Effect of Regional Brain Activity Following Repeat Transcranial Magnetic Stimulation in SCA3: A Secondary Analysis of a Randomized Clinical Trial.

Repetitive transcranial magnetic stimulation (rTMS), a noninvasive neuroregulatory technique used to treat neurodegenerative diseases, holds promise for spinocerebellar ataxia type 3 (SCA3) treatment, although its efficacy and mechanisms remain unclear. This study aims to observe the short-term impact of cerebellar rTMS on motor function in SCA3 patients and utilize resting-state functional magnetic resonance imaging (RS-fMRI) to assess potential therapeutic mechanisms. Twenty-two SCA3 patients were randomly assigned to receive actual rTMS (AC group, n = 11, three men and eight women; age 32-55 years) or sham rTMS (SH group, n = 11, three men and eight women; age 26-58 years). Both groups underwent cerebellar rTMS or sham rTMS daily for 15 days. The primary outcome measured was the ICARS scores and parameters for regional brain activity. Compared to baseline, ICARS scores decreased more significantly in the AC group than in the SH group after the 15-day intervention. Imaging indicators revealed increased Amplitude of Low Frequency Fluctuation (ALFF) values in the posterior cerebellar lobe and cerebellar tonsil following AC stimulation. This study suggests that rTMS enhances motor functions in SCA3 patients by modulating the excitability of specific brain regions and associated pathways, reinforcing the potential clinical utility of rTMS in SCA3 treatment. The Chinese Clinical Trial Registry identifier is ChiCTR1800020133.

Transcranial Alternating Current Stimulation in a Patient with Ataxia-Ocular Apraxia 2: a Case Report.

Ataxia-ocular apraxia 2 (AOA2) is a rare neurodegenerative autosomal recessive disorder with no effective treatment. In this study, we present the case of a patient diagnosed with AOA2, who experienced walking instability and uncoordinated movement. The patient underwent transcranial alternating current stimulation (tACS) treatment for 4 weeks with follow-up after 1 month. The effectiveness of the treatment was evaluated using the International Cooperative Ataxia Rating Scale (ICARS), the Scale for the Assessment and Rating of Ataxia (SARA), the 9-Hole Peg Test (9HPT), and functional near-infrared spectroscopy (fNIRS). Following treatment, the patient's ataxia symptoms showed significant improvement and continued to be alleviated during the follow-up period, suggesting a lasting effect of tACS treatment. Our findings from this case study provide compelling evidence for the potential of tACS as a treatment option for AOA2.

Short-Term Efficacy of Cerebello-spinal tDCS and Body Weight-Supported Treadmill Training in the Hypertrophic Olivary Degeneration: a Rare Case Report.

The present case study reported a patient diagnosed with hypertrophic olivary degeneration, a rare condition characterized by a trans-neuronal degeneration and signal enhancement in T2-weighted images on magnetic resonance imaging, usually caused by cerebral hemorrhage, cerebral infarction, and trauma. Furthermore, the relevant literature review was performed. The existing pharmacological treatment has limited clinical benefits on the patient. Since spontaneous remission hardly occurs in the disease, there are no other effective treatments. In this case, the patient was a 55-year-old Chinese male who presented progressive gait difficulty for several months due to both-sided ataxia. Neurological examination revealed upper extremity and lower limb bilateral spasticity, ataxia, slurred speech, and dysmetria. Therefore, our study treated the patient through the inventive application of cerebello-spinal transcranial direct current stimulation and body weight-supported treadmill training. After a 4-week treatment, the patient could walk independently, without aid, speeding up by 7%, as well as the ataxia symptoms, and balance has improved significantly. It was demonstrated in this case report that the combination of cerebello-spinal tDCS and body weight-supported treadmill training can be an effective treatment for patients with Hypertrophic olivary degeneration.

Visualization Analysis of Research Trends and Hotspots in Inspiratory Muscle Training.

BACKGROUND Inspiratory muscle training (IMT) aims to train inspiratory muscles based mainly on the diaphragm by applying a load resistance during the inspiratory process. Many papers related to IMT have been published in various journals; however, no articles objectively and directly present the development trends and research hotspots of IMT. Therefore, this study used CiteSpace to visually analyze recent IMT-related publications to provide valuable information for future IMT-related studies. MATERIAL AND METHODS CiteSpace was applied to analyze the IMT-related publications by countries, institutions, journals, authors, references, and keywords. RESULTS We included 504 papers. The number of IMT-related publications trended upward between 2009 and 2022. Leuven had the highest number of publications by an institution. The American Journal of Respiratory and Critical Care Medicine was the most frequently co-cited journal. Half of the top 10 references cited were from Journal Citation Reports (JCR) Q1 and half were about the application of IMT in chronic obstructive pulmonary disorder. Gosselink was the author with the highest number of publications and Aldrich was the author with the highest co-citation frequency. The preponderance of studies on the surgical population and postoperative pulmonary complications reflects potential application of IMT in enhanced recovery after surgery. CONCLUSIONS This study provides scholars with important information related to IMT research. It analyzes IMT research trends and status, which can help researchers identify primary topics in the field and find ways to explore new research directions to promote the application of IMT in clinical practice and the cooperation of IMT-related disciplines.

Development of Combretastatin A-4 Analogues as Potential Anticancer Agents with Improved Aqueous Solubility.

Combretastatin A-4 (CA-4) is a potent tubulin polymerisation inhibitor. However, the clinical application of CA-4 is limited owing to its low aqueous solubility and the easy conversion of the olefin double bond from the more active cis- to the less active trans-configuration. Several structural modifications were investigated to improve the solubility of CA-4 derivatives. Among the compounds we synthesized, the kinetic solubility assay revealed that the solubility of compounds containing a piperazine ring increased the most, and the solubility of compounds 12a1, 12a2, 15 and 18 was increased 230-2494 times compared with that of the control compound (Z)-3-(4-aminophenyl)-2-(3,4,5-trimethoxyphenyl)acrylonitrile (9a). In addition, these synthesised stilbene nitriles had high anticancer cell (AGS, BEL-7402, MCF-7, and HCT-116) selectivity over L-02 and MCF-10A normal cells while maintaining micromolar activity against cancer cells. The most cytotoxic compound is 9a, and the IC50 value is 20 nM against HCT-116 cancer cells. Preliminary studies indicated that compound 12a1 had excellent plasma stability and moderate binding to rat plasma proteins, suggesting it is a promising lead compound for the development of an anticancer agent.

Analysis of Fusarium graminearum Species Complex from Freshly Harvested Rice in Jiangsu Province (China).

Members of Fusarium graminearum species complex (FGSC) are the major pathogens that cause Fusarium head blight (FHB) in cereals worldwide. Symptoms of FHB on rice, including dark staining or browning of rice glumes, were recently observed in Jiangsu Province, China. To improve our understanding of the pathogens involved, 201 FGSC isolates were obtained from freshly harvested rice samples and identified by phylogenetic analyses. Among the 201 FGSC isolates, 196 were F. asiaticum and the remaining 5 were F. graminearum. Trichothecene chemotype and chemical analyses showed that 68.4% of the F. asiaticum isolates were the 3-acetyldeoxynivalenol (3ADON) chemotype and the remainder were the nivalenol (NIV) chemotype. All of the F. graminearum isolates were the 15-acetyldeoxynivalenol chemotype. Pathogenicity assays showed that both the 3ADON and NIV chemotypes of F. asiaticum could infect wheat and rice spikes. FHB severity and trichothecene toxin analysis revealed that F. asiaticum with the NIV chemotype was less aggressive than that with the 3ADON chemotype in wheat, while the NIV-producing strains were more virulent than the 3ADON-producing strains in rice. F. asiaticum isolates with different chemotypes did not show significant differences in mycelial growth, sporulation, conidial dimensions, or perithecial production. These findings would provide useful information for developing management strategies for the control of FHB in China.

[The brain imaging studies of obstructive sleep apnea: evidence from resting-state EEG and fMRI].

Obstructive sleep apnea (OSA) is a common clinic sleep disorder, and characterized by obstruction of upper airway during sleep, resulting in sleep fragmentation and intermittent hypoxemia. We reviewed the brain imaging studies in OSA patients compared with healthy subjects, including studies of functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). The resting-state EEG studies showed increased power of δ and θ in the front and central regions of the cerebral cortex in OSA patients. While resting-state fMRI studies demonstrated altered large-scale networks in default-mode network (DMN), central executive network (CEN) and salience network (SN). Evidence from resting-state studies of both fMRI and EEG focused on the abnormal activity in prefrontal cortex (PFC), which is correlated with OSA severity. These findings suggested that the PFC may play a key role in the abnormal function of OSA patients. Finally, based on the perspectives of treatment effect, multimodal data acquisition, and comorbidities, we discussed the future research direction of the neuroimaging study of OSA.

Synthesis and Selective Anticancer Activity Evaluation of 2-phenylacrylonitrile Derivatives as Tubulin Inhibitors.

OBJECTIVE: This study aimed at synthesizing 13 series of novel derivatives with 2-phenylacrylonitrile, evaluating antitumor activity both in vivo and in vitro, and obtaining novel tubulin inhibitors. METHOD: The 13 series of 2-phenylacrylonitrile derivatives were synthesized by Knoevenagel condensation and the anti-proliferative activities were determined by MTT assay. The cell cycle and apoptosis were analyzed by flow cytometer. Quantitative cell migration was performed using 24-well Boyden chambers. The proteins were detected by western blotting. in vitro kinetics of microtubule assembly was measured using ELISA kit for Human ß-tubulin (TUBB). Molecular docking was done by Discovery Studio (DS) 2017 Client online tool. RESULTS: Among the derivatives, compound 1g2a possessed strong inhibitory activity against HCT116 (IC50 = 5.9 nM) and BEL-7402 (IC50 = 7.8 nM) cells. Compound 1g2a exhibited better selective antiproliferative activities and specificities than all the positive control drugs, including taxol. Compound 1g2a inhibited proliferation of HCT116 and BEL-7402 cells by arresting them in the G2/M phase of the cell cycle, inhibited the migration of HCT116 and BEL-7402 cells and the formation of cell colonies. Compound 1g2a showed excellent tubulin polymerization inhibitory activity on HCT116 and BEL-7402 cells. The results of molecular docking analyses showed that 1g2a may inhibit tubulin to exert anticancer effects. CONCLUSION: Compound 1g2a shows outstanding antitumor activity both in vivo and in vitro and has the potential to be further developed into a highly effective antitumor agent with little toxicity to normal tissues.

Disease Progression and Multiparametric Imaging Characteristics of Spinocerebellar Ataxia Type 3 With Spastic Paraplegia.

Background and Objectives: Spinocerebellar ataxia type 3 (SCA3) is a hereditary ataxia that occurs worldwide. Clinical patterns were observed, including the one characterized by marked spastic paraplegia. This study investigated the clinical features, disease progression, and multiparametric imaging aspects of patients with SCA3. Methods: We retrospectively analyzed 249 patients with SCA3 recruited from the Organization for Southeast China for cerebellar ataxia research between October 2014 and December 2020. Of the 249 patients, 145 were selected and assigned to 2 groups based on neurologic examination: SCA3 patients with spastic paraplegia (SCA3-SP) and SCA3 patients with nonspastic paraplegia (SCA3-NSP). Participants underwent 3.0-T brain MRI examinations, and voxel-wise and volume-of-interest-based approaches were used for the resulting images. A tract-based spatial statistical approach was used to investigate the white matter (WM) alterations using diffusion tensor imaging, neurite orientation dispersion, and density imaging metrics. Multiple linear regression analyses were performed to compare the clinical and imaging parameters between the 2 groups. The longitudinal data were evaluated using a linear mixed-effects model. Results: Forty-three patients with SCA3-SP (mean age, 37.58years ± 11.72 [SD]; 18 women) and 102 patients with SCA3-NSP (mean age, 47.42years ± 12.50 [SD]; 39 women) were analyzed. Patients with SCA3-SP were younger and had a lower onset age but a larger cytosine-adenine-guanine repeat number, as well as higher clinical severity scores (all corrected p < 0.05). The estimated progression rates of the Scale for the Assessment and Rating of Ataxia (SARA) and International Cooperative Ataxia Rating Scale scores were higher in the SCA3-SP subgroup than in the SCA3-NSP subgroup (SARA, 2.136 vs 1.218 points; ICARS, 5.576 vs 3.480 points; both p < 0.001). In addition, patients with SCA3-SP showed gray matter volume loss in the precentral gyrus with a decreased neurite density index in the WM of the corticospinal tract and cerebellar peduncles compared with patients with SCA3-NSP. Discussion: SCA3-SP differs from SCA3-NSP in clinical features, multiparametric brain imaging findings, and longitudinal follow-up progression.

Cognitive impairment associated with cerebellar volume loss in spinocerebellar ataxia type 3.

BACKGROUND: Many neuroscience and neurology studies have forced a reconsideration of the traditional motor-related scope of cerebellar function, which has now expanded to include various cognitive functions. Spinocerebellar ataxia type 3 (SCA3; the most common hereditary ataxia) is neuropathologically characterized by cerebellar atrophy and frequently presents with cognitive impairment. OBJECTIVE: To characterize cognitive impairment in SCA3 and investigate the cerebellum-cognition associations. METHODS: This prospective, cross-sectional cohort study recruited 126 SCA3 patients and 41 healthy control individuals (HCs). Participants underwent a brain 3D T1-weighted images as well as neuropsychological tests. Voxel-based morphometry (VBM) and region of interest (ROI) approaches were performed on the 3D T1-weighted images. CERES was used to automatically segment cerebellums. Patients were grouped into cognitively impaired (CI) and cognitively preserved (CP), and clinical and MRI parameters were compared. Multivariable regression models were fitted to examine associations between cerebellar microstructural alterations and cognitive domain impairments. RESULTS: Compared to HCs, SCA3 patients showed cognitive domain impairments in information processing speed, verbal memory, executive function, and visuospatial perception. Between CI and CP subgroups, the CI subgroup was older and had lower education, as well as higher severity scores. VBM and ROI analyses revealed volume loss in cerebellar bilateral lobule VI, right lobule Crus I, and right lobule IV of the CI subgroup, and all these cerebellar lobules were associated with the above cognitive domain impairments. CONCLUSIONS: Our findings demonstrate the multiple cognitive domain impairments in SCA3 patients and indicate the responsible cerebellar lobules for the impaired cognitive domain(s).

The effect of nurses' perceived stress on their work engagement and perceived professional benefit during the routine management of the Corona Virus Disease 2019 Pandemic.

BACKGROUND: In a previous study, more attention has been given to the psychological state of doctors than to that of nurses although the workload, working hours, and patient contact time are generally higher for nurses than doctors. The current status of nurses' perceived stress, work engagement, and perceived professional benefit during the routine management of the Corona Virus Disease 2019(COVID-19) pandemic and how their perceived stress affects the other two variables are topics that merit research attention. OBJECTIVE: In this study, the status of nurses' perceived stress, work engagement, and perceived professional benefit during the routine management of the Corona Virus Disease 2019 pandemic was investigated to explore whether their perceived stress level has any effect on the other two variables. METHODS: The convenience sampling method was adopted, and 669 nurses from the First People's Hospital of Jingzhou were selected to participate in this study. Questionnaires on perceived stress, work engagement, and perceived professional benefit were used in the survey, and the data were processed using the SPSS 20.0 program for the descriptive statistics, independent sample t-test, analysis of variance. RESULTS: The total score of the nurses' perceived stress was 18.58±4.37 points. The total scores of their work engagement (43.32±14.01) and perceived professional benefit (140.23±17.75). CONCLUSION: The nurses' total perceived stress score was at an upper-middle level, and their total work engagement and perceived professional benefit scores were relatively high. Overall, perceived stress has a negative effect on nurses' work engagement and perceived professional benefit. That is, the higher the pressure perception of nurses, the lower the degree of work engagement and perceived professional benefit.

Short-term efficacy of repetitive transcranial magnetic stimulation in SCA3: A prospective, randomized, double-blind, sham-controlled study.

OBJECTIVE: Spinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant ataxia globally. No effective treatment is currently available for SCA3. Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive form of brain stimulation, demonstrated to improve symptoms in patients with neurodegenerative cerebellar ataxias. The present study investigated whether treatment with rTMS over the cerebellum for 15 consecutive days improved measures of ataxia in SCA3 patients. METHODS: A double-blind, prospective, randomized, sham-controlled trial was carried out on 44 SCA3 patients. Participants were randomly assigned to two groups: real or sham stimulation. Each participant underwent 30 minutes of 1Hz rTMS stimulation (a total of 900 pulses) for 15 consecutive days. The primary outcome measure was the score on the International Cooperative Ataxia Rating Scale (ICARS), and secondary outcomes were from the Scale for the Assessment and Rating of Ataxia (SARA) and the Berg Balance Scale (BBS). RESULTS: Nausea was the only adverse effect reported by 2 participants from the sham and real group. After 15 days of treatment, there was a significant improvement in all performance scores in both real and sham stimulation groups. However, compared to the sham group, the improvements were significantly larger in the real group for the ICARS (P = 0.002), SARA (P = 0.001), and BBS (P = 0.001). INTERPRETATION: A 15 days treatment with rTMS over the cerebellum improves the symptoms of ataxia in SCA3 patients. Our results suggest that rTMS is a promising tool for future rehabilitative approaches in SCA3.

Altered brain white matter structural motor network in spinocerebellar ataxia type 3.

OBJECTIVES: Spinocerebellar ataxia type 3 is a disorder within the brain network. However, the relationship between the brain network and disease severity is still unclear. This study aims to investigate changes in the white matter (WM) structural motor network, both in preclinical and ataxic stages, and its relationship with disease severity. METHODS: For this study, 20 ataxic, 20 preclinical SCA3 patients, and 20 healthy controls were recruited and received MRI scans. Disease severity was quantified using the SARA and ICARS scores. The WM motor structural network was created using probabilistic fiber tracking and was analyzed using graph theory and network-based statistics at global, nodal, and edge levels. In addition, the correlations between network topological measures and disease duration or clinical scores were analyzed. RESULTS: Preclinical patients showed increasing assortativity of the motor network, altered subnetwork including 12 edges of 11 nodes, and 5 brain regions presenting reduced nodal strength. In ataxic patients assortativity of the motor network also increased, but global efficiency, global strength, and transitivity decreased. Ataxic patients showed a wider altered subnetwork and a higher number of reduced nodal strengths. A negative correlation between the transitivity of the motor network and SARA and ICARS scores was observed in ataxic patients. INTERPRETATION: Changes to the WM motor network in SCA3 start before ataxia onset, and WM motor network involvement increases with disease progression. Global network topological measures of the WM motor network appear to be a promising image biomarker for disease severity. This study provides new insights into the pathophysiology of disease in SCA3/MJD.

Effects of cerebellar transcranial alternating current stimulation in cerebellar ataxia: study protocol for a randomised controlled trial.

Background: Cerebellar ataxia (CA) is a movement disorder that can affect balance and gait, limb movement, oculomotor control, and cognition. Multiple system atrophy-cerebellar type (MSA-C) and spinocerebellar ataxia type 3 (SCA3) are the most common forms of CA, for which no effective treatment is currently available. Transcranial alternating current stimulation (tACS) is a non-invasive method of brain stimulation supposed to alter cortical excitability and brain electrical activity, modulating functional connectivity within the brain. The cerebellar tACS can modulate the cerebellar outflow and cerebellum-linked behavior and it is a proven safe technique for humans. Therefore, the aim of this study is to 1) examine whether cerebellar tACS improves ataxia severity and various non-motor symptoms in a homogeneous cohort of CA patients consisting of MSA-C and SCA3, 2) explore the time course of these effects, and 3) assess the safety and tolerance of cerebellar tACS in all participants. Methods/design: This is a 2-week, triple-blind, randomised, sham-controlled study. 164 patients (MSA-C: 84, SCA3: 80) will be recruited and randomly assigned to either active cerebellar tACS or sham cerebellar tACS, in a 1:1 ratio. Patients, investigators, and outcome assessors are unaware of treatment allocation. Cerebellar tACS (40 min, 2 mA, ramp-up and down periods of 10s each) will be delivered over 10 sessions, distributed in two groups of five consecutive days with a two-day break in between. Outcomes are assessed after the tenth stimulation (T1), and after 1 month (T2) and 3 months (T3). The primary outcome measure is the difference between the active and sham groups in the proportion of patients with an improvement of 1.5 points in the Scale for the Assessment and Rating of Ataxia (SARA) score after 2 weeks of treatment. In addition, effects on a variety of non-motor symptoms, quality of life, and autonomic nerve dysfunctions are assessed via relative scales. Gait imbalance, dysarthria, and finger dexterity are objectively valued via relative tools. Finally, functional magnetic resonance imaging is performed to explore the possible mechanism of treatment effects. Discussion: The results of this study will inform whether repeated sessions of active cerebellar tACS benefit CA patients and whether this form of non-invasive stimulation might be a novel therapeutic approach to consider in a neuro-rehabilitation setting.Clinical Trial Registration: ClinicalTrials.gov, identifier NCT05557786; https://www.clinicaltrials.gov/ct2/show/NCT05557786.

Comparison of Overall Complication Rates in VCR-Based vs Non-VCR-Based Corrective Techniques in Severe Rigid Kyphoscoliosis Patients: A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: Compilation of complication outcomes data from the surgical management of severe rigid kyphoscoliosis patients using VCR-based vs non-VCR-based corrective maneuvers is lacking. This meta-analysis aimed to compare complication outcomes between those classified osteotomy approaches. METHODS: Thorough literature review and meta-analysis were conducted between January 2000 and September 2021. The selection criteria were studies: i) reporting major curve Cobb angle of ≥80° and flexibility of <25% or 30%; ii) comparing VCR or ≥ Type V Schwab osteotomy defined as VCR-based vs [non-VCR-based] techniques, (any osteotomy or technique other than VCR); iii) published in English with ≥10 patients; iv) reporting complication rates; and v) having minimum of 2-year follow-up. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Significance level was set at (P < .05). RESULTS: Of the 174 patients included, 52.30% (n = 91) and 47.70% (n = 83) were VCR-based and non-VCR-based, respectively. The incidence of dural tears/nerve injuries/significant intraoperative-neuromonitoring changes was significantly higher; [OR = 6.78, CI= (1.75 to 26.17), I2 = 0%, (P = .006)] in the VCR-based group than the non-VCR-based group. The 'overall surgical and medical' complication rate was significantly higher in the VCR-based group, [OR = 1.94, CI= (1.02 to 3.67), I2 = 31%, (P = .04)]. CONCLUSION: Both VCR-based and non-VCR-based surgical techniques for management of severe rigid scoliosis and kyphoscoliosis patients pose comparable overall surgical complication rates, while a significantly higher perioperative neurological complication incidence was associated with VCR-based technique compared to the non-VCR-based techniques. The VCR-based technique was associated with 6.78 times higher incidence of neurological complications compared to non-VCR-based techniques.

[Complications and short-term outcomes of intraoperative electron radiotherapy (IOERT) in patients with periarticular soft-tissue sarcomas of the extremities].

OBJECTIVE: To analyze the complications and short-term outcomes of patients receiving intraoperative electron radiotherapy (IOERT) for locally advanced and recurrent periarticular soft tissue sarcomas of the extremities. METHODS: Twenty-one adult patients with locally advanced and/or recurrent periarticular soft tissue sarcomas of the extremities treated with IOERT were included in this study. Among them 14 patients had recurrent diseases after prior operation and 7 patients with locally advanced disease with primary treatment. The total dose of radiation ranged from 11 Gy to 21 Gy of 6 - 12 MeV beta ray given by intraoperative radiotherapy after complete tumor resection with negative margins. Five patients were given external beam radiotherapy (EBRT) with a total dose of 40 - 50 Gy, and 10 patients received chemotherapy. RESULTS: The median follow-up time was 15 months. Five patients (23.8%) had tumor relapse, including one patients with local recurrence, one patient with regional recurrence, two patients with distant metastasis and one patient with local recurrence and distant metastasis. The actuarial local control rate at 1 year was 95.2% (20/21), and at 2 years was 90.5% (19/21). Acute skin toxicity (RTOG) within 3 months after surgery included grade I in 6 patients and grade II in 3 patients. Two year late skin toxicity (RTOG/EORTC) included grade I in 4 patients and grade II in 2 patients. Fibrosis included grade I in 3 patients and grade II in 3 patients. Six patients had joint dysfunction (3 patients with grade I and 3 with grade II) and 6 patients had healing problems. One patient got ipsilateral schiatic neuritis 9 months after IOERT. No adverse events occurred during surgery. CONCLUSIONS: IOERT brings tolerable complications of acute and late toxicities and favorable local control rate. IOERT should be followed by postoperative radiotherapy or increase the intraoperative radiation dose for locally advanced and recurrent sarcomas to get a better local control. Otherwise, distant metastasis is one of the main reasons of treatment failure, so chemotherapy should be added to the treatment regimen.

3-Cyano-anilinium hydrogen oxalate hemihydrate.

In the title hydrated mol-ecular salt, C(7)H(7)N(2) (+)·C(2)HO(4) (-)·0.5H(2)O, contains a 3-cyano-anilinium cation, a hydrogen oxalate anion and half a water mol-ecule in an asymmetric unit. The dihedral angle between the CO(2)(H) and CO(2) planes of the hydrogen oxalate ion is 7.96 (1)°. In the crystal, the components are linked by N-H⋯O and O-H⋯O hydrogen bonds, forming a layer lying parallel to the ac plane.

Effects of Repetitive Transcranial Magnetic Stimulation on Cerebellar Metabolism in Patients With Spinocerebellar Ataxia Type 3.

Background: Spinocerebellar ataxia type 3 (SCA3) is the most common autosomal dominant hereditary ataxia, and, thus far, effective treatment remains low. Repetitive transcranial magnetic stimulation (rTMS) can improve the symptoms of spinal cerebellar ataxia, but the mechanism is unclear; in addition, whether any improvement in the symptoms is related to cerebellar metabolism has not yet been investigated. Therefore, the purpose of this study was to investigate the effects of low-frequency rTMS on local cerebellar metabolism in patients with SCA3 and the relationship between the improvement in the symptoms and cerebellar metabolism. Methods: A double-blind, prospective, randomized, sham-controlled trial was carried out among 18 SCA3 patients. The participants were randomly assigned to the real stimulation group (n = 9) or sham stimulation group (n = 9). Each participant in both the groups underwent 30 min of 1 Hz rTMS stimulation (a total of 900 pulses), differing only in terms of stimulator placement, for 15 consecutive days. To separately compare pre- and post-stimulation data (magnetic resonance spectroscopy (MRS) data and the International Cooperative Ataxia Rating Scale (ICARS) score) in the real and sham groups, paired-sample t-tests and Wilcoxon's signed-rank tests were used in the analyses. The differences in the ICARS and MRS data between the two groups were analyzed with independent t-tests and covariance. To explore the association between the changes in the concentration of cerebellar metabolism and ICARS, we applied Pearson's correlation analysis. Results: After 15 days of treatment, the ICARS scores significantly decreased in both the groups, while the decrease was more significant in the real stimulation group compared to the sham stimulation group (p < 0.001). The analysis of covariance further confirmed that the total ICARS scores decreased more dramatically in the real stimulation group after treatment compared to the sham stimulation group (F = 31.239, p < 0.001). The values of NAA/Cr and Cho/Cr in the cerebellar vermis, bilateral dentate nucleus, and bilateral cerebellar hemisphere increased significantly in the real stimulation group (p < 0.05), but no significant differences were found in the sham stimulation group (p > 0.05). The analysis of covariance also confirmed the greater change in the real stimulation group. This study also demonstrated that there was a negative correlation between NAA/Cr in the right cerebellar hemisphere and ICARS in the real stimulation group (r = - 0.831, p = 0.02). Conclusion: The treatment with rTMS over the cerebellum was found to induce changes in the cerebellar local metabolism and microenvironment in the SCA3 patients. The alterations may contribute to the improvement of the symptoms of ataxia in SCA3 patients.

GARP Polymorphisms Associated with Susceptibility to House Dust Mite-Sensitized Persistent Allergic Rhinitis in a Chinese Population.

Background: Genetic variants in GARP (also known as LRRC32) have been reported to have significant associations with asthma and eczema in special populations, but little is known about allergic rhinitis. This study purposes to evaluate the association of single nucleotide polymorphisms (SNPs) in GARP with house dust mite (HDM)-sensitized persistent allergic rhinitis (PER) in a population of Han Chinese. Methods: In this hospital-based case-control study, 534 HDM-sensitized PER patients and 451 healthy controls were recruited from East China. In this population, six SNPs in GARP were identified. Serum total and specific IgE levels were measured with ImmunoCAP. Secondary structure and minimum free energy were predicted by RNAfold. Results: rs79525962 was associated with the risk of HDM-sensitized PER (P < 0.05). The individuals with CT+TT genotype demonstrated a higher risk of HDM-sensitized PER than those with CC genotype (adjusted OR = 1.393, 95% CI = 1.019-1.904). The homozygous genotype CC of rs3781699 rendered a lower risk of HDM-sensitized PER than the wild-type genotype AA (adjusted OR = 0.646, 95% CI = 0.427-0.976); however, the genotype and allele frequencies of rs3781699 demonstrated no associations with HDM-sensitized PER (P > 0.05). rs79525962 increased the risk of HDM-sensitized PER in the subgroup aged ≥16 years (adjusted OR = 1.745, 95% CI = 1.103-2.760), and this high risk was also found in the females (adjusted OR = 1.708, 95% CI = 1.021-2.856). The G-C haplotype of rs1320646-rs3781699 rendered a lower risk of HDM-sensitized PER than the common haplotype G-A (adjusted OR = 0.819, 95% CI = 0.676-0.993). The secondary structure of GARP altered in response to different genotypes of rs79525962 and rs3781699. Conclusion: SNP rs79525962 in the GARP gene marks a risk locus of HDM-sensitized PER in Chinese Hans.

5-(Pyridinium-3-yl)tetra-zol-1-ide hexa-aqua-magnesium dichloride.

In the title compound, (C(6)H(5)N(5))(2)[Mg(H(2)O)(6)]Cl(2), the asymmetric unit contains one zwitterionic 5-(pyridinium-3-yl)tetra-zol-1-ide mol-ecule, one half of an [Mg(H(2)O)(6)](2+) cation ( symmetry) and one chloride ion. The Mg(II) ion is surrounded by six water mol-ecules, with their O atoms located at the apices, exhibiting a slightly distorted octa-hedral coordination. Mg-O bond lengths range from 2.0526 (14) to 2.0965 (16) Š[mean value = 2.068 Å]. The pyridine and tetra-zole rings are nearly coplanar and only twisted from each other by a dihedral angle of 5.68 (1)°. The zwitterionic organic mol-ecules, anions and cations are connected by O-H⋯Cl, O-H⋯N and N-H⋯Cl hydrogen bonds, leading to the formation of a three-dimensional network.