Purpose: Tumor radioresistance and dose-limiting toxicity restrict the curative potential of radiotherapy, requiring novel approaches to overcome the limitations and augment the efficacy. Here, we investigated the effects of signal transducer and activator of transcription 3 (STAT3) activation and autophagy induction by irradiation on antiapoptotic proteins and the effectiveness of the BH3 mimetic ABT-737 as a radiosensitizer using K-ras mutant non-small cell lung cancer (NSCLC) cells and a Kras G12D :p53 fl/fl mouse (KP mouse) model. Materials and Methods: A549 and H460 cells were irradiated, and the expression of Bcl-2 family proteins, JAK/STAT transcriptional pathway, and autophagic pathway were evaluated by immunoblotting. The radiosensitizing effects of ABT-737 were evaluated using A549 and H460 cell lines with clonogenic assays and also by a KP mouse model with microcomputed tomography and immunohistochemistry. Results: In A549 and H460 cells and mouse lung tissue, irradiation-induced overexpression of the antiapoptotic molecules BclxL, Bcl-2, Bcl-w, and Mcl-1 through JAK/STAT transcriptional signaling induced dysfunction of the autophagic pathway. After treatment with ABT-737 and exposure to irradiation, the number of surviving clones in the cotreatment group was significantly lower than that in the group treated with radiation or ABT-737 alone. In the KP mouse lung cancer model, cotreatment with ABT-737 and radiation-induced significant tumor regression; however, body weight changes in the combination group were not significantly different, suggesting that combination treatment did not cause systemic toxicity. Conclusion These findings supported the radiosensitizing activity of ABT-737 in preclinical models, and suggested that clinical trials using this strategy may be beneficial in K-ras mutant NSCLC.

Background: Studies have shown that adequate protein intake (API) in patients with diabetes is associated with a reduction in cardiovascular risk factors. High-sensitivity C-reactive protein (hs-CRP) has emerged as a new screening test to predict the risk of cardiovascular disease. This study aimed to investigate the association between protein intake and hs-CRP levels in elderly Korean patients with diabetes. Methods: Data were derived from the Seventh Korea National Health and Nutrition Examination Survey (2016–2018). Participants included 889 adults aged 65 years or older with diabetes. They were grouped by dietary protein intake per body weight (g/kg BW) into a low protein intake group (LPI, <1.0 g/kg BW) and adequate protein intake group (API, ≥1.0 g/kg BW). Multiple linear regression analysis was performed to determine the association between protein intake and hs-CRP levels. Results: The mean hs-CRP level was significantly higher in the LPI group than in the API group (1.3±1.6 mg/L vs. 1.0±1.0 mg/L). In model 1, which was adjusted for age, sex, body mass index, and waist circumstance, hs-CRP was decreased by 7.8% (P=0.024) in the API group compared to that in the LPI group. In model 3, which was additionally adjusted for smoking, systolic blood pressure, fasting glucose, total cholesterol, triglyceride, and highdensity lipid cholesterol, hs-CRP was decreased by 7.1% in the API group compared to that in the LPI group (P=0.036). Conclusion There was a significant negative correlation between protein intake and hs-CRP in elderly Korean patients with diabetes. Therefore, this study provides some evidence that adequate protein intake should be recommended to reduce cardiovascular risk in elderly patients with diabetes.

PURPOSE: Childhood asthma has a considerable social impact and economic burden, especially in severe asthma. This study aimed to identify the proportion of childhood asthma severity and to evaluate associated factors for greater asthma severity. METHODS: This study was performed on 667 children aged 5–15 years with asthma from the nationwide 19 hospitals in the Korean childhood Asthma Study (KAS). Asthma was classified as mild intermittent, mild persistent, and moderate/severe persistent groups according to the National Asthma Education and Prevention Program recommendations. Multinomial logistic regression models were used to identify the associated factors for greater asthma severity. RESULTS: Mild persistent asthma was most prevalent (39.0%), followed by mild intermittent (37.6%), moderate persistent (22.8%), and severe persistent asthma (0.6%). Onset later than 6 years of age (adjusted odds ratio [aOR], 1.69 for mild persistent asthma; aOR, 1.92 for moderate/severe persistent asthma) tended to increase asthma severity. Exposure to environmental tobacco smoke (aOR, 1.53 for mild persistent asthma; aOR, 1.85 for moderate/severe persistent asthma), and current dog ownership with sensitization to dog dander (aOR, 5.86 for mild persistent asthma; aOR, 6.90 for moderate/severe persistent asthma) showed increasing trends with greater asthma severity. Lower maternal education levels (aOR, 2.32) and no usage of an air purifier in exposure to high levels of outdoor air pollution (aOR, 1.76) were associated with moderate/severe persistent asthma. CONCLUSIONS: Modification of identified environmental factors associated with greater asthma severity might help better control childhood asthma, thereby reducing the disease burden due to childhood asthma.
Air Filters ; Air Pollution ; Animals ; Asthma ; Child ; Dander ; Dogs ; Education ; Environmental Exposure ; Humans ; Logistic Models ; Odds Ratio ; Ownership ; Risk Factors ; Smoke ; Social Change ; Tobacco

Purpose: Single-photon emission computed tomography/computed tomography (SPECT/CT) is an advanced hybrid nuclear medicine technology that generates both functional and anatomical images in a single study. As utilization of SPECT/CT in Korea has been increasing, the purpose of this study was to survey its application of cardiac and skeletal SPECT/CT imaging for protocol optimization. Methods: We surveyed CT protocols established for cardiac and skeletal SPECT/CT. We searched the guidelines for the CT protocols for SPECT/CT and reviewed the literature recently published. Results: Among 36 hybrid SPECT scanners equipped with four or more multi-channel detector CTs (MDCTs), 18 scanners were used to perform cardiac studies at both very low current CT (30–80 mA; 11.1%) and ultra-low current CT (13–30 mA; 88.9%). Among the 33 canners, very low current (≤ 80 mA) CT or low current CT (80–130 mA) was used in 23.5%, and 41.8% for spine disorders, and in 36.4% or 30.3% for foot/ankle disorders, respectively. In the CT reconstructions, slice thickness of 5 mm for cardiac studies was most commonly used (94.4%); thinner slices (0.6–1.0 mm) for spine and foot/ankle studies were used in 24.2% and 45.5%, respectively. We also reviewed the international guidelines. Conclusions The results and current recommendations will be helpful for optimizing CT protocols for SPECT/CT. Optimization of SPECT/CT protocols will be required for generating the proper strategy for the specific lesions and clinical purpose.

PURPOSE: To investigate the clinical outcomes of combined vitrectomy and intrascleral fixation of a new posterior chamber intraocular lens (PC IOL) as a treatment for IOL dislocation. METHODS: We conducted a retrospective interventional study at our medical facility from January 2015 to January 2017. Posteriorly dislocated IOLs were removed with pars plana vitrectomy. Two intrascleral tunnels, 2.0 mm in length, were created 1.5 mm to the limbus at 6 and 12 o'clock positions. Both haptics of new foldable acrylic 3-piece IOLs were inserted into the tunnel until the IOL was secured in a central position. We analyzed the preexisting ocular condition, visual acuity (VA), and refractive error preoperatively and postoperatively, and recorded postoperative complications. RESULTS: Forty-nine patients (50 eyes) were enrolled in the study. The mean follow-up period was 12.8 ± 6.6 months. A best-corrected VA of 6/12 or better was achieved in 43 eyes (86%). The mean VA significantly improved from 0.32 logarithm of the minimum angle of resolution (logMAR) at baseline to 0.18 logMAR at last follow-up (p = 0.03). The refractive status after intrascleral fixation of the PC IOL revealed a mean hyperopic shift of +1.09 ± 1.28 diopters from the predicted spherical equivalent. Postoperative vitreous hemorrhages occurred in six cases and were cleared without visual compromise. Cystoid macular edema was well-controlled by topical nonsteroidal anti-inflammatory drugs (NSAID) medications in two cases. In two cases, IOL dislocation recurred and required re-operation. There were no serious adverse events of suture-related complications, retinal detachment, corneal compromise, or endophthalmitis in any of the patients. CONCLUSIONS: Our data revealed that use of combined vitrectomy and intrascleral fixation of PC IOLs is a safe and efficient technique to correct IOL dislocation. We observed good visual outcomes with only minor complications.
Dislocations ; Endophthalmitis ; Follow-Up Studies ; Humans ; Lenses, Intraocular ; Macular Edema ; Postoperative Complications ; Refractive Errors ; Retinal Detachment ; Retrospective Studies ; Visual Acuity ; Vitrectomy ; Vitreous Hemorrhage

PURPOSE: To determine influences of intraoperative foveal traction during membrane peeling in idiopathic epiretinal membrane (ERM) surgery. METHODS: This retrospective observational study included 46 eyes of 46 patients with idiopathic ERM who underwent pars plana vitrectomy with ERM and internal limiting membrane peeling from February 2015 to September 2015. The presence of intraoperative foveal traction during membrane peeling was reviewed using video records. The main outcome measures were best-corrected visual acuity (BCVA), central foveal thickness (CFT), foveal contour, and photoreceptor inner segment/outer segment junction disruption using optical coherence tomography at baseline and at 1, 3, 6, and 12 months after surgery. RESULTS: Group 1 (ERM with intraoperative foveal traction) included 22 eyes, and group 2 (ERM without intraoperative foveal traction) included 24 eyes. Preoperatively, convex pattern ERM was observed more often in group 1. Group 1 had a significantly thicker CFT and a lower BCVA compared to group 2 at baseline and during the first 6 months, but the final postoperative BCVA and CFT were not significantly different between the groups at 12 months. Among 22 eyes, 12 eyes (54.5%) were restored to flat or concave ERM patterns at an average of 5.4 months after surgery in group 1, and 18 out of 24 eyes (75%) recovered at 2.4 months (p < 0.01) in group 2. CONCLUSIONS: Preoperative thick CFT and convex pattern ERM indicated a high possibility of intraoperative foveal traction in idiopathic ERM surgery. There were no differences in long-term BCVA and restoration of foveal configuration according to foveal traction during membrane peeling.
Epiretinal Membrane ; Humans ; Membranes ; Observational Study ; Outcome Assessment (Health Care) ; Retrospective Studies ; Tomography, Optical Coherence ; Traction ; Visual Acuity ; Vitrectomy

Corrections for Table. 1 in page 125 are needed. We apologize for any inconvenience that this may have caused.

BACKGROUND: OneTouch Diabetes Management Software (OTDMS) is an efficient way to track and monitor the blood glucose level. It is possible to download data from the OneTouch Ultra via the meter's data port, and to transform the numbers of the blood glucose level into a graph, a chart, or statistics. The objectives of this study were to evaluate whether the use of OTDMS in consultation hours would improve patients' knowledge of diabetes mellitus (DM), compliance, satisfaction with doctor and medical treatment, doctor-patient reliability, and glucose control. METHODS: All patients were randomized into either the OTDMS group using OneTouch Ultra or the control groups not using it. Both groups had conventional DM education and only the OTDMS group used data from OTDMS as explanation materials during consultation hours. At enrollment and after 6 months, we performed a questionnaire survey consisting of the diabetes knowledge test, items for compliance of treatment, patient's satisfaction, doctor-patient reliability, and glycosylated hemoglobin (HbA1c). RESULTS: We analyzed 6-month follow-up data from 92 patients (OTDMS 42 vs. control 50). Both groups showed significant improvements in HbA1c, diabetes knowledge, compliance, reliability, and satisfaction after 6 months. However, there were no significant differences between OTDMS and control groups overall. Only "weekly frequency of checking blood glucose level" of compliance and "trying to follow doctor's order" of reliability showed better results in the OTDMS group. CONCLUSION: Using the OTDMS system for explanation during consultation hours seems to be more helpful to improve patient's compliance and reliability, especially for checking blood glucose level and trying to follow the doctor's order.
Blood Glucose ; Compliance ; Diabetes Mellitus ; Diabetes Mellitus, Type 2* ; Disease Management ; Education ; Follow-Up Studies ; Glucose ; Hemoglobin A, Glycosylated ; Humans ; Self Care

PURPOSE: Recently, component-resolved diagnosis (CRD) using microarray technology has been introduced to the field of clinical allergy. This study was aimed to investigate the clinical usefulness of microarray-based IgE detection for diagnosing clinical raw fruit allergy in birch pollen-sensitized children. METHODS: Thirty-one children with allergic disease who had been sensitized to pollen were studied. A pollen-sensitized patient was defined as having an allergen-specific history with concomitant positive skin-prick tests (SPTs) to natural allergen extracts or positive allergen-specific IgE. All subjects underwent SPTs for pollen and fruit. In all subjects, specific IgE to pollen and fruit were measured by ImmunoCAP. Specific IgE antibodies to allergen components were determined by a customized allergen microarray (ISAC). RESULTS: Thirteen of the 31 patients (41.9%) had a history of fruit hypersensitivity with positive SPTs. Measuring IgE to allergen components by ISAC, all the 13 patients with fruit hypersensitivity were positive to at least one of Mal d 1, Pru p 1, Pru p 3, Act d 8, and Act d 2 compared to 12 of the 13 patients (92.3%) who had at least 1 positive IgE to fruits (apple, peach, and kiwi) using ImmunoCAP. The sensitivity of ISAC microarray was 100.0% for the diagnosis of fruit hypersensitivity, but its specificity was 27.7% (5/18). The sensitivity of ImmunoCAP was 92.3%, and its specificity was 83.3%. CONCLUSION: The sensitivity of allergen components tested using microarray for the diagnosis of clinical fruit hypersensitivity in children with pollen allergy was high; however, its specificity was low.
Antibodies ; Betula* ; Child* ; Diagnosis* ; Fruit* ; Humans ; Hypersensitivity* ; Immunoglobulin E ; Pollen* ; Prunus persica ; Rhinitis, Allergic, Seasonal

Drug metabolism mostly occurs in the liver. Cytochrome P450 (CYP) is a drug-metabolizing enzyme that is responsible for many important drug metabolism reactions. Recently, the US FDA and EU EMA have suggested that CYP enzyme induction can be measured by both enzymatic activity and mRNA expression. However, these experiments are time-consuming and their inter-assay variability can lead to misinterpretations of the results. To resolve these problems and establish a more powerful method to measure CYP induction, we determined CYP induction by using luminescent assay. Luminescent CYP assays link CYP enzyme activity to firefly luciferase luminescence technology. In this study, we measured the induction of CYP isozymes (1A2, 2B6, 2C9, and 3A4) in cryopreserved human hepatocytes (HMC424, 478, and 493) using a luminometer. We then examined the potential induction abilities (unknown so far) of mesalazine, a drug for colitis, and mosapride citrate, which is used as an antispasmodic drug. The results showed that mesalazine promotes CYP2B6 and 3A4 activities, while mosapride citrate promotes CYP1A2, 2B6, and 3A4 activities. Luminescent CYP assays offer rapid and safe advantages over LC-MS/MS and qRT-PCR methods. Furthermore, luminescent CYP assays decrease the interference between the optical properties of the test compound and the CYP substrates. Therefore, luminescent CYP assays are less labor intensive, rapid, and can be used as robust tools for high-throughput CYP screening during early drug discovery.
Citric Acid* ; Colitis ; Cytochrome P-450 CYP1A2 ; Cytochrome P-450 Enzyme System* ; Cytochromes* ; Drug Discovery ; Enzyme Induction* ; Fireflies ; Hepatocytes ; Humans* ; Isoenzymes ; Liver ; Luciferases ; Luminescence ; Luminescent Measurements* ; Mass Screening ; Mesalamine* ; Metabolism ; RNA, Messenger