Organotypic sinonasal airway culture systems are predictive of the mucociliary phenotype produced by bronchial airway epithelial cells

Published online: 10 November 2022Differentiated air-liquid interface models are the current standard to assess the mucociliary phenotype using clinically-derived samples in a controlled environment. However, obtaining basal progenitor airway epithelial cells (AEC) from the lungs is invasive and resource-intensive. Hence, we applied a tissue engineering approach to generate organotypic sinonasal AEC (nAEC) epithelia to determine whether they are predictive of bronchial AEC (bAEC) models. Basal progenitor AEC were isolated from healthy participants using a cytological brushing method and differentiated into epithelia on transwells until the mucociliary phenotype was observed. Tissue architecture was assessed using H&E and alcian blue/Verhoeff-Van Gieson staining, immunofluorescence (for cilia via acetylated α-tubulin labelling) and scanning electron microscopy. Differentiation and the formation of tight-junctions were monitored over the culture period (day 1-32) by quantifying trans-epithelial electrical resistance. End point (day 32) tight junction protein expression was assessed using Western blot analysis of ZO-1, Occludin-1 and Claudin-1. Reverse transcription qPCR-array was used to assess immunomodulatory and autophagy-specific transcript profiles. All outcome measures were assessed using R-statistical software. Mucociliary architecture was comparable for nAEC and bAEC-derived cultures, e.g. cell density P = 0.55, epithelial height P = 0.88 and cilia abundance P = 0.41. Trans-epithelial electrical resistance measures were distinct from day 1-14, converged over days 16-32, and were statistically similar over the entire culture period (global P  0.05). Transcript analysis for inflammatory markers demonstrated significant variation between nAEC and bAEC epithelial cultures, and favoured increased abundance in the nAEC model (e.g. TGFβ and IL-1β; P < 0.05). Conversely, the abundance of autophagy-related transcripts were comparable and the range of outcome measures for either model exhibited a considerably more confined uncertainty distribution than those observed for the inflammatory markers. Organotypic air-liquid interface models of nAEC are predictive of outcomes related to barrier function, mucociliary architecture and autophagy gene activity in corresponding bAEC models. However, inflammatory markers exhibited wide variation which may be explained by the sentinel immunological surveillance role of the sinonasal epithelium.Juliette Delhove, Moayed Alawami, Matthew Macowan, Susan E. Lester, Phan T. Nguyen, Hubertus P. A. Jersmann, Paul N. Reynolds and Eugene Rosciol

Global overview of the management of acute cholecystitis during the COVID-19 pandemic (CHOLECOVID study)

Background: This study provides a global overview of the management of patients with acute cholecystitis during the initial phase of the COVID-19 pandemic. Methods: CHOLECOVID is an international, multicentre, observational comparative study of patients admitted to hospital with acute cholecystitis during the COVID-19 pandemic. Data on management were collected for a 2-month study interval coincident with the WHO declaration of the SARS-CoV-2 pandemic and compared with an equivalent pre-pandemic time interval. Mediation analysis examined the influence of SARS-COV-2 infection on 30-day mortality. Results: This study collected data on 9783 patients with acute cholecystitis admitted to 247 hospitals across the world. The pandemic was associated with reduced availability of surgical workforce and operating facilities globally, a significant shift to worse severity of disease, and increased use of conservative management. There was a reduction (both absolute and proportionate) in the number of patients undergoing cholecystectomy from 3095 patients (56.2 per cent) pre-pandemic to 1998 patients (46.2 per cent) during the pandemic but there was no difference in 30-day all-cause mortality after cholecystectomy comparing the pre-pandemic interval with the pandemic (13 patients (0.4 per cent) pre-pandemic to 13 patients (0.6 per cent) pandemic; P = 0.355). In mediation analysis, an admission with acute cholecystitis during the pandemic was associated with a non-significant increased risk of death (OR 1.29, 95 per cent c.i. 0.93 to 1.79, P = 0.121). Conclusion: CHOLECOVID provides a unique overview of the treatment of patients with cholecystitis across the globe during the first months of the SARS-CoV-2 pandemic. The study highlights the need for system resilience in retention of elective surgical activity. Cholecystectomy was associated with a low risk of mortality and deferral of treatment results in an increase in avoidable morbidity that represents the non-COVID cost of this pandemic

Variation in postoperative outcomes of patients with intracranial tumors: insights from a prospective international cohort study during the COVID-19 pandemic

Background: This study assessed the international variation in surgical neuro-oncology practice and 30-day outcomes of patients who had surgery for an intracranial tumor during the COVID-19 pandemic. Methods: We prospectively included adults aged ≥18 years who underwent surgery for a malignant or benign intracranial tumor across 55 international hospitals from 26 countries. Each participating hospital recorded cases for 3 consecutive months from the start of the pandemic. We categorized patients’ location by World Bank income groups (high [HIC], upper-middle [UMIC], and low- and lower-middle [LLMIC]). Main outcomes were a change from routine management, SARS-CoV-2 infection, and 30-day mortality. We used a Bayesian multilevel logistic regression stratified by hospitals and adjusted for key confounders to estimate the association between income groups and mortality. Results: Among 1016 patients, the number of patients in each income group was 765 (75.3%) in HIC, 142 (14.0%) in UMIC, and 109 (10.7%) in LLMIC. The management of 200 (19.8%) patients changed from usual care, most commonly delayed surgery. Within 30 days after surgery, 14 (1.4%) patients had a COVID-19 diagnosis and 39 (3.8%) patients died. In the multivariable model, LLMIC was associated with increased mortality (odds ratio 2.83, 95% credible interval 1.37–5.74) compared to HIC. Conclusions: The first wave of the pandemic had a significant impact on surgical decision-making. While the incidence of SARS-CoV-2 infection within 30 days after surgery was low, there was a disparity in mortality between countries and this warrants further examination to identify any modifiable factors

The Relationship Between Acculturation, Racial Discrimination, Test Anxiety, and Neuropsychological Test Performance among a Racialised Minority Sample in the UK.

Objective: It has been suggested that variables such as education, culture and acculturation, and psychosocial factors such as racism and test anxiety could be associated with test performance among racialised minorities. Therefore, this study aimed to investigate the relationship between acculturation, racial discrimination, test anxiety, and neuropsychological test scores in a UK sample of racialised minorities. Method: A total of 57 racialised minority individuals residing in the UK were recruited online. Participants completed online questionnaires and a battery of neuropsychological tasks. Acculturation, test anxiety, and racial discrimination served as predictor variables, while neuropsychological test scores were the outcome variables. Regression analysis was used to examine the associations between the predictor variables and test scores. Results: Regression analysis indicated that most predictors were not significant across analyses. However, acculturation showed a significant negative association with working memory performance (Digit span backward). Racial discrimination predicted poorer executive function performance (Trail-making-test B), while test anxiety was associated with fewer errors on a processing speed task (Trail-making-test A). Conclusion: The study's findings highlight the importance of considering cultural and psychosocial variables in neuropsychological assessments with racialised minorities. Clinicians should be mindful of the relationship of these variables with test performance to ensure culturally sensitive evaluations. However, the findings are limited by the small sample size, lack of racial/ethnic diversity, and the relatively high education and young age of participants. Further research with larger and more diverse samples is needed to enhance our understanding of these associations with neuropsychology test performance

DNA Carrier-Assisted Molecular Ping-Pong in an Asymmetric Nanopore.

Publication status: PublishedNanopore analysis relies on ensemble averaging of translocation signals obtained from numerous molecules, requiring a relatively high sample concentration and a long turnaround time from the sample to results. The recapture and subsequent re-reading of the same molecule is a promising alternative that enriches the signal information from a single molecule. Here, we describe how an asymmetric nanopore improves molecular ping-pong by promoting the recapture of the molecule in the trans reservoir. We also demonstrate that the molecular recapture could be improved by linking the target molecule to a long DNA carrier to reduce the diffusion, thereby achieving over 100 recapture events. Using this ping-pong methodology, we demonstrate its use in accurately resolving nanostructure motifs along a DNA scaffold through repeated detection. Our method offers novel insights into the control of DNA polymer dynamics within nanopore confinement and opens avenues for the development of a high-fidelity DNA detection platform

EEFECTS OF DIETARY FLAVONOIDS INTAKE IN SAUDI PATIENTS WITH CORONARY HEART DISEASE.

Objectives: The aim of the study was to assess the dietary intake of flavonoids and their effect on serum lipid levels in Saudi patients with coronary heart disease (CHD). Methodology: A cross-sectional study with a sample of 50 CHD patients and 50 controls. A 24-hour recall method was used to collect data on the dietary intake of macronutrients, flavonoids, and antioxidant vitamins. A food frequency questionnaire (FFQ) was used to collect data on habitual consumption during the year preceding the interview. Baseline data collection included medical history, anthropometric measurements, physical activity, and smoking status. Results: CHD patients showed significantly less intake of fruits and vegetables compared to the controls. Serum lipids including total cholesterol (TC), triglycerides (TG), and low density lipoproteins (LDL) were found to be significantly higher in CHD patients than in the controls. The main sources of flavonoids in a typical Saudi diet are tea, fruits (apples), vegetables (onions), and chocolate. The intake of flavonoids and antioxidant vitamins was significantly lower in CHD patients compared to the controls. A negative correlation between the dietary intake of different flavonoids and serum LDL was observed in CHD patients. Significant correlation was found between the intake of flavonol and waist to hip ratio Conclusions: The findings of the study support a potential protective effect of dietary flavonoids in relation to CHD. The study showed that consuming more Flavonoids may have positive effect on lowering blood lipids.King saud universit

Associations between polypharmacy and potentially inappropriate medications with risk of falls among the elderly in Saudi Arabia

Abstract Background Falls are dangerous to the health of older adults and can impact their functional status leading to frailty. The use of potentially inappropriate medications (PIMs) among older adults may lead to adverse health outcomes and increase the risk of falls. Polypharmacy increases the incidence of falls. Beers criteria by the American Geriatric Society is one of the many criteria used to detect PIMs. It assesses the appropriateness of drug prescriptions (i.e., correct dose, duration, and indications) to ensure the safety of these drugs, reducing drug interactions and decreasing the hazards of side effects. This epidemiological study aims to explore the association between polypharmacy and Beers criteria with the risk of falls in the elderly. Method A total of 387 outpatients aged 60 or older were interviewed in person. The patients were recruited from the University Hospital and the Family and Community Medicine Center in Khobar city, Saudi Arabia, between the period of November 2021 to March 2022. All patients were able to walk independently. The survey began by collecting patients’ demographics, gathering medication history, and asking three key questions to detect the risk of falls which was developed by the Center of Disease Control (CDC). Polypharmacy (defined as concurrent use of five or more medications) and PIMs (defined as use of one or more medications in the Beers list) were examined against risk of falls in the elderly. Multiple logistic regression analyses were used to estimate adjusted Odds Ratios (ORs). Result A total of 387 patients participated in the study; 62% were male, and most participants belonged to the 60 < 65 years age category (47.80%). Among all patients, 55% had a high risk of falling, and 21% of patients had fell during the past year. Polypharmacy applied to 50.90% of all patients, while Beers criteria positive group applied to 51.42%. Risk of falls and prior falls were associated with polypharmacy both before and after adjustment. Conclusion The results showed a significant association between risk of falls with polypharmacy and PIMs, and more than half of our study population had a high risk of falls. Of those at a higher risk, one out of five had indeed experienced a fall in the last 12 months. Higher rates of falls were associated with older aged patients, lower educational levels, female gender, and cardiovascular medications