Including 'seldom heard' views in research: opportunities, challenges and recommendations from focus groups with British South Asian people with type 2 diabetes.

BACKGROUND: The inclusion of 'seldom heard' groups in health and social care research is increasingly seen as important on scientific, policy and ethical grounds. British South Asians, the largest minority ethnic group in the United Kingdom (UK), are under-represented in health research yet over-represented in the incidence of certain conditions such as type 2 diabetes. With the growing requirement of patient involvement in research and the inclusion of diverse populations, methodological guidance on how to include, engage and conduct research with UK South Asian populations is essential if services and interventions are to be relevant and impactful. However, such guidance for researchers is limited. METHODS: The aim of the paper is to reflect on our experiences of conducting focus groups with UK South Asian communities with type 2 diabetes, which involved experienced community partners and researchers working closely together. We discuss the factors that aided the successful delivery of the project, the challenges that we encountered, how we dealt with these, and recommendations. RESULTS: Our study suggests ways to involve and conduct focus groups with UK South Asian populations. Key considerations are categorised under four headings: co-working with community partners; linguistic competency; cultural competency and awareness; and reflexivity, power and acknowledgement. Having an experienced team of researchers and community experts - with the relevant linguistic and cultural competencies and different kinds of knowledge and skills - was key to the successful delivery of the study. Working collaboratively enabled us to recruit a diverse sample, to navigate the challenges of recruitment, to be present at every discussion which helped contribute to data richness, and to reflect on our own roles in the research process. CONCLUSIONS: Focus groups with UK South Asian communities can be a useful way of exploring new topics and involving seldom heard views. While a useful method, focus groups are only one way of exploring a research topic and provide an insight into context-specific attitudes and views. Future research should explore British South Asian participants' views on how they would like to be involved in research, including new methods of collecting data and coproducing research.

Role of Antiplatelet Therapy in Patients with Severe Coronary Artery Disease Undergoing Coronary Artery Endarterectomy within Coronary Artery Bypass Surgery.

Background-Coronary endarterectomy (CEA) has been introduced to allow revascularization in end-stage coronary artery disease (CAD). After CEA, the injured remnants of the vessel's media could result in fast neo intimal tissue ingrowth, which require an anti-proliferation agent (antiplatelet therapy (APT). We aimed to review outcomes of patients undergoing CEA within bypass surgery who received either single-APT (SAPT) or dual-APT (DAPT). Methods-We retrospectively evaluated 353 consecutive patients undergoing CEA within isolated coronary artery bypass grafting (CABG) in the period 01/2000-07/2019. After surgery, patients received either SAPT (n = 153), or DAPT (n = 200) for six months then lifelong SAPT. Endpoints included early, late survival, and freedom from major-adverse-cardiac and cerebrovascular events (MACCE), which were defined as incidence of stroke, myocardial infarction, need for coronary intervention (PCI or CABG) or death for any cause. Results-Patients' mean age was 67 ± 9.3 years; they were predominantly male 88.1%. Both DAPT- and SAPT-groups had the same extent of CAD (mean SYNTAX-Score-II: 34.1 ± 11.6 vs. 34.4 ± 17.2, p = 0.91). Postoperatively, no difference between DAPT- and SAPT-groups was reported in the incidence of low-cardiac-output syndrome (5% vs. 9.8%, p = 0.16), revision for bleeding (5% vs. 6.5% p = 0.64), 30-day mortality (4.5% vs. 5.2%, p = 0.8) or MACCE (7.5% vs. 11.8%, p = 0.19). Imaging follow-up reported significantly higher CEA and total grafts patency (90% vs. 81.5% and 95% vs. 81%, p = 0.017) in DAPT patients. Late outcomes within 97.4 ± 67.4 months show lower incidence of overall mortality (19 vs. 51%, p < 0.001) and MACCE (24.5 vs. 58.2%, p < 0.001) in the DAPT patients when compared with SAPT patients. Conclusions-Coronary endarterectomy allows revascularization in end-stage CAD when the myocardium is still viable. The use of dual APT after CEA for at least six months seems to improve mid-to-long-term patency rates and survival, and reduced the incidence of major adverse cardiac and cerebrovascular events.

Molecular detection of plasmid-derived AmpC ß-lactamase among clinical strains of Enterobacteriaceae in Bahrain.

BACKGROUND: Enterobacteriaceae with AmpC ß-lactamase are multidrug-resistant organisms and represent a significant challenge to patient care. This study aims to determine the prevalence of plasmid-derived AmpC ß-lactamase among extended spectrum ß-lactamases (ESBL)-producing Enterobacteriaceae strains in Bahrain. METHODS: It was a cross-sectional study. A total of 185 ESBL-producing Enterobacteriaceae isolates were recovered from clinically significant specimens from January 2018 to December 2019. The samples underwent initial screen for cefoxitin resistance by disc diffusion test and subsequent phenotypic confirmation of AmpC production with phenyl boronic acid assays as well as genotypic analysis by multiplex polymerase chain reactions for AmpC subtypes. Drug-resistant features of these clinical isolates were also examined. RESULTS: Twenty-nine ESBL-producing Enterobacteriaceae isolates were cefoxitin resistant. Phenotypic and genotypic analyses confirmed that 8 and 12 cefoxitin-resistant isolates are AmpC positive, respectively. These AmpC producers are multidrug resistant, and Escherichia coli is the dominant strain among them. CONCLUSIONS: Plasmid-mediated spread of AmpC is present in clinically relevant Enterobacteriaceae species in Bahrain. Rational antimicrobial therapy against these multidrug-resistant organisms and continued surveillance of antimicrobial resistance mechanisms among the clinical isolates are recommended for optimal patient care.

Effect of meloxicam (cyclooygenase-2 inhibitor) versus vitamin D3 (cholecalciferol) as ameliorating agents of progressive doxorubicin-induced nephrotoxicity in rats / 대한해부학회지

Doxorubicin (DOX)-induced nephropathy hampered its antineoplastic efficiency. The objective of the current work is to assess the prospective ameliorating effects of meloxicam versus vitamin D3 (Vit D3, cholecalciferol) against progressive DOX-induced nephropathy in rats trying to ascertain the possible mechanism underlying such amelioration. Ninety Male Wistar rats were randomly distributed to five experimental groups for 3 weeks, with saline, meloxicam (daily), DOX (single dose), Vit D3+DOX, or both meloxicam and DOX. We measured levels of urinary protein, serum creatinine, malondialdehyde (MDA) and renal reduced glutathione (GSH). In addition, tumor necrosis factor-alpha (TNF-α) expression and renal histopathology were assessed. Meloxicam alone treated group revealed no significant difference in urinary protein and serum creatinine. It also presented non-significant reduction in the MDA content while an increase in the reduced GSH content in contrast to the control group, which is more evident after the first week. Renal sections of rats received meloxicam only showed no significant histological changes and negative immunoreactivity compared to the control group. DOX induced a significant increase in urinary protein, serum creatinine, decrease reduced GSH, increased renal MDA and disrupted renal morphometric parameters and histology with increased TNF-α expression. Combination groups of Vit D3+DOX and meloxicam+DOX showed improvement of all DOX disturbed parameters. Meloxicam showed better results most likely due to anti-inflammatory and antioxidant activities superimposing the immune-modulatory effect of Vit D3. So, it is recommended to use meloxicam in patients receiving DOX as a renoprotective agent in addition to its analgesic effects required by cancer patients.

Effect of meloxicam (cyclooygenase-2 inhibitor) versus vitamin D3 (cholecalciferol) as ameliorating agents of progressive doxorubicin-induced nephrotoxicity in rats / 대한해부학회지

Doxorubicin (DOX)-induced nephropathy hampered its antineoplastic efficiency. The objective of the current work is to assess the prospective ameliorating effects of meloxicam versus vitamin D3 (Vit D3, cholecalciferol) against progressive DOX-induced nephropathy in rats trying to ascertain the possible mechanism underlying such amelioration. Ninety Male Wistar rats were randomly distributed to five experimental groups for 3 weeks, with saline, meloxicam (daily), DOX (single dose), Vit D3+DOX, or both meloxicam and DOX. We measured levels of urinary protein, serum creatinine, malondialdehyde (MDA) and renal reduced glutathione (GSH). In addition, tumor necrosis factor-alpha (TNF-α) expression and renal histopathology were assessed. Meloxicam alone treated group revealed no significant difference in urinary protein and serum creatinine. It also presented non-significant reduction in the MDA content while an increase in the reduced GSH content in contrast to the control group, which is more evident after the first week. Renal sections of rats received meloxicam only showed no significant histological changes and negative immunoreactivity compared to the control group. DOX induced a significant increase in urinary protein, serum creatinine, decrease reduced GSH, increased renal MDA and disrupted renal morphometric parameters and histology with increased TNF-α expression. Combination groups of Vit D3+DOX and meloxicam+DOX showed improvement of all DOX disturbed parameters. Meloxicam showed better results most likely due to anti-inflammatory and antioxidant activities superimposing the immune-modulatory effect of Vit D3. So, it is recommended to use meloxicam in patients receiving DOX as a renoprotective agent in addition to its analgesic effects required by cancer patients.

The temperature-dependent conformational ensemble of SARS-CoV-2 main protease (Mpro)

The COVID-19 pandemic, instigated by the SARS-CoV-2 coronavirus, continues to plague the globe. The SARS-CoV-2 main protease, or Mpro, is a promising target for development of novel antiviral therapeutics. Previous X-ray crystal structures of Mpro were obtained at cryogenic temperature or room temperature only. Here we report a series of high-resolution crystal structures of unliganded Mpro across multiple temperatures from cryogenic to physiological, and another at high humidity. We interrogate these datasets with parsimonious multiconformer models, multi-copy ensemble models, and isomorphous difference density maps. Our analysis reveals a temperature-dependent conformational landscape for Mpro, including mobile solvent interleaved between the catalytic dyad, mercurial conformational heterogeneity in a key substrate-binding loop, and a far-reaching intramolecular network bridging the active site and dimer interface. Our results may inspire new strategies for antiviral drug development to counter-punch COVID-19 and combat future coronavirus pandemics. SynopsisX-ray crystallography at variable temperature for SARS-CoV-2 Mpro reveals a complex conformational landscape, including mobile solvent at the catalytic dyad, mercurial conformational heterogeneity in a key substrate-binding loop, and an intramolecular network bridging the active site and dimer interface.