Plasma miR-203a-3p as a Novel Predictor of Dementia in Patients with Parkinson's Disease.

The early detection of cognitive decline in Parkinson's disease is important for providing drug therapy and non-pharmacological management. The circulating microRNAs present in plasma are promising biomarkers of PD with dementia (PDD) due to their critical roles in synaptic plasticity and the regulation of neurodegeneration-associated proteins. In this study, we aimed to identify plasma microRNAs that may differentiate PD with or without cognitive impairment. Global microRNA expression was obtained from a discovery set of 123 participants who were divided into four groups, namely normal controls (HC), PD with no dementia (PDND), PD with mild cognitive impairment (PD-MCI), and PDD, using next-generation sequencing. The BOLD selector was used for microRNA candidate selection. Six miRNAs, namely miR-203a-3p, miR-626, miR-662, miR-3182, miR-4274, and miR-4295, were clustered as potential candidates for use in identifying PDND from PD-MCI. Another independent cohort of 120 participants was further recruited in a validation step in order to detect candidate microRNAs via droplet digital PCR (ddPCR), which was used for its high sensitivity in detecting low miRNA concentrations. Our results show that the ratio of miR-203a-3p/miR-16-5p, in which miR-16-5p was used as a reference control miRNA, was significantly increased in PDD compared to that seen in PD-MCI and PDND individually, and was negatively correlated with the MoCA scores (r = -0.237, p = 0.024) in patients with PD. However, there was no significant difference in the ratio of miR-203a-3p/miR-16-5p between HC and PDND, PD-MCI, or PDD individually. The ROC curve of the logistic regression model, factoring in the variables of age, the ratio of miR-203a-3p/miR-16-5p, and the UPDRS III score, demonstrated an AUC of 0.883. Our findings suggest that the ratio of miR-203a-3p/miR-16-5p, used with age and motor score, could be a predictor of dementia among PD patients.

Gamification in medical education: identifying and prioritizing key elements through Delphi method.

BACKGROUND: Gamification has gained popularity in medical education, but key elements have not been formally identified. This study aimed to generate and prioritize a list of key elements of gamification in medical education. METHODS: This study utilized a two-stage approach, including the Delphi method and qualitative interview. Nineteen medical educators with expertise in gamification participated in the Delphi method stage. Experts who had more than three years of experience with gamification in medical education constituted the expert panel. The experts were then asked to rate the gamification elements using the Likert five-point scale through at least two consensus-seeking rounds. Consensus for key elements was predefined as ≥ 51% of respondents rating an element as 'important' or"very important." In the qualitative interview stage, 10 experts provided feedback on the application of these key gamification elements. RESULTS: Eighteen participants (11 males and 7 females) completed the entire Delphi process for this study. After two rounds of surveys, the consensus was reached on all elements. Thirteen elements scored more than 4 points (37%) and reached the criteria of key elements of gamification in medical education. The top five key elements were integration with instruction objectives, game rules, rapid feedback, fairness, and points/scoring. The thirteen key elements for successful gamification in medical education were further organized into two main categories: (1) gamification design principles and (2) game mechanisms. CONCLUSIONS: Integration with educational objectives, gamification in curriculum design and teaching methods, and balancing between the mechanisms and principles were the three key components for successful gamification. This study explored the gamification key elements, providing practical tips for medical educators in their efforts to gamify medical education. Future studies involving learners could be performed to examine the efficacy of these key elements in gamification.

The role of noncoding RNAs in Parkinson's disease: biomarkers and associations with pathogenic pathways.

The discovery of various noncoding RNAs (ncRNAs) and their biological implications is a growing area in cell biology. Increasing evidence has revealed canonical and noncanonical functions of long and small ncRNAs, including microRNAs, long ncRNAs (lncRNAs), circular RNAs, PIWI-interacting RNAs, and tRNA-derived fragments. These ncRNAs have the ability to regulate gene expression and modify metabolic pathways. Thus, they may have important roles as diagnostic biomarkers or therapeutic targets in various diseases, including neurodegenerative disorders, especially Parkinson's disease. Recently, through diverse sequencing technologies and a wide variety of bioinformatic analytical tools, such as reverse transcriptase quantitative PCR, microarrays, next-generation sequencing and long-read sequencing, numerous ncRNAs have been shown to be associated with neurodegenerative disorders, including Parkinson's disease. In this review article, we will first introduce the biogenesis of different ncRNAs, including microRNAs, PIWI-interacting RNAs, circular RNAs, long noncoding RNAs, and tRNA-derived fragments. The pros and cons of the detection platforms of ncRNAs and the reproducibility of bioinformatic analytical tools will be discussed in the second part. Finally, the recent discovery of numerous PD-associated ncRNAs and their association with the diagnosis and pathophysiology of PD are reviewed, and microRNAs and long ncRNAs that are transported by exosomes in biofluids are particularly emphasized.

ß-Oscillations Reflect Recovery of the Paretic Upper Limb in Subacute Stroke.

Background. Recovery of upper limb function post-stroke can be partly predicted by initial motor function, but the mechanisms underpinning these improvements have yet to be determined. Here, we sought to identify neural correlates of post-stroke recovery using longitudinal magnetoencephalography (MEG) assessments in subacute stroke survivors. Methods. First-ever, subcortical ischemic stroke survivors with unilateral mild to moderate hand paresis were evaluated at 3, 5, and 12 weeks after stroke using a finger-lifting task in the MEG. Cortical activity patterns in the ß-band (16-30 Hz) were compared with matched healthy controls. Results. All stroke survivors (n=22; 17 males) had improvements in action research arm test (ARAT) and Fugl-Meyer upper extremity (FM-UE) scores between 3 and 12 weeks. At 3 weeks post-stroke the peak amplitudes of the movement-related ipsilesional ß-band event-related desynchronization (ß-ERD) and synchronization (ß-ERS) in primary motor cortex (M1) were significantly lower than the healthy controls (p<0.001) and were correlated with both the FM-UE and ARAT scores (r=0.51-0.69, p<0.017). The decreased ß-ERS peak amplitudes were observed both in paretic and non-paretic hand movement particularly at 3 weeks post-stroke, suggesting a generalized disinhibition status. The peak amplitudes of ipsilesional ß-ERS at week 3 post-stroke correlated with the FM-UE score at 12 weeks (r=0.54, p=0.03) but no longer significant when controlling for the FM-UE score at 3 weeks post-stroke.Conclusions. Although early ß-band activity does not independently predict outcome at 3 months after stroke, it mirrors functional changes, giving a potential insight into the mechanisms underpinning recovery of motor function in subacute stroke.

One-Year Risk of Pneumonia and Mortality in Patients with Poststroke Dysphagia: A Nationwide Population-Based Study.

BACKGROUND: In the early stages of stroke, the use of a nasogastric tube can reduce complications such as malnutrition, dehydration, and pneumonia. However, its long-term efficacy is controversial. METHODS: This retrospective cohort study used Taiwan's National Health Insurance Research Database to investigate associations among dysphagia, rate of readmission due to pneumonia, and mortality 1 year after stroke. Patients who had received their first stroke diagnosis and inpatient rehabilitation from January 1, 2006, to December 31, 2010, were enrolled. The presence of dysphagia was determined by the number of nasogastric tubes received (≥2 was classified as dysphagia, <2 as control). Kaplan-Meier plots with log-rank tests revealed differences between the 2 groups, and a Cox regression model was used to estimate the hazard ratio. RESULTS: There were 5032 patients in the dysphagia group and 52,323 patients in the control group. The dysphagia group had a higher probability and incidence of pneumonia (18.78% versus 6.52%, P < .001 and adjusted hazard ratio [AHR] = 2.00, 95% confidence interval [CI] = 1.84-2.16) and a higher mortality rate (10.45% versus 4.77%, P < .001; AHR = 1.61, 95% CI = 1.46-1.79) 1 year after stroke. CONCLUSIONS: The association persisted until the 5-year poststroke time point. Our results suggest that prolonged nasogastric tube use has negative effects. Intensive evaluation of dysphagia and removal of the nasogastric tube in the early stages of stroke might reduce pneumonia incidence and mortality.

Intermittent theta burst stimulation over ipsilesional primary motor cortex of subacute ischemic stroke patients: a pilot study.

BACKGROUND: We demonstrated that prolonged transcranial magnetic intermittent theta burst stimulation (iTBS, 1200 pulses/session=iTBS1200) produces longer-lasting facilitation in corticospinal excitability than ordinary form of iTBS in healthy subjects. OBJECTIVE: Here we show the safety and small-scale efficacy of iTBS1200 over ipsilesional primary motor cortex (M1) in subacute stroke patients. METHODS: Twelve patients with first-time, subacute ischemic stroke of the middle cerebral artery were randomized into two groups that received 10 daily-sessions of either iTBS1200 or sham stimulation (n=6/group) over ipsilesional M1 hand region in addition to medical and rehabilitation treatments. The primary outcome measures were safety and tolerability. The secondary outcome measures included the National Institute of Health Stroke Scale (NIHSS), Upper Extremity Fugl-Meyer Test (UE-FMT), Action Research Arm Test (ARAT), active motor thresholds (aMTs)/motor-evoked potentials (MEPs) from the extensor carpi radialis (ECR), and magnetoencephalography on post-intervention day 1 and post-stroke day 60. RESULTS: iTBS or sham stimulation was well tolerated by all patients without seizures or significant adverse effects. Compared with the matched controls, the iTBS group showed measurable improvements in the NIHSS and the proximal UE-FMT scores on post-intervention day 1 and post-stroke day 60. Nevertheless, the hand ARAT scores, aMT and MEPs from the paretic ECR were not different between groups. Post-movement beta synchronization increased over iTBS-conditioned M1 on post-intervention day 1 in testable patients. CONCLUSIONS: Repetitive sessions of iTBS1200 over ipsilesional M1 of subacute stroke patients are safe and the potential benefits encourage a larger trial to determine the efficacy in stroke patients. (ClinicalTrials.gov: NCT-01323881).

Intermittent θ burst stimulation over primary motor cortex enhances movement-related ß synchronisation.

OBJECTIVE: The objective of this study is to investigate how transcranial magnetic intermittent theta burst stimulation (iTBS) with a prolonged protocol affects human cortical excitability and movement-related oscillations. METHODS: Using motor-evoked potentials (MEPs) and movement-related magnetoencephalography (MEG), we assessed the changes of corticospinal excitability and cortical oscillations after iTBS with double the conventional stimulation time (1200 pulses, iTBS1200) over the primary motor cortex (M1) in 10 healthy subjects. Continuous TBS (cTBS1200) and sham stimulation served as controls. RESULTS: iTBS1200 facilitated MEPs evoked from the conditioned M1, while inhibiting MEPs from the contralateral M1 for 30 min. By contrast, cTBS1200 inhibited MEPs from the conditioned M1. Importantly, empirical mode decomposition-based MEG analysis showed that the amplitude of post-movement beta synchronisation (16-26 Hz) was significantly increased by iTBS1200 at the conditioned M1, but was suppressed at the nonconditioned M1. Alpha (8-13 Hz) and low gamma-ranged (35-45 Hz) rhythms were not notably affected. Movement kinetics remained consistent throughout. CONCLUSIONS: TBS1200 modulated corticospinal excitability in parallel with the direction of conventional paradigms with modestly prolonged efficacy. Moreover, iTBS1200 increased post-movement beta synchronisation of the stimulated M1, and decreased that of the contralateral M1, probably through interhemispheric interaction. SIGNIFICANCE: Our results provide insight into the underlying mechanism of TBS and reinforce the connection between movement-related beta synchronisation and corticospinal output.