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.

Cortical atrophy is associated with cognitive impairment in Parkinson's disease: a combined analysis of cortical thickness and functional connectivity.

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.

Association between levels of high-sensitivity C-reactive protein in plasma and freezing of gait in Parkinson's disease.

This study explored the potential relationship between levels of high-sensitivity C-reactive protein (hs-CRP) in plasma and freezing of gait (FOG) in Parkinson's disease (PD) in China. A total of 72 healthy subjects, 62 PD patients with FOG, and 83 PD patients without FOG from our center were enrolled in this prospective study. Patients with FOG showed significantly higher hs-CRP levels than controls, but patients without FOG did not. Binary logistic regression analysis identified levels of hs-CRP in plasma to be an independent risk factor for FOG among the patients in our cohort (OR 6.371, 95% CI 2.589-15.678, p < 0.001). In fact, a cut-off level of 0.935 mg/L distinguished patients with or without FOG [area under the ROC curve (AUC) = 0.908, sensitivity 87.1%, specificity 89.2%]. Our study suggests that high levels of hs-CRP in plasma are associated with the occurrence of FOG in PD. The pooled data combined with a previous study carried out in Spain also indicate a positive association between plasma hs-CRP levels and FOG in PD. However, more research is still needed to verify the plasma hs-CRP as a potential biomarker of FOG.

Maternal anti-tumour necrosis factor-α drug use during pregnancy and risk of infection in the offspring: A systematic review and meta-analysis.

BACKGROUND: Anti-tumour necrosis factor (TNF)-α drugs are used by increasing numbers of reproductive-age women. Although the neonatal outcomes have been described, there are concerns regarding the risk of infection in offspring following exposure to anti-TNF-α. METHODS: A literature search was conducted using Pubmed, EMBASE, and the Cochrane Database, from inception through August 2020. We evaluated the risk of infection in autoimmune disease (AID) offspring unexposed to anti-TNF-α compared to AID offspring exposed to anti-TNF-α, as well as to unexposed non-AID offspring. RESULTS: Our primary analysis showed that both AID offspring unexposed to anti-TNF-α [risk ratio (RR) 1.09; 95% confidence interval (CI), 1.03-1.16; I2=0%] and AID offspring exposed to anti-TNF-α (RR 1.39; 95% CI, 1.2-1.61; I2=0%] was associated with an increased risk of infection during the first year of life compared with the unexposed non-AID offspring. However, our secondary analysis demonstrated that AID offspring exposed to anti-TNF-α was not associated with an increased risk of infection when compared with AID offspring unexposed to anti-TNF-α (RR=1.1; 95% CI, 0.86-1.4). CONCLUSION: Our results suggest that in utero exposure to anti-TNF-α does not appear to increase the risk of infection during the first year of life in the offspring; however, AID itself was associated with a marked excess risk of infection in the children.

The involvement of PybZIPa in light-induced anthocyanin accumulation via the activation of PyUFGT through binding to tandem G-boxes in its promoter.

To gain insight into how anthocyanin biosynthesis is controlled by light in fruit, transcriptome and metabolome analyses were performed in the Chinese sand pear cultivar "Mantianhong" (Pyrus pyrifolia) after bagging and bag removal. We investigated transcriptional and metabolic changes and gene-metabolite correlation networks. Correlation tests of anthocyanin content and transcriptional changes revealed that 1,530 transcripts were strongly correlated with 15 anthocyanin derivatives (R 2 > 0.9, P-value < 0.05), with the top 130 transcripts categorized as being associated with flavonoid metabolism, transcriptional regulation, and light signaling. The connection network revealed a new photosensitive transcription factor, PybZIPa, that might play an important role during light-induced anthocyanin accumulation. The overexpression of PybZIPa promoted anthocyanin accumulation in pear and strawberry fruit as well as tobacco leaves. Dual luciferase and Y1H assays further verified that PybZIPa directly activated the expression of PyUFGT by binding to tandem G-box motifs in the promoter, which was key to differential anthocyanin accumulation in debagged pear skin, and the number of G-box motifs affected the transcriptional activation of PyUFGT by PybZIPa. The results indicate that the light-induced anthocyanin biosynthesis regulatory mechanism in pear differs from that described in previous reports suggesting that a bZIP family member co-regulates anthocyanin biosynthesis with other transcription factors in apple and Arabidopsis. It was found that, in response to light, PybZIPa promoted anthocyanin biosynthesis by regulating important transcription factors (PyMYB114, PyMYB10, and PyBBX22) as well as structural genes (PyUFGT) via binding to G-boxes within promoters. This activation was amplified by the self-binding of PybZIPa to activate its own promoter. Overall, we demonstrate the utility of a multiomics integrative approach for discovering new functional genes and pathways underlying light-induced anthocyanin biosynthesis.

[Clinical and genetic study of a family affected with spinocerebellar ataxia 3 and polycystic kidney disease].

OBJECTIVE: To investigate clinical features and genetic mutations of a family affected with spinocerebellar ataxia 3 and polycystic kidney disease. METHODS: Polymerase chain reaction and DNA sequencing were employed to analyze exon 10 of the SCA3 gene, in addition with all exons and flanking sequences of PKD1 and PKD2 genes. The clinical features were also carefully analyzed. RESULTS: The numbers of CAG repeat in the proband's SCA3 gene were 28/76, with the number of repeats in the mutant allele being in the full range. The sequence of exon 23 of the PKD1 gene was also found to be abnormal. Clinical symptoms of the proband were very serious, which were characterized by obvious ataxia, pyramidal signs, Meige syndrome, depression and high blood pressure. CONCLUSION: Hereditary spinocerebellar ataxia 3 and autonomic dominant polycystic kidney disease may co-occur, and genetic testing is the primary means of diagnosis.