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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.
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Attitude determination based on a micro-electro-mechanical system inertial measurement unit (MEMS-IMU) has attracted extensive attention. The non-gravitational components of the MEMS-IMU have a significant effect on the accuracy of attitude estimation. To improve the attitude estimation of low-dynamic vehicles under uneven soil conditions or vibrations, a robust Kalman filter (RKF) was developed and tested in this paper, where the noise covariance was adaptively changed to compensate for the external acceleration of the vehicle. The state model for MEMS-IMU attitude estimation was initially constructed using a simplified direction cosine matrix. Subsequently, the variance of unmodeled external acceleration was estimated online based on filtering innovations of different window lengths, where the acceleration disturbance was addressed by tradeoffs in time-delay and prescribed computation cost. The effectiveness of the RKF was validated through experiments using a three-axis turntable, an automatic vehicle, and a tractor tillage test. The turntable experiment demonstrated that the angle result of the RKF was 0.051° in terms of root mean square error (RMSE), showing improvements of 65.5% and 29.2% over a conventional KF and MTi-300, respectively. The dynamic attitude estimation of the automatic vehicle showed that the RKF achieves smoother pitch angles than the KF when the vehicle passes over speed bumps at different speeds; the RMSE of pitch was reduced from 0.875° to 0.460° and presented a similar attitude trend to the MTi-300. The tractor tillage test indicated that the RMSE of plough pitch was improved from 0.493° with the KF to 0.259° with the RKF, an enhancement of approximately 47.5%, illustrating the superiority of the RKF in suppressing the external acceleration disturbances of IMU-based attitude estimation.
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The objective of our study was to use quantum dots for the purpose of seeing and detecting C-C motif chemokine ligand 5 (CCL5) inside the tissue of sentinel lymph nodes (SLN) and primary tumors. This endeavor aimed to enhance the accuracy of predicting the condition of non-sentinel lymph nodes and provide valuable insights for making informed treatment choices. We analyzed breast cancer patients who underwent sentinel lymph node biopsy followed by axillary lymph node removal due to one or two positive sentinel lymph nodes at the Second People's Hospital of Wuhu, China, between August 2018 and July 2022. Quantum dot technology was employed to visualize and determine CCL5 in the tissue samples from 84 patients. Out of a group diagnosed with breast cancer, 208 underwent sentinel lymph node biopsy. From this pool, 84 tested positive and subsequently underwent axillary lymph node removal. The presence of distinct orange-red fluorescence, linked to quantum dots, was evident in the cellular components of both primary tumors and positive sentinel lymph node tissues. We found a significant relationship between higher levels of SLNCCL5 and advanced tumor growth (P < 0.05). To understand the predictive value of SLN CCL5 related to non-sentinel lymph node status, we utilized the receiver operating characteristic (ROC) method. The area under the curve (AUC) calculated was 0.745 with a cutoff point of 23.285. Multivariate logistic regression was used to understand the effect of tumor dimensions and SLNCCL5 levels on non-sentinel lymph node status in specific patients. Both the size of the tumor and SLNCCL5 levels were found to have a significant impact (P < 0.05). Data suggested that the presence of positive SLNCCL5 might serve as an assessment parameter for anticipating the condition of non-SLN in cases of breast cancer involving T1 or T2 tumors with one or two positive sentinel lymph nodes.
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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.
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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.
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Enfermedad de Parkinson , Humanos , Predisposición Genética a la Enfermedad/genética , Genotipo , Enfermedad de Parkinson/genética , Polimorfismo Genético , Saposinas/genéticaRESUMEN
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.
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Enfermedad de Parkinson , Trastornos del Sueño-Vigilia , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico , Ácido Úrico , Calidad del Sueño , Trastornos del Sueño-Vigilia/etiología , BiomarcadoresRESUMEN
Objective: This study aimed to investigate the association of altered cortical thickness and functional connectivity (FC) with depression in Parkinson's disease (PD). Materials and methods: A total of 26 non-depressed PD patients (PD-ND), 30 PD patients with minor depression (PD-MnD), 32 PD patients with major depression (PD-MDD), and 30 healthy controls (HC) were enrolled. Differences in cortical thickness among the four groups were assessed, and the results were used to analyze FC differences in regions of cortical atrophy. Binary logistic regression and receiver operating characteristic (ROC) curve analyses were also performed to identify clinical features and neuroimaging biomarkers that might help in the prediction of PD-MDD. Results: Patients with PD-MDD showed decreased cortical thickness compared to patients with PD-ND in the left superior temporal and right rostral middle frontal gyri (RMFG), as well as weak FC between the left superior temporal gyrus and right cerebellum posterior lobe and between right RMFG and right inferior frontal gyrus and insula. The combination of cortical thickness, FC, and basic clinical features showed strong potential for predicting PD-MDD based on the area under the ROC curve (0.927, 95% CI 0.854-0.999, p < 0.001). Conclusion: Patients with PD-MDD show extensive cortical atrophy and FC alterations, suggesting that cortical thickness and FC may be neuroimaging-based diagnostic biomarkers for PD-MDD.
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We aimed to perform a combined analysis of cortical thickness and functional connectivity to explore their association with cognitive impairment in Parkinson's disease (PD). A total of 53 PD and 15 healthy control subjects were enrolled. PD patients were divided into PD with normal cognition (PD-NC, n = 25), PD with mild cognitive impairment (PD-MCI, n = 11), and PD with dementia (PDD, n = 17). In some analyses, the PD-MCI and PDD groups were aggregated to represent "PD patients with cognitive impairment". Cognitive status was assessed with the Mini-Mental State Examination (MMSE). Anatomical magnetic resonance imaging and resting-state functional connectivity analysis were performed in all subjects. First, surface-based morphometry measurements of cortical thickness and voxels with cortical thickness reduction were detected. Then, regions showing reduced thickness were analyzed for changes in resting-state functional connectivity in PD involving cognitive impairment. Our results showed that, compared with PD-NC, patients with cognitive impairment showed decreased cortical thickness in the left superior temporal, left lingual, right insula, and right fusiform regions. PD-MCI patients showed these alterations in the right lingual region. Widespread cortical thinning was detected in PDD subjects, including the left superior temporal, left fusiform, right insula, and right fusiform areas. We found that cortical thinning in the left superior temporal, left fusiform, and right temporal pole regions positively correlated with MMSE score. In the resting-state functional connectivity analysis, we found a decrease in functional connectivity between the cortical atrophic brain areas mentioned above and cognition-related brain networks, as well as an increase in functional connectivity between those region and the cerebellum. Alterations in cortical thickness may result in a dysfunction of resting-state functional connectivity, contributing to cognitive decline in patients with PD. However, it is more probable that the relation between structure and FC would be bidirectional,and needs more research to explore in PD cognitve decline.
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Disfunción Cognitiva , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/patología , Imagen por Resonancia Magnética/métodos , Adelgazamiento de la Corteza Cerebral , Disfunción Cognitiva/etiología , Disfunción Cognitiva/complicaciones , AtrofiaRESUMEN
BACKGROUND: Parkinson's disease (PD) is associated with coiled-coil-helix-coiled-coilhelix domain containing 2 (CHCHD2) downregulation, which has been linked to reduced cyclocytase activity and increased levels of oxygen free radicals, leading to mitochondrial fragmentation and apoptosis. Little is known about how CHCHD2 normally functions in the cell and, therefore, how its downregulation may contribute to PD. OBJECTIVE: This study aimed to identify such target genes using chromatin immunoprecipitation sequencing from SH-SY5Y human neuroblastoma cells treated with neurotoxin 1-methyl-4- phenylpyridinium (MPP+) as a PD model. METHODS: In this study, we established a MPP+ -related SH-SY5Y cell model and evaluated the effects of CHCHD2 overexpression on cell proliferation and apoptosis. At the same time, we used high-throughput chromatin immunoprecipitation sequencing to identify its downstream target gene in SH-SY5Y cells. In addition, we verified the possible downstream target genes and discussed their mechanisms. RESULTS: The expression level of α-synuclein increased in SH-SY5Y cells treated with MPP+, while the protein expression level of CHCHD2 decreased significantly, especially after 24 h of treatment. Chip-IP results showed that CHCHD2 might regulate potential target genes such as HDX, ACP1, RAVER2, C1orf229, RN7SL130, GNPTG, erythroid 2 Like 2 (NFE2L2), required for cell differentiation 1 homologue (RQCD1), solute carrier family 5 member 7 (SLA5A7), and NAcetyltransferase 8 Like (NAT8L). NFE2L2 and RQCD1 were validated as targets using PCR and western blotting of immunoprecipitates, and these two genes together with SLA5A7 and NAT8L were upregulated in SH-SY5Y cells overexpressing CHCHD2. Downregulation of CHCHD2 may contribute to PD by leading to inadequate expression of NFE2L2 and RQCD1 as well as, potentially, SLA5A7 and NAT8L. CONCLUSION: Our results suggest that CHCHD2 plays a protective role by maintaining mitochondrial homeostasis and promoting proliferation in neurons. In this study, the changes of CHCHD2 and downstream target genes such as NFE2L2/RQCD1 may have potential application prospects in the future. These findings provide leads to explore PD pathogenesis and potential treatments.
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Neuroblastoma , Enfermedad de Parkinson , Apoptosis , Diferenciación Celular , Línea Celular Tumoral , Proteínas de Unión al ADN/genética , Regulación hacia Abajo , Humanos , Mitocondrias/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Factor 2 Relacionado con NF-E2/farmacología , Neuroblastoma/metabolismo , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
OBJECTIVES: Freezing of gait (FOG) is a common and complex disabling episodic gait disturbance in patients with Parkinson's disease (PD). Currently, the treatment of FOG remains a challenge for clinicians. The aim of our study was to develop a nomogram for FOG risk based on data collected from Chinese patients with PD. MATERIALS & METHODS: A total of 379 PD patients (197 with FOG) from Kunming Medical University were recruited as a training cohort. Additionally, 339 PD patients (166 with FOG) were recruited from West China Hospital of Sichuan University, to serve as the validation cohort. The least absolute shrinkage and selection operator regression model was used to select clinical and demographic characteristics as well as blood markers, which were incorporated into a predictive model using multivariate logistic regression to predict the risk of developing FOG. The model was validated using the validation dataset, and model performance was evaluated using the C-index, calibration plot, and decision curve analyses. RESULTS: The final predictive model included the REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) score, Parkinson's Disease Questionnaire (PDQ39), H-Y stage, and visuospatial function. The model showed good calibration and good discrimination, with a C-index value of 0.772 against the training cohort and 0.766 against the validation cohort. Decision curve analysis demonstrated the clinical utility of the nomogram. CONCLUSION: A nomogram incorporating RBDSQ, PDQ39, H-Y stage, and visuospatial function may reliably predict the risk of FOG in PD patients.
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Trastornos Neurológicos de la Marcha , Enfermedad de Parkinson , China , Marcha , Trastornos Neurológicos de la Marcha/diagnóstico , Trastornos Neurológicos de la Marcha/etiología , Humanos , Nomogramas , Enfermedad de Parkinson/diagnósticoRESUMEN
The present study aimed to explore the association of plasma neurofilament light chain (NfL) levels with depression and anxiety in Parkinson's disease (PD). This prospective study enrolled 116 patients with PD and 38 healthy controls, and found plasma NfL levels were higher in patients with depression or anxiety than in those without these symptoms. Binary logistic regression identified NfL concentration as an independent predictor of depression and anxiety in PD. In conclusion, elevated plasma NfL may be associated with severity of depression and anxiety in PD patients and may serve as a diagnostic biomarker of PD with moderate to severe depression or anxiety.
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Enfermedad de Parkinson , Ansiedad/etiología , Biomarcadores , Depresión/etiología , Humanos , Filamentos Intermedios , Proteínas de Neurofilamentos , Enfermedad de Parkinson/diagnóstico , Estudios ProspectivosRESUMEN
The aetiology and pathogenesis of medial temporal lobe epilepsy (MTLE) remain unclear, and effective treatments are lacking. The involvement of a dysregulated competing endogenous RNA (ceRNA) network in MTLE is only partially understood. The purpose of this study was to investigate MTLE regulatory networks composed of messenger RNAs (mRNAs), circular RNAs (circRNAs), long non-coding RNAs (lncRNAs), and microRNAs (miRNAs) through a ceRNA network map. RNA sequencing (RNA-seq) and small RNA-seq were used to detect mRNAs, circRNAs, miRNAs, and lncRNAs differentially expressed between post-operation hippocampal tissues of MTLE patients (n = 3) and paracancer tissues (n = 3). We performed bioinformatics analysis to identify differentially expressed RNAs and construct the corresponding ceRNA network. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of differentially expressed RNAs were conducted to explore the biological processes and pathways involved in MTLE. We identified 352 differentially expressed mRNAs, 179 circRNAs, and 42 miRNAs in MTLE. A ceRNA network composed of mRNAs, circRNAs, and miRNAs was constructed. GO and KEGG analysis of the network suggested a key role of synapses and mTOR, cAMP, ErbB, FoxO, and HIF-1 signalling pathways in MTLE. We identify a new circRNA-miRNA-mRNA ceRNA network in MTLE. These results can help clarify the aetiology of MTLE and identify targeted molecular therapies.
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Epilepsia del Lóbulo Temporal , MicroARNs , ARN Largo no Codificante , Epilepsia del Lóbulo Temporal/genética , Redes Reguladoras de Genes , Humanos , MicroARNs/genética , MicroARNs/metabolismo , ARN Circular/genética , ARN Largo no Codificante/genética , ARN Mensajero/genética , ARN Mensajero/metabolismoRESUMEN
PURPOSE: The purpose of this study was to evaluate the association between clinically possible rapid eye movement (REM) sleep behavioral disorder (pRBD) and orthostatic hypotension (OH) in PD patients, as well as to explore the mechanisms underlying the association. METHODS: PD patients (n = 116) were assigned to a group with OH (PD-OH) or without OH (PD-NOH). General demographic and clinical data were collected. A series of scales were used to assess the clinical symptoms in the two groups. RESULTS: A total of 27 patients (23.3%) had OH. The PD-OH group showed significantly higher H-Y staging score and significantly higher frequencies of pRBD, anxiety, depression, and cognitive impairment than the PD-NOH group. Binary logistic regression analysis identified the following factors as independently associated with PD-OH: H-Y staging [odds ratio (OR) 2.565, 95% confidence interval (CI) 1.160-5.673; P = 0.020], RBD (OR 7.680, 95% CI 1.944-30.346; P = 0.004), UPDRS II (OR 1.021, 95% CI 0.980-1.063; P = 0.020), depression (OR 7.601, 95% CI 1.492-38.718; P = 0.015), and cognitive impairment (OR 0.824, 95% CI 0.696-0.976; P = 0.025). CONCLUSIONS: Our results suggest that pRBD is an independent risk factor for OH in patients with PD. We speculate that there may be a close relationship between RBD and OH, which requires attention. Early diagnosis of RBD may help predict the appearance of OH in PD patients.
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Hipotensión Ortostática , Enfermedad de Parkinson , Trastorno de la Conducta del Sueño REM , Humanos , Hipotensión Ortostática/complicaciones , Hipotensión Ortostática/epidemiología , Enfermedad de Parkinson/complicaciones , Trastorno de la Conducta del Sueño REM/complicaciones , Trastorno de la Conducta del Sueño REM/epidemiología , Factores de Riesgo , Sueño REMRESUMEN
In humans, breast cancer affects a large number of females and causes a high rate of mortality worldwide. Chemokine (C-C motif) ligand 5 (CCL5) is one of the cytokines that is highly correlated to the invasive and metastatic stages of breast cancer. Our previous study has suggested the prognostic value of CCL5 expression in luminal B (HER2 - ) breast cancer. In this study, CCL5 expression was upregulated or knockdown in a luminal B breast cancer cell line, ZR7530. Further, we elucidated the effects of CCL5 on the differentiation of THP-1 monocytes into M2 macrophages. Overexpression of CCL5 affected THP-1-M2 differentiation and phosphorylation of MEK1/2, ERK1/2, and STAT2 in the cocultivated cell lines. We report that the knockdown of CCR5, a receptor of CCL5 in THP-1, inhibited the effect of ZR7530 in promoting THP-1-M2 differentiation. Furthermore, our data revealed that the inhibition of MEK1/2 and STAT3 in THP-1 cells produced equivalent results similar to those of CCL5 knockdown. In summary, we revealed the role of CCL5 in the polarization of M2 macrophages. Furthermore, we studied its interaction with CCR5 and MEK/STAT3 signaling members. These targets could be used as key regulatory members in human breast cancer therapy.
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Neoplasias de la Mama/metabolismo , Quimiocina CCL5/genética , Macrófagos/citología , Factor de Transcripción STAT3/metabolismo , Neoplasias de la Mama/genética , Butadienos/farmacología , Diferenciación Celular/efectos de los fármacos , Línea Celular Tumoral , Polaridad Celular , Quimiocina CCL5/metabolismo , Técnicas de Cocultivo , Óxidos S-Cíclicos/farmacología , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Nitrilos/farmacología , Células THP-1RESUMEN
This study investigated the potential association between levels of plasma neurofilament light chain (NfL) and cognitive function in patients suffering from Parkinson's disease (PD) in P.R. China.We collected a total of 168 participants (130 PD patients and 38 healthy controls),and evaluated the relationship of plasma NfL levels with cognitive dysfunction in PD patients. Our results shown that plasma NfL levels increased with an increase in cognitive impairment across the three groups of PD patients: PD with normal cognition (PD-NC), 17.9 ± 8.9 pg/ml; PD with mild cognitive impairment (PD-MCI),21.9 ± 10.3 pg/ml; and PD dementia (PDD), 35.7 ± 21.7 pg/ml. Higher MMSE scores were associated with lower plasma NfL levels (r = -0.49, 95% CI -0.61 to -0.34, p < 0.0001). Our results associating plasma NfL levels with cognitive dysfunction in PD are consistent with previous studies carried out in several countries/district, based on our meta-analysis.
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Disfunción Cognitiva/sangre , Disfunción Cognitiva/psicología , Proteínas de Neurofilamentos/sangre , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/psicología , Anciano , Biomarcadores/sangre , Cognición/fisiología , Disfunción Cognitiva/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Enfermedad de Parkinson/diagnósticoRESUMEN
PURPOSE: Visuospatial disorders (VSDs) are common in Parkinson's disease (PD). VSDs may involve cerebellar vermis, but evidence from functional connectivity (FC) studies is lacking. Here we compared FC between cerebellar vermis and the entire brain between PD patients with or without VSD, and between patients and healthy controls. METHODS: Resting-state 3.0-T functional magnetic resonance imaging was performed on 19 controls, 31 PD patients with VSD and 12 PD patients without VSD. Correlations in brain network were calculated between eight regions of interest in the cerebellar vermis (I-VIII) and other voxels in the brain, and voxel-based FC was analyzed. Patients were assessed in terms of cognitive function as well as motor and non-motor symptoms. RESULTS: In both types of patients, cerebellar vermis VIII, IX and X showed positive FC with the default-mode network (DMN), executive control network and sensorimotor network. Cerebellar vermis I and II showed positive FC with the visual network and DMN in controls, but negative FC in PD patients without VSD. Cerebellar vermis X showed negative FC with lobules VIII and IX of the left cerebellar hemisphere in controls, but positive FC in PD patients with VSD. CONCLUSION: Positive FC connecting the cerebellar vermis VIII and X with associated brain networks in PD patients with VSD may be compensatory activation. PD may involve disruption of functional coupling between the cerebellar vermis and cerebral cortex.
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Agnosia/fisiopatología , Vermis Cerebeloso/fisiopatología , Corteza Cerebral/fisiopatología , Enfermedad de Parkinson/fisiopatología , Anciano , Agnosia/etiología , Mapeo Encefálico , Estudios de Casos y Controles , Vermis Cerebeloso/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Femenino , Voluntarios Sanos , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Red Nerviosa/fisiología , Vías Nerviosas/fisiopatología , Enfermedad de Parkinson/complicaciones , Descanso/fisiología , Navegación Espacial/fisiologíaRESUMEN
The aim of this study is to explore whether the single nucleotide polymorphism rs2275294 in the ZNF512B gene is related to the length of survival of patients with amyotrophic lateral sclerosis (ALS). This prospective study examined 212 patients with ALS, who were genotyped at the rs2275294 locus in ZNF512B using the ligase method. Genotype was compared with clinical data and survival. Kaplan-Meier survival analysis and Cox hazard regression were used to identify risk factors of shorter survival. Our results were meta-analyzed together with previous work in order to examine the potential association between the rs2275294-C allele and survival. Of the 212 patients, 166 carried the CC + CT genotype at the rs2275294 locus, while 46 carried the TT genotype. Patients with the C allele showed significantly shorter survival than those without it (34.13 ± 1.9 vs. 45.32 ± 5.7 months, p = 0.036). Cox analysis identified the C allele and time from symptom onset to diagnosis as risk factors for shorter survival. Meta-analysis of 447 patients in China and Japan confirmed the rs2275294-C allele to be an independent risk factor of shorter survival in ALS patients. The C allele at the rs2275294 locus in ZNF512B is a risk factor for shorter survival in patients with ALS.
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Esclerosis Amiotrófica Lateral/genética , Proteínas Portadoras/genética , Polimorfismo de Nucleótido Simple , Adulto , Alelos , Esclerosis Amiotrófica Lateral/mortalidad , China/epidemiología , Diagnóstico Tardío , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Japón/epidemiología , Estimación de Kaplan-Meier , Esperanza de Vida , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Factores de RiesgoRESUMEN
BACKGROUND: Deep-brain stimulation is a well-established, effective treatment for patients with advanced Parkinson's disease. Recent studies examining rates of suicide attempts and suicides after deep-brain stimulation in the bilateral subthalamic nucleus have reported varying results. Using this systematic review and meta-analysis, we aim to obtain a comprehensive understanding of suicidality in Parkinson's patients after subthalamic nucleus deep brain stimulation. METHODS: We systematically examined Medline, PubMed, Web of Science, and Embase databases to identify studies published before November 2019 that measured rates of suicidality in Parkinson's patients who underwent subthalamic nucleus stimulation. A meta-analysis of the data from the included studies was conducted using Stata 12.0. RESULTS: A total of 18 studies met the eligibility criteria of this study. We found that the pooled rate of suicidal ideation was 4% (95% CI 0.00-7.2%, range 2-17%). The pooled rate of suicide attempts was 1% (95% CI 1.0-2.0%), while the pooled rate of suicide was 1% (95% CI 0.0-1.0%). CONCLUSIONS: Our findings indicate a relatively high rate of suicidality among Parkinson's patients after subthalamic nucleus deep-brain stimulation. It is important for clinicians to carefully monitor psychiatric disorders, especially suicidal ideation and suicide attempts, in Parkinson's patients before and after subthalamic nucleus deep-brain stimulation.
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Estimulación Encefálica Profunda , Enfermedad de Parkinson , Núcleo Subtalámico , Humanos , Enfermedad de Parkinson/terapia , Intento de Suicidio , Resultado del TratamientoRESUMEN
For underwater Strapdown Inertial Navigation System (SINS)/Doppler Velocity Log (DVL) integration system, there are intervals between DVL's transmitting and receiving epochs, which introduces velocity errors when the attitude dynamic occurs. To accelerate the coarse alignment process for SINS/DVL with attitude dynamics, an improved in-motion coarse alignment solution is proposed. First, the DVL aided in-motion coarse alignment method is explored. Then, a DVL velocity compensation algorithm for coarse alignment is proposed. Simulations and a field test are conducted to evaluate the effectiveness of the proposed algorithm under various trajectories. The results indicate that the proposed coarse alignment solution effectively applies the velocity compensation algorithm to the coarse alignment mission, which shows greater performance than the traditional optimization-based alignment (OBA) method in various trajectories.
RESUMEN
BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease associated with both genetic and environmental risk factors. Previous studies trying to find an association between ALS and unc-13 homolog A (UNC13A) gene variants have shown inconsistent results. This study aimed to conduct a meta-analysis of the association between the C allele of rs12608932, a single-nucleotide polymorphism located in an intron of UNC13A, and risk of ALS and patient survival. METHODS: PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure, Wanfang, and SinoMed databases were systematically searched for genome-wide association studies or case-control studies published up to January 2019 on the association between this variant in UNC13A and risk and/or prognosis of ALS. Data from eligible studies were extracted and analyzed. RESULTS: The pooled data (28,072 patients with sporadic ALS and 56,545 controls) showed that rs12608932(C) was associated with an increased risk of ALS (OR = 1.13, 95%CI 1.07-1.20). Subgroup analysis revealed that rs12608932(C) increased the risk of sporadic ALS in non-Asian individuals, including those from the USA and Europe (OR 1.17, 95%CI 1.10-1.25, P < 0.000), but not in Japanese or Chinese subjects (OR 1.01, 95%CI 0.92-1.10, P = 0.85). The available data demonstrated that the CC genotype decreased the survival time of patients with ALS (OR 1.33, 95%CI 1.19-1.49, P < 0.001). CONCLUSION: The present meta-analysis suggests that rs12608932(C) is associated with increased ALS susceptibility, especially in Caucasian and European subjects, and that the CC genotype of rs12608932 is associated with reduced ALS patient survival.