Design and synthesis of spiro[pyrrolidine-3,3'-quinoline]-2,2'-dione derivatives as novel antifungal agents targeting chitin synthase.

A novel spiro [pyrrolidine-3',3'-quinoline]-2,2'-dione scaffold was constructed using fragments of quinoline and pyrrolidine. Subsequently, two series of derivatives were designed based on this scaffold. The enzyme inhibition experiments revealed that all designed compounds had moderate to good inhibitory activity against chitin synthase (CHS). The inhibitory effects of compounds 5i, 5j, 8i and 8n were approximately equal to that of control drug polyoxin B (PB, IP = 86.4 ± 2.9 %, IC50 = 0.082 ± 0.013 mM) which is a well-established CHS inhibitor. The results from enzyme kinetic parameters assays proved that these compounds act as non-competitive inhibitors of CHS. The sorbitol protection experiments demonstrated the tested compounds disrupted the synthesis of cell wall, which further verified that the target of these compounds is CHS. The experiments of antimicrobial showed that compounds 5b, 5f, 5i, 5j, 8f, 8i, 8m, 8n and 8o had strong antifungal activity against the four tested pathogenic fungi strains frequently emerging in clinical setting, with MIC values ranging from 4 to 32 µg/mL, which were either superior to or comparable with those of PB or fluconazole. Furthermore, these compounds displayed synergistic or additive effects when combined with fluconazole and these active compounds also showed promising activity against fluconazole-resistant and micafungin-resistant fungi variants. The result of antimicrobial experiments indicated that these compounds had minimal activity to tested bacterial strains. This suggests that they had selective antifungal activity. The results of ADME prediction, in conjunction with the cytotoxicity assay results, indicated that these compounds had favorable pharmacokinetic profiles and low toxicity. In addition, molecular docking studies illustrated that the compound had a strong affinity with the CHS, which was consistent with the results of enzymatic assays. These findings indicated that the designed compounds are non-competitive inhibitors of CHS with good selectivity and broad-spectrum antifungal activity, and possess significant antifungal activity against drug-resistant fungi, suggesting their potential as lead compounds for the development of novel drugs against drug-resistant fungi.

Association of bacterial overgrowth in the small intestine with cortical thickness and functional connectivity in Parkinson's disease involving mild cognitive impairment.

This study explored potential associations of bacterial overgrowth in the small intestine, as detected based on levels of hydrogen and methane in breath after lactulose consumption, with cortical thickness and resting-state functional connectivity in different brain regions. Prospective comparison of 35 patients with Parkinson's disease (PD) involving mild cognitive impairment, 35 patients with PD with normal cognitive function and 17 healthy controls showed the largest level of hydrogen alone and the largest combined level of hydrogen and methane in patients with mild cognitive impairment. The comparison also revealed a significant negative correlation between those levels and thickness of the right insular cortex. Mild cognitive patients showed different functional connectivity between the right insula and cognition-related brain networks from normal cognitive patients. Our results suggest that bacterial overgrowth in the small intestine may contribute to cortical thinning and alterations in resting-state functional connectivity in PD involving mild cognitive impairment. These insights support and deepen previous observations implicating the gut-brain axis in the neurological disorder.

Study on the Application of Comprehensive Gas Control Technology for Source-Separated Three-Dimensional Gas Extraction in Large Mining Faces.

In order to address the challenges of high gas outburst in both the adjacent layers and the coal seam itself faced by large mining faces, a study on the three-dimensional extraction of gas from different sources at a large mining face was conducted. Based on the research on the instability and failure characteristics of the overlying strata during mining and the gas outburst characteristics at the large mining face, a source-separated three-dimensional gas extraction system was established. A comprehensive gas management model for the large mining face, involving the extraction of gas from different sources, has been proposed. This model is suitable for gas management at large mining faces where there is a high gas emission in the adjacent layers and a complex structure of the coal seam. Through numerical simulations using FLAC3D, the height of the "three zones" of the overlying strata and the range of the floor fracture zone at the large mining face were obtained, providing guidance for the layout of high-level drainage roadway, low-level drainage roadway, and floor drainage roadways. Following the coordinated layout of high-level drainage roadway, inclined high-level drainage roadway, and low-level drainage roadway, the reasonable optimization of gas extraction techniques in the coal seam, and the reasonable arrangement of floor rock predrainage roadways, the methane capture efficiency of the large 15115 mining face reached 87.5%. The methane concentrations at the upper corner and in the return airflow being below 0.8%. The methane concentration extracted from the coal seam boreholes is 2.9 times higher than that from the ordinary mining face after adopting "ordinary boreholes + large-diameter boreholes". This gas management model effectively addresses the gas-related challenges of the large mining face and improves the gas extraction rate, achieving harmonious mining and extraction of coal and methane.

Cognitive function in Parkinson's disease: associations with perivascular space in basal ganglia.

BACKGROUND: Cognitive impairment is one of the most common symptoms of Parkinson's disease (PD), and may be detectable through changes in neural features visualized by magnetic resonance imaging (MRI). Mild cognitive impairment is a transitional state between normal aging and dementia, and early recognition of Parkinson's disease with mild cognitive impairment (PD-MCI) can help improve the quality of life and treatment for patients. This study investigated the association of enlarged perivascular space (EPVS) and white matter hyperintensity (WMH) with PD-MCI. AIMS: This study aimed to evaluate whether EPVS and WMH can be used as potential MRI markers for PD-MCI. METHODS: This retrospective study involved 200 patients with PD who underwent cranial MRI in our hospital from April 2021 to April 2022. Patients were divided into those with no cognitive impairment (PD-NCI) or mild cognitive impairment. Uni- and multivariate logistic regression analyzed associations of EPVS, WMH, and clinicodemographic characteristics with cognitive decline. RESULTS: Univariate regression identified severe EPVS in basal ganglia, severe WMH, older age, late-onset, male sex, low educational level, longer duration of disease, low triglycerides, low uric acid, and low scores on the Mini-mental State Exam as risk factors for PD-MCI. After adjusting for clinicodemographic risk factors in multivariate regression, low education level and EPVS in basal ganglia remained risk factors for cognitive impairment. CONCLUSIONS: Severe EPVS in basal ganglia and poor education, but not WMH, are independent risk factors of PD-MCI. Our findings suggest that non-invasive detection of EPVS in basal ganglia by MRI may be a valuable early indicator of cognitive decline in PD patients.

The association between TLR2/4 and clinical outcome in intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Toll-like receptors (TLRs) are involved in innate immunity and inflammatory responses in various diseases. Our study aimed to investigate the association between the levels of soluble TLR4 (sTLR4) and soluble TLR2 (sTLR2) and clinical outcomes following intracerebral hemorrhage (ICH). METHODS: Patients admitted to department of Neurology with acute ICH were included. Plasma levels of sTLR4 and sTLR2 after ICH were measured by enzyme-linked immunosorbent assay. Poor clinical outcome was defined as a modified Rankin score (mRS) of 3-6 at 3-month and 12-month after onset. RESULTS: All 207 patients with ICH and 100 non-stroke controls were included in our analysis. The mean sTLR4 level was 4.53±1.51 ng/ml and mean sTLR2 level was 3.65±0.72 ng/ml. There was significant trend towards worse clinical outcomes with increasing sTLR4 and sTLR2 terciles at 3 and 12 months. According to receiver operating curve (ROC), the sTLR4 was reliable predictor for poor clinical outcome at 3 months (ROC=0.75) and 12 months (ROC=0.74). The sTLR2 was less reliable predictor for poor clinical outcome at 3 months (ROC=0.64) and 12 months (ROC=0.65). The level of sTLR4 was an independent predictor of poor clinical outcome at 12-month (OR 1.24, 95 % CI 1.16-1.80; P=0.019). CONCLUSIONS: The sTLR4 quantification may provide accurate prognostic information after ICH.

Systematic Review and Meta-Analysis of the Association Between Appearance of Lesions on Diffusion-Weighted Imaging and Poor Outcomes Among Patients with Intracerebral Hemorrhage.

OBJECTIVE: Some patients with intracerebral hemorrhage show lesions on diffusion-weighted magnetic resonance imaging, and such lesions have been associated with a greater risk of worse prognosis. Here we meta-analyzed the available evidence for such an association. METHODS: Studies that reported the presence or absence of lesions on diffusion-weighted imaging (DWI) after intracerebral hemorrhage as well as clinical or radiological outcomes were systematically reviewed and meta-analyzed. Clinical outcome was defined as a score of modified Rankin scale (mRS) at admission to 90 days. RESULTS: Ten studies involving 3575 patients were included in the meta-analysis, and the incidence of DWI lesions ranged from 11.1% to 49.6%. Lesions were associated with a significantly higher risk of poor outcome (mRS scores 3-6) across 6 studies (odds ratio: 2.91; 95% confidence interval: 1.62-5.23; P < 0.001). In subgroup analysis, mRS scores 4-6 were associated with the presence of lesions on DWI (odds ratio: 2.18; 95% confidence interval: 1.31-3.60; P = 0.003). We observed similar results using 3 different definitions of lesions on DWI. Some studies have reported that recurrence of intracerebral hemorrhage was also related with DWI lesions. But there was controversy on the relationship between mortality, ischemic stroke, and hematoma volume and DWI lesions. CONCLUSIONS: Lesions on DWI after intracerebral hemorrhage were associated with a higher risk of poor outcome, but large longitudinal studies are needed to verify this association.

Differences in gray matter atrophy and functional connectivity between motor subtypes of Parkinson's disease.

Parkinson's disease (PD) patients with postural gait abnormalities exhibit poorer motor function scores, more severe non-motor symptoms, faster cognitive function deterioration, and a less favorable response to drugs and surgery compared to PD patients with tremor. This discrepancy is believed to be associated with more pronounced gray matter atrophy and abnormal functional connectivity. To investigate the distinctive pathological mechanisms between PD subtypes, we examined gray matter volume (GMV) and functional connectivity in patients with Parkinson's disease presenting with postural instability/gait difficulty (PD-PIGD), patients with tremor-dominant Parkinson's disease (PD-TD), and healthy controls. Voxel-based morphometry (VBM) of T1-weighted images was conducted to compare GMV among 64 PD-PIGD patients, 44 PD-TD patients, and 32 controls. Subsequently, functional connectivity within regions showing reduced GMV was compared across the groups. We analyzed whether differences among the groups were associated with clinical characteristics and neuroimaging biomarkers using partial correlation and binary logistic regression. Our comparison between PD-PIGD and PD-TD patients revealed a link between PD-PIGD and more extensive frontotemporal atrophy, potentially indicating increased basal ganglia activity accompanied by decreased cerebellum activity. Furthermore, in addition to the smaller GMV in the left middle temporal gyrus, the increased functional connectivity between this brain region and the right caudate was also the independent risk factor for PD-PIGD. In addition, we compared brain network connectivity between the PIGD and TD subtypes, using an independent component analysis (ICA). We found that Compared to PD-TD, PD-PIGD patients showed an enhanced sensorimotor network (SMN) around the left supplementary motor area. These findings suggest that severe gray matter atrophy and abnormal functional connectivity and brain networks may serve as pathophysiological mechanisms distinguishing PD-PIGD patients from other subtypes.

Integrating Mendelian Randomization with Single-cell Sequencing Data Reveals the Causal Effect and Related Mechanisms of Smoking on Parkinson's Disease.

INTRODUCTION: Smoking (nicotine) has been reported to possibly be neuroprotective and conducive to patients with early Parkinson's disease (PD). However, the causal effect of smoking on PD and the molecular mechanisms of smoking-related genes (SRGs) are vague. METHODS: First, genome-wide association study summary data on smoking (ukb-b-6244) and PD (ieu-b-7) were retrieved from the Integrative Epidemiology Unit OpenGWAS database for Mendelian randomization (MR) analysis. Sensitivity analyses were performed to validate the results of the MR analyses. Subsequently, a differential analysis of PD patients and controls was performed to identify differentially expressed SRGs (DE-SRGs). Finally, the expression of DE-SRGs was analyzed in annotated cell types. RESULTS: The MR analysis revealed that smoking was a protective factor causally related to PD (P=0.008, odds ratio=0.288). Furthermore, a total of five DE-SRGs enriched in Toll-like receptor signaling pathways were identified in GSE7621 dataset. Regarding single-cell analysis of GSE184950 dataset, a total of nine cell types were annotated. The expression of LRRN1 in oligodendrocyte progenitor cells and oligodendrocytes, respectively, differed significantly between PD patients and controls. CONCLUSIONS: Our study supported a causal relationship between smoking and PD and found that five SRGs (MAPK8IP1, LRRN1, LINC00324, HIST1H2BK, and YOD1) enriched in Toll-like receptor signaling pathways might be beneficial in PD. In addition, single-cell sequencing indicated that four SRGs were differentially expressed in different cell types. All four genes except MAPK8IP1 were significantly correlated with the 10 genes calculated by scPagwas. Thus, this evidence provides a theoretical basis for further research on the effect of nicotine (smoking) on PD. IMPLICATIONS: In order to explore the potential etiology and pathogenesis of Parkinson's disease, this study combined Mendelian randomization, transcriptomics and single-cell sequencing analysis to explore the association between exposure factors and Parkinson's disease, observe and confirm the relationship and mechanism between the two from the perspective of genetics, and provide more reliable evidence for causal inference.

Broadband Green Luminescence and Phase Transition in Low-Dimensional Organic-Inorganic Hybrid Iodate.

Organic-inorganic hybrid iodide systems, which can form highly ordered chromophores and uniformly oriented transition dipole moments, serve as optimal host-guest systems for the fabrication of micrometer-scale optical devices. In particular, those with low-dimensional structures can exhibit strong quantum-limited and highly localized charges, enabling the generation of high exciton energies and stable excitation emission. In this study, we report a novel instance of an organic-inorganic hybrid iodate, (C13H11N2)(IO3), which was synthesized by incorporating the optically active organic compound, 9-aminoacridine. Upon crystallization in the monoclinic space group P21/c, this compound exhibits a direct optical band gap of 2.66 eV. The incorporation of discrete organic units within the low-dimensional structures induces pronounced local charges, culminating in broadband green luminescence with a peak at 540 nm under UV excitation. This corresponds to the CIE coordinates (0.37, 0.56). A potential phase transition was inferred through a comprehensive analysis of the variable temperature structure and emission spectra. Furthermore, first-principles calculations revealed the pivotal role of organic cations in facilitating broadband luminescence.

MRI brain structural and functional networks changes in Parkinson disease with REM sleep behavior disorders.

Background: Rapid eye movement sleep behavior disorder (RBD) is common in individuals with Parkinson's disease (PD). In spite of that, the precise mechanism underlying the pathophysiology of RBD among PD remains unclear. Objective: The aim of the present study was to analyze gray matter volumes (GMVs) as well as the changes of functional connectivity (FC) among PD patients with RBD (PD-RBD) by employing a combination of voxel-based morphometry (VBM) and FC methods. Methods: A total of 65 PD patients and 21 healthy control (HC) subjects were included in this study. VBM analyses were performed on all subjects. Subsequently, regions with significant different GMVs between PD patients with and without RBD (PD-nRBD) were selected for further analysis of FC. Correlations between altered GMVs and FC values with RBD scores were also investigated. Additionally, receiver operating characteristic (ROC) curves were employed for the evaluation of the predictive value of GMVs and FC in identifying RBD in PD. Results: PD-RBD patients exhibited lower GMVs in the left middle temporal gyrus (MTG) and bilateral cuneus. Furthermore, we observed higher FC between the left MTG and the right postcentral gyrus (PoCG), as well as lower FC between the bilateral cuneus (CUN) and the right middle frontal gyrus (MFG) among PD-RBD patients in contrast with PD-nRBD patients. Moreover, the GMVs of MTG (extending to the right PoCG) was positively correlated with RBD severity [as measured by REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) score]. Conversely, the FC value between the bilateral CUN and the right MTG in PD-RBD patients was negatively correlated with RBDSQ score. Conclusion: This study revealed the presence replace with GMV and FC changes among PD-RBD patients, which were closely linked to the severity of RBD symptoms. Furthermore, the combination of basic clinical characteristics, GMVs and FC values effectively predicted RBD for individuals with PD.

Accelerometer-measured sedentary volume and bouts during the segmented school day among Chinese school students.

Background: This study examined sedentary volume and bouts of Chinese primary and middle school students during different segments of a school day and determined whether gender and school level are associated with their sedentary volume and bouts. Methods: A total of 472 students participated in this study. Accelerometers were used to measure the sedentary volume and sedentary bouts of different durations (i.e., 1-4 min, 5-9 min and ≥10 min) during all segments. Results: The participants spent the majority of their time in sitting (61.7%) and sitting bouts of ≥10 min (37.3%). They spent higher percentages of time in sitting during regular classes (76.7%) and out-of-school time (54.5%), and lower during physical education (PE) classes (32.2%), lunch break (35.4%) and recess (38.0%). The highest proportions of time were in sedentary bouts of ≥10 min during regular classes (50.2%), out-of-school time (28.0%) and lunch break (18.8%), while the greatest percentages occurred in sitting bouts of 1-4 min during PE class (16.4%) and recess (18.6%). Girls and middle school students had higher percentages of sedentary volume than boys and primary school students during most segments. They spent greater proportions of time in sitting bouts of ≥10 min during regular classes, lunch break, and out-of-school time, and higher proportions in sedentary bouts of 1-4 min than boys and primary students during PE classes. Conclusion: Regular class and out-of-school time were identified as key segments for reducing sedentary volume and breaking up prolonged sitting. Interventions on interrupting prolonged sitting during lunch break should also be explored. Girls and middle school students should receive more attention in future interventions.

Meta-analysis of the association of prosaposin polymorphisms rs4747203 and rs885828 with risk of Parkinson's disease.

BACKGROUND: Previous research has established a connection between polymorphisms rs4747203 and rs885828 in the prosaposin (PSAP) gene and an increased risk of Parkinson's disease (PD). However, other studies have found no significant difference in risk compared to the general population. METHODS: To evaluate the current evidence linking rs4747203 and rs885828 to PD risk, we conducted a comprehensive search of PubMed, the Web of Science, Embase, and the Cochrane Library for relevant studies up until May 2023. In addition, we analyzed data from the publicly available "PD Variant Browser". We performed a meta-analysis using Stata 17.0 to synthesize the findings from the selected studies. RESULTS: Our meta-analysis, which included data from six published studies and the public database, revealed no significant association between PD risk and either rs4747203 [OR (95% CI) = 0.99 (0.93-1.05), I2 = 90.3%, P = 0.635] or rs885828 [OR (95% CI) = 1.01 (0.95-1.07), I2 = 90.7%, P = 0.773]. These results remained consistent when examining subgroups of individuals within or outside of Asia. CONCLUSION: The available evidence does not support an association between the genotype at rs4747203 or rs885828 and the risk of PD.

Similar Material Proportioning Tests and Mechanical Properties Based on Orthogonal Design.

Shaking table tests serve as an effective method to simulate landslides triggered by seismic activities. These laboratory experiments necessitate the use of materials that mimic those encountered in real-world scenarios. For this investigation, materials analogous to field conditions for the shaking table tests were formulated using quartz sand, barite powder, iron powder, gypsum, rosin, and alcohol. Within the model test compositions, iron powder, barite powder, and quartz sand acted as aggregates; gypsum functioned as an additive, and a solution of rosin and alcohol was employed as a binder. Employing the orthogonal design method, the physical and mechanical parameters of these analogous materials were ascertained through double-sided shear tests, as well as uniaxial compression and splitting tests. Subsequent analyses included extreme difference and regression assessments targeting the determinants influencing the physical and mechanical characteristics of these materials. The ultimate goal was to determine the optimal mixing ratios for the model test materials. The findings revealed that the physical and mechanical properties of analogous materials at varying ratios span a broad spectrum, fulfilling the criteria for distinct rock model experiments. A thorough examination of the factors impacting the physical and mechanical properties of these materials was undertaken, elucidating their respective influences. Based on the relative significance of each determinant on the mechanical attributes of the analogous materials, dominant factors were identified for a multiple regression analysis, from which the regression equations corresponding to the test ratios were derived.

Potential Effect of Combined Exposure of Crystalline Silica Dust and Cigarette Smoking on the Incidence of Silicosis among Chinese Male Stone Processing Workers: A Cross-Sectional Study.

Background: Silicosis is a progressive and irreversible disease primarily caused by exposure to crystalline silica dust and, to a lesser extent, cigarette smoking. However, further research is needed to validate the potential combined effect of these risk factors on the increased incidence of the disease. Methods: A total of 1688 male workers employed at a Chinese stone processing plant between 1 January 1999 and 31 December 2019, were included in the study. Cumulative exposure to industrial crystalline silica dust and packyears of smoking were collected through health surveillance, and odds ratios (ORs) with 95% confidence intervals (CIs) for silicotic changes due to industrial silica exposure and cigarette smoking were estimated using logistic regression models. Results: Among all participants, a significant exposure-response relationship was observed between long-term exposure to industrial silica dust and radiographic findings resembling silicosis (OR 1.74, 95% CI 1.25 to 2.41). However, among middle-aged workers, a weak and statistically insignificant relationship was found between prolonged cigarette smoking and X-ray evidence of lung silicosis (OR 1.59, 95% CI 1.00 to 2.53). Furthermore, significant combined effects, exceeding the additive models, were identified in each age group and employment sector (relative risk due to interaction 0.51, 95% CI 0.08 to 3.42). Conclusions: It is critically important to implement effective dust removal measures and tobacco control strategies in order to enhance respiratory health among employees across all age groups in the stone processing industry.

Theoretical and experimental investigation of the molecular depolarization ratio for broadband polarization lidar techniques.

The molecular depolarization ratio (MDR) is of great significance for polarization lidar techniques in terms of validating the measurement accuracy, etc. However, previous studies mainly focused on cases with narrowband laser linewidths, and the transmittance of the Cabannes line in the receiver has been assumed constant. In this work, the narrowband theoretical model of MDR has been re-examined by taking the transmittance of the Cabannes line into account. A large relative deviation of beyond 200% has been found if the wavelength-shift reaches up to 0.5 nm for a receiving bandwidth of 0.5 nm at 532 nm, which is much larger than the case without considering the transmittance of the Cabannes line, i.e., only 15%, reported in previous studies. Besides, a broadband theoretical model has been proposed to evaluate the MDR for polarization lidar using high-power multimode laser diodes as light sources. Simulation studies have revealed that the MDR is highly related to the laser linewidth, the receiving bandwidth, as well as the wavelength-shift between the laser wavelength and the center wavelength of the receiver. The MDR at 520 nm calculated by the broadband theoretical model is about 21% larger than the value evaluated without considering the laser linewidth, when the receiving bandwidth is equivalent to the laser linewidth (e.g., 2 nm). Validation measurements, employing a 520-nm imaging-based polarization lidar with a 3.4-nm laser linewidth and a 10-nm receiving bandwidth, illustrated that the volume depolarization ratio in a clean atmospheric region (0.129±0.0025) was highly consistent with the theoretical MDR (0.132). The good agreement between theoretical and experimental results demonstrated a high measurement accuracy of the imaging-based polarization lidar and excellent feasibility of the broadband theoretical model.

Differences in risk factors and outcome after acute stroke in patients with tandem occlusion and those with isolated intracranial occlusion after endovascular treatment.

OBJECTIVE: This study aimed to compare the clinical features, treatment, and clinical outcome of patients with tandem occlusion and isolated intracranial occlusion through endovascular treatment (EVT). METHODS: Patients with acute cerebral infarction who received EVT in two stroke centers were retrospectively included. According to MRI or CTA results, the patients were divided into tandem occlusion group or isolated intracranial occlusion group. The baseline data, etiological classification, treatment, post-stroke complications, image features, and clinical outcome were compared. Multivariate logistic regression analysis was used to evaluate the related factors affecting the prognosis of patients with EVT. RESULTS: Among 161 patients with acute cerebral infarction, there were 33 cases (20.5%) in the tandem occlusion group and 128 cases (79.5%) in the isolated intracranial occlusion group. Compared with isolated intracranial occlusion, the patients with tandem occlusion had higher rates of large artery atherosclerosis (P = 0.028), symptomatic intracerebral hemorrhage (sICH) (P = 0.023), bilateral infarction (P = 0.042), and longer time for endovascular procedure (P = 0.026). There was no significant statistical difference in 90-day mRS score between the two groups (P = 0.060). Multivariate logistic regression identified the following independent predictors of poor functional outcome: older age, high fasting blood glucose, infarction area > 1/3, and hemorrhagic transformation. CONCLUSIONS: Compared with isolated intracranial occlusion, there was not a worse prognosis among patients with tandem occlusion who received EVT.

Prevalence and risk factors for abnormal tandem gait in patients with essential tremor syndrome: A cross-sectional study in Southwest China.

Objectives: Patients with essential tremor (ET) syndrome have more prevalent and more serious gait and balance impairments than healthy controls. In this cross-sectional study, we explored whether balance impairments are associated with falls as well as more pronounced non-motor symptoms in patients with ET syndrome. Methods: We assessed the tandem gait (TG) test, as well as falls or near-falls that occurred over the previous year. Non-motor symptoms-including cognitive deficits, psychological and sleep disorders-were evaluated. In univariate analyses, statistical significance was corrected for multiple comparisons using the Benjamini-Hochberg method. Multiple logistic regression was utilized to evaluate the risk factors of poor TG performance in patients with ET syndrome. Results: A total of 358 patients with ET syndrome were divided into the abnormal TG (a-TG) and normal TG (n-TG) groups based on their performances in the TG test. We revealed that 47.2% of patients with ET syndrome had a-TG. The patients with a-TG were older, were more likely female, and were more likely present with cranial tremors and falls or near-falls (all adjusted P < 0.01). The patients with a-TG had significantly lower Mini-Mental Status Examination scores, as well as significantly higher Hamilton Depression/Anxiety Rating Scale and Pittsburgh Sleep Quality Index scores. Multiple logistic regression analysis demonstrated that female sex (OR 1.913, 95% CI: 1.180-3.103), age (OR 1.050, 95% CI: 1.032-1.068), cranial tremor scores (OR 1.299, 95% CI: 1.095-1.542), a history of falls or near-falls (OR 2.952, 95% CI: 1.558-5.594), and the presence of depressive symptoms (OR 1.679, 95% CI: 1.034-2.726) were associated with the occurrence of a-TG in patients with ET syndrome. Conclusion: TG abnormalities may be a predictor of fall risk in patients with ET syndrome and are associated with non-motor symptoms, especially depression.

Low serum uric acid levels may be a potential biomarker of poor sleep quality in patients with Parkinson's disease.

BACKGROUND: Sleep disorders are common non-motor symptoms in patients with Parkinson's disease (PD). However, the pathogenesis of sleep disorders in PD patients remains unclear. Previous studies have implicated oxidative stress in sleep disorders associated with PD. Considering uric acid (UA) acts as a natural antioxidant, in this study, we aimed to assess the use of serum UA as a potential biomarker of sleep disorder in PD patients. METHODS: This study recruited 149 PD patients and 84 Age- and sex-matched individuals. According to the Pittsburgh Sleep Quality Index (PSQI) score, PD patients were divided into three groups, good (≤5), intermediate (6-10), and poor (>10). Multivariate logistic regression and receiver operating characteristic (ROC) curve analyses were also performed to identify clinical features and serum UA levels that help establish an accurate diagnostic model for poor sleep quality in PD patients. RESULTS: PD patients who experienced poor sleep quality had lower serum UA levels. PSQI scores have significant negative relationships with serum UA levels and significant positive relationships with Hamilton Depression Scale (HAMD) scores in PD. Poor sleep quality was independently associated with serum UA levels and HAMD scores. A serum UA level of 328.7 µmol/L and HAMD scores of 19.5 could distinguish PD patients with poor or intermediate sleep to a certain extent, sensitivity of 79.4% and specificity of 76.6%. CONCLUSIONS: Low serum UA levels may correlate with the severity of sleep disorder in PD patients and may serve as a biomarker for poor sleep quality in PD.

A Simple Grading Scale for Predicting Symptomatic Intracranial Hemorrhage after Mechanical Thrombectomy.

INTRODUCTION: Hemorrhagic transformation, especially symptomatic intracranial hemorrhage (sICH), is a common complication after mechanical embolectomy. This study explored a grading scale based on clinical and radiological parameters to predict sICH after mechanical embolectomy. METHODS: Demographic and clinical data were retrospectively collected from patients with acute ischemic stroke treated with mechanical embolectomy at West China Hospital. Clinical and radiological factors associated with sICH were identified and used to develop the "STBA" grading scale. This score was then validated using data from an independent sample at the First Affiliated Hospital of Kunming Medical University. RESULTS: We analyzed 268 patients with acute ischemic stroke who were treated with mechanical embolectomy at West China Hospital, of whom 30 (11.2%) had sICH. Patients were rated on an "STBA" score ranging from 0 to 6 based on whether systolic blood pressure was ≥145 mm Hg at admission (yes = 2 points; no = 0 points), time from acute ischemic stroke until groin puncture was ≥300 min (yes = 1; no = 0), blood glucose was ≥8.8 mmol/L (yes = 1; no = 0), and the Alberta Stroke Program Early Computed Tomography score at admission was 0-5 (2 points), 6-7 (1 point), or 8-10 (0 points). The STBA score showed good discrimination in the derivation sample (area under the receiver operating characteristic curve = 0.858) and in the validation sample (area = 0.814). CONCLUSIONS: The STBA score may be a reliable clinical scoring system to predict sICH in acute ischemic stroke patients treated with mechanical embolectomy.