Undifferentiated HepaRG cells show reduced sensitivity to the toxic effects of M8OI through a combination of CYP3A7-mediated oxidation and a reduced reliance on mitochondrial function

\ua9 2024 The AuthorsThe methylimidazolium ionic liquid M8OI (1-octyl-3-methylimidazolium chloride, also known as [C8mim]Cl) has been detected in the environment and may represent a hazard trigger for the autoimmune liver disease primary biliary cholangitis, based in part on studies using a rat liver progenitor cell. The effect of M8OI on an equivalent human liver progenitor (undifferentiated HepaRG cells; u-HepaRG) was therefore examined. u-HepaRG cells were less sensitive (>20-fold) to the toxic effects of M8OI. The relative insensitivity of u-HepaRG cells to M8OI was in part, associated with a detoxification by monooxygenation via CYP3A7 followed by further oxidation to a carboxylic acid. Expression of CYP3A7 - in contrast to the related adult hepatic CYP3A4 and CYP3A5 forms - was confirmed in u-HepaRG cells. However, blocking M8OI metabolism with ketoconazole only partly sensitized u-HepaRG cells. Despite similar proliferation rates, u-HepaRG cells consumed around 75% less oxygen than B-13 cells, reflective of reduced dependence on mitochondrial activity (Crabtree effect). Replacing glucose with galactose, resulted in an increase in u-HepaRG cell sensitivity to M8OI, near similar to that seen in B-13 cells. u-HepaRG cells therefore show reduced sensitivity to the toxic effects of M8OI through a combination of metabolic detoxification and their reduced reliance on mitochondrial function

Does a Mobile Phone Depression-Screening App Motivate Mobile Phone Users With High Depressive Symptoms to Seek a Health Care Professional’s Help?

The objective of disease screening is to encourage high-risk subjects to seek health care diagnosis and treatment. Mobile phone apps can effectively screen mental health conditions, including depression. However, it is not known how effective such screening methods are in motivating users to discuss the obtained results of such apps with health care professionals. Does a mobile phone depression-screening app motivate users with high depressive symptoms to seek health care professional advice? This study aimed to address this question.This was a single-cohort, prospective, observational study of a free mobile phone depression app developed in English and released on Apple’s App Store. Apple App Store users (aged 18 or above) in 5 countries, that is, Australia, Canada, New Zealand (NZ), the United Kingdom (UK), and the United States (US), were recruited directly via the app’s download page. The participants then completed the Patient Health Questionnaire (PHQ-9), and their depression screening score was displayed to them. If their score was 11 or above and they had never been diagnosed with depression before, they were advised to take their results to their health care professional. They were to follow up after 1 month.A group of 2538 participants from the 5 countries completed PHQ-9 depression screening with the app. Of them, 322 participants were found to have high depressive symptoms and had never been diagnosed with depression, and received advice to discuss their results with health care professionals. About 74% of those completed the follow-up; approximately 38% of these self-reported consulting their health care professionals about their depression score. Only positive attitude toward depression as a real disease was associated with increased follow-up response rate (odds ratio (OR) 3.2, CI 1.38-8.29).A mobile phone depression-screening app motivated some users to seek a depression diagnosis. However, further study should investigate how other app users use the screening results provided by such apps

Are there interindividual responses of cardiovascular disease risk markers to acute exercise? A replicated crossover study

Purpose: Using a replicated crossover design, we quantified the response heterogeneity of postprandial cardiovascular disease (CVD) risk marker responses to acute exercise. Methods: Twenty men (mean (SD) age, 26 (6) years; BMI, 23.9 (2.4) kg·m-2) completed four, 2-day conditions (two control, two exercise) in randomised orders. On days 1 and 2, participants rested and consumed two high-fat meals over 9-h. Participants ran for 60-mins (61 (7)% of peak oxygen uptake) on day 1 (6.5-7.5 h) of both exercise conditions. Time-averaged total-area-under-the-curve (TAUC) for triacylglycerol (TAG), glucose and insulin were calculated from 11 venous blood samples on day 2. Arterial stiffness and blood pressure responses were calculated from measurements at baseline on day 1 and at 2.5-h on day 2. Consistency of individual differences was explored by correlating the two replicates of control-adjusted exercise responses for each outcome. Within-participant covariate-adjusted linear mixed models quantified participant-by-condition interactions and individual-response SDs. Results: Acute exercise reduced mean TAUC-TAG (-0.27 mmol·L-1 h; Cohen’s d = 0.29, P = 0.017) and TAUC-insulin (-24.45 pmol·L-1 h; Cohen’s d = 0.35, P = 0.022) vs. control, but led to negligible changes in TAUC-glucose and the vascular outcomes (Cohen’s d ≤ 0.41, P ≥ 0.106). Small-to-moderate, but nonsignificant, correlations were observed between the two response replicates (r = -0.40 to 0.15, P ≥ 0.066). We did not detect any individual response heterogeneity. All participant-by-condition interactions were P ≥ 0.137, and all individual-response SDs were small with wide 95% confidence intervals overlapping zero. Conclusion: Large trial-to-trial within-subject variability inhibited detection of consistent inter-individual variability in postprandial metabolic and vascular responses to acute exercise

Managing High Frequency of Ambulance Calls in Hospitals: A Systematic Review

Abdullah Alruwaili,1– 4 Ahmed Alanazy,1– 3 Turki M Alanazi,1– 3 Nowaf Alobaidi,1– 3 Ahmad Saleh Almamary,1– 3 Bandar M Faqihi,1– 3 Fahad H Al Enazi,1– 3 Rayan Siraj,5 Yasir Almukhlifi,6,7 Ziyad F Al Nufaiei,6,7 Maher Alsulami6,7 1College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Al-Ahsa, Saudi Arabia; 2King Abdullah International Medical Research Center, Al-Ahsa, Saudi Arabia; 3Ministry of National Guard- Health Affairs, Al Ahsa, Saudi Arabia; 4School of Health: Faculty of Medicine and Health, University of New England, Armidale, New South Wales, Australia; 5Department of Respiratory Therapy, College of Applied Medical Sciences, King Faisal University, Al-Hasa, Saudi Arabia; 6College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Jeddah, Saudi Arabia; 7King Abdullah International Medical Research Center, Jeddah, Saudi ArabiaCorrespondence: Maher Alsulami, Department of Emergency Medical Services, College of Applied Medical Sciences-Jeddah, King Saud bin Abdulaziz University for Health Sciences, Mail Code 6610, P.O.Box.9515, Jeddah, 21423, Saudi Arabia, Tel +966501596230 Ext 46087, Email [email protected]: This study addresses the critical issue of high-volume emergency calls in hospitals, focusing on the strain caused by frequent caller patients on ambulance services. The aim was to synthesize various management methods for handling high-frequency hospital calls.Methods: The systematic review was conducted following the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines and guided by the Cochrane Handbook for systematic reviews. Inclusion criteria encompassed studies focusing on the management of emergency departments in hospitals, exploring various medical conditions requiring ambulance attention, and reporting on the impact of a high volume of ambulance calls on hospitals. Databases including PubMed, Web of Science, and Google Scholar were searched from January 1, 2005, to May 1, 2022. The quality of included studies was assessed using the Critical Appraisal Skills Programme (CASP) Checklist.Results: Out of 2390 identified citations, 18 studies met the inclusion criteria. These studies, from 12 countries, presented diverse methods categorized into country policy-based management, modeling approaches, and general strategies. Key findings included the effectiveness of risk stratification models and community-based interventions in managing high call frequencies and improving patient care. Our review identified effective strategies such as risk stratification models and community-based interventions, which have shown significant impacts in managing high call frequencies, aligning closely with our objective. These approaches have been pivotal in reducing the burden on emergency services and improving patient care.Conclusion: The study synthesizes effective management methods for high-frequency ambulance calls, including predictive modeling and community interventions. It highlights the need for multi-faceted management strategies in different healthcare settings and underscores the importance of continued research and implementation of these methods to improve emergency service efficiency.Keywords: systematic review, ambulance calls, emergency service

Exploring the Relationship Between Stress and Satisfaction During Clinical Training Among Respiratory Therapy Students: A Nationwide Cross-Sectional Survey

Rayan Siraj,1 Abdulelah M Aldhahir,2 Jaber S Alqahtani,3 Samah Bakhadlq,3 Saeed Alghamdi,4 Abdullah A Alqarni,5 Turki M Alanazi,6,7 Abdullah Alruwaili,6,7 Saleh S Algarni,8,9 Abdulrhman S Alghamd,10 Mushabbab Alahmari,11 Abdulmajeed Baogbah,12 Nawaf A Alsolami,13 Mufleh Alrougi,14 Kamal Hamed Al Khodidi,15 Fahad Alahmadi16 1Department of Respiratory Care, College of Applied Medical Sciences, King Faisal University, Al-Ahasa, 31982, Saudi Arabia; 2Respiratory Therapy Department, Faculty of Applied Medical Sciences, Jazan University, Jazan, 45142, Saudi Arabia; 3Department of Respiratory Care, Prince Sultan Military College of Health Sciences, Dammam, 34313, Saudi Arabia; 4Department of Clinical Technology, Respiratory Care Program, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia; 5Department of Respiratory Therapy, Faculty of Medical Rehabilitation Sciences, King Abdulaziz University, Jeddah, 22254, Saudi Arabia; 6College of Applied Medical Sciences, King Saud Bin Abdulaziz University for Health Sciences, Al Ahsa, 31982, Saudi Arabia; 7King Abdullah International Medical Research Center, Al Ahsa, 31982, Saudi Arabia; 8Department of Respiratory Therapy, College of Applied Medical Sciences, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 9King Abdullah International Medical Research Center, Riyadh, Saudi Arabia; 10Department of Rehabilitation Science, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia; 11Department of Respiratory Therapy, College of Applied Medical Sciences, University of Bisha, Bisha, Saudi Arabia; 12Department of Respiratory Therapy, Byrdine F. Lewis College of Nursing and Health Professions, Georgia State University, Atlanta GA, 30303, USA; 13Department of Respiratory Therapy, East Jeddah Hospital, Jeddah, Saudi Arabia; 14Department of Respiratory Care, King Abdulaziz Specialist Hospital, Taif, Saudi Arabia; 15Respiratory Therapy Unit, Children’s Hospital, Taif, Saudi Arabia; 16Respiratory Therapy Department, College of Medical Rehabilitation Sciences, Taibah University, Madinah, Saudi ArabiaCorrespondence: Rayan Siraj, Department of Respiratory Care, College of Applied Medical Sciences, King Faisal University, Al-Ahasa, 31982, Saudi Arabia, Email [email protected]: Although clinical training is an important component of healthcare education, it is nevertheless a significant source of stress for students. There is limited information on stress and satisfaction perceived by clinical-level undergraduate students studying respiratory therapy (RT) in Saudi Arabia.Methods: A descriptive, cross-sectional study design with an online questionnaire was employed to conduct this study. Data collection occurred during the academic year 2022– 2023 among RT students throughout Saudi Arabia. Patricians responded to demographic questions, the Students Stress Scale and Students Professional Satisfaction questionnaires. Descriptive, inferential, and correlational statistics were used to analyze the collected responses.Results: A total of 1001 undergraduate RT students completed the online survey. RT students and interns had an overall moderate to high stress level (mean (SD); 3.55 (0.49)), while satisfaction was perceived as mild to moderate (mean (SD): 2.56 (0.65)). In addition, 38% of the study participants have considered quitting the RT program. Female students showed higher stress levels in the following domains: inadequate knowledge and training, adverse and embarrassing experiences, clinical supervision, patients’ pain, and Education–reality conflict (p< 0.005) compared to male students. Additionally, students who considered quitting the RT program revealed higher stress levels in all domains (p< 0.005). There were negative correlations between satisfaction and stress domains: inadequate knowledge and training (r = − 0.32; p = 0.001), adverse and embarrassing experience (r = − 0.31; p = 0.025), close supervision (r = − 0.24; p = 0.001), insufficient hospital resources (r = − 0.30; p 0.002), patients’ pain and suffering (r = 0.28; p = 0.04), and education – reality conflict (r = − 0.30; p = 0.001).Conclusion: During clinical training, respiratory therapy students experience moderate to high-stress levels and low satisfaction. There need to be tailored interventions to reduce stress and intention to quit and increase students’ clinical experience satisfaction.Keywords: stress, satisfaction, clinical training, intention to qui

Exploring the acute effects of running on cerebral blood flow and food cue reactivity in healthy young men using functional magnetic resonance imaging

Acute exercise suppresses appetite and alters food-cue reactivity, but the extent exercise-induced changes in cerebral blood flow (CBF) influences the blood-oxygen-level-dependent (BOLD) signal during appetite-related paradigms is not known. This study examined the impact of acute running on visual food-cue reactivity and explored whether such responses are influenced by CBF variability. In a randomised crossover design, 23 men (mean ± SD: 24 ± 4 years, 22.9 ± 2.1 kg/m2) completed fMRI scans before and after 60 min of running (68% ± 3% peak oxygen uptake) or rest (control). Five-minute pseudo-continuous arterial spin labelling fMRI scans were conducted for CBF assessment before and at four consecutive repeat acquisitions after exercise/rest. BOLD-fMRI was acquired during a food-cue reactivity task before and 28 min after exercise/rest. Food-cue reactivity analysis was performed with and without CBF adjustment. Subjective appetite ratings were assessed before, during and after exercise/rest. Exercise CBF was higher in grey matter, the posterior insula and in the region of the amygdala/hippocampus, and lower in the medial orbitofrontal cortex and dorsal striatum than control (main effect trial p ≤.018). No time-by-trial interactions for CBF were identified (p ≥.087). Exercise induced moderate-to-large reductions in subjective appetite ratings (Cohen's d = 0.53–0.84; p ≤.024) and increased food-cue reactivity in the paracingulate gyrus, hippocampus, precuneous cortex, frontal pole and posterior cingulate gyrus. Accounting for CBF variability did not markedly alter detection of exercise-induced BOLD signal changes. Acute running evoked overall changes in CBF that were not time dependent and increased food-cue reactivity in regions implicated in attention, anticipation of reward, and episodic memory independent of CBF.</p