Low-density lipoprotein cholesterol levels and adverse clinical outcomes in chronic kidney disease: Results from the KNOW-CKD.

BACKGROUND AND AIMS: The optimal low-density lipoprotein cholesterol (LDL-C) level to prevent cardiovascular disease in chronic kidney disease (CKD) patients remains unknown. This study aimed to explore the association of LDL-C levels with adverse cardiovascular and kidney outcomes in Korean CKD patients and determine the validity of "the lower, the better" strategy for statin intake. METHODS AND RESULTS: A total of 1886 patients from the KoreaN cohort study for Outcome in patients With CKD (KNOW-CKD) were included. Patients were classified into four LDL-C categories: <70, 70-99, 100-129, and ≥130 mg/dL. The primary outcome was extended major adverse cardiovascular events (eMACEs). Secondary outcomes included all-cause mortality, and CKD progression. During the follow-up period, the primary outcome events occurred in 136 (7.2%) patients (16.9 per 1000 person-years). There was a graded association between LDL-C and the risk of eMACEs. The hazard ratios (95% confidence intervals) for LDL-C categories of 70-99, 100-129, and ≥130 mg/dL were 2.06 (1.14-3.73), 2.79 (1.18-6.58), and 4.10 (1.17-14.3), respectively, compared to LDL-C <70 mg/dL. Time-varying analysis showed consistent findings. The predictive performance of LDL-C for eMACEs was affected by kidney function. Higher LDL-C levels were also associated with significantly higher risks of CKD progression. However, LDL-C level was not associated with all-cause mortality. CONCLUSIONS: This study showed a graded relationship between LDL-C and the risk of adverse cardiovascular outcome in CKD patients. The lowest risk was observed with LDL-C <70 mg/dL, suggesting that a lower LDL-C target may be acceptable.

Tinea capitis in adults: A 18-year retrospective, single-centre study in Korea.

BACKGROUND: Tinea capitis (TC) is a dermatophyte infection involving hair and scalp and occurs primarily in prepubertal children. However, data on adults are limited. OBJECTIVES: The aim of this study was to evaluate epidemiological, clinical and mycological characteristics of TC in adults in Korea. PATIENTS/METHODS: We retrospectively evaluated 82 adults (44.3%) among 185 TC patients at a tertiary hospital during June 2000-2017. RESULTS: Mean patient age was 66.9 ± 15.8 (20-90) years with female predominance; mean disease duration until mycological diagnosis, 22.5 (1-144) weeks; and misdiagnosis rate, 65.9%. Most common presumptive initial diagnoses were seborrhoeic dermatitis (24.4%) and bacterial folliculitis (18.3%). Chronic systemic illness and accompanying alopecia were found in 61 (74.4%) and 46 (56.1%) patients, respectively. Pustular type was found in 26.8% patients, followed by seborrhoeic dermatitis-like 25.6%, grey patch 23.2%, kerion celsi 22.0% and black dot 2.4%. Forty-eight patients (58.5%) had tinea infection at other skin areas. Microsporum canis (56.5%) and Trichophyton rubrum (21.7%) were the most common causative organisms; 92.7% patients achieved complete resolution, and seven patients (9.2%) had a recurrence. CONCLUSIONS: We report the largest, most recent series of case studies of adult TC. Adult TC is not an uncommon problem, especially in elderly women, and has distinctive epidemiological and clinicomycological characteristics compared to those in prepubertal children. Recognising adult TC profile will help clinicians avoid misdiagnosis and provide appropriate treatment.

Sebaceous Carcinoma: Clinicopathologic Analysis of 29 Cases in a Tertiary Hospital in Korea.

Sebaceous carcinoma (SC) is a neoplasm derived from the adnexal epithelium of the sebaceous glands, and most studies on this neoplasm have been conducted in Caucasians. We retrospectively reviewed the records of 29 patients with SC (16 extraocular and 13 ocular lesions) who were diagnosed from 2001 to 2014 to analyze the clinical and histopathological features of SC in the Korean population. Sixteen of the patients were women and 13 were men. There was an equal sex distribution for extraocular lesions, and a female predilection (M:F = 1:1.6) for ocular lesions. The mean ages at presentation of extraocular and ocular lesions were 69.19 ± 37.19 (range, 32-87) and 67.46 ± 24.46 (range, 43-85) years, respectively. Most lesions occurred in the eyelid (13/29, 44.83%), and most extraocular lesions occurred in the head and neck area (13/16, 81.25%). There was no recurrence or death during the follow-up period. Most lesions were poorly differentiated (extraocular, 43.75%; ocular, 38.46%), had a lobular infiltrative growth pattern (extraocular, 68.75%; ocular, 76.92%), and were basaloid (extraocular, 56.25%; ocular, 61.54%). Only 5 cases (2 extraocular and 3 ocular lesions) showed pagetoid spread. Extraocular lesions were marginally more common than the ocular form. There were higher incidences in elderly patients, who also had the highest incidence of eyelid lesions. The proportion of cells with sebaceous differentiation and prominent growth patterns were variable. Our results show that SC may not be very aggressive in Koreans.

Combined Embedding of N/F-Doping and CaCO3 Surface Modification in the TiO2 Photoanode for Dye-Sensitized Solar Cells.

N/F-doping and CaCO3 surface modification was carried out in TiO2 photoelectrodes for dye-sensitized solar cells (DSSCs). The combined effect of the N/F doped TiO2 and the CaCO3 coating showed a great increase of the short-circuit current (J(sc)), and photoelectric conversion efficiency (η) of the prepared cells; the efficiency (η) was improved from 7.00% of a commercial TiO2 photoelectrode to 7.90% of an uncoated N/F-doped electrode, and to 9.09% of a N/F-doped and CaCO3 surface modified electrode. An enhanced photoresponse in N/F-doped TiO2 nanoparticles generate more photo-excited electrons, as supported by measured UV-Vis diffuse reflectance spectra. A successive CaCO3 surface modification then forms a barrier on the surface of the N/F-doped TiO2 particles; the higher basicity of the CaCO3 modified TiO2 facilitates the dye adsorption, as supported by the direct measurement of the amount of adsorbed dye.

Prevention of inflammation-mediated neurotoxicity by butylidenephthalide and its role in microglial activation.

Microglial cells are the prime effectors in immune and inflammatory responses of the central nervous system (CNS). During pathological conditions, the activation of these cells helps restore CNS homeostasis. However, chronic microglial activation endangers neuronal survival through the release of various proinflammatory molecules and neurotoxins. Thus, negative regulators of microglial activation have been considered as potential therapeutic candidates to target neurodegeneration, such as that in Alzheimer's and Parkinson's diseases. The rhizome of Ligusticum chuanxiong Hort. (Ligusticum wallichii Franch) has been widely used for the treatment of vascular diseases in traditional oriental medicine. Butylidenephthalide (BP), a major bioactive component from L. chuanxiong, has been reported to have a variety of pharmacological activities, including vasorelaxant, anti-anginal, anti-platelet and anti-cancer effects. The aim of this study was to examine whether BP represses microglial activation. In rat brain microglia, BP significantly inhibited the lipopolysaccharide (LPS)-induced production of nitric oxide (NO), tumour necrosis factor-α and interleukin-1ß. In organotypic hippocampal slice cultures, BP clearly blocked the effect of LPS on hippocampal cell death and inhibited LPS-induced NO production in culture medium. These results newly suggest that BP provide neuroprotection by reducing the release of various proinflammatory molecules from activated microglia.

Intravascular Papillary Endothelial Hyperplasia in Association with Eccrine Angiokeratomatous Hamartoma.

Eccrine angiokeratomatous hamartoma is a variant of eccrine angiomatous hamartoma. Histopathologically, it shows both features of eccrine angiomatous hamartoma with components of angiokeratoma. Eccrine angiokeratomatous hamartoma is extremely rare. Eccrine angiokeratomatous hamartoma in our case co-existed with intravascular papillary endothelial hyperplasia. This is the first reported case.

Effect of an Integrative Mobile Health Intervention in Patients With Hypertension and Diabetes: Crossover Study.

BACKGROUND: Obesity, hypertension, and type 2 diabetes mellitus (T2DM) are worldwide epidemics that inflict burdens on both public health and health care costs. Self-management plays an important role in the proper management of these 3 chronic diseases, and in this context, mobile health (mHealth) can be a cost-effective self-management tool. OBJECTIVE: The aim of this pilot study is to evaluate the effects of an integrative mHealth approach for obesity, hypertension, and T2DM on body fat, blood pressure, and blood glucose levels and demonstrate the clinical outcomes. The participants were patients aged 40 to 70 years who were treated for T2DM (hemoglobin A1c [HbA1c] above 6.0%) without insulin or hypertension and obesity, controlled with pharmacotherapy. METHODS: This pilot study was performed using a controlled, randomized, 3-month, 2-period crossover design. A total of 37 participants were recruited from 2 university hospitals in South Korea. Integrative mHealth comprised 4 parts: self-measuring home devices for monitoring blood glucose and blood pressure; 2 smartphone apps, where one gathered lifestyle data, giving them feedback with health information, and the other provided drug information and reminders of the medication schedule; unmanned kiosks for official measurement of blood pressure and body composition; and web-based access to participants' health information. RESULTS: Data from the 32 participants were analyzed. Their mean HbA1c level was 7.5% (SD 0.8, ranging from 6.1% to 9.4%). Approximately 38% (12/32) of the participants had hypertension. BMIs of all participants except 1 were >23 kg/m2. The input rates of food intake and exercise to the smartphone app were very low (24.9% and 5.3%, respectively). On the contrary, the input rate of medicine intake was high (84.0%). Moreover, there was no significant difference in the input rate of taking medicine irrespective of whether the mHealth period was before or after the conventional treatment period (80.3% and 87.3%, respectively; P=.06). Among the 3 input functions of food intake, exercise, and medicine intake in smartphone apps, the input of medicine intake was a more helpful, easier to use, and better-designed function than the others. There were no significant differences in changes in body weight (-0.519 kg vs 0 kg), BMI (-0.133 kg/m2 vs -0.167 kg/m2), body composition (body fat -0.255% vs 0.172%), blood pressure (systolic -0.226 mm Hg vs -2.839 mm Hg), and HbA1c (-0.269% vs -0.009%) between the integrative mHealth and conventional treatment groups. However, in proportion to the elevation in the input rate of taking medicine, body fat mass (P=.04) and HbA1c (P=.03) were lower in the integrative mHealth group. CONCLUSIONS: Although smartphone apps can influence body fat and blood glucose levels, they have failed to show clinical improvement. A higher input rate of taking medicine was related to significantly lower body fat mass and HbA1c levels.

Effects of Short-term Mobile Application Use on Weight Reduction for Patients with Type 2 Diabetes.

BACKGROUND: The increasing prevalence of type 2 diabetes mellitus (T2DM) has led to a significant health burden. Technological advancements have highlighted the benefits of digital therapeutics for chronic diseases. In this study, we aimed to investigate the effects of a mobile application on weight reduction in patients with T2DM. METHODS: A total of 48 patients with T2DM was included in this single-center, randomized, controlled trial. In addition to conventional treatment, participants in the intervention group used a mobile application-based self-management system for diet, exercise, and medication adherence. The primary outcome of this study was weight change after 3 months of intervention, and secondary outcomes were metabolic parameters. RESULTS: After 12 weeks, no significant differences in body weight change were observed between the intervention and control groups (P=0.229). However, a significant difference was found in waist circumference (WC) between the two groups, wherein the control group showed an increase in WC (from 95.00±8.89 cm to 95.76±9.72 cm), while the intervention group showed a reduction (from 91.93±6.25 cm to 90.75±6.01 cm) with a significant time by group interaction (P=0.016). Additionally, participants with good compliance exhibited a more evident reduction in WC (P=0.037). However, no significant differences were found in other metabolic parameters between the two groups. CONCLUSION: Lifestyle modification using short-term mobile applications effectively reduced WC, especially in patients with good adherence to the application. However, weight reduction was not achieved.

Cutaneous Mycobacterium massiliense Infection Caused by Skin Coining 'Gua Sha' in Korean Healthy Female.

Nontuberculous mycobacteria are ubiquitous environmental organisms that are rare pathogens in immunocompetent individuals. However, cutaneous nontuberculous mycobacteria infections have been increasingly associated with invasive procedures, including surgery, liposuction, filler injection, intramuscular injection, mesotherapy, piercing, acupuncture, and cupping therapy. Herein, we report the first case of cutaneous nontuberculous mycobacteria infection caused by the East-Asian traditional treatment 'Gua Sha', also known as scraping, coining or spooning in English. A 35-year-old healthy female presented with widespread, painful skin nodules and pustules on her upper and lower extremities that had developed after Gua Sha treatment for body contouring. Histopathologic examination of the lesions revealed granulomatous inflammation in the dermis and the culture isolates were identified as Mycobacterium massiliense with molecular identification. The patient was successfully treated with intermittent incision and drainage of persistent nodules and oral clarithromycin based on antimicrobial susceptibility testing. We recommend implementation of a standard safety protocol for Gua Sha practitioners to minimize the risk of infection transmission.

Non-contact home-adapted device estimates sleep stages in middle-aged men: A preliminary study.

BACKGROUND: Sleep monitoring is essential to maintain a healthy life, especially for the elderly who want to age well. Among various forms of sleep devices, the non-wearable and home-adapted device might be preferred because it can be easily used. OBJECTIVE: In this study, we evaluated the performance of a non-contact home-adapted device compared to polysomnography (PSG), a gold standard method. METHODS: As a preliminary study, eight subjects were recorded over fourteen nights through PSG. The non-contact home-adapted device comprised a microwave sensor, passive infrared sensor, and smartphone application. Through the device, heart rate, respiratory rate, and body movement were collected and used to estimate sleep stages. Sleep structure was labeled in four classes: wake, REM, light, and deep sleep, and were classified using a weighted k-nearest neighbor algorithm. RESULTS: The device correctly estimated sleep structures with an overall epoch-by-epoch accuracy of 98.65% ± 0.05% based on leave-one-out cross-validation. The device showed significantly positive correlations with PSG in sleep indices including total sleep time, sleep efficiency, and wake after sleep onset. CONCLUSIONS: Our findings demonstrate a good performance of this non-contact and home-adapted device and suggest its suitability for sleep monitoring.

Provision of oral hygiene services as a potential method for preventing periodontal disease and control hypertension and diabetes in a community health centre in Korea.

This study aimed to evaluate the effects of a community-based oral hygiene service on general and periodontal health indicators of patients with hypertension and type 2 diabetes mellitus visiting a community health centre in Korea. The study used a one-group pretest-posttest and interrupted time-series design. A total of 151 participants (45% male), with a mean age of 63 ± 8.4 years, were included in the study; these included patients with hypertension (62%), diabetes (12%) and both hypertension and diabetes (26%). Two dental hygienists dedicated 2 days per week to this project, providing oral hygiene services to 10-13 participants per day. Four oral hygiene service sessions were provided per patient. The objective oral hygiene status and subjective self-reported periodontal status were compared before and after the service. The changes in blood pressure and glycosylated haemoglobin levels were also assessed. A lower frequency of subjective swelling was reported at the fourth session (37.9%) compared to the first (55.6%) session. Further, significantly fewer cases of calculus and bleeding were observed (p < .05), and significantly more patients reported having no gum problems at the fourth session (43.1% vs. 27.2%; p < .05) than at the first session. Finally, the participants maintained stable blood pressures at each of the four sessions, and their glycosylated haemoglobin levels were significantly lower at the fourth session. In conclusion, the findings of this study suggest that community oral hygiene services provided by dental hygienists can promote objective oral hygiene and subjective periodontal status in the local community, and may help in the control of hypertension and diabetes.

Tumor Necrosis Factor Alpha Blocker-Induced Erythrodermic Sarcoidosis in with Juvenile Rheumatoid Arthritis: A Case Report and Review of the Literature.

The development of cutaneous sarcoidosis as a paradoxical adverse event of tumor necrosis factor alpha (TNF-α) blockers has been reported in the literature; however, an erythrodermic form of cutaneous sarcoidosis during anti-TNF-α therapy has not yet been reported. Herein, we report the first case of an erythrodermic form of cutaneous sarcoidosis during anti-TNF-α therapy and review previous studies of cutaneous sarcoidosis. A 6-year-old Korean girl who had been suffering from juvenile rheumatoid arthritis presented with generalized erythematous skin eruption involving more than about 90% of her body surface area. After 14 months of etanercept treatment, the new erythematous skin eruption had developed and progressed into generalized erythroderma. Exclusion of suspected co-medication had been performed based on medication history. She had no other systemic symptoms, and ophthalmologic and neurologic examinations were normal. Histopathologic findings of the skin lesion revealed diffuse non-caseating granulomatous infiltrates composed of epithelioid histiocytes with sparse lymphocytes involving the entire dermis. Periodic-acid-Schiff and acid-fast stains were negative, and acid-fast bacilli was not detected by polymerase chain reaction of the skin biopsy. Based on clinicopathologic findings, she was diagnosed with etanercept-induced sarcoidal granuloma. After discontinuation of the suspected agent, the lesions spontaneously disappeared.

Protein arginine methylation facilitates KCNQ channel-PIP2 interaction leading to seizure suppression.

KCNQ channels are critical determinants of neuronal excitability, thus emerging as a novel target of anti-epileptic drugs. To date, the mechanisms of KCNQ channel modulation have been mostly characterized to be inhibitory via Gq-coupled receptors, Ca(2+)/CaM, and protein kinase C. Here we demonstrate that methylation of KCNQ by protein arginine methyltransferase 1 (Prmt1) positively regulates KCNQ channel activity, thereby preventing neuronal hyperexcitability. Prmt1+/- mice exhibit epileptic seizures. Methylation of KCNQ2 channels at 4 arginine residues by Prmt1 enhances PIP2 binding, and Prmt1 depletion lowers PIP2 affinity of KCNQ2 channels and thereby the channel activities. Consistently, exogenous PIP2 addition to Prmt1+/- neurons restores KCNQ currents and neuronal excitability to the WT level. Collectively, we propose that Prmt1-dependent facilitation of KCNQ-PIP2 interaction underlies the positive regulation of KCNQ activity by arginine methylation, which may serve as a key target for prevention of neuronal hyperexcitability and seizures.

Fabrication N, F, and N/F-Doped TiO2 Photoelectrodes for Dye-Sensitized Solar Cells.

In this study, pure TiO2, N-doped TiO2, F-doped TiO2, and N/F-doped TiO2 particles were successfully synthesized through the hydrolysis of TiCl4 in the presence of ammonia water and NH4F, respectively. The introduction of doping materials did not affect the crystalline structure. No absorption peak for pure TiO2 was observed above the wavelength of 400 nm. However, the N-doped TiO2 and N/F-doped TiO2 powders exhibited a new absorption peak in the visible light region between 400 and 530 nm. The Jsc value of DSSCs based on the N/F-doped TiO2 electrode was increased by 10% compared to DSSCs using a pure TiO2 electrode, and the energy conversion efficiency was increased by 12%.

Preparation of Carbon-Doped TiO2 and Its Application as a Photoelectrodes in Dye-Sensitized Solar Cells.

In this study, C-doped TiO2 particles were successfully synthesized by a hydrothermal method. Three binding energy peaks were observed at 284.6, 286.2, and 288.5 eV in the C is region of the XPS. The signals at 286.2 and 288.5 eV were attributed to chemically bound C-O and Ti-C-O linkages within the crystalline TiO2 lattice, respectively. The introduction of carbon did not affect the crystallite structure or BET surface area of TiO2. The JSC value of DSSCs based on a C-doped TiO2 electrode was increased by 20% compared to DSSCs using a pure TiO2 electrode, and the energy conversion efficiency was increased by 23%. This was due to the enhancement of dye adsorption and high electrical conductivity of the carbon. High energy conversion efficiency was achieved with the DSSCs based on the C-doped TiC2 electrode.

The Effect of Scattering Layer on the Performance of Dye-Sensitized Solar Cells Using TiO2 Hollow Spheres/TiO2 Nanoparticles Films as Photoanodes.

TiO2 hollow spheres were successfully synthesized using poly styrene as the template. Dye-sensitized solar cells are fabricated based on double-layered composite films of TiO2 nanoparticles and TiO2 hollow spheres. The photoelectric conversion performances of Dye-sensitized solar cells based on TiO2 nanoparticles/TiO2 nanoparticles, TiO2 nanoparticles/TiO2 hollow spheres and TiO2 hollow spheres/TiO2 hollow spheres double-layered films are investigated, and their photoelectric conversion efficiencies were determined to 4.52, 7.10 and 5.48%, respectively. Dye-sensitized solar cells based on double layered composite films of TiO2 nanoparticles and TiO2 hollow spheres exhibit the highest photo-electric conversion efficiency mainly due to the combined effect of two factors, the high light scattering of over-layer hollow spheres that enhance harvesting light of the Dye-sensitized solar cells and the under-layer TiO2 nanoparticle layer that ensures good electronic contact between TiO2 film and FTO conducting glass. The double layered composite TiO2 film electrodes are a promising development in enhancing the performance of dye-sensitized solar cells.

Salt-Inducible Kinase 1 Terminates cAMP Signaling by an Evolutionarily Conserved Negative-Feedback Loop in ß-Cells.

Pancreatic ß-cells are critical in the regulation of glucose homeostasis by controlled secretion of insulin in mammals. Activation of protein kinase A by cAMP is shown to be responsible for enhancing this pathway, which is countered by phosphodiesterase (PDE) that converts cAMP to AMP and turns off the signal. Salt-inducible kinases (SIKs) were also known to inhibit cAMP signaling, mostly by promoting inhibitory phosphorylation on CREB-regulated transcription coactivators. Here, we showed that SIK1 regulates insulin secretion in ß-cells by modulating PDE4D and cAMP concentrations. Haploinsufficiency of SIK1 led to the improved glucose tolerance due to the increased glucose-stimulated insulin secretion. Depletion of SIK1 promoted higher cAMP concentration and increased insulin secretion from primary islets, suggesting that SIK1 controls insulin secretion through the regulation of cAMP signaling. By using a consensus phosphorylation site of SIK1, we identified PDE4D as a new substrate for this kinase family. In vitro kinase assay as well as mass spectrometry analysis revealed that the predicted Ser(136) and the adjacent Ser(141) of PDE4D are critical in SIK1-mediated phosphorylation. We found that overexpression of either SIK1 or PDE4D in ß-cells reduced insulin secretion, while inhibition of PDE4 activity by rolipram or knockdown of PDE4D restored it, showing indeed that SIK1-dependent phosphorylation of PDE4D is critical in reducing cAMP concentration and insulin secretion from ß-cells. Taken together, we propose that SIK1 serves as a part of a self-regulatory circuit to modulate insulin secretion from pancreatic ß-cells by controlling cAMP concentration through modulation of PDE4D activity.

Efficacious and orally bioavailable thrombin inhibitors based on a 2,5-thienylamidine at the P1 position: discovery of N-carboxymethyl-d-diphenylalanyl-l-prolyl[(5-amidino-2-thienyl)methyl]amide.

Thrombin, a crucial enzyme in the blood coagulation, has been a target for antithrombotic therapy. Orally active thrombin inhibitors would provide effective and safe prophylaxis for venous and arterial thrombosis. We conducted optimization of a highly efficacious benzamidine-based thrombin inhibitor LB30812 (3, K(i) = 3 pM) to improve oral bioavailability. Of a variety of arylamidines investigated at the P1 position, 2,5-thienylamidine effectively replaced the benzamidine without compromising the thrombin inhibitory potency and oral absorption. The sulfamide and sulfonamide derivatization at the N-terminal position in general afforded highly potent thrombin inhibitors but with moderate oral absorption, while the well-absorbable N-carbamate derivatives exhibited limited metabolic stability in S9 fractions. The present work culminated in the discovery of the N-carboxymethyl- and 2,5-thienylamidine-containing compound 22 that exhibits the most favorable profiles of anticoagulant and antithrombotic activities as well as oral bioavilability (K(i) = 15 pM; F = 43%, 42%, and 15% in rats, dogs, and monkeys, respectively). This compound on a gravimetric basis was shown to be more effective than a low molecular weight heparin, enoxaparin, in the venous thrombosis models of rat and rabbit. Compound 22 (LB30870) was therefore selected for further preclinical and clinical development.