45-4.21) compared to women who were not bothered. Seeking a consultation was less among women who reported embarrassment as a barrier (aOR: 0.534; 95% CI: 0.34-0.84) compared to women who were not embarrassed.CONCLUSION: Four in 10 women with UI sought care, but with a considerable delay between the onset of symptoms and actual care seeking. These outcomes could be explained by the impact of various barriers. Additionally, barriers might vary in different cultures and countries, so culture-sensitive questionnaires should be considered when healthcare-seeking consultations and barriers are studied.</p

Analysis and Prediction of Patient Survival After Radiotherapy For Liver Cancer Based On Volumetric Segmental Response and Clinically Relevant Factors

https://openworks.mdanderson.org/sumexp23/1121/thumbnail.jp

Applications of coxsackievirus A21 in oncology

The clinical management of cancer continues to be dominated by macroscopic surgical resection, radiotherapy, and cytotoxic drugs. The major challenge facing oncology is to achieve more selective, less toxic and effective methods of targeting disseminated tumors, a challenge oncolytic virotherapy may be well-placed to meet. Characterization of coxsackievirus A21 (CVA21) receptor-based mechanism of virus internalization and lysis in the last decade has suggested promise for CVA21 as a virotherapy against malignancies which overexpress those receptors. Preclinical studies have demonstrated proof of principle, and with the results of early clinical trials awaited, CVA21 may be one of the few viruses to demonstrate benefit for patients. This review outlines the potential of CVA21 as an oncolytic agent, describing the therapeutic development of CVA21 in preclinical studies and early stage clinical trials. Preclinical evidence supports the potential use of CVA21 across a range of malignancies. Malignant melanoma is the most intensively studied cancer, and may represent a “test case” for future development of the virus. Although there are theoretical barriers to the clinical utility of oncolytic viruses like CVA21, whether these will block the efficacy of the virus in clinical practice remains to be established, and is a question which can only be answered by appropriate trials. As these data become available, the rapid journey of CVA21 from animal studies to clinical trials may offer a model for the translation of other oncolytic virotherapies from laboratory to clinic