Displaying publications 81 - 100 of 169 in total

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  1. Fulltext Analysis of non-synonymous-coding variants of Parkinson's disease-related pathogenic and susceptibility genes in East Asian populations
    Foo JN, Tan LC, Liany H, Koh TH, Irwan ID, Ng YY, et al.
    Hum Mol Genet, 2014 Jul 15;23(14):3891-7.
    PMID: 24565865 DOI: 10.1093/hmg/ddu086
    To evaluate the contribution of non-synonymous-coding variants of known familial and genome-wide association studies (GWAS)-linked genes for Parkinson's disease (PD) to PD risk in the East Asian population, we sequenced all the coding exons of 39 PD-related disease genes and evaluated the accumulation of rare non-synonymous-coding variants in 375 early-onset PD cases and 399 controls. We also genotyped 782 non-synonymous-coding variants of these genes in 710 late-onset PD cases and 9046 population controls. Significant enrichment of LRRK2 variants was observed in both early- and late-onset PD (odds ratio = 1.58; 95% confidence interval = 1.29-1.93; P = 8.05 × 10(-6)). Moderate enrichment was also observed in FGF20, MCCC1, GBA and ITGA8. Half of the rare variants anticipated to cause loss of function of these genes were present in healthy controls. Overall, non-synonymous-coding variants of known familial and GWAS-linked genes appear to make a limited contribution to PD risk, suggesting that clinical sequencing of these genes will provide limited information for risk prediction and molecular diagnosis.
    Matched MeSH terms: Parkinson Disease/genetics*
  2. Inter-hemispheric EEG coherence analysis in Parkinson's disease: assessing brain activity during emotion processing
    Yuvaraj R, Murugappan M, Ibrahim NM, Sundaraj K, Omar MI, Mohamad K, et al.
    J Neural Transm (Vienna), 2015 Feb;122(2):237-52.
    PMID: 24894699 DOI: 10.1007/s00702-014-1249-4
    Parkinson's disease (PD) is not only characterized by its prominent motor symptoms but also associated with disturbances in cognitive and emotional functioning. The objective of the present study was to investigate the influence of emotion processing on inter-hemispheric electroencephalography (EEG) coherence in PD. Multimodal emotional stimuli (happiness, sadness, fear, anger, surprise, and disgust) were presented to 20 PD patients and 30 age-, education level-, and gender-matched healthy controls (HC) while EEG was recorded. Inter-hemispheric coherence was computed from seven homologous EEG electrode pairs (AF3-AF4, F7-F8, F3-F4, FC5-FC6, T7-T8, P7-P8, and O1-O2) for delta, theta, alpha, beta, and gamma frequency bands. In addition, subjective ratings were obtained for a representative of emotional stimuli. Interhemispherically, PD patients showed significantly lower coherence in theta, alpha, beta, and gamma frequency bands than HC during emotion processing. No significant changes were found in the delta frequency band coherence. We also found that PD patients were more impaired in recognizing negative emotions (sadness, fear, anger, and disgust) than relatively positive emotions (happiness and surprise). Behaviorally, PD patients did not show impairment in emotion recognition as measured by subjective ratings. These findings suggest that PD patients may have an impairment of inter-hemispheric functional connectivity (i.e., a decline in cortical connectivity) during emotion processing. This study may increase the awareness of EEG emotional response studies in clinical practice to uncover potential neurophysiologic abnormalities.
    Matched MeSH terms: Parkinson Disease/pathology*
  3. Molecular diagnosis using multi drug delivery network and stability
    Jalil MA, Innate K, Suwanpayak N, Yupapin PP, Ali J
    Artif Cells Blood Substit Immobil Biotechnol, 2011 Dec;39(6):357-65.
    PMID: 21999106 DOI: 10.3109/10731199.2011.618134
    By using a pair of tweezers to generate the intense optical vortices within the PANDA ring resonator, the required molecules (drug volumes) can be trapped and moved dynamically within the molecular bus networks, in which the required diagnosis or drug delivery targets can be performed within the network. The advantage of the proposed system is that the proposed diagnostic method can perform within the tiny system (thin film device or circuit), which can be available for a human embedded device for diagnostic use. The channel spacing of the trapped volumes (molecules) within the bus molecular networks can be provided.
    Matched MeSH terms: Parkinson Disease/diagnosis
  4. Sleep disturbances in Malaysian patients with Parkinson's disease using polysomnography and PDSS
    Norlinah MI, Afidah KN, Noradina AT, Shamsul AS, Hamidon BB, Sahathevan R, et al.
    Parkinsonism Relat Disord, 2009 Nov;15(9):670-4.
    PMID: 19362875 DOI: 10.1016/j.parkreldis.2009.02.012
    Sleep disturbances such as sleep fragmentation, sleep disordered breathing (SDB), periodic limb movements (PLM), excessive daytime somnolence (EDS) and insomnia are prevalent in Parkinson's disease (PD). However, studies in the Asian population are limited.
    Matched MeSH terms: Parkinson Disease/complications*
  5. Determination of the longitudinal validity and minimally important difference of the 8-item Parkinson's Disease Questionnaire (PDQ-8)
    Luo N, Tan LC, Zhao Y, Lau PN, Au WL, Li SC
    Mov Disord, 2009 Jan 30;24(2):183-7.
    PMID: 18972545 DOI: 10.1002/mds.22240
    The aim of our study was to assess the longitudinal validity of the 8-item Parkinson's Disease Questionnaire (PDQ-8) in terms of responsiveness and test-retest reliability and to determine the minimally important difference (MID) for PDQ-8 using the anchor-based approach in Asians with Parkinson's disease (PD). A consecutive sample of PD patients attending a tertiary neuroscience clinic in Singapore completed the English or Chinese version of PDQ-8 twice during two different clinic visits. During the second visit, patients were also asked to rate their changes in health in general, PD severity, and overall impact of PD since at the time of their first visit 1 year ago using a 5-point response scale. A total of 96 patients participated in the study. For patients who reported changed conditions in the second visit, responsiveness measured by Cohen's effect size, standardized response mean, and Guyatt's responsiveness index ranged from 0.21 to 0.68. The intraclass correlation coefficient values calculated using patients reporting no change in health or PD status ranged from 0.64 to 0.76. The mean changed PDQ-8 summary index score in patients who reported that their health or PD status worsened only "a little bit" ranged from 5.8 to 7.4 points. Our current results show that PDQ-8 is a longitudinally reliable and responsive measure for assessing the health-related quality of life in patients with PD. The MID of the PDQ-8 estimated in the study will further support the use of this instrument in both clinical research and practice.
    Matched MeSH terms: Parkinson Disease/psychology*
  6. Fulltext Tubulin and Tau: Possible targets for diagnosis of Parkinson's and Alzheimer's diseases
    Salama M, Shalash A, Magdy A, Makar M, Roushdy T, Elbalkimy M, et al.
    PLoS One, 2018;13(5):e0196436.
    PMID: 29742117 DOI: 10.1371/journal.pone.0196436
    Neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD) are characterized by progressive neuronal loss and pathological accumulation of some proteins. Developing new biomarkers for both diseases is highly important for the early diagnosis and possible development of neuro-protective strategies. Serum antibodies (AIAs) against neuronal proteins are potential biomarkers for AD and PD that may be formed in response to their release into systemic circulation after brain damage. In the present study, two AIAs (tubulin and tau) were measured in sera of patients of PD and AD, compared to healthy controls. Results showed that both antibodies were elevated in patients with PD and AD compared to match controls. Curiously, the profile of elevation of antibodies was different in both diseases. In PD cases, tubulin and tau AIAs levels were similar. On the other hand, AD patients showed more elevation of tau AIAs compared to tubulin. Our current results suggested that AIAs panel could be able to identify cases with neuro-degeneration when compared with healthy subjects. More interestingly, it is possible to differentiate between PD and AD cases through identifying specific AIAs profile for each neurodegenerative states.
    Matched MeSH terms: Parkinson Disease/metabolism*
  7. Fulltext A systems biology approach towards the identification of candidate therapeutic genes and potential biomarkers for Parkinson's disease
    Sakharkar MK, Kashmir Singh SK, Rajamanickam K, Mohamed Essa M, Yang J, Chidambaram SB
    PLoS One, 2019;14(9):e0220995.
    PMID: 31487305 DOI: 10.1371/journal.pone.0220995
    Parkinson's disease (PD) is an irreversible and incurable multigenic neurodegenerative disorder. It involves progressive loss of mid brain dopaminergic neurons in the substantia nigra pars compacta (SN). We compared brain gene expression profiles with those from the peripheral blood cells of a separate sample of PD patients to identify disease-associated genes. Here, we demonstrate the use of gene expression profiling of brain and blood for detecting valid targets and identifying early PD biomarkers. Implementing this systematic approach, we discovered putative PD risk genes in brain, delineated biological processes and molecular functions that may be particularly disrupted in PD and also identified several putative PD biomarkers in blood. 20 of the differentially expressed genes in SN were also found to be differentially expressed in the blood. Further application of this methodology to other brain regions and neurological disorders should facilitate the discovery of highly reliable and reproducible candidate risk genes and biomarkers for PD. The identification of valid peripheral biomarkers for PD may ultimately facilitate early identification, intervention, and prevention efforts as well.
    Matched MeSH terms: Parkinson Disease/etiology*
  8. Method for Evaluating Neuromodulatory Properties of Dental Pulp Stem Cell as an In Vitro Model for Parkinson's Disease
    Gnanasegaran N, Thimiri Govinda Raj DB, Arumugam S
    Methods Mol Biol, 2020;2125:193-196.
    PMID: 31489601 DOI: 10.1007/7651_2019_261
    Several research groups have utilized dental pulp stem cells for numerous studies as treatment modality for Parkinson's disease (PD). However, the roles of dental pulp stem cells in governing the Parkinson's disease inflammatory microenvironment remain to be evaluated. In this article, we elaborate the method where we can investigate the effects of dental pulp stem cells on neurons and microglia in an in vitro inflammatory microenvironment.
    Matched MeSH terms: Parkinson Disease/pathology*
  9. Delivering patient-centered care in Parkinson's disease: Challenges and consensus from an international panel
    Bhidayasiri R, Panyakaew P, Trenkwalder C, Jeon B, Hattori N, Jagota P, et al.
    Parkinsonism Relat Disord, 2020 03;72:82-87.
    PMID: 32146380 DOI: 10.1016/j.parkreldis.2020.02.013
    An international panel of movement disorders specialists explored the views and perceptions of people with Parkinson's disease (PD) about their condition and its treatment, including the potential mismatch between the clinician's view of the patient's condition and their own view of what aspects of the disease most affect their daily lives. The initiative was focused on Asian countries, so participants comprised experts in the management of PD from key centers in Asia, with additional insight provided by European and the North American movement disorders experts. Analysis of peer-reviewed publications on patient perceptions of PD and the factors that they consider important to their wellbeing identified several contributing factors to the mismatch of views, including gaps in knowledge of PD and its treatment, an understanding of the clinical heterogeneity of PD, and the importance of a multidisciplinary approach to patient care. The faculty proposed options to bridge these gaps to ensure that PD patients receive the personalized treatment they need to achieve the best possible outcomes. It was considered essential to improve patient knowledge about PD and its treatment, as well as increasing the awareness of clinicians of PD heterogeneity in presentation and treatment response. A multidisciplinary and shared-care approach to PD was needed alongside the use of patient-centered outcome measures in clinical trials and clinical practice to better capture the patient experience and improve the delivery of individualized therapy.
    Matched MeSH terms: Parkinson Disease/therapy*
  10. Plant Polyphenols as Neuroprotective Agents in Parkinson's Disease Targeting Oxidative Stress
    Hor SL, Teoh SL, Lim WL
    Curr Drug Targets, 2020;21(5):458-476.
    PMID: 31625473 DOI: 10.2174/1389450120666191017120505
    Parkinson's disease (PD) is the second most prevalent progressive neurodegenerative disorder characterized by the degeneration of dopaminergic neurons in the human midbrain. Various ongoing research studies are competing to understand the pathology of PD and elucidate the mechanisms underlying neurodegeneration. Current pharmacological treatments primarily focused on improving dopamine metabolism in PD patients, despite the side effects of long-term usage. In recent years, it is recognized that oxidative stress-mediated pathways lead to neurodegeneration in the brain, which is associated with the pathophysiology of PD. The importance of oxidative stress is often less emphasized when developing potential therapeutic approaches. Natural plant antioxidants have been shown to mediate the oxidative stress-induced effects in PD, which has gained considerable attention in both in vitro and in vivo studies. Yet, clinical trials on natural polyphenol compounds are limited, restricting the potential use of these compounds as an alternative treatment for PD. Therefore, this review provides an understanding of the oxidative stress-induced effects in PD by elucidating the underlying events contributing to oxidative stress and explore the potential use of polyphenols in improving the oxidative status in PD. Preclinical findings have supported the potential of polyphenols in providing neuroprotection against oxidative stress-induced toxicity in PD. However, limiting factors, such as safety and bioavailability of polyphenols, warrant further investigations so as to make them the potential target for clinical applications in the treatment and management of PD.
    Matched MeSH terms: Parkinson Disease/drug therapy*
  11. Evaluation of novel Parkinson's disease candidate genes in the Chinese population
    Chew EGY, Liany H, Tan LCS, Au WL, Prakash KM, Annuar AA, et al.
    Neurobiol Aging, 2019 02;74:235.e1-235.e4.
    PMID: 30337193 DOI: 10.1016/j.neurobiolaging.2018.09.013
    Recent whole-exome sequencing studies in European patients with Parkinson's disease (PD) have identified potential risk variants across 33 novel PD candidate genes. We aim to determine if these reported candidate genes are similarly implicated in Asians by assessing common, rare, and novel nonsynonymous coding variants by sequencing all 33 genes in 198 Chinese samples and genotyping coding variants in an independent set of 9756 Chinese samples. We carried out further targeted sequencing of CD36 in an additional 576 Chinese and Korean samples. We found that only 8 of 43 reported risk variants were polymorphic in our Chinese samples. We identified several heterozygotes for rare loss-of-function mutations, including the reported CD36 p.Gln74Ter variant, in both cases and controls. We also observed 2 potential compound heterozygotes among PD cases for rare loss-of-function mutations in CD36 and SSPO. The other reported variants were common in East Asians and not associated with PD, completely absent, or only found in controls. Therefore, the 33 reported candidate genes and associated variants are unlikely to confer significant PD risk in the East Asian population.
    Matched MeSH terms: Parkinson Disease/genetics*
  12. Fulltext Clinical Phenotype of LRRK2 R1441C in 2 Chinese Sisters
    Lim SY, Lim JL, Ahmad-Annuar A, Lohmann K, Tan AH, Lim KB, et al.
    Neurodegener Dis, 2020;20(1):39-45.
    PMID: 32580205 DOI: 10.1159/000508131
    Pathogenic and risk variants in the LRRK2 gene are among the main genetic contributors to Parkinson's disease (PD) worldwide, and LRRK2-targeted therapies for patients with PARK-LRRK2are now entering clinical trials. However, in contrast to the LRRK2 G2019S mutation commonly found in Caucasians, North-African Arabs, and Ashkenazi Jews, relatively little is known about other causative LRRK2 mutations, and data on genotype-phenotype correlations are largely lacking. This report is from an ongoing multicentre study in which next-generation sequencing-based PD gene panel testing has so far been conducted on 499 PD patients of various ethnicities from Malaysia. We describe 2 sisters of Chinese ancestry with PD who carry the R1441C mutation in LRRK2 (which in Asians has been reported in only 2 Chinese patients previously), and highlight interesting clinical observations made over a decade of close follow-up. We further explored the feasibility of using a brief, expert-administered rating scale (the Clinical Impression of Severity Index; CISI-PD) to capture data on global disease severity in a large (n = 820) unselected cohort of PD patients, including severely disabled individuals typically excluded from research studies. All patients in this study were managed and evaluated by the same PD neurologist, and these data were used to make broad comparisons between the monogenic PD cases versus the overall "real world" PD cohort. This report contributes to the scarce literature on R1441C PARK-LRRK2, offering insights into natural history and epidemiological aspects, and provides support for the application of a simple and reliable clinical tool that can improve the inclusion of under-represented patient groups in PD research.
    Matched MeSH terms: Parkinson Disease/genetics*
  13. Analysis of model-based and model-free CEST effect quantification methods for different medical applications
    Foo LS, Yap WS, Hum YC, Manan HA, Tee YK
    J Magn Reson, 2020 01;310:106648.
    PMID: 31760147 DOI: 10.1016/j.jmr.2019.106648
    Chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) holds great potential to provide new metabolic information for clinical applications such as tumor, stroke and Parkinson's Disease diagnosis. Many active research and developments have been conducted to translate this emerging MRI technique for routine clinical applications. In general, there are two CEST quantification techniques: (i) model-free and (ii) model-based techniques. The reliability of these quantification techniques depends heavily on the experimental conditions and quality of the collected data. Errors such as noise may lead to misleading quantification results and thus inaccurate diagnosis when CEST imaging becomes a standard or routine imaging scan in the future. This paper investigates the accuracy and robustness of these quantification techniques under different signal-to-noise (SNR) levels and magnetic field strengths. The quantified CEST effect before and after adding random Gaussian White Noise using model-free and model-based quantification techniques were compared. It was found that the model-free technique consistently yielded larger average percentage error across all tested parameters compared to its model-based counterpart, and that the model-based technique could withstand SNR of about 3 times lower than the model-free technique. When applied on noisy brain tumor, ischemic stroke, and Parkinson's Disease clinical data, the model-free technique failed to produce significant differences between normal and abnormal tissue whereas the model-based technique consistently generated significant differences. Although the model-free technique was less accurate and robust, its simplicity and thus speed would still make it a good approximate when the SNR was high (>50) or when the CEST effect was large and well-defined. For more accurate CEST quantification, model-based techniques should be considered. When SNR was low (<50) and the CEST effect was small such as those acquired from clinical field strength scanners, which are generally 3T and below, model-based techniques should be considered over model-free counterpart to maintain an average percentage error of less than 44% even under very noisy condition as tested in this work.
    Matched MeSH terms: Parkinson Disease/diagnosis
  14. Pharmacology and toxicology of α- and β-Asarone: A review of preclinical evidence
    Chellian R, Pandy V, Mohamed Z
    Phytomedicine, 2017 Aug 15;32:41-58.
    PMID: 28732807 DOI: 10.1016/j.phymed.2017.04.003
    BACKGROUND: Asarone is one of the most researched phytochemicals and is mainly present in the Acorus species and Guatteria gaumeri Greenman. In preclinical studies, both α- and β-asarone have been reported to have numerous pharmacological activities and at the same time, many studies have also revealed the toxicity of α- and β-asarone.

    PURPOSE: The purpose of this comprehensive review is to compile and analyze the information related to the pharmacokinetic, pharmacological, and toxicological studies reported on α- and β-asarone using preclinical in vitro and in vivo models. Besides, the molecular targets and mechanism(s) involved in the biological activities of α- and β-asarone were discussed.

    METHODS: Databases including PubMed, ScienceDirect and Google scholar were searched and the literature from the year 1960 to January 2017 was retrieved using keywords such as α-asarone, β-asarone, pharmacokinetics, toxicology, pharmacological activities (e.g. depression, anxiety).

    RESULTS: Based on the data obtained from the literature search, the pharmacokinetic studies of α- and β-asarone revealed that their oral bioavailability in rodents is poor with a short plasma half-life. Moreover, the metabolism of α- and β-asarone occurs mainly through cytochrome-P450 pathways. Besides, both α- and/or β-asarone possess a wide range of pharmacological activities such as antidepressant, antianxiety, anti-Alzheimer's, anti-Parkinson's, antiepileptic, anticancer, antihyperlipidemic, antithrombotic, anticholestatic and radioprotective activities through its interaction with multiple molecular targets. Importantly, the toxicological studies revealed that both α- and β-asarone can cause hepatomas and might possess mutagenicity, genotoxicity, and teratogenicity.

    CONCLUSIONS: Taken together, further preclinical studies are required to confirm the pharmacological properties of α-asarone against depression, anxiety, Parkinson's disease, psychosis, drug dependence, pain, inflammation, cholestasis and thrombosis. Besides, the anticancer effect of β-asarone should be further studied in different types of cancers using in vivo models. Moreover, further dose-dependent in vivo studies are required to confirm the toxicity of α- and β-asarone. Overall, this extensive review provides a detailed information on the preclinical pharmacological and toxicological activities of α-and β-asarone and this could be very useful for researchers who wish to conduct further preclinical studies using α- and β-asarone.

    Matched MeSH terms: Parkinson Disease/drug therapy
  15. Immunotherapies for Parkinson's Disease: Progression of Clinical Development
    Teng JS, Ooi YY, Chye SM, Ling APK, Koh RY
    CNS Neurol Disord Drug Targets, 2021;20(9):802-813.
    PMID: 34042040 DOI: 10.2174/1871527320666210526160926
    Parkinson's disease is a common neurodegenerative disease affecting the movement and well-being of most elderly. The manifestations of Parkinson's disease often include resting tremor, stiffness, bradykinesia, and muscular rigidity. The typical hallmark of Parkinson's disease is the destruction of neurons in the substantia nigra and the presence of Lewy bodies in different compartments of the central nervous system. Due to various limitations to the currently available treatments, immunotherapies have emerged to be the new approach to Parkinson's disease treatment. This approach shows some positive outcomes on the efficacy by removing the aggregated species of alpha-synuclein, which is believed to be one of the causes of Parkinson's disease. In this review, an overview of how alpha-synuclein contributes to Parkinson's disease and the effects of a few new immunotherapeutic treatments, including BIIB054 (cinpanemab), MEDI1341, AFFITOPE, and PRX002 (prasinezumab) that are currently under clinical development, will be discussed.
    Matched MeSH terms: Parkinson Disease/therapy*
  16. Fulltext Association of LRRK2 Haplotype With Age at Onset in Parkinson Disease
    Xiao B, Deng X, Ng EY, Allen JC, Lim SY, Ahmad-Annuar A, et al.
    JAMA Neurol, 2018 01 01;75(1):127-128.
    PMID: 29131875 DOI: 10.1001/jamaneurol.2017.3363
    Matched MeSH terms: Parkinson Disease/genetics*
  17. Empirical Wavelet Transform Based Features for Classification of Parkinson's Disease Severity
    Oung QW, Muthusamy H, Basah SN, Lee H, Vijean V
    J Med Syst, 2017 Dec 29;42(2):29.
    PMID: 29288342 DOI: 10.1007/s10916-017-0877-2
    Parkinson's disease (PD) is a type of progressive neurodegenerative disorder that has affected a large part of the population till now. Several symptoms of PD include tremor, rigidity, slowness of movements and vocal impairments. In order to develop an effective diagnostic system, a number of algorithms were proposed mainly to distinguish healthy individuals from the ones with PD. However, most of the previous works were conducted based on a binary classification, with the early PD stage and the advanced ones being treated equally. Therefore, in this work, we propose a multiclass classification with three classes of PD severity level (mild, moderate, severe) and healthy control. The focus is to detect and classify PD using signals from wearable motion and audio sensors based on both empirical wavelet transform (EWT) and empirical wavelet packet transform (EWPT) respectively. The EWT/EWPT was applied to decompose both speech and motion data signals up to five levels. Next, several features are extracted after obtaining the instantaneous amplitudes and frequencies from the coefficients of the decomposed signals by applying the Hilbert transform. The performance of the algorithm was analysed using three classifiers - K-nearest neighbour (KNN), probabilistic neural network (PNN) and extreme learning machine (ELM). Experimental results demonstrated that our proposed approach had the ability to differentiate PD from non-PD subjects, including their severity level - with classification accuracies of more than 90% using EWT/EWPT-ELM based on signals from motion and audio sensors respectively. Additionally, classification accuracy of more than 95% was achieved when EWT/EWPT-ELM is applied to signals from integration of both signal's information.
    Matched MeSH terms: Parkinson Disease/diagnosis*
  18. Fulltext Exploring causality of the association between smoking and Parkinson's disease
    Gallo V, Vineis P, Cancellieri M, Chiodini P, Barker RA, Brayne C, et al.
    Int J Epidemiol, 2019 Jun 01;48(3):912-925.
    PMID: 30462234 DOI: 10.1093/ije/dyy230
    BACKGROUND: The aim of this paper is to investigate the causality of the inverse association between cigarette smoking and Parkinson's disease (PD). The main suggested alternatives include a delaying effect of smoking, reverse causality or an unmeasured confounding related to a low-risk-taking personality trait.

    METHODS: A total of 715 incident PD cases were ascertained in a cohort of 220 494 individuals from NeuroEPIC4PD, a prospective European population-based cohort study including 13 centres in eight countries. Smoking habits were recorded at recruitment. We analysed smoking status, duration, and intensity and exposure to passive smoking in relation to PD onset.

    RESULTS: Former smokers had a 20% decreased risk and current smokers a halved risk of developing PD compared with never smokers. Strong dose-response relationships with smoking intensity and duration were found. Hazard ratios (HRs) for smoking <20 years were 0.84 [95% confidence interval (CI) 0.67-1.07], 20-29 years 0.73 (95% CI 0.56-0.96) and >30 years 0.54 (95% CI 0.43-0.36) compared with never smokers. The proportional hazard assumption was verified, showing no change of risk over time, arguing against a delaying effect. Reverse causality was disproved by the consistency of dose-response relationships among former and current smokers. The inverse association between passive smoking and PD, HR 0.70 (95% CI 0.49-0.99) ruled out the effect of unmeasured confounding.

    CONCLUSIONS: These results are highly suggestive of a true causal link between smoking and PD, although it is not clear which is the chemical compound in cigarette smoking responsible for the biological effect.

    Matched MeSH terms: Parkinson Disease/epidemiology*
  19. Fulltext Biomechanical System Versus Observational Rating Scale for Parkinson's Disease Tremor Assessment
    Chan PY, Mohd Ripin Z, Abdul Halim S, Kamarudin MI, Ng KS, Eow GB, et al.
    Sci Rep, 2019 May 31;9(1):8117.
    PMID: 31148550 DOI: 10.1038/s41598-019-44142-1
    There is a lack of evidence that either conventional observational rating scale or biomechanical system is a better tremor assessment tool. This work focuses on comparing a biomechanical system and the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale in terms of test-retest reliability. The Parkinson's disease tremors were quantified by biomechanical system in joint angular displacement and predicted rating, as well as assessed by three raters using observational ratings. Qualitative comparisons of the validity and function are made also. The observational rating captures the overall severity of body parts, whereas the biomechanical system provides motion- and joint-specific tremor severity. The tremor readings of the biomechanical system were previously validated against encoders' readings and doctors' ratings; the observational ratings were validated with previous ratings on assessing the disease and combined motor symptoms rather than on tremor specifically. Analyses show that the predicted rating is significantly more reliable than the average clinical ratings by three raters. The comparison work removes some of the inconsistent impressions of the tools and serves as guideline for selecting a tool that can improve tremor assessment. Nevertheless, further work is required to consider more variabilities that influence the overall judgement.
    Matched MeSH terms: Parkinson Disease/diagnosis*
  20. Neuroimmunomodulatory properties of DPSCs in an in vitro model of Parkinson's disease
    Gnanasegaran N, Govindasamy V, Mani V, Abu Kasim NH
    IUBMB Life, 2017 09;69(9):689-699.
    PMID: 28685937 DOI: 10.1002/iub.1655
    In neurodegenerative diseases, such as Alzheimer's and Parkinson's, microglial cell activation is thought to contribute to their degeneration by producing neurotoxic compounds. While dental pulp stem cells (DPSCs) have been regarded as the next possible cell source for cell replacement therapy (CRT), their actual role when exposed in such harsh environment remains elusive. In this study, the immunomodulatory behavior of DPSCs from human subjects was investigated in a coculture system consisting of neuron and microglia which were treated with 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine, which mimics the inflammatory conditions and contribute to degeneration of dopaminergic (DA-ergic) neurons. Assessments were performed on their proliferation, extent of DNA damage, productions of reactive oxygen species (ROS) and nitric oxide (NO), as well as secretion of inflammatory mediators. Notably, DPSCs were shown to attenuate their proliferation, production of ROS, and NO significantly (P 
    Matched MeSH terms: Parkinson Disease/immunology; Parkinson Disease/metabolism; Parkinson Disease/pathology; Parkinson Disease/therapy*
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