Hydroxychloroquine interaction with phosphoinositide 3-kinase modulates prostate cancer growth in bone microenvironment: In vitro and molecular dynamics based approach.

Patients with advanced prostate cancer (PCa) are more likely to develop bone metastases. Tumor cells thrive in the bone microenvironment, interacting with osteoblasts and osteoclasts. Given the PI3K/AKT pathway's metastatic potential and signal integration's ability to modulate cell fates in PCa development, drugs targeting this system have great therapeutic promise. Hydroxychloroquine (HCQ) is an anti-malarial medication commonly used to treat clinical conditions such as rheumatology and infectious disorders. We explored the anti-neoplastic effect of HCQ on PC3 and C4-2B cell lines in the bone microenvironment. Interestingly, HCQ treatment substantially decreases the viability, proliferation, and migration potential of PCa cells in the bone microenvironment. HCQ induces apoptosis and cell cycle arrest, even in the presence of osteoblast-secreted factors. Mechanistically, HCQ inhibited the activity of the PI3K/AKT signaling pathway, which ultimately regulates the proliferation and migration of PCa cells in the bone. The binding energy for docking HCQ with PI3K was -6.7 kcal/mol, and the complex was stabilized by hydrogen bonds, hydrophobic forces, and van der Waals forces. Molecular simulations further validated the structural integrity of the HCQ-PI3K complex without altering PI3K's secondary structure. Our findings underscore the efficacy of HCQ as a potential therapeutic agent in treating PCa.

Flexible sensor-based biomechanical evaluation of low-back exoskeleton use in lifting.

This study aimed to establish an ambulatory field-friendly system based on miniaturised wireless flexible sensors for studying the biomechanics of human-exoskeleton interactions. Twelve healthy adults performed symmetric lifting with and without a passive low-back exoskeleton, while their movements were tracked using both a flexible sensor system and a conventional motion capture (MoCap) system synchronously. Novel algorithms were developed to convert the raw acceleration, gyroscope, and biopotential signals from the flexible sensors into kinematic and dynamic measures. Results showed that these measures were highly correlated with those obtained from the MoCap system and discerned the effects of the exoskeleton, including increased peak lumbar flexion, decreased peak hip flexion, and decreased lumbar flexion moment and back muscle activities. The study demonstrated the promise of an integrated flexible sensor-based system for biomechanics and ergonomics field studies as well as the efficacy of exoskeleton in relieving the low-back stress associated with manual lifting.

This study established and tested a flexible sensor-based ambulatory system for biomechanical evaluation of human-exoskeleton interactions and as a promising new tool for field ergonomics studies in practical or naturalistic settings.Abbreviations: MoCap: motion capture; WMSD: Work-related musculoskeletal disorders; EMG: electromyography; IMU: inertial measurement unit; TES: thoracic erector spinae; LES: lumbar erector spinae; WITH: tasks performed with wearing the exoskeleton; WITHOUT: tasks performed without wearing the exoskeleton; RMS: root mean square; RMSE: root-mean-square error; r: Pearson's correlation coefficient; ASIS: anterior superior iliac spine.

Sex-specific Neural Strategies During Fatiguing Work in Older Adults.

BACKGROUND: Historical biases in ergonomics-related studies have been attributed to lack of participant diversity and sensitivity of measurements to capture variability between diverse groups. We posit that a neuroergonomics approach, that is, study of brain-behavior relationships during fatiguing work, allows for unique insights on sex differences in fatigue mechanisms that are not available via traditional "neck down" measurement approaches. OBJECTIVE: This study examined the supraspinal mechanisms of exercise performance under fatigue and determined if there were any sex differences in these mechanisms. METHODS: Fifty-nine older adults performed submaximal handgrip contractions until voluntary fatigue. Traditional ergonomics measures, namely, force variability, electromyography (EMG) of arm muscles, and strength and endurance times, and prefrontal and motor cortex hemodynamic responses were recorded. RESULTS: There were no significant differences observed between older males and females in fatigability outcomes (i.e., endurance times, strength loss, and EMG activity) and brain activation. Effective connectivity from prefrontal to motor areas was significant for both sexes throughout the task, but during fatigue, males had higher interregional connectivity than females. DISCUSSION: While traditional metrics of fatigue were comparable between the sexes, we observed distinct sex-specific neuromotor strategies (i.e., information flow between frontal-motor regions) that were adopted by older adults to maintain motor performance. APPLICATION: The findings from this study offer insights into the capabilities and adaptation strategies of older men and women under fatiguing conditions. This knowledge can facilitate in the development of effective and targeted ergonomic strategies that accommodate for the varying physical capacities of diverse worker demographics.

Neurophysiological, muscular, and perceptual adaptations of exoskeleton use over days during overhead work with competing cognitive demands.

This study captured neurophysiological, muscular, and perceptual adaptations to shoulder exoskeleton use during overhead work with competing physical-cognitive demands. Twenty-four males and females, randomly divided into control and exoskeleton groups, performed an overhead reaching and pointing task over three days without (single task) and with (dual task) a working memory task. Task performance, electromyography (EMG), neural activity, heart rate, and subjective responses were collected. While task completion time reduced for both groups at the same rate over days, EMG activity of shoulder muscles was lower for the exoskeleton group for both tasks, specifically for females during the dual task. Dual task reduced the physiological benefits of exoskeletons and neuromotor strategies to adapt to the dual task demands differed between the groups. Neuromuscular benefits of exoskeleton use were immediately realized irrespective of cognitive demand, however the perceptual, physiological, and neural adaptations with exoskeleton use were task- and sex-specific.

Modeling Brain Dynamics During Virtual Reality-Based Emergency Response Learning Under Stress.

BACKGROUND: Stress affects learning during training, and virtual reality (VR) based training systems that manipulate stress can improve retention and retrieval performance for firefighters. Brain imaging using functional Near Infrared Spectroscopy (fNIRS) can facilitate development of VR-based adaptive training systems that can continuously assess the trainee's states of learning and cognition. OBJECTIVE: The aim of this study was to model the neural dynamics associated with learning and retrieval under stress in a VR-based emergency response training exercise. METHODS: Forty firefighters underwent an emergency shutdown training in VR and were randomly assigned to either a control or a stress group. The stress group experienced stressors including smoke, fire, and explosions during the familiarization and training phase. Both groups underwent a stress memory retrieval and no-stress memory retrieval condition. Participant's performance scores, fNIRS-based neural activity, and functional connectivity between the prefrontal cortex (PFC) and motor regions were obtained for the training and retrieval phases. RESULTS: The performance scores indicate that the rate of learning was slower in the stress group compared to the control group, but both groups performed similarly during each retrieval condition. Compared to the control group, the stress group exhibited suppressed PFC activation. However, they showed stronger connectivity within the PFC regions during the training and between PFC and motor regions during the retrieval phases. DISCUSSION: While stress impaired performance during training, adoption of stress-adaptive neural strategies (i.e., stronger brain connectivity) were associated with comparable performance between the stress and the control groups during the retrieval phase.

Physiological and perceptual consequences of trust in collaborative robots: An empirical investigation of human and robot factors.

Measuring trust is an important element of effective human-robot collaborations (HRCs). It has largely relied on subjective responses and thus cannot be readily used for adapting robots in shared operations, particularly in shared-space manufacturing applications. Additionally, whether trust in such HRCs differ under altered operator cognitive states or with sex remains unknown. This study examined the impacts of operator cognitive fatigue, robot reliability, and operator sex on trust symptoms in collaborative robots through both objective measures (i.e., performance, heart rate variability) and subjective measures (i.e., surveys). Male and female participants were recruited to perform a metal surface polishing task in partnership with a collaborative robot (UR10), in which they underwent reliability conditions (reliable, unreliable) and cognitive fatigue conditions (fatigued, not fatigued). As compared to the reliable conditions, unreliable robot manipulations resulted in perceived trust, an increase in both sympathetic and parasympathetic activity, and operator-induced reduction in task efficiency and accuracy but not precision. Cognitive fatigue was shown to correlate with higher fatigue scores and reduced task efficiency, more severely impacting females. The results highlight key interplays between operator states of fatigue, sex, and robot reliability on both subjective and objective responses of trust. These findings provide a strong foundation for future investigations on better understanding the relationship between human factors and trust in HRC as well as aid in developing more diagnostic and deployable measures of trust.

To kill a cancer: Targeting the immune inhibitory checkpoint molecule, B7-H3.

Targeting the anti-tumor immune response via the B7 family of immune-regulatory checkpoint proteins has revolutionized cancer treatment and resulted in punctuated responses in patients. B7-H3 has gained recent attention given its prominent deregulation and immunomodulatory role in a multitude of cancers. Numerous cancer studies have firmly established a strong link between deregulated B7-H3 expression and poorer outcomes. B7-H3 has been shown to augment cancer cell survival, proliferation, metastasis, and drug resistance by inducing an immune evasive phenotype through its effects on tumor-infiltrating immune cells, cancer cells, cancer-associated vasculature, and the stroma. Given the complex interplay between each of these components of the tumor microenvironment, a deeper understanding of B7-H3 signaling properties is inherently crucial to developing efficacious therapies that can target and inhibit these cancer-promoting interactions. This review delves into the various ways B7-H3 acts as an immunomodulator to facilitate immune evasion and promote tumor growth and spread. With post-transcriptional and post-translational modifications giving rise to different active isoforms coupled with recent discoveries of its putative receptors, B7-H3 can perform diverse functions. Here, we first discuss the dual co-stimulatory/co-inhibitory functions of B7-H3 in the context of normal physiology and cancer. We then discuss the crosstalk facilitated by B7-H3 between stromal components and tumor cells that promote tumor growth and metastasis in different populations of tumor cells, associated vasculature, and the stroma. Concurrently, we highlight therapeutic strategies that can exploit these interactions and their associated limitations, concluding with a special focus on the promise of next-gen in silico-based approaches to small molecule inhibitor drug discovery for B7-H3 that may mitigate these limitations.

Trust in Shared-Space Collaborative Robots: Shedding Light on the Human Brain.

BACKGROUND: Industry 4.0 is currently underway allowing for improved manufacturing processes that leverage the collective advantages of human and robot agents. Consideration of trust can improve the quality and safety in such shared-space human-robot collaboration environments. OBJECTIVE: The use of physiological response to monitor and understand trust is currently limited due to a lack of knowledge on physiological indicators of trust. This study examines neural responses to trust within a shared-workcell human-robot collaboration task as well as discusses the use of granular and multimodal perspectives to study trust. METHODS: Sixteen sex-balanced participants completed a surface finishing task in collaboration with a UR10 collaborative robot. All participants underwent robot reliability conditions and robot assistance level conditions. Brain activation and connectivity using functional near infrared spectroscopy, subjective responses, and performance were measured throughout the study. RESULTS: Significantly, increased neural activation was observed in response to faulty robot behavior within the medial and right dorsolateral prefrontal cortex (PFC). A similar trend was observed for the anterior PFC, primary motor cortex, and primary visual cortex. Faulty robot behavior also resulted in reduced functional connectivity strengths throughout the brain. DISCUSSION: These findings implicate regions in the prefrontal cortex along with specific connectivity patterns as signifiers of distrusting conditions. The neural response may be indicative of how trust is influenced, measured, and manifested for human-robot collaboration that requires active teaming. APPLICATION: Neuroergonomic response metrics can reveal new perspectives on trust in automation that subjective responses alone are not able to provide.

A Window Into the Tired Brain: Neurophysiological Dynamics of Visuospatial Working Memory Under Fatigue.

OBJECTIVE: We examine the spatiotemporal dynamics of neural activity and its correlates in heart rate and its variability (HR/HRV) during a fatiguing visuospatial working memory task. BACKGROUND: The neural and physiological drivers of fatigue are complex, coupled, and poorly understood. Investigations that combine the fidelity of neural indices and the field-readiness of physiological measures can facilitate measurements of fatigue states in operational settings. METHOD: Sixteen healthy adults, balanced by sex, completed a 60-minute fatiguing visuospatial working memory task. Changes in task performance, subjective measures of effort and fatigue, cerebral hemodynamics, and HR/HRV were analyzed. Peak brain activation, functional and effective connections within relevant brain networks were contrasted against spectral and temporal features of HR/HRV. RESULTS: Task performance elicited increased neural activation in regions responsible for maintaining working memory capacity. With the onset of time-on-task effects, resource utilization was seen to increase beyond task-relevant networks. Over time, functional connections in the prefrontal cortex were seen to weaken, with changes in the causal relationships between key regions known to drive working memory. HR/HRV indices were seen to closely follow activity in the prefrontal cortex. CONCLUSION: This investigation provided a window into the neurophysiological underpinnings of working memory under the time-on-task effect. HR/HRV was largely shown to mirror changes in cortical networks responsible for working memory, therefore supporting the possibility of unobtrusive state recognition under ecologically valid conditions. APPLICATIONS: Findings here can inform the development of a fieldable index for cognitive fatigue.

Mind over body: A neuroergonomic approach to assessing motor performance under stress in older adults.

Stress impairs motor performance, which is exacerbated with age. Stress also impairs brain activity in the prefrontal cortex, which communicates with the motor areas of the brain to regulate exercise and motor performance. To develop ergogenic strategies for the aging workforce, mind (brain)-body mechanisms behind the effect of stress on neuromuscular performance need to be well understood. This study investigated the influence of social stress on motor performance and information flow between the frontal and motor regions of the brain during intermittent handgrip contractions among older adults. Thirty older adults, balanced by gender, performed intermittent handgrip contractions at 30% of maximum strength before and after being subjected to a social stressor. Force steadiness, strength loss, root mean square electromyogram (EMG) activity, activation of the brain regions, and functional and effective connectivity between the frontal and motor brain regions were computed for pre- and post-stressor handgrip contractions. Older men exhibited improved motor performance after the stressor and concomitant reduction in functional connectivity between the frontal-motor brain regions ipsilateral to the contracting hand. Additionally, while both sexes exhibited significant causal information flow, i.e., effective connectivity, from the frontal to the motor regions of the brain, irrespective of the stressor, older women exhibited a bidirectional effective connectivity between the frontal-motor brain regions after the stressor. Stress had a facilitative effect on the motor performance of older men through compensatory brain network reorganization. Older women exhibited comparable motor performance pre/post stress, despite showing an increase in bidirectional information flow between the frontal-motor areas. Employing brain hemodynamics can facilitate better understanding of the impact of stress on neuromuscular performance and its differential impacts on brain network reorganization between the sexes.

Rethinking the chemokine cascade in brain metastasis: Preventive and therapeutic implications.

Brain metastasis (BrM) is one of the major causes of death in cancer patients and is associated with an estimated 10-40 % of total cancer cases. The survival rate of brain metastatic patients has not improved due to intratumor heterogeneity, the survival adaptations of brain homing metastatic cells, and the lack of understanding of underlying molecular mechanisms that limit the availability of effective therapies. The heterogeneous population of immune cells and tumor-initiating cells or cancer stem cells in the tumor microenvironment (TME) release various factors, such as chemokines that upon binding to their cognate receptors enhance tumor growth at primary sites and help tumor cells metastasize to the brain. Furthermore, brain metastatic sites have unique heterogeneous microenvironment that fuels cancer cells in establishing BrM. This review explores the crosstalk of chemokines with the heterogeneous TME during the progression of BrM and recognizes potential therapeutic approaches. We also discuss and summarize different targeted, immunotherapeutic, chemotherapeutic, and combinatorial strategies (with chemo-/immune- or targeted-therapies) to attenuate chemokines mediated BrM.

MiR-212-3p functions as a tumor suppressor gene in group 3 medulloblastoma via targeting nuclear factor I/B (NFIB).

Haploinsufficiency of chromosome 17p and c-Myc amplification distinguish group 3 medulloblastomas which are associated with early metastasis, rapid recurrence, and swift mortality. Tumor suppressor genes on this locus have not been adequately characterized. We elucidated the role of miR-212-3p in the pathophysiology of group 3 tumors. First, we learned that miR-212-3p undergoes epigenetic silencing by histone modifications in group 3 tumors. Restoring its expression reduced cancer cell proliferation, migration, colony formation, and wound healing in vitro and attenuated tumor burden and improved survival in vivo. MiR-212-3p also triggered c-Myc destabilization and degradation, leading to elevated apoptosis. We then isolated an oncogenic target of miR-212-3p, i.e. NFIB, a nuclear transcription factor implicated in metastasis and recurrence in various cancers. Increased expression of NFIB was confirmed in group 3 tumors and associated with poor survival. NFIB silencing reduced cancer cell proliferation, migration, and invasion. Concurrently, reduced medullosphere formation and stem cell markers (Nanog, Oct4, Sox2, CD133) were noted. These results substantiate the tumor-suppressive role of miR-212-3p in group 3 MB and identify a novel oncogenic target implicated in metastasis and tumor recurrence.

Correction: Kaushal et al. Repurposing Niclosamide for Targeting Pancreatic Cancer by Inhibiting Hh/Gli Non-Canonical Axis of Gsk3ß. Cancers 2021, 13, 3105.

The authors would like to make a correction to their published paper [...].

rbcL, a potential candidate DNA barcode loci for aconites: conservation of himalayan aconites.

BACKGROUND: Aconitum heterophyllum Wall. ex Royle and Aconitum balfourii Stapf, are two highly important, threatened medicinal plants of the Indian Himalayan Region. Root-tubers of Aconites have occupied an important place in Indian pharmacopoeia from very ancient times. India is a hub of the wild-collected medicinal herbs industry in Asia and these two aconites are known to have been heavily traded from the region in illicit manner. Prosecution of these illegal trading crimes is hampered by lack of pharma-forensic expertise and tools. METHODS AND RESULTS: Present study was conducted to evaluate the discriminatory potential of rbcL, a Chloroplast based DNA barcode marker for the authentication of these two Himalayan Aconites. Fresh plant samples were collected from their natural distributional range as well as raw materials were procured from herbal market and a total of 32 sequences were generated for the rbcL region. Analysis demonstrated that rbcL region can successfully be used for authentication and importantly, both the aconites, were successfully discriminated by rbcL locus with high bootstrap support (> 50%). CONCLUSION: Molecular markers could certainly be relied upon morphological and chemical markers being tissue specific, having a higher discriminatory power and not age dependent. Phylogenetic analysis using Maximum Likelihood Method revealed that the rbcL gene could successfully discriminate Himalayan Aconites to species level and have potential to be used in pharma-forensic applications as well as to curb illicit trade of these invaluable medicinal plants.

Anodal tDCS augments and preserves working memory beyond time-on-task deficits.

Transcranial direct current stimulation (tDCS) of the left dorsolateral prefrontal cortex (DLPFC) has been shown to promote working memory (WM), however, its efficacy against time-on-task-related performance decline and associated cognitive fatigue remains uncertain. This study examined the impact of anodal tDCS of the left DLPFC on performance during a fatiguing visuospatial WM test. We adopted a repeated measures design, where 32 healthy adults (16 female), underwent anodal, control and sham tDCS on separate days. They completed an hour long two-back test, with stimulation intensity, onset, and duration set at 1 mA, at the 20th minute for 10 minutes respectively. Task performance, subjective responses, and heart rate variability (HRV) were captured during the experiment. Anodal tDCS substantially improved WM relative to sham tDCS and control in both sexes. These benefits lasted beyond the stimulation interval, and were unique across performance measures. However, no perceptual changes in subjective effort or fatigue levels were noted between conditions, although participants reported greater discomfort during stimulation. While mood and sleepiness changed with time-on-task, reflecting fatigue, these were largely similar across conditions. HRV increased under anodal tDCS and control, and plateaued under sham tDCS. We found that short duration anodal tDCS at 1 mA was an effective countermeasure to time-on-task deficits during a visuospatial two-back task, with enhancement and preservation of WM capacity. However, these improvements were not available at a perceptual level. Therefore, wider investigations are necessary to determine "how" such solutions will be operationalized in the field, especially within human-centered systems.

Brain Activity-Based Metrics for Assessing Learning States in VR under Stress among Firefighters: An Explorative Machine Learning Approach in Neuroergonomics.

The nature of firefighters` duties requires them to work for long periods under unfavorable conditions. To perform their jobs effectively, they are required to endure long hours of extensive, stressful training. Creating such training environments is very expensive and it is difficult to guarantee trainees' safety. In this study, firefighters are trained in a virtual environment that includes virtual perturbations such as fires, alarms, and smoke. The objective of this paper is to use machine learning methods to discern encoding and retrieval states in firefighters during a visuospatial episodic memory task and explore which regions of the brain provide suitable signals to solve this classification problem. Our results show that the Random Forest algorithm could be used to distinguish between information encoding and retrieval using features extracted from fNIRS data. Our algorithm achieved an F-1 score of 0.844 and an accuracy of 79.10% if the training and testing data are obtained at similar environmental conditions. However, the algorithm's performance dropped to an F-1 score of 0.723 and accuracy of 60.61% when evaluated on data collected under different environmental conditions than the training data. We also found that if the training and evaluation data were recorded under the same environmental conditions, the RPM, LDLPFC, RDLPFC were the most relevant brain regions under non-stressful, stressful, and a mix of stressful and non-stressful conditions, respectively.

Repurposing Niclosamide for Targeting Pancreatic Cancer by Inhibiting Hh/Gli Non-Canonical Axis of Gsk3ß.

Niclosamide (Nic), an FDA-approved anthelmintic drug, is reported to have anti-cancer efficacy and is being assessed in clinical trials for various solid tumors. Based on its ability to target multiple signaling pathways, in the present study, we evaluated the therapeutic efficacy of Nic on pancreatic cancer (PC) in vitro. We observed an anti-cancerous effect of this drug as shown by the G0/G1 phase cell cycle arrest, inhibition of PC cell viability, colony formation, and migration. Our results revealed the involvement of mitochondrial stress and mTORC1-dependent autophagy as the predominant players of Nic-induced PC cell death. Significant reduction of Nic-induced reactive oxygen species (ROS) and cell death in the presence of a selective autophagy inhibitor spautin-1 demonstrated autophagy as a major contributor to Nic-mediated cell death. Mechanistically, Nic inhibited the interaction between BCL2 and Beclin-1 that supported the crosstalk of autophagy and apoptosis. Further, Nic treatment resulted in Gsk3ß inactivation by phosphorylating its Ser-9 residue leading to upregulation of Sufu and Gli3, thereby negatively impacting hedgehog signaling and cell survival. Nic induced autophagic cell death, and p-Gsk3b mediated Sufu/Gli3 cascade was further confirmed by Gsk3ß activator, LY-294002, by rescuing inactivation of Hh signaling upon Nic treatment. These results suggested the involvement of a non-canonical mechanism of Hh signaling, where p-Gsk3ß acts as a negative regulator of Hh/Gli1 cascade and a positive regulator of autophagy-mediated cell death. Overall, this study established the therapeutic efficacy of Nic for PC by targeting p-Gsk3ß mediated non-canonical Hh signaling and promoting mTORC1-dependent autophagy and cell death.

Neural and biomechanical tradeoffs associated with human-exoskeleton interactions.

Industrial passive low-back exoskeletons have gained recent attention as ergonomic interventions to manual handling tasks. This research utilized a two-armed experimental approach (single vs dual-task paradigms) to quantify neural and biomechanical tradeoffs associated with short-term human-exoskeleton interaction (HEI) during asymmetrical lifting in twelve healthy adults balanced by gender. A dynamic, electromyography-assisted spine model was employed that indicated statistical, but marginal, biomechanical benefits of the tested exoskeleton, which diminished with the introduction of the cognitive dual-task. Using Near Infrared Spectroscopy (fNIRS)-based brain connectivity analyses, we found that the tested exoskeleton imposed greater neurocognitive and motor adaptation efforts by engaging action monitoring and error processing brain networks. Collectively, these findings indicate that a wearer's biomechanical response to increased cognitive demands in the workplace may offset the mechanical advantages of exoskeletons. We also demonstrate the utility of ambulatory fNIRS to capture the neural cost of HEI without the need for elaborate dual-task manipulations.

Relationship Between Acute Physical Fatigue and Cognitive Function During Orthostatic Challenge in Men and Women: A Neuroergonomics Investigation.

BACKGROUND: Postflight orthostatic challenge (OC), resulting from blood pooling in lower extremities, is a major health concern among astronauts that fly long-duration missions. Additionally, astronauts undergo physical demanding tasks resulting in acute fatigue, which can affect performance. However, the effects of concurrent OC and acute physical fatigue on performance have not been adequately investigated. OBJECTIVE: The purpose of this study was to determine the relationship between acute physical fatigue and cognitive function during OC. METHODS: Sixteen healthy participants performed the mental arithmetic task and psychomotor tracking tasks in the absence and presence of a prior 1-hour physically fatiguing exercise, on separate days under OC (induced via lower body negative pressure). We recorded task performances on the cognitive tests and prefrontal cortex oxygenation using functional near-infrared spectroscopy, along with physiological and subjective responses. RESULTS: The introduction of the cognitive tasks during OC increased cerebral oxygenation; however, oxygenation decreased significantly with the cognitive tasks under the acute fatigue conditions, particularly during the tracking task and in males. These differences were accompanied by comparable task performances. DISCUSSION: The findings suggest that mental arithmetic is a more effective countermeasure than psychomotor tracking under acute physical fatigue during OC. Whereas females did not show a significant difference in cerebral oxygenation due to task, males did, suggesting that it may be important to consider gender differences when developing countermeasures against OC.

Revealing Sex Differences During Upper and Lower Extremity Neuromuscular Fatigue in Older Adults Through a Neuroergonomics Approach.

Background: Sex differences in neuromuscular fatigue is well-documented, however the underlying mechanisms remain understudied, particularly for the aging population. Objective: This study investigated sex differences in fatigability of the upper and lower extremity of older adults using a neuroergonomics approach. Methods: Thirty community-dwelling older adults (65 years or older; 15 M, 15 F) performed intermittent submaximal fatiguing handgrip and knee extension exercises until voluntary exhaustion on separate days. Muscle activity from prime muscles of the hand/arm and knee extensors were monitored using electromyography, neural activity from the frontal, motor, and sensory areas were monitored using functional near infrared spectroscopy, and force output were obtained. Results: While older males were stronger than females across both muscle groups, they exhibited longer endurance times and greater strength loss during knee extension exercises. These lower extremity findings were associated with greater force complexity over time and concomitant increase in left motor and right sensory motor regions. While fatigability during handgrip exercises was comparable across sexes, older females exhibited concurrent increases in the activation of the ipsilateral motor regions over time. Discussion: We identified differences in the underlying central neural strategies adopted by males and females in maintaining downstream motor outputs during handgrip fatigue that were not evident with traditional ergonomics measures. Additionally, enhanced neural activation in males during knee exercises that accompanied longer time to exhaustion point to potential rehabilitation/exercise strategies to improve neuromotor outcomes in more fatigable older adults.