Biomarkers are urgently needed for the diagnosis and monitoring of disease progression in Parkinson’s disease. Both DJ-1 and α-synuclein, two proteins critically involved in Parkinson’s disease pathogenesis, have been tested as disease biomarkers in several recent studies with inconsistent results. These have been largely due to variation in the protein species detected by different antibodies, limited numbers of patients in some studies, or inadequate control of several important variables. In this study, the nature of DJ-1 and α-synuclein in human cerebrospinal fluid was studied by a combination of western blotting, gel filtration and mass spectrometry. Sensitive and quantitative Luminex assays detecting most, if not all, species of DJ-1 and α-synuclein in human cerebrospinal fluid were established. Cerebrospinal fluid concentrations of DJ-1 and α-synuclein from 117 patients with Parkinson’s disease, 132 healthy individuals and 50 patients with Alzheimer’s disease were analysed using newly developed, highly sensitive Luminex technology while controlling for several major confounders. A total of 299 individuals and 389 samples were analysed. The results showed that cerebrospinal fluid DJ-1 and α-synuclein levels were dependent on age and influenced by the extent of blood contamination in cerebrospinal fluid. Both DJ-1 and α-synuclein levels were decreased in Parkinson’s patients versus controls or Alzheimer’s patients when blood contamination was controlled for. In the population aged ≥65 years, when cut-off values of 40 and 0.5 ng/ml were chosen for DJ-1 and α-synuclein, respectively, the sensitivity and specificity for patients with Parkinson’s disease versus controls were 90 and 70% for DJ-1, and 92 and 58% for α-synuclein. A combination of the two markers did not enhance the test performance. There was no association between DJ-1 or α-synuclein and the severity of Parkinson’s disease. Taken together, this represents the largest scale study for DJ-1 or α-synuclein in human cerebrospinal fluid so far, while using newly established sensitive Luminex assays, with controls for multiple variables. We have demonstrated that total DJ-1 and α-synuclein in human cerebrospinal fluid are helpful diagnostic markers for Parkinson’s disease, if variables such as blood contamination and age are taken into consideration.
8 May 2020 in Journal of Medical Internet Research
Disasters and pandemics pose unique challenges to health care delivery. As health care resources continue to be stretched due to the increasing burden of the coronavirus disease (COVID-19) pandemic, telemedicine, including tele-education, may be an effective way to rationally allocate medical resources. During the COVID-19 pandemic, a multimodal telemedicine network in Sichuan Province in Western China was activated immediately after the first outbreak in January 2020. The network synergizes a newly established 5G service, a smartphone app, and an existing telemedicine system. Telemedicine was demonstrated to be feasible, acceptable, and effective in Western China, and allowed for significant improvements in health care outcomes. The success of telemedicine here may be a useful reference for other parts of the world.
Objective: To explore the structure and composition of the fecal microbiota of patients with epilepsy. Methods: Variations in the fecal microbiota between patients with epilepsy and healthy controls (HCs) from the same household were investigated and validated by utilizing 16S ribosomal RNA sequencing in two independent cohorts [exploration cohort (N = 55 patients and N = 46 HCs) and validation cohort (N = 13 patients and N = 10 HCs)]. Results: The alpha diversity indexes of the specimens from patients with epilepsy were much lower than those from the HCs (p < 0.05). The structure and composition of the fecal microbiota differed between patients with different clinical prognoses and between patients and HCs (Adonis: p < 0.05). Microbiome alterations in patients with epilepsy included increases in Actinobacteria and Verrucomicrobia and decreases in Proteobacteria at the phylum level and increases in Prevotella_9, Blautia, Bifidobacterium, and others at the genus level [linear discriminant analysis (LDA): 3.5] Patients with drug-resistant epilepsy showed enrichment of bacterial taxa in Actinobacteria, Verrucomicrobia, and Nitrospirae and the genera Blautia, Bifidobacterium, Subdoligranulum, Dialister, and Anaerostipes (Kruskal-Wallis test: p < 0.05). Analysis of gut microbiome indicated predictive ability for disease diagnosis, with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.97 (95% CI, 0.84–0.98). Applying the model to our validation cohort resulted in an AUC of 0.96 (95% CI, 0.75–0.97). Notably, the model could distinguish drug-resistant from drug-sensitive epilepsy (AUC = 0.85, 95% CI: 0.69–0.94). Conclusion: Patients with epilepsy exhibit substantial alterations of fecal microbiota composition, and specific gut commensal strains are altered depending on different clinical phenotypes and thus could serve as potential biomarkers for disease diagnosis.