Ocular vestibular-evoked myogenic potential assists in differentiation of multiple system atrophy from Parkinson's disease.

Vestibular-evoked myogenic potentials (VEMPs) can help assess otolithic neural pathway in the brainstem that may also participate in cardiovascular autonomic function. Parkinson's disease (PD) is associated with altered VEMP responses; however, the association between VEMP abnormalities and multiple system atrophy (MSA) remains unknown. Therefore, we compared the extent of otolith dysfunction using ocular (oVEMP) and cervical VEMP (cVEMP) between MSA and PD. We analyzed the clinical features and VEMP and head-up tilt table test (HUT) findings using the Finometer in 24 patients with MSA and 52 with de-novo PD, who had undergone neurotologic evaluation in a referral-based university hospital in South Korea from January 2021 to March 2023. MSA was associated with bilateral oVEMP abnormality (odds ratio [95% confidence interval] = 9.19 [1.77-47.76], p=0.008). n1-p1 amplitude was negatively correlated with Unified Multiple System Atrophy Rating Scale I-II scores in patients with MSA (r=-0.571, p=0.033), whereas it did not correlate with Movement Disorder Society-Unified Parkinson's Disease Rating Scale-III scores in patients with PD (r=-0.051, p=0.687). n1 latency was negatively correlated with maximum changes in systolic blood pressure within 15 s during HUT in patients with PD (r=-0.335, p=0.040) but not in those with MSA (r=0.277, p=0.299). In conclusion, bilaterally abnormal oVEMP responses may indicate the extent of brainstem dysfunction in MSA. oVEMP reflects the integrity of otolith-autonomic interplay, reliably assists in differentiating between MSA and PD, and helps infer clinical decline.

Developing a device for simultaneously investigating pivoting neuromuscular control and muscle properties toward a multi-axis rehabilitation.

Understanding the pivoting neuromuscular control of the lower limb and its associated muscle properties is critical for developing diagnostic and rehabilitation tools. However, to the best of our knowledge, a device that can evaluate these factors simultaneously remains lacking. To address this gap, a device that can investigate pivoting neuromuscular control and associated muscle properties was developed in this study. The proposed device consisted of a pivoting mechanism and height-adjustable chair with a brace interface. The device can control a footplate at various speeds to facilitate pivoting stretching and quantify neuromuscular control. Time-synchronized ultrasonographic images can be acquired simultaneously to quantify muscle properties during both active and passive pivoting movements. The muscle displacement, fascicle length/displacement, pennation angle, pivoting stiffness, and pivoting instability were investigated using the proposed device. Further, the feasibility of the device was demonstrated through a cross-sectional study with healthy subjects. The proposed device successfully quantified changes in muscle displacement during passive and active pivoting movements, pivoting stiffness during passive movements, and neuromuscular control during active movements. Therefore, the proposed device is expected to be used as a research and therapeutic tool for improving pivoting neuromuscular control and muscle functions and investigating the underlying mechanisms associated between muscle properties and joint movement in the transverse plane.

Four-hour-delayed 3D-FLAIR MRIs in patients with acute unilateral peripheral vestibulopathy.

OBJECTIVE: Conventionally, MRI aids in differentiating acute unilateral peripheral vestibulopathy/vestibular neuritis (AUPV/VN) from mimickers. Meanwhile, the diagnostic utility of MRIs dedicated to the inner ear remains to be elucidated for diagnosing AUPV/VN. METHODS: We prospectively recruited 53 patients with AUPV/VN (mean age ± SD = 60 ± 15 years, 29 men). Initial MRIs were performed with a standard protocol, and an additional axial 3D-fluid-attenuated inversion recovery (3D-FLAIR) sequence was obtained 4 h after intravenous injection of gadoterate meglumine. Abnormal enhancement was defined as a signal intensity that exceeded the mean + 2SD value on the healthy side. The findings of neurotologic evaluation and MRIs were compared. RESULTS: Overall, the inter-rater agreement for gadolinium enhancement was 0.886 (Cohen's kappa coefficient). Enhancement was observed in 26 patients (49%), most frequently in the vestibule (n = 20), followed by the anterior (n = 12), horizontal (HC, n = 8), posterior canal (n = 5), and superior (n = 3) and inferior (n = 1) vestibular nerves. In multivariable logistic regression analysis, the enhancement was associated with decreased HC gain in video head-impulse tests (p = 0.036), increased interaural difference in ocular vestibular-evoked myogenic potentials (p = 0.001), and a longer onset-to-MRI time span (p = 0.024). The sensitivity and specificity were 92.3% and 81.5%, respectively, with an area under the curve of 0.90 for predicting gadolinium enhancement. INTERPRETATION: Robust gadolinium enhancement was observed on 4-hour-delayed 3D-FLAIR images in nearly half of the patients with AUPV/VN, with a good correlation with the results of neurotologic evaluation. The positivity may be determined by the extent of vestibular deficit, timing of imaging acquisition, and possibly by the underlying etiology causing AUPV/VN. MRIs may aid in delineating the involved structures in AUPV/VN.

Grapefruit-Inspired Polymeric Capsule with Hierarchical Microstructure: Advanced Nanomaterial Carrier Platform for Energy Storage, Drug Delivery, Catalysis, and Environmental Applications.

Efficient support materials are crucial for maximizing the efficacy of nanomaterials in various applications such as energy storage, drug delivery, catalysis, and environmental remediation. However, traditional supports often hinder nanomaterial performance due to their high weight ratio and limited manageability, leading to issues like tube blocking and secondary pollution. To address this, a novel grapefruit-inspired polymeric capsule (GPC) as a promising carrier platform is introduced. The millimeter-scale GPC features a hydrophilic shell and an internal hierarchical microstructure with 80% void volume, providing ample space for encapsulating diverse nanomaterials including metals, polymers, metal-organic frameworks, and silica. Through liquid-phase bottom-up methods, it is successfully loaded Fe2O3, SiO2, polyacrylic acid, and Prussian blue nanomaterials onto the GPC, achieving high mass ratio (1776, 488, 898, and 634 wt.%, respectively). The GPC shell prevents nanomaterial leakage and the influx of suspended solids, while its internal framework enhances structural stability and mass transfer rates. With long-term storage stability, high carrying capacity, and versatile applicability, the GPC significantly enhances the field applicability of nanomaterials.

Multi-Task Heterogeneous Ensemble Learning-Based Cross-Subject EEG Classification Under Stroke Patients.

Robot-assisted motor training is applied for neurorehabilitation in stroke patients, using motor imagery (MI) as a representative paradigm of brain-computer interfaces to offer real-life assistance to individuals facing movement challenges. However, the effectiveness of training with MI may vary depending on the location of the stroke lesion, which should be considered. This paper introduces a multi-task electroencephalogram-based heterogeneous ensemble learning (MEEG-HEL) specifically designed for cross-subject training. In the proposed framework, common spatial patterns were used for feature extraction, and the features according to stroke lesions are shared and selected through sequential forward floating selection. The heterogeneous ensembles were used as classifiers. Nine patients with chronic ischemic stroke participated, engaging in MI and motor execution (ME) paradigms involving finger tapping. The classification criteria for the multi-task were established in two ways, taking into account the characteristics of stroke patients. In the cross-subject session, the first involved a direction recognition task for two-handed classification, achieving a performance of 0.7419 (±0.0811) in MI and 0.7061 (±0.1270) in ME. The second task focused on motor assessment for lesion location, resulting in a performance of 0.7457 (±0.1317) in MI and 0.6791 (±0.1253) in ME. Comparing the specific-subject session, except for ME on the motor assessment task, performance on both tasks was significantly higher than the cross-subject session. Furthermore, classification performance was similar to or statistically higher in cross-subject sessions compared to baseline models. The proposed MEEG-HEL holds promise in improving the practicality of neurorehabilitation in clinical settings and facilitating the detection of lesions.

Crosstalk between Signaling Pathways and Energy Metabolism in Pluripotency.

The sequential change from totipotency to multipotency occurs during early mammalian embryo development. However, due to the lack of cellular models to recapitulate the distinct potency of stem cells at each stage, their molecular and cellular characteristics remain ambiguous. The establishment of isogenic naïve and primed pluripotent stem cells to represent the pluripotency in the inner cell mass of the pre-implantation blastocyst and in the epiblast from the post-implantation embryo allows the understanding of the distinctive characteristics of two different states of pluripotent stem cells. This review discusses the prominent disparities between naïve and primed pluripotency, including signaling pathways, metabolism, and epigenetic status, ultimately facilitating a comprehensive understanding of their significance during early mammalian embryonic development.

Erectile dysfunction in patient with obstructive sleep apnea: effects of continuous positive airway pressure.

BACKGROUND: Obstructive sleep apnea (OSA) is linked to various health complications, including erectile dysfunction (ED), which is more prevalent in individuals with OSA. This study explored ED in Korean OSA patients and assessed the impact of continuous positive airway pressure (CPAP) therapy on ED. METHODS: A total of 87 male patients with OSA from four different sleep centers underwent physical measurements and completed sleep and mental health (MH) questionnaires, including the Korean version of the International index of erectile function (IIEF), before and three months after initiating CPAP therapy. RESULTS: After three months of CPAP therapy, the patients demonstrated a significant improvement in ED as measured on the IIEF. However, the study found no significant correlation between the duration of CPAP use and the improvement in IIEF score. It did identify the SF36 quality of life assessment as a significant factor influencing ED improvement after CPAP. CONCLUSIONS: ED is a prevalent issue that escalates with age and is associated with OSA. CPAP therapy has shown potential in alleviating ED symptoms, particularly in those with underlying psychological conditions, although further research is required to confirm these findings and understand the underlying mechanisms.

Differentiating changes in movement-related EEG response induced by transcranial direct current stimulation using convolutional neural network.

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique that can modulate neuronal excitability and induce brain plasticity. Although tDCS has been studied with various methods, more research is needed on the movement-related electroencephalography (EEG) changes induced by tDCS. Moreover, it is necessary to investigate whether these changes can be distinguished through a convolutional neural network (CNN)-based classifier. In this study, we measured the EEG during the voluntary foot-tapping task of participants who received tDCS or sham stimulation and evaluated the classification performance. As a result, significantly higher classification accuracy was shown using the ß band (88.7±9.4%), which is more related to motor function, than in the other bands (71.4±10.6% for δ band, 64.1±13.4% for θ band, and 65.7±10.9% for α band). Consequently, EEG changes during the voluntary foot-tapping task induced by tDCS appeared large in the ß band, implying that it is effective in classifying whether tDCS was given or not, and plays an important role in identifying the effect of tDCS.

Association Between Electronic Device Use at Bedtime and COVID-19 Vaccine-Related Adverse Events During the COVID-19 Pandemic in Korean Adults: A Nationwide Cross-Sectional Population-Based Study.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has led to heightened mood disturbances linked to increased electronic device use at bedtime (EUB). General anxiety may contribute to an increased likelihood of experiencing nocebo responses, which have been reported to be associated with COVID-19 vaccine-related adverse events (CAEs). However, no related studies have been conducted to examine this association to date. METHODS: We executed a nationwide cross-sectional study to explore these correlations during the pandemic. Using data from the 2022 National Sleep Survey of South Korea, we analyzed the sleep health of 4,000 adults aged 20-69 years between January and February 2022. Shift workers and those with severe sleep disorders were excluded. Participants with EUB more than four days a week were labeled as high frequency EUB, and those reporting CAEs after both vaccine doses were marked as having a presence of CAEs. The survey also included details about anthropometric data, socioeconomic status, and sleep status. RESULTS: Of the 3,702 participants, 92.6% had received two or more vaccine doses, with 41.2% experiencing CAEs. Furthermore, 73.7% had a high EUB frequency. Factors associated with CAE reporting included younger age, female sex, and high EUB frequency, while heavy alcohol use was found to be less likely to be associated with CAE reporting. Notably, a high EUB frequency was significantly associated with reported CAEs (odds ratio, 1.223; 95% confidence interval, 1.028-1.455; P = 0.023). CONCLUSION: A nationwide online survey conducted in South Korea during the pandemic found that individuals who engaged in the relatively frequent use of electronic devices during bedtime had worse sleep quality and increased COVID-19-related adverse events compared with those using these devices less frequently. These findings have the potential to enhance our understanding of the impact of the use of electronic devices at bedtime on health.

Redefining the role of the cerebellum in restless legs syndrome.

OBJECTIVES: We aimed to investigate alterations in cerebellar volume and the intrinsic cerebellar network in patients with restless legs syndrome (RLS). METHODS: We recruited 69 patients with RLS and 50 healthy controls who underwent brain magnetic resonance imaging (MRI), including three-dimensional T1-weighted imaging. The total cerebellar volume and cerebellar volume subdivisions were analyzed through automatic cerebellum anatomical parcellation using U-Net with locally constrained optimization program. The intrinsic cerebellar network was calculated through brain analysis using a graph theory program based on the cerebellar volume subdivisions. The cerebellar volumes and intrinsic cerebellar networks were compared between patients with RLS and healthy controls. RESULTS: The cerebellar volume and subdivisions in patients with RLS did not show significant differences compared to those in healthy controls. However, significant alterations were observed in the intrinsic cerebellar network of patients with RLS. Increased mean clustering coefficient (0.185 vs. 0.114; p = 0.047) and small-worldness index (0.927 vs. 0.800; p = 0.047) were observed in patients with RLS. Additionally, total cerebellar volume was negatively correlated with the Pittsburgh Sleep Quality Index (r = -0.398; p = 0.020) and Insomnia Severity Index (ISI; r = -0.396; p = 0.011). Negative correlations were additionally observed between the right X lobule volume and the International Restless Legs Syndrome Severity Scale (r = -0.425; p = 0.008) and between the vermis VIII volume and ISI score (r = -0.399; p = 0.011). CONCLUSION: We demonstrated alterations in the intrinsic cerebellar network in patients with RLS compared with healthy controls, showing increased connectivity with increased segregation in patients with RLS. This suggests a potential role of the cerebellum in RLS pathophysiology.

Partial in vivo reprogramming enables injury-free intestinal regeneration via autonomous Ptgs1 induction.

Tissue regeneration after injury involves the dedifferentiation of somatic cells, a natural adaptive reprogramming that leads to the emergence of injury-responsive cells with fetal-like characteristics. However, there is no direct evidence that adaptive reprogramming involves a shared molecular mechanism with direct cellular reprogramming. Here, we induced dedifferentiation of intestinal epithelial cells using OSKM (Oct4, Sox2, Klf4, and c-Myc) in vivo. The OSKM-induced forced dedifferentiation showed similar molecular features of intestinal regeneration, including a transition from homeostatic cell types to injury-responsive-like cell types. These injury-responsive-like cells, sharing gene signatures of revival stem cells and atrophy-induced villus epithelial cells, actively assisted tissue regeneration following damage. In contrast to normal intestinal regeneration involving Ptgs2 induction, the OSKM promotes autonomous production of prostaglandin E2 via epithelial Ptgs1 expression. These results indicate prostaglandin synthesis is a common mechanism for intestinal regeneration but involves a different enzyme when partial reprogramming is applied to the intestinal epithelium.

Correlation of Diffusion Tensor Tractography with Restless Legs Syndrome Severity.

This prospective study investigated white matter tracts associated with restless legs syndrome (RLS) severity in 69 patients with primary RLS using correlational tractography based on diffusion tensor imaging. Fractional anisotropy (FA) and quantitative anisotropy (QA) were analyzed separately to understand white matter abnormalities in RLS patients. Connectometry analysis revealed positive correlations between RLS severity and FA values in various white matter tracts, including the left and right cerebellum, corpus callosum forceps minor and major, corpus callosum body, right cingulum, and frontoparietal tract. In addition, connectometry analysis revealed that the FA of the middle cerebellar peduncle, left inferior longitudinal fasciculus, left corticospinal tract, corpus callosum forceps minor, right cerebellum, left frontal aslant tract, left dentatorubrothalamic tract, right inferior longitudinal fasciculus, left corticostriatal tract superior, and left cingulum parahippocampoparietal tract was negatively correlated with RLS severity in patients with RLS. However, there were no significant correlations between QA values and RLS severity. It is implied that RLS symptoms may be potentially reversible with appropriate treatment. This study highlights the importance of considering white matter alterations in understanding the pathophysiology of RLS and in developing effective treatment strategies.

Structural and functional multilayer network analysis in restless legs syndrome patients.

The combination of brain structural and functional connectivity offers complementary insights into its organisation. Multilayer network analysis explores various relationships across different layers within a single system. We aimed to investigate changes in the structural and functional multilayer network in 69 patients with primary restless legs syndrome (RLS) compared with 50 healthy controls. Participants underwent diffusion tensor imaging (DTI) and resting state-functional magnetic resonance imaging (rs-fMRI) using a three-tesla MRI scanner. We constructed a structural connectivity matrix derived from DTI using a DSI program and made a functional connectivity matrix based on rs-fMRI using an SPM program and CONN toolbox. A multilayer network analysis, using BRAPH program, was then conducted to assess the connectivity patterns in both groups. At the global level, significant differences there were between the patients with RLS and healthy controls. The average multiplex participation was lower in patients with RLS than in healthy controls (0.804 vs. 0.821, p = 0.042). Additionally, several regions showed significant differences in the nodal level in multiplex participation between patients with RLS and healthy controls, particularly the frontal and temporal lobes. The regions affected included the inferior frontal gyrus, medial orbital gyrus, precentral gyrus, rectus gyrus, insula, superior and inferior temporal gyrus, medial and lateral occipitotemporal gyrus, and temporal pole. These results represent evidence of diversity in interactions between structural and functional connectivity in patients with RLS, providing a more comprehensive understanding of the brain network in RLS. This may contribute to a precise diagnosis of RLS, and aid the development of a biomarker to track treatment effectiveness.

Glymphatic system dysfunction in restless legs syndrome: evidenced by diffusion tensor imaging along the perivascular space.

STUDY OBJECTIVES: There is growing evidence pointing at glymphatic system dysfunction in diseases with circadian disruption, such as sleep disorders. Lower diffusivity in the direction of perivascular space has been shown in several neurological and sleep-related disorders; however, its role in restless legs syndrome (RLS) is unclear. We hypothesized that similarly, in RLS the diffusivity in glymphatic system is decreased. Here, we aimed to evaluate glymphatic system functionality in patients with RLS, compare it to healthy controls, and analyze the correlation between its function and clinical characteristics. METHODS: Sixty-nine patients with primary RLS and 51 healthy controls were recruited at a tertiary hospital. All participants underwent diffusion tensor imaging (DTI) and magnetic resonance imaging (MRI) using a 3T MRI scanner, and the DTI along the perivascular space (DTI-ALPS) index was calculated using DTI data. We compared the DTI-ALPS index between the patients with RLS and healthy controls. We also conducted the correlation analysis between the DTI-ALPS index and clinical characteristics, including age, age of onset, symptom duration, and RLS severity. RESULTS: DTI-ALPS index differed significantly between the patients with RLS and healthy controls; the DTI-ALPS index in the patients with RLS was lower than that in the healthy controls (1.48 vs. 0.60, p = 0.008). There was no significant correlation between the DTI-ALPS index and clinical characteristics. CONCLUSION: A significantly lower DTI-ALPS index in patients with RLS suggests that the glymphatic system function is impaired in patients with RLS.

Clinical Features and Neurotologic Findings in Patients With Acute Unilateral Peripheral Vestibulopathy Associated With Antiganglioside Antibody.

BACKGROUND AND OBJECTIVES: Anecdotal studies have reported the presence of antiganglioside antibodies in acute unilateral peripheral vestibulopathy (AUPV). This study aimed to determine the prevalence, clinical characteristics, and neurotologic findings of AUPV associated with antiganglioside antibodies. METHODS: Serum antigangliosides were measured in consecutive patients with AUPV according to the Bárány Society criteria during the acute and recovery phases in a referral-based university hospital in South Korea from September 2019 to January 2023. Clinical characteristics and neurotologic findings were compared between those with and without antiganglioside antibodies. The results of video-oculography, video head impulse and bithermal caloric tests, and other neurotologic evaluations including ocular and cervical vestibular-evoked myogenic potentials and subjective visual vertical were compared between the 2. MRIs dedicated to the inner ear were also conducted when considered necessary. RESULTS: One hundred five patients (mean age ± SD = 60 ± 13 years, 57 male) were included for analyses. During the acute phase, 12 patients (12/105, 11%) were tested positive for serum antiganglioside antibodies, including anti-GQ1b immunoglobulin (Ig) G (n = 5) or IgM (n = 4), anti-GM1 IgM (n = 3), and anti-GD1a IgG (n = 1, including 1 patient with a positive anti-GQ1b antibody). Patients with antiganglioside antibodies showed lesser intensity of spontaneous nystagmus (median [interquartile range] = 1.8 [1.2-2.1] vs 3.4 [1.5-9.5], p = 0.003) and a lesser degree of canal paresis (30 [17-47] vs 58 [34-79], p = 0.028) and gain asymmetry of the vestibulo-ocular reflex for the horizontal semicircular canal during head impulse tests (0.07 [-0.04 to 0.61] vs 0.36 [0.18-0.47], p = 0.032) than those without antibodies. Negative conversion of antibodies and vestibular recovery were observed in most patients (6/8, 75%). Among 30 patients with AUPV with 4-hour delayed 3D fluid-attenuated inversion recovery dedicated to the inner ear, gadolinium enhancement was observed in 18 (18/30, 60%), either in the vestibule (n = 9), semicircular canal (n = 6), or vestibular nerve (n = 5). The positivity rates based on specific antibodies could not be determined due to limited sample sizes. DISCUSSION: The association between antiganglioside antibodies and AUPV suggests an immune-mediated mechanism in acute vestibular failure and extends the clinical spectrum of antiganglioside antibody syndrome.

Venous congestion affects neuromuscular changes in pigs in terms of muscle electrical activity and muscle stiffness.

Early detection of venous congestion (VC)-related diseases such as deep vein thrombosis (DVT) is important to prevent irreversible or serious pathological conditions. However, the current way of diagnosing DVT is only possible after recognizing advanced DVT symptoms such as swelling, pain, and tightness in affected extremities, which may be due to the lack of information on neuromechanical changes following VC. Thus, the goal of this study was to investigate acute neuromechanical changes in muscle electrical activity and muscle stiffness when VC was induced. The eight pigs were selected and the change of muscle stiffness from the acceleration and muscle activity in terms of integral electromyography (IEMG) was investigated in three VC stages. Consequently, we discovered a significant increase in the change in muscle stiffness and IEMG from the baseline to the VC stages (p < 0.05). Our results and approach can enable early detection of pathological conditions associated with VC, which can be a basis for further developing early diagnostic tools for detecting VC-related diseases.

Enhanced functional connectivity in the reward circuitry in healthy adults with weekend catch-up sleep.

We aimed to identify structural and functional changes in healthy adults with catch-up sleep (CUS), we applied seed-based functional connectivity (FC) analysis using resting-state functional magnetic resonance imaging (MRI). We hypothesized that deficits in reward processing could be a fundamental mechanism underlying the motivation of taking CUS. Then, 55 healthy adults voluntarily (34 with CUS and 21 without CUS) participated in this study. Voxel-based morphometry was performed to explore region of gray matter volume (GMV) difference between CUS and non-CUS groups. Between-group comparison of FC was then carried out using resting-state functional MRI analysis seeding at the region of volume difference. Moreover, the region of volume difference and the strength of FC were correlated with scores of questionnaires for reward-seeking behavior and clinical variables. CUS group had a higher reward-seeking tendency, and increased GMV in the bilateral nucleus accumbens and right superior frontal gyrus relative to non-CUS group. FC analysis seeding at the bilateral accumbens revealed increases of FC in the bilateral medial prefrontal cortex in CUS group compared to non-CUS group. The questionnaire scores reflecting the reward-seeking tendency were correlated with the FC strength between bilateral accumbens and medial prefrontal cortex. Our results indicate that CUS is associated with reward-seeking tendency and increased GMV and FC in regions responsible for reward network. Our findings suggest that enhanced reward network could be the crucial mechanism underlying taking CUS and might be implicated in the detrimental effects of circadian misalignment.

Ferric carboxymaltose effects on restless legs syndrome and on brain iron in patients with iron deficiency anemia.

OBJECTIVE: Brain iron status is fundamental in RLS pathogenesis. The aim of this study was to determine the clinical efficacy and brain iron concentration improvement in RLS patients with IDA, using 1500 mg FCM. METHODS: This is a randomized, double-blinded, placebo-controlled study. RLS patients with IDA were grouped into either 1500 mg FCM or placebo. The primary outcomes were the change from baseline on the International Restless Legs Syndrome Study Group scale (IRLS) and brain iron measured by QSM and R2∗. RESULTS: A total of 18 RLS patients with IDA were enrolled, 10 in the FCM group and 8 in the placebo. At the week 6 endpoint, the FCM group showed significant improvement in both IRLS (-13.60 ± 9.47 vs. -3.63 ± 5.40, p = 0.011) and VAS (-40.50 ± 28.81 vs. -0.63 ± 28.28, p = 0.004) from baseline. Change from baseline with R2∗ techniques showed a treatment effect for the thalamus and QSM technique for both the substantia nigra and pulvinar. A correlation was proved between the IRLS difference and the difference of QSM in thalamus (p = 0.028). CONCLUSION: This study demonstrates that 1500 mg FCM effectively treats RLS symptoms in IDA patients over six weeks, with MRI measurements of improved brain iron content serving as a potential biomarker for RLS patients.

Gene editing with 'pencil' rather than 'scissors' in human pluripotent stem cells.

Owing to the advances in genome editing technologies, research on human pluripotent stem cells (hPSCs) have recently undergone breakthroughs that enable precise alteration of desired nucleotide bases in hPSCs for the creation of isogenic disease models or for autologous ex vivo cell therapy. As pathogenic variants largely consist of point mutations, precise substitution of mutated bases in hPSCs allows researchers study disease mechanisms with "disease-in-a-dish" and provide functionally repaired cells to patients for cell therapy. To this end, in addition to utilizing the conventional homologous directed repair system in the knock-in strategy based on endonuclease activity of Cas9 (i.e., 'scissors' like gene editing), diverse toolkits for editing the desirable bases (i.e., 'pencils' like gene editing) that avoid the accidental insertion and deletion (indel) mutations as well as large harmful deletions have been developed. In this review, we summarize the recent progress in genome editing methodologies and employment of hPSCs for future translational applications.

Insomnia during coronavirus disease 2019 pandemic in Korea: a National sleep survey.

Coronavirus disease 2019 (COVID-19) pandemic has caused widespread increase in stress and affected sleep quality and quantity, with up to 30% prevalence of sleep disorders being reported after the declaration of the pandemic. This study aimed to assess perceived changes due to the pandemic in the prevalence of insomnia and excessive daytime sleepiness (EDS) in Korea, and identify the associated factors. An online survey was conducted among 4000 participants (2035 men and 1965 women) aged 20-69 years enrolled using stratified multistage random sampling according to age, sex, and residential area, between January, 2021 and February, 2022. The questionnaire included various items, such as socio-demographics, Insomnia Severity Index, and Epworth Sleepiness Scale (ESS). Insomnia was defined as difficulty falling asleep and difficulty maintaining sleep more than twice a week. EDS was classified as an ESS score ≥ 11. Insomnia was reported by 32.9% (n = 1316) of the participants (37.3% among women and 28.6% among men). Multivariate logistic regression revealed that insomnia was associated with female sex [odds ratio (OR) = 1.526, 95% confidence interval (CI) = 1.297-1.796], night workers (OR 1.561, 95% CI 1.160-2.101), and being unmarried (OR 1.256, 95% CI 1.007-1.566). EDS was reported by 12.8% (n = 510) of the participants (14.7% among men and 10.7% among women). EDS was associated with male sex (OR 1.333, 95% CI 1.062-1.674), and being employed (OR 1.292, 95% CI 1.017-1.641). During the COVID-19 pandemic, the prevalence of insomnia increased in Korea, while there was no significant change in EDS compared with pre-pandemic evidence.