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Partial trisomy 1q is a rare chromosomal disorder characterized by ventriculomegaly with craniofacial, renal, cardiac, and finger and toe anomalies. Most reported cases of partial trisomy1q have involved stillborn or premature deaths due to cardiac or liver failure. This case report describes an 18-month-old patient with partial duplication of the 1q32-44 segments and consequent developmental delays who exhibited improvement in developmental status with rehabilitation. Prenatal ultrasonography and magnetic resonance imaging of the mother revealed ventriculomegaly and atrophic changes in the left cerebral hemisphere of the fetus. The infant was born with micrognathia, microphthalmia, macrocephaly, low-set ears, polydactyly, and long feet at 37+5 weeks of gestation. A chromosomal study revealed an abnormal male karyotype of 46,XY,rec(1)dup(1)(q32.1q44)inv(1)(p36.3q32.1)pat. In this rare case of a patient with partial trisomy, we observed improvement in developmental delays following treatment using appropriate rehabilitation techniques. Further research is required to help validate the findings of this case study and establish a standardized rehabilitation technique that can be subsequently applied to such cases.

Objective Fenestrated screw fixation with bone cement augmentation has been demonstrated to increase the pullout strength. Bone cement augmentation is performed to prevent screw failure. The study aimed to investigate the safety and efficacy of multilevel percutaneous fenestrated screw fixation with bone cement augmentation in the adult lumbar spinal deformity. Methods We performed a retrospective study of 15 patients who underwent multilevel percutaneous fenestrated screw fixation (PFSF) with bone cement augmentation between January 2018 and December 2020. Visual analogue scale (VAS) score, Oswestry disability index (ODI), sagittal vertical axis (SVA), and lumbar lordosis (LL) were investigated in the patients. Results Mean BMD was -2.0. The mean percutaneous fenestrated screw fixation level was 6. The mean VAS score changed from 7.14 preoperatively to 4.57 postoperatively, to 3.71 at the last follow-up. The mean ODI changed from 45.21 preoperatively to 32.5 postoperatively, to 27.0 at the last follow-up. The mean LL changed from 23.6 preoperatively to 32.96 postoperatively, to 31.67 at the last follow-up. The mean SVA changed from 76.65 preoperatively to 46.15 postoperatively, to 48.46 at the last follow-up. The bony fusion rate was 73.3%. There were screw loosening in 4 patients and screw fracture in 3 patients. Cement leakage occurred towards the anterior body of the vertebrae in 2 patients but no symptoms were observed. Conclusion Our study results demonstrate that multilevel PFSF with bone cement augmentation can result in good clinical and radiological outcomes for lumbar spinal deformity. However, larger size screws or smaller through-hole screws are required to prevent screw fracture.

Objective: Henoch–Schönlein purpura is a systemic vasculitis that mainly occurs in children. Renal impairment is a major complication of Henoch–Schönlein purpura, but there is no established predictive marker for renal involvement. Thus, in this study, we investigated the risk factors for renal involvement in children with Henoch–Schönlein purpura. Method: The medical records of children newly diagnosed as having Henoch–Schönlein purpura between 2005 and 2020 were reviewed retrospectively. Selected laboratory data were recorded before treatment initiation. The date and the age at diagnosis; sex; and the presence of arthralgia, gastrointestinal and renal involvement were obtained retrospectively. Results: This study included a total of 186 patients with Henoch–Schönlein purpura. Among them, 36.0% had renal involvement; 28.4% had only microscopic hematuria, 53.7% had non-nephrotic range proteinuria, and 17.9% had nephrotic-range proteinuria during follow-up. The mean age was higher (p = 0.016) and female sex was predominant (p = 0.001) in patients with renal involvement than in those without renal involvement. Blood neutrophil/lymphocyte ratio (p = 0.002) and platelet/lymphocyte ratio (p = 0.002) were significantly higher than that of the patients without renal involvement. No statistically significant differences were observed in the hemoglobin concentration, platelet count, presence of arthralgia, and gastrointestinal involvement between patients with and without renal involvement. Logistic regression analysis revealed female sex (odd ratio = 3.213) and neutrophil/lymphocyte ratio (odd ratio = 1.329) as risk factors for renal involvement. Conclusions: Female sex and high neutrophil/lymphocyte ratio were risk factors for renal involvement in Henoch–Schönlein purpura.

Objective Previous literatures have demonstrated widely variable clinical results after transsacral epiduroscopic laser decompression (SELD) and the factors predicting outcomes are not yet established. Therefore, we analyzed the clinical outcome and associated predictive factors of SELD in patients with lumbar disc herniation. Methods Between 2015 and 2018, 82 patients who underwent single-level SELD and followed up at least 6 months were enrolled. The overall success rate (excellent or good results at final follow-up) was 58.5% according to Odom’s criteria. Based on this result, patients were divided to 2 groups: a favorable group (n = 48) and an unfavorable group (n = 34). A retrospective review of the baseline characteristics and clinical outcome were conducted to reveal the predictive factors. Results As expected, improvement of pain and patient satisfaction, was more favorable in the favorable group (p < 0.05). Moreover, the rate of additional procedure was lower in the favorable group (4.2%, 2 of 48 patients) than in the unfavorable group (35.3%, 12 of 34 patients) (p = 0.011). Among the various baseline characteristics, the only significant predictive factor for favorable outcome was the presence of a high-intensity zone (HIZ) on preoperative magnetic resonance imaging (50.0% [24 of 48 patients] in the favorable group vs. 11.8% [4 of 34 patients] in the unfavorable group; odds ratio, 15.67; p = 0.024). Conclusion Although SELD for lumbar disc herniation resulted in a less favorable clinical outcome than that reported in previous studies, in patients with a HIZ, SELD can be an effective minimally invasive surgery to relieve low back pain and/or leg pain.

Abstract Patients with brain metastases (BM) can benefit from radiotherapy (RT), although the long-term benefits of RT remain unclear. We searched a Korean national health insurance claims database and identified 135,740 patients with newly diagnosed BM during 2002–2017. Propensity score matching (PSM) was used to evaluate survival according to RT modality, which included whole-brain radiotherapy (WBRT) and/or stereotactic radiosurgery (SRS). The 84,986 eligible patients were followed for a median interval of 6.6 months, and 37,046 patients underwent RT (43.6%). After the PSM, patients who underwent RT had significantly better overall survival after 1 year (42.4% vs. 35.3%, P

Natural products are promising drug candidates with various pharmacological effects. However, they can be difficult to use due to poor bioavailability or low stability. In this experiment, while developing topical formulations containing 0.1% Agrimonia pilosa extract, a simple and rapid method of analyzing flavonoid glucuronides, which are representative ingredients, was developed and validated, and the physicochemical properties and stability of flavonoid glucuronides were observed. As a result, an optimized cream formulation was developed. The oil phase comprised tween 60, liquid paraffin, propylene glycol, cetanol, stearyl alcohol, span 60, benzyl alcohol, and A. pilosa extracts, and the water phase comprised water and citric acid hydrate. Then, physicochemical and microbial stability tests of the formulation were conducted under long-term (12 months) and accelerated conditions (6 months). It was thus confirmed that both physicochemical and biological properties were stable during the test period. Consequently, an optimized formulation for the extract was developed and stability was confirmed.

Background: Insufficient physical activity (PA) has a negative effect on mental health. Many countries try to promote PA. The Korea National Health and Nutrition Examination Survey (KNHANES) aims to promote PA and the importance of the recognition of subjective health and body image and mental health. Objectives: The study aimed to analyze the relationship among body factors, PA, and mental health of Korean adults using the seventh KNHANES (2018) survey. Methods: KNHANES is a cross-sectional survey and investigates every 3 years. Data contain 4416 households (19–65-year-old) responses, and it was weighted average or sample fraction by reflecting the sampling and response rate of population ratio. International PA Questionnaire, metabolic equivalents tasks, Health Enhancing PA, Patient Health Questionnaire-9, Body factors, subjective health recognition, and subjective body image recognition were analyzed by t-test, ANOVA, Chi-square test, and Pearson's r. Results: Correlation among PA and mental health, PA of females was correlated with stress. The PA of males was highly related to the overall mental health. In the differences by gender and PA, females enjoying exercise have a tendency of less body mass index (BMI) and more satisfied with subjective body image. Males showed no difference in BMI but on body factors; males with vigorous activity were higher on height and weight than males with walking activity. Mental health with PA, females with walking activity showed higher depression than females with moderate activity. Likewise, males with walking activity exhibited higher depression than males with moderate and vigorous activity. Females and males showed their PA affects perceived stress. Conclusion: These results suggest promoting PA may lead to enhance mental health.

Collecting and monitoring data in low-latency from numerous sensing devices is one of the key foundations in networked cyber-physical applications such as industrial process control, intelligent traffic control, and networked robots. As the delay in data updates can degrade the quality of networked monitoring, it is desirable to continuously maintain the optimal setting on sensing devices in terms of transmission rates and bandwidth allocation, taking into account application requirements as well as time-varying conditions of underlying network environments. In this paper, we adapt deep reinforcement learning (RL) to achieve a bandwidth allocation policy in networked monitoring. We present a transferable RL model Repot in which a policy trained in an easy-to-learn network environment can be readily adjusted in various target network environments. Specifically, we employ flow embedding and action shaping schemes in Repot that enable the systematic adaptation of a bandwidth allocation policy to the conditions of a target environment. Through experiments with the NS-3 network simulator, we show that Repot achieves stable and high monitoring performance across different network conditions, e.g., outperforming other heuristics and learning-based solutions by 14.5~20.8% in quality-of-experience (QoE) for a target network environment. We also demonstrate the sample-efficient adaptation in Repot by exploiting only 6.25% of the sample amount required for model training from scratch. We present a case study with the SUMO mobility simulator and verify the benefits of Repot in practical scenarios, showing performance gains over the others, e.g., 6.5% in urban-scale and 12.6% in suburb-scale.

Background It is challenging to diagnose asthma in preschool children. The asthma predictive index (API) has been used to predict asthma and decide whether to initiate treatment in preschool children. Purpose This study aimed to investigate the association between questionnaire-based current asthma with API, pulmonary function, airway hyperreactivity (AHR), fractional expiratory nitric oxide (FeNO), and atopic sensitization in preschool children. Methods We performed a population-based cross-sectional study in 916 preschool children aged 4–6 years. We defined current asthma as the presence of both physician-diagnosed asthma and at least one wheezing episode within the previous 12 months using a modified International Study of Asthma and Allergies in Childhood questionnaire. Clinical and laboratory parameters were compared between groups according to the presence of current asthma. Results The prevalence of current asthma was 3.9% in the study population. Children with current asthma showed a higher rate of positive bronchodilator response and loose and stringent API scores than children without current asthma. The stringent API was associated with current asthma with 72.2% sensitivity and 82.0% specificity. The diagnostic accuracy of the stringent API for current asthma was 0.771. However, no intergroup differences in spirometry results, methacholine provocation test results, FeNO level, or atopic sensitization rate were observed. Conclusion The questionnaire-based diagnosis of current asthma is associated with API, but not with spirometry, AHR, FeNO, or atopic sensitization in preschool children.

In this study, we aimed to develop and validate a pretreatment method for separating and analyzing the small amounts of biomarkers contained in topical cream formulations. Analyzing semisolid formulations that contain low concentrations of active ingredients is difficult. Cream formulations containing an aqueous ethanol extract of 0.1% Agrimonia pilosa is an example. Approximately 0.0013% of apigenin-7-O-glucuronide(A7OG) was contained as a biomarker in the cream. To determine the A7OG content present in the cream formulation, liquid–liquid extraction using dichlormethane was applied. In addition, the volume of the distribution liquid was measured using the peak ratios of the indicator component, A7OG, and an internal standard, baicalin. Subsequently, the A7OG content in the cream formulation was calculated. Using this time-saving method, A7OG can be simply analyzed without additional pretreatment steps, such as evaporation and reconstitution. Moreover, the validation results confirmed that this analytical method met all of the criteria. Consequently, A7OG was successfully isolated from the cream, analyzed, and quantified using the developed method.

Abstract Background Asthma is a syndrome composed of heterogeneous disease entities. Although it is agreed that proper asthma endo-typing and appropriate type-specific interventions are crucial in the management of asthma, little data are available regarding pediatric asthma. Methods We designed a cluster-based, prospective, observational cohort study of asthmatic children in Korea (Korean childhood Asthma Study [KAS]). A total of 1000 Korean asthmatic children, aged from 5 to 15 years, will be enrolled at the allergy clinics of the 19 regional tertiary hospitals from August 2016 to December 2018. Physicians will verify the relevant histories of asthma and comorbid diseases, as well as airway lability from the results of spirometry and bronchial provocation tests. Questionnaires regarding subjects’ baseline characteristics and their environment, self-rating of asthma control, and laboratory tests for allergy and airway inflammation will be collected at the time of enrollment. Follow-up data regarding asthma control, lung function, and environmental questionnaires will be collected at least every 6 months to assess outcome and exacerbation-related aggravating factors. In a subgroup of subjects, peak expiratory flow rate will be monitored by communication through a mobile application during the overall study period. Cluster analysis of the initial data will be used to classify Korean pediatric asthma patients into several clusters; the exacerbation and progression of asthma will be assessed and compared among these clusters. In a subgroup of patients, big data-based deep learning analysis will be applied to predict asthma exacerbation. Discussion Based on the assumption that asthma is heterogeneous and each subject exhibits a different subset of risk factors for asthma exacerbation, as well as a different disease progression, the KAS aims to identify several asthma clusters and their essential determinants, which are more suitable for Korean asthmatic children. Thereafter we may suggest cluster-specific strategies by focusing on subjects’ personalized aggravating factors during each exacerbation episode and by focusing on disease progression. The KAS will provide a good academic background with respect to each interventional strategy to achieve better asthma control and prognosis.

Background Pathologic diagnosis of central nervous system (CNS) neoplasms is made by comparing light microscopic, immunohistochemical, and molecular cytogenetic findings with clinicoradiologic observations. Intraoperative frozen cytology smears can improve the diagnostic accuracy for CNS neoplasms. Here, we evaluate the diagnostic value of cytology in frozen diagnoses of CNS neoplasms. Methods Cases were selected from patients undergoing both frozen cytology and frozen sections. Diagnostic accuracy was evaluated. Results Four hundred and fifty-four cases were included in this retrospective single-center review study covering a span of 10 years. Five discrepant cases (1.1%) were found after excluding 53 deferred cases (31 cases of tentative diagnosis, 22 cases of inadequate frozen sampling). A total of 346 cases of complete concordance and 50 cases of partial concordance were classified as not discordant cases in the present study. Diagnostic accuracy of intraoperative frozen diagnosis was 87.2%, and the accuracy was 98.8% after excluding deferred cases. Discrepancies between frozen and permanent diagnoses (n = 5, 1.1%) were found in cases of nonrepresentative sampling (n = 2) and misinterpretation (n = 3). High concordance was observed more frequently in meningeal tumors (97/98, 99%), metastatic brain tumors (51/52, 98.1%), pituitary adenomas (86/89, 96.6%), schwannomas (45/47, 95.8%), high-grade astrocytic tumors (47/58, 81%), low grade astrocytic tumors (10/13, 76.9%), non-neoplastic lesions (23/36, 63.9%), in decreasing frequency. Conclusions Using intraoperative cytology and frozen sections of CNS tumors is a highly accurate diagnostic ancillary method, providing subtyping of CNS neoplasms, especially in frequently encountered entities.

Background As one of the main components of mangosteen (Garcinia mangostana), a tropical fruit, α-mangostin has been reported to have numerous pharmacological benefits such as anti-cancer, anti-inflammatory, and anti-allergic effects through various mechanisms of action. The effects of α-mangostin on intracellular signaling proteins is well studied, but the effects of α-mangostin on ion channels and its physiological effects in immune cells are unknown. Generation of intracellular calcium signaling is a fundamental step for T cell receptor stimulation. This signaling is mediated not only by the ORAI1 calcium channel, but also by potassium ion channels, which provide the electrical driving forces for generating sufficient calcium ion influx. This study investigated whether α-mangosteen suppress T cell stimulation by inhibiting ORAI1 and two kinds of potassium channels (Kv1.3 and KCa3.1), which are normally expressed in human T cells. Methods This study analyzed the inhibitory effect of α-mangostin on immune cell activity via inhibition of calcium and potassium ion channels expressed in immune cells. Results α-mangostin inhibited ORAI1 in a concentration-dependent manner, and the IC50 value was 1.27 ± 1.144 µM. Kv1.3 was suppressed by 41.38 ± 6.191% at 3 µM, and KCa3.1 was suppressed by 51.16 ± 5.385% at 3 µM. To measure the inhibition of cytokine secretion by immune cells, Jurkat T cells were stimulated to induce IL-2 secretion, and α-mangostin was found to inhibit it. This study demonstrated the anti-inflammatory effect of α-mangostin, the main component of mangosteen, through the regulation of calcium signals.

BackgroundDecompressive craniectomy is an important surgical treatment for patients with severe traumatic brain injury (TBI). Several reports have been published on the efficacy of non-watertight sutures in duraplasty performed in decompressive craniectomy. This study sought to determine the safety and feasibility of the non-suture dural closure technique in decompressive craniectomy.MethodsA total of 106 patients were enrolled at a single trauma center between January 2017 and December 2018. We retrospectively collected data and classified the patients into non-suture and suture duraplasty craniectomy groups. We compared the characteristics of patients and their intra/postoperative findings such as operative time, blood loss, imaging findings, complications, and Glasgow Outcome Scale scores.ResultsThere were 37 and 69 patients in the non-suture and suture duraplasty groups, respectively. There were no significant differences between the two groups concerning general characteristics. The operative time was significantly lower in the non-suture duraplasty group than in the suture duraplasty group (150 min vs. 205 min; p = 0.002). Furthermore, blood loss was significantly less severe in the non-suture duraplasty group than in the suture duraplasty group (1000 mL vs. 1500 mL; p = 0.028). There were no other significant differences.ConclusionNon-suture duraplasty involved shorter operative times and less severe blood losses than suture duraplasty. Other complications and prognoses were similar across groups. Therefore, the non-suture duraplasty in decompressive craniectomy is a safe and feasible surgical technique.

ObjectiveMany studies on the clinical outcome of full endoscopic spine surgery versus open spine surgery have been published. However, only a few studies have compared the learning curves of percutaneous endoscopic interlaminar lumbar discectomy (PEILD) and open lumbar microdiscectomy (OLM) at the L5-S1 level. This study included patients with disc herniation at the L5-S1 level, who underwent PEILD or OLM performed by a single novice surgeon and compared the learning curves.MethodsFifty-six patients who underwent PEILD or OLM at the L5-S1 level and completed a minimum 1-year follow-up were enrolled in the study. The patients were allocated to the PEILD group (n = 27, September 2014 to August 2016) or an OLM group (n = 29, September 2012 to August 2014). The learning curves were retrospectively compared based on operation time and surgical outcomes, including complication, failure, and recurrence rates were retrospectively compared.ResultsSignificant intergroup differences were not noted with respect to the baseline characteristics, including age, sex, body mass index, preoperative symptoms, or preoperative radiological findings. The mean operation time was significantly shorter in the PEILD group than in the OLM group (63.89±17.99 min versus 78.03±19.01 min, p = 0.006). Based on the operation time according to the number of cases, the learning curve was more difficult in the PEILD group according to the cumulative analysis (case number cut-off for proficiency was 18 in the PEILD group versus 10 in the OLM group) and linear regression analysis (proportionality constant for decrease in the operation time was -0.922 in the PEILD group versus -1.738 in the OLM group) than that in the OLM group. However, the surgical outcomes, including failure, surgical efficacy based on nerve root decompression, complication, and recurrence rates did not differ between the two groups.ConclusionAlthough the learning curve of PEILD was more difficult than that of OLM, the mean operation time was shorter in the PEILD group than that in the OLM group. Moreover, based on the surgical outcomes, PEILD showed efficacy and safety similar to those of OLM.

Objective. Nowadays, trans-sacral epiduroscopic laser decompression (SELD) using slender epiduroscopy and laser is one of the preferred options for minimally invasive treatment in lumbar disc diseases. However, SELD is still in the initial stages of the global field of spine surgery, and the clinical outcomes in patients with lumbar disc herniation are not established yet. Therefore, the authors investigated patients undergoing SELD to report the clinical results. Methods. Between November 2015 and November 2018, a total of 82 patients who underwent single-level SELD for lumbar disc herniation with a minimum follow-up of 6.0 months were enrolled. A retrospective review of clinical data was conducted. Clinical outcomes were evaluated using the visual analogue scale (VAS) for low back and leg pain and Odom’s criteria. Also, surgical outcomes, including complications and symptom recurrences, and radiological outcomes were analyzed. Results. Low back pain and leg pain as determined by the VAS improved from an average of 5.43 ± 1.73 and 6.10 ± 1.67 to 2.80 ± 1.43 and 3.58 ± 2.08 at the final follow-up (p

KELCH-ECH-associated protein 1 (KEAP1) is an adaptor protein of Cullin 3 (CUL3) E3 ubiquitin ligase that targets a redox sensitive transcription factor, NF-E2-related factor 2 (NRF2). BRCA1-associated protein 1 (BAP1) is a tumor suppressor and deubiquitinase whose mutations increase the risk of several types of familial cancers. In the present study, we have identified that BAP1 deubiquitinates KEAP1 by binding to the BTB domain. Lentiviral transduction of BAP1 decreased the expression of NRF2 target genes, suppressed the migration and invasion, and sensitized cisplatin-induced apoptosis in human lung adenocarcinoma (LUAD) A549 cells. Examination of the lung tissues in KrasG12D/+ mice demonstrated that the level of Bap1 and Keap1 mRNAs progressively decreases during lung tumor progression, and it is correlated with NRF2 activation and the inhibition of oxidative stress. Supporting this observation, lentiviral transduction of BAP1 decreased the growth of A549 xenografts in athymic nude mice. Transcriptome analysis of human lung tissues showed that the levels of Bap1 mRNA are significantly higher in normal samples than LUAD samples. Moreover, the expression of Bap1 mRNA is associated with a better survival of LUAD patients. Together, our study demonstrates that KEAP1 deubiquitination by BAP1 is novel tumor suppressive mechanism of LUAD.

Background: Solar irradiation affects sensitization to aeroallergens and the prevalence of allergic diseases. Little is known, however, about how the time and amount of solar irradiation during pregnancy affects such risks in children. We aimed to find out how solar irradiation during pregnancy affects sensitization to aero-allergens and the prevalence of allergic diseases in children. Methods: This population-based cross-sectional study involved 7301 aged 6 years and aged 12 years children. Maternal exposure to solar irradiation during pregnancy was evaluated using data from weather stations closest to each child's birthplace. Monthly average solar irradiation during the second and third trimesters was calculated with rank by quartiles. Risks of allergic sensitization and allergic disease were estimated. Results: Relative to the first (lowest) quartile, the adjusted odds ratio (aOR) for allergic sensitization in the fourth (highest) quartile was lowest within solar irradiation during pregnancy months 5–6 (aOR = 0.823, 95% CI 0.720–0.942, p

This study aims to evaluate the accuracy and effectiveness of real-time personal monitoring of exposure to PM concentrations using low-cost sensors, in comparison to conventional data collection method based on fixed stations. PM2.5 data were measured every 5 min using a low-cost sensor attached to a bag carried by 47 asthmatic children living in the Seoul Metropolitan area between November 2019 and March 2020, along with the real-time GPS location, temperature, and humidity. The mobile sensor data were then matched with station-based hourly PM2.5 data using the time and location. Despite some uncertainty and inaccuracy of the sensor data, similar temporal patterns were found between the two sources of PM2.5 data on an aggregate level. However, average PM2.5 concentrations via personal monitoring tended to be lower than those from the fixed stations, particularly when the subjects were indoors, during nighttime, and located farther from the fixed station. On an individual level, a substantial discrepancy is observed between the two PM2.5 data sources while staying indoors. This study provides guidance to policymakers and researchers on improving the feasibility of personal monitoring via low-cost mobile sensors as an alternative or supplement to the conventional station-based monitoring.

Context: Spirodela polyrhiza (L.) Schleid. (Lemnaceae), Spirodelae Herba (SH), has been known to relieve inflammation, urticaria and skin symptoms including pruritus, eczema and rash. Objective: The effects of SH extract on two calcium ion channels, Orai1 and TRPV3, and their potential as novel therapeutics for atopic dermatitis (AD) were investigated. The regulatory role of Orai1 on mast cell degranulation was evaluated. Materials and methods: The dried leaves of SH were extracted by 70% methanol. Effects of SH extract (100 μg/mL) in an HEK293T cell line overexpressing human Orai1 or TRPV3 were assessed. Ion channel modulation in transfected HEK293T cells was measured using a conventional whole-cell patch-clamp technique. IgE-antigen complex-stimulated mast cell degranulation was measured by β-hexosaminidase assay with morphological observation after treatment with 20, 50 and 100 μg/mL SH extract. Results: SH extract (100 μg/mL) significantly inhibited Orai1 activity (63.8 ± 0.97%) in Orai1-STIM1 co-overexpressed HEK293T cells. SH extract significantly increased TRPV3 activity (81.29 ± 0.05% at −100 mV) compared with the positive control 2-APB (100 μM), which induced full activation. SH extract inhibited degranulation in IgE-antigen complex-stimulated RBL-2H3 mast cells by decreasing β-hexosaminidase activity (3.14 ± 0.03, 2.56 ± 0.12 and 2.29 ± 0.08 mU/mg, respectively). Conclusion: Our results suggested that SH extract could treat abnormal skin barrier pathologies in AD through modulation of the activities of the calcium ion channels Orai1 and TRPV3 and inhibition of mast cell degranulation. This is the first report of an herbal effect on the modulation of ion channels associated with skin barrier disruption in AD pathogenesis.

Objective The conventional microsurgical interlaminar approach for upper lumbar disc herniation (LDH) can increase the risk of postoperative spinal instability due to excessive laminectomy and/or facetectomy. The authors present a key-hole laminotomy (microsurgical translaminar approach) for upper LDH, which allows less destructive laminotomy, and review the results of this surgical technique. Methods Between 2007 and 2014, 20 patients underwent single level discectomy in the upper lumbar spine (L1-2 or L2-3) using a microsurgical translaminar approach. Mean patient age was 58.0±12.0 years and minimum follow-up was 1.0 years. A retrospective review of clinical and radiological data was conducted. Results Back pain and leg pain were improved from an average of 4.9±1.1 and 8.3±0.9 to 0.9±0.7 and 0.9±1.6 at 1-year postoperatively (p

Objective: To examine the effects of Tribulus terrestris L. (T. terrestris) extract on the modulation of calcium channels to evaluate its use in topical agents for treatment of atopic dermatitis. Methods: The 70% methanol extract of T. terrestris was prepared. Human HEK293T cells with over-expressed calcium release-activated calcium channel protein 1 (Orai1), transient receptor potential vanilloid 1, or transient receptor potential vanilloid 3 (TRPV3) were treated with T. terrestris extract. Modulation of ion channels was measured using a conventional whole-cell patch-clamp technique. Results: T. terrestris extract (100 μg/mL) significantly inhibited Orai1 activity in Orai1-stromal interaction molecule 1 co-overexpressed HEK293T cells. In addition, T. terrestris extract significantly increased the TRPV3 activity compared with 2-Aminoethyl diphenylborinate (100 μmol/L), which induces the full activation of TRPV3. Conclusions: Our results suggest that T. terrestris extract may have a therapeutic potential for recovery of abnormal skin barrier pathologies in atopic dermatitis through modulating the activities of calcium ion channels, Orai1 and TRPV3. This is the first study to report the modulatory effect of a medicinal plant on the function of ion channels in skin barrier.

BACKGROUND:Education on inhaler technique is critical for effective asthma treatment. However, traditionally used face-to-face education is time-consuming, costly, and often laborious. The current study evaluated the efficacy of a newly developed video-based inhaler technique education method. METHODS:A total of 184 subjects with well-controlled or partly-controlled asthma were enrolled from 12 hospitals in South Korea from 30 November 2015 to 01 June 2016. Subjects were randomly divided into two groups in a 1:1 ratio; a control group that received face-to-face education, and a study group that received video education. All subjects received fluticasone propionate plus salmeterol xinafoate (Fluterol® 250/50 inhalation capsules) for 12 weeks. The primary outcome measure was forced expiratory volume in the 1st second (FEV1) at 12 weeks. The secondary outcome measures were change in FEV1 at 4 weeks, change in asthma control test (ACT) score, and changes in various inhaler technique parameters. These measures were assessed with a non-inferiority margin of 10% between the control group and the study group. RESULTS:FEV1 was significantly improved at 12 weeks in the control group and the study group. After adjustment, FEV1 improvement was not significantly inferior in the study group compared to the control group. The secondary outcome measures, including change in FEV1 at 4 weeks, ACT score, and various parameters pertaining to inhaler technique and satisfaction at 4 and 12 weeks did not differ significantly in the two groups. In subgroup analysis of elderly subjects and subjects with well-controlled asthma, FEV1 was significantly improved at 12 weeks in the study group but not the control group. CONCLUSION:The newly developed video education technique investigated functioned as a suitable substitute for face-to-face education on inhaler technique (dry powder inhalation capsule) in patients with stable asthma, particularly in elderly patients and patients with well-controlled asthma.

Dysfunction of T helper 17 (Th17) cells leads to chronic inflammatory disorders. Signal transducer and activator of transcription 3 (STAT3) orchestrates the expression of proinflammatory cytokines and pathogenic cell differentiation from interleukin (IL)-17-producing Th17 cells. However, the pathways mediated by STAT3 signaling are not fully understood. Here, we observed that Fos-related antigen 1 (FRA1) and JUNB are directly involved in STAT3 binding to sites in the promoters of Fosl1 and Junb. Promoter binding increased expression of IL-17 and the development of Th17 cells. Overexpression of Fra1 and Junb in mice resulted in susceptibility to collagen-induced arthritis and an increase in Th17 cell numbers and inflammatory cytokine production. In patients with rheumatoid arthritis, FRA1 and JUNB were colocalized with STAT3 in the inflamed synovium. These observations suggest that FRA1 and JUNB are associated closely with STAT3 activation, and that this activation leads to Th17 cell differentiation in autoimmune diseases and inflammation.

Contractile response of a pulmonary artery (PA) to hypoxia (hypoxic pulmonary vasoconstriction; HPV) is a unique physiological reaction. HPV is beneficial for the optimal distribution of blood flow to differentially ventilated alveolar regions in the lung, thereby preventing systemic hypoxemia. Numerous in vitro studies have been conducted to elucidate the mechanisms underlying HPV. These studies indicate that PA smooth muscle cells (PASMCs) sense lowers the oxygen partial pressure (PO2) and contract under hypoxia. As for the PO2-sensing molecules, a variety of ion channels in PASMCs had been suggested. Nonetheless, the modulator(s) of the ion channels alone cannot mimic HPV in the experiments using PA segments and/or isolated organs. We compared the hypoxic responses of PASMCs, PAs, lung slices, and total lungs using a variety of methods (e.g., patch-clamp technique, isometric contraction measurement, video analysis of precision-cut lung slices, and PA pressure measurement in ventilated/perfused lungs). In this review, the relevant results are compared to provide a comprehensive understanding of HPV. Integration of the influences from surrounding tissues including blood cells as well as the hypoxic regulation of ion channels in PASMCs are indispensable for insights into HPV and other related clinical conditions.

PurposePrevious studies suggest that the concentration of 25-hydroxyvitamin D [25(OH)D] in cord blood may show an inverse association with respiratory tract infections (RTI) during childhood. The aim of the present study was to examine the influence of 25(OH)D concentrations in cord blood on infant RTI in a Korean birth cohort.MethodsThe levels of 25(OH)D in cord blood obtained from 525 Korean newborns in the prospective COhort for Childhood Origin of Asthma and allergic diseases were examined. The primary outcome variable of interest was the prevalence of RTI at 6-month follow-up, as diagnosed by pediatricians and pediatric allergy and pulmonology specialists. RTI included acute nasopharyngitis, rhinosinusitis, otitis media, croup, tracheobronchitis, bronchiolitis, and pneumonia.ResultsThe median concentration of 25(OH)D in cord blood was 32.0 nmol/L (interquartile range, 21.4 to 53.2). One hundred and eighty neonates (34.3%) showed 25(OH)D concentrations less than 25.0 nmol/L, 292 (55.6%) showed 25(OH)D concentrations of 25.0-74.9 nmol/L, and 53 (10.1%) showed concentrations of ≥75.0 nmol/L. Adjusting for the season of birth, multivitamin intake during pregnancy, and exposure to passive smoking during pregnancy, 25(OH)D concentrations showed an inverse association with the risk of acquiring acute nasopharyngitis by 6 months of age (P for trend=0.0004).ConclusionThe results show that 89.9% of healthy newborns in Korea are born with vitamin D insufficiency or deficiency (55.6% and 34.3%, respectively). Cord blood vitamin D insufficiency or deficiency in healthy neonates is associated with an increased risk of acute nasopharyngitis by 6 months of age. More time spent outdoors and more intensified vitamin D supplementation for pregnant women may be needed to prevent the onset of acute nasopharyngitis in infants.

Many patients assume that allergic reactions against foods are responsible for triggering or worsening their allergic symptoms. Therefore, it is important to identify patients who would benefit from an elimination diet, while avoiding unnecessary dietary restrictions. The diagnosis of food allergy depends on the thorough review of the patients's medical history, results of supplemented trials of dietary elimination, and in vivo and in vitro tests for measuring specific IgE levels. However, in some cases the reliability of such procedures is suboptimal. Oral food challenges are procedures employed for making an accurate diagnosis of immediate and occasionally delayed adverse reactions to foods. The timing and type of the challenge, preparation of patients, foods to be tested, and dosing schedule should be determined on the basis of the patient's history, age, and experience. Although double-blind, placebo-controlled food challenges(DBPCFC) are used to establish definitively if a food is the cause of adverse reactions, they are time-consuming, expensive and troublesome for physician and patients. In practice, An open challenge controlled by trained personnel is sufficient especially in infants and young children. The interpretation of the results and follow-up after a challenge are also important. Since theses challenges are relatively safe and informative, controlled oral food challenges could become the measure of choice in children.

The increase in cytoplasmic Ca2+ concentration (Δ[Ca2+]c) mediated by the Ca2+-release–activated Ca2+ channel (CRAC) is a critical signal for the activation of lymphocytes. Also, the voltage-gated K+ channel (Kv) and intermediate-conductance Ca2+–activated K+ channel (IKCa1/SK4) have drawn attention as pharmacological targets for regulating immune responses. Since polyphenolic agents have various immunomodulatory effects, here we compared the effects of curcumin, rosmarinic acid, resveratrol, and epigallocatechin gallate on the ionic currents through CRAC (ICRAC), Kv (IKv), SK4 (ISK4) and on the Δ[Ca2+]c of Jurkat-T cells using the patch clamp technique and fura-2 spectrofluorimetry. Curcumin (10 μM) inhibited store-operated Ca2+ entry (SOCE). Consistently, dose-dependent inhibition of ICRAC by curcumin was confirmed in Jurkat-T (IC50, 5.9 μM) and the HEK293 cells overexpressing Orai1 and STIM1 (IC50, 0.6 μM). Also, curcumin inhibited both IKv (IC50, 11.9 μM) and ISK4 (IC50, 4.2 μM). The other polyphenols (rosmarinic acid, resveratrol, and epigallocatechin gallate at 10 – 30 μM) had no effect on SOCE and showed only a partial inhibition of the K+ currents. In summary, among the tested polyphenolic agents, curcumin showed prominent inhibition of major ion channels in lymphocytes, which might contribute to the anti-inflammatory effects of curcumin.[Supplementary Figures: available only at http://dx.doi.org/10.1254/jphs.10209FP] Keywords:: curcumin, T cell, Ca2+-release–activated Ca2+ channel, K+ channel, polyphenol

Human rhinoviruses (HRVs) is a nonenveloped, single stranded RNA virus belonging to the family Picornavirudae. Transmission by direct contact such as hand-to-hand, hand-to-nose, and hand-to-eye has been readily demonstrated in experimental settings. HRV are the most frequent causes of common cold infection, however, they are also known to replicate in the lower respiratory tract and associated with more severe respiratory illnesses such as asthma. New technique such as reverse transcriptase polymerase chain reaction and molecular typing in HRV has been developed and our understanding of the importance of these respiratory viruses. HRVs consisted of 101 serotypes that are classified into groups A and B according to sequence variations. And there is a newly identified set of HRVs, called Group C, and it is currently under investigation. In recent study using PCR techniques, HRVs accounted for approximate 50-80% of common colds and 85 % of childhood asthma exacerbations and in more than half of adult exacerbations. However, the mechanisms of HRV- induced asthma exacerbations are poorly understood. This review discusses the association between HRVs and childhood asthma.

In this study, we investigated the secretome of human oligodendrocytes (F3.Olig2 cells) generated from human neural stem cells by transduction with the gene encoding the Olig2 transcription factor. Using mRNA sequencing and protein cytokine arrays, we identified a number of biologically important secretory proteins whose expression has not been previously reported in oligodendrocytes. We found that F3.Olig2 cells secrete IL-6, PDGF-AA, GRO, GM-CSF, and M-CSF, and showed prominent expression of their corresponding receptors. Co-expression of ligands and receptors suggests that autocrine signaling loops may play important roles in both differentiation and maintenance of oligodendrocytes. We also found that F3.Olig2 cells secrete matrix metalloproteinases and matrix metalloproteinase-associated proteins associated with functional competence of oligodendrocytes. The results of our secretome analysis provide insights into the functional and molecular details of human oligodendrocytes. To the best of our knowledge, this is the first systematic analysis of the secretome of oligodendrocytes.

The carbohydrate response element binding protein (ChREBP), a basic helix-loop-helix/leucine zipper transcription factor, plays a critical role in the control of lipogenesis in the liver. To identify the direct targets of ChREBP on a genome-wide scale and provide more insight into the mechanism by which ChREBP regulates glucose-responsive gene expression, we performed chromatin immunoprecipitation-sequencing and gene expression analysis. We identified 1153 ChREBP binding sites and 783 target genes using the chromatin from HepG2, a human hepatocellular carcinoma cell line. A motif search revealed a refined consensus sequence (CABGTG-nnCnG-nGnSTG) to better represent critical elements of a functional ChREBP binding sequence. Gene ontology analysis shows that ChREBP target genes are particularly associated with lipid, fatty acid and steroid metabolism. In addition, other functional gene clusters related to transport, development and cell motility are significantly enriched. Gene set enrichment analysis reveals that ChREBP target genes are highly correlated with genes regulated by high glucose, providing a functional relevance to the genome-wide binding study. Furthermore, we have demonstrated that ChREBP may function as a transcriptional repressor as well as an activator.

Inflammation in atherosclerotic plaques causes plaque vulnerability and rupture, leading to thromboembolic complications. Cathepsin B (CatB) proteases secreted by macrophages play a major role in plaque inflammation. We used a CatB-activatable near-infrared fluorescence (NIRF) imaging agent to demonstrate the inflammatory component in mice atheromata and the atherosclerosis-modulating effects of atorvastatin or glucosamine treatments. Apolipoprotein E knockout mice ( n = 35) were fed normal chow, a Western diet, a Western diet + atorvastatin, a Western diet + glucosamine, or a Western diet + atorvastatin + glucosamine for 14 weeks. Twenty-four hours after the intravenous injection of a CatB-activatable probe, ex vivo NIRF imaging of the aortas and brains was performed, followed by histology. The CatB-related signal, observed in the aortas but not in the cerebral arteries, correlated very well with protease activity and the presence of macrophages on histology. Animals on Western diets could be distinguished from animals on a normal diet. The antiatherosclerotic effects of atorvastatin and glucosamine could be demonstrated, with reduced CatB-related signal compared with untreated animals. Plaque populations were heterogeneous within individuals, with some plaques showing a high and others a lower CatB-related signal. These differences in signal intensity could not be predicted by visual inspection of the plaques but did correlate with histologic evidence of inflammation in every case. This suggests that vulnerable inflamed plaques can be identified by optical molecular imaging.

Mutations within the SCN5A gene, which encodes the a-subunit 5 (NaV1.5) of the voltage-gated Na+ channel, have been linked to three distinct cardiac arrhythmia disorders: long QT syndrome type 3, Brugada syndrome (BrS), and cardiac conduction disorder. In this study, we have identified novel missense mutations (p.A385T/R504T) within SCN5A in a patient exhibiting overlap arrhythmia phenotypes. This study aims to elucidate the functional consequences of SCN5A mutants (p.A385T/R504T) to understand the clinical phenotypes. Whole-cell patch-clamp technique was used to analyze the NaV1.5 current (INa) in HEK293 cells transfected with the wild-type and mutant SCN5A with or without SCN1B co-expression. The amplitude of INa was not altered in mutant SCN5A (p.A385T/R504T) alone. Furthermore, a rightward shift of the voltage-dependent inactivation and faster recovery from inactivation was observed, suggesting a gain-of-function state. Intriguingly, the coexpression of SCN1B with p.A385T/R504T revealed significant reduction of INa and slower recovery from inactivation, consistent with the loss-of-function in Na+ channels. The SCN1B dependent reduction of INa was also observed in a single mutation p.R504T, but p.A385T co-expressed with SCN1B showed no reduction. In contrast, the slower recovery from inactivation with SCN1B was observed in A385T while not in R504T. The expression of SCN1B is indispensable for the electrophysiological phenotype of BrS with the novel double mutations; p.A385T and p.R504T contributed to the slower recovery from inactivation and reduced current density of NaV1.5, respectively. [ABSTRACT FROM AUTHOR]