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Up to 50% of adult patients with epilepsy experience comorbid depression or anxiety, complicating post-treatment recovery and requiring tailored outcome assessment. No core outcome set (COS) exists for this dual-diagnosis population, unlike broader epilepsy COSs or quality-of-life COSs for drug-resistant epilepsy, which do not prioritize mental health comorbidities. This protocol outlines the development of a standardized COS to evaluate post-treatment recovery in adults with epilepsy and comorbid depression or anxiety, using the International Classification of Functioning, Disability, and Health (ICF) framework to ensure a biopsychosocial perspective. This COS aims to enhance cross-study comparability and inform personalized care for this underserved group. This study will employ a three-phase process: (1) A systematic review of outcomes in epilepsy with comorbid depression or anxiety in adult patients, searching PubMed, Embase, and Cochrane Library per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, including outcomes such as seizure control, mood stability, cognitive function, social reintegration, and suicide-related outcomes; (2) Mapping outcomes to ICF domains (body functions, activities, participation) for comprehensive coverage; and (3) A three-round Delphi survey using a 9-point Likert scale to achieve consensus among an international panel of ≥60 stakeholders, including neurologists, psychiatrists, psychologists, patients, and caregivers, with ≥20% from low- and middle-income countries. Consensus requires ≥70% agreement on scores of 7-9 (critically important) and ≤15% on 1-3 (low importance). The COS will capture domains like seizure control, mood stability, cognitive function, and social reintegration. This COS will address a critical gap by standardizing outcome measurement for adults with epilepsy and mental health comorbidities, complementing broader COSs, such as the Epilepsy Outcome Set for Effectiveness Trials (EPSET), by focusing on mental health recovery, including suicide-related outcomes, and extending quality-of-life-focused sets, such as those using the Quality of Life in Epilepsy (QOLIE) scales, to include neurological and functional outcomes. The ICF-guided, patient-inclusive approach ensures global relevance. Potential limitations, including stakeholder bias, will be mitigated through diverse recruitment and robust consensus methods. This protocol leverages Delphi methodology and ICF principles to develop a novel COS for a complex dual-diagnosis population. By prioritizing mental health recovery in adults, including critical outcomes like suicide prevention, it offers a distinct tool to enhance research and clinical practice, with future validation planned to ensure applicability across settings. CRD42024576141.

[This corrects the article DOI: 10.1371/journal.pone.0330617.].

Excessive daytime sleepiness (EDS), which is common in Parkinson's disease (PD), has been reported to exacerbate gait disturbance in patients with PD, but there is a lack of objective assessment, as well as an unknown specific mechanism. The purpose of our study is to explore the relationship between EDS and gait parameters. Sixty-one patients with PD were recruited and divided into the EDS group (  = 29) and the non-EDS group (  = 32) based on the scores of the Epworth Sleepiness Scale (ESS). The gait metrics of the two groups were then assessed by wearable devices and compared under various walking scenarios. Compared with the non-EDS group, the EDS group showed significantly shorter step lengths and stride lengths, slower walk speed and gait speed, reduced shank-max forward swing and sagittal angular velocity, and increased phase coordination indices and mean duration of turns. Pearson correlation analysis revealed a significant association between ESS scores and various gait parameters. Furthermore, multiple linear regression analysis confirmed that EDS is an independent factor influencing gait in patients with PD. EDS was independently associated with gait disturbances in patients with PD, suggesting that EDS symptoms warrant serious attention in clinical practice.

Background Early Parkinson’s disease (PD) presents with subtle symptoms and lacks specific diagnostic methods. Clinical diagnosis primarily relies on subjective assessment, with confirmation often occurring at mid-to-late stages. Therefore, identifying objective and quantifiable biomarkers to assist in early PD diagnosis and intervention is of significant clinical value. Method This study recruited 20 early PD patients and 18 healthy controls who performed a visually guided motor-cognitive task (VMC) under three visual feedback gain conditions (low, medium, and high), while electroencephalography (EEG) and grip strength data were recorded simultaneously. Subsequently, EEG microstate analysis was used to extract temporal dynamic parameters (Duration, Occurrence, Coverage, and Transition probability), while grip strength parameters (RMSE, CV) were computed. Finally, machine learning models were developed using EEG microstate parameters, grip strength parameters, and their multimodal fusion features to systematically evaluate classification performance in distinguishing early PD patients from healthy individuals. Result In the resting-state, PD patients exhibited a significant increase in the Occurrence and Coverage of microstate A, while the Coverage of microstate B significantly decreased. During the VMC task, PD patients exhibited a microstate pattern significantly different from that of HC. PD patients exhibited significantly lower temporal parameters for microstate B but higher values for microstate A and C under medium/high gain conditions, which was exactly the opposite of the performance at low gain. Moreover, PD patients exhibited poorer grip performance across all gain conditions. Finally, compared with the grip strength parameter model and the multidimensional parameter model, the microstate parameter model based on the VMC task demonstrated higher sensitivity in identifying early PD patients. At low, medium, and high visual feedback gains, the highest classification accuracy reached 100% in all cases. Notably, under high-gain conditions, all classification algorithms achieved 100% accuracy. Conclusion This study, through EEG microstate analysis, revealed abnormal brain network dynamics in early PD patients under resting-state and various visual feedback gain conditions. The EEG microstate parameter model based on the VMC task exhibited high sensitivity in identifying early PD patients, particularly under high gain conditions. These findings suggest that EEG microstate parameters during the VMC task hold potential as objective biomarkers for early PD diagnosis and have significant clinical value.

Globally, more than 10 million new stroke cases occur annually, of which aphasia accounts for about one-third. Aphasia has become an independent predictor of functional dependence and death for the stroke population. The closed-loop rehabilitation of combining behavioral therapy with central nerve stimulation seems to be the research trend of post-stroke aphasia (PSA) due to its advantages in improving linguistic deficits. To verify the clinical efficacy of a closed-loop rehabilitation program combining melodic intonation therapy (MIT) with transcranial direct current stimulation (tDCS) for PSA. This was a single-center, assessor-blinded, randomized controlled clinical trial, which screened 179 patients and included 39 PSA subjects, with the registration number ChiCTR2200056393 in China. Demographic and clinical data were documented. The primary outcome was the Western Aphasia Battery (WAB) used to assess language function, and the secondary outcomes included Montreal Cognitive Assessment (MoCA), Fugl-Meyer Assessment (FMA), and Barthel Index (BI) for evaluating cognition, motor, and activities of daily living, respectively. With the computer-generated randomization sequence, subjects were randomly divided into the conventional group (CG), MIT combined with sham stimulation group (SG), and MIT combined with tDCS group (TG). After the three-week intervention, the functional changes in each group were analyzed by the paired sample -test, and the functional difference between the three groups was analyzed by ANOVA. There was no statistical difference on the baseline. After the intervention, the WAB's aphasia quotient (WAB-AQ), MoCA, FMA, and BI were statistically different in SG and TG, including all the sub-items in WAB and FMA, while only listening comprehension, FMA, and BI were statistically different in CG. The differences of WAB-AQ, MoCA, and FMA were statistically different among the three groups, but BI was not. The test results revealed that the changes of WAB-AQ and MoCA in TG were more significant than the others. MIT combined with tDCS can augment the positive effect on language and cognitive recovery in PSA.

Renal dysfunction and disruption of renal endothelial glycocalyx are two important events during septic acute kidney injury (AKI). Here, the role and mechanism of hyaluronidase 1 (HYAL1) in regulating renal injury and renal endothelial glycocalyx breakdown in septic AKI were explored for the first time. BALB/c mice were injected with lipopolysaccharide (LPS, 10 mg/kg) to induce AKI. HYAL1 was blocked using lentivirus-mediated short hairpin RNA targeting HYAL1 (LV-sh-HYAL1). Biochemical assays were performed to measure the levels and concentrations of biochemical parameters associated with AKI as well as levels of inflammatory cytokines. Renal pathological lesions were determined by hematoxylin-eosin (HE) staining. Cell apoptosis in the kidney was detected using terminal-deoxynucleoitidyl transferase-mediated nick end labeling (TUNEL) assay. Immunofluorescence and immunohistochemical (IHC) staining assays were used to examine the levels of hyaluronic acid in the kidney. The protein levels of adenosine monophosphate-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling, endothelial glycocalyx, and autophagy-associated indicators were assessed by western blotting. The knockdown of HYAL1 in LPS-subjected mice by LV-sh-HYAL1 significantly reduced renal inflammation, oxidative stress, apoptosis and kidney dysfunction in AKI, as well as alleviated renal endothelial glycocalyx disruption by preventing the release of hyaluronic acid to the bloodstream. Additionally, autophagy-related protein analysis indicated that knockdown of HYAL1 significantly enhanced autophagy in LPS mice. Furthermore, the beneficial actions of HYAL1 blockade were closely associated with the AMPK/mTOR signaling. HYAL1 deficiency attenuates LPS-triggered renal injury and endothelial glycocalyx breakdown in septic AKI in mice.

Treatment of severe burn wound injury remains a significant clinical challenge as serious infections/complex repair process and irregulating inflammation response. Human umbilical cord mesenchymal stem cells (hUC-MSCs) have a multidirectional differentiation potential and could repair multiple injuries under appropriate conditions. Poly(L-lysine)-graft-4-hydroxyphenylacetic acid (PLL-g-HPA) hydrogel is an enzyme-promoted biodegradable in hydrogel with good water absorption, biocompatibility and anti-bacterial properties. Therefore, the aim of this study was to evaluate the therapeutic effect of hUC-MSCs combined with PLL-g-HPA hydrogel on full thickness burn injury in rat model. The PLL-g-HPA hydrogel was developed and characterized by Scanning Electron Microscopy (SEM), Fourier-Transform Infrared Spectroscopy (FTIR), Hydrogen-1 nuclear magnetic resonance (H-NMR). The cytotoxicity to human foreskin fibroblasts (HFF) were assessed by CCK-8 assay and live/dead quantification and antibacterial activity against and was also detected by colony forming unit. A full-thickness burn wound injury model in 12 SD rats was established, and the therapeutic effect of PLL-g-HPA hydrogel combined with hUC-MSCs was detected by healing time/Histology/inflammation factor expression level. The findings from SEM, FTIR, and HFF analyses demonstrated the successful synthesis of PLL-g-HPA hydrogels. These hydrogels exhibited low cytotoxicity at minimal concentrations while maintaining excellent moisture retention and antibacterial properties. Compared to the control group, treatment with PLL-g-HPA hydrogel in conjunction with hUC-MSCs significantly enhanced wound healing, modulated inflammatory responses, and promoted angiogenesis as well as re-epithelialization in rat models. The PLL-g-HPA hydrogel in conjunction with hUC-MSCs represents a promising therapeutic approach for the management of burn wounds.

The leaves of Engelhardia roxburghiana Wall (LERW) has been used as sweet tea in China throughout history. In this study, the ethanol extract of LERW (E-LERW) was prepared and the compositions were identified by HPLC-MS/MS. It indicates that astilbin was the predominant component in E-LERW. In addition, E-LERW was abundant in polyphenols. Compared to astilbin, E-LERW presented much more powerful antioxidant activity. The E-LERW also had stronger affinity with α-glucosidase and exerted more vigorous inhibitory effect on the enzyme. Alloxan-induced diabetic mice had significantly elevated glucose and lipid levels. Treatment with E-LERW at the medium dose (M) of 300 mg/kg could reduce the levels of glucose, TG, TC, and LDL by 16.64%, 12.87%, 32.70%, and 22.99%, respectively. In addition, E-LERW (M) decreased food intake, water intake, and excretion by 27.29%, 36.15%, and 30.93%, respectively. Moreover, E-LERW (M) therapy increased the mouse weight and insulin secretion by 25.30% and 494.52%. With respect to the astilbin control, E-LERW was more efficient in reducing the food and drink consumption and protecting pancreatic islet and body organs from alloxan-induced damage. The study demonstrates that E-LERW may be a promising functional ingredient for the adjuvant therapy of diabetes.

Parkinson’s disease (PD) is a chronic neurodegenerative disorder characterized by dopaminergic neuron loss, which is related to excessive reactive oxygen species (ROS) accumulation. Endogenous peroxiredoxin-2 (Prdx-2) has potent anti-oxidative and anti-apoptotic effects. Proteomics studies revealed plasma levels of Prdx-2 were significantly lower in PD patients than in healthy individuals. For further study of the activation of Prdx-2 and its role in vitro, SH-SY5Y cells and the neurotoxin 1-methyl-4-phenylpyridinium (MPP + ) were used to model PD. ROS content, mitochondrial membrane potential, and cell viability were used to assess the effect of MPP + in SH-SY5Y cells. JC-1 staining was used to determine mitochondrial membrane potential. ROS content was detected using a DCFH-DA kit. Cell viability was measured using the Cell Counting Kit-8 assay. Western blot detected the protein levels of tyrosine hydroxylase (TH), Prdx-2, silent information regulator of transcription 1 (SIRT1), Bax, and Bcl-2. The results showed that MPP + -induced accumulation of ROS, depolarization of mitochondrial membrane potential, and reduction of cell viability occurred in SH-SY5Y cells. In addition, the levels of TH, Prdx-2, and SIRT1 decreased, while the ratios of Bax and Bcl-2 increased. Then, Prdx-2 overexpression in SH-SY5Y cells showed significant protection against MPP + -induced neuronal toxicity, as evidenced by the decrease in ROS content, increase in cell viability, increase in the level of TH, and decrease in the ratios of Bax and Bcl-2. Meanwhile, SIRT1 levels increase with the level of Prdx-2. This suggests that the protection of Prdx-2 may be related to SIRT1. In conclusion, this study indicated that overexpression of Prdx-2 reduces MPP + -induced toxicity in SH-SY5Y cells and may be mediated by SIRT1.

Background Excessive daytime sleepiness (EDS) and freezing of gait (FOG) are prevalent non-motor and motor symptoms in patients with Parkinson’s disease (PD), significantly impacting their quality of life. However, the correlation between EDS and FOG progression in  de novo  PD patients remains controversial. Methods A total of 328 participants from the Parkinson’s Progression Markers Initiative (PPMI) were divided into two groups: 43 with EDS (EDS group) and 285 without EDS (nEDS group). The cumulative incidence of FOG was assessed at the 5-year follow-up using Kaplan–Meier and log-rank tests. Multivariate Cox proportional hazards models were used to assess the impact of EDS on FOG progression in PD patients, with validation for robustness through sensitivity and subgroup analyses. Results The EDS group experienced a higher incidence of FOG throughout the 5-year follow-up than did the nEDS group. Multivariate Cox proportional hazards models showed significantly association between EDS severity and enhanced risk of developing FOG (HR = 1.076, 95% CI:1.007 ~ 1.149, P  = 0.031). For sensitivity analysis, parallel analyses were performed by substituting the independent variable with categorical variables, which yielded analogous outcomes (HR = 1.837, 95% CI:1.063 ~ 3.174,  P  = 0.029). Furthermore, subgroup analyses based on sex, age, TD/PIGD classification, depressive symptoms, cognitive impairment, mean caudate nucleus uptake level, mean putamen nucleus uptake level and CSF Aβ-42 level revealed no significant interactions between subgroups (all  P  values for interaction were > 0.05). Conclusion EDS is a potential prognosis factor for the progression of FOG in patients with PD.