Biomarker of Neuroinflammation in Parkinson's Disease.

Parkinson's disease (PD) is caused by abnormal accumulation of α-synuclein in dopaminergic neurons of the substantia nigra, which subsequently causes motor symptoms. Neuroinflammation plays a vital role in the pathogenesis of neurodegeneration in PD. This neuroinflammatory neurodegeneration involves the activation of microglia, upregulation of proinflammatory factors, and gut microbiota. In this review, we summarized the recent findings on detection of PD by using inflammatory biomarkers, such as interleukin (IL)-1ß, IL-2, IL-6, IL-10, tumor necrosis factor (TNF)-α; regulated upon activation, normal T cell expressed and presumably secreted (RANTES) and high-sensitivity c-reactive protein (hsCRP); and radiotracers such as [11C]PK11195 and [18F]-FEPPA, as well as by monitoring disease progression and the treatment response. Many PD-causing mutations in SNCA, LRRK2, PRKN, PINK1, and DJ-1 are also associated with neuroinflammation. Several anti-inflammatory medications, including nonsteroidal anti-inflammatory drugs (NSAID), inhibitors of TNF-α and NLR family pyrin domain containing 3 (NLRP3), agonists of nuclear factor erythroid 2-related factor 2 (NRF2), peroxisome proliferator-activated receptor gamma (PPAR-γ), and steroids, have demonstrated neuroprotective effects in in vivo or in vitro PD models. Clinical trials applying objective biomarkers are required to investigate the therapeutic potential of anti-inflammatory medications for PD.

Association of SOD2 p.V16A polymorphism with Parkinson's disease: A meta-analysis in Han Chinese.

BACKGROUND: Oxidative stress could participate in the pathogenesis of Parkinson's disease (PD). However, the role of genetic variation of superoxide dismutase 2 (SOD2), an important regulator against oxidative stress, in PD remains to be elucidated. METHODS: We screened SOD2 gene variation by sequencing cDNA from 72 patients with early onset PD. A cohort of PD (n = 609) and ethnically matched controls (n = 681) were further examined for the identified sequence variant by PCR and NaeI restriction analysis. RESULTS: Only a reported c.47T>C polymorphism (rs4880, SOD2 p.V16A) was found by cDNA sequencing. Case-control study of c.47T>C revealed that genotype and allele frequencies were in Hardy-Weinberg equilibrium in both patients and healthy controls. In a recessive model, those with CC genotype had a 2.61-fold increased risk of PD (95% CI: 1.08-6.30, P = 0.03) compared to subjects with TT and TC genotypes. Significant association between CC genotype and PD in non-smokers was also observed after stratification according to the history of smoking (3.54-fold increased risk of PD, 95% CI: 1.17-10.72, P = 0.02). Meta-analysis by combining studies of Chinese in China, Singapore, and Taiwan (total 2302 cases and 2029 controls) consistently showed CC genotype with increased risk of PD (OR = 1.77, 95% CI: 1.15-2.71, P = 0.01). CONCLUSION: Our findings demonstrate that SOD2 p.V16A may play a role in the susceptibility of PD in Han Chinese.

Differential Diagnostic Value of Machine Learning-Based Models for Embolic Stroke.

Cancer-associated thrombosis (CAT) and atrial fibrillation (AF)-related stroke are two subtypes of acute embolic stroke with distinct lesion patterns on diffusion weighted imaging (DWI). This pilot study aimed to evaluate the feasibility and performance of DWI-based machine learning models for differentiating between CAT and AF-related stroke. Patients with CAT and AF-related stroke were enrolled. In this pilot study with a small sample size, DWI images were augmented by flipping and/or contrast shifting to build convolutional neural network (CNN) predicative models. DWI images from 29 patients, including 9 patients with CAT and 20 with AF-related stroke, were analyzed. Training and testing accuracies of the DWI-based CNN model were 87.1% and 78.6%, respectively. Training and testing accuracies were 95.2% and 85.7%, respectively, for the second CNN model that combined DWI images with demographic/clinical characteristics. There were no significant differences in sensitivity, specificity, accuracy, and AUC between two CNN models (all P = n.s.).The DWI-based CNN model using data augmentation may be useful for differentiating CAT from AF-related stroke.

The body image, weight satisfaction, and eating disorder tendency of school children: the 2-year follow-up study.

OBJECTIVE: This 2-year follow-up study was conducted to enhance our understanding of changes and rates of disturbed eating attitudes/behaviors, weight satisfaction, and prevalence of obesity in elementary school students between the ages of 10 and 12 years. METHODS: Questionnaires consisted of the following sections: (A) Demographics, (B) Body image, (C) Pubertal Development Scale, and (D) Children's Eating Attitudes Test-26 (ChEAT-26). School-based randomly selected participants completed the questionnaire at 10 years of age and repeated the same questionnaire 2 years later, at 12 years of age. RESULTS: The following findings were reported: (1) when changes at 2 years were compared, it was seen that the actual body weight of boys tended to increase, and perceived body size and desired body weight showed significant changes; (2) the percentage of children who wanted to be thinner increased, especially among girls; and (3) the percentage of participants with a tendency toward eating disorders (measured by ChEAT-26, ≥20) decreased from 10.4% to 10.1% in boys, and increased from 10.9% to 12.3% in girls. CONCLUSION: Nutritional education should emphasize the importance of correct body image and eating attitudes for the prevention of unhealthy body weight concerns and eating disorders in children. Caregivers' attitudes about weight and how caregivers deliver information on weight issues to children should be recognized as important factors related to healthy body image and eating attitudes among children.

Polymorphisms of Interleukin-6 and Interleukin-8 Are Not Associated with Parkinson's Disease in Taiwan.

BACKGROUND: Studies have suggested that cytokines are crucial mediators in the pathogenesis of Parkinson's disease (PD). The multifunctional cytokine interleukin (IL)-6 and its single nucleotide polymorphisms (SNPs) were found to have an impact on the development of PD. However, different studies in associations of IL-6 genetic variants with PD showed inconsistent results and it has never been explored in a Taiwanese population. Both IL-1α and IL-8 contribute to the same inflammation pathway. IL-1α genetic polymorphism has an effect on late-onset PD in Taiwan, whereas the associations of IL-8 genetic variants with PD in Taiwan remain to be investigated. METHODS: This study examined the frequencies of polymorphisms within the critical promoter areas of the proinflammatory cytokine genes: IL-6 G-174C (rs1800795) and IL-8 A-251T (rs4073) in Taiwanese PD patients compared with age-and gender-matched healthy subjects. Comparisons were also made in genotype and allele frequencies of IL-6 G-174C (rs1800795) and IL-8 A-251T (rs4073) among different populations in previous studies. RESULTS: In total, 1120 subjects, including 509 PD patients (female/male: 259/250) and 511 control subjects (female/male: 252/259), were recruited. We found no statistically significant differences in IL-6 G-174C (rs1800795) or IL-8 A-251T (rs4073) genotypic and allelic distribution between PD and controls, even after being stratified by age at onset and gender. CONCLUSIONS: The results did not demonstrate any association of IL-6 G-174C (rs1800795) or IL-8 A-251T (rs4073) with PD in a Taiwanese population. Despite the negative results, this is the first study in associations of IL-6 G-174C (rs1800795) and IL-8 A-251T (rs4073) with PD in Taiwan. The relevance of genetic variants of IL-6 G-174C (rs1800795) or IL-8 A-251T (rs4073) on PD susceptibility warrants further investigation.

Association of RIT2 and RAB7L1 with Parkinson's disease: a case-control study in a Taiwanese cohort and a meta-analysis in Asian populations.

Several genome-wide association studies and meta-analyses on Parkinson's disease (PD)-related genes have identified several risk foci in Ras-related genes, particularly among Caucasian individuals. However, the corresponding results have been controversial among Asian individuals. We investigated whether 2 single-nucleotide polymorphisms of Ras-related genes, RIT2 (rs12456492) and RAB7L1 (rs823118), are associated with PD risk in Taiwanese individuals. In addition, we conducted a meta-analysis of all studies related to rs12456492 in Asian populations to resolve inconsistency in this locus. In total, 1103 Taiwanese individuals (588 patients with PD and 515 controls) and 1111 Taiwanese individuals (594 patients with PD and 517 controls) were genotyped for rs12456492 and rs823118. However, we could not confirm the association of rs12456492 and rs823118 with PD. Our current meta-analysis involving the rs12456492(A/G) variant demonstrated that the GG + GA genotypes, GG genotypes, and G allele may be risk factors for PD. RIT2 may increase PD risk in Asian individuals. The discrepancies between Caucasian and Asian populations may be due to differences in geographic region-specific genetic backgrounds and gene-environmental interactions.