Prolonged intermittent theta burst stimulation for post-stroke aphasia: protocol of a randomized, double-blinded, sham-controlled trial.

Background: Post-stroke aphasia (PSA) is one of the most devastating symptoms after stroke, yet limited treatment options are available. Prolonged intermittent theta burst stimulation (piTBS) is a promising therapy for PSA. However, its efficacy remains unclear. Therefore, we aim to investigate the efficacy of piTBS over the left supplementary motor area (SMA) in improving language function for PSA patients and further explore the mechanism of language recovery. Methods: This is a randomized, double-blinded, sham-controlled trial. A total of 30 PSA patients will be randomly allocated to receive either piTBS stimulation or sham stimulation for 15 sessions over a period of 3 weeks. The primary outcome is the Western Aphasia Battery Revised (WAB-R) changes after treatment. The secondary outcomes include The Stroke and Aphasia Quality of Life Scale (SAQOL-39 g), resting-state electroencephalogram (resting-state EEG), Event-related potentials (ERP), brain derived neurotrophic factor (BDNF). These outcome measures are assessed before treatment, after treatment, and at 4-weeks follow up. This study was registered in Chinese Clinical Trial Registry (No. ChiCTR23000203238). Discussion: This study protocol is promising for improving language in PSA patients. Resting-state EEG, ERP, and blood examination can be used to explore the neural mechanisms of PSA treatment with piTBS. Clinical trial registration: https://www.chictr.org.cn/index.html, ChiCTR2300074533.

Insights into the structure and function of the hippocampus: implications for the pathophysiology and treatment of autism spectrum disorder.

The hippocampus is one of the brain areas affected by autism spectrum disorder (ASD). Individuals with ASD typically have impairments in hippocampus-dependent learning, memory, language ability, emotional regulation, and cognitive map creation. However, the pathological changes in the hippocampus that result in these cognitive deficits in ASD are not yet fully understood. In the present review, we will first summarize the hippocampal involvement in individuals with ASD. We will then provide an overview of hippocampal structural and functional abnormalities in genetic, environment-induced, and idiopathic animal models of ASD. Finally, we will discuss some pharmacological and non-pharmacological interventions that show positive impacts on the structure and function of the hippocampus in animal models of ASD. A further comprehension of hippocampal aberrations in ASD might elucidate their influence on the manifestation of this developmental disorder and provide clues for forthcoming diagnostic and therapeutic innovation.

Predictors of Cognitive Functions After Stroke Assessed Using the Wechsler Adult Intelligence Scale: A Retrospective Study.

Background: The mechanism(s) of cognitive impairment remains complex, making it difficult to confirm the factors influencing poststroke cognitive impairment (PSCI). Objective: This study quantitatively investigated the degree of influence and interactions of clinical indicators of PSCI. Methods: Information from 270 patients with PSCI and their Wechsler Adult Intelligence Scale (WAIS-RC) scores, totaling 18 indicators, were retrospectively collected. Correlations between the indicators and WAIS scores were calculated. Multiple linear regression model(MLR), genetic algorithm modified Back-Propagation neural network(GA-BP), logistic regression model (LR), XGBoost model (XGB), and structural equation model were used to analyze the degree of influence of factors on the WAIS and their mediating effects. Results: Seven indicators were significantly correlated with the WAIS scores: education, lesion side, aphasia, frontal lobe, temporal lobe, diffuse lesions, and disease course. The MLR showed significant effect of education, lesion side, aphasia, diffuse lesions, and frontal lobe on the WAIS. The GA-BP included five factors: education, aphasia, frontal lobe, temporal lobe, and diffuse lesions. LR predicted that the lesion side contributed more to mild cognitive impairment, while education, lesion side, aphasia, and course of the disease contributed more to severe cognitive impairment. XGB showed that education, side of the lesion, aphasia, and diffuse lesions contributed the most to PSCI. Aphasia plays a significant mediating role in patients with severe PSCI. Conclusions: Education, lesion side, aphasia, frontal lobe, and diffuse lesions significantly affected PSCI. Aphasia is a mediating variable between clinical information and the WAIS in patients with severe PSCI.

Divergent Synthesis of F- and CF3-Containing N-Fused Heterocycles Enabled by Fragmentation Cycloaddition of ß-CF3-1,3-Enynes with N-Aminopyridiniums Ylides.

The two novel cyclization modes of ß-CF3-1,3-enynes are presented herein for the divergent construction of F- and CF3-containing N-fused heterocycles. Fluorinated pyrazolo[1,5-a]pyridines were afforded from ß-CF3-1,3-enynes with N-aminopyridiniums ylides via detrifluoromethylative [2 + 3] cyclizations, followed by fluorine transfer from a CF3 unit. Whereas reaction with N-aminoisoquinoliniums ylides gave CF3-substituted pyrrolo[2,1-a]isoquinoline by unprecedented fragmentation [3 + 2]-cycloadditions. Additionally, gram-scale experiments and synthetic utility are demonstrated by further derivatization of fluorinated heterocycles.

The effects of rTMS on motor recovery after stroke: a systematic review of fMRI studies.

Repetitive transcranial magnetic stimulation (rTMS) has been widely used in motor rehabilitation after stroke, and functional magnetic resonance imaging (fMRI) has been used to investigate the neural mechanisms of motor recovery during stroke therapy. However, there is no review on the mechanism of rTMS intervention for motor recovery after stroke based on fMRI explicitly. We aim to reveal and summarize the neural mechanism of the effects of rTMS on motor function after stroke as measured by fMRI. We carefully performed a literature search using PubMed, EMBASE, Web of Science, and Cochrane Library databases from their respective inceptions to November 2022 to identify any relevant randomized controlled trials. Researchers independently screened the literature, extracted data, and qualitatively described the included studies. Eleven studies with a total of 420 poststroke patients were finally included in this systematic review. A total of 338 of those participants received fMRI examinations before and after rTMS intervention. Five studies reported the effects of rTMS on activation of brain regions, and four studies reported results related to brain functional connectivity (FC). Additionally, five studies analyzed the correlation between fMRI and motor evaluation. The neural mechanism of rTMS in improving motor function after stroke may be the activation and FCs of motor-related brain areas, including enhancement of the activation of motor-related brain areas in the affected hemisphere, inhibition of the activation of motor-related brain areas in the unaffected hemisphere, and changing the FCs of intra-hemispheric and inter-hemispheric motor networks.

Different doses of intermittent theta burst stimulation for upper limb motor dysfunction after stroke: a study protocol for a randomized controlled trial.

Background: Upper limb motor recovery is one of the important goals of stroke rehabilitation. Intermittent theta burst stimulation (iTBS), a new type of repetitive transcranial magnetic stimulation (rTMS), is considered a potential therapy. However, there is still no consensus on the efficacy of iTBS for upper limb motor dysfunction after stroke. Stimulus dose may be an important factor affecting the efficacy of iTBS. Therefore, we aim to investigate and compare the effects and neural mechanisms of three doses of iTBS on upper limb motor recovery in stroke patients, and our hypothesis is that the higher the dose of iTBS, the greater the improvement in upper limb motor function. Methods: This prospective, randomized, controlled trial will recruit 56 stroke patients with upper limb motor dysfunction. All participants will be randomized in a 1:1:1:1 ratio to receive 21 sessions of 600 pulses active iTBS, 1,200 pulses active iTBS, 1,800 pulses active iTBS, or 1,800 pulses sham iTBS in addition to conventional rehabilitation training. The primary outcome is the Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) score from baseline to end of intervention, and the secondary outcomes are the Wolf Motor Function Test (WMFT), Grip Strength (GS), Modified Barthel Index (MBI), and Stroke Impact Scale (SIS). The FMA-UE, MBI, and SIS are assessed pre-treatment, post-treatment, and at the 3-weeks follow-up. The WMFT, GS, and resting-state functional magnetic resonance imaging (rs-fMRI) data will be obtained pre- and post-treatment. Discussion: The iTBS intervention in this study protocol is expected to be a potential method to promote upper limb motor recovery after stroke, and the results may provide supportive evidence for the optimal dose of iTBS intervention.

Effects of excitatory transcranial magnetic stimulation over the different cerebral hemispheres dorsolateral prefrontal cortex for post-stroke cognitive impairment: a systematic review and meta-analysis.

Background: Post-stroke cognitive impairment (PSCI) is a significant health concern. Transcranial magnetic stimulation (TMS) is considered a promising rehabilitation therapy for improving cognition, and the effects of excitatory TMS on PSCI have received much attention in recent years. However, the effects of different cerebral hemispheres on excitatory TMS treatment of cognitive impairment have not been studied. This review aimed to study the effects of excitatory TMS over the dorsolateral prefrontal cortex (DLPFC) of different cerebral hemispheres on the cognitive function of patients with PSCI. Methods: Literature published in PubMed, Web of Science, Embase, Cochrane Library, Scopus, and Wiley from inception to September 30, 2022, were searched. Two researchers independently performed literature screening, data extraction, and quality assessment. Furthermore, we conducted a meta-analysis using RevMan software (version 5.4) and rated the strength of evidence using GRADEpro. Results: A total of 19 studies were included in this meta-analysis. The results showed that excitatory TMS over the left hemisphere DLPFC was significantly better in improving global cognition (SMD = 2.26, 95% CI 1.67-2.86, P < 0.00001; vs. SMD = 2.53, 95% CI 1.86-3.20, P < 0.00001), memory (SMD = 1.29, 95% CI 0.72-1.87, P < 0.0001), attention (SMD = 2.32, 95% CI 1.64-3.01, P < 0.00001), executive (SMD = 0.64, 95% CI 0.21-1.07, P = 0.004), P300 latency (SMD = 2.69, 95% CI 2.13-3.25, P < 0.00001), and depression (SMD = 0.95, 95% CI 0.26-1.63, P = 0.007) than that of the control group, but the effect on improving activities of daily living (ADL) was unclear (P = 0.03 vs. P = 0.17). Subgroup analysis further showed that excitatory TMS over the right hemisphere DLPFC was effective in improving the global cognition of PSCI patients (P < 0.00001), but the stimulation effect over the ipsilateral hemisphere DLPFC was unclear (P = 0.11 vs. P = 0.003). Additionally, excitatory TMS over the ipsilateral hemisphere DLPFC showed no statistical difference in improving ADL between the two groups (P = 0.25). Conclusions: Compared to other hemispheric sides, excitatory TMS over the left hemisphere DLPFC was a more effective stimulation area, which can significantly improved the global cognitive function, memory, attention, executive, P300 latency, and depression in patients with PSCI. There was no apparent therapeutic effect on improving activities of daily living (ADL). In the future, more randomized controlled trials with large-sample, high quality, and follow-up are necessary to explore a usable protocol further. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022369096.

Enhanced recovery after surgery in patients undergoing craniotomy: A meta-analysis.

BACKGROUND AND OBJECTIVE: Enhanced recovery after surgery (ERAS) is a multidisciplinary,and evidence-based perioperative care method. It is effective in shortening hospital stays and improving clinical outcomes. However, the application of ERAS in craniotomy lacks reliable evidence. The purpose of this study is to investigate the efficacy and safety of ERAS in craniotomy. METHODS: Studies of ERAS in craniotomy were systematically searched in PubMed, Embase, Cochrane, and Web of Science. Primary outcomes (total hospital stay and postoperative hospital stay, hospitalization cost, percent of patients with moderate to severe pain) and secondary outcomes (readmission rate and incidence of complication) were compared between ERAS and traditional perioperative care. RESULT: Of the 10 studies included in this meta-analysis, 6 were randomized-controlled trials (RCTs), 3 were cohort studies, and 1 was non-RCT. A total of 1275 patients were included, with 648 in the ERAS group and 627 in the control group. Compared with the control group, the ERAS group had a significantly shortened total length of stay (LOS) (MD = -2.437, 95% CI: -3.616, -1.077, P = 0.001) and postoperative LOS, reduced hospitalization cost (SMD = -0.631, 95% CI: -0.893, -0.369, P = 0.001), and lower percent of patients with moderate to severe pain. There was no significant difference in readmission rate between the two groups. Though, the ERAS group had a significantly lower risk of pneumonia than the control group. CONCLUSION: ERAS is safe and effective for craniotomy as it shortens total and postoperative LOS, reduces hospitalization costs, decreases the percent of patients with moderate to severe pain.

Characteristics of cognition impairment in patients after stroke based on the Wechsler Adult Intelligence Scale-Revised in China.

We aimed to explore the cognitive characteristics of patients with post-stroke cognition impairment (PSCI) on the basis of the Wechsler Adult Intelligence Scale-Revised in China (WAIS-RC) and the individual contribution of the subtests to WAIS score. We included 227 patients with PSCI who were assessed using the WAIS-RC. We described the characteristics and score distribution of the scale and subtests individually and compared them with those of the normal group to measure the damage degree of these patients. We performed item response theory analysis to explore the best criterion score for all dimensions that allowed ideal discrimination and difficulty for reflecting cognitive level. Finally, we analyzed the contribution of each dimension to the overall cognitive function. Patients with PSCI showed worse cognition levels than healthy individuals in terms of overall intelligence quotient (73.26-100, -1.78 SD), with a difference of 4.54-7.96 points in each dimension (-0.68 to -1.82 SD), and a range of 5-7 points is the appropriate range for reflecting cognitive ability in patients with PSCI. The average cognitive level of patients with PSCI was significantly inferior to normal people (-1.78 SD, 96.25%). Vocabulary contributes most to WAIS score.

Corrigendum: Prediction of motor function in patients with traumatic brain injury using genetic algorithms modified back propagation neural network: a data-based study.

[This corrects the article DOI: 10.3389/fnins.2022.1031712.].

Effects of combined cognitive and physical intervention on enhancing cognition in older adults with and without mild cognitive impairment: A systematic review and meta-analysis.

Background: Combined cognitive and physical intervention is commonly used as a non-pharmacological therapy to improve cognitive function in older adults, but it is uncertain whether combined intervention can produce stronger cognitive gains than either single cognitive or sham intervention. To address this uncertainty, we performed a systematic review and meta-analysis to evaluate the effects of combined intervention on cognition in older adults with and without mild cognitive impairment (MCI). Methods: We systematically searched eight databases for relevant articles published from inception to November 1, 2021. Randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) were used to compare the effects of the combined intervention with a single cognitive or sham intervention on cognition in older adults with and without MCI aged ≥ 50 years. We also searched Google Scholar, references of the included articles, and relevant reviews. Two independent reviewers performed the article screening, data extraction, and bias assessment. GRADEpro was used to rate the strength of evidence, and RevMan software was used to perform the meta-analysis. Results: Seventeen studies were included in the analysis, comprising eight studies of cognitively healthy older adults and nine studies of older adults with MCI. The meta-analysis showed that the combined intervention significantly improved most cognitive functions and depression (SMD = 0.99, 95% CI 0.54-1.43, p < 0.0001) in older adults compared to the control groups, but the intervention effects varied by cognition domains. However, there was no statistically significant difference in the maintenance between the combined and sham interventions (SMD = 1.34, 95% CI -0.58-3.27, p = 0.17). The subgroup analysis also showed that there was no statistical difference in the combined intervention to improve global cognition, memory, attention, and executive function between cognitive healthy older adults and older adults with MCI. Conclusions: Combined intervention improves cognitive functions in older adults with and without MCI, especially in global cognition, memory, and executive function. However, there was no statistical difference in the efficacy of the combined intervention to improve cognition between cognitive healthy older adults and older adults with MCI. Moreover, the maintenance of the combined intervention remains unclear due to the limited follow-up data and high heterogeneity. In the future, more stringent study designs with more follow-ups are needed further to explore the effects of combined intervention in older adults. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/#recordDetails, identifier: CRD42021292490.

Excitatory Repetitive Transcranial Magnetic Stimulation Over the Ipsilesional Hemisphere for Upper Limb Motor Function After Stroke: A Systematic Review and Meta-Analysis.

Background: Repetitive transcranial magnetic stimulation (rTMS) is a promising therapy to promote recovery of the upper limb after stroke. According to the regulation of cortical excitability, rTMS can be divided into excitatory rTMS and inhibitory rTMS, and excitatory rTMS includes high-frequency rTMS (HF-rTMS) or intermittent theta-burst stimulation (iTBS). We aimed to evaluate the effects of excitatory rTMS over the ipsilesional hemisphere on upper limb motor recovery after stroke. Methods: Databases of PubMed, Embase, ISI Web of Science, and the Cochrane Library were searched for randomized controlled trials published before 31 December 2021. RCTs on the effects of HF-rTMS or iTBS on upper limb function in patients diagnosed with stroke were included. Two researchers independently screened the literature, extracted the data, and assessed quality. The meta-analysis was performed by using Review Manager Version 5.4 software. Results: Fifteen studies with 449 participants were included in this meta-analysis. This meta-analysis found that excitatory rTMS had significant efficacy on upper limb motor function (MD = 5.88, 95% CI, 3.32-8.43, P < 0.001), hand strength (SMD = 0.53, 95% CI, 0.04-1.01, P = 0.03), and hand dexterity (SMD = 0.76, 95% CI, 0.39-1.14, P < 0.001). Subgroup analyses based on different types of rTMS showed that both iTBS and HF-rTMS significantly promoted upper limb motor function (iTBS, P < 0.001; HF-rTMS, P < 0.001) and hand dexterity (iTBS, P = 0.01; HF-rTMS, P < 0.001) but not hand strength (iTBS, P = 0.07; HF-rTMS, P = 0.12). Further subgroup analysis based on the duration of illness demonstrated that applying excitatory rTMS during the first 3 months (<1 month, P = 0.01; 1-3 months, P = 0.001) after stroke brought significant improvement in upper limb motor function but not in the patients with a duration longer than 3 months (P = 0.06). We found that HF-rTMS significantly enhanced the motor evoked potential (MEP) amplitude of affected hemisphere (SMD = 0.82, 95% CI, 0.32-1.33, P = 0.001). Conclusion: Our study demonstrated that excitatory rTMS over the ipsilesional hemisphere could significantly improve upper limb motor function, hand strength, and hand dexterity in patients diagnosed with stroke. Both iTBS and HF-rTMS which could significantly promote upper limb motor function and hand dexterity, and excitatory rTMS were beneficial to upper limb motor function recovery only when applied in the first 3 months after stroke. HF-rTMS could significantly enhance the MEP amplitude of the affected hemisphere. High-quality and large-scale randomized controlled trials in the future are required to confirm our conclusions. Clinical Trial Registration: www.crd.york.ac.uk/prospero/, identifier: CRD42022312288.

Prediction of motor function in patients with traumatic brain injury using genetic algorithms modified back propagation neural network: A data-based study.

Objective: Traumatic brain injury (TBI) is one of the leading causes of death and disability worldwide. In this study, the characteristics of the patients, who were admitted to the China Rehabilitation Research Center, were elucidated in the TBI database, and a prediction model based on the Fugl-Meyer assessment scale (FMA) was established using this database. Methods: A retrospective analysis of 463 TBI patients, who were hospitalized from June 2016 to June 2020, was performed. The data of the patients used for this study included the age and gender of the patients, course of TBI, complications, and concurrent dysfunctions, which were assessed using FMA and other measures. The information was collected at the time of admission to the hospital and 1 month after hospitalization. After 1 month, a prediction model, based on the correlation analyses and a 1-layer genetic algorithms modified back propagation (GA-BP) neural network with 175 patients, was established to predict the FMA. The correlations between the predicted and actual values of 58 patients (prediction set) were described. Results: Most of the TBI patients, included in this study, had severe conditions (70%). The main causes of the TBI were car accidents (56.59%), while the most common complication and dysfunctions were hydrocephalus (46.44%) and cognitive and motor dysfunction (65.23 and 63.50%), respectively. A total of 233 patients were used in the prediction model, studying the 11 prognostic factors, such as gender, course of the disease, epilepsy, and hydrocephalus. The correlation between the predicted and the actual value of 58 patients was R 2 = 0.95. Conclusion: The genetic algorithms modified back propagation neural network can predict motor function in patients with traumatic brain injury, which can be used as a reference for risk and prognosis assessment and guide clinical decision-making.

Female sex hormones are associated with the reduction of serum sodium and hypertension complications in patients with aldosterone-producing adenoma.

This study was conducted to evaluate gender-related differences in clinical characteristics and vascular complications in patients with aldosterone-producing adenomas (APA). Clinical characteristics, biochemical markers and incidence of vascular complications were compared by gender in 187 consecutive patients with APA confirmed by pathological diagnosis. Patients were separated into two groups based on ages either older or younger than 49 years, the average age of menopause among Chinese women (<49 y and ≥49 y). Males had significantly higher BMI than females in the age group of <49 years (p = 0.017). In the <49 years group, males had significantly higher serum sodium levels (p = 0.003). However, no such gender differences in clinical characteristics were observed in patients ≥49 years. A higher proportion of vascular complications was observed in males as compared to females aged <49 years but the difference was not statistically significant (51.4% vs. 34.8%, p = 0.105). The only gender difference observed in vascular complications between patients aged ≥49 years was that a significantly greater proportion of males had cerebrovascular complication compared to females (p = 0.006). Our data suggest that female sex hormones are implicated in reducing serum sodium concentration and vascular complications in female APA patients.

The invasion of tobacco mosaic virus RNA induces endoplasmic reticulum stress-related autophagy in HeLa cells.

The ability of human cells to defend against viruses originating from distant species has long been ignored. Owing to the pressure of natural evolution and human exploration, some of these viruses may be able to invade human beings. If their 'fresh' host had no defences, the viruses could cause a serious pandemic, as seen with HIV, SARS (severe acute respiratory syndrome) and avian influenza virus that originated from chimpanzees, the common palm civet and birds, respectively. It is unknown whether the human immune system could tolerate invasion with a plant virus. To model such an alien virus invasion, we chose TMV (tobacco mosaic virus) and used human epithelial carcinoma cells (HeLa cells) as its 'fresh' host. We established a reliable system for transfecting TMV-RNA into HeLa cells and found that TMV-RNA triggered autophagy in HeLa cells as shown by the appearance of autophagic vacuoles, the conversion of LC3-I (light chain protein 3-I) to LC3-II, the up-regulated expression of Beclin1 and the accumulation of TMV protein on autophagosomal membranes. We observed suspected TMV virions in HeLa cells by TEM (transmission electron microscopy). Furthermore, we found that TMV-RNA was translated into CP (coat protein) in the ER (endoplasmic reticulum) and that TMV-positive RNA translocated from the cytoplasm to the nucleolus. Finally, we detected greatly increased expression of GRP78 (78 kDa glucose-regulated protein), a typical marker of ERS (ER stress) and found that the formation of autophagosomes was closely related to the expanded ER membrane. Taken together, our data indicate that HeLa cells used ERS and ERS-related autophagy to defend against TMV-RNA.