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Background After the revision of the Korean Pharmaceutical Affairs Act, the certification of specialized pharmacists is scheduled to be legally recognized in 2023. Considering that the specialized pharmacist certification was developed based on the working model of hospital clinical pharmacists, standards for clinical pharmacists in hospital and appropriate manpower calculation are needed. AimTo develop practical standards for clinical pharmacists and to present the standards for calculating the level of manpower based on the actual workload survey. Method In order to develop clinical pharmacy services standards, literature review was performed. To classify essential tasks, a modified Delphi study was performed in a tertiary hospital. Based on this, manpower calculation was performed through a multi-center survey for pharmacists in hospitals with more than 1,000 beds. The survey respondents were working in one out of four fields: pediatrics, organ transplantation, oncology, and critical care. Results Clinical pharmacy services were classified into 4 types: medication therapy management, medication education, medication use evaluation, and multidisciplinary team activities. Essential tasks accounted for 93% of the total tasks for clinical pharmacy services. The required full-time equivalent (FTE) through workload calculation was 2.5±1.9 on average for each field, while the FTE allocated to actual practice was 2.1±1.6. Conclusion An agreement was reached on the essential work of clinical pharmacy services. However, the FTE of clinical pharmacists in actual practice was insufficient compared to the required amount. In order to establish and expand clinical pharmacy services in hospital, it is necessary to ensure manpower for essential tasks.

The biocomposites of hydroxypropyl methylcellulose (HPMC)/silver nanoparticles (AgNPs) were synthesized using the solution plasma process (SPP). HPMC/AgNPs were synthesized in 1-5 % HPMC solutions using silver electrodes. UV-Vis spectroscopy showed a peak near 400 nm and the peak increased as the concentration of HPMC and discharge time increased. FTIR analysis indicated no change in the chemical structure of the HPMC based biocomposites. Spherical shaped AgNPs with size ranges about 2-18 nm and well dispersed in the porous HPMC matrices with fringed edges were observed by TEM and SEM/EDS analyses. The synthesized biocomposites were found to be thermo-stable by TGA analysis. The inhibition zones of bacterial growth formed by the HPMC/AgNPs biocomposites were in the range of 8-14.3 mm; minimal inhibition concentrations, in the range of 10-15 μg·mL

Noni fruit (Morinda citrifolia) has been widely used in traditional medicine across tropical and subtropical regions, and is now being paid more attention in Western medicine. The present study aimed to investigate the effects of noni extract on the change in the cellular morphology, maintenance of cellular viability and enhancement of osteogenic differentiation of stem cells. Stem cells obtained from gingiva were cultured where noni extracts existed at concentrations ranging from 10-200 ng/ml. Evaluations of cell morphology and cellular viability were performed. Alkaline phosphatase activity assays were performed to assess the osteogenic differentiation. Alizarin Red S staining was performed to evaluate the calcium deposits in the culture, with the addition of noni extract. Global gene expression was analyzed via next-generation mRNA sequencing. Gene ontology and pathway analyses were performed to determine the associated mechanisms. Validation procedures were performed via quantitative (q)PCR analysis. The addition of noni at concentrations ranging from 10-200 ng/ml did not produce significant morphological changes. There were significantly higher values of cellular viability, with the highest value at 100 ng/ml compared with the control (P

Background: Statins have emerged as protective agents against sensorineural hearing loss (SNHL) associated with dyslipidemia, but the effects of statins on SNHL are not consistent. The purpose of this study was to investigate the association between statin use and the risk of SNHL using a hospital cohort. Methods: This nested case-control study included type 2 diabetic patients over the age of 18 years without a history of hearing loss. Of these, 1379 patients newly diagnosed with SNHL or tinnitus were classified as cases, and 5512 patients matched to the cases based on age, sex, and index year were classified as controls. Chi-squared tests were used to compare categorical variables between the two groups. Odds ratios (ORs) and adjusted odds ratios (AOR) were calculated from univariate and multivariable unconditional logistic regression analyses, respectively. Results: There was a significant difference in the prevalence of statin use between the cases and controls (53.7% vs. 61.2%, respectively, p &lt, 0.001). The use of statins in type 2 diabetic patients significantly reduced the risk of SNHL or tinnitus by 24.8% (95% CI 14.2–34.1%, p &lt, 0.001) after controlling for confounders. Similar results were found for the association between statin use and SNHL (AOR = 0.706, 95% CI 0.616–0.811, p &lt, 0.001). The protective effects of statins against SNHL were consistent regardless of age and sex. Conclusion: The use of statins for type 2 diabetic patients was significantly associated with a reduced risk of SNHL, regardless of age and sex. Further studies are needed, especially large cohort studies, to evaluate the long-term protective effects of statins.

Background This analysis investigated whether baseline characteristics affect the survival benefit derived from palbociclib‐fulvestrant and the optimal timing of cyclin‐dependent kinase 4/6 inhibitor therapy for advanced breast cancer (ABC) in patients from PALOMA‐3. Patients and Methods In total, 521 patients were randomized 2:1 to receive palbociclib (125 mg/day, 3/1 schedule)–fulvestrant (500 mg, intramuscular injection, on days 1 and 15 of cycle 1, and then day 1 of each subsequent cycle) or matching placebo‐fulvestrant. Median overall survival (OS) and progression‐free survival were estimated using the Kaplan‐Meier method. Results Multivariable analysis identified endocrine sensitivity, nonvisceral disease, no prior chemotherapy for ABC, and Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 as significant prognostic factors for OS. Patients without chemotherapy for ABC had fewer prior lines of treatment in any setting and in the ABC setting versus patients with prior chemotherapy for ABC (two or fewer prior systemic therapies: 69% vs. 42%; no more than one prior line for ABC: 82% vs. 33%, respectively). Median OS was prolonged with palbociclib‐fulvestrant in patients without prior chemotherapy for ABC (39.7 vs. 29.5 months; hazard ratio, 0.75; 95% confidence interval [CI]: 0.56–1.01) and was similar in patients with prior chemotherapy for ABC (25.6 vs. 26.2 months; hazard ratio, 0.91 [95% CI: 0.63–1.32]) versus placebo‐fulvestrant. Conclusion Prognostic factors for OS included endocrine sensitivity, nonvisceral disease, ECOG PS of 0, and no prior chemotherapy for ABC. Exploratory analyses suggest improved OS with palbociclib‐fulvestrant versus placebo‐fulvestrant in patients with no prior chemotherapy for ABC, prior endocrine sensitivity, and fewer prior regimens of systemic therapy. (Clinical trial identification number: NCT01942135). Implications for Practice Prognostic factors for overall survival in HR+/HER2− advanced breast cancer (ABC) include the absence of prior chemotherapy in the advanced setting, endocrine sensitivity, nonvisceral disease, and an ECOG performance status of 0. Improved overall survival benefit was observed with palbociclib‐fulvestrant versus placebo‐fulvestrant in patients (regardless of menopausal status or visceral involvement) with no prior chemotherapy for ABC, with prior endocrine sensitivity, and fewer prior regimens of systemic therapy. Progression‐free survival was prolonged with palbociclib across subgroups (regardless of chemotherapy exposure in ABC). These exploratory findings suggest that patients may receive greater clinical benefit from palbociclib‐fulvestrant if they receive the combination before chemotherapy in the advanced setting., This article focuses on whether baseline characteristics affect the survival benefit derived from palbociclib‐fulvestrant and the optimal timing of cyclin‐dependent kinase 4/6 inhibitor therapy for advanced breast cancer in patients from the PALOMA‐3 clinical trial.

Background and objectives: NELL-1 is a competent growth factor and it reported to target cells committed to the osteochondral lineage. The secreted, osteoinductive glycoproteins are reported to rheostatically control skeletal ossification. This study was performed to determine the effects of NELL-1 on spheroid morphology and cell viability and the promotion of osteogenic differentiation of stem cell spheroids. Materials and Methods: Cultures of stem cell spheroids of gingiva-derived stem cells were grown in the presence of NELL-1 at concentrations of 1, 10, 100, and 500 ng/mL. Evaluations of cell morphology were performed using a microscope, and cell viability was assessed using a two-color assay and Cell Counting Kit-8. Evaluation of the activity of alkaline phosphatase and calcium deposition assays involved anthraquinone dye assay to determine the level of osteogenic differentiation of cell spheroids treated with NELL-1. Real-time quantitative polymerase chain reaction (qPCR) was used to evaluate the expressions of RUNX2, BSP, OCN, COL1A1, and β-actin mRNAs. Results: The applied stem cells produced well-formed spheroids, and the addition of NELL-1 at tested concentrations did not show any apparent changes in spheroid shape. There were no significant changes in diameter with addition of NELL-1 at 0, 1, 10, 100, and 500 ng/mL concentrations. The quantitative cell viability results derived on Days 1, 3, and 7 did not show significant disparities among groups (p &gt, 0.05). There was statistically higher alkaline phosphatase activity in the 10 ng/mL group compared with the unloaded control on Day 7 (p &lt, 0.05). A significant increase in anthraquinone dye staining was observed with the addition of NELL-1, and the highest value was noted at 10 ng/mL (p &lt, 0.05). qPCR results demonstrated that the mRNA expression levels of RUNX2 and BSP were significantly increased when NELL-1 was added to the culture. Conclusions: Based on these findings, we conclude that NELL-1 can be applied for increased osteogenic differentiation of stem cell spheroids.

The growth of bone morphogenetic protein 7 (BMP-7) has been applied for tissue regeneration due to its osteoinductive properties. The aim of this research is to analyze the enhancing effects of BMP-7 on the osteogenic differentiation and mineralization of human bone marrow-derived stem cells cultured on the bovine bone particle. After the stem cells were loaded onto the bone graft material, their morphology was observed on day 7. Viability assays based on the application of fluorescent stains were used for qualitative analyses. Alkaline phosphatase activity assays and Alizarin red staining were used for the assessment of osteogenic differentiation on days 7 and 14. Next-generation mRNA sequencing was applied to evaluate global gene expression. Gene ontology and pathway analysis was used to propose the underlying mechanism. Fibroblast-like morphology was attained with the stem cells. The cells were shown to be firmly attached to the bone particle. Most of the stem cells produced an intense green fluorescence. The relative cellular viability assay values for BMP-7 groups at 0, 10, and 100 ng/mL on day 7 were 0.295 ± 0.003, 0.250 ± 0.002, and 0.240 ± 0.003, respectively (p &lt, 0.05). Alkaline phosphatase activity was significantly higher in BMP-7 groups at concentration of 100 ng/mL compared to the control on days 7 and 14 (p &lt, 0.05). The results of the mineralization assay showed significantly higher values for BMP-7 groups at 100 ng/mL concentration when compared with the control (p &lt, 0.05). The expression of RUNX2 was increased with application of BMP-7 and mitogen-activated protein kinase pathway was associated with the target genes. Overall, this study shows that in vitro application of BMP-7 increases alkaline phosphorylase activity and mineralization of stem cells culture on deproteinized bovine bone mineral. The study suggests that combining stem cells with osteoinductive growth factors with scaffolds can have synergy effects on osteogenic differentiation.

The potential applications of nanomaterials used in nanomedicine as ingredients in drug delivery systems and in other products continue to expand. When nanomaterials are introduced into physiological environments and driven by energetics, they readily associate proteins forming a protein corona (PC) on their surface. This PC could result in an alteration of the nanomaterial’s surface characteristics, affecting their interaction with cells due to conformational changes in adsorbed protein molecules. However, our current understanding of nanobiological interactions is still very limited. Utilizing a liquid chromatography–mass spectroscopy/mass spectroscopy technology and a Cytoscape plugin (ClueGO) approach, we examined the composition of the PC for a set of zinc oxide nanoparticles (ZnONP) from cell culture media typically and further analyzed the biological interaction of identified proteins, respectively. In total, 36 and 33 common proteins were investigated as being bound to ZnONP at 5 min and 60 min, respectively. These proteins were further analyzed with ClueGO, a Cytoscape plugin, which provided gene ontology and the biological interaction processes of identified proteins. Proteins bound to the surface of nanoparticles that may modify the structure, therefore the function of the adsorbed protein could be consequently affect the complicated biological processes.

Background and Objectives: Cuminum cyminum L. has long been used in the treatment of various diseases in multiple geographical regions. This study was performed to determine the effects of C. cyminum methanolic extract (CCT) on the cellular viability, alkaline phosphatase activity and mineralization of human mesenchymal stem cells. Materials and Methods: Bone marrow-derived stem cells were cultured in the presence of CCT at concentrations of 0, 0.001, 0.01, 0.1 and 1 &mu, g/mL. Evaluations of cell morphology were performed on days 1, 3, 7 and 14. Cellular viability was evaluated on days 1, 3, 5 and 7. On the 7th and 14th day, alkaline phosphatase activity measurements and Alizarin red S staining were conducted to assess the osteogenic differentiation of stem cells. A real-time polymerase chain reaction was used to determine the expression levels of RUNX2, BSP, OCN, COL2A1 and &beta, catenin mRNAs. Results: Stem cells in the control group showed fibroblast-like morphology and the addition of CCT at 0.001, 0.01, 0.1 and 1 &mu, g/mL did not generate noticeable changes in morphology compared with the untreated control group. The application of CCT did not produce significant changes in cellular viability or alkaline phosphatase activity compared with controls. Alizarin Red S staining was significantly increased with the application of CCT. Treatment with CCT increased the expressions of RUNX2, BSP and OCN. Conclusions: These results indicate that CCT enhanced the osteogenic differentiation of stem cells derived from bone marrow by regulating the expressions of RUNX2, BSP and OCN. Thus, the use of CCT may be applied to achieve beneficial effects on the mineralization of stem cells.

Background and Objectives: Cuminum cyminum L. has long been used in the treatment of various diseases in multiple geographical regions. This study was performed to determine the effects of C. cyminum methanolic extract (CCT) on the cellular viability, alkaline phosphatase activity and mineralization of human mesenchymal stem cells. Materials and Methods: Bone marrow-derived stem cells were cultured in the presence of CCT at concentrations of 0, 0.001, 0.01, 0.1 and 1 μg/mL. Evaluations of cell morphology were performed on days 1, 3, 7 and 14. Cellular viability was evaluated on days 1, 3, 5 and 7. On the 7th and 14th day, alkaline phosphatase activity measurements and Alizarin red S staining were conducted to assess the osteogenic differentiation of stem cells. A real-time polymerase chain reaction was used to determine the expression levels of RUNX2, BSP, OCN, COL2A1 and β-catenin mRNAs. Results: Stem cells in the control group showed fibroblast-like morphology and the addition of CCT at 0.001, 0.01, 0.1 and 1 μg/mL did not generate noticeable changes in morphology compared with the untreated control group. The application of CCT did not produce significant changes in cellular viability or alkaline phosphatase activity compared with controls. Alizarin Red S staining was significantly increased with the application of CCT. Treatment with CCT increased the expressions of RUNX2, BSP and OCN. Conclusions: These results indicate that CCT enhanced the osteogenic differentiation of stem cells derived from bone marrow by regulating the expressions of RUNX2, BSP and OCN. Thus, the use of CCT may be applied to achieve beneficial effects on the mineralization of stem cells.

Numerous carrier scatterers, such as atomic defects, fixed oxide charges, impurities, chemical residues, and undesired surface adsorbates, including oxygen and water molecules, strongly degrade the carrier mobility of atomically thin two-dimensional (2D) materials. However, the effect of surface adsorbates and surface oxidation on the carrier density profile along the thickness of 2D multilayers is not well known, particularly for a substantial interruption in the formation of the top-surface channel. Here, we uncover a hidden surface channel in p-type black phosphorus and n-type rhenium disulfide multilayers originating from undesired ambient adsorbates and surface oxides that not only populate hole density (or reduce electron density) but also suppress carrier mobility. The absence of a second peak in the transconductance curve under ambient conditions indicates the disappearance of the top-surface channel inside the 2D multilayers, which is a possible indicator for the cleanliness of the top surface and can be used in gas sensor applications. Moreover, the negligible variation in the drain bias polarity-dependent turn-on voltage for the bottom channel under ambient conditions validates the exclusive contribution of surface adsorbates to the formation of the top channel in 2D multilayers. Our results provide a novel insight into the distinct carrier transport in 2D optoelectronic devices and diverse sensors.

Bone morphogenetic protein-4 (BMP-4) is engaged in the migration ability of mesenchymal stem cells and the transition of mesenchymal stem cells into osteogenic and adipocytic lines. The aim of this study was to evaluate the effects of BMP-4 on the cellular viability, osteogenic differentiation, and genome-wide mRNA levels using three-dimensional cell spheroids composed of stem cells. Stem cell spheroids were formed using concave microwells in the presence of BMP-4 with final concentrations of 0, 2, 6, and 10 ng/mL. Cellular viability was measured qualitatively using a microscope and quantitatively using an assay kit based on water-soluble tetrazolium salt. Osteogenic differentiation was assessed by measuring the level of alkaline phosphatase activity. Global gene expression was assessed using next-generation mRNA sequencing and performing gene ontology and pathway analyses. Spheroids were well-maintained with the addition of BMP-4 up to Day 7. No significant differences were observed in cell viability between each group. There were significantly higher alkaline phosphatase values in the 2 ng/mL BMP-4 groups when compared with the control (p &lt, 0.05). A total of 25,737 mRNAs were differentially expressed. Expression of &beta, catenin (CTNNB1) was increased with higher dosages of BMP-4. The expression of runt-related transcription factor 2 (RUNX2) was increased up to 6 ng/mL. The phosphoinositide-3-kinase&ndash, protein kinase B/Akt signaling pathway was associated with the target genes. This study demonstrates that the application of BMP-4 enhanced alkaline phosphatase activity and the expression of CTNNB1 and RUNX2 without affecting cellular viability.

Insulin-like growth factors (IGFs) plays various roles, including differentiation and mitogenesis, and IGFs are reported to regulate the bone growth and maintenance. This study was performed to analyze the enhancing effects of IGF-2 on osteogenic differentiation and the mineralization of stem cells cultured on deproteinized bovine bone mineral. Stem cell loaded bone graft material was cultured in the presence of the IGF-2 at final concentrations of 10 and 100 ng/mL and the morphology of the cells was observed on Days 1, 3, and 7. The commercially available, two-color assay based on plasma membrane integrity and esterase activity was also used for qualitative analyses on Days 1, 3, and 7. The level of alkaline phosphatase activity and anthraquinone dye assay were used to evaluate osteogenic differentiation on Days 7 and 14. Real-time polymerase chain reaction was applied in order to identify the mRNA expression of BGLAP, Runx2, and &beta, catenin. The stem cells were well-attached with fibroblast morphology and most of the stem cells produced a high intensity of green fluorescence, indicating that there were live cells on Day 1. The relative cellular viability assay values for IGF-2 groups at 0, 10, and 100 ng/mL on Day 1 were 0.419 &plusmn, 0.015, 0.427 &plusmn, 0.013, and 0.500 &plusmn, 0.030, respectively (p &lt, 0.05). The absorbance values at 405 nm for alkaline phosphatase activity on Day 7 for IGF-2 at 0, 10, and 100 ng/mL were 2.112 &plusmn, 0.152, 1.897 &plusmn, 0.144, and 2.067 &plusmn, 0.128, respectively (p &gt, 0.05). The mineralization assay results at Day 7 showed significantly higher values for IGF-2 groups at 10 and 100 ng/mL concentration when compared to the control (p &lt, 0.05). The application of IGF-2 groups of 10 and 100 ng/mL produced a significant increase of BGLAP. Conclusively, this study indicates that the use of IGF-2 on stem cell loaded bone graft increased cellular viability, Alizarin red staining, and BGLAP expression of stem cells. This report suggests the combined approach of stem cells and IGF-2 with scaffold may have synergistic effects on osteogenesis.

The purpose of this case report was to introduce the concept of orthodontic and orthopedic treatment for a growing patient with Tessier number 0 cleft. A 5-year-old boy patient with Tessier number 0 cleft presented congenitally missing maxillary central incisors (MXCI), a bony defect at the premaxilla, a constricted maxillary arch, an anterior openbite, and maxillary hypoplasia. His treatment was divided into three stages: management of the bony defect at the premaxilla and the congenitally missing MXCIs using a fan-type expansion plate, iliac bone grafting, and eruption guidance of the maxillary lateral incisors into the graft area for substitution of MXCIs; management of the maxillary hypoplasia using sequential facemask therapy with conventional and skeletal anchorage; and management of the remaining occlusal problems using fixed orthodontic treatment. The total treatment duration was 15 years and 10 months. Class I canine and Class II molar relationships and normal overbite and overjet were achieved at the end of treatment. Although the long-term use of facemask therapy resulted in significant protraction of the retrusive maxilla, the patient exhibited Class III profile because of continued mandibular growth. However, the treatment result was well maintained after 2 years of retention. The findings from this case suggest that interdisciplinary and customized approaches are mandatory for successful management of maxillary hypoplasia, bony defect, and dental problems in Tessier number 0 cleft. Moreover, considering the potential of orthognathic surgery or distraction osteogenesis, meticulous monitoring of mandibular growth until growth completion is important.

Background The epidemiology of Adamantiades-Behcet's disease varies among ethnic populations worldwide. Trends in the incidence of Adamantiades-Behcet's disease have not been investigated based on the Korean National Health Insurance database. Objectives This study investigated the incidence and mortality of Adamantiades-Behcet's disease by age using nationwide population data in Korea. Methods A nationwide population-based cohort study was performed using the Korean National Health Insurance Claims Database from 2006 to 2015. The incidence of Adamantiades-Behcet's disease was calculated by age, sex, calendar year and habitat. And comorbid metabolic diseases were also analysed in patients with Adamantiades-Behcet's disease. Results The annual incidence of Adamantiades-Behcet's disease per 100 000 person-years was 3.976 (2.587 for males and 5.373 for females) from 2006 to 2015. The incidence of Adamantiades-Behcet's disease peaked among people in their 40s (6.561 per 100 000 person-years). Incidence was significantly higher in subjects with comorbid metabolic conditions, such as diabetes mellitus, hypertension and dyslipidemia. The mortality rate per 1000 person-years increased with age in patients with Adamantiades-Behcet's disease. Conclusions This study showed the incidence, prevalence and mortality of Adamantiades-Behcet's disease. Metabolic conditions increased the risk of Adamantiades-Behcet's disease among Koreans.

The purpose of this study was to investigate the amount and pattern of postsurgical relapse after 2-jaw surgery in cleft lip and palate patients in terms of the sagittal and vertical aspects. The samples consisted of 21 adult patients who had the similar initial skeletodental pattern before surgery and underwent 2-jaw surgery. They were divided into high relapse (n = 11) and low relapse groups (n = 10) (criteria, 30% forward relapse of the B point). After the cephalometric variables of cephalograms taken at 1 month before surgery (T0), immediately after surgery (T1), and at least 1 year after surgery (T2) were measured, the Wilcoxon test, Mann-Whitney U test, and Pearson correlation test were performed for statistical analysis. When compared with the low relapse group, the high relapse group exhibited significant counterclockwise rotation of the distal segment of the mandible resulting in more forward movement of the mandible and significant labioversion of the maxillary incisors during T1-T2. The amount of postsurgical relapse of the mandible had a positive relationship with the amounts of setback and clockwise rotation of the mandible with surgery. In addition, the more decrease in overbite through surgery occurred, the more relapse (forward movement of the mandible) produced. Therefore, for the prevention of significant postsurgical relapse of the mandible in cleft patients, it is necessary to reduce unnecessary clockwise rotation of the mandible and to increase the vertical stability of maxilla during orthognathic surgery.

Although there are several studies on the association between use of proton pump inhibitors (PPIs) and increased Clostridium difficile infection (CDI) risk, detailed studies analyzing the effects of PPI use on CDI risk are lacking. The present study investigated the association of the dose, duration, and types of PPIs with CDI risk. A single-center, cohort study was conducted on patients admitted to a hospital. The exposed cohort comprised patients who were prescribed PPIs at least once during the study period, and a control cohort was prepared by randomly assigning an index date to patients who did not use PPIs ensuring the same distribution of index dates as in the exposed cohort and matching sex, age, hospitalization period, and date of admission. PPI use increased the risk of CDI by 1.8-fold [95% confidence interval (CI) 1.5–2.2]. CDI risk increased by 1.8-fold with esomeprazole (95% CI 1.4–2.2) and 2.0-fold with pantoprazole (95% CI 1.5–2.8). Patients who used a high dose had a higher risk than those who used a medium dose [adjusted hazard ratio (HR) 2.0 vs 1.3]. The risk of CDI increased 4.2-fold when the PPI exposure period was 6 days or shorter than 6 days. Our study showed that PPI use was associated with an increased risk of developing CDI and the risk of CDI was dose dependent. Therefore, PPIs should only be used at proper doses and only for the necessary indications to avoid CDI risk.

Objective Human papillomavirus (HPV) infection is the most important risk factor for cervical cancer, which progresses from precursor lesions with no symptom if left untreated. We compared the risk of cervical dysplasia among HPV-positive Korean women based on HPV types and infection patterns. Methods We observed participants of a 5-year multicenter prospective cohort study, comprising HPV-positive women with either atypical squamous cells of undetermined significance or low-grade squamous intraepithelial lesion of the cervix at their enrollment. Follow-ups, comprising cytology and HPV DNA testing results, were included in the final analysis. Incidence was calculated for each infection pattern (persistent infection, incidental infection, and clearance). To investigate cervical dysplasia risk, we used Cox proportional hazard models adjusted for variables that were significantly different among infection patterns. From April 2010 to September 2017, 71 of 1,027 subjects developed cervical dysplasia more severe than high-grade squamous intraepithelial lesion of the cervix. Results Of these 71 subjects, persistent infection, incidental infection, and clearance were noted in 30, 39, and 2 individuals, respectively. Based on changes in DNA results during follow-up, cumulative incidence was 27.2%, 10.4%, and 0.5% for persistent infection, incidental infection, and clearance, respectively. Compared to clearance, the adjusted hazard ratios for cervical dysplasia were 51.6 and 24.1 for persistent and incidental infections, respectively (p

Prior studies have reported the presence of lung fibrosis and enhanced airway hyperresponsiveness (AHR) in mice with high-fat-diet (HFD)-induced obesity. This study evaluated the role of TGF-β1 in HFD-induced AHR and lung fibrosis in a murine model. We generated HFD-induced obesity mice and performed glucose and insulin tolerance tests. HFD mice with or without ovalbumin sensitization and challenge were also treated with an anti-TGF-β1 neutralizing antibody. AHR to methacholine, inflammatory cells in the bronchoalveolar lavage fluid (BALF), and histological features were evaluated. Insulin was intranasally administered to normal diet (ND) mice, and in vitro insulin stimulation of BEAS-2b cells was performed. HFD-induced obesity mice had increased insulin resistance, enhanced AHR, peribronchial and perivascular fibrosis, and increased numbers of macrophages in the BALF. However, they did not have meaningful eosinophilic or neutrophilic inflammation in the lungs compared with ND mice. The HFD enhanced TGF-β1 expression in the bronchial epithelium, but we found no differences in the expression of interleukin (IL)−4 or IL-5 in lung homogenates. Administration of the anti-TGF-β1 antibody attenuated HFD-induced AHR and lung fibrosis. It also attenuated goblet cell hyperplasia, but did not affect the AHR and inflammatory cell infiltration induced by OVA challenge. The intranasal administration of insulin enhanced TGF-β1 expression in the bronchial epithelium and lung fibrosis. Stimulating BEAS-2b cells with insulin also increased TGF-β1 production by 24 h. We concluded that HFD-induced obesity-associated insulin resistance enhances TGF-β1 expression in the bronchial epithelium, which may play an important role in the development of lung fibrosis and AHR in obesity., Obesity: A trigger for asthma onset Insulin resistance may be an important causative factor underlying the increased risk of asthma and other respiratory issues in obese individuals. Obesity doubles the likelihood of developing asthma, with symptoms that are more difficult to control than in non-obese patients. The connection between these conditions is poorly understood, but researchers led by Jung-Won Park, Yonsei University College of Medicine, Seoul, South Korea, have identified a potential mechanism. They demonstrated that a signaling molecule called TGF-β1 contributes to airway sensitivity and tissue scarring in a mouse model of diet-induced obesity. Subsequent experiments showed that treatment with insulin also gives rise to increased TGF-β1 production in the mouse lung. Since insulin resistance is a common feature of obesity, resulting in abnormally high levels of circulating insulin, this could also account for the increased risk of respiratory problems.

Gefitinib is an oral tyrosine kinase inhibitor targeting the epidermal growth factor receptor (EGFR) for non-small-cell lung cancer with EGFR mutations. Although a few studies have analyzed the causes of gefitinib-induced hepatotoxicity, research focusing on the time intervals before and after hepatotoxicity has yet to be reported. Therefore, this study investigated two types of factors: the time to reach gefitinib-induced hepatotoxicity and the time for recovery. From January 2013 to December 2014, a retrospective study was carried out on 473 non-small-cell lung cancer patients who were treated with gefitinib. The following data were collected: sex, age, body weight, height, body surface area, underlying disease, Eastern Cooperative Oncology Group Performance Status, smoking history, gefitinib dose, EGFR mutation, and concomitant drugs. Multivariate models showed that patients with mutations in exon 19 had around two-fold higher hepatotoxicity (≥grade 2). Use of CYP3A4 inhibitors and smoking shortened time to hepatotoxicity ∼5-2-fold, respectively, whereas mutations in exon 21 prolonged time to hepatotoxicity by about 2.4-fold. Termination of gefitinib therapy showed 3.8-fold faster recovery. Our study showed that the concomitant use of CYP3A4 inhibitors, smoking, and exon 21 affected the time to reach gefitinib-induced hepatotoxicity. Among the factors examined in this study including hepatotonic use and gefitinib termination, only cessation of gefitinib therapy significantly accelerated recovery.

CD93 is a membrane-associated glycoprotein, which can be released in a soluble form (sCD93) into the serum. CD93 has received renewed attention as a candidate biomarker of inflammation in various inflammatory and immune-mediated diseases, including asthma.We aimed to evaluate the effects of airway inflammation on CD93 levels in murine models.We established an ovalbumin (OVA)-induced acute asthma murine model (OVA model) and a lipopolysaccharide (LPS)-induced airway inflammation murine model (LPS model). Dexamethasone was administered by gavage to attenuate the airway inflammation.The OVA model demonstrated typical allergic asthma features with increased airway hyper-responsiveness, inflammatory cell infiltration, increased Th2 cytokine levels, compared to the control group. CD93 levels were decreased in lung homogenates and, respiratory epithelial cells, whereas serum sCD93 levels were increased in the OVA model, as compared to the control group. Dexamethasone reversed these effects of OVA. In contrast, in the LPS model, CD93 levels were not affected in neither respiratory epithelial cells nor serum.Our findings demonstrate the potential of using sCD93 as a biomarker for allergic asthma.

The purpose of this study was to compare the alignment pattern of the constricted maxillary dental arch by fixed orthodontic treatment (FOT) in the well-aligned and constricted arches of unilateral cleft lip and palate (UCLP) patients. 19 UCLP patients were divided into Group 1 (well-aligned arch, n = 9) and Group 2 (constricted arch, n = 10). After the cephalometric and maxillary dental arch variables before (T1) and after FOT (T2) were measured, statistical analysis was performed. There were no significant differences in the surgical timing of cheiloplasty, palatoplasty, and secondary alveolar bone grafting and in the surgical method of cheiloplasty between the 2 groups. However, Group 2 had a higher percentage of palatoplasty method, which could leave the denuded bone for secondary healing than Group 1 (P < 0.05). Although Group 2 showed more constriction and asymmetry in the maxillary dental arch compared to Group 1 at the T1 stage (inter-second premolar width, greater segment angle [GSA], and lesser segment angle [LSA], all P < 0.05), these problems could be effectively resolved by FOT. As a result, at the stage T2, there was no significant difference in all the variables between the 2 groups. During T1-T2, there was a different pattern in change of variables between Groups 1 and 2 (anterior segment angle in the greater segment [P < 0.05] in Group 1 and U1-SN [P < 0.01], inter-molar width [P < 0.05], GSA [P < 0.05[, and LSA [P < 0.01] in Group 2). Therefore, according to the maxillary dental arch shape, different strategy is necessary to obtain proper alignment by FOT.

Childhood and adolescence are critical periods that affect adults’ health status. Therefore, the factors influencing the health of children and adolescents should be analyzed. In Korea, a wide range of youth-related health data has been obtained, both on the regional level and on the national level. This report summarizes the current status of studies related to the health of Korean children and adolescents. Data for which open access is offered include the Korea Youth Risk Behavior Web-based Study, the Panel Study on Korean Children, the Korean Youth Panel Survey, the Korean Children and Youth Panel Survey, and the Student Health Examination. In addition, the Health Examination of Korean Youth Outside of School, the Korean Children and Adolescents Obesity Cohort Study, the Korean Children’s Environmental Health Study, the Korea Youth Media Use and Harmful Environment Survey, the Comprehensive Survey of Korean Youth, and the Multicultural Adolescents Panel Study are summarized.

Reactive oxygen species (ROS) are important contributors to tumor cell invasion. ROS enhanced by reactive oxygen species modulator 1 (Romo1) expression has been reported to increase invasive potential and constitutive activation of nuclear factor-κB (NF-κB) in hepatocellular carcinoma (HCC). Therefore, we investigated whether constitutive NF-κB activation due to Romo1 expression is associated with breast cancer tumor cell invasion. In this study, we show that oxidative stress-induced invasion is mediated by Romo1 expression. The Romo1-induced increase of invasive activity was blocked by an inhibitor of κB kinase (IKK). These results demonstrate that tumor cell invasion in response to oxidative stress is associated with Romo1 expression and the NF-κB signaling pathway. Romo1 is therefore a promising therapeutic target for diseases characterized by NF-κB deregulation.

Zinc Oxide nanoparticles (ZnO NPs) in its small size with large reactive surfaces can lead to toxicological injury by generating reactive oxygen species (ROS) and oxidative stress. Recently, ZnO NPs were shown to play a role in acute or chronic toxicities with mammalian cells, where its mechanism of toxicity is not fully characterized yet. In this study, the potential mechanisms of ZnO NPs in inducing and increasing oxidative stress for causing cellular apoptosis were investigated with human keratinocytes. Indeed, ZnO NPs induced significant intracellular ROS and mitochondrial ROS productions. And it seemed that cellular ROS levels induced by ZnO NPs led to the dissipation of the mitochondrial membrane potentials and elicited the cellular apoptosis. The induced ROS production by ZnO NPs was blocked with chelator treatment, which inhibited the ZnO ion. The present study demonstrates that increased levels of ROS by ZnO NPs cause mitochondrial dysfunction and cellular apoptosis.

Background No clear association between hepatitis B virus (HBV) infection and atopic dermatitis (AD) has been established. Some studies have reported that subjects with HBV had an increased risk of atopy; other studies reported an inverse association between HBV seropositivity and allergic diseases. Objective We evaluated the association between AD and hepatitis B antigen (HBsAg) positivity using Korean National Health and Nutrition Examination Survey data. Methods In total, 14,776 participants aged > 19 years were included in the analysis. Multiple logistic regression analyses were used to evaluate the odds ratio of HBsAg positivity in association with AD and asthma. Results: The prevalence of HBsAg positivity was lower in individuals with AD than in those without AD (mean [SE], 0.7% [0.4] vs. 3.7% [0.2]; P < 0.001). However, HBsAg positivity was not significantly associated with asthma (3.7% [0.2] vs. 2.8% [0.8]; P < 0.001). HBsAg positivity decreased the risk of AD significantly (OR = 0.223; 95% CI = 0.069–0.72). Conclusions This study demonstrates an inverse association between AD and HBsAg positivity using a nationwide, population-based, cross-sectional health examination and survey. This article is protected by copyright. All rights reserved.

Quantum dots (QDs) have shown great potential for biomedical use in a broad range including diagnostic agents. However, the regulatory mechanism of dermal toxicity is poorly understood. In this study, we investigated how QDs-induced apoptosis is regulated in human keratinocytes. We also examined the effect of carboxylic acid-coated QDs (QD 565 and QD 655) on reactive oxygen species (ROS) production and apoptosis-related cellular signalling. The viability of keratinocyte was inhibited by two types of QDs in a concentration-dependent manner. QDs induce ROS production and blockade of AKT phosphorylation. Moreover, the cleavage of AKT-dependent pro-apoptotic proteins such as poly (ADP-ribose) polymerase, caspases-3 and caspases-9 was significantly increased. We also found that a decrease in cellular ROS level by ROS scavenger, N-acetylcysteine (NAC), resulting in the abolishment of QDs-induced AKT de-phosphorylation and cellular apoptosis. Interestingly, QD 655 had a more cytotoxic effect including oxidative stress and AKT-dependent apoptosis than QD 565. In addition, QD 655 had the cytotoxic potential in the human skin equivalent model (HSEM). These data show that QD-induced intracellular ROS levels may be an important parameter in QD-induced apoptosis. These findings from this study indicate that intracellular ROS levels might determine the apoptotic potential of keratinocyte by QD via blockade of AKT phosphorylation.

PURPOSE CD93 is receiving renewed attention as a biomarker of inflammation. We aimed to evaluate the potential for serum sCD93 to serve as a novel biomarker for allergic inflammation. MATERIALS AND METHODS We enrolled 348 subjects with an allergic disease [allergic rhinitis (AR), chronic spontaneous urticaria (CSU), or bronchial asthma (BA)], including 14 steroid-naive BA patients who were serially followed-up. RESULTS The serum sCD93 levels (ng/mL) in patients with exacerbated AR (mean±standard deviation, 153.1±58.4) were significantly higher than in patients without AR (132.2±49.0) or with stable AR (122.3±42.1). Serum sCD93 levels in exacerbated CSU (169.5±42.8) were also significantly higher than those in non-CSU (132.4±51.6) and stable CSU (122.8±36.2). This trend was also seen in BA. Serum levels in patients with ICS-naive BA (161.4±53.1) were significantly higher than those in healthy controls without BA (112.2±30.8), low- and medium-dose ICS users. Serum sCD93 levels in high-dose ICS users (72.2±20.6) were significantly lower than those in low- and medium-dose users. The serum sCD93 levels in steroid-naive patients with BA (195.1±72.7) decreased after ICS use for 4 weeks (134.4±42.8) and 8 weeks (100.7±13.4), serially. CONCLUSION Elevated serum sCD93 levels reflected exacerbated status of allergic diseases, including CSU, AR, and asthma. ICS use significantly diminished serum sCD93 levels in steroid-naive patients with BA. This result may suggest sCD93 in serum as a therapeutic marker for allergic inflammation.

Background: Silica nanoparticles (SNPs) can easily enter in respiratory system via inhalation because of their low molecular weight and ease of dispersion. Toxicity and adverse effects of SNPs vary according to the physical characteristics of the particle. Methods: To evaluate the toxic and adjuvant effects of 3 types of SNPs in the airway system, six-week-old female BALB/c mice were intranasally administered 3 types of SNPs (spherical [S-SNP], mesoporous [M-SNP], and polyethylene glycol-conjugated [P-SNP]) alone or SNPs/ovalbumin (OVA), three times weekly for 2 weeks. Airway hyper-responsiveness (AHR), bronchoalveolar lavage fluid (BALF), cytokine levels, and histology of the lungs were analyzed. Results: The S-SNPs/OVA group and M-SNPs/OVA group showed significant AHR, compared to the control group. Among all SNP-treated groups, the group administered SNPs/OVA showed greater inflammatory cell infiltration in BALF, extensive pathological changes, and higher cytokine levels (IL-5, IL-13, IL-1 beta, and IFN-gamma) than those administered SNPs alone or saline/OVA. Conclusion: Exposure to SNPs alone and SNPs/OVA induced toxicity in the respiratory system. SNPs alone showed significant toxic effects on the airway system. Meanwhile, SNPs/OVA exerted adjuvant effects to OVA of inducing allergic airway inflammation. In particular, M-SNPs showed the most severe airway inflammation in both direct toxicity and adjuvant effect assays. P-SNPs induced less inflammation than the other types of SNPs in both models.

Obese patients with asthma respond poorly to conventional asthma medications, resulting in severe symptoms and poor prognosis. Roflumilast, a phosphodiesterase-4 inhibitor that lowers the levels of various substances that are implicated in obese subjects with asthma, may be effective in the treatment of those subjects. We evaluated the potential of roflumilast as a novel therapeutic agent for obese subjects with asthma. We designed three models: diet-induced obesity (DIO); DIO with ovalbumin (OVA); and OVA. We fed C57BL/6J mice a high-fat diet for 3 months with or without OVA sensitization and challenge. Roflumilast or dexamethasone was administered orally three times at 2-day intervals in the last experimental week. Airway hyperresponsiveness resulting from DIO significantly improved in the roflumilast-treated group compared with the dexamethasone-treated groups. Although DIO did not affect the cell proliferation in bronchoalveolar lavage fluid, increased fibrosis was seen in the DIO group, which significantly improved from treatment with roflumilast. DIO-induced changes in adiponectin and leptin levels were improved by roflumilast, whereas dexamethasone aggravated them. mRNA levels and proteins of TNF-α, transforming growth factor-β, IL-1β, and IFN-γ increased in the DIO group and decreased with roflumilast. The reactive oxygen species levels were also increased in the DIO group and decreased by roflumilast. In the DIO plus OVA and OVA models, roflumilast improved Th1 and Th2 cell activation to a greater extent than dexamethasone. Roflumilast is significantly more effective than dexamethasone against airway hyperresponsiveness caused by DIO in the murine model. Roflumilast may represent a promising therapeutic agent for the treatment of obese patients with asthma.