Adsorption behavior of O2 on U-Nb surface: a first-principles study.

CONTEXT: Oxygen is a chemically active gas. Metal uranium will be rapidly oxidized when exposed to oxygen directly, forming a complex and uncompacted oxide layer on the surface. The U-O2 reaction system is a very complex metal oxidation system. The surface oxidation reaction of uranium-niobium alloy is more complex, and it is also the main corrosion form of uranium-niobium alloy. Exploring the microscopic mechanism of surface oxidation corrosion of uranium-niobium alloy is of great significance for understanding the surface corrosion phenomenon in practical applications. The adsorption of O2 on U-Nb (5at.%) surface was investigated by first-principles calculation using a periodic slab model within the density functional theory (DFT). The effect of different levels of Nb doping on O adsorption was investigated, and the stability of O-U and O-Nb adsorption was studied in conjunction with the Bader charge distribution, differential charge density map, electron density of states, and surface work function. The results showed that physical adsorption happens when O2 is vertically adsorbed at the top site of Nb atom, whereas dissociative adsorption happened in all other configurations considered here. The interaction between adsorbed O2 and U-Nb surface was essentially the hybridization between the O/2p orbital electrons and the U/6d, U/5f, Nb/4p, Nb/5s, and Nb/4d orbital electrons to form a relatively stable ionic bond. When Nb was doped into the second layer of the surface, the most stable O2 adsorption configuration was top-site horizontal adsorption. The adsorption energy was - 22.38 eV, which was more negative than the adsorption energy of - 21.38 eV for the first doped layer horizontal adsorption at hollow-site. The interaction was essentially the hybridization between O/2p orbital electrons and U/6d and U/5f electrons and between O/2s orbital electrons and U/6p orbital electrons to form a relatively stable ionic bond. METHOD: In this paper, the adsorption and dissociation of oxygen molecules on the surface of U-Nb system were systematically studied by first-principles calculations, in order to explore the surface oxidation corrosion mechanism of uranium-niobium alloy from the micro level. The VASP program uses PAW pseudopotential, which belongs to the density functional method, and uses DSP.

Black mulberry (Morus nigra) fruit extract alleviated AD-Like symptoms induced by toxic Aß protein in transgenic Caenorhabditis elegans via insulin DAF-16 signaling pathway.

Alzheimer's disease (AD) is one of the most severe neurodegenerative disorders. Recently, there is no effective treatment drug for AD. Morus nigra (M. nigra) is a black mulberry and widely distributed fruit in the Moraceae family with various undiscovered biological activities. The study aimed to investigate the potential anti-AD effect of M. nigra. Mulberry fruit extract (MF) was obtained from M. nigra and treated up to 1.00 mg/mL on transgenic AD Caenorhabditis elegans (C. elegans) models. MF inhibited Amyloid-ß (Aß)-induced paralysis symptoms by about 55.65 %, reduced Aß accumulation more than 50 % via immunoblotting, and suppressed over-sensitivity to exogenous serotonin in C. elegans. Furthermore, MF decreased the Aß oligomeric depositions in worm CL2006. MF activated the DAF-16 nuclear translocation and its downstream SOD-3 and GST-4. AD is a major age-related disorder. Therefore, MF treated for an aging test and proved to be expanded the lifespan of the worms up to 34.7 %. Besides, we have evaluated the MF in vivo antioxidative properties, where MF reduced reactive oxygen species (ROS) generations in C. elegans and remitted the activation of HSP-16.2 induced by the oxidative action of Juglone. Gene knockout and extended the lifespan of AD worms. However, RNA interference (RNAi) successfully silenced the daf-16 on the Aß phenotypic paralysis proved by MF effect. Our results indicate that MF alleviates AD-Like symptoms by activating the DAF-16 insulin signal pathway in C. elegans. Therefore, this MF study may provide new insights for mulberry application in safe AD treatment and clinical study.

Autophagy activation by Terminalia chebula Retz. reduce Aß generation by shifting APP processing toward non-amyloidogenic pathway in APPswe transgenic SH-SY5Y cells.

BACKGROUND: Alzheimer's disease (AD) is the most common neurodegenerative disease. Deposition of amyloid ß plaques (Aß) is a central hallmark of AD. Accumulating evidence suggest that shifting amyloid precursor protein (APP) metabolism pathway to non-amyloidogenic ways and inducing autophagy play key roles in AD pathology. In published reports, there is no research on the APP metabolic process of Terminalia chebula Retz. (T. Chebula). PURPOSE: The study aims to assess the effects of T. Chebula in AD transgenic SH-SY5Y cells to determine its underlying mechanisms on reducing Aß level by regulating APP metabolic process. METHODS: The effects of T. Chebula water extract (TWE) on APPswe transgenic SH-SY5Y cells were analyzed by cell viability. ELISA used to quantify extracellular Aß1-40 and Aß1-42 generations. Western blot and RT-PCR assays were chosen to detect the expression of proteins and genes. The acridine orange (AO) stain was used to label autophagic-vesicles. RESULTS: Treatment with TWE significantly suppressed the Aß1-40 and Aß1-42 generations of APPswe transgenic cells. TWE inhibited amyloidogenic pathway by reducing BACE1 expression, and promote non-amyloidogenic pathway by inducing ADAM10 level of APP metabolism. Additionally, TWE induced autophagy in APPswe transgenic cells involved in APP metabolism to shift the balance to non-amyloidogenic pathway. CONCLUSION: In summary, our finding first time expounded that TWE can inhibit the generation of Aß1-40 and Aß1-42 in APPswe transgenic SH-SY5Y cells, which were regulated APP metabolism tends to non-amyloid metabolism pathway and mediated by autophagy. The results presented a novel finding for AD treatment of traditional natural medicines.

Anti-α-synuclein Toxicity and Anti-neurodegenerative Role of Chrysin in Transgenic Caenorhabditis elegans Models of Parkinson's Disease.

Parkinson's disease (PD) is the second most progressive neurodegenerative disorder of the central nervous system in the elderly, causing motor impediments and cognitive dysfunctions. Dopaminergic (DA) neuron degeneration and α-synuclein (α-Syn) accumulation in substantia nigra pars compacta are the major contributors to this disease. At present, PD remains untreatable with a huge burden on the quality of life. Therefore, we attempt to explore novel treatment strategies by detecting effective drugs that stop or arrest PD's progression via modifying disease-specific pathways. Chrysin is a flavonoid derived from passion flowers and possesses anti-cancer, anti-inflammatory, anti-oxidant, and anti-depression properties. In the present study, we assessed the neuroprotective potential of chrysin in transgenic Caenorhabditis elegans models of PD. We observed that chrysin reduced the aggregative toxicity of α-Syn and diminished DA neuron degeneration induced by 6-hydroxydopamine (6-OHDA), reduced food-sensing behavioral disabilities, and expanded the nematodes' lifespan. Moreover, chrysin augmented the ubiquitin-like proteasome and superoxide dismutase activities in transgenic C. elegans models. Further, we observed the anti-oxidative role of chrysin by reducing the internal cellular reactive oxygen species levels in 6-OHDA-intoxicated C. elegans. Together, these findings supported chrysin as a possible treatment for PD and encouraged further investigation of chrysin's mechanism of action as a neuroprotective medicine in the future.

Ursolic acid ameliorates amyloid ß-induced pathological symptoms in Caenorhabditis elegans by activating the proteasome.

BACKGROUND: Amyloid ß induces pathological symptoms in various neurodegenerative disorders. It is the hallmark of these neurodegenerative disorders, such as Alzheimer's disease, and is reported to induce neurotoxicity leading to neuronal impairment. The continuous development of neurodegenerative disease accompanies pathological changes in amyloid ß deposition in the brain. After amyloid ß accumulates, the inadequate clearance of amyloid ß further accelerates the development of events in the pathological cascade. In eukaryotes, the proteasome is responsible for the degradation of misfolded and damaged proteins to maintain proteostasis. Therefore, screening candidates that preserve proteasomal activity may promote amyloid ß homeostasis, which is expected to provide new therapeutic opportunities for these neurodegenerative diseases. Ursolic acid, a natural triterpenoid, has prominent pharmacological antioxidant, anti-inflammatory, neuroprotective, and nontoxic activities. Here, we explored the protective effects of ursolic acid on amyloid ß-induced pathological symptoms. METHODS: This study investigated the therapeutic potential of ursolic acid and its underlying molecular mechanisms using a Caenorhabditis elegans transgenic pathological model. RESULTS: In our study, ursolic acid successfully repressed amyloid ß-induced paralysis and hypersensitivity to serotonin in Caenorhabditis elegans. The levels of amyloid ß monomers, oligomers, and deposits were decreased after treatment with ursolic acid in transgenic nematodes overexpressing human amyloid ß; however, ursolic acid did not affect exogenous transgene transcription and expression levels. Ursolic acid transcriptionally enhanced the ubiquitin-proteasome system and augmented proteasome activity in vivo. However, the proteasome inhibitor MG132 abolished the therapeutic effect of ursolic acid on behavioral paralysis, and Parkinson's disease-related-1 was required for the therapeutic effect of ursolic acid. CONCLUSIONS: Our study revealed that ursolic acid prevented amyloid ß-induced proteotoxic stress, specifically by reducing the amount of amyloid ß and increasing proteasome activity in vivo. Furthermore, the therapeutic effect of ursolic acid on transgenic nematodes expressing amyloid ß depended on the increased activity of the proteasome. This work provides an essential supplement to the information on the pharmacological mechanism of ursolic acid.

Antioxidative role of Traditional Chinese Medicine in Parkinson's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Neuroprotective Traditional Chinese Medicine (TCM) has been practiced in alternative medicine from early days. TCM-derived neuroprotective compounds, such as Chrysin, Cannabidiol, Toonasinoids, and ß-asaron, exert significant effectiveness's towards Parkinson's disease (PD). Further, these neuroprotective TCM showed antioxidative, anti-inflammatory, anti-tumor, anti-septic, analgesic properties. Recent research showed that the reduction in the reactive oxygen species (ROS) decreased the α-synuclein (α-syn) toxicity and enhanced the dopaminergic neuron regenerations, the main hallmarks of PD. Therefore, the neuroprotective effects of novel TCM due to its antiradical activities needed deep investigations. AIMS OF THE STUDY: This review aims to enlighten the neuroprotective TCM and its components with their antioxidative properties to the scientific community for future research. METHOD: The relevant information on the neuroprotective TCM was gathered from scientific databases (PubMed, Web of Science, Google Scholar, ScienceDirect, SciFinder, Wiley Online Library, ACS Publications, and CNKI). Information was also gained from MS and Ph.D. thesis, books, and online databases. The literature cited in this review dates from 2001 to June 2, 0201. RESULTS: Novel therapies for PD are accessible, mostly rely on Rivastigmine and Donepezil, offers to slow down the progression of disease at an early stage but embraces lots of disadvantages. Researchers are trying to find a potential drug against PD, which is proficient at preventing or curing the disease progress, but still needed to be further identified. Oxidative insult and mitochondrial dysfunction are thought to be the main culprit of neurodegenerations. Reactive oxygen species (ROS) are the only causative agent in all interactions, leading to PD, from mitochondrial dysfunctions, α-syn aggregative toxicity, and DA neurons degenerations. It is evident from the redox balance, which seems an imperative therapeutic approach against PD and was necessary for the significant neuronal activities. CONCLUSION: Our study is explaining the newly discovered TCM and their neuroprotective and antioxidative properties. But also bring up the possible treatment approaches against PD for future researchers.

miR-21 regulates osteogenic and adipogenic differentiation of BMSCs by targeting PTEN.

OBJECTIVE: To explore the effects and mechanism of miR-21 on the osteogenic/adipogenic differentiation of mouse BMSCs. METHODS: The bilateral ovaries of C57BL/6J mice (n=24) were removed to construct an osteoporosis model. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-21, osteogenic/adipogenic genes, and PTEN. ALP and ARS and ORO staining were used to detect the formation of calcium nodules and lipid droplets in BMSCs. Western blot was used to detect the expression of PTEN. RESULTS: miR-21 was significantly down-regulated in osteoporotic mice. The expression of miR-21 was significantly up-regulated after the osteogenic induction of BMSCs, and the expression of miR-21 was significantly down-regulated after the adipogenic induction. Overexpression of miR-21 significantly promoted the osteogenic differentiation of BMSCs and inhibits the adipogenic differentiation of BMSCs. CONCLUSION: MiR-21 can promote osteogenic differentiation of BMSCs and inhibit their adipogenic differentiation by negatively regulating PTEN.

Altered Cerebellar Resting-State Functional Connectivity in Early-Stage Parkinson's Disease Patients With Cognitive Impairment.

Background: Cognitive impairment is one of the most prominent non-motor symptoms in Parkinson's disease (PD), due in part to known cerebellar dysfunctions. Furthermore, previous studies have reported altered cerebellar functional connectivity (FC) in PD patients. Yet whether these changes are also due to the cognitive deficits in PD remain unclear. Methods: A total of 122 non-dementia participants, including 64 patients with early PD and 58 age- and gender-matched elderly controls were stratified into four groups based on their cognitive status (normal cognition vs. cognitive impairment). Cerebellar volumetry and FC were investigated by analyzing, respectively, structural and resting-state functional MRI data among groups using quality control and quantitative measures. Correlation analysis between MRI metrics and clinical features (motor and cognitive scores) were performed. Results: Compared to healthy control subjects with no cognitive deficits, altered cerebellar FC were observed in early PD participants with both motor and cognitive deficits, but not in PD patients with normal cognition, nor elderly subjects showing signs of a cognitive impairment. Moreover, connectivity between the "motor" cerebellum and SMA was positively correlated with motor scores, while intracerebellar connectivity was positively correlated with cognitive scores in PD patients with cognitive impairment. No cerebellar volumetric difference was observed between groups. Conclusions: These findings show that altered cerebellar FC during resting state in early PD patients may be driven not solely by the motor deficits, but by cognitive deficits as well, hence highlighting the interplay between motor and cognitive functioning, and possibly reflecting compensatory mechanisms, in the early PD.

Association of Posture Instability with Dopamine Drop of Nigrostriatal System and Hypometabolism of Cerebral Cortex in Parkinson's Disease.

BACKGROUND: Posture Instability (PI) is known to be a severe complication in Parkinson's Disease (PD), and its mechanism remains poorly understood. Our study aims to explore the changes of brain network in PI of PD, and further investigate the role of peripheral inflammation on activities of different brain regions in PD with PI. METHODS: 167 individuals were recruited, including 36 PD cases with PI and 131 ones without PI. We carefully assessed the status of motor and cognitive function, measured serum inflammatory factors, and detected the dopaminergic pathways and the metabolism of different brain regions by Positron Emission Tomography (PET). Data analysis was conducted by variance, univariate analysis, chi-square analysis, logistic regression, and partial correlation. RESULTS: No difference was found for age or onset age between the two groups (P>0.05). Female patients were susceptible to posture impairment and had a 2.14-fold risk for PI compared with male patients in PD (P<0.05). Patients with PI had more severe impairment of motor and cognitive function for a longer duration than those without PI (P<0.05). The mean uptake ratios of presynaptic vesicular monoamine transporter (VMAT2), which were detected in the caudate nucleus and putamen, were lower in PI group than those without PI (P<0.05). There were lower activities of the midbrain, caudate nucleus, and anterior medial temporal cortex in PI group than those in the non-PI group (P<0.05). Although serum concentrations of immunoglobulins (IgG, IgM, and IgA) and complements (C3, C4) were higher in the PI group than those in the non-PI group, only serum IgM concentration had a significant difference between the two groups (P<0.05). We further explored significant inverse correlations of IgG, IgM, IgA, and C4 with activities of some cerebral cortex in PI of PD (P<0.05). CONCLUSION: Female patients were susceptible to posture instability and had a 2.14-fold risk for PI of PD. Patients with PI had more severe impairments of motor and cognitive function for a longer duration than those without PI. PI was associated with a dopamine drop of the nigrostriatal system and lower activities of the limbic cortex in PD. Peripheral inflammation may be involved in degeneration of the cerebral cortex in PD combined with PI.

Detection of Motor Dysfunction With Wearable Sensors in Patients With Idiopathic Rapid Eye Movement Disorder.

Patients with idiopathic rapid eye movement sleep behavior disorder (iRBD) are at high risk for conversion to synucleinopathy and Parkinson disease (PD). This can potentially be monitored by measuring gait characteristics of iRBD patients, although quantitative data are scarce and previous studies have reported inconsistent findings. This study investigated subclinical gait changes in polysomnography-proven iRBD patients compared to healthy controls (HCs) during 3 different walking conditions using wearable motor sensors in order to determine whether gait changes can be detected in iRBD patients that could reflect early symptoms of movement disorder. A total 31 iRBD patients and 20 HCs were asked to walk in a 10-m corridor at their usual pace, their fastest pace, and a normal pace while performing an arithmetic operation (dual-task condition) for 1 min each while using a wearable gait analysis system. General gait measurements including stride length, stride velocity, stride time, gait length asymmetry, and gait variability did not differ between iRBD patients and HCs; however, the patients showed decreases in range of motion (P = 0.004) and peak angular velocity of the trunk (P = 0.001) that were significant in all 3 walking conditions. iRBD patients also had a longer step time before turning compared to HCs (P = 0.035), and the difference between groups remained significant after adjusting for age, sex, and height. The decreased trunk motion while walking and increased step time before turning observed in iRBD may be early manifestations of body rigidity and freezing of gait and are possible prodromal symptoms of PD.

A 36-week multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 3 clinical trial of sodium oligomannate for mild-to-moderate Alzheimer's dementia.

BACKGROUND: New therapies are urgently needed for Alzheimer's disease (AD). Sodium oligomannate (GV-971) is a marine-derived oligosaccharide with a novel proposed mechanism of action. The first phase 3 clinical trial of GV-971 has been completed in China. METHODS: We conducted a phase 3, double-blind, placebo-controlled trial in participants with mild-to-moderate AD to assess GV-971 efficacy and safety. Participants were randomized to placebo or GV-971 (900 mg) for 36 weeks. The primary outcome was the drug-placebo difference in change from baseline on the 12-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog12). Secondary endpoints were drug-placebo differences on the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC+), Alzheimer's Disease Cooperative Study-Activities of Daily Living (ADCS-ADL) scale, and Neuropsychiatric Inventory (NPI). Safety and tolerability were monitored. RESULTS: A total of 818 participants were randomized: 408 to GV-971 and 410 to placebo. A significant drug-placebo difference on the ADAS-Cog12 favoring GV-971 was present at each measurement time point, measurable at the week 4 visit and continuing throughout the trial. The difference between the groups in change from baseline was - 2.15 points (95% confidence interval, - 3.07 to - 1.23; p < 0.0001; effect size 0.531) after 36 weeks of treatment. Treatment-emergent adverse event incidence was comparable between active treatment and placebo (73.9%, 75.4%). Two deaths determined to be unrelated to drug effects occurred in the GV-971 group. CONCLUSIONS: GV-971 demonstrated significant efficacy in improving cognition with sustained improvement across all observation periods of a 36-week trial. GV-971 was safe and well-tolerated. TRIAL REGISTRATION: ClinicalTrials.gov, NCT0229391 5. Registered on November 19, 2014.

Customized Incubation Services and Growth of Tenants: The Mediating Effect of Behavior Orientation of Social Networking Services.

The third-generation incubator is generally characterized by embedment of social networking and customized incubation services are closely embedded in the social networking. How the social networking play their role in the process that customized incubation services facilitate the growth of tenant? In order to disclose whether social networking services (SNS) mediate the impact of customized incubation services on the growth of tenants, this article focuses on the whole process where customized services facilitate the growth of tenants by means of social networking services. First, it employs situational theory and contingency theory to analysis why customized services result in behavior of social networking services; second, it explores why behavior of social networking services facilitates the growth of tenants based on co-production theory and social network theory; next, it conduct a study on the direct relationship between customized services and growth of tenants anchoring on the theory of co-production, customer satisfaction, and dynamic environment. Based on these theories, it develops the overall theoretical model of mediating effect. Following that, it conducts empirical test: it has first ascertained whether there is a positive relationship between customized services and growth of tenants. Then, three paths of the theoretical model have been measured by means of the structural model. At the same time, the t-test and the Sobel test are employed to justify their significance. If we only contemplate customized incubation services and growth of tenants, they are positively correlative. On the other hand, if referring to the role of social networking services in this process, we disclosed that not only customized incubation services positively impact behavior of social networking services, but also behavior of social networking services positively facilitates the growth of tenants; at the same time, the customized incubation services exhibit no direct impact on the growth of tenants otherwise. It witnesses that the behavior of social networking services fully mediates the relationship between customized services and the growth of tenants. As a result, we should promote incubation services to be deeply embedded in social networking services; incubator management should even improve the capability to deal with big data embedded in social networking services. In additional, entrepreneurial ecosystems should be also embedded in social networks intensively.

Effects of Top Management Team Characteristics on Patent Strategic Change and Firm Performance.

Patent strategy is increasingly recognized as a vital contributor in promoting core competitiveness of an enterprise. A top management team (TMT) has been indicated as one of the key factors driving changes in patent strategy. Based on upper echelons theory, this study examines how TMT characteristics, including, team diversity, emotional intelligence, and safety climate, influence enterprise patent strategic change and, hence, the business outcome. The data from 930 top managers in 228 enterprises showed that the changes in patent strategies are significantly influenced by the characteristics of top managers. These aforementioned internal TMT factors have diverse effects on the speed and scope of the enterprise patent strategic change, which in turn affects firm performance in a positive and negative way, respectively.

Ferulic acid delayed amyloid ß-induced pathological symptoms by autophagy pathway via a fasting-like effect in Caenorhabditis elegans.

The amyloid ß (Aß) generation or aggregation plays a crucial role in Alzheimer's disease (AD). Autophagy agonists, which function as the clearance of Aß, could be the potential drug candidates against AD. In staple food crops, ferulic acid (FA) is an enormously copious and almost ubiquitous phenolic antioxidant. In the present study, FA significantly inhibited Aß-induced pathological symptoms of paralysis and hypersensitivity to exogenous serotonin, meanwhile restrained Aß monomers, oligomers, and deposits in AD C. elegans. FA increased the expression of autophagy reporter LGG-1 and enhanced autophagy flux. However, the autophagy inhibitors abolished the restrictive action of FA on the worm paralysis phenotype. According to these results, FA triggered autophagy and ameliorated Aß-induced pathological symptoms by the autophagy pathway. Moreover, FA activated the HLH-30 transcription factor to nuclear localization, which acts upstream of autophagy in fasted animals, reduced the level of lipids, but affected nor the growth of E. coli OP50, neither animal food intake behavior. These suggest that FA induced a fasting-like effect to activate the autophagy pathway. Additionally, FA ameliorated poly Q aggregations in Huntington's disease worm. Thus, FA could not only affect AD, broadly but also neurodegenerative diseases characterized by misfolded or aggregated proteins.

Risk Factors and Metabolism of Different Brain Regions by Positron Emission Tomography in Parkinson Disease with Disabling Dyskinesia.

OBJECTIVE: Dyskinesia is the most common motor complication in advanced Parkinson's Disease (PD) and has a severe impact on daily life. But the mechanism of dyskinesia is still poorly understood. This study aims to explore risk factors for disabling dyskinesia in PD and further analyze the Vesicular Monoamine Transporter 2 (VMAT2) distribution (labeled with 18F-AV133) in the corpus striatum and the 18F-fluorodeoxyglucose (18F-FDG) metabolism of different brain regions by PET-CT. METHODS: This is a cross-sectional study involving 135 PD patients. They were divided into disabling dyskinesia group (DD group, N=22) and non-dyskinesia group (ND group, N=113). All the patients were agreed to undergo PET-CT scans. Clinical data were analyzed between two groups by using multivariate logistic regression analysis, and risk factors for disabling dyskinesia were then determined. The standard uptake value ratios (SUVr) of 18F-AV133 in the corpus striatum and the 18F-FDG metabolism of different brain regions were identified and calculated by the software. RESULTS: 16.3% patients have disabling dyskinesia. DD group were more likely to have longer Disease Duration, higher Hoehn-Yahr degree, more severe clinic symptoms, more frequent sleep behavior disorder, and higher levodopa dose equivalency than ND group (P < 0.05). After adjusting confounding factors by multivariate logistic regression, DD group had longer PD duration and high levodopa dose equivalency compared with ND group (P < 0.05). There is no significant difference between the VMAT2 distribution (labeled with 18F- AV133) in the putamen and caudate between two groups. And the 18F-FDG metabolic changes in cortical and subcortical regions did not show a significant difference between the two groups either (P > 0.05). CONCLUSION: Long PD duration and high levodopa dose equivalency were two independent risk factors for disabling dyskinesia in PD patients. Compared to non-dyskinesia PD patients, there was no significant dopamine decline of the nigrostriatal system in disabling dyskinesia PD patients. Activities of different brain regions were not different between the two groups by 18F-FDG PETCT.

Impaired Fine Motor Function of the Asymptomatic Hand in Unilateral Parkinson's Disease.

The early detection of Parkinson's disease (PD) still remains a challenge to date. Although studies have previously reported subtle motor function abnormalities in early PD patients, it is unclear whether such clinical signs can be better detected while patients are concurrently performing a cognitive task, and whether they can be useful in predicting patients' clinical conversion state. Seventy-two right-handed participants (40 drug-naive patients with idiopathic unilateral PD and 32 age-matched healthy controls) were enrolled in this study. All participants were asked to perform the Purdue Pegboard test (PPT) either alone (single-task condition) or during a concurrent mental subtraction-by-3 task (dual-task condition). A 4-year telephone follow-up was later conducted to determine whether PD patients converted to bilateral signs. We found that PD patients showed a significant reduction in dexterity on the PPT compared to the controls in both single- and dual-task conditions. Yet patients' performance in the dual-task condition revealed a greater interference effect when patients performed the task with their right hand than with their left hand. PPT also revealed reasonable discriminative ability for prediagnosing PD. However, dual-tasking did not have added value in differentiating early patients and controls. At follow-up, the baseline PPT performance of the asymptomatic hands was positively correlated with time to convert from unilaterally to bilaterally affected states (r = 0.62, P = 0.031). Together, these findings suggest that PPT can serve as a useful auxiliary tool in evaluating early PD, and shed light on the neuroplasticity mechanism of fine motor deficit at this very early stage.

Dopaminergic pathway and primary visual cortex are involved in the freezing of gait in Parkinson's disease: a PET-CT study.

Background: Freezing of gait (FOG) could be partly alleviated by dopaminergic drugs but the mechanism still needs to be elucidated. The purpose of this study is to explore the mechanisms of FOG by vesicular monoamine transporter VMAT2 distribution with the 18F-AV133 tracer and 18-fludeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT). Methods: Clinical material and PET-CT data were collected from 20 patients with FOG and 147 patients without FOG from November 1, 2017 to October 31, 2018. Brain scans of all participants were acquired over an approximately 20-min period, 120 min after injection of approximately 250 MBq 18F-AV133. The mean uptake ratios of different regions were identified by NeuroQ software of 18F-FDG PET-CT. Data analysis included variance, chi-square analysis, covariance analysis, and logistic regression. Results: Our data showed that patients with FOG were provided with greater doses of dopaminergic drugs (p<0.05). The frequency of FOG was 11.98% and increased as Parkinson's disease progressed. FOG was more common in the elderly and strongly associated with the duration. Cognitive impairments were obvious, assessed by Mini-Mental State Examination and Montreal Cognitive Assessment (p<0.05). The VMAT2 distribution with 18F-AV133 was decreased significantly in the caudate nucleus and lentiform nucleus while the metabolism of these areas was elevated, determined by 18F-FDG PET-CT (p<0.05). The metabolism of the primary visual cortex decreased obviously in patients with FOG compared with those without FOG (p<0.05). Conclusion: FOG mainly occurred in the advanced stage, and was strongly associated with the duration and larger dose of dopaminergic drugs. The dopamine level of the nigrostriatal system decreased significantly and the uptake ratios of the primary visual cortex dropped obviously in the FOG group compared with the non-FOG group. Our study suggests that both the dopaminergic pathway and the primary visual cortex are involved in the pathogenesis of FOG.

Visual dysfunction in patients with idiopathic rapid eye movement sleep behavior disorder.

OBJECTIVE: Visual dysfunction is a common feature in α-synucleiopathies but rarely assessed in patients with idiopathic rapid eye movement sleep behavior disorder (iRBD). The current study is set to investigate the comprehensive visual function in iRBD as compared to patients of Parkinson's disease (PD) with RBD. METHODS: Eighty-three iRBD subjects diagnosed with polysomnograph (PSG), 52 early PD patients (Hoehn-Yahr stages<3) with RBD symptom prior to onset of motor symptoms and 79 healthy controls without RBD diagnosed based on RBD Questionnaire-Hong Kong (RBDQ-HK) were enrolled in this study. Visual function including color discrimination, stereopsis function, visual illusion (VI) or hallucination (VH) were assessed in addition to UPDRS, Purdue Pegboard test (PPT) and cognitive tests. RESULTS: Abnormal color discrimination and stereopsis were presented significantly higher in both iRBD and PD patients as compared to controls and more severe in PD than in iRBD. Color discrimination was decreased in all four color in PD patients but not green color in iRBD subjects. Stereopsis test was abnormal in both iRBD and PD, but the proportion of subjects with abnormal stereopsis was significantly higher in PD patients (69.6% vs 42%). Similar number of subjects with iRBD and PD were presented with illusion but only PD patients reported more hallucination. Changes of visual function were associated with age and cognition in both iRBD and PD subjects but was also affected independently by disease duration and clinical stage or fine motor function in PD. In addition, decreased fine motor function demonstrated by PPT was also observed in some iRBD subjects. CONCLUSION: Our results demonstrated comprehensively that visual dysfunction was present in iRBD subjects similar but in a less degree of severity to PD patients, and associated with age, cognition and motor deficit. Whether or not it can be useful in predicting iRBD conversion to PD warrants further investigation.

Constipation Increases Disability and Decreases Dopamine Levels in the Nigrostriatal System through Gastric Inflammatory Factors in Parkinson's Disease.

OBJECTIVE: Recent studies suggest that not only is constipation a clinical marker of premotor phase in Parkinson's Disease (PD), but is also correlated with the duration and severity. Some reports indicated that inflammatory from gut dysbiosis might be involved in the pathogenesis of PD, but the correlation between them remains poorly understood. This study aims to investigate how the presence of constipation affects the dopamine level of nigrostriatal system and whether gastrointestinal (GI) inflammation is involved in the brain-gut axis. METHODS: Clinical materials, serum inflammatory factors, and datum of dopamine level including 84 cases and 83 controls, were collected consecutively and randomly from November 1, 2017 to October 31, 2018. Dopamine levels of nigrostriatal system were detected by [18F]-DTBZ radiotracer (18F-AV-133). Data analysis was conducted by variance, covariance analysis, bicorrelation, partial correlation, chi-square analysis and logistic regression. RESULTS: The mean age of cases was older than that of controls, and male predominance was also observed (P<0.05). The mean scores of Hoehn-Yahr and unified Parkinson's disease rating scale Ⅲ (UPDRS-Ⅲ) were of significantly different duration between two groups (P<0.05). The total dose of levodopa was not different between two groups (P>0.05). The dopamine levels of putamen and caudate nucleus, especially in the dorsal part of putamen, were significantly decreased in cases than that in controls (P<0.05). There were significant differences of complement 3 (C3) and complement 4 (C4) between cases and controls (P<0.05). Dopamine levels in putamen and caudate nucleus were negatively correlated with serum concentrations of immunoglobulin A (IgA), immunoglobulin G (IgG) and C3 in cases (P<0.05). But we did not observe similar negative correlations in controls (P>0.05). CONCLUSION: The presence of constipation may increase the severity of motor symptoms and decrease dopamine levels of nigrostriatal system in PD. Inflammatory factors may be involved in the brain-gut axis of PD.