OBJECTIVES: The aim of this study is to evaluate the polysomnographic characteristics and prescription status of restless legs syndrome (RLS) patients in naturalistic setting. METHODS: We reviewed medical record of the patients over 18 years olds who (i) satisfied the clinical RLS diagnostic criteria and (ii) had the polysomnography and got treatment related thereto. As a baseline, we evaluated the four diagnostic criteria of the International Restless Legs Syndrome Study Group (IRLSSG) and the International Restless Legs Scale (IRLS) of the subjects. Then the polysomnography and the suggested immobilization test (SIT) were conducted and, after one month of pharmacotherapy using dopamine agonist, the IRLS was evaluated again. RESULTS: A total of 211 subjects participated in this analysis and 94 (44.5%) of them were male and the other 117 (55.5%) were female and the average age of the 211 subjects was 46.9+/-14.2. Out of such 211 subjects, 136 subjects (64.5%) also had the obstructive sleep apnea (OSA), and 53 subjects (25.1%) also had the periodic limb movement disorder (PLMD). 185 subjects (87.7%) out of the 211 subjects had some other sleep disorders except RLS. The results of the polysomnography were as follows : 78.0% of sleep efficiency, 86.8 min of wake after sleep onset, and 3.4% of N3. More specifically, 12.4/h of the average apnea hypopnea index, 14.8/h of the periodic limb movement during sleep (PLMS), 41.2/h of the periodic limb movement during wake during SIT and 21.6/h of total arousal index during sleep. Out of the total subjects, 149 (70.6%) of them took the ropinirole and 47 (22.3%) of them took the pramipexole, and the average dosage of ropinirole was 0.9mg(dosage range 0.125-5 mg) while the average dosage of pramipexole was 0.5 mg (dosage range 0.125-4 mg). The dosage of the ropinirole showed a significant positive correlation with the age (r=0.25, p=0.002) and also with the IRLS (r=0.23, p=0.038). The IRLS at the baseline was 24.9 while the same was decreased down to 13.4 after one month. CONCLUSIONS: Analyzing the result of this study, a majority of clinical RLS subjects demonstrated comorbidity with some other sleep disorder such as the OSA or PLMD. 25.1% of the subjects showed a PLMD, which was less than in previous researches and the average PLMS was not very high as 14.8/h. The dosage of dopamine agonist taken was often a bit more than the amount recommended in Korea. A prospective research using a large scale controlled subjects will be necessary with respect to this topic.
Apnea ; Arousal ; Benzothiazoles ; Comorbidity ; Dopamine Agonists ; Extremities ; Female ; Humans ; Immobilization ; Indoles ; Isothiocyanates ; Korea ; Male ; Medical Records ; Nocturnal Myoclonus Syndrome ; Polysomnography ; Prescriptions ; Restless Legs Syndrome ; Sleep Apnea, Obstructive ; Sleep Wake Disorders

Digital therapeutics is an evidence-based intervention using high-quality software, with the sole purpose of treatment. As many healthcare systems are encountering high demands of quality outcomes, the need for digital therapeutics is gradually increasing in the clinical field. We conducted review of the implications of digital therapeutics in the treatment of neurological deficits for stroke patients. The implications of digital therapeutics have been discussed in four domains: cognition, speech and aphasia, motor, and vision. It was evident that different forms of digital therapeutics such as online platforms, virtual reality trainings, and iPad applications have been investigated in many trials to test its feasibility in clinical use. Although digital therapeutics may deliver high-quality solutions to healthcare services, the medicalization of digital therapeutics is accompanied with many limitations. Clinically validated digital therapeutics should be developed to prove its efficacy in stroke rehabilitation.
Aphasia ; Aphasia, Broca ; Cognition ; Delivery of Health Care ; Hemianopsia ; Hemiplegia ; Humans ; Medicalization ; Neurologic Manifestations ; Rehabilitation ; Stroke

OBJECTIVES: The consumption, sales, and output of tobacco products each suggest different areas of intervention for tobacco control. In the era of the tobacco endgame, as increasingly stronger supply-side measures are implemented, multifaceted indicators that assess both supply and/or demand are required. We aimed to estimate the consumption of cigarette and heated tobacco products (HTPs) and sought agreement between the various indicators. METHODS: The annual cigarette and HTP consumption in 2014-2020 was calculated using the frequency and intensity of cigarette use from representative surveys of adults and adolescents by sex and age. Sales and output data were acquired from governmental sources. Spearman correlation coefficients and Bland–Altman plots were used to compare the indicators. RESULTS: Tobacco output, cigarette sales, and cigarette consumption were greatest in 2014. The HTP consumption calculated for 2020 was 292.28 million packs. Cigarette consumption and sales correlated significantly, as did tobacco output and tobacco sales. A Bland–Altman plot comparing the difference between cigarette consumption and sales showed that this difference was largest in 2014, immediately before cigarette prices increased. With the exception of a single year, all cigarette consumption values were within the limits of agreement for cigarette sales and tobacco output. CONCLUSIONS Our analyses showed agreement between demand-side (tobacco consumption) and supply-side (sales and output) indicators. We recommend using all indicators to monitor the impacts of tobacco control on both demand and supply sides. The systematic use of various indicators is critical to achieve the end of the tobacco epidemic.

Purpose: Although the mechanism underlying interstitial cystitis/bladder pain syndrome (IC/BPS) remains unclear, oxidative stress is suggested to be implicated in IC/BPS development. Sea buckthorn (SB; Hippophae rhamnoides L.) contains several compounds with antioxidant properties. In addition, intravesical application of hydrochloric acid (HCl) in rats induces histological changes similar to those observed in humans with IC. Therefore, the aim of this study was to evaluate the anti-inflammatory effects of SB in an HCl-induced rat cystitis model. Materials and Methods: Twenty 8-week-old female Sprague–Dawley rats were instilled with HCl in their bladders to create an IC/BPS model. The model rats were divided into three groups and orally administrated distilled water (control, n=4), concentrated SB (n=8), or pentosan polysulfate (PPS, n=8) daily. Pathologic inflammation grade (H&E staining), number of mast cells per square millimeter (toluidine blue staining), fibrotic changes (Masson’s trichrome staining), and apoptosis (terminal deoxynucleotidyl transferase dUTP nick end labeling staining) of bladder tissue samples were compared among the groups. Results: Compared to the control group, the SB and PPS groups showed reduced edema (5.25±0.96 vs. 2.25±0.46 vs. 2.50±0.54, p=0.004, p=0.005, respectively), number of mast cells (12.5±3.6 vs. 6.8±1.9 vs. 6.6±1.8, p=0.010, p=0.002, respectively), ratio of fibrotic submucosal tissue (63.9%±7.0% vs. 43.6%±9.9% vs. 40.5%±5.2%, p<0.001, p<0.001, respectively), and ratio of apoptotic nucleus (40.7%±11.7% vs. 7.7%±6.5% vs. 5.1%±4.9%, p<0.001, p<0.001, respectively). Conclusions SB exhibited anti-inflammatory effects comparable to those of PPS in the HCl-induced chemical cystitis model.

OBJECTIVES: Smoke-free areas have expanded and related campaigns have been implemented since 1995 in Korea. As a result, household secondhand smoke (SHS) exposure has decreased over the past 15 years. We assessed the cohort effect, the effect of a 2008 campaign on household SHS exposure, and the impact of a complete smoking ban in public places along with increased penalties, as implemented in December 2011. METHODS: Nationally representative cross-sectional 15-wave survey data of Korean adolescents were used. The 810,516 participants were classified into 6 grade groups, 15 period groups, and 20 middle school admission cohorts. An age-period-cohort analysis, conducted with the intrinsic estimator method, was used to assess the cohort effect of household SHS exposure, and interrupted-time series analyses were conducted to evaluate the effects of the smoke-free policy and the campaign. RESULTS: For cohorts who entered middle school from 2002 to 2008, the risk of household SHS exposure decreased among both boys and girls. Immediately after implementation of the smoke-free policy, the prevalence of household SHS exposure by period decreased significantly for boys (coefficient, -8.96; p<0.05) and non-significantly for girls (coefficient, -6.99; p=0.07). After the campaign, there was a significant decrease in household SHS exposure by cohort among boys, both immediately and post-intervention (coefficient, -4.84; p=0.03; coefficient, -1.22; p=0.02, respectively). CONCLUSIONS A school-admission-cohort effect was found on household SHS exposure among adolescents, which was associated with the smoke-free policy and the campaign. Anti-smoking interventions should be implemented consistently and simultaneously.

Background and Objectives: The directed differentiation of pluripotent stem cells into motor neurons is critical for the development of disease modelling and therapeutics to intervene degenerative motor neuron diseases. Cell surface receptor Cdo functions as a coreceptor for Sonic hedgehog (Shh) with Boc and Gas1 in the patterning of ventral spinal cord neurons including motor neurons. However, the discrete function of Cdo is not fully understood. Methods: and Results: In this study, we examined the role of Cdo in motor neuron generation by utilizing in vitro differentiation of Cdo＋/＋ and Cdo−/− embryonic stem cells (ESCs). In response to Shh, Cdo−/− ESCs exhibited impaired expression of motor neuron specification markers while dorsal interneuron specification markers were significantly increased, compared to Cdo＋/＋ ESCs. Reactivation of Shh signalling pathway with Smoothened (Smo) agonist (SAG) restored motor neuron specification in Cdo−/− ESCs. In addition, electrophysiological analysis revealed the immature electrical features of Cdo−/− ESCs-derived neurons which was restored by SAG. Conclusions Taken together, these data suggest that Cdo as a Shh coreceptor is required for the induction of motor neuron generation by fully activating Shh signalling pathway and provide additional insights into the biology of motor neuron development.

PKD1 regulates a number of cellular processes through the formation of complexes with the PKD2 ion channel or transient receptor potential classical (TRPC) 4 in the endothelial cells. Although Ca 2+ modulation by polycystins has been reported between PKD1 and TRPC4 channel or TRPC1 and PKD2, the function with TRPC subfamily regulated by PKD2 has remained elusive. We confirmed TRPC4 or TRPC5 channel activation via PKD1 by modulating G-protein signaling without change in TRPC4/C5 translocation. The activation of TRPC4/C5 channels by intracellular 0.2 mM GTPγS was not significantly different regardless of the presence or absence of PKD1. Furthermore, the C-terminal fragment (CTF) of PKD1 did not affect TRPC4/C5 activity, likely due to the loss of the N-terminus that contains the G-protein coupled receptor proteolytic site (GPS). We also investigated whether TRPC1/C4/C5 can form a heterodimeric channel with PKD2, despite PKD2 being primarily retained in the endoplasmic reticulum (ER). Our findings show that PKD2 is targeted to the plasma membrane, particularly by TRPC5, but not by TRPC1. However, PKD2 did not coimmunoprecipitate with TRPC5 as well as with TRPC1. PKD2 decreased both basal and La 3+ -induced TRPC5 currents but increased M 3 R-mediated TRPC5 currents. Interestingly, PKD2 increased STAT3 phosphorylation with TRPC5 and decreased STAT1 phosphorylation with TRPC1. To be specific, PKD2 and TRPC1 compete to bind with TRPC5 to modulate intracellular Ca 2+ signaling and reach the plasma membrane. This interaction suggests a new therapeutic target in TRPC5 channels for improving vascular endothelial function in polycystic kidney disease.

PKD1 regulates a number of cellular processes through the formation of complexes with the PKD2 ion channel or transient receptor potential classical (TRPC) 4 in the endothelial cells. Although Ca 2+ modulation by polycystins has been reported between PKD1 and TRPC4 channel or TRPC1 and PKD2, the function with TRPC subfamily regulated by PKD2 has remained elusive. We confirmed TRPC4 or TRPC5 channel activation via PKD1 by modulating G-protein signaling without change in TRPC4/C5 translocation. The activation of TRPC4/C5 channels by intracellular 0.2 mM GTPγS was not significantly different regardless of the presence or absence of PKD1. Furthermore, the C-terminal fragment (CTF) of PKD1 did not affect TRPC4/C5 activity, likely due to the loss of the N-terminus that contains the G-protein coupled receptor proteolytic site (GPS). We also investigated whether TRPC1/C4/C5 can form a heterodimeric channel with PKD2, despite PKD2 being primarily retained in the endoplasmic reticulum (ER). Our findings show that PKD2 is targeted to the plasma membrane, particularly by TRPC5, but not by TRPC1. However, PKD2 did not coimmunoprecipitate with TRPC5 as well as with TRPC1. PKD2 decreased both basal and La 3+ -induced TRPC5 currents but increased M 3 R-mediated TRPC5 currents. Interestingly, PKD2 increased STAT3 phosphorylation with TRPC5 and decreased STAT1 phosphorylation with TRPC1. To be specific, PKD2 and TRPC1 compete to bind with TRPC5 to modulate intracellular Ca 2+ signaling and reach the plasma membrane. This interaction suggests a new therapeutic target in TRPC5 channels for improving vascular endothelial function in polycystic kidney disease.

PKD1 regulates a number of cellular processes through the formation of complexes with the PKD2 ion channel or transient receptor potential classical (TRPC) 4 in the endothelial cells. Although Ca 2+ modulation by polycystins has been reported between PKD1 and TRPC4 channel or TRPC1 and PKD2, the function with TRPC subfamily regulated by PKD2 has remained elusive. We confirmed TRPC4 or TRPC5 channel activation via PKD1 by modulating G-protein signaling without change in TRPC4/C5 translocation. The activation of TRPC4/C5 channels by intracellular 0.2 mM GTPγS was not significantly different regardless of the presence or absence of PKD1. Furthermore, the C-terminal fragment (CTF) of PKD1 did not affect TRPC4/C5 activity, likely due to the loss of the N-terminus that contains the G-protein coupled receptor proteolytic site (GPS). We also investigated whether TRPC1/C4/C5 can form a heterodimeric channel with PKD2, despite PKD2 being primarily retained in the endoplasmic reticulum (ER). Our findings show that PKD2 is targeted to the plasma membrane, particularly by TRPC5, but not by TRPC1. However, PKD2 did not coimmunoprecipitate with TRPC5 as well as with TRPC1. PKD2 decreased both basal and La 3+ -induced TRPC5 currents but increased M 3 R-mediated TRPC5 currents. Interestingly, PKD2 increased STAT3 phosphorylation with TRPC5 and decreased STAT1 phosphorylation with TRPC1. To be specific, PKD2 and TRPC1 compete to bind with TRPC5 to modulate intracellular Ca 2+ signaling and reach the plasma membrane. This interaction suggests a new therapeutic target in TRPC5 channels for improving vascular endothelial function in polycystic kidney disease.

PKD1 regulates a number of cellular processes through the formation of complexes with the PKD2 ion channel or transient receptor potential classical (TRPC) 4 in the endothelial cells. Although Ca 2+ modulation by polycystins has been reported between PKD1 and TRPC4 channel or TRPC1 and PKD2, the function with TRPC subfamily regulated by PKD2 has remained elusive. We confirmed TRPC4 or TRPC5 channel activation via PKD1 by modulating G-protein signaling without change in TRPC4/C5 translocation. The activation of TRPC4/C5 channels by intracellular 0.2 mM GTPγS was not significantly different regardless of the presence or absence of PKD1. Furthermore, the C-terminal fragment (CTF) of PKD1 did not affect TRPC4/C5 activity, likely due to the loss of the N-terminus that contains the G-protein coupled receptor proteolytic site (GPS). We also investigated whether TRPC1/C4/C5 can form a heterodimeric channel with PKD2, despite PKD2 being primarily retained in the endoplasmic reticulum (ER). Our findings show that PKD2 is targeted to the plasma membrane, particularly by TRPC5, but not by TRPC1. However, PKD2 did not coimmunoprecipitate with TRPC5 as well as with TRPC1. PKD2 decreased both basal and La 3+ -induced TRPC5 currents but increased M 3 R-mediated TRPC5 currents. Interestingly, PKD2 increased STAT3 phosphorylation with TRPC5 and decreased STAT1 phosphorylation with TRPC1. To be specific, PKD2 and TRPC1 compete to bind with TRPC5 to modulate intracellular Ca 2+ signaling and reach the plasma membrane. This interaction suggests a new therapeutic target in TRPC5 channels for improving vascular endothelial function in polycystic kidney disease.