Combining HD-tDCS with music stimulation for patients with prolonged disorders of consciousness: Study protocol for an RCT trial.

BACKGROUND: Patients with prolonged disorders of consciousness (pDOC) pose significant challenges to healthcare workers due to their severe motor impairments and limited interaction with the environment. Non-invasive brain stimulation such as high-definition transcranial direct current stimulation (HD-tDCS) and music stimulation show promise in awakening this population. OBJECTIVE: In this study, we present a protocol aiming at investigating the efficacy of combined HD-tDCS and music stimulation in awakening patients with pDOC through a single-blind, randomized controlled trial. METHODS: Ninety patients with pDOC will be randomly divided into three groups: active HD-tDCS with music stimulation, active HD-tDCS, and sham HD-tDCS. All participants will receive 20 treatment sessions over a period of 10 days and the Coma Recovery Scale-Revised, Glasgow Outcome Scale and electroencephalogram will be used as assessment measures to evaluate their level of consciousness throughout the study. Adverse events and complications will be recorded during treatment. Within-group pre-post comparisons and between-group efficacy comparisons will be conducted to identify the most effective intervention approach. Statistical analysis will be performed using SPSS software with a significance level set at P < 0.05. CONCLUSION: The pursuit of awakening therapy for patients with pDOC remains a clinical research challenge. This study protocol is designed with the aim of introducing an innovative non-pharmacological approach which combined HD-tDCS and music stimulation to facilitate the reinstatement of consciousness in patients with pDOC.

Inverted U-shaped relationship between Barthel Index Score and falls in Chinese non-bedridden patients: a cross-sectional study.

BACKGROUND: Performing activities of daily living comprise an important risk factor for falls among non-bedridden stroke inpatients in rehabilitation departments. OBJECTIVES: To explore the correlation between Barthel Index score and the occurrence of falls in non-bedridden stroke rehabilitation inpatients. METHODS: In this cross-sectional study, information of patients grouped as non-bedridden patients by the Longshi Scale was collected. RESULTS: A total of 3097 patients were included in this study, with a fall incidence of 10.43%. After adjusting covariates, the total score of Barthel Index and falls in non-bedridden inpatients after stroke presented an inverted U-shaped curve relationship, in which inflection point was 60. The effect sizes on the left and right sides of infection point were 1.02 (95%CI 1.00-1.04) and 0.97 (95%CI 0.96-0.99), respectively. CONCLUSIONS: Non-bedridden stroke patients with moderate activities of daily living (ADL) capacity may be at particularly increased risk of falls in rehabilitation departments.

PITX1 plays essential functions in cancer.

PITX1, also known as the pituitary homeobox 1 gene, has emerged as a key regulator in animal growth and development, attracting significant research attention. Recent investigations have revealed the implication of dysregulated PITX1 expression in tumorigenesis, highlighting its involvement in cancer development. Notably, PITX1 interacts with p53 and exerts control over crucial cellular processes including cell cycle progression, apoptosis, and chemotherapy resistance. Its influence extends to various tumors, such as esophageal, colorectal, gastric, and liver cancer, contributing to tumor progression and metastasis. Despite its significance, a comprehensive review examining PITX1's role in oncology remains lacking. This review aims to address this gap by providing a comprehensive overview of PITX1 in different cancer types, with a particular focus on its clinicopathological significance.

Content comparison of long-term care instruments based on the international classification of functioning, disability and health (ICF).

BACKGROUND: Ageing poses a huge challenge to the Chinese social welfare system. However, a national long-term care (LTC) instrument has not been established yet. This study aimed to analyse and compare the content of six selected LTC instruments based on the linkage of the International Classification of Functioning, Disability and Health (ICF) to provide a content reference from a functioning perspective for the development of a Chinese national LTC instrument. METHODS: Two trained health professionals performed the linkage analysis according to the refined ICF linking rules. The main concepts included in the items of three international LTC instruments, namely Minimum Data Set 3.0 (MDS 3.0), Initial Assessment Instrument (IAI), and New Assessment Tool for Determining Dependency on Nursing Care (NBA), as well as three Chinese instruments, namely Disability Assessment of Long-Term Care (DA-LTC), Specification for Elderly Care Unified Need Assessment in Shanghai Version 2.0 (SEC-UNA 2.0), and pictorial-based Longshi Scale (LS), were selected and linked to the ICF categories. The six selected LTC instruments were analysed and compared at the levels of ICF components, chapters, and categories. RESULTS: The main concepts of 340 items of the six LTC instruments were linked to 112 different ICF categories. Within the ICF framework, the 'Activities and Participation' component was most frequently addressed in the LTC instruments, followed by 'Body functions', at 52% and 38%, respectively. At the chapter level, 'b1 mental functions', 'd4 mobility', and 'd5 self-care' were addressed by the majority of LTC instruments. CONCLUSION: The ICF provides a general reference for the analysis and comparison of different LTC instruments. The findings indicate that all LTC instruments focused on older adults' physical needs; however, various important issues regarding their psychological and social participation needs were not addressed. Specific for China, the core elements of LTC instruments varied, and the ICF chapters 'b1', 'd4', and 'd5' are recommended to develop a national uniform one.

Reliability of pictorial Longshi Scale for informal caregivers to evaluate the functional independence and disability.

AIM: The pictorial Longshi Scale was designed to assess patients' functional ability in the Chinese context, which is gradually used by some informal caregivers. However, its reliability compared with healthcare professionals has not been examined. DESIGN: A multi-centre cross-sectional study conducted in 24 Chinese hospitals. METHODS: We recruited patients undergoing rehabilitation treatment and informal caregiver dyads. Informal caregivers and healthcare professionals evaluated patients' functional ability using the Longshi Scale according to three levels (bedridden, domestic and community). The Kappa coefficient and McNemar-Bowker test were used to examine the consistency and accuracy between the two parallel assessments. RESULTS: This study involved 947 patients (mean age: 46.07 ± 11.72 years) and informal caregiver dyads (64.86 ± 12.94 years). Most patients were males (66.3%), while most caregivers were females (60.7%). Over 70% of patients and caregiver dyads had a secondary-school education and lower. Around 90% of caregivers were relatives (spouse, 42.8%; offspring, 20.7%; siblings: 13.3%; parent, 12.0%) of patients. The agreement in sub-levels of the Longshi Scale between caregivers and healthcare professionals ranges from 73%-89%, and the corresponding Kappa coefficients range from 0.504-0.786. Caregivers were more likely to assign fewer patients to the bedridden group and more to the domestic group than healthcare professionals. The subgroup analysis by education level indicated that the difference in assigning patients into three degrees of functional disability was only significant in those with primary-school education, while non-significant in those with secondary-school education and higher. CONCLUSION: The evaluation outcomes of functional ability using the Longshi Scale are similar between informal caregivers and healthcare professionals. However, informal caregivers' education level is a dominant factor in affecting the assessment accuracy compared with healthcare professionals. Informal caregivers with a secondary-school education and higher are supported to evaluate patients' functional ability independently.

Efficacy of Transcranial Direct Current Stimulation Over Dorsolateral Prefrontal Cortex in Patients With Minimally Conscious State.

BACKGROUND: The treatment of patients in a minimally conscious state (MCS) remains challenging. Transcranial direct current stimulation (tDCS) is a non-invasive therapeutic method in treating neurologic diseases by regulating the cortical excitability. The aim is to investigate the effect of tDCS in patients with MCS in this study. METHODS: Eleven patients in MCS were enrolled in the study. All the patients received 5 daily sessions of 20-min sham tDCS, followed by 10 sessions of 20-min real tDCS. The anodal electrode and cathodal electrodes were placed over the left dorsolateral prefrontal cortex (DLPFC) and the right eyebrow, respectively. Assessment of Coma Recovery Scale-Revised (CRS-R) scores and resting-state functional MRI (rs-fMRI) scans was conducted three times in each patient: before tDCS (baseline, T0), post-sham tDCS at week 1 (T1), and post-real tDCS at week 2 (T2). The whole-brain functional connectivity (FC) was obtained by bilaterally computing FC from six seed regions: precuneus, middle frontal gyrus, supplemental motor area, angular gyrus, superior temporal gyrus, and occipital lobe. One-way repeated measure ANOVA was used to compare the differences of CRS-R scores and FC at T0, T1, and T2. The false discovery rate correction of p < 0.001 was adopted for controlling multiple comparisons in FC analysis. RESULTS: Five patients with MCS showed obvious clinical improvement represented by increased CRS-R scores post- 2-week real tDCS. The CRS-R scores did not change post- 1-week sham treatment. No side effects were reported during the study. The FC of the bilateral supplementary motor area, right angular gyrus, and right superior temporal gyrus were significantly enhanced after 2-week real tDCS compared with that after 1-week sham-tDCS. In addition, FC of bilateral occipital lobe and right precuneus were significantly enhanced post- 2-week real tDCS compared with the baseline. CONCLUSION: Our findings indicated that tDCS over DLPFC could serve as a potentially effective therapy for improving the consciousness state in patients with MCS. The FC in rs-fMRI can be modulated by tDCS at both the stimulation site (left DLPFC) and the distant regions.

Functional Independence and Disability Evaluation in Stroke Patients: Optimal Cutoff Scores for a Pictorial-Based Longshi Scale, Barthel Index, and Modified Rankin Scale.

INTRODUCTION: The modified Rankin Scale (mRS) and Barthel Index (BI) are widely used to measure functional outcomes worldwide. The Longshi Scale (LS), a novel pictorial-based instrument, was designed to improve the simplicity and convenience of measuring functional outcomes in the Chinese context. However, the disagreements in functional outcomes assessed by the mRS, BI, and LS are misleading, particularly in stroke patients. This study aimed to identify the optimal cutoff scores of LS and BI according to the mRS in Chinese stroke patients with different levels of functional disability. METHODS: The mRS, BI, and LS were applied to evaluate functional independence and disability in 7364 stroke patients in a multi-center cross-sectional study. Stroke patients were categorized into bedridden, domestic, and community groups in advance using the LS, indicating severe, moderate, and mild functional disability, respectively. The optimal cut-off scores of the LS and BI according to the mRS were identified via sensitivity, specificity, and Youden's index and stratified by different levels of functional disability determined by LS. We also plotted the receiver operator characteristic (ROC) curves of sensitivity and specificity and determined the area under the curve (AUC). RESULTS: In the bedridden group, LS and BI cutoff scores with the highest Youden's index were 5 and 10 for mRS 4, and the AUCs for the ROC curve were 0.848 and 0.863 for mRS 4. In the domestic group, LS and BI cutoff scores with the highest Youden's index were 5 and 65 for mRS 3, and the AUCs for the ROC curve were 0.796 and 0.826 for mRS 3. In the community group, LS cutoff scores with the highest sum of sensitivity and specificity were 9, 9, and 8 for mRS grades 0, 1, and 2, respectively, while the BI cutoff scores with the highest sum of sensitivity and specificity were 100, 100, and 95, respectively, while the AUCs for the ROC curve were 0.697 and 0.735 for mRS 2, 0.694 and 0.716 for mRS 1, and 0.628, and 0.660 for mRS 0. CONCLUSIONS: The mRS is more precise to determine mild functional disability, whereas BI can provide more specific information on moderate and severe levels in stroke patients. Although LS was a less precise was to determine moderate and severe levels than BI, it is much simpler and more convenient to be applied to a large-scale population.

Case Report: Visual Deprivation in Pusher Syndrome Complicated by Hemispatial Neglect After Basal Ganglia Stroke.

We aimed to explore whether motor function and activities of daily life (ADL) could be improved with the application of visual deprivation in two patients with Pusher syndrome complicated by hemispatial neglect after right basal ganglia stroke. We assessed two stroke patients suffering from severe motor disturbances, both tilting heavily to the left, with diagnoses of Pusher syndrome and left hemispatial neglect. Vision in the left eye was deprived using patches during clinical rehabilitation. Motor function promotion was confirmed using the Burke Lateropulsion Scale (BLS), Fugl-Meyer Balance Scale (FMBS), and Holden grade (HG), while the Barthel index (BI) assessed ADL immediately and 1 week after intervention. Both patients regained standing balance immediately using visual deprivation, as well as walking ability, although both scored 0 on the FMBS and HG. After 1 week of treatment, one patient increased to 11 and 3 on the FMBS and HG, respectively, while the BLS score decreased from 12 to 2, and the ADL increased from 23 to 70. The other patient demonstrated increases to 10 and 3 on the FMBS and HG, respectively, with the BLS decreasing from 13 to 3, and the ADL increasing from 25 to 60. Therefore, in the rehabilitation treatment of Pusher syndrome complicated by hemispatial neglect due to basal ganglia stroke, visual deprivation can significantly improve motor function and shorten the treatment course.

Combined association of multiple chronic diseases and social isolation with the functional disability after stroke in elderly patients: a multicenter cross-sectional study in China.

BACKGROUND: Multiple chronic diseases (MCDs) and social isolation are independent risk factors related to stroke and disability, but it is unknown whether the combination of these two conditions resulted from aging-related to functional disability in stroke patients. This study aimed to probe the relationship between the combination of MCDs, social isolation, and functional disability after stroke in elderly patients. METHODS: A multicenter and cross-sectional study was conducted in the Departments of Rehabilitation of 103 hospitals located in 23 cities across China. Stroke patients aged 60-90 years were selected for analysis. Demographic characteristics, lifestyles, and clinical information were investigated by questionnaires and medical records. MCDs (hypertension/ diabetes/ hyperlipidemia/heart disease/kidney disease) were categorized into three levels: 0, 1, and ≥ 2. Functional disability was assessed by the Barthel Index and categorized into four groups: no, mild, moderate, and severe disability. The multi-nominal logistic regression model was used to explore the independent and combined association of MCDs and social isolation with functional disability. RESULTS: A total of 4046 elderly stroke patients (55 % males) were included in the final analysis. The prevalence of social isolation, MCDs ≥ 2, and severe disability increased with aging. In the fully adjusted model, patients with social isolation or MCDs had a higher risk of functional disability significantly than those without. Patients with social isolation combined MCDs ≥ 2 were 35 times (95 % CI: 18.89-64.69) more likely to suffer severe disability after stroke, and 8 times (95 % CI: 18.89-64.69) for moderate disability than those without social isolation and MCDs. CONCLUSIONS: MCDs, social isolation, and their combination were associated with a higher risk of functional disability after stroke in Chinese elderly patients. The elderly population should be encouraged to participate in more social activities, particularly in those with MCDs. Future secondary prevention and rehabilitation treatments to the functional ability of elderly stroke patients should underscore both social activity and the combined treatments of MCDs. TRIAL REGISTRATION: NO: ChiCTR2000034067 .

A novel Longshi Scale measured activity of daily living disability in elderly patients affected by neurological diseases: a multi-center cross-sectional study in China.

BACKGROUND: Ability in the activities of daily life is often impaired in the older adults with a neurological disease. The Barthel Index is an instrument used worldwide to assess such ability. The Longshi Scale is a picture-based alternative, but its effectiveness has not been evaluated with older adult subjects. This study was to determine whether the Longshi Scale can effectively quantify the ability of older adults in the activities of daily living by comparing its ratings with those using the Barthel Index. METHODS: A multi-center cross-sectional study was conducted among patients over 65 years. A total of 2438 patients were divided into three groups, including bedridden, domestic, or community group based on their ability to go out of bed, move outdoors, and return indoors. Their ability in the activities of daily living among three groups was evaluated using both the Longshi Scale and the Barthel Index, and the results were compared. RESULTS: There was a significant difference in the average Barthel Index scores of three groups classified using the Longshi Scale. The average Longshi Scale scores also showed significant differences between the four groups classified using the Barthel Index. Spearman correlation coefficients showed strong correlation(>0.83) between the Longshi Scale and Barthel Index scores. CONCLUSIONS: The Longshi Scale can efficiently distinguish the ability in the activities of daily living of people with a neurological disease. Its rating correlate well with those using the Barthel Index.

Disability assessment in stroke: Relationship among the pictorial-based Longshi Scale, the Barthel Index, and the modified Rankin Scale.

OBJECTIVE: To explore the correlations among the Longshi Scale, the Barthel Index, and the modified Rankin Scale and the differentiate ability of the Longshi Scale and the modified Rankin Scale to Barthel Index scores. DESIGN: Prospective study. SETTING: The inpatient rehabilitation units of three teaching hospitals in China. SUBJECTS: A total of 343 stroke inpatients were recruited through convenience sampling. MAIN MEASURES: Pictorial-based Longshi Scale, Barthel Index, and modified Rankin Scale. RESULTS: The Longshi Scale was highly and moderately correlated with the Barthel Index and modified Rankin Scale, respectively. The median frequency distribution of the Barthel Index was slightly overlapped between Longshi Scale grades 2 and 3 but was considerably overlapped among modified Rankin Scale grades 1, 2, and 3. The Kruskal-Wallis and multiple comparison tests showed that, among the modified Rankin Scale grades, the median Barthel Index scores did not differentiate between grades 1 and 2 (χ2 = 20.643, P = 1.000), between grades 1 and 3 (χ2 = 60.404, P = 0.070), and between grades 2 and 3 (χ2 = 39.760, P = 0.232). Among the Longshi Scale grades, the median Barthel Index scores did not differentiate between grades 2 and 3 (χ2 = 48.778, P = 1.000), between grades 3 and 4 (χ2 = 57.094, P = 1.000), and between grades 5 and 6 (χ2 = 24.709, P = 1.000). CONCLUSION: Using the Barthel Index as reference, the proposed Longshi Scale has better ability than the modified Rankin Scale in differentiating stroke patients' disability, especially for those with higher level of activities of daily living.

Exercise improves recognition memory and synaptic plasticity in the prefrontal cortex for rats modelling vascular dementia.

OBJECTIVES: Functional electrical stimulation (FES) may induce involuntary exercise and make beneficial effects on vascular dementia (VD) by strengthening the BDNF-pCREB-mediated pathway and hippocampal plasticity. Whether FES improves recognition memory and synaptic plasticity in the prefrontal cortex (PFC) was investigated by establishing a VD model. METHODS: The VD rats were administered with two weeks of voluntary exercise, forced exercise, or involuntary exercise induced with FES. Sham-operated and control groups were also included. The behavioral changes were assessed with the novel object recognition test and novel object location test. The expression levels of key proteins related to synaptic plasticity in the PFC were also detected. RESULTS: All types of exercise improved the rats' novel object recognition index, but only voluntary exercise and involuntary exercise induced with FES improved the novel object location index. Any sort of exercise enhanced the expression of key proteins in the PFC. CONCLUSION: Involuntary exercise induced with FES can improve recognition memory in VD better than forced exercise. The mechanism is associated with increased synaptic plasticity in the PFC. FES may be a useful alternative tool for cognitive rehabilitation.

Involuntary, Forced and Voluntary Exercises Equally Attenuate Neurocognitive Deficits in Vascular Dementia by the BDNF-pCREB Mediated Pathway.

A rat model of vascular dementia was used to compare the effects of involuntary exercise induced by functional electrical stimulation (FES), forced exercise and voluntary exercise on the recovery of cognitive function recovery and its underlying mechanisms. In an involuntary exercise (I-EX) group, FES was used to induce involuntary gait-like running on ladder at 12 m/min. A forced exercise group (F-EX) and a voluntary exercise group (V-EX) exercised by wheel running. The Barnes maze was used for behavioral assessment. Brain-derived neurotrophic factor (BDNF), phosphorylated extracellular signal-regulated kinase 1 and 2 (ERK1/2) and cAMP response element binding protein (CREB) positive cells in hippocampal CA1, CA2/3 and dentate gyrus (DG) regions were evaluated using immunohistochemical methods. Western blotting was used to assess the levels of BDNF, phosphorylated protein kinase B (Akt), tropomyosin receptor kinase B (TrkB), mitogen-activated protein kinase 1 and 2 (MEK1/2), ERK1/2 and CREB in BDNF-pCREB signaling in the hippocampus and prefrontal cortex. Involuntary, forced and voluntary exercises were all found to reverse the cognitive deficits of vascular dementia with about equal effectiveness. The number of BDNF, pCREB and pERK1/2 immunopositive cells was significantly increased in the hippocampal CA1, CA2/3 and DG regions in all three exercise groups. In addition, involuntary exercise activated BDNF and the phosphorylation of Akt, TrkB, MEK1/2, ERK1/2 and CREB in the hippocampus and prefrontal cortex equally as well as voluntary or forced exercise. These results suggest that involuntary exercise induced by FES may be as beneficial for alleviating cognitive deficits after cerebral ischemia.

The link between impaired theory of mind and executive function in children with cerebral palsy.

The aim of the study was to explore the relationship between theory of mind (ToM) deficits and executive function (EF) impairments in children with cerebral palsy (CP), 42 CP with children and 42 typically developing (TD) children, acting as controls, were assessed on the tasks of ToM (false belief and faux pas) and EF (inhibition, updating and shifting). Results showed that CP children had deficits both in ToM and EF tasks. The correlation analyses showed that two EF components (inhibition and updating) were strongly related to false belief and faux pas in both two groups. We also found correlation between shifting and false belief and faux pas. However, this correlation was only found in TD children and not in children with CP. These findings suggest that children with CP lag behind TD children in both ToM and EF. Further, the results reveal, interestingly, that ToM deficits in CP children might be related to their inhibition and updating impairments, but not to shifting impairments.

miR-29b and miR-29c are involved in Toll-like receptor control of glucocorticoid-induced apoptosis in human plasmacytoid dendritic cells.

Glucocorticoids (GCs) are frequently used to treat many of the acute disease manifestations associated with inflammatory and autoimmune disorders. However, Toll-like receptor (TLR) pathway-activated plasmacytoid dendritic cells (pDCs) are resistant to GC-induced apoptosis, which leads to the inefficiency of GCs in the treatment of type I interferon-related autoimmune diseases, such as systemic lupus erythematosus (SLE). Therefore, compounds promoting pDC apoptosis may be helpful for improving the efficacy of GCs. In this study, we performed screening to identify microRNAs (miRNAs) involved in TLR-inhibited GC-induced pDC apoptosis and found an array of miRNAs that may regulate pDC apoptosis. Among those demonstrating altered expression, 6 miRNAs were inhibited in TLR-activated pDCs. Bioinformatics analysis and functional studies indicated that miR-29b and miR-29c were 2 key miRNAs involved in TLR-inhibited GC-induced pDC apoptosis. Furthermore, both of these miRNAs promoted pDC apoptosis by directly targeting Mcl-1 and Bcl-2 in human primary pDCs. Our findings provide new targets that could improve the efficacy of GCs for the treatment of SLE.