Correlation analysis between 18F-fluorodeoxyglucose positron emission tomography and cognitive function in first diagnosed Parkinson’s disease patients

ObjectiveEvaluation of the correlation between 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG PET) and cognitive function in first-diagnosed and untreated Parkinson’s disease (PD) patients.Materials and methodThis cross-sectional study included 84 first diagnosed and untreated PD patients. The individuals were diagnosed by movement disorder experts based on the 2015 MDS Parkinson’s disease diagnostic criteria. The patients also underwent 18F-FDG PET scans and clinical feature assessments including the Montreal Cognitive Assessment (MoCA) scale. Glucose metabolism rates were measured in 26 brain regions using region of interest (ROI) and pixel-wise analyses with displayed Z scores. The cognitive function was assessed by professionals using the MoCA scale, which covers five cognitive domains. Spearman’s linear correlation and linear regression models were used to compare the correlations between 18F-FDG metabolism in each brain region and cognitive domain, using SPSS 25.0 software.ResultThe results indicated a positive correlation between executive function and glucose metabolism in the lateral prefrontal cortex of the left hemisphere (p = 0.041). Additionally, a positive correlation between memory function and glucose metabolism in the right precuneus (p = 0.014), right lateral occipital cortex (p = 0.017), left lateral occipital cortex (p = 0.031), left primary visual cortex (p = 0.008), and right medial temporal cortex (p = 0.046). Further regression analysis showed that for every one-point decrease in the memory score, the glucose metabolism in the right precuneus would decrease by 0.3 (B = 0.30, p = 0.005), the glucose metabolism in the left primary visual cortex would decrease by 0.25 (B = 0.25, p = 0.040), the glucose metabolism in the right lateral occipital cortex would decrease by 0.38 (B = 0.38, p = 0.012), and the glucose metabolism in the left lateral occipital cortex would decrease by 0.32 (B = 0.32, p = 0.045).ConclusionThis study indicated that cognitive impairment in PD patients mainly manifests as changes in executive function, visual-spatial function and memory functions, while glucose metabolism mainly decreases in the frontal and posterior cortex. Further analysis shows that executive function is related to glucose metabolism in the left lateral prefrontal cortex. On the other hand, memory ability involves changes in glucose metabolism in a more extensive brain region. This suggests that cognitive function assessment can indirectly reflect the level of glucose metabolism in the relevant brain regions

Characteristics and influencing factors of 11C-CFT PET imaging in patients with early and late onset Parkinson’s disease

ObjectiveThis study aims to explore the difference between 11C-methyl-N-2β-carbomethoxy-3β-(4-fluorophenyl)-tropanel (11C-CFT) positron emission tomography (PET) imaging in the early-onset Parkinson’s disease (EOPD) and late-onset Parkinson’s disease (LOPD), and to analyze the correlation between 11C-CFT PET imaging and disease duration, Hoehn & Yahr (H&Y) stage, motor symptoms, and non-motor symptoms in patients with idiopathic Parkinson’s disease (PD), so as to explore its application value in assessing the severity of Parkinson’s disease.Materials and methodsA total of 113 patients with idiopathic PD were included in this study. The patients were divided into EOPD and LOPD groups according to the age of 60 years, of which 58 were early-onset and 55 were late-onset. All patients underwent 11C-CFT PET imaging and manually sketched regions of interest (ROI) to delineate the caudate nucleus, anterior putamen, and posterior putamen ROI layer-by-layer, and the corresponding values were recorded. Clinical data [age of onset, disease duration, H&Y stage, total Unified Parkinson’s Disease Rating Scale (UPDRS) score, UPDRS III score, tremor score, postural instability/gait difficulty (PIGD) score, rigidity score, bradykinesia score, and Montreal Cognitive Assessment (MoCA) score] were collected from all patients. The differences in striatal 11C-CFT uptake between patients with EOPD and LOPD were compared, and the correlation between striatal 11C-CFT uptake and the clinical data of patients with idiopathic PD was evaluated.ResultsThe caudate nucleus 11C-CFT uptake was higher in EOPD than in the LOPD group (t = 3.002, p = 0.003). 11C-CFT uptake in the caudate nucleus in patients with PD was negatively correlated with the age of onset, H&Y stage, disease duration, total UPDRS score, UPDRS III score, rigidity score, and bradykinesia score (p < 0.05). The anterior and posterior putamen 11C-CFT uptake was negatively correlated with H&Y stage, disease duration, total UPDRS score, UPDRS III score, PIGD score, rigidity score, and bradykinesia score (p < 0.05).Conclusion11C-CFT PET provides an objective molecular imaging basis for the difference in disease progression rates between patients with EOPD and LOPD. Secondly, 11C-CFT PET can be used as an important objective indicator to assess disease severity and monitor disease progression

Could social robots facilitate children with autism spectrum disorders in learning distrust and deception?

Social robots have been increasingly involved in our daily lives and provide a new environment for children\u27s growth. The current study aimed to examine how children with and without Autism Spectrum Disorders (ASD)learned complex social rules from a social robot through distrust and deception games. Twenty children with ASD between the ages of 5–8 and 20 typically-developing (TD)peers whose age and IQ were matched participated in distrust and deception tasks along with an interview about their perception of the human-likeness of the robot. The results demonstrated that: 1)children with ASD were slower to learn to and less likely to distrust and deceive a social robot than TD children and 2)children with ASD who perceived the robot to appear more human-like had more difficulty in learning to distrust the robot. Besides, by comparing to a previous study the results showed that children with ASD appeared to have more difficulty in learning to distrust a human compared to a robot, particularly in the early phase of learning. Overall, our study verified that social robots could facilitate children with ASD\u27s learning of some social rules and showed that children\u27s perception of the robot plays an important role in their social learning, which provides insights on robot design and its clinical applications in ASD intervention

Expression and function of APELA : a potential regulator of cell growth in human cancers

Apela, a novel gene identified by our laboratory, is expressed in mouse definitive endoderm, neural tube, and mouse embryonic stem cells (mESCs). In humans, APELA is expressed in embryonic stem cells, induced adult pluripotent stem cells (iPSCs) as well as adult kidney and prostate. APELA peptide signals through the G-protein coupled receptor, the APJ receptor, to regulate zebrafish definitive endoderm migration and cardiac development. Interestingly, the mRNA of Apela can mediate p53-dependent mESCs cell apoptosis. These findings suggest that Apela can functions as a peptide or as a lncRNA. Signaling pathways that are critical during embryogenesis are also important in cancer development and progression. However, thus far, whether APELA exerts any biological functions that regulate cancer progression is completely unknown. In this study, analysis of the cancer genome atlas (TCGA) RNA sequencing datasets reveals that APELA mRNA is expressed in different human cancer including in ovarian cancer. Real-time quantitative PCR analyses of clinical human ovarian cancer samples show that APELA mRNA levels are higher in ovarian clear cell carcinoma (OCCC), than other subtypes. Using a CRISPR/Cas9-mediated knockout approach, I have demonstrated that APELA knockout suppresses cell growth in the ovarian clear cell carcinoma cell line, OVISE. Decreased cell growth induced by APELA knockout can be partially attenuated by treating cells with recombinant human APELA protein. In addition, flow cytometry analyses show that APELA knockout induces G2/M phase arrest in OVISE cells. Western blot results show that the phosphorylation levels of ERK1/2, AKT, and cyclin B1 expression levels are significantly down-regulated in the APELA deficient OVISE cells. Moreover, our results indicate that in the APELA knockout cells, decreased cell growth is dependent on the expression of wildtype p53. Unexpectedly, knockout APELA does not affect cell growth in Ewing sarcoma cell line A673, which has high expression of APELA at mRNA level. Interestingly, the APJ receptor is expressed in A673 cells but not in OVISE cells, which strongly suggests that APELA can exert its function through APJ-independent pathway in OVISE cells. In summary, our study demonstrates that APLEA may be an important factor that mediates the progression of OCCC.Medicine, Faculty ofGraduat

Bone morphogenetic protein 2 governs invasive trophoblast functions by regulating extracellular matrix and adhesion molecules at the maternal-fetal interface

Many pregnancy disorders, including pregnancy loss, preeclampsia, preterm birth and intrauterine growth restriction are associated with defects in placental development, including abnormal placental trophoblast invasion and differentiation. Bone morphogenetic protein 2 (BMP2) belongs to the transforming growth factor-β (TGF-β) superfamily and controls various physiological and developmental processes. Previous studies have demonstrated the pro-invasive action of BMP2 signaling in human trophoblasts in vitro. However, the expression of BMP2 in the placenta and underlying molecular mechanisms of how BMP2 regulates trophoblast function remain unclear. In this study, we analyzed several publicly available microarray datasets and revealed that BMP2 was expressed in the placenta across all three trimesters. Importantly, BMP2 levels were significantly reduced in placenta samples from early-onset preeclampsia pregnancies compared with gestational age-matched normal pregnancies. RNAscope in situ hybridization showed that in the first trimester BMP2 was localized in all subtypes of trophoblasts as well as in decidua. To further investigate downstream transcriptional targets of BMP2 signaling, we performed mRNA-sequencing on control and BMP2-treated primary human trophoblasts (n=5). This analysis identified 431 differentially expressed genes, of which 253 were upregulated and 178 were downregulated, with a false discovery rate < 0.05. We found that BMP2 enhances first-trimester placental trophoblast invasion by regulating a network of cellular adhesion and extracellular matrix genes. Furthermore, we identified SOX4 as a direct target gene of BMP2 in trophoblasts. Importantly, SOX4 can transcriptionally regulate the expression of SOX4-dependent BMP2 targets by binding to the regulatory elements such as enhancers, thereby promoting BMP2-induced trophoblast invasion. Lastly, we assessed the effect of BMP2 on gene expression in decidual stromal cells and the resulting regulation of trophoblast invasion by decidual stromal cells. The results suggest BMP2 induces the production of SPON2 by decidual stromal cells, which in turn restricts trophoblast invasion. Collectively, this study demonstrates the association of dysregulated placental BMP2 expression with EOPET and elucidates novel mechanisms of BMP2 action at the first-trimester maternal-fetal interface.Medicine, Faculty ofObstetrics and Gynaecology, Department ofGraduat

The Manufacturer Decision Analysis for Corporate Social Responsibility under Government Subsidy

Charitable donation and energy-saving R&D are two common approaches to fulfill corporate social responsibility (CSR). A recent survey in China shows that most firms prefer donating to investing in energy-saving research and development. To understand firms’ preference, we develop a game model to investigate the optimal CSR decisions and profit of the firm, which considers donation and energy-saving R&D approaches, respectively. Then, we analyze how the government subsidies for CSR, as well as the unit production cost and the R&D cost of energy-saving product, affect the firm’s CSR decisions and the CSR rate of return. Finally, we study the triple bottom line approach, i.e., considering donation and energy-saving R&D approaches simultaneously, and investigate the interaction between the above two approaches. The results show the following. (1) Government subsidy is an important driver for the firm’s CSR fulfillment and the triple bottom line approach is optimal if the government simultaneously provides two subsidies. (2) When the government subsidy for energy-saving product is moderate, the firm will choose the approach with high profit and high CSR rate of return. (3) The CSR rates of return of different approaches are also compared to reveal the efficiency of the CSR fulfillment and the firm may sometimes choose an approach with low CSR rate of return to pursue high profit. We identify why and when firms prefer charitable donation to energy-saving R&D approach and determine the threshold of the firm engaging CSR for the government to formulate CSR subsidy policies

Information Investment and Sharing in a Two-Echelon Supply Chain under Government Subsidy and Consumer Preference for Energy-Saving Products

This study establishes a two-echelon supply chain with one manufacturer who invests in energy-saving products (ESPs) and one retailer who sells the products and may possess demand-forecast advantage. Considering government subsidy and consumer preference for ESPs and a random demand, we develop a four-stage Stackelberg game model to research the optimal strategies of the information investment and sharing of the retailer and the energy-saving R&D of the manufacturer. The results show the following: (1) When incurring a low information investment cost, the retailer is willing to invest in information acquisition techniques, while the retailer agreeing to share market information is related to the government subsidies and the probability of a high demand. The optimal strategy for the retailer is to share information when the probability of a high demand is less than 50% and the government subsidies for ESPs are high. Otherwise, the optimal strategy is not to share information. (2) The manufacturer not always expects the retailer to share information, which depends on the probability of a high demand and manufacturing cost. Especially, when the probability of a high demand is less than 50%, only a manufacturer incurring high cost will expect. (3) If the retailer refuses to share the information, the manufacturer can motivate the retailer to change his/her decision by sharing the information investment cost

Bone morphogenetic protein 2 inhibits growth differentiation factor 8-induced cell signaling via upregulation of gremlin2 expression in human granulosa-lutein cells

Background Bone morphogenetic protein 2 (BMP2), growth differentiation factor 8 (GDF8) and their functional receptors are expressed in human ovarian follicles, and these two intrafollicular factors play essential roles in regulating follicle development and luteal function. As BMP antagonists, gremlin1 (GREM1) and gremlin2 (GREM2) suppress BMP signaling through blockage of ligand-receptor binding. However, whether BMP2 regulates the expression of GREM1 and GREM2 in follicular development remains to be determined. Methods In the present study, we investigated the effect of BMP2 on the expression of GREM1 and GREM2 and the underlying mechanisms in human granulosa-lutein (hGL) cells. An established immortalized human granulosa cell line (SVOG) and primary hGL cells were used as study models. The expression of GREM1 and GREM2 were examined following cell incubation with BMP2 at different concentrations and time courses. The TGF-β type I inhibitors (dorsomorphin, DMH-1 and SB431542) and small interfering RNAs targeting ALK2, ALK3, SMAD2/3, SMAD1/5/8 and SMAD4 were used to investigate the involvement of the SMAD-dependent pathway. Results Our results showed that BMP2 significantly increased the expression of GREM2 (but not GREM1) in a dose- and time-dependent manner. Using a dual inhibition approach combining kinase inhibitors and siRNA-mediated knockdown, we found that the BMP2-induced upregulation of GREM2 expression was mediated by the ALK2/3-SMAD1/5-SMAD4 signaling pathway. Moreover, we demonstrated that BMP2 pretreatment significantly attenuated the GDF8-induced phosphorylation of SMAD2 and SMAD3, and this suppressive effect was reversed by knocking down GREM2 expression. Conclusions Our findings provide new insight into the molecular mechanisms by which BMP2 modulates the cellular activity induced by GDF8 through the upregulated expression of their antagonist (GREM2).Medicine, Faculty ofNon UBCObstetrics and Gynaecology, Department ofReviewedFacultyResearche