Live Performance Research Articles

Prevalence and impact of scapular muscle pain among video gamers in Rawalpindi and Islamabad: A cross-sectional study

Scapular muscle pain is common among individuals who engage in prolonged video gaming sessions. Poor posture, repetitive movements, and extended screen time contribute to musculoskeletal discomfort, particularly in the muscles surrounding the scapula. With the rise in Esports and video gaming as a primary source of entertainment, there is a growing need to understand the prevalence and impact of scapular muscle pain among gamers. This study aimed to identify the prevalence of scapular muscle pain among video gamers in Rawalpindi and Islamabad and to investigate the impact of this pain on gaming performance and quality of life. A cross-sectional descriptive study was conducted over six months in various gaming centers, communities, and universities in Rawalpindi and Islamabad. 100 male video gamers aged 15 to 40 were selected using non-probability convenience sampling. Pain and functional limitations were measured using the Numerical Pain Rating Scale (NPRS), Shoulder Pain and Disability Index (SPADI), and Scapular Assistance Test. Data were analyzed using SPSS version 26. Most participants (86%) were aged 15-25 years, with gaming hours ranging from 3-7 hours per day. Pain intensity assessment revealed that 59% of participants experienced moderate pain, while 8% reported severe pain. SPADI results indicated that 56% of gamers had very severe pain and disability. The Scapular Assistance Test showed that 68% of participants tested positive, indicating the presence of scapular muscle pain. Scapular muscle pain is prevalent among video gamers in Rawalpindi and Islamabad, particularly younger gamers who engage in prolonged gaming sessions. The study highlights the need for interventions to address poor posture and reduce the risk of musculoskeletal issues in this population.

Pediatric SARS-CoV-2 long term outcomes study (PECOS): cross sectional analysis at baseline.

PECOS is an ongoing study aimed to characterize long-term outcomes following pediatric SARS-CoV-2 infection. This is a cross-sectional analysis of infected and uninfected cohorts at baseline. Participants (0-21 years) with laboratory-confirmed SARS-CoV-2 infection were enrolled as infected. Uninfected were defined as individuals without history or laboratory evidence of SARS-CoV-2 infection. Outcome measures included demographics, medical history, review of symptoms, physical exam, cardiopulmonary evaluation and validated psychological and developmental surveys. Primary outcomes were cohort comparisons for abnormalities on all measures. 654 participants (541 infected, 113 uninfected) completed baseline visits by June 30, 2023. Infected participants were more likely to report constitutional (OR: 2.24), HEENT (OR: 3.74); respiratory (OR: 2.41), or gastrointestinal (OR: 2.58) symptoms. Infected had worse scores in domains of Pain, Fatigue, Global Health, Physical and Cognitive functioning, Mobility and Sleep disturbances when compared to uninfected controls using Patient Reported Outcomes. Cardiopulmonary findings were similar among cohorts. The first report of this ongoing longitudinal study demonstrates that infected participants were more likely to report symptoms compared to uninfected controls, which may affect performance and quality of life of these individuals. Longitudinal data will increase understanding of long-term effects of SARS-CoV-2 infection in children. gov Identifier: NCT04830852 IMPACT: This study establishes a large, diverse, prospective, longitudinal, multi-center cohort of children with history of SARS-CoV-2 infection compared to an uninfected cohort to be followed for 3 years. Cross-sectional cohort analysis at study entry showed infected participants were more likely to report constitutional, respiratory, and GI symptoms compared to uninfected controls. Infected participants were more likely to have significantly worse parent-reported performance in 6 of 10 Patient Reported Outcome Measures domains. Continued study of this cohort will help identify clinical sequelae of COVID-19, characterize the immune response to SARS-CoV-2 infection, and identify potential genetic/immunologic factors associated with long-term outcomes.

New Mechanisms of Phase Transition in Olivine‐Type LixMn0.7Fe0.3PO4 Cathodes: a Finding on Relaxation Behavior and its Implications for Battery Performance

AbstractPhosphates of the olivine type, LiMnyFe1‐yPO4 (LMFP), have garnered significant attention due to their higher energy density compared to LiFePO4 (LFP). However, their limited cycle life and rate performance remain key obstacles to their commercialization. Therefore, elucidating the intricate phase transition mechanisms during electrochemical cycling is paramount to overcoming this bottleneck. This study investigates the relaxation behavior of LixMn0.7Fe0.3PO4 (0≤x≤1) under various conditions revealed a remarkable memory characteristic in its crystal structure: the lattice parameters of different delithiated states return to their fully lithiated configuration upon complete relaxation. Moreover, the relaxation rate is influenced by the charging/discharging conditions and storage environment: higher rates, greater delithiation, and longer relaxation times are observed, as are extended relaxation time at lower temperatures and in the absence of electrolyte. These findings provide a rational explanation for the complexity of the phase transition mechanisms in LMFP and highlight the significant differences in phase transition and relaxation behaviors, advancing the understanding of LMFP materials.

Effects of a symptom-titrated exercise program on fatigue and quality of life in people with post-COVID condition – a randomized controlled trial

Fatigue is the most prevalent symptom within the post-COVID condition (PCC). Furthermore, many patients suffer from decreased physical performance capacity and post-exertional malaise. Although exercise has been proposed as an effective therapeutic strategy for PCC, there is limited evidence on individualised and symptom-titrated exercise interventions in patients with fatigue and PEM. Therefore, we conducted a multi-centre randomised controlled trial to investigate the effectiveness of an individualised and symptom-titrated exercise program. We measured fatigue, health-related quality of life, hand-grip strength, endurance capacity and PEM before and after the 10-week intervention. A total of 118 individuals with PCC were included in the final intention-to-treat analysis. All tests and training sessions took place in commercial fitness and health facilities. We found significant effects on fatigue severity, health-related quality of life and physical performance capacity. Adjusting the individual exercise load to daily fatigue has proven to be an effective and safe strategy in PCC patients with fatigue. Under the guidance of qualified professionals and by utilising symptom-titrated training recommendations, commercial fitness and health facilities present an appropriate setting for outpatient exercise rehabilitation in PCC.

Functional Vision Questionnaire Detects Near Triad Impairments in Adolescent Athletes With Concussion History.

Concussions are mild traumatic brain injuries that often cause vision problems. They have significant impacts on everyday life, cognitive capacity, and sports performance, and may affect injury prevalence in fast contact sports such as ice hockey. A functional vision questionnaire specifically designed for sports was used here to study the correlation between vision problems and concussion history. In this national cross-sectional concussion study, 860 Finnish elite-level male adolescent ice hockey players (aged 13-21 years) answered a functional vision questionnaire and performed a computerized neurocognitive test, ImPACT. Totally 265 athletes reported a history of at least 1 concussion. All data were statistically compared with age-matched athletes with no concussion history (n = 595). For further analysis, athletes were divided into subgroups by age and number of previous concussions. Previously concussed athletes reported more general and eye-specific symptoms than their healthy controls. Increases in eye fatigue, frontal headaches, and blinking were statistically significant. Also statistically more problems with depth perception and evaluating distances, concentration problems, blurred vision, and losing the object in sight were observed among athletes with concussion history. Concussion history reflects an increase in the prevalence of vision deficits, as determined by multiple disturbances in the near triad. The significant number of vision problems in the concussion history groups strongly suggests that functional vision should routinely be evaluated in athletes. The vision problems observed in the athletes with concussion history may indicate an increased injury risk that should be addressed.

Intensity of <em>Haemoproteus</em> spp. blood infection differs between wild birds captured using different trapping methods

Infection with haemoparasites (Haemosporida spp.) is common within wild birds’ populations and has been associated with adverse effects on birds’ fitness and life performance. Existing literature suggests a hypothesis that birds infected with haemosporidians and exhibiting high parasitemia levels may demonstrate reduced activity, potentially leading to their underrepresentation in captures which use stationary traps, such as mist nets. However, there are limited studies demonstrating this phenomenon in wild birds. To study the possible under representation of highly parasitized birds, captured with commonly used stationary mist nets, we compared parasitemia levels of haemosporidian parasites in wild birds captured during spring migration using both actively startling of birds and birds trapped passively into the mist nets. Utilizing cumulative link mixed models, we assessed the influence of trapping methods on parasitemia scores, controlling for factors such as species identity, season progression, and migration distance. Our dataset comprised 1815 individuals of 60 species, including 142 actively captured and 1673 passively captured ones. Although the number of infected individuals was higher in passively caught birds (24 % in active vs 43 % in passive), the study revealed a significant difference between infected birds within two capture methods: despite challenges in balancing sample sizes, and trapping dates, the findings affirm the underestimation of birds having high parasitemia levels with prevalent mist net techniques. We highlight the importance of considering potential biases in trapping methods when studying haemosporidian parasites in avian hosts during migration.

Effect of Aerobic Training on Quality of Life in the Elderly with Idiopathic Chronic Fatigue

Objective: Idiopathic chronic fatigue (ICF) is described as clinically diagnosed physical and/or psychological chronic fatigue of more than 6 months, with no known/detected underlying pathologies/disorders. As no study has discussed the effect of scheduled, regular, and supervised aerobic exercise on fatigue severity, physical performance, and quality of life (QoL) in ICF elderly, this study was applied to achieve this aim. Material and Methods: Forty ICF elderly (from both genders) were divided evenly into the study group that received 8-week aerobic exercises plus traditional physical therapy balance and stretching exercises (n=20) and the control group (n=20) who received traditional physical therapy balance and stretching exercises only. The fatigue severity assessment scale (FSAS), The elderly’s Brief-Version Quality-of-Life Questionnaire (EBVQOLQ), six-minute walking distance (6MWD), and serum glutathione (as an anti-oxidative substance) were assessed. Results: Only the study group’s outcomes (EBVQOLQ, six minute walk distance (SMWD), serum glutathione, and FSAS) showed significant improvements. Conclusion: Eight-week aerobic exercises in ICF elderly can improve fatigue perception, physical performance/capacity, QoL, and anti-oxidative defense.

Scourge of replacing contemporary work environment with artificial intelligence (AI-dark-side): the role of capacity development in quality of work-life and organisational performance

Purpose The emergence of artificial intelligence (AI) which operates through technology and digital workspace has proven to transform organisations in recent times. However, there has been key concern over its efficiency among the workforce on how it may replace human intelligence in the contemporary work environment. This study aims to investigate the drawbacks otherwise known as the dark side of AI and its effect on employee quality of work−life and organisational performance through the lens of employee capacity development in reducing its shortcomings. Design/methodology/approach This study used a descriptive research design using a cross-sectional survey approach to administer the research instrument to 1,847 customer service officers of banks, customer agents of telecoms, customer care of retail organisations in Nigeria business environment across various units were respondents of this study, however, 862 participants were finally used. A simple random strategy was used to survey the study participants, and existing scales were adopted to form a new research instrument. A partial least square (PLS) based structural equation model (SEM) was adapted to analyse the collected data from the respondents. Findings The outcome of the study indicated that AI lacks creativity and has a negative impact on both employee quality of work−life and overall organisational performance. The outcome of the study demonstrated the drawbacks and the dark sides of AI as lack of emotional intelligence, lack of in-depth contextual knowledge, over-reliance on data quality and lack of ethical and moral decision analysis are the possible dark side of AI which adversely affect quality of work−life and overall performance of the organisations. The study concluded that it is difficult to replace human intelligence because of AI’s drawbacks and dark side. AI cannot function effectively beyond what is programmed in the system. Originality/value This study has offered a novel trajectory against the efficiency and possible benefits of AI that people are familiar with. It has changed the understanding of the researchers, policymakers and organisations that AI cannot replace human intelligence in the workplace without improvement on those established AI dark sides.

Formative Evaluation of Post-Opera Live Discussion of the Center Cannot Hold Part 2 and Resilience Workshop

AbstractThere are few studies of impacts of arts on recovery in schizophrenia, on audience and cast responses. We developed a formative qualitative evaluation of audience and cast discussions after viewing live performances in a university setting of an opera based on Elyn Saks’ journey from psychosis, teaching law and falling in love, coupled with pre-opera workshop on community approaches to resilience. Live discussions were conducted with audience, cast members, and workshop presenters after performance of the opera, with recording and transcription, and reflexive thematic qualitative analysis sequentially conducted by 3 investigators/2 event leaders). Across 3 events, there were 81 comments (65’10” total time) from facilitator, audience members, cast and creators. Key themes across participant groups were: (1) Connecting with the story; (2) Identifying “normal” lifestyles with mental illness; (3) Refocusing goals of care for providers; (4) Increasing awareness around mental health; with an overarching theme the value of art on mental health to highlight awareness of these issues. Live art events (opera with pre-workshop) on mental health with author with lived experience present, were noted by audience and cast as enhancing connection, enhancing understanding of mental illness and clarifying goals for care, through the shared experience of art. This may inform future research and art events on mental health.

Voicing (Medical) Complexity in the Theatre of Sarah Kane: 4.48 Psychosis (1999) and its Stage Adaptation by Deafinitely Theatre (2018)

This paper proposes a reading of Sarah Kane’s 4.48 Psychosis (1999) from a theoretical perspective combining medical humanities, disability, and performance studies (Henderson and Ostrander; Murray); the aim is to expand upon previous scholarship which sought to analyse Kane’s multifarious ways of aestheticising—and questioning—illness and pain (e.g. Guarracino, “Scene”; Simon; Soncini), by reading medical discourse through the notion of ‘complexity’ (Kuppers, Theatre; Siebers). Firstly, I will focus on how complexity comes to the surface through the dramatic text: as Jolene Armstrong has pointed out, the linguistic renderings of a psychotic mind—staged as a medical spectacle—make 4.48 Psychosis a peculiar case study because it is “less like a play than a prose poem intended for interpretative performance” (Armstrong 177). Secondly, I will look at how Deafinitely Theatre attempted to translate the dramatic text into a bilingual performance (i.e. in spoken English and British Sign Language), set in a mixed-reality environment (e.g. the incorporation of video material into the live performance). Ultimately, this dual dimension will hopefully shed new light on the degree of performability of (medical) complexity in 4.48 Psychosis.

Labor Law Analysis of the Implementation of Menstrual Leave for Female Workers

Menstruation is a biological function that occurs naturally and is important in contributing to reproduction for all women. Even though it is a reproductive function that is experienced naturally by women, the experience of menstruation can vary, from mild symptoms to severe symptoms. As a result of menstrual symptoms on the first and second day experienced by almost all women, this causes their activities, performance and quality of life to be disrupted. This is a consideration for the Government to implement menstrual leave for companies in Indonesia. Menstrual leave was implemented by the government in labor law No.13 of 2003. The creation of labor law regulations was nothing more than a relief to working conditions for female workers. Although the law recognizes the right to menstrual leave, there are many obstacles to exploiting the right which requires a lot of practical activities and a deep understanding of more real situations or actions.

Indirect Effect of Organizational Commitment on The Relationship Between Quality of Work Life and Job Performance Among Academics in Malaysia

Indirect Effect of Organizational Commitment on The Relationship Between Quality of Work Life and Job Performance Among Academics in Malaysia

Serious Game-Based Balance Training with Augmented Kinesthetic Feedback Enhances Aspects of Postural Control in Poststroke Patients: A Randomized Clinical Trial.

Background: Poststroke hemiparesis presents with motor asymmetry and decreased postural control leading to functional limitations. Serious games (SG) for balance rehabilitation of people with stroke may improve motor recovery, and the visual and auditory feedback provided by the SGs helps to explain the therapeutic benefits. However, the contribution of SG combined with kinesthetic and verbal cues during balance training has not been investigated. The aim of this study is to compare the effects of two feedback conditions for an SG balance intervention, with or without the addition of kinesthetic and verbal cues, on balance performance of people with stroke. Methods: Thirty people with chronic poststroke hemiparesis and balance impairment participated in this randomized controlled trial and performed 14 individual SG training sessions combined with kinesthetic and verbal cues provided by the physical therapist or with SG's feedback only. Outcomes were assessed before training (pre), 1 week after the end of training (post), and 8 weeks after the end of training, which were adopted as the follow-up period, using the Balance Evaluation Systems Test, Lower Limb Subscale of Fugl-Meyer, six-minute walk test, and Stroke-Specific Quality of Life Scale. Results: The results showed that SG combined with kinesthetic and verbal cues improved outcomes relating to lower limb function and some balance domains (biomechanical constraints and limits of stability outcomes) better than with SG's feedback only. Both groups had similar significant improvement in quality of life and long-distance walking performance. Conclusion: This study is the first to directly compare two feedback conditions for SG-based balance intervention. The addition of kinesthetic and verbal cues during the SG balance improved aspects of postural control better than without this form of feedback.

Evaluation of the Influence of Quality of Life on Work Performance in the Population with Diabetes Mellitus

To evaluate the influence of quality of life on work performance in Type II Diabetes Mellitus, determining the main factors and dimensions that make up the study variables. This research has a quantitative approach and a correlational scope through an instrument designed to estimate the quality of life and work performance. 387 surveys were obtained as a result of Cronbach’s alpha of 0.88, and the results of the exploratory factor analysis showed an adequacy of KMO of 0.869. For the Bartlett sphericity test, a significant value p < 0.001 was obtained. This confirms that the 8 dimensions indicate that the instrument adequately evaluates the construct in the population studied. Little is known about the influence of quality of life on work performance in diabetes mellitus; in this research, it was found that there is a statistically significant relationship between the variable quality of life and work performance in a population with Type II Diabetes Mellitus, the better the quality of life, the greater the work performance. An interest in employees with diabetes mellitus (DM) should be shown in companies by making the subject’s own well-being part of goal 3, “Health and well-being,” and target 3.4 of reducing premature mortality from this type of disease by one-third, which aims to ensure a healthy life and promote well-being for all at all ages, through prevention and treatment and promoting mental health as one of the company’s sustainable development goals, carry out an annual survey to evaluate the quality of life and work performance and in this way the organization can carry out programs to detect early employees diagnosed and not diagnosed with DM. This research provides data and information that has been little studied on the influence on the variables of quality of life and work performance in Type II Diabetes Mellitus, given that this disease is the second leading cause of death in the country.

Effects of Virtual Reality–Based Activities of Daily Living Rehabilitation Training in Older Adults With Cognitive Frailty and Activities of Daily Living Impairments: A Randomized Controlled Trial

ObjectivesCognitive frailty, which is notably prevalent in nursing homes, correlates with a range of adverse health outcomes; however, interventions targeting this population are scarce, particularly those addressing activities of daily living (ADLs). The objective of this study was to evaluate the effects of virtual reality–based ADL rehabilitation training on older adults with cognitive frailty and ADL impairments. DesignA 2-arm randomized controlled trial. Setting and ParticipantsOlder adults with cognitive frailty and mild ADL impairments in a nursing home. MethodsSixty-six eligible participants were equally randomized into intervention and control groups. The intervention involved 45-minute sessions conducted twice weekly for 12 weeks. Outcomes evaluated included ADL performance, cognition, frailty, depression, and quality of life. Assessments were performed at baseline, 6 weeks (T1), and 12 weeks (T2). ResultsThere was no statistically significant difference between the 2 groups at baseline. The mean age of the participants was 80.20 ± 9.14 years, and most were women (54.55%). Compared with the control group, the intervention group showed significant improvements in ADLs (T1: β = 6.33, T2: β = 12.79), basic ADLs (T1: β = 4.09, T2: β = 6.97), instrumental ADLs (T1: β = 2.24, T2: β = 4.12), cognition (T1: β = 3.67, T2: β = 4.42), frailty (T1: β = −0.76, T2: β = −1.27), and mental component summary of quality of life (T1: β = 8.49, T2: β = 16.44) at T1 and T2. By T2, significant improvements were observed in depression (T2: β = −2.06) and physical component summary of quality of life (T2: β = 8.52). Conclusions and ImplicationsFor older adults with cognitive frailty and mild ADL impairments residing in a nursing home, the virtual reality–based ADL rehabilitation program was safe and effective. Following the 12-week intervention, significant improvements were observed in ADL performance, cognition, frailty, depression, and quality of life.

Visual performance and quality of life in myopic adolescents with pupil-optimised multifocal versus single-vision contact lenses

ABSTRACT Clinical relevance Myopia control is a prominent area of global research, with multifocal contact lenses identified as an effective intervention for adolescents. Background This study aims to evaluate the visual performance and vision-related quality of life (QoL) of myopic adolescents when corrected with pupil-optimised multifocal soft contact lenses (MFSCLs) versus single-vision contact lenses (SVCLs), with each participant serving as their own control. Methods Thirty-five myopic adolescents, habitually wearing SVCLs and fitted with pupil-optimised MFSCL with mid-addition power, were recruited. The assessment included distance visual acuity (DVA), near visual acuity (NVA), maximum reading speed (MRS), reading acuity (RA), contrast sensitivity (CS), and stereoacuity (SA) in photopic conditions for both types of lenses. Vision-related QoL was quantified twice for both lens types using the National Eye Institute Visual Function Questionnaire (NEI VFQ-42), covering 13 vision-specific domains. Results Comparisons of visual outcomes between MFSCLs and SVCLs for the same subjects revealed statistically significant differences in DVA (p = 0.010), NVA (p = 0.014), MRS (p = 0.044), and RA (p < 0.001), with SVCLs outperforming in DVA only. No significant difference in CS and SA was observed between the two lens types. According to the NEI VFQ-42, scores for clarity of vision, far vision, glare, and satisfaction with correction were higher with SVCLs, while the score for near vision was higher with MFSCLs. When fitted with MFSCLs, no significant correlations were found between pupil size and age of the patient with any visual examination parameters. However, there was a significant negative correlation between the DVA, NVA and the spherical equivalent of the lens. Conclusion MFSCLs with mid-add power significantly improve NVA, MRS, and RA, albeit with a reduction in DVA compared to SVCLs. While SVCLs were associated with better clarity of vision, far vision, and satisfaction with correction, MFSCLs offered superior performance in near vision tasks, according to the NEI VFQ-42 scores.

Psychological Aspects of Stage Performance: a Pianist’s Perspective

This article discusses the psychological dimensions inherent in stage performance, particularly from the perspective of pianists, including the difficulties a pianist must face at individual stages in their preparation for a stage performance. The analysis commences by examining excerpts from a pianist’s diary with the objective of enumerating the emotions typically connected to a pianist’s stage performance. The article undertakes an analysis of the emotional constructs outlined within the aforementioned diary to deconstruct the stressors encountered during the preparation for a public performance and the performance itself, as well as to investigate the effect which mental states have on the pianist’s ability to manage their emotions and anxiety. It also discusses the pragmatic methods that seek to reduce anxiety, not only during the preparatory phase but also during a live performance. The article demonstrates that stage performance psychology plays a pivotal role in the musician’s ability to deliver a successful live performance.

An audience response study on Korean translation of culture-specific items in licensed musicals

ABSTRACT This study explores the Korean translation of culture-specific items (CSIs) in licensed musicals by analyzing audience responses to different translation strategies. Musicals such as Les Misérables, Urinetown, Little Women, Rent, Blood Brothers, and The Spitfire Grill were examined. Foreignized and domesticated translations of units of measurement, idioms, proper nouns, and customs were performed consecutively, followed by audience surveys to assess comprehension and preferences. Results show that audiences generally find foreignized translations less understandable, though preferences vary by CSI. Audiences are receptive to content adaptation and free translation, but they react negatively to the domestication of currency units and proper names. In contrast, there is a strong preference for the domestication of social and legal culture, customs, and humor. This study, using live performances to gather real-time audience responses, provides valuable insights for translators. However, it acknowledges limitations due to the time constraints of live performances, which restricted the depth of analysis.

Constraints and creativity: Transforming a live artistic experience for children into Zoom

This article explores how the Portuguese ensemble Companhia de Música Teatral (CMT) adapted their live performance PaPI – Opus 8 for Zoom in response to the 2020 COVID-19 pandemic, which severely limited in-person gatherings and artistic events. Originally planned for a nationwide tour, PaPI – Opus 8 faced major challenges due to pandemic restrictions, prompting CMT to rework the piece for an online audience. The result was a transformed version titled PaPI – Opus 8.z, crafted specifically for the Zoom video-conferencing platform. The article gives a detailed examination of this performance piece and its reception, providing a comprehensive understanding of the challenges and achievements associated with the adaptation of this live performance to the virtual realm. The article explores the transformation process into an online format, examining both the losses and gains incurred. To facilitate this exploration, an introduction to CMT and a contextualization of their work is given. Subsequently, PaPI – Opus 8 is situated within CMT's body of work, including its "sister" pieces, with a particular focus on evaluating the significance of interaction with the audience during the performance. This is followed by an overview of the pandemic-related constraints and the strategies employed by CMT to continue creating performances. To illustrate these strategies, two other CMT creations developed during quarantine are discussed as pivotal steps on the pathway from PaPI – Opus 8 to the transformed online performance PaPI – Opus 8.z. Cover photo by Companhia de Música Teatral

PKR downregulation prevents copper-induced synaptic dysfunction and cognitive impairment in a murine model of Wilson's disease.

Synaptic efficacy is critical for memory formation and consolidation. Accumulating evidence suggest that synapses are impaired during Wilson's disease (WD), contributing to neuronal dysfunction and cognitive decline. WD is a prototypical condition among the copper metabolism disorders. Cognitive impairment is a common feature of affected patients with neurological symptoms, presenting as memory deficits, decreased cognitive flexibility, and impaired learning capabilities. These cognitive deficits can significantly impact the quality of life, affecting work and academic performance. However, the mechanisms mediating the inhibitory synaptic dysfunction in WD are incompletely understood. We investigated the effects of the double-stranded RNA-dependent protein kinase/eukaryotic initiation factor 2α (PKR/eIF2α) pathway on synaptic structure and function in WD using a murine model, toxic milk (TX mice). During mouse open-field tests, we noted a substantial rise in the mobility/immobility ratio among WD model animals compared to that in WT mice. Additionally, WD mice exhibited diminished central area exploration, as evidenced by reduced travel distance. Moreover, they displayed prolonged escape latency in the Barnes maze, suggesting that chronic copper accumulation is associated with neuropsychiatric alterations and cognitive impairment. We also found a decrease in the expression of synapse-associated proteins (synapsin 1, synaptophysin, postsynaptic density protein-93 [PSD93], postsynaptic density protein-95 [PSD95]), and vesicle-associated membrane protein2 [VAMP2]) besides abnormal neurotransmitter levels (including glutamate and GABA), indicating the presence of synaptic dysfunction in TX mice. Inhibiting PKR via C16 prevented these changes, suggesting that dysfunctional cognition is associated with the PKR/eIF2α pathway. We also observed changes in synapses, vesicles, dendritic spine density, and dendritic length that were associated with the presence of cognitive dysfunction. Further investigation revealed that C16 treatment decreased the TUNEL-positive cell numbers in the hippocampus of TX mice and prevented 8-OHdG-induced synaptic dysfunction. Results suggest that PKR downregulation prevents copper-induced synaptic dysfunction in the murine WD model. Therefore, targeting PKR pharmacologically may be a potential therapeutic strategy for treating the copper-induced neuropathology of patients with WD.