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European Journal of Translational... Mar 2022Neuromuscular disorders are a heterogeneous group of acquired or hereditary conditions that affect striated muscle function. The resulting decrease in muscle strength...
Neuromuscular disorders are a heterogeneous group of acquired or hereditary conditions that affect striated muscle function. The resulting decrease in muscle strength and motility irreversibly impacts quality of life. In addition to directly affecting skeletal muscle, pathogenesis can also arise from dysfunctional crosstalk between nerves and muscles, and may include cardiac impairment. Muscular weakness is often progressive and paralleled by continuous decline in the ability of skeletal muscle to functionally adapt and regenerate. Normally, the skeletal muscle resident stem cells, named satellite cells, ensure tissue homeostasis by providing myoblasts for growth, maintenance, repair and regeneration. We recently defined 'Satellite Cell-opathies' as those inherited neuromuscular conditions presenting satellite cell dysfunction in muscular dystrophies and myopathies (doi:10.1016/j.yexcr.2021.112906). Here, we expand the portfolio of Satellite Cell-opathies by evaluating the potential impairment of satellite cell function across all 16 categories of neuromuscular disorders, including those with mainly neurogenic and cardiac involvement. We explore the expression dynamics of myopathogenes, genes whose mutation leads to skeletal muscle pathogenesis, using transcriptomic analysis. This revealed that 45% of myopathogenes are differentially expressed during early satellite cell activation (0 - 5 hours). Of these 271 myopathogenes, 83 respond to Pax7, a master regulator of satellite cells. Our analysis suggests possible perturbation of satellite cell function in many neuromuscular disorders across all categories, including those where skeletal muscle pathology is not predominant. This characterisation further aids understanding of pathomechanisms and informs on development of prognostic and diagnostic tools, and ultimately, new therapeutics.
PubMed: 35302338
DOI: 10.4081/ejtm.2022.10064 -
Cannabis and Cannabinoid Research Aug 2022The endocannabinoid (eCB) system plays a key role in maintaining homeostasis, including the regulation of metabolism and stress responses. Chronic stress may blunt eCB... (Meta-Analysis)
Meta-Analysis
The endocannabinoid (eCB) system plays a key role in maintaining homeostasis, including the regulation of metabolism and stress responses. Chronic stress may blunt eCB signaling, and disruptions in eCB signaling have been linked to stress-related psychiatric disorders and physical health conditions, including anxiety, depression, post-traumatic stress disorder (PTSD), diabetes, and obesity. Pharmacological and nonpharmacological behavioral interventions (e.g., exercise) that target the eCB system may be promising therapeutic approaches for the prevention and treatment of stress-related diseases. In this study, we perform a systematic review and the first meta-analysis to examine the impact of exercise on circulating eCB concentrations. We performed a review of the MEDLINE (PubMed) database for original articles examining the impact of exercise on eCBs in humans and animal models. A total of 262 articles were screened for initial inclusion. Thirty-three articles (reporting on 57 samples) were included in the systematic review and 10 were included in the meta-analysis. The majority of samples that measured anandamide (AEA) showed a significant increase in AEA concentrations following acute exercise (74.4%), whereas effects on 2-arachidonoylglycerol (2-AG) were inconsistent. The meta-analysis, however, revealed a consistent increase in both AEA and 2-AG following acute exercise across modalities (e.g., running, cycling), species (e.g., humans, mice), and in those with and without pre-existing health conditions (e.g., PTSD, depression). There was substantial heterogeneity in the magnitude of the effect across studies, which may relate to exercise intensity, physical fitness, timing of measurement, and/or fasted state. Effects of chronic exercise were inconsistent. Potential interpretations and implications of exercise-induced mobilization of eCBs are discussed, including refilling of energy stores and mediating analgesic and mood elevating effects of exercise. We also offer recommendations for future work and discuss therapeutic implications for exercise in the prevention and treatment of stress-related psychopathology.
Topics: Affect; Animals; Anxiety; Endocannabinoids; Humans; Mice; Running; Stress Disorders, Post-Traumatic
PubMed: 34870469
DOI: 10.1089/can.2021.0113 -
Journal of Affective Disorders Mar 2021Inadequate treatment response and emotional blunting are common challenges with selective serotonin reuptake inhibitors/serotonin-noradrenaline reuptake inhibitors...
INTRODUCTION
Inadequate treatment response and emotional blunting are common challenges with selective serotonin reuptake inhibitors/serotonin-noradrenaline reuptake inhibitors (SSRIs/SNRIs) for major depressive disorder (MDD). We investigated the effectiveness of vortioxetine on emotional blunting in patients with partial response to treatment with SSRIs/SNRIs.
METHODS
Patients with MDD who experienced a partial response to SSRI/SNRI monotherapy at adequate dose for ≥6 weeks were switched to 8 weeks of vortioxetine treatment 10-20 mg/day (Study NCT03835715). Key inclusion criteria were Montgomery-Åsberg Depression Rating Scale (MADRS) total score >21 and <29, current major depressive episode <12 months, Oxford Depression Questionnaire (ODQ) total score ≥50, and confirmation of emotional blunting by standardized screening question. Emotional blunting was assessed by ODQ and depressive symptoms by MADRS. Other outcomes assessed included motivation and energy (Motivation and Energy Inventory [MEI]), cognitive performance (Digit Symbol Substitution Test [DSST]), and overall functioning (Sheehan Disability Scale [SDS]).
RESULTS
At week 8, patients (N=143) had improved by -29.8 points (p<0.0001) in ODQ total score; 50% reported no emotional blunting in response to standardized screening question. Significant improvements were observed on the DSST, MEI, and SDS at all time points assessed, and 47% of patients were in remission (MADRS total score ≤10) at week 8. The most common treatment-emergent adverse events included nausea, headache, dizziness, vomiting, and diarrhea.
LIMITATIONS
No prospective phase before medication switch.
CONCLUSION
Vortioxetine 10-20 mg effectively improved emotional blunting, overall functioning, motivation and energy, cognitive performance, and depressive symptoms in patients with MDD with partial response to SSRI/SNRI therapy and emotional blunting.
Topics: Depressive Disorder, Major; Double-Blind Method; Humans; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Treatment Outcome; Vortioxetine
PubMed: 33516560
DOI: 10.1016/j.jad.2020.11.106 -
Ulusal Travma Ve Acil Cerrahi Dergisi =... May 2022The objective of the study is to investigate diagnostic and clinical processes performed for cardiac contusion in patients with blunt thoracic trauma.
BACKGROUND
The objective of the study is to investigate diagnostic and clinical processes performed for cardiac contusion in patients with blunt thoracic trauma.
METHODS
This study was conducted retrospectively on 65 patients admitted with isolated blunt thoracic trauma to the Emergency Medicine Department. The CT images, the cardiac enzyme levels, the periodic 4-h follow-up electrocardiography (ECGs) in the emer-gency department, and the results of echocardiography, performed at admission and when required according to the clinical status, were investigated. The 1-h and 4-h high-sensitivity troponin I levels were studied, and values above 0.04 ng/ml were considered as positive.
RESULTS
Sixty-five patients with isolated thoracic trauma were included in the study, 23 (35.38%) had pulmonary and cardiac contu-sions both. In 23 (35.38%) patients, pulmonary contusion had been present, and cardiac contusion had not been identified at the initial evaluation. However, during clinical follow-up, troponin became positive, dysrhythmia developed, and the trauma affected the heart in four of these patients. In six (9.24%) patients, cardiac contusion was identified without pulmonary contusion. In 13 (20%) patients, no cardiac or pulmonary contusion was identified. troponin elevation was detected in 10 patients without a diagnosis of cardiac contusion who had a pulmonary contusion, hemothorax, and/or pneumothorax at the time of hospital admission and then with normal troponin levels at 4-h control. We found that there was a statistical agreement between cardiac contusion and troponin-ECG results at 4th h.
CONCLUSION
We advise that all blunt thoracic trauma patients should be screened for cardiac contusion by continuous ECG monitoring and troponin levels.
Topics: Attention; Contusions; Humans; Lung Injury; Myocardial Contusions; Retrospective Studies; Thoracic Injuries; Troponin I; Wounds, Nonpenetrating
PubMed: 35485460
DOI: 10.14744/tjtes.2021.11290 -
Journal of Thoracic Disease Feb 2019Lung contusion resulting from chest trauma may be present various clinical pictures. It quite often remains unrecognized and is only suspected later when severe... (Review)
Review
Lung contusion resulting from chest trauma may be present various clinical pictures. It quite often remains unrecognized and is only suspected later when severe complications have developed. Lung contusion may present in association with chest trauma but may also occur alone. It has to be emphasized, that lung contusion as a clinical identity does not necessarily require a blunt or penetrating chest to be in the background. Nowadays, as a result of traffic accidents, following high energy deceleration, lung contusion may present without an actual tissue damage in the chest wall as a condition initiating an independent, life-threatening generalised process. Although lung contusion shows similarities to blast injury of the lung with respect to clinical consequences, other factors play a role in its aetiology and pathology. Its description and recognition as an independent pathology is not simple. Several approaches exist: thoracic trauma, pulmonary contusion, pulmonary laceration, lung contusion; although these may show similar clinical signs, manifest in different pathologies. Pathologies with similar meaning and possibly similar clinical course cannot, actually, be differentiated; they may accompany other injuries to the trunk, skull or extremities, which, alone, are associated with high morbidity and mortality. Generally, it can be declared that besides high energy, blunt injuries affecting the trunk, lung contusion, has been an often neglected additional radiological finding attached to the main report, despite the fact, that its late consequences crucially determine the prospects of the injured.
PubMed: 30906578
DOI: 10.21037/jtd.2018.11.53 -
The Journal of Neuroscience : the... Oct 2022Humans routinely learn the value of actions by updating their expectations based on past outcomes - a process driven by reward prediction errors (RPEs). Importantly,...
Humans routinely learn the value of actions by updating their expectations based on past outcomes - a process driven by reward prediction errors (RPEs). Importantly, however, implementing a course of action also requires the investment of effort. Recent work has revealed a close link between the neural signals involved in effort exertion and those underpinning reward-based learning, but the behavioral relationship between these two functions remains unclear. Across two experiments, we tested healthy male and female human participants ( = 140) on a reinforcement learning task in which they registered their responses by applying physical force to a pair of hand-held dynamometers. We examined the effect of effort on learning by systematically manipulating the amount of force required to register a response during the task. Our key finding, replicated across both experiments, was that greater effort increased learning rates following positive outcomes and decreased them following negative outcomes, which corresponded to a differential effect of effort in boosting positive RPEs and blunting negative RPEs. Interestingly, this effect was most pronounced in individuals who were more averse to effort in the first place, raising the possibility that the investment of effort may have an adaptive effect on learning in those less motivated to exert it. By integrating principles of reinforcement learning with neuroeconomic approaches to value-based decision-making, we show that the very act of investing effort modulates one's capacity to learn, and demonstrate how these functions may operate within a common computational framework. Recent work suggests that learning and effort may share common neurophysiological substrates. This raises the possibility that the very act of investing effort influences learning. Here, we tested whether effort modulates teaching signals in a reinforcement learning paradigm. Our results showed that effort resulted in more efficient learning from positive outcomes and less efficient learning from negative outcomes. Interestingly, this effect varied across individuals, and was more pronounced in those who were more averse to investing effort in the first place. These data highlight the importance of motivational factors in a common framework of reward-based learning, which integrates the computational principles of reinforcement learning with those of value-based decision-making.
Topics: Humans; Male; Female; Decision Making; Reinforcement, Psychology; Reward; Motivation; Affect
PubMed: 36096671
DOI: 10.1523/JNEUROSCI.2223-21.2022 -
Journal of Clinical Medicine Apr 2023Blunt thoracic aortic injury (BTAI) is a potentially fatal condition that needs prompt recognition and expedited management. Clinical manifestations of BTAI are not... (Review)
Review
Blunt thoracic aortic injury (BTAI) is a potentially fatal condition that needs prompt recognition and expedited management. Clinical manifestations of BTAI are not straight forwarding and may be misdiagnosed. The grade of aortic injury is an important determinant of perioperative mortality and morbidity, as well as the indication of treatment, along with the presence of concomitant lesions of other involved organs. The mainstay of treatment nowadays for hemodynamically stable patients who survive the trauma scene is represented by delayed endovascular repair whenever anatomically and clinically feasible. Endovascular repair, in fact, is burdened by lower perioperative mortality and morbidity rates if compared to open surgical repair, but concerns remain about the need for long-term surveillance and radiation exposure in patients who are at a younger age than patients treated for the aneurysmal disease. The aim of the paper is to provide an update on the diagnostic modalities and strategies of treatment for patients affected by BTAI.
PubMed: 37109240
DOI: 10.3390/jcm12082903