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Parkinson's disease (PD) and carbon monoxide (CO) poisoning demonstrate parkinsonian features related to presynaptic dopaminergic deficits. However, their clinical features and treatment responses are different, indicating other roles of neurotransmitters in symptomatic modulation. In this study, we used 18 F-FP-(+)-DTBZ PET to explore vesicular monoamine transporter type 2 (VMAT2) distributions in 31 patients with PD, 39 patients with CO poisoning and parkinsonian features (n = 39), and 24 age-matched controls. In addition to the disease-specific VMAT2 topographies in PD and CO poisoning, we also constructed feature-specific functional networks. The cardinal features included tremor, rigidity, akinesia, and rapid alternating movements (RAM), and the overall motor severity was scored using Unified Parkinson Disease Rating Scale (UPDRS) and modified Hoehn-Yahr (mH-Y) Scale scores. Our results suggested that a reduction in VMAT2 signals in the caudate, amygdala, and hippocampus were more specific to CO poisoning, while low uptake in the putamen and substantia nigra was more specific to PD. UPDRS and mH-Y scores were related to striatum signals in both groups and hippocampus and raphe in the CO poisoning group. With regards to the cardinal features, the putamen was related to akinesia in both groups. The substantia nigra was related to rigidity in PD, and the caudate and nucleus accumbens were related to akinesia, RAM and rigidity in CO poisoning. Our study enhances the current understanding of different patterns of monoaminergic terminal deficits in patients with CO poisoning and PD., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Selenium is an essential trace mineral element for humans. Although previous in vitro and animal studies have reported the vital role of selenium in bone, the results of the relationship between the selenium status and bone health were inconsistent in epidemiological studies. The risk of selenium deficiency is negligible for U.S. general population, however, the relationship between selenium status and bone health has never been surveyed in a nationally representative sample. In this study, we analyzed the data of 2983 adults (aged ≥40 years) in the National Health and Nutrition Examination Survey (NHANES) 2013-2014 to investigate the association among three markers of the selenium status (measured from whole blood, serum, and dietary intake), total spine and femur bone mineral density (BMD), and FRAX scores, and history of bone fractures. We found a one-unit increase in the ln-whole-blood selenium level was correlated with an increase in the total femur BMD of 0.064 g/cm 2 (S.E. = 0.025; P = 0.022) in all participants and 0.086 g/cm 2 (S.E. = 0.031; P = 0.013) in menopausal women. Additionally, a one-unit increase in the ln-selenium intake amount was associated with an increase in the total femur BMD of 0.014 g/cm 2 (S.E. = 0.007; P = 0.043) in all participants. We also found that the dietary and whole-blood selenium statuses were negatively associated with the FRAX score, while levels of all the three selenium biomarkers were negatively associated with a history of bone fractures. In conclusion, increased selenium status is correlated with an increased total femur BMD, decreased FRAX scores, and a reduced incidence of previous bone fractures in the U.S. representative survey of adults. Further study is warranted to clarify the causal inference., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Achilles tendinopathy has a high re-injury rate and poor prognosis. Development of effective therapy for Achilles tendinopathy is important. Excessive accumulation of ROS and resulting oxidative stress are believed to cause tendinopathy. Overproduction of hydrogen peroxide (H 2 O 2 ), the most common ROS, could lead to the tendinopathy by causing oxidative damage, activation of endoplasmic reticulum (ER) stress and apoptotic death of tenocytes. Activation of mitochondrial aldehyde dehydrogenase 2 (ALDH2) is expected to alleviate oxidative stress and ER stress. Alda-1 is a selective and potent activator of ALDH2. In this study, we examined the cytoprotective benefit of Alda-1, an activator of ALDH2, on H 2 O 2 -induced Achilles tendinopathy in cellular and mouse models. We prepared cellular and mouse models of Achilles tendinopathy by treating cultured Achilles tenocytes and Achilles tendons with oxidative stressor H 2 O 2 . Subsequently, we studied the protective benefit of Alda-1 on H 2 O 2 -induced Achilles tendinopathy. Alda-1 pretreatment attenuated H 2 O 2 -induced cell death of cultured Achilles tenocytes. Treatment of Alda-1 prevented H 2 O 2 -induced oxidative stress and depolarization of mitochondrial membrane potential in tenocytes. Application of Alda-1 attenuated H 2 O 2 -triggered mitochondria- and ER stress-mediated apoptotic cascades in cultured tenocytes. Alda-1 treatment ameliorated the severity of H 2 O 2 -induced Achilles tendinopathy in vivo by preventing H 2 O 2 -induced pathological histological features of Achilles tendons, apoptotic death of Achilles tenocytes and upregulated expression of inflammatory cytokines IL-1β and TNF-α. Our results provide the evidence that ALDH2 activator Alda-1 ameliorates H 2 O 2 -induced Achilles tendinopathy. Alda-1 could be used for preventing and treating Achilles tendinopathy., (Copyright © 2020 Elsevier Inc. All rights reserved.)

In thalassemia major or transfusion-dependent thalassemia patients, osteoporosis-related bone complications such as fracture events are common. However, no studies have investigated the risk of fracture in transfusion-naïve thalassemia population. Therefore, we conducted a longitudinal nationwide cohort study to determine whether this population has an increased risk of fracture. This nationwide, population-based cohort study analyzed data from 1998 to 2010 obtained from the Taiwanese National Health Insurance Research Database, with a follow-up period extending until the end of 2011. We identified cases with transfusion-naïve thalassemia and selected a comparison cohort that was frequency-matched according to age and year of diagnosis of thalassemia at a ratio of one subject with thalassemia to four subjects in the control group. We analyzed the risk of fracture events to occur in transfusion-naïve thalassemia cases by using Cox proportional hazards regression models. Totally, the study recruited 1369 transfusion-naïve thalassemia subjects and 5416 controls. We identified a total of 71 cases with fracture events within the thalassemia group and 204 within the control group. The overall risks for developing fracture events were 1.35-fold higher in transfusion-naïve thalassemia individuals than the comparison cohort after adjusting for age, sex and comorbidities. Most fracture events were observed in male transfusion-naïve thalassemia individuals rather than the normal population. In subgroup analysis, there was a 1.46-fold higher risk to develop upper-limb fracture in the thalassemia group than in the control groups. In conclusion, our long-term, cohort study results showed that there was a higher risk for the development of fractures in transfusion-naïve thalassemia individuals, particularly in male cases., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Parkinson's disease (PD) is one of the most prevalent age-related neurodegenerative diseases and usually refers to a complex disorder with multiple genetic and environmental factors influencing disease risk. We here performed a gene-based case-control association study to scrutinize whether genetic variants in SNCA and LRRK2 genes could predispose to sporadic, late-onset form of PD in Taiwanese population., Methods: 17 Single Nucleotide Polymorphisms (SNPs) markers located within SNCA gene as well as the 16 SNP markers within LRRK2 gene were chosen for genotyping and evaluated their haplotype structure in a cohort of sporadic PD patients and control individuals., Results: This study showed that two SNPs near the promoter region (rs2301134 and rs2301135) of SNCA gene gave the greatest evidence for an association with PD (p ≤ 0.01) and a haplotype block with two SNPs in the 3' UTR (rs356221 and rs11931074) revealed another evidence of association (p ≤ 0.02). For the LRRK2 gene, only R1628P variants of total 16 SNPs giving a marginal significant association with PD across the whole gene (p = 0.0058) and no haplotype block was constructed. Many genetic variants (A419V, I1122V, R1441C, R1441G, R1441H, Y1699C, M1869V, M1869T, I2012T, G2019S, and I2020T) from previous reports were not detected in our cohort., Conclusions: We have replicated a population-based PD association study in a collection of 626 cases and 473 control subjects and confirm that genetic variants of both SNCA and LRRK2 genes are associated with susceptibility to sporadic PD but in a different distribution., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

We report three novel deletions of the SGCE gene in three families with myoclonus-dystonia (M-D) syndrome in Taiwan. Their clinical characteristics included: early onset, dominant myoclonus and dystonia in the neck, trunk and upper limbs. By direct sequencing of the SGCE gene coding regions, we identified a small heterozygous deletion (c.842delA) in exon 7 of the three sibs and asymptomatic father in the first family and an eight-base heterozygous deletion (c.524_531del) in exon 5 of the mother and a daughter in the second family. Using multiple ligation-dependent probe amplification (MLPA), a large heterozygous deletion of 2-11 exons was identified in the father and a son in the third family which was undetected by initial sequencing. It is the largest intragenic deletion ever reported. In conclusion, we have identified three novel mutations of SGCE in the respective three M-D families. The large deletion was responsible for one third of these M-D families which might implicate an important contribution to Taiwanese M-D syndrome. We suggest that the contribution of large deletion should be further verified in a large cohort of patients with M-D syndrome in Han Chinese., (Crown Copyright © 2010. Published by Elsevier Ltd. All rights reserved.)

Objective: To analyze the Gly2385Arg (G2385R) mutation in Taiwanese Alzheimer's disease (AD) patients., Background: The leucine-rich repeat kinase 2 (LRRK2) gene is well known to predispose subjects to Parkinson's disease (PD). The Gly2385Arg (G2385R) variant of LRRK2 is believed to be "East Asian"-specific, particularly in the Han Chinese population; however, whether the LRRK2 G2385R is associated with a risk of AD in pure Han-Chinese patients has not often been studied., Methods: A total of 209 AD patients (87 men, 122 women) and 180 age- and gender-matched controls were recruited and the demographic data of the AD patients were analyzed. Genotyping of the Gly2385Arg variant was studied using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry., Results: Subjects with the Gly2385Arg variant were all heterozygous carriers. The frequency of Gly2385Arg carriers did not differ significantly between the AD patients and controls (4.78% versus 4.44%, odds ratio=1.04, 95% CI=0.62-1.77, P=0.87). In the AD patient group, the age of symptom onset, the length of education, or the MMSE score showed no significant differences between wild-type carriers and heterozygous variant carriers (P=0.51, 0.43, and 0.09)., Conclusion: The Gly2385Arg variant of LRRK2 may not be a major risk factor for AD in pure Han Chinese patient. Among the AD patients, Gly2385Arg carriers were not clinically different from wild-type carriers.

The c.G7153A variant in the LRRK2 gene (protein effect: Gly2385Arg) is emerging as an important risk factor for Parkinson's disease (PD) in the Han Chinese and Japanese populations. The prevalence of this variant in other neurodegenerative diseases and movement disorders remains almost completely unexplored. Using MALDI-TOF, we studied the Gly2385Arg variant in a large cohort of patients with primary dystonia (n=335) and a smaller series of patients with clinically diagnosed multiple system atrophy (MSA, n=57). The Gly2385Arg variant was identified in heterozygous state in 14 patients with primary dystonia (4.18%) and in three patients with MSA (5.26%). These frequencies do not differ statistically from that reported previously by us in Taiwanese controls (5%). We conclude that the Gly2385Arg variant is not associated with primary dystonia in Taiwan, supporting the specificity of the association between this variant and PD. Whether the Gly2385Arg variant modifies the risk for MSA deserves further study in larger samples.

We investigated the clinical features and progression of four patients with chronic manganese intoxication, 18 years after cessation of exposure. Because the results were to be compared with previous observations, we employed the same scoring system. The clinical manifestations were foot dystonia, wide based gait, rigidity, and difficulty in walking backwards. Resting tremor was rarely seen, but tongue tremor was found in 2 patients. The asymmetry initially present in 2 patients persisted 18 years later. Measurements had previously revealed rapid progression in the initial 10 years. We found a plateau over the following decade.

To investigate the DYT1 gene mutation in Chinese ethnic, we examined a series of 200 patients with primary dystonias (11 familial and 189 sporadic), 53 of their asymptomatic relatives, 97 patients with familial or early-onset parkinsonism, and 200 healthy subjects. The GAG deletion at codon 946 was only found in three sporadic dystonia patients and seven of their asymptomatic familial members. The frequency of GAG deletion was 1.5% in dystonia patients, and was 6.7% in early-onset dystonias (< or = 26 years). We conclude that DYT1 mutation is a minor cause of primary dystonias in a cohort of Taiwanese population.

We report a parkinsonian phenotype of spinocerebellar ataxia type 3 (SCA3) in three female sibs from one Taiwanese family, found in a genetic analysis of 60 patients from 49 families with familial parkinsonism. Initially, all three patients presented with early onset resting tremor, rigidity, bradykinesia, and good response to levodopa. In the later stages, peripheral neuropathy developed in one sib and mild ataxia in another one. Decreased concentration of dopamine transporter in the striatum was demonstrated by (99m)Tc-TRODAT-1 SPECT imaging in the two sibs studied. Therefore, SCA3 should be considered as an important etiology of familial parkinsonism.

A woman, aged 27 years, developed acute headache and fever followed by tremor, rigidity, and bradykinesia. Masked face, drooling saliva, monotonous voice, and dysphagia were observed. She was totally bedridden during the worst period because of marked generalized rigidity and bradykinesia. There was no neurological disturbance other than parkinsonism. Several herpetic vesicles were noticed at the left angle of her mouth. The cerebrospinal fluid revealed a mononuclear pleocytosis with a normal concentration of sugar and protein. The antibody test for Type I herpes simplex virus was positive in the serum but negative in the cerebrospinal fluid. Brain CT and EEG were normal. However, MRI study showed markedly increased signals in the bilateral substantia nigra on T2-weighted, proton density, and in gradient recall acquisition imagings. Those abnormal findings had almost disappeared in a follow-up MRI study 2 months later. Her parkinsonian symptoms were substantially resolved by the time. However, PET scans, performed 8 months later, disclosed: (1) mild reduction of fluorodopa uptake; and (2) increased raclopride binding, predominantly in the putamen. These findings suggest a subclinical nigrostriatal dopaminergic deficit and a relative excess of the D2 receptors, with a pattern similar to that found in typical idiopathic parkinsonism.