Design of an fNIRS-EEG hybrid terminal for wearable BCI systems.

The importance of brain-computer interfaces (BCI) is increasing, and various methods have been developed. Among the developed BCI methods, functional near-infrared spectroscopy (fNIRS) and electroencephalography (EEG) are favored due to their non-invasive feature and compact device sizes. EEG monitors the electrical potentials generated by the activation of neurons, and fNIRS monitors the blood flow also generated by neurons, resulting in signals with different properties between the two methods. As the two BCI methods greatly differ in the characteristics of the acquired neural activity signals, for cases of estimating the intention or thought of a subject by BCI, it has been proven that further accurate information may be extracted by utilizing both methods simultaneously. Both systems are powered by electricity, and as EEG systems are greatly sensitive to electrical noises, application of two separate fNIRS and EEG systems together may result in electrical interference as the systems are required to be in contact with the skin and stray currents from the fNIRS system may flow along the surface of the skin into the EEG system. This research proposes a wearable fNIRS-EEG hybrid BCI system, where a single terminal is capable of operating both as a continuous wave fNIRS emitter and as a detector, and also as an EEG electrode. The system has been designed such that the fNIRS and EEG components are electrically separated to avoid electrical interference between each other. It is expected that by utilizing the developed fNIRS-EEG hybrid terminals, the development of BCI analysis may be further accelerated in various fields.

Fenofibrate and risk of end-stage renal disease: A nationwide cohort study.

AIM: Previous studies have shown that fenofibrate improves outcomes such as albuminuria and estimated glomerular filtration rate decline. We hypothesize that fenofibrate has renoprotective effects and prevents or delays the development of end-stage renal disease. The objective of this study is to investigate the risk of incident end-stage renal disease in relation to fenofibrate treatment in patients who are already taking statins. MATERIALS AND METHODS: We performed a nationwide population-based cohort study using data from the Korea National Health Information Database from 2010 to 2017. Among adults using statins, 413 715 fenofibrate users were compared with 413 715 fenofibrate non-users after 1:1 age, sex and triglyceride matching. The endpoint of this study was incident end-stage renal disease. RESULTS: During a median 3.96-year follow-up, the incidence per 1000 person years of end-stage renal disease was lower in fenofibrate users than in fenofibrate non-users (0.885 vs. 0.960, p < 0.0001). The hazard ratio for end-stage renal disease was lower (0.763, 95% confidence interval 0.710-0.821) in fenofibrate users. This association was significant in patients with hypertension, proteinuria and an estimated glomerular filtration rate <60 mL/min/1.732. CONCLUSIONS: Fenofibrate use in patients taking statins with either hypertension, proteinuria, or decreased estimated glomerular filtration rate is associated with a low risk of incident end-stage renal disease. To confirm the renoprotective effect of fenofibrate in chronic kidney disease, a randomized controlled trial is warranted.

Efficacy and Safety of Pioglitazone Add-on in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Metformin and Dapagliflozin: A Multicenter, Randomized, Double-blind, and Placebo-Controlled Study.

PURPOSE: The purpose of this study was to determine the efficacy and safety profile of pioglitazone compared with placebo (PBO) in patients with type 2 diabetes (T2D) inadequately controlled with metformin and dapagliflozin. METHODS: In this prospective, multicenter, randomized, double-blind, PBO-controlled trial, 366 patients with T2D who did not meet glycemic targets (7.0% ≤ glycosylated hemoglobin [HbA1c] ≤ 10.5%), despite treatment with metformin ≥1000 mg and dapagliflozin 10 mg, received either a PBO, 15 mg of pioglitazone daily (PIO15), or 30 mg of pioglitazone daily (PIO30). The primary end point was the mean change in HbA1c from baseline at 24 weeks across the groups. FINDINGS: For the 366 participants (PBO, n = 124; PIO15, n = 118; PIO30, n = 124), the mean age was 55.6 years and mean duration of diabetes was 8.7 years, with a baseline HbA1c of 7.9%. After 24 weeks, HbA1c reduced significantly in the PIO15 and PIO30 groups from baseline, with intergroup differences of -0.38% and -0.83%, respectively, compared with the PBO group. The proportion of patients with HbA1c levels <7% was significantly higher in the PIO15 and PIO30 groups than in the PBO group. The adverse event rates did not significantly differ across the groups, indicating favorable safety profiles for triple combination therapy using metformin, dapagliflozin, and pioglitazone. IMPLICATIONS: The addition of pioglitazone as a third oral antidiabetic medication is an appropriate option for patients with T2D inadequately controlled with metformin and dapagliflozin based on the resulting significant efficacy in glycemic control and favorable safety profile. CLINICALTRIALS: gov identifier: NCT04885712.

Long-term efficacy and safety of enavogliflozin in Korean people with type 2 diabetes: A 52-week extension of a Phase 3 randomized controlled trial.

AIMS: To evaluate the long-term safety and efficacy of enavogliflozin monotherapy (0.3 mg/day) in individuals with type 2 diabetes mellitus (T2DM). MATERIALS AND METHODS: Following a 24-week randomized, double-blind treatment period with enavogliflozin 0.3 mg/day (n = 77) or placebo (n = 69), consenting participants received enavogliflozin 0.3 mg/day for an additional 28 weeks during an open-label extension (OLE) period. The safety and efficacy of enavogliflozin were assessed at Week 52. RESULTS: A total of 37 participants continued enavogliflozin (maintenance group), and 26 participants switched from placebo to enavogliflozin (switch group). No additional adverse drug reactions related to enavogliflozin were observed during the OLE period. At Week 52, glycated haemoglobin (HbA1c) and fasting plasma glucose were significantly lower than at the baseline, by 0.9% and 24.9 mg/dL, respectively, in the maintenance group (p < 0.0001 for both), and by 0.7% and 18.0 mg/dL, respectively, in the switch group (p < 0.0001 and p = 0.002). The proportions of participants reaching HbA1c 7.0% (53 mmol/mol) at Week 52 were 69.4% in the maintenance group and 65.4% in the switch group. A significant increase in urine glucose-to-creatinine ratio was observed at Week 52, by 84.9 g/g and 67.1 g/g in the maintenance and switch groups, respectively (p < 0.0001 for both). Body weight in both groups decreased significantly (p < 0.0001) from baseline to Week 52, by 3.5 kg and 3.8 kg in the maintenance and switch groups, respectively. CONCLUSIONS: Enavogliflozin 0.3 mg monotherapy provides long-term glycaemic control in T2DM and is safe and well tolerated during a 52-week treatment period.

Fenofibrate's impact on cardiovascular risk in patients with diabetes: a nationwide propensity-score matched cohort study.

BACKGROUND: The beneficial effects of fenofibrate on atherosclerotic cardiovascular disease (ASCVD) outcomes in patients with diabetes and statin treatment are unclear. We investigated the effects of fenofibrate on all-cause mortality and ASCVD in patients with diabetes, high triglyceride (TG) levels and statin treatment. METHODS: We performed a nationwide propensity-score matched (1:1) cohort study using data from the National Health Information Database in the Republic of Korea from 2010 to 2017. The study included 110,723 individuals with diabetes, TG levels ≥ 150 mg/dL, and no prior diagnoses of ASCVD who used statins and fenofibrate, and an equal matched number of similar patients who used statins alone (control group). The study outcomes included newly diagnosed myocardial infarction (MI), stroke, both (MI and/or stroke), and all-cause mortality. RESULTS: Over a mean 4.03-year follow-up period, the hazard ratios (HR) for outcomes in the fenofibrate group in comparison to the control group were 0.878 [95% confidence interval (CI) 0.827-0.933] for MI, 0.901 (95% CI 0.848-0.957) for stroke, 0.897 (95% CI 0.858-0.937) for MI and/or stroke, and 0.716 (95% CI 0.685-0.749) for all-cause death. These beneficial effects of fenofibrate were consistent in the subgroup with TG 150-199 mg/dL but differed according to low-density lipoprotein cholesterol (LDL-C) levels. CONCLUSION: In this nationwide propensity-score matched cohort study involving individuals with diabetes and TG ≥ 150 mg/dL, the risk of all-cause death and ASCVD was significantly lower with fenofibrate use in conjunction with statin treatment compared to statin treatment alone. However, this finding was significant only in individuals with relatively high LDL-C levels.

Association between exercise habits and incident type 2 diabetes mellitus in patients with thyroid cancer: nationwide population-based study.

BACKGROUND: We investigated the association between exercise habits before or after thyroidectomy and incident type 2 diabetes mellitus (T2DM) in patients with thyroid cancer. METHODS: An observational cohort study of 69,526 thyroid cancer patients who underwent thyroidectomy for the treatment of thyroid cancer between 2010 and 2016 was performed using the Korean National Health Information Database. Regular exercise was defined as mid-term or vigorous exercise at least 1 day in a week based on a self-reported questionnaire. Patients were divided into four groups according to exercise habits before and after thyroidectomy: persistent non-exercisers, new exercisers, exercise dropouts, and exercise maintainers. RESULTS: During a median follow-up of 4.5 years, 2,720 (3.91%) patients developed T2DM. The incidence of T2DM per 1,000 person years was lower in patients who performed regular exercise before or after thyroidectomy than in persistent non-exercisers (10.77 in persistent non-exerciser group, 8.28 in new exerciser group, 8.59 in exercise dropout group, and 7.61 in exercise maintainer group). Compared with the persistent non-exerciser group, the new exerciser group (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.78-0.97), the exercise dropout group (HR 0.81, 95% CI 0.72-0.91), and the exercise maintainer group (HR 0.84, 95% CI 0.76-0.93) had lower risks of incident T2DM. Exercising < 1,500 MET-minutes/week in the exercise maintainer group was associated with a lower risk of incident T2DM compared with persistent non-exercisers (< 500: HR 0.80, 95% CI 0.67-0.96, P = 0.002; 500 to < 1,000: HR 0.81, 95% CI 0.71-0.93, P < 0.001; 1,000 to < 1,500: HR 0.81, 95% CI 0.69-0.94, P < 0.001). CONCLUSIONS: Regular exercise before or after thyroidectomy was associated with a lower risk of incident T2DM in patients with thyroid cancer.

Efficacy and Safety of Metformin and Atorvastatin Combination Therapy vs. Monotherapy with Either Drug in Type 2 Diabetes Mellitus and Dyslipidemia Patients (ATOMIC): Double-Blinded Randomized Controlled Trial.

BACKGRUOUND: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. METHODS: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. RESULTS: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. -0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (-55.20% vs. -7.69%, P<0.001) without previously unknown adverse drug events. CONCLUSION: The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin's preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

Stress hyperglycemia exacerbates inflammatory brain injury after stroke.

Post-stroke hyperglycemia occurs in 30% - 60% of ischemic stroke patients as part of the systemic stress response, but neither clinical evidence nor pre-clinical studies indicate whether post-stroke hyperglycemia affects stroke outcome. Here we investigated this issue using a mouse model of permanent ischemia. Mice were maintained either normoglycemic or hyperglycemic during the interval of 17 - 48 hours after ischemia onset. Post-stroke hyperglycemia was found to increase infarct volume, blood-brain barrier disruption, and hemorrhage formation, and to impair motor recovery. Post-stroke hyperglycemia also increased superoxide formation by peri-infarct microglia/macrophages. In contrast, post-stroke hyperglycemia did not increase superoxide formation or exacerbate motor impairment in p47 phox-/- mice, which cannot form an active superoxide-producing NADPH oxidase-2 complex. These results suggest that hyperglycemia occurring hours-to-days after ischemia can increase oxidative stress in peri-infarct tissues by fueling NADPH oxidase activity in reactive microglia/macrophages, and by this mechanism contribute to worsened functional outcome.

A compact six-axis force/torque sensor using photocouplers for impact robustness.

This paper presents a novel six-axis force/torque (F/T) sensor design for robotics, combining ease of manufacturing with compactness. It features a high measuring range of ∼3700 N, an exceptional resolution of 0.1 N, and a rapid 5 kHz sampling rate. The sensor's design, focusing on durability and a wider sensing range, utilizes noncontact sensors and a streamlined structure. A novel force sensing scheme aligns sensing elements in-plane on a single printed circuit board, reducing the part count to four and the weight to under 80 g, while integrating an analog-to-digital converter to eliminate the need for external communication devices. The lightweight, efficient prototype demonstrates a superior performance and a high response frequency, validated against a reference F/T sensor.

LNK/SH2B3 loss of function increases susceptibility to murine and human atrial fibrillation.

AIMS: The lymphocyte adaptor protein (LNK) is a negative regulator of cytokine and growth factor signalling. The rs3184504 variant in SH2B3 reduces LNK function and is linked to cardiovascular, inflammatory, and haematologic disorders, including stroke. In mice, deletion of Lnk causes inflammation and oxidative stress. We hypothesized that Lnk-/- mice are susceptible to atrial fibrillation (AF) and that rs3184504 is associated with AF and AF-related stroke in humans. During inflammation, reactive lipid dicarbonyls are the major components of oxidative injury, and we further hypothesized that these mediators are critical drivers of the AF substrate in Lnk-/- mice. METHODS AND RESULTS: Lnk-/- or wild-type (WT) mice were treated with vehicle or 2-hydroxybenzylamine (2-HOBA), a dicarbonyl scavenger, for 3 months. Compared with WT, Lnk-/- mice displayed increased AF duration that was prevented by 2-HOBA. In the Lnk-/- atria, action potentials were prolonged with reduced transient outward K+ current, increased late Na+ current, and reduced peak Na+ current, pro-arrhythmic effects that were inhibited by 2-HOBA. Mitochondrial dysfunction, especially for Complex I, was evident in Lnk-/- atria, while scavenging lipid dicarbonyls prevented this abnormality. Tumour necrosis factor-α (TNF-α) and interleukin-1 beta (IL-1ß) were elevated in Lnk-/- plasma and atrial tissue, respectively, both of which caused electrical and bioenergetic remodelling in vitro. Inhibition of soluble TNF-α prevented electrical remodelling and AF susceptibility, while IL-1ß inhibition improved mitochondrial respiration but had no effect on AF susceptibility. In a large database of genotyped patients, rs3184504 was associated with AF, as well as AF-related stroke. CONCLUSION: These findings identify a novel role for LNK in the pathophysiology of AF in both experimental mice and humans. Moreover, reactive lipid dicarbonyls are critical to the inflammatory AF substrate in Lnk-/- mice and mediate the pro-arrhythmic effects of pro-inflammatory cytokines, primarily through electrical remodelling.

Association of non-alcoholic fatty liver disease with cardiovascular disease and all cause death in patients with type 2 diabetes mellitus: nationwide population based study.

OBJECTIVE: To investigate the risk of non-alcoholic fatty liver disease (NAFLD) for cardiovascular disease and all cause death in patients with type 2 diabetes mellitus (T2DM). DESIGN: Nationwide population based study. SETTING: Longitudinal cohort study in Korea. PARTICIPANTS: 7 796 763 participants in the National Health Screening Programme in 2009 were divided into three groups based on NAFLD status: no NAFLD (fatty liver index<30); grade 1 NAFLD (30≤fatty liver index<60); and grade 2 NAFLD (fatty liver index≥60). Median follow-up was 8.13 years. MAIN OUTCOME MEASURES: The primary outcome was incident cardiovascular disease (myocardial infarction, ischaemic stroke) or all cause death. RESULTS: Of 7 796 763 participants, 6.49% (n=505 763) had T2DM. More patients with T2DM had grade 1 NAFLD (34.06%) and grade 2 NAFLD (26.73%) than those without T2DM (grade 1 NAFLD: 21.20%; grade 2 NAFLD: 10.02%). The incidence rate (per 1000 person years) of cardiovascular disease and all cause death increased in the order of no NAFLD, grade 1 NAFLD, and grade 2 NAFLD, and the incidence rates in patients with T2DM were higher than those in patients without T2DM. The five year absolute risk for cardiovascular disease and all cause death increased in the order of no NAFLD, grade 1 NAFLD, and grade 2 NAFLD in patients without and with T2DM (no NAFLD, without T2DM: 1.03, 95% confidence interval 1.02 to 1.04, and 1.25, 1.24 to 1.26, respectively; grade 1 NAFLD, without T2DM: 1.23, 1.22 to 1.25, and 1.50, 1.48 to 1.51, respectively; grade 2 NAFLD, without T2DM: 1.42, 1.40 to 1.45, and 2.09, 2.06 to 2.12, respectively; no NAFLD, with T2DM: 3.34, 3.27 to 3.41, and 3.68, 3.61 to 3.74, respectively; grade 1 NAFLD, with T2DM: 3.94, 3.87 to 4.02, and 4.25, 4.18 to 4.33, respectively; grade 2 NAFLD, with T2DM: 4.66, 4.54 to 4.78, and 5.91, 5.78 to 6.05, respectively). Patients with T2DM and without NAFLD had a higher five year absolute risk for cardiovascular disease and all cause death than those without T2DM and with grade 2 NAFLD. Risk differences for cardiovascular disease and all cause death between no NAFLD and grade 1 or grade 2 NAFLD were higher in patients with T2DM than in those without T2DM. CONCLUSIONS: NAFLD in patients with T2DM seems to be associated with a higher risk of cardiovascular disease and all cause death, even in patients with mild NAFLD. Risk differences for cardiovascular disease and all cause death between the no NAFLD group and the grade 1 or grade 2 NAFLD groups were higher in patients with T2DM than in those without T2DM.

Clinical Characteristics of Patients With Statin Discontinuation in Korea: A Nationwide Population-Based Study.

Objective: To investigate the clinical characteristics of patients with statin discontinuation in Korea, using a nationwide database. Methods: We analyzed 1,308,390 patients treated with statin for the first time in their life between 2016 and 2017 using the Korean National Health Information Database. The patients participated in the Korean National Health Screening Program within two years before taking statin. Patients with statin discontinuation were defined as those who were not prescribed statin between 365 days and 730 days after the initial statin prescription. Results: The overall prevalence of statin discontinuation was 39.44%. Patients with statin discontinuation were younger, had lower body mass index (BMI), included a higher number of smokers and drinkers, did not exercise regularly, with fewer cases of hypertension and diabetes mellitus than those without statin discontinuation (p<0.001). Compared with patients aged 20-29 years, the risk of statin discontinuation showed a U-shaped relationship with age (odds ratios [ORs]: 0.619 in 30-39 years; 0.454 in 40-49 years; 0.345 in 50-59 years; 0.307 in 60-69 years; 0.324 in 70-79 years; and 0.415 in ≥80 years). In addition, increased BMI was associated with decreased risk of statin discontinuation (ORs: 0.969 with 25.0-29.9 kg/m2, and 0.890 with ≥30.0 kg/m2). Patients with hypertension and diabetes mellitus were at a lower risk of statin discontinuation (OR: 0.414 for hypertension; 0.416 for diabetes mellitus). Conclusion: The prevalence of patients with statin discontinuation in Korea was 39.44% at 1 to 2 years after initial statin treatment.

ent-Verticilide B1 Inhibits Type 2 Ryanodine Receptor Channels and is Antiarrhythmic in Casq2 -/- Mice.

Intracellular Ca2+ leak from cardiac ryanodine receptor (RyR2) is an established mechanism of sudden cardiac death (SCD), whereby dysregulated Ca2+ handling causes ventricular arrhythmias. We previously discovered the RyR2-selective inhibitor ent-(+)-verticilide (ent-1), a 24-membered cyclooligomeric depsipeptide that is the enantiomeric form of a natural product (nat-(-)-verticilide). Here, we examined its 18-membered ring-size oligomer (ent-verticilide B1; "ent-B1") in RyR2 single channel and [3H]ryanodine binding assays, and in Casq2 -/- cardiomyocytes and mice, a gene-targeted model of SCD. ent-B1 inhibited RyR2 single channels and RyR2-mediated spontaneous Ca2+ release in Casq2 -/- cardiomyocytes with sub-micromolar potency. ent-B1 was a partial RyR2 inhibitor, with maximal inhibitory efficacy of less than 50%. ent-B1 was stable in plasma, with a peak plasma concentration of 1460 ng/ml at 10 minutes and half-life of 45 minutes after intraperitoneal administration of 3 mg/kg in mice. In vivo, ent-B1 significantly reduced catecholamine-induced ventricular arrhythmias in Casq2 -/- mice in a dose-dependent manner. Hence, we have identified a novel chemical entity - ent-B1 - that preserves the mechanism of action of a hit compound and shows therapeutic efficacy. These findings strengthen RyR2 as an antiarrhythmic drug target and highlight the potential of investigating the mirror-image isomers of natural products to discover new therapeutics. SIGNIFICANCE STATEMENT: The cardiac ryanodine receptor (RyR2) is an untapped target in the stagnant field of antiarrhythmic drug development. We have confirmed RyR2 as an antiarrhythmic target in a mouse model of sudden cardiac death and shown the therapeutic efficacy of a second enantiomeric natural product.

Enhancing the production of recombinant human TGF-ß1 through an understanding of TGF-ß1 synthesis, signaling, and endocytosis in CHO cells.

To enhance the production of recombinant human transforming growth factor-beta1 (rhTGF-ß1) in Chinese hamster ovary (CHO) cells, rhTGF-ß1 was first characterized for endocytosis, signaling pathway, and overall maturation process. The mature rhTGF-ß1 used for clinical application was internalized into CHO cells and inhibited the growth of CHO cells in a dose-dependent manner. However, mature rhTGF-ß1 was mostly produced in the form of latent rhTGF-ß1 in cultures of recombinant CHO (rCHO) cells producing rhTGF-ß1 (CHO-rhTGF-ß1). The concentration of active mature rhTGF-ß1 in the culture supernatant of CHO-rhTGF-ß1 cells was not high enough to compromise yield. In addition, a significant amount of unprocessed precursors was produced by CHO-rhTGF-ß1 cells. Overexpression of PACEsol, a soluble form of furin, in CHO-rhTGF-ß1 cells was effective for the proteolytic cleavage of unprocessed precursors. The highest mature rhTGF-ß1 concentration (6.4 µg mL-1 ) was obtained with the PACEsol-expressing clone, which was approximately 45% higher than that of the parental clone (P < 0.01). Thus, a comprehensive understanding of the intrinsic properties of rhTGF-ß1 with respect to the overall maturation process, signaling pathway, and endocytosis is essential for effectively enhancing the production of mature rhTGF-ß1 in CHO cells.

Accuracy and Safety of the 15-Day CareSens Air Continuous Glucose Monitoring System.

Background: We evaluated the accuracy and safety of the CareSens Air, a novel real-time continuous glucose monitoring system (CGMS), during 15 days of use in adults with diabetes. Methods: Adults with either type 1 diabetes or type 2 diabetes requiring intensive insulin therapy participated at four sites in South Korea. All participants wore the sensor for 15 days. Participants were scheduled for four 8-h clinic sessions on Day 1, 5 ± 1, 10 ± 1, and 15. Accuracy was evaluated based on the proportion of continuous glucose monitoring (CGM) values within 15% of YSI values ≥100 mg/dL or within 15 mg/dL of YSI values <100 mg/dL (%15/15), along with the %20/20, %30/30, and %40/40 agreement rates. The mean absolute relative difference (MARD) between the CGM and YSI values was calculated. Results: Data from 83 participants (83 sensors, 10,029 CGM-YSI matched pairs) were analyzed. The overall MARD was 10.42%, and the overall %15/15, %20/20, %30/30, and %40/40 accuracy were 78.55%, 89.04%, 96.47%, and 98.87%, respectively. The consensus error grid analysis showed that 99.92% of CGM values fell into Zone A or B (Zone A: 89.83%, Zone B: 10.09%). The %20/20 accuracy of CGMS was 88.11% on Day 1, 90.11% on Day 3-5, 92.09% on Day 8-10, and 85.63% on Day 15. No serious adverse events were reported. Conclusions: The CareSens Air demonstrated accurate performance across the wide glycemic range and was well tolerated during the 15-day sensor use period.

Emergence of task-related spatiotemporal population dynamics in transplanted neurons.

Loss of nervous system tissue after severe brain injury is a main determinant of poor functional recovery. Cell transplantation is a promising method to restore lost tissue and function, yet it remains unclear if transplanted neurons can demonstrate the population level dynamics important for movement control. Here we present a comprehensive approach for long-term single neuron monitoring and manipulation of transplanted embryonic cortical neurons after cortical injury in adult male mice performing a prehension task. The observed patterns of population activity in the transplanted network strongly resembled that of healthy networks. Specifically, the task-related spatiotemporal activity patterns of transplanted neurons could be represented by latent factors that evolve within a low dimensional manifold. We also demonstrate reliable modulation of the transplanted networks using minimally invasive epidural stimulation. Our approach may allow greater insight into how restoration of cell-type specific network dynamics in vivo can restore motor function.

Effectiveness of low-intensity atorvastatin 5 mg and ezetimibe 10 mg combination therapy compared with moderate-intensity atorvastatin 10 mg monotherapy: A randomized, double-blinded, multi-center, phase III study.

BACKGROUND: We compared the efficacy and safety of low-intensity atorvastatin and ezetimibe combination therapy with moderate-intensity atorvastatin monotherapy in patients requiring cholesterol-lowering therapy. METHODS: At 19 centers in Korea, 290 patients were randomized to 4 groups: atorvastatin 5 mg and ezetimibe 10 mg (A5E), ezetimibe 10 mg (E), atorvastatin 5 mg (A5), and atorvastatin 10 mg (A10). Clinical and laboratory examinations were performed at baseline, and at 4-week and 8-week follow-ups. The primary endpoint was percentage change from baseline in low-density lipoprotein (LDL) cholesterol levels at the 8-week follow-up. Secondary endpoints included percentage changes from baseline in additional lipid parameters. RESULTS: Baseline characteristics were similar among the study groups. At the 8-week follow-up, percentage changes in LDL cholesterol levels were significantly greater in the A5E group (49.2%) than in the E (18.7%), A5 (27.9%), and A10 (36.4%) groups. Similar findings were observed regarding the percentage changes in total cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B levels. Triglyceride levels were also significantly decreased in the A5E group than in the E group, whereas high-density lipoprotein levels substantially increased in the A5E group than in the E group. In patients with low- and intermediate-cardiovascular risk, 93.3% achieved the target LDL cholesterol levels in the A5E group, 40.0% in the E group, 66.7% in the A5 group, and 92.9% in the A10 group. In addition, 31.4% of patients in the A5E group, 8.1% in E, 9.7% in A5, and 7.3% in the A10 group reached the target levels of both LDL cholesterol < 70 mg/dL and reduction of LDL ≥ 50% from baseline. CONCLUSIONS: The addition of ezetimibe to low-intensity atorvastatin had a greater effect on lowering LDL cholesterol than moderate-intensity atorvastatin alone, offering an effective treatment option for cholesterol management, especially in patients with low and intermediate risks.

Emergence of preparatory dynamics in VIP interneurons during motor learning.

To determine what actions to perform in each context, animals must learn how to execute motor programs in response to sensory cues. In rodents, the interface between sensory processing and motor planning occurs in the secondary motor cortex (M2). Here, we investigate dynamics in vasointestinal peptide (VIP) and somatostatin (SST) interneurons in M2 during acquisition of a cue-based, reach-to-grasp (RTG) task in mice. We observe the emergence of preparatory activity consisting of sensory responses and ramping activation in a subset of VIP interneurons during motor learning. We show that preparatory and movement activities in VIP neurons exhibit compartmentalized dynamics, with principal component 1 (PC1) and PC2 reflecting primarily movement and preparatory activity, respectively. In contrast, we observe later and more synchronous activation of SST neurons during the movement epoch with learning. Our results reveal how VIP population dynamics might support sensorimotor learning and compartmentalization of sensory processing and movement execution.