Huntington's disease (HD) is a neurodegenerative disorder that manifests with movement dysfunction. The expression of mutant Huntingtin (mHTT) disrupts the functions of brain cells. Galectin-3 (Gal3) ...is a lectin that has not been extensively explored in brain diseases. Herein, we showed that the plasma Gal3 levels of HD patients and mice correlated with disease severity. Moreover, brain Gal3 levels were higher in patients and mice with HD than those in controls. The up-regulation of Gal3 in HD mice occurred before motor impairment, and its level remained high in microglia throughout disease progression. The cell-autonomous up-regulated Gal3 formed puncta in damaged lysosomes and contributed to inflammation through NFκB- and NLRP3 inflammasome-dependent pathways. Knockdown of Gal3 suppressed inflammation, reduced mHTT aggregation, restored neuronal DARPP32 levels, ameliorated motor dysfunction, and increased survival in HD mice. Thus, suppression of Gal3 ameliorates microglia-mediated pathogenesis, which suggests that Gal3 is a novel druggable target for HD.
The pathogenesis of Parkinson’s disease (PD) remains to be elucidated. Metabolomic analysis has the potential to identify biochemical pathways and metabolic profiles that are involved in PD ...pathogenesis. Here, we performed a targeted metabolomics to quantify the plasma levels of 184 metabolites in a discovery cohort including 82 PD patients and 82 normal controls (NCs) and found two up-regulated (dopamine, putrescine/ornithine ratio) and four down-regulated (octadecadienylcarnitine C18:2, asymmetric dimethylarginine, tryptophan, and kynurenine (KYN)) metabolites in the plasma of PD patients. We then measured the plasma levels of a panel of metabolic products of KYN pathway in an independent validation cohort including 118 PD patients, 22 Huntington’s disease (HD) patients, and 37 NCs. Lower kynurenic acid (KA)/KYN ratio, higher quinolinic acid (QA) level, and QA/KA ratio were observed in PD patients compared to HD patients and NCs. PD patients at advanced stage (Hoehn-Yahr stage > 2) showed lower KA and KA/KYN ratio, as well as higher QA and QA/KA ratio compared to PD patients at early stage (Hoehn-Yahr stage ≤ 2) and NCs. Levels of KA and QA, as well as the ratios of KA/KYN and QA/KA between PD patients with and without psychiatric symptoms, dementia, or levodopa-induced dyskinesia in the advanced PD were similar. This metabolomic analyses demonstrate a number of plasma biomarker candidates for PD, suggesting a shift toward neurotoxic QA synthesis and away from neuroprotective KA production in KYN pathway.
Highlights • Increased plasma IL-6, MMP-9, VEGF, and TGF-β1 in HD patients. • Decreased IL-18 plasma levels in HD patients. • Plasma IL-6 reversely correlates with independence scale and functional ...capacity. • Alterations of the inflammatory markers were found in R6/2 mice at different ages. • These inflammatory markers may serve as the potential biomarkers for HD.
Parkinson's disease (PD) is the second most common neurodegenerative disease, and α-synuclein plays a critical role in the pathogenesis of PD. Studies have revealed controversial results regarding ...the correlation between motor severity and α-synuclein levels in peripheral blood from patients with PD.
We examined α-synuclein levels in plasma or serum in patients with PD and investigated the relationship between plasma or serum α-synuclein level and motor symptom severity.
We recruited 88 participants (48 patients with PD and 40 healthy controls). Clinical information was collected, and venous blood was drawn from each participant to be processed to obtain plasma or serum. The plasma or serum α-synuclein level was detected using monoclonal antibodies with magnetic nanoparticles, and was measured through immunomagnetic reduction. Plasma or serum α-synuclein levels were quantitatively detected.
In patients with PD, the means of plasma and serum α-synuclein level were 3.60 ± 2.53 and 0.03 ± 0.04 pg/mL, respectively. The areas under the receiver operating characteristic curve of plasma and serum α-synuclein for distinguishing patients with PD from healthy controls were 0.992 and 0.917, respectively. The serum α-synuclein level also showed a significant correlation with patients in H-Y stages 1-3 (
= 0.40,
= 0.025), implying that the serum α-synuclein level may be a potential marker of motor symptom severity in patients with early PD.
Our data suggest that the α-synuclein level in serum or plasma can differentiate between healthy controls and patients with PD. Serum α-synuclein levels moderately correlate with motor severity in patients with early PD.
Aims
To examine the association of the working stress with posttraumatic stress disorder symptoms (PTSD), and burnout as the mediator for this association among emergency nurses during COVID‐19 ...pandemic.
Design
Longitudinal survey study.
Methods
Online survey was used to collect data during the period from August to November 2020 with a sample of 169 emergency nurses. They were invited to complete the following questionnaires at the 6th and 9th months after COVID‐19 outbreak: Posttraumatic Symptom Scale (PTSS‐10), the emergency nurses' COVID‐19 stress questionnaire and Chinese version of 21‐item Copenhagen Burnout Inventory (CBI).
Results
During the 3‐month follow‐up, there were no changes in the number of suspected PTSD cases (6 and above symptoms): 41% at the 6th month and 33.3% at the 9th month. The increases of the personal burnout levels and living apart from families were the main factors associated with the PTSD symptoms. The risk for emergency nurses suffering from PTSD is through stress levels increasing their burnout levels.
Conclusions
Over 30 percent of emergency nurses remained at high risk for suspected PTSD. The burnout levels mediated the relationship between the stress levels and the risks of PTSD.
Impact
Little as know about the impact of COVID‐19 on emergency nurses' stress. This study found emergency nurses remained to be the high risk for the suspected PTSD cases. It is urged to develop a stress‐reduction program targeting at causes of stress and improving burnout for emergency nurses during COVID‐19 pandemic.
Our study aimed to investigate the incidence, risk factors and time to occurrence of malignancy in patients with dermatomyositis (DM) and polymyositis (PM). The electronic medical records of 1100 ...patients with DM and 1164 patients with PM were studied between January 2001 and May 2019. Malignancies after myositis were diagnosed in 61 (5.55%) patients with DM and 38 (3.26%) patients with PM. The cumulative incidence of malignancies in patients with DM were significantly higher than patients with PM (hazard ratio = 1.78, log-rank p = 0.004). Patients with DM had a greater risk of developing malignancy than those with PM at 40-59 years old (p = 0.01). Most malignancies occurred within 1 year after the initial diagnosis of DM (n = 35; 57.38%). Nasopharyngeal cancer (NPC) was the most common type of malignancy in patients with DM (22.95%), followed by lung, and breast cancers. In patients with PM, colorectal, lung and hepatic malignancies were the top three types of malignancy. The risk factors for malignancy included old age (≥ 45 years old) and low serum levels of creatine phosphokinase (CPK) for patients with DM and male sex and low serum levels of CPK for patients with PM. Low serum levels of CPK in patients with myositis with malignancy represented a low degree of muscle destruction/inflammation, which might be attributed to activation of the PD-L1 pathway by tumor cells, thus inducing T-cell dysfunction mediating immune responses in myofibers. A treatment and follow-up algorithm should explore the occurrence of malignancy in different tissues and organs and suggested annual follow-ups for at least 5.5 years to cover the 80% cumulative incidence of malignancy in patients with DM and PM.
Diminished cognitive and physical functions negatively affect the daily functions of individuals. Although combined cognitive and physical training prevents instrumental activities of daily living ...(IADL) disability in older adults, no predictive model or mediation analysis of IADL after combined training exists. This study aims to employ prediction and mediation analysis to identify the predictors of IADL performance and to elucidate the mediators of the association between baseline global cognition and subsequent IADL performance following combined cognitive and physical training. This study involved 177 participants aged 60 years and older who underwent combined training. Cognitive function was measured with the Montreal Cognitive Assessment (MoCA), Digit Symbol Substitution Test (DSST), Color Trails Test, Word List, and a dual task; physical function with the Timed Up and Go (TUG) test; daily function with the Lawton IADL Scale. We conducted regression analyses to identify the predictors of IADL performance, and mediation analysis to examine whether DSST and TUG mediate the relationship between MoCA and IADL. The pre-intervention DSST and TUG were significant independent predictors of post-intervention IADL. The association between the pre-intervention MoCA and post-intervention IADL was mediated by pre-intervention DSST and TUG. This study highlighted the importance of measuring and improving processing speed and functional mobility before and during interventions to enhance IADL outcomes.Trial registration: NCT03619577, 23/07/2018; NCT04689776, 29/12/2020.
Parkinson's disease in the Western Pacific Region Lim, Shen-Yang; Tan, Ai Huey; Ahmad-Annuar, Azlina ...
Lancet neurology,
September 2019, 2019-Sep, 2019-09-00, 20190901, Letnik:
18, Številka:
9
Journal Article
Recenzirano
1·8 billion people of diverse ethnicities and cultures live in the Western Pacific Region. The increasing longevity of populations in this region is a major contributor to the exponential increase in ...Parkinson's disease prevalence worldwide. Differences exist between Parkinson's disease in the Western Pacific Region and in Europe and North America that might provide important insights into our understanding of the disease and approaches to management. For example, some genetic factors (such as LRRK2 mutations or variants) differ, environmental exposures might play differential roles in modulating the risk of Parkinson's disease, and fewer dyskinesias are reported, with some differences in the profile of non-motor symptoms and comorbidities. Gaps in awareness of the disease and inequitable access to treatments pose challenges. Further improvements in infrastructure, clinical governance, and services, and concerted collaborative efforts in training and research, including greater representation of the Western Pacific Region in clinical trials, will improve care of patients with Parkinson's disease in this region and beyond.
Introduction/Aims
A model for predicting responsiveness to immunotherapy in patients with chronic inflammatory demyelinating polyneuropathy (CIDP) has not been well established. We aimed to establish ...a new classifier for CIDP patients based on clinical characteristics, laboratory findings, and electrophysiological features.
Methods
The clinical, laboratory, and electrophysiological features of 172 treatment‐naïve patients with CIDP between 2003 and 2019 were analyzed using an unsupervised hierarchical clustering. The identified pivotal features were used to establish simple classifications using a tree‐based model.
Results
Three clusters were identified: 1, n = 65; 2, n = 70; and 3, n = 37. Patients in Cluster 1 scored lower on the disability assessment score before treatment. More patients in Clusters 2 (90.0%) fulfilled demyelinating criteria than patients in Cluster 1 (30.8%, p < .001). Cluster 3 had more patients with chronic kidney disease (CKD) (27.0%) and hypoalbuminemia (3.40 g/dL) than did Cluster 2 (CKD: 0%, p < .001; hypoalbuminemia: 4.09 g/dL, p < .001). The responsiveness to pulse steroid therapy was higher in Cluster 2 (70.0%) than in Clusters 1 (31.8%; p = .043) and 3 (25.0%; p = .014). A tree‐based model with four pivotal features classified patients in our cohort into new clusters with high accuracy (89.5%).
Discussion
The established hierarchical clustering with the tree‐based model identified key features contributing to differences in disease severity and response to pulse steroid therapy. This classification system could assist clinicians in the selection of treatments and could also help researchers by clustering patients for clinical treatment trials.
Common genetic variants that increase the risk for Parkinson's disease may differentiate patient subgroups and influence future individualized therapeutic strategies. Herein we show evidence for ...leucine‐rich repeat kinase 2 (LRRK2) c.4883G>C (R1628P) as a risk factor in ethnic Chinese populations. A study of 1,986 individuals from 3 independent centers in Taiwan and Singapore demonstrates that Lrrk2 R1628P increases risk for Parkinson's disease (odds ratio, 1.84; 95% confidence interval, 1.20–2.83; p = 0.006). Haplotype analysis suggests an ancestral founder for carriers approximately 2,500 years ago. These findings support the importance of LRRK2 variants in sporadic Parkinson's disease. Ann Neurol 2008
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