Effectiveness of a healthy lifestyle program based on a mobile serious game for childhood cancer survivors: A quasi-randomized trial.

PURPOSE: This study aimed to develop and evaluate the effectiveness of a healthy lifestyle program based on a mobile serious game (HLP-MSG) to enhance the lifestyles of childhood cancer survivors (CCSs). METHODS: This program proceeded in two stages: development and evaluation, using a non-synchronized design with a quasi-randomized trial. The participants were CCSs aged 6-13 years whose treatment was terminated at least 12 months prior. Data were collected at baseline, and post-intervention, with a follow-up after four weeks using the Child Healthy Lifestyle Profile (CHLP). The experimental (n = 26) and control groups (n = 25) were compared. Data were analyzed using descriptive statistics, chi-squared tests, t-tests, and repeated-measures ANOVA. RESULTS: The HLP-MSG promoted a healthy lifestyle by solving 26 quests, including seven sub-elements (nutrition, exercise, hygiene, interpersonal relationships, stress management, meaning of life, and health responsibility). This study revealed significant differences in the interaction between measurement time and group assignment in the CHLP (p = .006) and physical activity (p = .013), one of the seven sub-dimensions. CONCLUSIONS: A healthy lifestyle program based on a mobile serious game is a feasible health education modality to enhance the physical, psychological, social, and spiritual health of CCSs. IMPLICATIONS TO PRACTICE: The findings add to scientific evidence on a mobile serious game for health education among CCSs. The HLP-MSG provides an evolutionary educational modality that can be delivered non-face-to-face to promote CCSs' continuous healthy behavior maintenance. Moreover, the HLP-MSG is adolescent-friendly and can be utilized as a healthcare tool for parents and children to cooperate.

Overweight and obesity as risk factors for biochemical recurrence of prostate cancer after radical prostatectomy.

BACKGROUND: Previous studies have shown a relationship between the occurrence and recurrence of prostate cancer; however, this relationship remains controversial. We investigated the relationship between obesity and biochemical recurrence in patients with prostate cancer. METHODS: Clinicopathological factors were analyzed after dividing the patient population according to the Asian population-specific body mass index (BMI) criteria for "normal" (< 23 kg/m2), "overweight" (23-27.5 kg/m2), and "obese" (≥ 27.5 kg/m2). Among the 389 patients included in this study, 108 were classified as normal, while 227 and 54 patients were classified as overweight and obese, respectively. The relationships between clinicopathological factors and biochemical recurrence were analyzed by univariate and multivariate Cox ≤ proportional hazard models. Biochemical recurrence was defined as two consecutive prostate-specific antigen (PSA) measurements ≥ 0.2 ng/mL. RESULTS: In univariate analysis, the categorical variables of "overweight" and "obese" were significant prognostic factors for biochemical recurrence. In multivariate analysis models including PSA density [hazard ratio (HR) 1.8, p = 0.01], extraprostatic extension (HR 2.0, p < 0.001), Gleason score (HR 1.7, p = 0.01), surgical margin positivity (HR 2.46, p < 0.001), and lymphovascular invasion (HR 2.53, p < 0.001), the categorical variables of "overweight" (HR 1.6, p = 0.03) and "obese" (HR 1.76, p = 0.035) were prognostic factors for biochemical recurrence. CONCLUSION: The obesity status of patients with prostate cancer as "overweight" and "obese" was a risk factor for biochemical recurrence after adjusting for other clinicopathological factors.

Prospective pharmacological methodology for establishing and evaluating anti-cancer drug resistant cell lines.

BACKGROUND: Cell lines are often used to assess the resistance of anticancer drugs when in vivo analysis is not possible. However, the process for establishing anti-cancer drug resistance in cell cultures in vitro and the subsequent method of then evaluating resistance are not clearly established. Traditionally, the IC50 is the most commonly used indicator of resistance evaluation but it cannot represent the effectiveness of anti-cancer drugs in a clinical setting and lacks reliability because it is heavily affected by the cell doubling time. Hence, new indicators that can evaluate anti-cancer drug resistance are needed. METHODS: A novel resistance evaluation methodology was validated in this present study by establishing sunitinib resistance in renal cell carcinoma cells and assessing the cross-resistance of five different anti-cancer drugs. RESULTS: It was confirmed in this present study that the IC50 does not reflect the cell proliferation rates in a way that represents anti-cancer drug resistance. An alternative indicator that can also be clinically meaningful when using in vitro cell line systems is GI100. Additionally, the GR100 allows different cell populations to be calibrated on the same basis when multiple experimental results are compared. CONCLUSION: Since the GR100 has properties that indicate the efficiency of anti-cancer drugs, both the efficacy and GR100 of a particular anti-cancer drug can be used to effectively assess the resistance.

Nephrotoxicity of amikacin in noncritically ill patients
.

AIMS: Several studies have reported that critically ill patients who require amikacin for the treatment of severe infection require therapeutic drug monitoring (TDM) to prevent acute kidney injury. Moreover, studies so far have mainly focused on patients with critical illnesses; therefore, the probability of occurrence of nephrotoxicity in noncritically ill patients is less known and tends to be overestimated. Recently, with the emergence of multidrug resistant bacteria, the need for aminoglycosides has resurfaced. Therefore, the aim of this study was to investigate the nephrotoxicity and tolerability of amikacin in noncritically ill patients. MATERIALS AND METHODS: This was a retrospective study that included 224 patients who were administered amikacin. Relevant data on patients' clinical course of disease, comorbidities, and clinical laboratory measurements were statistically analyzed. Nephrotoxicity was defined as a serum creatinine level increase by ≥ 0.3 mg/dL or ≥ 50% after therapy initiation. RESULTS: The mean (SD) daily amikacin dose was 13.04 (4.21) mg/kg. The mean (SD) duration of treatment was 12.09 (12.89) days. The incidence rate (95% CI) of amikacin-induced nephrotoxicity was 1.076/person-year (0.46 - 2.12) for the total person-time (3.44 years). In the risk analysis, no risk factor associated with nephrotoxicity could be found. However, an increasing trend of AKI risk was observed in patients with low baseline estimated glomerular filtration rate. CONCLUSION: In noncritically ill patients, the incidence of amikacin-induced nephrotoxicity was lower than that reported in previous studies. The initial monitoring for kidney function in clinical laboratories may be useful, and therapeutic drug monitoring (TDM) may not be necessary in patients with normal kidney function.

Effect of pharmacokinetic model misspecification on antibiotic probability of target attainment predicted by Monte Carlo simulation
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OBJECTIVE: The first aim of this study was to compare the predictability of efficacy by Monte Carlo simulation between a true one-compartment model and a true two-compartment model for doripenem. The second aim was to explore how we can identify the usefulness of a one-compartment model when the pharmacokinetic/pharmacodynamic (PK/PD) indices between three misspecified one-compartment models and a true two-compartment model are compared. MATERIALS AND METHODS: The reported two-compartment model parameters of two doripenem studies and a vancomycin study were used to generate 200 virtual concentration-time profiles for each study. Sparse and dense sampling designs were selected to build the one- and two-compartment models, respectively. The probability of target attainment (PTA) for the PK/PD indices were compared between the one- and two-compartment models of the same drug, applying the clinical breakpoint distribution of minimum inhibitory concentrations (MICs). RESULTS: The simulated concentration-time profiles reproduced the original data well. In addition, PTAs were similar between the one- and two-compartment models when infusion time and MIC were the same in the doripenem studies. For vancomycin simulations, the maximum difference was 65.9% between a misspecified one-compartment model and the true two-compartment model. CONCLUSION: When a misspecified one-compartment model was established with sparse sampling data, the PTA was significantly different from that of the two-compartment model. Thus, a useful PK model must be verified through diagnostic plots and visual predictive checks and the range of sampling time should be sufficient to explain the PK of a drug.

A new population pharmacokinetic model for vancomycin in patients with variable renal function: Therapeutic drug monitoring based on extended covariate model using CKD-EPI estimation.

WHAT IS KNOWN AND OBJECTIVE: Although patients may have received vancomycin therapy with therapeutic drug monitoring (TDM), those treated with high-strength and long-term vancomycin therapy might have unstable and time-varying renal function. The methods used to estimate renal function should not be considered interchangeable with pharmacokinetic (PK) modeling and model-based estimation of vancomycin pharmacokinetics. While Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) for renal function estimation has been widely integrated into clinical practice, a population PK model including CKD-EPI has not been established. The study was aimed at developing a new population PK model for optimal vancomycin prediction in patients with time-varying and variable renal function to evaluate the interchangeability of estimation methods. METHODS: The most suitable population PK model was explored and evaluated using non-linear mixed-effect modelling for the best fit of vancomycin concentrations from patients who needed to maintain high trough vancomycin concentrations of >10 mg/L or >15 mg/L. Renal function was estimated using the Cockcroft-Gault (CG), Modification of Diet in Renal Disease (MDRD) and CKD-EPI equations. NONMEM 7.4 was used to develop the population PK model. RESULTS: A total of 328 vancomycin concentrations in 99 patients were used to develop the population PK model. Vancomycin pharmacokinetics was best described by a two-compartment model. The CKD-EPI equation for vancomycin clearance was included in the final model among the estimation methods of renal function. A new covariate model, including extended covariate parameters that explain changes in renal function from the population-predicted value and individual dosing time, provided the best explanation for vancomycin pharmacokinetics among the various models tested. WHAT IS NEW AND CONCLUSION: A new extended covariate model for vancomycin using the CKD-EPI method may afford suitable dose adjustment for high-strength and long-term vancomycin therapy that results in unstable renal function.

Curcumin Treatment in Combination with Glucose Restriction Inhibits Intracellular Alkalinization and Tumor Growth in Hepatoma Cells.

Dysregulation of cellular energy metabolism is closely linked to cancer development and progression. Calorie or glucose restriction (CR or GR) inhibits energy-dependent pathways, including IGF-1/PI3K/Akt/mTOR, in cancer cells. However, alterations in proton dynamics and reversal of the pH gradient across the cell membrane, which results in intracellular alkalinization and extracellular acidification in cancer tissues, have emerged as important etiopathogenic factors. We measured glucose, lactate, and ATP production after GR, plant-derived CR-mimetic curcumin treatment, and curcumin plus GR in human hepatoma cells. Intracellular pH regulatory effects, in particular, protein-protein interactions within mTOR complex-1 and its structural change, were investigated. Curcumin treatment or GR mildly inhibited Na+/H+ exchanger-1 (NHE1). vATPase, monocarboxylate transporter (MCT)-1, and MCT4 level. Combination treatment with curcumin and GR further enhanced the inhibitory effects on these transporters and proton-extruding enzymes, with intracellular pH reduction. ATP and lactate production decreased according to pH change. Modeling of mTOR protein revealed structural changes upon treatments, and curcumin plus GR decreased binding of Raptor and GßL to mTOR, as well as of Rag A and Rag B to Raptor. Consequently, 4EBP1 phosphorylation was decreased and cell migration and proliferation were inhibited in a pH-dependent manner. Autophagy was increased by curcumin plus GR. In conclusion, curcumin treatment combined with GR may be a useful supportive approach for preventing intracellular alkalinization and cancer progression.

Pharmacokinetics of Doripenem in Healthy Koreans and Monte Carlo Simulations to Explore Optimal Dosage Regimens in Patients With Normal and Enhanced Renal Function.

BACKGROUND: Dose adjustment is often required in patients with normal or enhanced renal function. The aim of this study is to investigate the pharmacokinetic (PK) properties of doripenem and explore optimal dosing regimens in patients with normal or enhanced renal function according to various minimum inhibitory concentrations (MICs). METHODS: The authors conducted a clinical trial and analyzed PK samples in 11 healthy Korean subjects applying noncompartmental analysis and a population approach. The population PK parameter estimates were used in Monte Carlo simulations to explore optimal dosing regimens for a probability of target attainment of 90% at 40% fTMIC (free drug concentrations above MIC). RESULTS: The time course of doripenem concentrations was well described by a 2-compartment model. The population typical values of clearance and steady-state volume were 22.9 L/h and 19.1 L, respectively, and were consistent with our noncompartmental analysis results. When the MIC was greater than 1 mcg/mL, at least increasing the dose or prolonging the infusion time was essential in patients with normal or enhanced renal function. CONCLUSIONS: These results suggest that dosage adjustment such as increasing the dose or lengthening the infusion time should be considered in patients with normal or enhanced renal function.

Casein Kinase 2 (CK2)-mediated Phosphorylation of Hsp90ß as a Novel Mechanism of Rifampin-induced MDR1 Expression.

The P-glycoprotein (P-gp) encoded by the MDR1 gene is a drug-exporting transporter located in the cellular membrane. P-gp induction is regarded as one of the main mechanisms underlying drug-induced resistance. Although there is great interest in the regulation of P-gp expression, little is known about its underlying regulatory mechanisms. In this study, we demonstrate that casein kinase 2 (CK2)-mediated phosphorylation of heat shock protein 90ß (Hsp90ß) and subsequent stabilization of PXR is a key mechanism in the regulation of MDR1 expression. Furthermore, we show that CK2 is directly activated by rifampin. Upon exposure to rifampin, CK2 catalyzes the phosphorylation of Hsp90ß at the Ser-225/254 residues. Phosphorylated Hsp90ß then interacts with PXR, causing a subsequent increase in its stability, leading to the induction of P-gp expression. In addition, inhibition of CK2 and Hsp90ß enhances the down-regulation of PXR and P-gp expression. The results of this study may facilitate the development of new strategies to prevent multidrug resistance and provide a plausible mechanism for acquired drug resistance by CK2-mediated regulation of P-gp expression.

Fever lasting 48 hours as a predictive factor of ESBL-producing bacteria in non-critically ill patients with urinary tract infection.

Urinary tract infection (UTI) is the most prevalent urological condition worldwide. Choosing appropriate antibiotics for patients who have fever before receiving a culture result is challenging. This retrospective study enrolled patients 394 patients hospitalized at Gangneung Asan Hospital for UTI from May 2017 to April 2021. Fever at 48 h of hospitalization was the analysis point, as this is when the response to antibiotic therapy manifest, although the results of antibiogram are not available. Multivariate analysis was performed to assess the correlation between ESBL producing bacteria (EPB) and fever at 48 h. Overall, 36.3% of patients had EPB and 27.9% had fever at 48 h. In multivariate analysis, a significant positive association was found between EPB and fever (odds ratio 1.17, 95% CI 1.05-1.30, P = 0.004) Female had negative association with multivariate model (OR 0.83, 95% CI 0.73-0.94, P = 0.004). Diabetes did not demonstrate a significant association with EPB. (OR 1.10, 95% CI 0.99-1.22, P = 0.072). Fever at 48 h is associated with EPB and could be considered a predictive factor for EPB infection in patients with UTI. Antibiotic escalation may be considered in patients with fever at 48 h.

HER2 overexpression predicts pathological T2 stage and improved survival in de novo muscle-invasive bladder cancer after immediate radical cystectomy: a retrospective cohort study.

INTRODUCTION: Human epidermal growth factor receptor type 2 (HER2) overexpression is a prognostic factor and a therapeutic target for breast cancer; however, anti-HER2 therapies are ineffective in patients with bladder cancer. The authors investigated the effect of HER2 overexpression (HER2 + ) on the prognosis of muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: This retrospective cohort study included patients who underwent initial transurethral resection of bladder tumors between 2005 and 2013 and were registered in the Korea National Health Insurance Database, which provides data on overall survival (OS). Sixty-one patients with clinically nonmetastatic de novo MIBC were included in this study. As a subgroup, 33 patients who underwent immediate radical cystectomy (RC) were analyzed. Univariate and multivariate Cox proportional hazards models were used to identify prognostic factors for survival. A multivariable binary logistic regression model was used to identify the favorable T stage. RESULTS: Among the 61 patients with d-MIBC, 14 were HER2 + and 47 HER2 - . Age less than 70 years [hazard ratio (HR): 0.312, CI: 0.16-0.59, P <0.001] and HER2 + status (HR: 0.40, CI: 0.19-0.85, P =0.02) were favorable prognostic factors for OS after adjusting for clinical variables. In the RC subgroup, HER2 + status was a significant predictive factor for the pT2 stage (HR): 36.8, CI: 4.83-797.41, P <0.01). Age less than 70 years (HR: 0.15, CI: 0.05-0.42, P <0.001) and HER2 + status (HR: 0.11, CI: 0.02-0.54, P =0.01) were favorable prognostic factors for OS after adjusting for RC pathological variables. CONCLUSIONS: HER2 + status could be a marker for an indolent subset of MIBC and could predict favorable survival regardless of RC status. Moreover, HER2 + status not only consistently predicted a favorable T stage after RC, but also predicted better survival than pathological outcomes.

ABCB1 c.2677G>T variation is associated with adverse reactions of OROS-methylphenidate in children and adolescents with ADHD.

OBJECTIVES: Osmotic-release oral system (OROS)-methylphenidate (MPH) is a safe and well-tolerated drug. Some patients cannot continue this regimen with adverse drug reactions (ADRs). As drug efflux transporters of the central nervous system, ABCB1 plays an important role in the clearance of psychotropic drugs and their metabolites from brain tissues. We hypothesized that genetic variations in the ABCB1 gene may affect ADRs to OROS-MPH. METHODS: We analyzed ADRs of OROS-MPH in 134 children and adolescents with attention-deficit hyperactivity disorder who completed a 4-week trial of OROS-MPH. The ADRs of OROS-MPH were evaluated by administering the Barkley Stimulant Side Effects Rating Scale. RESULTS: Our study proved that MPH is a substrate for ABCB1 by using membrane vesicle assay. We analyzed the influence of ABCB1 polymorphisms on ADRs to OROS-MPH. From the association study between ABCB1 polymorphisms and ADRs of OROS-MPH, c.2677G>T (p.Ala893Ser, rs2032582) showed a strong association with OROS-MPH-related ADRs (P = 0.008; odds ratio, 5.72). Furthermore, logistic regression analysis indicated that the TT genotype at the ABCB1 2677 locus is an independent determinant of ADRs attributed to OROS-MPH. In a functional study, the 893Ser variant markedly reduced MPH transport across the cell membrane. CONCLUSIONS: This is the first study to demonstrate that the TT genotype at position 2677 in the ABCB1 gene is associated with ADRs to OROS-MPH.

Enhancing the Plasma-Resistance Properties of Li2O-Al2O3-SiO2 Glasses for the Semiconductor Etch Process via Alkaline Earth Oxide Incorporation.

To develop plasma-resistant glass materials suitable for semiconductor etching processes, we introduced alkaline earth oxides (ROs) into a Li2O-Al2O3-SiO2 (LAS) glass. Analysis of glass properties with respect to the additives revealed that among the analyzed materials, the LAS material in which Li2O was partially replaced by MgO (MLAS) exhibited the most favorable characteristics, including a low dielectric constant (6.3) and thermal expansion coefficient (2.302 × 10-6/°C). The high performance of MLAS is attributed to the high ionic field strength of Mg2+ ions, which restricts the movement of Li+ ions under the influence of electric fields and thermal vibrations at elevated temperatures. When exposed to CF4/O2/Ar plasma, the etching speed of RO-doped glasses decreased compared with that of quartz and LAS glass, primarily owing to the generation of a high-sublimation-point fluoride layer on the surface. Herein, MLAS demonstrated the slowest etching speed, indicating exceptional plasma resistance. X-ray photoelectron spectroscopy analysis conducted immediately after plasma etching revealed that the oxidation-to-fluorination ratio of Li was the lowest for MLAS. This observation suggests that the presence of Mg2+ ions in the plasma discharge inhibits the migration of Li+ ions toward the surface, thereby contributing to the excellent plasma resistance of MLAS.

Preparation of Remote Plasma Atomic Layer-Deposited HfO2 Thin Films with High Charge Trapping Densities and Their Application in Nonvolatile Memory Devices.

Optimization of equipment structure and process conditions is essential to obtain thin films with the required properties, such as film thickness, trapped charge density, leakage current, and memory characteristics, that ensure reliability of the corresponding device. In this study, we fabricated metal-insulator-semiconductor (MIS) structure capacitors using HfO2 thin films separately deposited by remote plasma (RP) atomic layer deposition (ALD) and direct-plasma (DP) ALD and determined the optimal process temperature by measuring the leakage current and breakdown strength as functions of process temperature. Additionally, we analyzed the effects of the plasma application method on the charge trapping properties of HfO2 thin films and properties of the interface between Si and HfO2. Subsequently, we synthesized charge-trapping memory (CTM) devices utilizing the deposited thin films as charge-trapping layers (CTLs) and evaluated their memory properties. The results indicated excellent memory window characteristics of the RP-HfO2 MIS capacitors compared to those of the DP-HfO2 MIS capacitors. Moreover, the memory characteristics of the RP-HfO2 CTM devices were outstanding as compared to those of the DP-HfO2 CTM devices. In conclusion, the methodology proposed herein can be useful for future implementations of multiple levels of charge-storage nonvolatile memories or synaptic devices that require many states.

Corticosteroid-Antibiotic Interactions in Bacteria that Cause Corneal Infection.

Purpose: Although a comprehensive knowledge of antibiotic/corticosteroid combinations is essential for the appropriate treatment of eye infections, the impact of their co-administration has not been well studied to date. A systematic pharmacodynamic/pharmacokinetic study to determine the effects of cotreatment with various antibiotics and corticosteroids was conducted. Methods: Four bacterial strains, seven antibiotics, and four corticosteroids were used in the analyses. Drug interactions were evaluated by considering antibacterial effects with a checkerboard assay and intracellular concentrations in human corneal epithelial cells. Results: The drug combinations that showed the most stable effects against Pseudomonas aeruginosa was levofloxacin-prednisolone. Stable combinations against the three types of Gram-positive bacteria were neomycin-prednisolone, ofloxacin-dexamethasone, ofloxacin-prednisolone, and polymyxin-dexamethasone. The cellular concentrations were changed for the gatifloxacin-fluorometholone, moxifloxacin-fluorometholone, tobramycin-dexamethasone, and tobramycin-prednisolone combinations. Conclusions: Loteprednol and fluorometholone reduced the antibacterial effects of all of the tested antibiotics in this study. Dexamethasone and prednisolone showed various effects in this regard, depending on the co-administered antibiotic. Prior knowledge of specific antibiotic/corticosteroid interactions provides valuable information to clinical practitioners by combining data on the antibacterial and intracellular uptake effects of their co-administration. Translational Relevance: When using antibiotics and corticosteroids, drug combinations can be selected by referring to the results of this study.

Synthesis of Planar-Type ZnO Powder in Non-Nano Scale Dimension and Its Application in Ultraviolet Protection Cosmetics.

ZnO is one of the most widely used inorganic sunscreens, owing to its fine particle size and UV light shielding capability. However, powders at nanosizes can be toxic and cause adverse effects. The development of non-nanosized particles has been slow. The present work investigated synthesis methods of non-nanosized ZnO particles for ultraviolet protection application. By altering the starting material, KOH concentration, and input speed, the ZnO particles can be obtained in different forms, including needle type, planar type, and vertical wall type. Cosmetic samples were made by mixing different ratios of synthesized powders. The physical properties and the UV blockage efficacy of different samples were evaluated using scanning electron microscopy (SEM), X-ray diffraction (XRD), particle size analyzer (PSA), and ultraviolet/visible (UV/Vis) spectrometer. The samples with 1:1 ratio of needle-type ZnO and vertical wall-type ZnO exhibited superior light blocking effect owing to improved dispersibility and prevention of particle agglomeration. The 1:1 mixed sample also complied with the European nanomaterials regulation due to the absence of nanosized particles. With superior UV protection in the UVA and UVB regions, the 1:1 mixed powder showed potential to be used as a main ingredient in UV protection cosmetics.

Characteristics of Hf0.5Zr0.5O2 Thin Films Prepared by Direct and Remote Plasma Atomic Layer Deposition for Application to Ferroelectric Memory.

Hf0.5Zr0.5O2 (HZO) thin film exhibits ferroelectric properties and is presumed to be suitable for use in next-generation memory devices because of its compatibility with the complementary metal-oxide-semiconductor (CMOS) process. This study examined the physical and electrical properties of HZO thin films deposited by two plasma-enhanced atomic layer deposition (PEALD) methods- direct plasma atomic layer deposition (DPALD) and remote plasma atomic layer deposition (RPALD)-and the effects of plasma application on the properties of HZO thin films. The initial conditions for HZO thin film deposition, depending on the RPALD deposition temperature, were established based on previous research on HZO thin films deposited by the DPALD method. The results show that as the measurement temperature increases, the electric properties of DPALD HZO quickly deteriorate; however, the RPALD HZO thin film exhibited excellent fatigue endurance at a measurement temperature of 60 °C or less. HZO thin films deposited by the DPALD and RPALD methods exhibited relatively good remanent polarization and fatigue endurance, respectively. These results confirm the applicability of the HZO thin films deposited by the RPALD method as ferroelectric memory devices.

A synonymous variation in protease-activated receptor-2 is associated with atopy in Korean children.

BACKGROUND: Atopic diseases are the most common chronic diseases of childhood, and the genetics of atopy are complex and heterogeneous. Protease-activated receptor-2 (PAR-2) is involved in various inflammatory diseases, but the association of PAR-2 with allergic diseases remains unclear. OBJECTIVE: To examine the contribution of genetic variation of PAR-2 to atopic phenotypes in the Korean childhood cohort. METHODS: We identified PAR-2 variations in a Korean population and conducted association analyses by using 316 unrelated atopic and 210 nonatopic subjects. We analyzed serum IgE and total eosinophil count levels and examined PAR-2 mRNA and protein expression levels. RESULTS: In the case-control association analysis, atopy was significantly associated with a single c.621C>T (p.I207I, rs631465) polymorphism of PAR-2 (P = .001, odds ratio = 1.95). Subjects with the c.621T risk allele had significantly higher serum IgE (P = .004) and total eosinophil count (P = .03) levels. Moreover, the positive association of c.621T was reproduced in the replication study (P = .01, joint P value of the replication < .001). An in silico analysis of RNA secondary structure prediction revealed that the C to T conversion at c.621 greatly increased predicted PAR-2 mRNA stability. This was also confirmed by an in vitro assay for mRNA stability. Furthermore, following an in vivo approach on gene expression in PBMCs showed that the expression levels of PAR-2 mRNA and protein in subjects with the c.621CT or TT genotype were significantly higher than in those with the c.621CC genotype. CONCLUSIONS: These results indicate that the synonymous c.621C>T polymorphism in PAR-2 might be associated with the risk of atopy, potentially by altering PAR-2 gene expression.

Design and Preparation of Self-Oscillating Actuators Using Piezoelectric Ceramics with High Coupling Factors and Mechanical Quality Factors.

Piezoelectric material properties were optimized to develop materials for an ultrasonic vibrator targeting a high vibration efficiency. Herein, novel materials were developed using a composition represented by 0.08Pb(Ni1/3Nb2/3)O3-0.07Pb(Mn1/3Nb2/3)O3-0.85Pb(Zr0.5Ti0.5)O3 + 0.3 wt.% CuO + 0.3 wt.% Fe2O3 with 0.3 wt.% Sb2O3 doping. A ceramic shape with a thickness of 2 mm was optimized using finite element analysis software, and high values of coupling factors (0.54) and mechanical quality factors (1151) were obtained. This ceramic was used to fabricate a bio-beauty device (frequency = 1 MHz), and the manufactured ultrasonic vibrator indicated that the actuator oscillated with the maximum amplitude at a frequency of 1.06 MHz.

Development of PZN-PMN-PZT Piezoelectric Ceramics with High d33 and Qm Values.

To achieve good long-term temperature stability in devices used in energy-conversion applications, this study is aimed at developing combined ceramics, referred to as PZN-PMN-PZT, comprising Pb(Zn1/3Nb2/3)O3 (PZN) and Pb(Mn1/3Nb2/3)O3 (PMN), which are typical relaxor ferroelectric materials, and Pb(Zr,Ti)O3 (PZT). The piezoelectric properties were compared based on several parameters according to the change in the composition ratio between relaxor materials, amounts of Sb2O3 dopant, and Zr/Ti ratio in the PZT system. Finally, we established optimal poling conditions to improve the electrical properties of the optimized piezoelectric material, based on the evaluation of ceramic properties according to the applied voltage during the poling process. The optimized composition of the investigated piezoelectric ceramics is represented by 0.14PZN-0.06PMN-0.80PbZr0.49Ti0.51 + 0.3 wt.% CuO + 0.3 wt.% Fe2O3 with 0.1 wt.% Sb2O3 doping, which yielded the superior properties (d33 = 361 pC/N, Qm = 1234, Tc = 306 °C).