Overload Stress Research Articles

ЯЗЫК ДЛЯ СПЕЦИАЛЬНЫХ ЦЕЛЕЙ: РАЦИОНАЛЬНОЕ, ЭМОЦИОНАЛЬНОЕ И ИНТУИТИВНОЕ В НАУЧНОМ ПОЗНАНИИ (НА ПРИМЕРЕ АНГЛИЙСКОГО ЯЗЫКА БИОЛОГОВ)

English for specific purposes (ESP) of biologists is one of the most dynamically developing variants of modern English that provides for efficient communication within life sciences exhibiting new tendencies in naming objects, facts and phenomena discovered by science. The article looks into a massive use in genetics – rightly considered the basis of modern biology due to its universal laws of heredity and variability – of expressive and colourful figurative terminological and nomenclature units based on cognitive metaphors and metonymies. The harmonious combination of rational, emotional and intuitive ways of scientific cognition allows the biological community to cope successfully with cognitive overload and psycho-emotional stress in the modern conditions of exponentially increasing volume of genetic information. It is demonstrated that the unusually metaphorical, figurative and humorous units of biological ESP carry out a new function of emotional discharge that requires no less attention than the traditional epistemic, cognitive and communicative functions which have already been studied quite well.

Well-being of Women Entrepreneurs in Pakistan: A Conceptual Review of Challenges and Opportunities

Purpose: The economic significance of women's entrepreneurship is globally recognized; yet, the pace of women's entrepreneurial activities is slow. The lowering share of women's participation in the entrepreneurial population has been attributed to many reasons but for health. Women entrepreneurs’ health and well-being are important, yet widely neglected notions in research and practice. Especially, in Pakistani patriarchal society women are expected to work (self-employed or organizationally employed) with disproportionate family and work responsibilities.
 Design/Methodology/Approach: The study provides a conceptual review of key challenges faced by women entrepreneurs. To serve this purpose, relevant literature was selected and reviewed following a four-step procedure.
 Findings: In fulfilling their traditional roles of house-maker and the need to support family, the mental and physical health of women entrepreneurs is compromised. Findings of this study reveal that role expectation, stress overload, work-life conflict, fear of harassment, and workaholism are among the key factors that challenge the well-being of women entrepreneurs. However, family support, societal approval of their business, and work engagement may serve as an opportunity to improve women entrepreneurs’ well-being.
 Implications/Originality/Value: The study sheds light on key challenges faced by women entrepreneurs in a developing country context and suggests avenues for further research.

Mechanical Factors Regulate Annulus Fibrosus (AF) Injury Repair and Remodeling: A Review.

Low back pain is a common chronic disease that can severely affect the patient's work and daily life. The breakdown of spinal mechanical homeostasis caused by intervertebral disc (IVD) degeneration is a leading cause of low back pain. Annulus fibrosus (AF), as the outer layer structure of the IVD, is often the first affected part. AF injury caused by consistent stress overload will further accelerate IVD degeneration. Therefore, regulating AF injury repair and remodeling should be the primary goal of the IVD repair strategy. Mechanical stimulation has been shown to promote AF regeneration and repair, but most studies only focus on the effect of single stress on AF, and lack realistic models and methods that can mimic the actual mechanical environment of AF. In this article, we review the effects of different types of stress stimulation on AF injury repair and remodeling, suggest possible beneficial load combinations, and explore the underlying molecular mechanisms. It will provide the theoretical basis for designing better tissue engineering therapy using mechanical factors to regulate AF injury repair and remodeling in the future.

The Effect of Oral Iron Chelator Deferiprone on Iron Overload and Oxidative Stress in Patients with Myelodysplastic Syndromes: A Study by the Israeli MDS Working Group

Background: Most patients with lower risk myelodysplastic neoplasms or syndromes (MDSs) become RBC transfusion-dependent, resulting in iron overload, which is associated with an increased oxidative stress state. Iron-chelation therapy is applied to attenuate the toxic effects of this state. Deferiprone (DFP) is an oral iron chelator, which is not commonly used in this patient population, due to safety concerns, mainly agranulocytosis. The purpose of this study was to assess the effect of DFP, on oxidative stress parameters in iron-overloaded RBC transfusion-dependent patients with lower risk MDSs. Methods: Adult lower risk MDS patients with a cumulative transfusion burden of >20 red blood cell units and evidence of iron overload (serum ferritin >1,000 ng/mL) were included in this study. DFP was administered (100 mg/kg/day) for 4 months. Blood samples for oxidative stress parameters and iron overload parameters were done at baseline and monthly: reactive oxygen species (ROS), phosphatidylserine, reduced glutathione, membrane lipid peroxidation, serum ferritin, and cellular labile iron pool. The primary efficacy variable was ROS. Tolerability and side effects were recorded as well. A paired t test was applied for statistical analyses. Results: Eighteen patients were treated with DFP. ROS significantly decreased in all cell lineages: median decrease of 58.6% in RBC, 33.3% in PMN, and 39.8% in platelets (p < 0.01 for all). Other oxidative stress markers improved: phosphatidylserine decreased by 57.95%, lipid peroxidase decreased by 141.3%, and reduced gluthathione increased by 72.8% (p < 0.01 for all). The iron-overload marker and cellular labile iron pool decreased by 35% in RBCs, 44.3% in PMN, and 46.3% in platelets (p < 0.01 for all). No significant changes were observed in SF levels. There were no events of agranulocytosis. All AEs were grades 1–2. Conclusions: Herein, we showed preliminary evidence that DFP decreases iron-induced oxidative stress in MDS patients with a good tolerability profile (albeit a short follow-up period). No cases of severe neutropenia or agranulocytosis were reported. The future challenge is to prove that reduction in iron toxicity will eventually be translated into a clinically meaningful improvement.

The effect of a mindfulness-based intervention on stress overload, depression, and mindfulness among nurses: Arandomized controlled trial.

Nurses experience various health-related issues due to the nature of their work. This study aimed to examine the effect of a mindfulness-based intervention on stress overload, depression and mindfulness among nurses. A secondary objective was to examine the role of the setting (i.e., in and out of the hospital as a natural setting) on mindfulness-based intervention effectiveness. A randomized controlled trial with three groups' pretest-posttest design was used in this study. A total of 195 nurses were recruited-65 intervention-inside hospital, 60 intervention-outside hospital, and 63 control. The mindfulness-based intervention was delivered by a certified mindfulness practitioner over 4 weeks in Jordan. Data were collected using a demographics questionnaire, the Stress Overload Scale Short, the Center for Epidemiologic Studies Depression Scale-Revised, and the Five Facet Mindfulness Questionnaire. Multivariate analysis showed a statistically significant effect of the intervention on the linear combination of the dependent variables V = 0.44, F[6, 368] = 17.56, p < .001. Follow-up analyses showed that a mindfulness-based intervention significantly decreased stress overload, depression, and increased mindfulness levels among nurses in intervention groups compared with the control group. In addition, conducting a mindfulness-based intervention outside the hospital has a better effect on mindfulness levels than the inside hospital. The effect of a mindfulness-based intervention on stress overload, depression, and mindfulness should be considered when planning for nurses' well-being and the quality of care provided. Nurse managers are encouraged to use the study's findings to promote nurses' well-being.

Cardiac radiation improves ventricular function in mice and humans with cardiomyopathy.

Rapidly dividing cells are more sensitive to radiation therapy (RT) than quiescent cells. In the failing myocardium, macrophages and fibroblasts mediate collateral tissue injury, leading to progressive myocardial remodeling, fibrosis, and pump failure. Because these cells divide more rapidly than cardiomyocytes, we hypothesized that macrophages and fibroblasts would be more susceptible to lower doses of radiation and that cardiac radiation could therefore attenuate myocardial remodeling. In three independent murine heart failure models, including models of metabolic stress, ischemia, and pressure overload, mice underwent 5 Gy cardiac radiation or sham treatment followed by echocardiography. Immunofluorescence, flow cytometry, and non-invasive PET imaging were employed to evaluate cardiac macrophages and fibroblasts. Serial cardiac magnetic resonance imaging (cMRI) from patients with cardiomyopathy treated with 25 Gy cardiac RT for ventricular tachycardia (VT) was evaluated to determine changes in cardiac function. In murine heart failure models, cardiac radiation significantly increased LV ejection fraction and reduced end-diastolic volume vs. sham. Radiation resulted in reduced mRNA abundance of B-type natriuretic peptide and fibrotic genes, and histological assessment of the LV showed reduced fibrosis. PET and flow cytometry demonstrated reductions in pro-inflammatory macrophages, and immunofluorescence demonstrated reduced proliferation of macrophages and fibroblasts with RT. In patients who were treated with RT for VT, cMRI demonstrated decreases in LV end-diastolic volume and improvements in LV ejection fraction early after treatment. These results suggest that 5 Gy cardiac radiation attenuates cardiac remodeling in mice and humans with heart failure. NIH, ASTRO, AHA, Longer Life Foundation.

Effects of work overload and job stress on employee performance: categorical moderation from polychronicity and work environment

The increasingly fierce competition in the world of work requires companies to work effectively and efficiently in order to survive and develop better. The right strategic steps are needed by the company in facing the competition. Companies must be able to manage resources in order to provide satisfactory services so that they can achieve the planned goals and objectives. Testing the moderation categorical model using path analysis based on OLS (Ordinary Least Square) regression and bootstrap method using SPSS version 25 and PROCESS version 3.5 statistical tools by Andrew F. Hayes the 76th model for the object of this research. The research sample was 235 health workers. The result of this research is that polychronicity and work environment effectively moderate the effect of work overload on employee performance through job stress. Work stress can be reduced by improving the quality of employees in the company and providing the best employees in the work environment.

Multifunctional Carbon Quantum Dots: Iron Clearance and Antioxidation for Neuroprotection in Intracerebral Hemorrhage Mice.

Iron overload and oxidative stress are pivotal in the pathogenesis of brain injury secondary to intracerebral hemorrhage (ICH). There is a compelling need for agents that can chelate iron and scavenge free radicals, particularly those that demonstrate substantial brain penetration, to mitigate ICH-related damage. In this study, we have engineered an amine-functionalized aspirin-derived carbon quantum dot (NACQD) with a nominal diameter of 6-13 nm. The NACQD possesses robust iron-binding and antioxidative capacities. Through intrathecal administration, NACQD therapy substantially reduced iron deposition and oxidative stress in brain tissue, alleviated meningeal inflammatory responses, and improved the recovery of neurological function in a murine ICH model. As a proof of concept, the intrathecal injection of NACQD is a promising therapeutic strategy to ameliorate the ICH injury.

Abstract 13045: Myofibroblasts Revert to an Inactive Phenotype During Regression of Heart Failure

Introduction: The therapy of left ventricular mechanical unloading, such as transcatheter aortic valve replacement(TAVR)and left ventricular assist devices(LVAD)has significantly improved prognosis for patients with heart failure. However, the detailed cellular and/or molecular mechanisms of recovery of cardiac function remain unknown. Objective: We aimed to build a cellular atlas of the heart that experienced stress and de-stress process, with a focus on myofibroblasts, specifically its cell fate of differentiation and function. Methods: We conducted single-cell and ATAC sequencing on non-myocardial cells from mouse heart samples of pressure overload-induced heart failure and recovery, using TAC (transverse aortic arch constriction)/deTAC (with suture for the constriction removed 2 weeks after TAC) model to identify the dynamic changes. Lineage tracing technique was also used to gain further insight into cell fate and reciprocal interactions. Macrophage subgroup was cleared using various approaches to investigate the cross-talk between myofibroblast and macrophage. Results: We generated a TAC/deTAC mouse model which can faithfully simulate a reversal process of functioning for the heart that underwent a pressure overload stress. Multi-omics sequencing reveals the genetic changes and transcriptional regulation of cell populations at different stages. Among the different cell types, significant changes in the gene expression pattern were observed in fibroblasts. Aided by myofibroblast lineage tracing, flow cytometry examinations suggested that remaining in a quiescent state rather than showing a decrease in its number appeared as the main fate of myofibroblasts. Surprisingly, however, simultaneous pressure unloading and macrophage clearance resulted in a significant reduction in the number of myofibroblasts. Conclusions: With a reliable TAC/deTAC mouse model, our multi-omics data revealed dynamic changes in cell populations of the heart that underwent pressure overload followed by unloading, our data demonstrated a quiescent state rather than a reduction in number was the major fate for the activated myofibroblasts for which macrophages were involved. These findings provide a theoretical basis for further treatment.

A moderated mediation investigation of the influence of enterprise social media visibility on work stress

Drawing upon the communication visibility theory, this study delves into the intricate dynamics of message transference and network translucence within the context of enterprise social media (ESM), unraveling their profound impact on information overload and social overload experienced by employees. Consequently, we examine the consequential relationship between these overwhelming cognitive burdens and the levels of work stress experienced by individuals in the organizational setting. Moreover, our study explores the moderating role of resilience, shedding light on how this intrinsic psychological trait can shape the connection among information overload, social overload, and work stress. Based on empirical analysis of the data collected from 351 ESM users, the findings demonstrate a significant positive association between message transference, network translucence, and the occurrence of information overload and social overload among employees. Furthermore, the results reveal a strong positive association among information overload and social overload over work stress. However, the salient contribution of this study lies in uncovering the pivotal moderating effect of resilience, revealing that high levels of resilience act as a buffer against the adverse impacts of information overload and social overload, leading to lower levels of work stress among individuals. By advancing our comprehension of communication visibility theory, this study adds to the theoretical underpinnings of communication visibility, resilience, and their interplay in the context of ESM while providing practical insights for employees and organizations to navigate the challenges posed by information overload, social overload, and work stress. Through its meticulous examination of these multifaceted phenomena, this study opens avenues for further research and invites scholars to probe deeper into the complex dynamics of communication visibility and resilience in the evolving landscape of contemporary organizations.

Mitral Stenosis Berat pada Penyakit Jantung Rematik

Rheumatic Heart Disease (RHD) has high morbidity and mortality. Cardiac valve disorders after rheumatic fever are the leading cause of heart failure in children and young adults. A comprehensive understanding of RHD can help early diagnosis and provide optimal management in the future. It has been reported that a 55-year-old man came to the heart clinic of Bhayangkara Hospital Denpasar for routine control of heart disease. The patient has been diagnosed with rheumatic heart disease since 2018. The patient complains of shortness of breath when walking long distances and doing strenuous activities. The patient was diagnosed with CHF FC II ec RHD + MS moderate-severe (Wilkins score 8) + AF NVR (CHA2DS2VASc 3) and treated with heart failure and antiplatelet medication. Mitral stenosis due to RHD produces the typical pathological features seen in Transthoracic echocardiography (TTE), including fibrous thickening and calcification of the valve leaflets, fusion of the commissures, and thickening and shortening of chordae tendineae. Chronic stress overload on the LA due to MS can cause LA dilatation and trigger AF. RHD patients with AF are recommended for anticoagulation for stroke prevention. Patients with acute rheumatic fever clinical features should be evaluated further and given long-term therapy to prevent more severe heart problems.Keywords: atrial fibrillation, mitral stenosis, rheumatic heart disease

NRF2 is essential for iron-overload stimulated osteoclast differentiation through regulation of redox and iron homeostasis.

Iron overload enhances osteoclastic bone resorption and induces osteoporosis. Excess iron is highly toxic. The modulation of redox and iron homeostasis is critical for osteoclast differentiation under iron-overload condition. Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that regulates the cellular defense against oxidative stress and iron overload through the expression of genes involved in anti-oxidative processes and iron metabolism. Our studies demonstrated that NRF2 activation was suppressed during osteoclast differentiation. Under iron-overload condition, NRF2 and its mediated antioxidant and iron metabolism genes were activated by reactive oxygen species (ROS), which enhanced antioxidant capability. NRF2 mediated the upregulation of iron exporter ferroportin 1 (FPN1) and iron storage protein ferritin, contributing to decreased levels of intracellular iron. Nfe2l2 knockout induced oxidative stress and promoted osteoclast differentiation under normal condition, but induced ferroptosis under iron-overload condition. Nfe2l2 knockout alleviated iron overload induced bone loss by inhibiting osteoclast differentiation. Our results suggest that NRF2 activation is essential for osteoclast differentiation by enhancing antioxidant capability and reducing intracellular iron under iron-overload condition. Targeting NRF2 to induce ferroptosis could be a potential therapy for the treatment of iron-overload induced osteoporosis.

Root cause analysis of flywheel gear failure in a marine diesel engine

Engine gear failures are of significant concern across a wide range of industries. It is important to investigate each gear failure in light of its unique loading and operating conditions for root cause analysis (RCA) and further corrective actions to avoid such failures in the future. The aim of this study was to investigate the premature failure of a flywheel gear of a marine diesel engine and establish the root cause and damage mechanisms using experimental and numerical analysis techniques. A bottom-up creative approach was adopted to assess the loading conditions on the failed gear by first estimating the bending deformation of the failed securing bolt, assuming overload torque on the flywheel caused an equivalent bending moment permanently bending the bolt. Von Mises equivalent stress acting on the gear was numerically estimated as σVM = 737 MPa, which was found significantly more than the specified yield strength of gear governing material AISI 1055 (σY = 550 MPa). SEM fractography revealed a quasi-cleavage failure mechanism in the ‘case’ region near the gear root and a ductile failure mechanism inside the ‘core’ region of the flywheel gear. A crack was found to initiate from the gear root consisting of high-stress concentration under overload stresses. RCA established that the flywheel gears had failed by overload stresses, caused due to overload torque generated from sudden inertial thrust in the internal combustion (IC) engine due to excess fuel throttle opening.

Sphingosylphosphorylcholine alleviates pressure overload-induced myocardial remodeling in mice via inhibiting CaM-JNK/p38 signaling pathway.

Apoptosis plays a critical role in the development of heart failure, and sphingosylphosphorylcholine (SPC) is a bioactive sphingolipid naturally occurring in blood plasma. Some studies have shown that SPC inhibits hypoxia-induced apoptosis in myofibroblasts, the crucial non-muscle cells in the heart. Calmodulin (CaM) is a known SPC receptor. In this study we investigated the role of CaM in cardiomyocyte apoptosis in heart failure and the associated signaling pathways. Pressure overload was induced in mice by trans-aortic constriction (TAC) surgery. TAC mice were administered SPC (10 μM·kg-1·d-1) for 4 weeks post-surgery. We showed that SPC administration significantly improved survival rate and cardiac hypertrophy, and inhibited cardiac fibrosis in TAC mice. In neonatal mouse cardiomyocytes, treatment with SPC (10 μM) significantly inhibited Ang II-induced cardiomyocyte hypertrophy, fibroblast-to-myofibroblast transition and cell apoptosis accompanied by reduced Bax andphosphorylation levels of CaM, JNK and p38, as well as upregulated Bcl-2, a cardiomyocyte-protective protein. Thapsigargin (TG) could enhance CaM functions by increasing Ca2+ levels in cytoplasm. TG (3 μM) annulled the protective effect of SPC against Ang II-induced cardiomyocyte apoptosis. Furthermore, we demonstrated that SPC-mediated inhibition of cardiomyocyte apoptosis involved the regulation of p38 and JNK phosphorylation, which was downstream of CaM. These results offer new evidence for SPC regulation of cardiomyocyte apoptosis, potentially providing a new therapeutic target for cardiac remodeling following stress overload.

Systemic hemodynamic atherothrombotic syndrome: from hypothesis to evidence.

Hypertension is a risk factor for cardiovascular disease (CVD). However, the association between blood pressure (BP) and CVD events has been based on mean BP alone. BP variability (BPV) is associated with increased organ damage and CVD events independently or beyond average home BP. To explain this association, we propose the systemic hemodynamic atherothrombotic syndrome (SHATS) hypothesis. The SHATS hypothesis indicates that hemodynamic stress increases vascular disease and vice versa, leading to a vicious cycle of the association between hemodynamic stress and a vascular disease; this association provides not only the risk but also the trigger for CVD events. The evidences of SHATS were gradually accumulating. We showed arterial stiffness synergistically amplified the association between hemodynamic stress and cardiac overload / CVD events in patients with at least one CVD risk factor.

Caspase 6 promotes innate immune activation by functional crosstalk between RIPK1-IκBα axis in liver inflammation

BackgroundCaspase 6 is an essential regulator in innate immunity, inflammasome activation and host defense. We aimed to characterize the causal mechanism of Caspase 6 in liver sterile inflammatory injury.MethodsHuman liver tissues were harvested from patients undergoing ischemia-related hepatectomy to evaluate Caspase 6 expression. Subsequently, we created Caspase 6-knockout (Caspase 6KO) mice to analyze roles and molecular mechanisms of macrophage Caspase 6 in murine models of liver ischemia/reperfusion (IR) injury.ResultsIn human liver biopsies, Caspase 6 expression was positively correlated with more severe histopathological injury and higher serum ALT/AST level at one day postoperatively. Moreover, Caspase 6 was mainly elevated in macrophages but not hepatocytes in ischemic livers. Unlike in controls, the Caspase 6-deficient livers were protected against IR injury, as evidenced by inhibition of inflammation, oxidative stress and iron overload. Disruption of macrophage NF-κB essential modulator (NEMO) in Caspase 6-deficient livers deteriorated liver inflammation and ferroptosis. Mechanistically, Caspase 6 deficiency spurred NEMO-mediated IκBα phosphorylation in macrophage. Then phosphorylated-inhibitor of NF-κBα (p-IκBα) co-localized with receptor-interacting serine/ threonine-protein kinase 1 (RIPK1) in the cytoplasm to degradate RIPK1 under inflammatory conditions. The disruption of RIPK1-IκBα interaction preserved RIPK1 degradation, triggering downstream apoptosis signal-regulating kinase 1 (ASK1) phosphorylation and inciting NIMA-related kinase 7/NOD-like receptor family pyrin domain containing 3 (NEK7/NLRP3) activation in macrophages. Moreover, ablation of macrophage RIPK1 or ASK1 diminished NEK7/NLRP3-driven inflammatory response and dampened hepatocyte ferroptosis by reducing HMGB1 release from macrophages.ConclusionsOur findings underscore a novel mechanism of Caspase 6 mediated RIPK1-IκBα interaction in regulating macrophage NEK7/NLRP3 function and hepatocytes ferroptosis, which provides therapeutic targets for clinical liver IR injury.Graphical DRFRodggEVQV_MBi1PPYnNVideo

Mediating effects of social support, mental health between stress overload, fatigue and turnover intention among operating theatre nurses

BackgroundThe high rate of nurses turnover and nursing staff shortage have been an ongoing concern issue and a challenge for global health systems. To explore the turnover intention among operating theatre nurses, and to test the hypothetical model for estimating the effects of stress overload and fatigue between social support, mental health and turnover intention.Designa multi-center and cross-sectional online survey.MethodsThis study was conducted from October 2020 to March 2021 comprised 1060 operating theatre nurses from 76 Chinese hospitals. The descriptive analysis, independent sample t test and one-way analysis of variance and Spearman correlation analysis were used to explore the relationships among variables by the SPSS software, and stepwise multiple linear regression analysis was utilized to identify influencing factors of turnover intention and its dimensions among operating theatre nurses. A structural equation model was analyzed by the AMOS software.ResultsSocial support, mental health, stress overload and fatigue were important predictors of turnover intention among operating theatre nurses. Besides, stress overload positively affected fatigue, mental health and turnover intention; fatigue negatively affected social support, however, fatigue positively affected mental health; social support negatively affected mental health and turnover intention; mental health positively affected turnover intention. Moreover, social support, mental health mediated between stress overload, fatigue and turnover intention among operating theatre nurses.ConclusionSocial support, mental health mediated between stress overload, fatigue and turnover intention among operating theatre nurses.

Simulated microgravity-induced oxidative stress and loss of osteogenic potential of osteoblasts can be prevented by protection of primary cilia.

Oxidative stress has been considered to be closely related to spaceflight-induced bone loss; however, mechanism is elusive and there are no effective countermeasures. Using cultured rat calvarial osteoblasts exposed to microgravity simulated by a random positioning machine, this study addressed the hypotheses that microgravity-induced shortening of primary cilia leads to oxidative stress and that primary cilium protection prevents oxidative stress and osteogenesis loss. Microgravity was found to induce oxidative stress (as represented by increased levels of reactive oxygen species (ROS) and malondialdehyde production, and decreased activities of antioxidant enzymes), which was perfectly replicated in osteoblasts growing in NG with abrogated primary cilia (created by transfection of an interfering RNA), suggesting the possibility that shortening of primary cilia leads to oxidative stress. Oxidative stress was accompanied by mitochondrial dysfunction (represented by increased mitochondrial ROS and decreased mitochondrial membrane potential) and intracellular Ca2+ overload, and the latter was found to be caused by increased activity of Ca2+ channel transient receptor potential vanilloid 4 (TRPV4), as also evidenced by TRPV4 agonist GSK1016790A-elicited Ca2+ influx. Supplementation of HC-067047, a specific antagonist of TRPV4, attenuated microgravity-induced mitochondrial dysfunction, oxidative stress, and osteogenesis loss. Although TRPV4 was found localized in primary cilia and expressed at low levels in NG, microgravity-induced shortening of primary cilia led to increased TRPV4 levels and Ca2+ influx. When primary cilia were protected by miR-129-3p overexpression or supplementation with a natural flavonoid moslosooflavone, microgravity-induced increased TRPV4 expression, mitochondrial dysfunction, oxidative stress, and osteogenesis loss were all prevented. Our data revealed a new mechanism that primary cilia function as a controller for TRPV4 expression. Microgravity-induced injury on primary cilia leads to increased expression and overactive channel of TRPV4, causing intracellular Ca2+ overload and oxidative stress, and primary cilium protection could be an effective countermeasure against microgravity-induced oxidative stress and loss of osteogenic potential of osteoblasts.

How a pilot’s brain copes with stress and mental load? Insights from the executive control network

In aviation, mental workload and stress are two major factors that can considerably impact a pilot’s flight performance and decisions. Their consequences can be even more dramatic in single-pilot aircraft or with the forthcoming single-pilot operations where the pilot will fly alone and will not be able to be assisted in case of difficulty. An accurate and automatic monitoring of the pilot’s mental state could help to prevent the potentially dangerous effects of an excess mental workload and stress. For example, some tasks could be allocated to automation or to a ground-based flight crew if a mental overload or significant stress is detected. In the current study, the brain activity of 20 private pilots was recorded with a fNIRS device during two realistic flight simulator scenarios. The mental workload was manipulated with the added difficulty of a secondary task and stress was induced by a social stressor. Our results confirmed the sensitivity of the fNIRS readings to variations in the mental workload, with increased HbO2 concentration in regions of the executive control network (ECN), in particular in the dorsolateral prefrontal cortex and in lateral parietal regions, when the difficulty of the secondary task was high. The social stressor also triggered an HbO2 increase in the ECN, especially when it was combined with high mental workload. This latter result suggests that mental workload and stress together can have cumulative effects, and coping with both factors is possible at the expense of an extra recruitment of the ECN. Finally, results also revealed a time-on-task effect, with a progressive reduction of the HbO2 signal in the ECN during the flight scenario, suggesting that these regions are sensitive to short term habituation to the tasks. Overall, fNIRS efficiently indexed mental load, stress, and practice effects.

Potential for Novel Therapeutic Uses of Alpha Lipoic Acid.

Alpha-lipoic acid (ALA) is a potent antioxidant used in the management of diabetic neuropathy due to its ability to prevent neuronal lipid peroxidation. ALA also chelates transition metals, which can be beneficial in some diseases related to metal overload. Due to its unique antioxidant properties, ALA has potential novel applications in other diseases related to oxidative stress and inflammation. This review summarizes aspects of recent clinical trials and describes the uses of ALA in managing neuropathies. The unique pharmacological actions of ALA, coupled with relatively low toxicity, have led to several trials on the potential therapeutic uses of ALA in the management of diseases associated with increased oxidative stress, inflammation, and metal overload.