Study of the effects of dietary polyunsaturated fatty acids: Molecular mechanisms involved in intestinal inflammation

The use of “omics” techniques in combination with model systems and molecular tools allows to understand how foods and food components act on metabolic pathways to regulate transcriptional processes. Polyunsaturated fatty acids have distinctive nutritional and metabolic effects because they give rise to lipid mediated products and affect the expression of various genes involved in intestinal inflammation. The present review focuses on the molecular effects of dietary polyunsaturated fatty acids on intestinal inflammatio

Undergraduate student led clinical skills events

Background: Undergraduate medical students frequently face limited opportunities to practice clinical skills and integrate these into patient encounters. They actively seek out practice opportunities for skills they perceive as integral to the practice of medicine. The current landscape of restricted patient access due to COVID 19, increasing competition for clinical placements with other health professional students, sicker patients and shorter inpatient stays all result in students looking for alternatives to improve their knowledge and skills. James Cook University (JCU) student associations and special interest groups offer student support and external opportunities for skills practice through guest speaker nights and student led clinical skills events. Summary of work: Development of these student skills events over the past 8+ years initially focused on providing practical skills exposure such as suturing using synthetic substitutes and urinary catheterisation using simulation trainers. With encouragement and academic staff expertise, these events have introduced high fidelity simulation in the form of case-based scenarios. These vary from simple ED management of chest pain through to paediatric near drowning scenarios. To support these events, a structured planning process incorporating regular meetings between academic, technical and student group representatives, staged completion of online documentation and full risk assessments is done. Formalising this process and integrating with student and university requirements fosters safe events, and just as importantly, mentors those student leaders with an interest in education. Summary of results: Students surveyed about their priorities for learning consistently score ‘increased opportunities for clinical skills practice’, and ‘participation in case-based simulation scenarios’ very highly in their feedback. Following a JCU Surgical Society event, (with staff supported practice sessions) JCU students earned third place in a state-wide competition involving theory, laparoscopic and suturing skill stations. Due to the multidisciplinary nature of some student interest groups, simulation scenarios have encouraged inter-professional interactions in an authentic, safe, and supported environment. This has helped students develop an understanding of different health professional roles without ‘real world’ stressors. Over the timeframe described, the number and variety of student led events has risen from 3 – 4 annually, to ten events in 2019. With the restrictions of COVID, that number is slowly returning with students very focussed on recouping some of the lost opportunities in clinical skills. Indicating their wish to be included in simulated patient focused, hybrid and high-fidelity simulation activities

Mechanisms of active laryngeal closure during non-invasive intermittent positive pressure ventilation in non-sedated lambs

The present study stems from our recent demonstration (Moreau-Bussiere F, Samson N, St-Hilaire M, Reix P, Lafond JR, Nsegbe E, Praud JP. J Appl Physiol 102: 2149-2157, 2007) that a progressive increase in nasal intermittent positive pressure ventilation (nIPPV) leads to active glottal closure in nonsedated, newborn lambs. The aim of the study was to determine whether the mechanisms involved in this glottal narrowing during nIPPV originate from upper airway receptors and/or from bronchopulmonary receptors. Two groups of newborn lambs were chronically instrumented for polysomnographic recording: the first group of five lambs underwent a two-step bilateral thoracic vagotomy using video-assisted thoracoscopic surgery (bilateral vagotomy group), while the second group, composed of six lambs, underwent chronic laryngotracheal separation (isolated upper airway group). A few days later, polysomnographic recordings were performed to assess glottal muscle electromyography during step increases in nIPPV (volume control mode). Results show that active glottal narrowing does not develop when nIPPV is applied on the upper airways only, and that this narrowing is prevented by bilateral vagotomy when nIPPV is applied on intact airways. In conclusion, active glottal narrowing in response to increasing nIPPV originates from bronchopulmonary receptors

Origins of the inhibiting effects of nasal CPAP on non-nutritive swallowing in newborn lambs

The present study was aimed at investigating the principal reflex mechanism by which non-nutritive swallowing (NNS) is inhibited by application of a nasal CPAP 6 cm H2O during quiet sleep (QS) in newborn lambs. Eighteen full-term lambs were chronically instrumented and evenly distributed into 3 separate groups to sort out whether reflex activity originates from the upper or lower airway receptors. Six lambs were tracheotomized, six other lambs underwent a 2-step bilateral intrathoracic vagotomy while the remaining 6 lambs underwent chronic laryngo-tracheal separation (isolated upper airway group). Forty-eight hours after surgery, each nonsedated lamb underwent polysomnographic recordings on 3 consecutive days. States of alertness, NNS and respiratory movements were recorded. Results demonstrate that a CPAP of 6 cm H2O inhibited NNS during QS while administered directly on the lower airways. This NNS inhibition was prevented by eliminating the vagal afferent messages originating from the bronchopulmonary receptors. However, application of CPAP on the upper airways only also inhibited NNS during QS. Finally, the application of a CPAP 6 cm H2O had no systematic effect on NNS-breathing coordination. In conclusion, our results suggest that the inhibiting effect of nasal CPAP 6 cm H2O on NNS is mainly mediated by bronchopulmonary receptors with some participation however of upper airway receptors. Our demonstration that spontaneous, non-nutritive swallowing can be modulated by bronchopulmonary receptor activity further illustrates the physiological interactions between upper and lower airways

The third PLeural Effusion And Symptom Evaluation (PLEASE-3) study: Bendopnoea in patients with pleural effusion

Background: Pleural effusions often cause disabling breathlessness, however the mechanism is unknown. Patients with pleural effusions are subjected to pleural fluid drainage on a ‘trial and error’ basis, as symptom relief varies. This population commonly complain of bendopnoea (breathlessness on bending forward) which has not been investigated. Our pilot data found bendopnoea was significantly associated with presence of pleural effusion. The PLEASE-3 study will evaluate bendopnoea as a screening test for effusion-related breathlessness, its predictive value of symptomatic benefits from fluid drainage and explore its underlying physiological mechanism. Methods: PLEASE-3 is a multi-centre prospective study. Eligible patients are assessed at baseline (pre-drainage) and for patients undergoing drainage, up to 72 h post-procedure. Outcome measures include the prevalence of bendopnoea, its correlation with size of effusion and its predictive value of breathlessness relief after drainage. The relationship of bendopnoea with breathlessness, physiological parameters, functional capacity and diaphragmatic characteristics will be assessed. The study will recruit 200 participants. Discussion: This is the first study to investigate bendopnoea in patients with pleural effusion. It has minimal exclusion criteria to ensure that the results are generalisable. The presence and clinical significance of bendopnoea in the context of pleural effusion requires thorough investigation. The post assessment of patients undergoing pleural fluid drainage will provide insight into whether the presence of bendopnoea is able to predict clinical outcomes. Trial Registration: Name of the registry: Australia New Zealand Clinical Trial Registry Trial registration number: ACTRN12622000465752. URL of the trial registry record for this trial: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=383639&isReview=true Date of registration: Registered on 24 March 2022. Funding of the trial: This study has received funding from the Sir Charles Gairdner Research Advisory Council research project grant. The study is sponsored by the Institute for Respiratory Health, a not-for-profit organisation. Name and contact information for the trial sponsor: Mr Bi Lam; Finance manager. Level 2, 6 Verdun Street, Nedlands WA 6009. t‖ + 61 8 6151 0877 e‖ [email protected] Role of sponsor: The funder is not involved in the planning of the study, gathering, analysing, and interpreting the data, or in preparing the manuscript

Estudio del efecto de los ácidos grasos poliinsaturados de la dieta: Mecanismos moleculares involucrados en la inflamación intestinal

The use of “omics” techniques in combination with model systems and molecular tools allows to understand how foods and food components act on metabolic pathways to regulate transcriptional processes. Polyunsaturated fatty acids have distinctive nutritional and metabolic effects because they give rise to lipid mediated products and affect the expression of various genes involved in intestinal inflammation. The present review focuses on the molecular effects of dietary polyunsaturated fatty acids on intestinal inflammation.El uso de técnicas «omic» en combinación con sistemas modelo y herramientas moleculares nos permiten entender como los alimentos y sus componentes actúan en las rutas metabólicas que regulan los procesos transcripcionales. Los ácidos grasos poliinsaturados tienen efectos nutricionales y metabólicos diferenciadores porque producen una elevación de los productos regulados por lípidos y afectan a la expresión de varios genes involucrados en la inflamación intestinal. La presente revisión se enfoca en los efectos moleculares de los ácidos grasos poliinsaturados de la dieta en la inflamación intestinal

Molecular Characterization of the Onset and Progression of Colitis in Inoculated Interleukin-10 Gene-Deficient Mice: A Role for PPARα

The interleukin-10 gene-deficient (Il10−/−) mouse is a model of human inflammatory bowel disease and Ppara has been identified as one of the key genes involved in regulation of colitis in the bacterially inoculated Il10−/− model. The aims were to (1) characterize colitis onset and progression using a histopathological, transcriptomic, and proteomic approach and (2) investigate links between PPARα and IL10 using gene network analysis. Bacterial inoculation resulted in severe colitis in Il10−/− mice from 10 to 12 weeks of age. Innate and adaptive immune responses showed differences in gene expression relating to colitis severity. Actin cytoskeleton dynamics, innate immunity, and apoptosis-linked gene and protein expression data suggested a delayed remodeling process in 12-week-old Il10−/− mice. Gene expression changes in 12-week-old Il10−/− mice were related to PPARα signaling likely to control colitis, but how PPARα activation might regulate intestinal IL10 production remains to be determined

Do Web-based Mental Health Literacy Interventions Improve the Mental Health Literacy of Adult Consumers? Results From a Systematic Review

Background: Low levels of mental health literacy (MHL) have been identified as an important contributor to the mental health treatment gap. Interventions to improve MHL have used traditional media (eg, community talks, print media) and new platforms (eg, the Internet). Evaluations of interventions using conventional media show improvements in MHL improve community recognition of mental illness as well as knowledge, attitude, and intended behaviors toward people having mental illness. However, the potential of new media, such as the Internet, to enhance MHL has yet to be systematically evaluated. Objective: Study aims were twofold: (1) To systematically appraise the efficacy of Web-based interventions in improving MHL. (2) To establish if increases in MHL translated into improvement in individual health seeking and health outcomes as well as reductions in stigma toward people with mental illness. Methods: We conducted a systematic search and appraisal of all original research published between 2000 and 2015 that evaluated Web-based interventions to improve MHL. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were used to report findings. Results: Fourteen studies were included: 10 randomized controlled trials and 4 quasi-experimental studies. Seven studies were conducted in Australia. A variety of Web-based interventions were identified ranging from linear, static websites to highly interactive interventions such as social media games. Some Web-based interventions were specifically designed for people living with mental illness whereas others were applicable to the general population. Interventions were more likely to be successful if they included “active ingredients” such as a structured program, were tailored to specific populations, delivered evidenced-based content, and promoted interactivity and experiential learning.Conclusions: Web-based interventions targeting MHL are more likely to be successful if they include active ingredients. Improvements in MHL see concomitant improvements in health outcomes, especially for individuals with mild to moderate depression. The most promising interventions suited to this cohort appear to be MoodGYM and BluePages, 2 interventions from Australia. However, the relationship between MHL and formal and informal help seeking is less clear; self-stigma appears to be an important mediator with results showing that despite improvements in MHL and community attitudes to mental illness, individuals with mental illness still seek help at relatively low rates. Overall, the Internet is a viable method to improve MHL. Future studies could explore how new technology interfaces (eg, mobile phones vs computers) can help improve MHL, mental health outcomes, and reduce stigma

¹⁸F-FDG PET/MRI for restaging esophageal cancer after neoadjuvant chemoradiotherapy

PURPOSE: The purpose of this study was to investigate whether 18F-fluorodeoxyglucose ( 18 F-FDG) PET/MRI may potentially improve tumor detection after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. METHODS: This was a prospective, single-center feasibility study. At 6-12 weeks after nCRT, patients underwent standard 18 F-FDG PET/computed tomography (CT) followed by PET/MRI, and completed a questionnaire to evaluate burden. Two teams of readers either assessed the 18 F-FDG PET/CT or the 18 F-FDG PET/MRI first; the other scan was assessed 1 month later. Maximum standardized uptake value corrected for lean body mass (SUL max ) and mean apparent diffusion coefficient (ADC mean ) were measured at the primary tumor location. Histopathology of the surgical resection specimen served as the reference standard for diagnostic accuracy calculations. When patients had a clinically complete response and continued active surveillance, response evaluations until 9 months after nCRT served as a proxy for ypT and ypN (i.e. 'ycT' and 'ycN'). RESULTS: In the 21 included patients [median age 70 (IQR 62-75), 16 males], disease recurrence was found in the primary tumor in 14 (67%) patients (of whom one ypM+, detected on both scans) and in locoregional lymph nodes in six patients (29%). Accuracy (team 1/team 2) to detect yp/ycT+ with 18 F-FDG PET/MRI vs. 18 F-FDG PET/CT was 38/57% vs. 76/61%. For ypN+, accuracy was 63/53% vs. 63/42%, resp. Neither SUL max (both scans) nor ADC mean were discriminatory for yp/ycT+ . Fourteen of 21 (67%) patients were willing to undergo a similar 18 F-FDG PET/MRI examination in the future. CONCLUSION: 18 F-FDG PET/MRI currently performs comparably to 18 F-FDG PET/CT. Improvements in the scanning protocol, increasing reader experience and performing serial scans might contribute to enhancing the accuracy of tumor detection after nCRT using 18 F-FDG PET/MRI. TRIAL REGISTRATION: Netherlands Trial Register NL9352.</p

¹⁸F-FDG PET/MRI for restaging esophageal cancer after neoadjuvant chemoradiotherapy

PURPOSE: The purpose of this study was to investigate whether 18F-fluorodeoxyglucose ( 18 F-FDG) PET/MRI may potentially improve tumor detection after neoadjuvant chemoradiotherapy (nCRT) for esophageal cancer. METHODS: This was a prospective, single-center feasibility study. At 6-12 weeks after nCRT, patients underwent standard 18 F-FDG PET/computed tomography (CT) followed by PET/MRI, and completed a questionnaire to evaluate burden. Two teams of readers either assessed the 18 F-FDG PET/CT or the 18 F-FDG PET/MRI first; the other scan was assessed 1 month later. Maximum standardized uptake value corrected for lean body mass (SUL max ) and mean apparent diffusion coefficient (ADC mean ) were measured at the primary tumor location. Histopathology of the surgical resection specimen served as the reference standard for diagnostic accuracy calculations. When patients had a clinically complete response and continued active surveillance, response evaluations until 9 months after nCRT served as a proxy for ypT and ypN (i.e. 'ycT' and 'ycN'). RESULTS: In the 21 included patients [median age 70 (IQR 62-75), 16 males], disease recurrence was found in the primary tumor in 14 (67%) patients (of whom one ypM+, detected on both scans) and in locoregional lymph nodes in six patients (29%). Accuracy (team 1/team 2) to detect yp/ycT+ with 18 F-FDG PET/MRI vs. 18 F-FDG PET/CT was 38/57% vs. 76/61%. For ypN+, accuracy was 63/53% vs. 63/42%, resp. Neither SUL max (both scans) nor ADC mean were discriminatory for yp/ycT+ . Fourteen of 21 (67%) patients were willing to undergo a similar 18 F-FDG PET/MRI examination in the future. CONCLUSION: 18 F-FDG PET/MRI currently performs comparably to 18 F-FDG PET/CT. Improvements in the scanning protocol, increasing reader experience and performing serial scans might contribute to enhancing the accuracy of tumor detection after nCRT using 18 F-FDG PET/MRI. TRIAL REGISTRATION: Netherlands Trial Register NL9352.</p