High Phenolic Extra Virgin Olive Oil Influences the Gut-brain Axis in Individuals Diagnosed with Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) is an umbrella term that incorporates a range of neurodevelopmental disorders which affect behaviour, emotion, and communication. In recent years, the effects of dietary habits in individuals with ASD have been mentioned and a distinct correlation has been observed between ASD and gastrointestinal (GI) disorders. We used the Autism Treatment Evaluation Checklist (ATEC) to evaluate whether we can observe differences in behaviour by administering High Phenolic Extra Virgin Olive Oil (HP EVOO) in combination with a special diet to reduce inflammation and consequently improve behaviour. We hypothesise that ASD symptoms will soothe at a proportional rate relative to their severity. Individuals that followed the protocol showed a decrease in severity of their symptoms. Regarding data analysis, we calculated the p-values to evaluate the significance of our results. Our objective is to establish the beneficial influence that HP EVOO has on the gut-brain axis by soothing ASD symptoms

Major histocompatibility complex I‐induced endoplasmic reticulum stress mediates the secretion of pro‐inflammatory muscle‐derived cytokines

© 2022 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd. This is an open access article distributed under the Creative Commons Attribution License, to view a copy of the license, see: This is an open access article under the terms of the Creative Commons Attribution License,https://creativecommons.org/licenses/by/4.0/Major histocompatibility complex (MHC) I is an important component of intracellular antigen presentation. However, improper expression of MHC I upon the cell surface has been associated with several autoimmune diseases. Myositis is a rare acquired autoimmune disease which targets skeletal muscle, and MHC I overexpression on the surface of muscle fibres and immune cell infiltration are clinical hallmarks. MHC I overexpression may have an important pathogenic role, mediated by the activation of the endoplasmic reticulum (ER) stress response. Given the evidence that muscle is a diverse source of cytokines, we aimed to investigate whether MHC I overexpression can modify the profile of muscle‐derived cytokines and what role the ER stress pathway may play. Using C2C12 myoblasts we overexpressed MHC I with a H‐2kb vector in the presence or absence of salubrinal an ER stress pathway modifying compound. MHC I overexpression induced ER stress pathway activation and elevated cytokine gene expression. MHC I overexpression caused significant release of cytokines and chemokines, which was attenuated in the presence of salubrinal. Conditioned media from MHC I overexpressing cells induced in vitro T‐cell chemotaxis, atrophy of healthy myotubes and modified mitochondrial function, features which were attenuated in the presence of salubrinal. Collectively, these data suggest that MHC I overexpression can induce pro‐inflammatory cytokine/chemokine release from C2C12 myoblasts, a process which appears to be mediated in‐part by the ER stress pathway.Peer reviewe

Targeting reactive oxygen species (ROS) to combat the age-related loss of muscle mass and function.

The loss of muscle mass and function with age, termed sarcopenia, is an inevitable process, which has a significant impact on quality of life. During ageing we observe a progressive loss of total muscle fibres and a reduction in cross-sectional area of the remaining fibres, resulting in a significant reduction in force output. The mechanisms which underpin sarcopenia are complex and poorly understood, ranging from inflammation, dysregulation of protein metabolism and denervation. However, there is significant evidence to demonstrate that modified ROS generation, redox dis-homeostasis and mitochondrial dysfunction may have an important role to play. Based on this, significant interest and research has interrogated potential ROS-targeted therapies, ranging from nutritional-based interventions such as vitamin E/C, polyphenols (resveratrol) and targeted pharmacological compounds, using molecules such as SS-31 and MitoQ. In this review we evaluate these approaches to target aberrant age-related ROS generation and the impact on muscle mass and function

Eukarion-134 Attenuates Endoplasmic Reticulum Stress-Induced Mitochondrial Dysfunction in Human Skeletal Muscle Cells

Maladaptive endoplasmic reticulum (ER) stress is associated with modified reactive oxygen species (ROS) generation and mitochondrial abnormalities; and is postulated as a potential mechanism involved in muscle weakness in myositis, an acquired autoimmune neuromuscular disease. This study investigates the impact of ROS generation in an in vitro model of ER stress in skeletal muscle, using the ER stress inducer tunicamycin (24 h) in the presence or absence of a superoxide dismutase/catalase mimetic Eukarion (EUK)-134. Tunicamycin induced maladaptive ER stress, which was mitigated by EUK-134 at the transcriptional level. ER stress promoted mitochondrial dysfunction, described by substantial loss of mitochondrial membrane potential, as well as a reduction in respiratory control ratio, reserve capacity, phosphorylating respiration, and coupling efficiency, which was ameliorated by EUK-134. Tunicamycin induced ROS-mediated biogenesis and fusion of mitochondria, which, however, had high propensity of fragmentation, accompanied by upregulated mRNA levels of fission-related markers. Increased cellular ROS generation was observed under ER stress that was prevented by EUK-134, even though no changes in mitochondrial superoxide were noticeable. These findings suggest that targeting ROS generation using EUK-134 can amend aspects of ER stress-induced changes in mitochondrial dynamics and function, and therefore, in instances of chronic ER stress, such as in myositis, quenching ROS generation may be a promising therapy for muscle weakness and dysfunction

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Investigating the non-immune cell mediated mechanisms of skeletal muscle weakness in myositis; developing an investigative platform to study human diseases

Idiopathic inflammatory myopathies, collectively termed as myositis, are a group of heterogeneous rare autoimmune muscle diseases, described by muscle weakness and fatigue leading to poor quality of life. Widely recognised by its immune mediated features, its current treatment focuses on immunosuppressive therapies, which however, seem to be ineffective in treating muscle weakness. Growing evidence support the involvement of non-immune mediated mechanisms including ER stress and mitochondrial impairements, as well as myokines up- or down-regulation, with major histocompatibility complex class I (MHC-I), a prominent myositis feature, being suggested to initiate those events. Thus, there is a great necessity for investigating the non-immune mediated mechanisms underlying myositis pathophysiology, providing the foundation for developing novel targeted therapeutic approaches. This thesis investigated the non-immune mediated mechanisms, focusing on mitochondrial bioenergetics and biodynamics, and reactive oxygen species generation, in three human in vitro models of myositic muscle: (a) pharmacological cell model of ER stress; (b) genetically modified cell model of MHC-I overexpression in presence or absence of type I interferons (IFNs); and (c) clinical cell model of primary human myositis skeletal muscle cell line. Lastly, the downstream mechanisms of the myokines secretome derived from the primary myositis cell line was assessed. Tunicamycin-induced ER stress activation led to an overall increase in mitochondrial respiration, potentially as an adaptive response to stress; however, mitochondrial dysfunction was evident by decreases in respiratory flux control ratios and mitochondrial membrane potential. A similar trend of mitochondrial changes was seen in IBM and DM primary cells, with effects being more drastic in DM compared to IBM primary cells. MHC-I overexpression caused significant depletion in mitochondrial respiration, accompanying by reduced respiratory flux control ratios and mitochondrial membrane potential. Interestingly, those effects seemed to exacerbate in presence of type I IFNs, suggesting the strong combinational effects of MHC-I and type I IFNs. MHC-I-induced effects were similar to those following exposure to myositic conditioned media, where DM conditioned media collected from DM primary cells showed greater mitochondrial respiratory deficiency compared to IBM primary cells-derived conditioned media. An interesting finding was that antioxidant intervention, using Eukarion-134, was able to amend aspects of mitochondrial dysfunction in those models, highlighting the potential role of ROS accumulation in myositis. Overall, this thesis has provided numerous models that can be used for further investigating the mechanisms involved in myositis pathogenesis and identify potential therapeutic targets. The findings suggest the involvement of multiple mechanisms that can be overlapping, but also act independently in inducing mitochondrial impairments, leading to muscle weakness in myositis. Lastly, these studies have indicated a possible role of ROS generation in mediating aspects of ER stress and mitochondrial abnormalities, suggesting that targeting ROS accumulation could be a promising therapeutic strategy for the persistent muscle weakness in individuals with myositis