Cardiac MR Feature Tracking Derived Strain Analysis can Predict Return to Training following Exertional Heatstroke.

BACKGROUND: Exertional heatstroke (EHS) is increasingly common in young trained soldiers. However, the prognosis marker in EHS patients remains unclear. To evaluate cardiac MRI feature tracking (CMR-FT) derived left ventricle (LV) strain as a biomarker for return to training (RTT) in trained soldiers with EHS in a prospective CMR cohort. METHODS: Trained soldiers (participants) with EHS underwent cardiac MR cine sequences between June 2020 and August 2023. Two-dimensional (2D) LV strain parameters were derived. At 3 months after index CMR, the participants with persistent cardiac symptoms including chest pain, dyspnea, palpitations, syncope, and recurrent heat-related illness were defined as non-RTT. Multivariable logistic regression analysis is used to develop a predictive RTT model. The performance of different models was compared using the area under curve (AUC). RESULTS: A total of 80 participants (median age, 21 years; interquartile range (IQR), 20-23 years) and 27 health controls (median age, 21 years; IQR, 20-22 years) were prospectively included. Of the 77 participants, 32 (41.6%) had persistent cardiac symptoms and were not able to RTT at 3 months follow-up after experiencing EHS. The 2D global longitudinal strain (GLS) was significantly impaired in EHS participants compared to the healthy control group (-15.81 ± 1.67% vs -16.93 ± 1.22%, P =.001), which also showed significantly statistical differences between participants with RTT and non-RTT (-14.99 ± 3.54% vs -16.53 ± 1.43%, P <.001). 2D-GLS (≤ -15.00%) (odds ratio, 1.53; 95% confidence interval (CI): 1.08, 2.17; P =.016) was an independent predictor for RTT even after adjusting known risk factors. 2D-GLS provided incremental prognostic value over the clinical model and conventional CMR parameters model (AUCs: 0.72 vs 0.88, P =.013; 0.79 vs 0.88, P =.023; respectively). CONCLUSIONS: Two-dimensional global longitudinal strain (≤ -15.00%) is an incremental prognostic CMR biomarker to predict return to training in exertional heatstroke soldiers.

Exogenous hydrogen sulphide promotes plant flowering through the Arabidopsis splicing factor AtU2AF65a.

Alternative splicing (AS) is an important regulatory mode at the post-transcriptional level, through which many flowering genes regulate floral transition by producing multiple transcripts, and splicing factors have essential roles in this process. Hydrogen sulphide (H2S) is a newly found gasotransmitter that has critical physiological roles in plants, and one of its potential modes of action is via persulfidation of target proteins at specific cysteine sites. Previously, it has been shown that both the splicing factor AtU2AF65a and H2S are involved in the regulation of plant flowering. This study found that, in Arabidopsis, the promoting effect of H2S on flowering was abolished in atu2af65a-4 mutants. Transcriptome analyses showed that when AtU2AF65a contained mutations, the regulatory function of H2S during the AS of many flowering genes (including SPA1, LUH, LUG and MAF3) was inhibited. The persulfidation assay showed that AtU2AF65a can be persulfidated by H2S, and the RNA immunoprecipitation data indicated that H2S could alter the binding affinity of AtU2AF65a to the precursor messenger RNA of the above-mentioned flowering genes. Overall, our results suggest that H2S may regulate the AS of flowering-related genes through persulfidation of splicing factor AtU2AF65a and thus lead to early flowering in plants.

Clinical Research Progress of the Post-Stroke Upper Limb Motor Function Improvement via Transcutaneous Auricular Vagus Nerve Stimulation.

Stroke is a disease with high morbidity and disability, and motor impairment is a common sequela of stroke. Transcutaneous auricular vagus nerve stimulation (taVNS) is a type of non-invasive stimulation, which can effectively improve post-stroke motor dysfunction. This review discusses stimulation parameters, intervention timing, and the development of innovative devices for taVNS. We further summarize the application of taVNS in improving post-stroke upper limb motor function to further promote the clinical research and application of taVNS in the rehabilitation of post-stroke upper limb motor dysfunction.

Case report: High-frequency repetitive transcranial magnetic stimulation for treatment of hereditary spastic paraplegia type 11.

Hereditary spastic paraplegia (HSP) is a heterogeneous group of inherited neurodegenerative disorders that currently have no cure. HSP type 11 (SPG11-HSP) is a complex form carrying mutations in the SPG11 gene. Neuropathological studies demonstrate that motor deficits in these patients are mainly attributed to axonal degeneration of the corticospinal tract (CST). Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive technique that can induce central nervous system plasticity and promote neurological recovery by modulating the excitability of cortical neuronal cells. Although rTMS is expected to be a therapeutic tool for neurodegenerative diseases, no previous studies have applied rTMS to treat motor symptoms in SPG11-HSP. Here, we report a case of SPG11-HSP with lower extremity spasticity and gait instability, which were improved by applying high-frequency rTMS (HF-rTMS) at the primary motor cortex (M1). Clinical and physiological features were measured throughout the treatment, including the Modified Ashworth Scale (MAS), Berg Balance Scale (BBS), the timed up and go (TUG) test and the 10-meter walk test time (10 MWT). The structure and excitability of the CST were assessed by diffusion tensor imaging (DTI) and transcranial magnetic stimulation (TMS), respectively. After treatment, the patient gained 17 points of BBS, along with a gradual decrease in MAS scores of the bilateral lower extremity. In addition, the TUG test and 10 MWT improved to varying degrees. TMS assessment showed increased motor evoked potential (MEP) amplitude, decreased resting motor threshold (RMT), decreased central motor conduction time (CMCT), and decreased difference in the cortical silent period (CSP) between bilateral hemispheres. Using the DTI technique, we observed increased fractional anisotropy (FA) values and decreased mean diffusivity (MD) and radial diffusivity (RD) values in the CST. It suggests that applying HF-rTMS over the bilateral leg area of M1 (M1-LEG) is beneficial for SPG11-HSP. In this study, we demonstrate the potential of rTMS to promote neurological recovery from both functional and structural perspectives. It may provide a clinical rationale for using rTMS in the rehabilitation of HSP patients.

A potential link between fibroblast growth factor-23 and the progression of AKI to CKD.

BACKGROUND: Patients who recover from acute kidney injury (AKI) have a 25% increase in the risk of chronic kidney disease (CKD) and a 50% increase in mortality after a follow-up of approximately 10 years. Circulating FGF-23 increases significantly early in the development of AKI, is significantly elevated in patients with CKD and has become a major biomarker of poor clinical prognosis in CKD. However, the potential link between fibroblast growth factor-23 levels and the progression of AKI to CKD remains unclear. METHOD: Serum FGF-23 levels in AKI patients and ischaemia‒reperfusion injury (IRI) mice were detected with ELISA. Cultured HK2 cells were incubated with FGF-23 and PD173074, a blocker of FGFR, and then TGFß/Smad and Wnt/ß-catenin were examined with immunofluorescence and immunoblotting. Quantitative real-time polymerase chain reaction was used to detect the expression of COL1A1 and COL4A1. Histologic staining confirmed renal fibrosis. RESULTS: The level of serum FGF-23 was significantly different between AKI patients and healthy controls (P < 0.01). Moreover, serum FGF-23 levels in the CKD progression group were significantly higher than those in the non-CKD progression group of AKI patients (P < 0.01). In the AKI-CKD mouse model, serum FGF-23 levels were increased, and renal fibrosis occurred; moreover, the protein expression of ß-catenin and p-Smad3 was upregulated. PD173074 downregulated the expression of ß-catenin and p-Smad3 and reduced fibrosis in both mice and HK2 cells. CONCLUSION: The increase in FGF-23 may be associated with the progression of AKI to CKD and may mediate renal fibrosis via TGF-ß and Wnt/ß-catenin activation.

Clinical features and prognosis of autosomal dominant polycystic kidney disease with cerebrovascular complications.

OBJECTIVES: This retrospective study was used to evaluate the clinical and imaging characteristics and the prognosis of autosomal dominant polycystic kidney disease (ADPKD) with cerebrovascular complications. MATERIALS AND METHODS: We retrospectively analyzed 30 patients with ADPKD complicated with intracerebral hemorrhage (ICH), subarachnoid hemorrhage (SAH), unruptured intracranial aneurysms (UIAs), or Moyamoya disease (MMD) who were admitted to Jinling Hospital from January 2001 to January 2022. We analyzed the clinical manifestations and imaging characteristics of ADPKD patients with cerebrovascular complications and followed up on their long-term outcomes. RESULTS: 30 patients, 17 men and 13 women, with an average age of 47.5 (40.0, 54.0) years were included in this study, including 12 cases of ICH, 12 cases of SAH, 5 cases of UIA, and 1 case of MMD. The 8 patients who died during follow-up had a lower Glasgow Coma Scale (GCS) on admission (p = 0.024) and a significantly higher serum creatinine (p = 0.004) and blood urea nitrogen (p = 0.006) than the 22 patients with long-term survival. CONCLUSION: Intracranial aneurysms, SAH, and ICH are the most common cerebrovascular diseases in ADPKD. Patients with low GCS score or worse renal function have a poor prognosis, which can lead to disability and even death.

Image Improved Intravoxel Incoherent Motion MRI With Optimized Trigger Delays Based on Strain Curve Analysis to Evaluate Myocardial Microvascular Dysfunction of Exertional Heat Illness.

BACKGROUND: Intravoxel incoherent motion (IVIM) MRI has not been widely used and its role in evaluating exertional heat illness (EHI)-related myocardial involvement remains unknown. PURPOSE: To investigate the feasibility of strain curve-derived trigger delay (TD) IVIM-MRI and its role in assessing myocardial diffusion and microvascular perfusion of EHI patients. STUDY TYPE: Prospective. SUBJECTS: A total of 42 male EHI patients (median age: 21 years) and 22 age- and sex-matched healthy controls (HC). FIELD STRENGTH/SEQUENCE: A 3-T, diffusion-weighted spin-echo echo-planar-imaging sequence. ASSESSMENT: IVIM-MRI was acquired by conventional TD method (group A) or strain curve-based TD method (group B) in random order. IVIM image quality was evaluated on a 3-point Likert scale (1, nondiagnostic; 2, moderate; 3, good). Technical success was defined as image quality score = 3. IVIM-MRI-derived parameters (pseudo diffusion in the capillaries [D*], perfusion fraction [f], and slow apparent diffusion coefficient [D]) were compared between EHI and HC. STATISTICAL TESTS: Student's t-tests, chi-square tests, one-way analysis of variance, receiver operating characteristic (ROC) curve analysis, Pearson's correlation coefficient (r). The statistical significance level was set at P < 0.05. RESULTS: IVIM-MRI image quality score (median [interquartile range]: 3 [2, 3] vs. 2 [1-3]) and technical success rate (61.9%[13/21] vs. 28.6%[6/21]) were significantly improved in group B. EHI patients showed significantly decreased D* (118.1 ± 23.3 × 10-3  mm2 /sec vs. 142.7 ± 42.6 × 10-3  mm2 /sec) and f values (0.42 ± 0.12 vs. 0.51 ± 0.11) and significantly higher D values (3.0 ± 0.9 × 10-3  mm2 /sec vs. 2.5 ± 0.6 × 10-3  mm2 /sec) compared to HC. Relative to D and D*, f showed the most robust efficacy for detecting EHI-related myocardial injury with the highest area under the ROC curve (0.906: 95% confidence interval, 0.799, 0.967) and sensitivity of 88.5% and specificity of 85.6%. CONCLUSION: The strain curve-based TD method significantly improved image quality and technical success rate of IVIM-MRI, and f value may be an effective biomarker to assess myocardial microcirculation abnormalities of EHI patients. EVIDENCE LEVEL: 2. TECHNICAL EFFICACY: Stage 3.

Persistent inflammation-immunosuppression-catabolism syndrome in patients with systemic lupus erythematosus.

OBJECTIVE: To evaluate the clinical characteristics and prognosis of systemic lupus erythematosus (SLE) with persistent inflammation-immunosuppression-catabolism syndrome (PICS). METHODS: We retrospectively analyzed patients with SLE who were admitted to the renal intensive care unit (ICU) for over 14 days at Jinling Hospital from July 2010 to July 2018. According to the diagnostic criteria of PICS, we divided the SLE patients into a PICS group and a non-PICS group. We performed a multivariate Cox regression analysis on the risk factors for death in these two groups by comparing the clinical features and prognosis. RESULTS: A total of 96 SLE patients met the inclusion and exclusion criteria of this study, including 61 patients in the PICS group and 35 patients in the non-PICS group. The PICS group patients required a longer length of stay in ICU with higher inflammatory indicators (such as C-reactive protein, procalcitonin and interleukin-6) and lower immune levels (such as total, CD3 + , CD4 + , CD8 + and CD20 + lymphocytes) compared to the non-PICS group patients (P < 0.01). Hemoglobin, platelets, serum creatinine, serum blood urea nitrogen and SLE Disease Activity Index (SLE-DAI) score in the PICS group were lower than those in the non-PICS group (P < 0.05), suggesting severe hematological injury in the PICS group and relatively severe renal damage in the non-PICS group. The rates of PICS combined with sepsis, acute respiratory distress syndrome, mechanical ventilation, gram-positive bacteria, gram-negative bacteria, fungi and double infections were higher than those in the non-PICS group (P < 0.05). The 3-year survival rate was 50.82% in the PICS group and 85.71% in the non-PICS group. The 3-year renal survival rate was 32.79% in the PICS group and 51.43% in the non-PICS group. Multivariate Cox regression found that the total lymphocyte count during ICU admission was an independent risk factor for death in SLE patients with PICS. CONCLUSION: Patients with SLE complicated with PICS had longer ICU stays, a lower level of SLE activity, a higher risk of secondary infection and a significantly lower survival rate than non-PICS patients.

Neural signatures for the n-back task with different loads: An event-related potential study.

The n-back task is widely used in working memory (WM) research. However, it remains unclear how the electrophysiological correlates of WM processes, the P2, N2, P300, and negative slow wave (NSW), are affected by differences in load. Specifically, while previous work has examined the P300, less attention has been paid to the other components assessing the load of the n-back paradigm. The present study aims to investigate whether other sub-processes in WM (such as inhibitory control) are as sensitive to n-back load changes as the update process by observing changes in the above event-related potential (ERP) components. The results showed poorer behavioral performance with increasing WM load. Greater NSW and smaller P300 amplitudes were elicited by n-back task with a higher load compared to that with lower load. In contrast, there was no significant effect of the n-back load on the amplitudes of P2 and N2. These findings suggest that the updating process and the maintenance process are sensitive to the n-back load change. Therefore, changes in the updating and maintenance processes should be considered when using the n-back task to manipulate the WM load in experiments. The present study may contribute to the understanding of the complexity of WM loads. Additionally, a theoretical basis for follow-up research to explore ways of improving WM performance with high load is provided.

Comparison of Sensory Observation and Somatosensory Stimulation in Mirror Neurons and the Sensorimotor Network: A Task-Based fMRI Study.

Objective: This study aimed to investigate brain plasticity by somatosensory stimulation (SS) and sensory observation (SO) based on mirror neuron and embodied cognition theory. Action observation therapy has been widely adopted for motor function improvement in post-stroke patients. However, it is uncertain whether the SO approach can also contribute to the recovery of sensorimotor function after stroke. In this study, we explored the therapeutic potential of SO for sensorimotor dysfunction and provided new evidence for neurorehabilitation. Methods: Twenty-six healthy right-handed adults (12 men and 14 women), aged 18-27 (mean, 22.12; SD, 2.12) years were included. All subjects were evaluated with task-based functional magnetic resonance imaging (fMRI) to discover the characteristics and differences in brain activation between SO and SS. We adopted a block design with two conditions during fMRI scanning: observing a sensory video of brushing (task condition A, defined as SO) and brushing subjects' right forearms while they watched a nonsense string (task condition B, defined as SS). One-sample t-tests were performed to identify brain regions and voxels activated for each task condition. A paired-sample t-test and conjunction analysis were performed to explore the differences and similarities between SO and SS. Results: The task-based fMRI showed that the bilateral postcentral gyrus, left precentral gyrus, bilateral middle temporal gyrus, right supramarginal gyrus, and left supplementary motor area were significantly activated during SO or SS. In addition to these brain regions, SO could also activate areas containing mirror neurons, like the left inferior parietal gyrus. Conclusion: SO could activate mirror neurons and sensorimotor network-related brain regions in healthy subjects like SS. Therefore, SO may be a promising novel therapeutic approach for sensorimotor dysfunction recovery in post-stroke patients.

The Modulation of Working-Memory Performance Using Gamma-Electroacupuncture and Theta-Electroacupuncture in Healthy Adults.

Working memory (WM), a central component of general cognition, plays an essential role in human beings' daily lives. WM impairments often occur in psychiatric, neurodegenerative, and neurodevelopmental disorders, mainly presenting as loss of high-load WM. In previous research, electroacupuncture (EA) has been shown to be an effective treatment for cognitive impairments. Frequency parameters are an important factor in therapeutic results, but the optimal frequency parameters of EA have not yet been identified. In this study, we chose theta-EA (θ-EA; 6 Hz) and gamma-EA (γ-EA; 40 Hz), corresponding to the transcranial alternating-current stimulation (tACS) frequency parameters at the Baihui (DU20) and Shenting (DU24) acupoints, in order to compare the effects of different EA frequencies on WM. We evaluated WM performance using visual 1-back, 2-back, and 3-back WM tasks involving digits. Each participant (N = 30) attended three different sessions in accordance with a within-subject crossover design. We performed θ-EA, γ-EA, and sham-EA in a counterbalanced order, conducting the WM task both before and after intervention. The results showed that d-prime (d') under all three stimulation conditions had no significance in the 1-back and 2-back tasks. However, in the 3-back task, there was a significant improvement in d' after intervention compared to d' before intervention under θ-EA (F [1, 29] = 22.64; P < 0.001), while we saw no significant difference in the γ-EA and sham-EA groups. Reaction times for hits (RT-hit) under all three stimulation conditions showed decreasing trends in 1-, 2-, and 3-back tasks but without statistically significant differences. These findings suggest that the application of θ-EA might facilitate high-load WM performance.

Augmentative and alternative communication intervention for in-patient individuals with post-stroke aphasia: study protocol of a parallel-group, pragmatic randomized controlled trial.

BACKGROUND: People with post-stroke aphasia commonly receive speech-language therapy (SLT) when they are admitted to hospitals. Commonly, these patients reported communication difficulties in in-patient settings. Augmentative and alternative communication (AAC) has been reported as an effective treatment approach to improve communication effectiveness, language performance, decreasing depression, and improving quality of life for this population. However, little evidence has demonstrated the use of AAC intervention (AACT) in early recovery from people with post-stroke aphasia in in-patient rehabilitation settings for improving these patients' communication effectiveness. The pilot randomized controlled trial (RCT) will explore the effectiveness and feasibility of including AACT in regular SLT for in-patient people with post-stroke aphasia. METHOD: This pilot RCT is a single-blind, randomized controlled trial with two parallel groups. Both groups receive a 1-h treatment session, including either both AACT and SLT or SLT only for ten consecutive days. We aim to include 22 in-patient participants with post-stroke aphasia in each group. Participants will be assessed at pre- and post-intervention and 2 weeks after intervention. The primary outcomes are the ability of communication measured by the communication of basic needs subtest in the Functional Assessment of Communication Skills for Adult (FACS) and the overall language performance measured by the Chinese Standard Aphasia Battery (ABC). The secondary outcomes include a 10-min conversation, the 10-item Hospital version of the Stroke Aphasic Depression Questionnaire (SADQH-10), the Stroke-Specific Quality of Life Scale (SS-QOL), and a patient and caregiver satisfaction questionnaire. DISCUSSION: This pilot RCT will contribute to new scientific evidence to the field of aphasia rehabilitation in early recovery during the in-patient period. The paper describes the trial, which will explore the effect of combining AACT and SLT and SLT only, our choice of primary and secondary outcome measures, and proposed analyses. The study results will provide information for implementing AACT in the regular in-patient SLT of future RCTs. TRIAL REGISTRATION: Chinese Clinical Trial Registry database (ChiCTR) ChiCTR2000028870 . Registered on 5 January 2020.

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.

Clinical and morphologic spectrum of renal involvement in idiopathic hypereosinophilic syndrome.

BACKGROUND: To explore the clinical and pathological features of renal lesions in patients with kidney involvement in idiopathic hypereosinophilic syndrome (IHES). METHODS: The demographic, clinical, and pathological characteristics and the treatment and follow-up data were analyzed. RESULTS: We identified 18 patients with IHES and renal involvement. Eleven patients presented with nephrotic syndrome, and 6 patients had impaired renal function. 15 patients underwent renal biopsy, and the pathological findings included the following: membranoproliferative glomerulonephritis in 3 patients; minimal-change disease in 3; mesangial proliferative nephritis in two; IgA nephropathy in 2; membranous nephropathy in two; chronic interstitial nephritis in two; focal segmental sclerosis in one; and eosinophil infiltration into the renal interstitium in 11 and into the glomerulus in 3. After treatment with glucocorticoids, the eosinophil count decreased. 15 patients were followed up, and 14 showed a decrease in urinary protein or renal function recovery. When glucocorticoids were discontinued, eosinophil increased (8 cases), urine protein increased (1 case), and 1 patient progressed to end-stage renal disease. CONCLUSIONS: Nephrotic syndrome with or without renal insufficiency is the main clinical manifestation. A wide spectrum of renal lesions can be observed in patients with IHES. Eosinophil infiltration into the renal interstitium was common in these patients. Most patients have a good prognosis after glucocorticoid therapy.

Transcranial pulse current stimulation improves the locomotor function in a rat model of stroke.

Previous studies have shown that transcranial pulse current stimulation (tPCS) can increase cerebral neural plasticity and improve patients' locomotor function. However, the precise mechanisms underlying this effect remain unclear. In the present study, rat models of stroke established by occlusion of the right cerebral middle artery were subjected to tPCS, 20 minutes per day for 7 successive days. tPCS significantly reduced the Bederson score, increased the foot print area of the affected limbs, and reduced the standing time of affected limbs of rats with stroke compared with that before intervention. Immunofluorescence staining and western blot assay revealed that tPCS significantly increased the expression of microtubule-associated protein-2 and growth-associated protein-43 around the ischemic penumbra. This finding suggests that tPCS can improve the locomotor function of rats with stroke by regulating the expression of microtubule-associated protein-2 and growth-associated protein-43 around the ischemic penumbra. These findings may provide a new method for the clinical treatment of poststroke motor dysfunction and a theoretical basis for clinical application of tPCS. The study was approved by the Animal Use and Management Committee of Shanghai University of Traditional Chinese Medicine of China (approval No. PZSHUTCM190315003) on February 22, 2019.

Effectiveness of theta and gamma electroacupuncture for post-stroke patients on working memory and electrophysiology: study protocol for a double-center, randomized, patient- and assessor-blinded, sham-controlled, parallel, clinical trial.

BACKGROUND: Practitioners of complementary and alternative medicine have suggested that electroacupuncture (EA) could improve post-stroke cognitive impairment, based on the clinical evidence. This study protocol is aimed at showing the effectiveness of theta and gamma EA for post-stroke patients on working memory (WM) and electrophysiology. METHODS: After assessing their eligibility, 66 patients with stroke will be enrolled from two Chinese medicine hospitals and randomly divided into theta frequency EA group, gamma frequency EA group, and sham-EA group according to the ratio of 1:1:1. All patients will receive 20 sessions of EA procedures for 4 weeks. Patients in three groups will receive EA at two same acupoints in the head: Baihui (GV20) and Shenting (GV24). The frequency of the three groups of EA is set as follows: 6 Hz (theta-EA group), 40 Hz (gamma-EA group), and no current through the electrodes (sham EA). Patients and assessors will be blinded throughout the entire study. The primary outcome is the performance accuracy of 1-back task which is a frequently used measure of WM in cognitive neuroscience research contexts. Secondary outcome measures will include the response time of 1-back task, the Rivermead Behavioral Memory Test, Trail Making Test, Loewenstein Occupational Therapy Cognitive Assessment Scale, modified Barthel Index, and electroencephalogram (EEG) signals during 1-back tasks. A blinding index will be assessed. Data will be statistically analyzed by one-way ANOVA, at 5% of significance level. DISCUSSION: We expect this double-center, randomized, patient- and assessor-blinded, sham-controlled, parallel, clinical trial to explore the effectiveness of theta and gamma EA therapy, compared with sham EA, for post-stroke WM. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2000031995 . Registered on 17 April 2020.

Case Report: Identification of a Novel Variant (m.8909T>C) of Human Mitochondrial ATP6 Gene and Its Functional Consequences on Yeast ATP Synthase.

With the advent of next generation sequencing, the list of mitochondrial DNA (mtDNA) mutations identified in patients rapidly and continuously expands. They are frequently found in a limited number of cases, sometimes a single individual (as with the case herein reported) and in heterogeneous genetic backgrounds (heteroplasmy), which makes it difficult to conclude about their pathogenicity and functional consequences. As an organism amenable to mitochondrial DNA manipulation, able to survive by fermentation to loss-of-function mtDNA mutations, and where heteroplasmy is unstable, Saccharomyces cerevisiae is an excellent model for investigating novel human mtDNA variants, in isolation and in a controlled genetic context. We herein report the identification of a novel variant in mitochondrial ATP6 gene, m.8909T>C. It was found in combination with the well-known pathogenic m.3243A>G mutation in mt-tRNALeu. We show that an equivalent of the m.8909T>C mutation compromises yeast adenosine tri-phosphate (ATP) synthase assembly/stability and reduces the rate of mitochondrial ATP synthesis by 20-30% compared to wild type yeast. Other previously reported ATP6 mutations with a well-established pathogenicity (like m.8993T>C and m.9176T>C) were shown to have similar effects on yeast ATP synthase. It can be inferred that alone the m.8909T>C variant has the potential to compromise human health.

Nocardiosis in patients with nephrotic syndrome: a retrospective analysis of 11 cases and a literature review.

OBJECTIVES: We evaluated the clinical manifestations and outcomes of nocardiosis, a rare opportunistic infection that occurs in patients with nephrotic syndrome. METHODS: The records of NS patients with nocardiosis in a single hospital during 2000-2019 were retrieved and studied in detail. RESULTS: Eleven patients were included. The mean time to develop nocardiosis after glucocorticoid therapy was 11.5 ± 14.8 months. Most patients had fever, elevated white blood cell counts and C-reactive protein, whereas procalcitonin levels were normal or slightly elevated in 91% (10/11) patients, except one patient suffered from septic shock. Nine patients were tested for CD4+ T-cell counts; of these, four patients had counts < 200 cells/µL. The most common site of nocardiosis involvement was lung (100%), followed by subcutaneous tissue (72.7%). Radiological findings for lungs in seven cases were characterized by isolated or scattered nodules and masses, usually located subpleural or close to the hilum. Positive smears of Nocardia were detected in 100% of samples of subcutaneous abscess and pleural fluid. Nine patients received oral trimethoprim-sulfamethoxazole, four of which received combined carbapenem, and the remaining two patients received carbapenem monotherapy. The long-term prognosis was excellent, with a treatment success rate of 100% in all patients. CONCLUSIONS: NS patients can develop immunodeficiency after treatment with glucocorticoid and immunosuppressants. In cases where patients develop systemic multiple abscesses, or lung images reveal isolated or scattered nodules and masses that are subpleural or close to the hilum, nocardial infection should be considered. Early diagnosis and specific treatment may improve patient outcomes.

Human Theta Burst Stimulation Combined with Subsequent Electroacupuncture Increases Corticospinal Excitability.

OBJECTIVE: Intermittent theta burst stimulation (iTBS) is a widely used noninvasive brain stimulation for the facilitation of corticospinal excitability (CSE). Previous studies have shown that acupuncture applied to acupoints associated with motor function in healthy people can reduce the amplitude of the motor-evoked potentials (MEPs), which reflects the inhibition of CSE. In our work, we wanted to test whether the combination of iTBS and electroacupuncture (EA) would have different effects on CSE in humans. METHODS: A single-blind sham-controlled crossover design study was conducted on 20 healthy subjects. Subjects received 20 minutes' sham or real EA stimulation immediately after sham or real iTBS. MEPs, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF), cortical silent period (CSP), and central motor conduction time (CMCT) were recorded before each trial, and immediately, 20 minutes, and 40 minutes after the end of stimulation. RESULTS: In the sham iTBS group, EA produced a reduction in MEPs amplitude, lasting approximately 40 minutes, while in the real iTBS group, EA significantly increased MEPs amplitude beyond 40 minutes after the end of stimulation. In sham EA group, the recorded MEPs amplitude showed no significant trend over time compared to baseline. Among all experiments, there were no significant changes in SICI, ICF, CSP, CMCT, etc. CONCLUSION: These data indicate that immediate application of EA after iTBS significantly increased corticospinal excitability. This trial was registered in the Chinese Clinical Trial Registry (registration no. ChiCTR1900025348).