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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, it is necessary to establish standards for clinical pharmacists in hospitals and to calculate appropriate manpower. Through this study, we aim to establish practical standards for clinical pharmacists and propose a method for calculating staffing levels based on an investigation of actual workloads. Methods This survey-based study consisted of two phases. In the first phase, a literature review was conducted to establish standards for clinical pharmacy services, and tasks in relevant literature were classified to identify clinical pharmacy service tasks that are applicable to the practice of Korean hospitals. Additionally, a preliminary survey was conducted to investigate the essential tasks. In the second phase of the investigation, a multicenter survey was conducted targeting pharmacists in facilities with more than 1,000 beds to explore their perceptions and actual workloads related to tasks. Results According to the standards for clinical pharmacists in Korea, clinical pharmacy services consist of a total of 23 tasks, of which 16 have been identified as essential tasks. Essential tasks accounted for 93% of the total tasks in clinical pharmacy services. The average full-time equivalent (FTE) through workload calculation was 2.5 ± 1.9 for each field, while the FTE allocated to actual practice was 2.1 ± 1.6. The distribution of each type of clinical pharmacy service was as follows: 77% for medication therapy management, 13% for medication education, 8% for multidisciplinary team activities, and 3% for medication use evaluation. Conclusion This study identified essential tasks common to clinical pharmacy services across different healthcare institutions. 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 a hospital, it is necessary to ensure an adequate workforce for essential tasks.

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. 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. There was a significant difference in the prevalence of statin use between the cases and controls (53.7% vs. 61.2%, respectively; p < 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 < 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 < 0.001). The protective effects of statins against SNHL were consistent regardless of age and sex. 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 and Objectives: Vitamin D is a bone modulator widely used in regenerative medicine. This study aimed to analyze the effects of vitamin D on the osteogenic differentiation and mineralization of human mesenchymal stem cells. Materials and Methods: Spheroids were fabricated using human bone marrow-derived stem cells, and were cultured in the presence of vitamin D at concentrations of 0, 0.1, 1, 10, and 100 nM. Stem cell spheroids were fabricated and the morphological evaluation was conducted on days 1, 3, 7 and 14. Determination of qualitative cellular viability was performed with Live/Dead Kit assay on days 1 and 7. Quantitative cellular viability was evaluated with Cell Counting Kit-8 on days 1, 3, 7, and 14. To analyze the osteogenic differentiation of cell spheroids, alkaline phosphatase activity assays were performed with commercially available kit on days 7 and 14. Real-time polymerase chain reaction was used to determine the expression levels of RUNX2, BSP, OCN, and COL1A1 on days 7 and 14. Results: The stem cells produced well-formed spheroids, and addition of vitamin D did not result in any noticeable changes in the shape. The addition of vitamin D did not significantly change the diameter of the spheroids at 0, 0.1, 1, 10, or 100 nM concentrations. Quantitative cell viability results from days 1, 3, 7 and 14 showed no significant difference between groups (p > 0.05). There was significantly higher alkaline phosphatase activity in the 0.1 nM group when compared with the control group on day 14 (p < 0.05). Real-time polymerase chain reaction results demonstrated that the mRNA expression levels of RUNX2, OCN, and COL1A1 were significantly increased when vitamin D was added to the culture. Conclusions: Based on these findings, we concluded that vitamin D could be applied to the increased osteogenicity of stem cell spheroids.

BackgroundAlthough 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.MethodsA 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.ResultsPPI 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.ConclusionsOur 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.

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.

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 > 0.05). There was statistically higher alkaline phosphatase activity in the 10 ng/mL group compared with the unloaded control on Day 7 (p < 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 < 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.

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 β-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 ± 0.015, 0.427 ± 0.013, and 0.500 ± 0.030, respectively (p < 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 ± 0.152, 1.897 ± 0.144, and 2.067 ± 0.128, respectively (p > 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 < 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.

Background/Objectives: Cuminum cyminum L. has been utilized as a medicinal plant for centuries. This research sought to examine the effects of cumin methanolic extract (CMT) on the chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells. Methods: Spheroids were generated using human stem cells and cultured with CMT at concentrations between 0 and 1 µg/mL. Morphological assessments and cell viability tests were conducted on days 1 and 3. Chondrogenic differentiation expression was evaluated through quantitative polymerase chain reaction, Western blot, and RNA sequencing. SOX9, FAM20B, COL2A1, and COL1A1 mRNA expression levels were determined using real-time polymerase chain reaction. Protein expression was analyzed via Western blot. Results: Throughout this study, the spheroids maintained their integrity and shape. No significant variations in spheroid diameter were observed among the groups. CMT treatment enhanced the expression of SOX9 and FAM20B. Conclusions: The methanolic extract of Cuminum cyminum facilitated chondrogenic differentiation in human bone marrow-derived mesenchymal stem cells by modulating SOX9 and FAM20B expression. This indicates its potential application in cartilage tissue engineering.

Background: Connective tissue growth factor (CTGF) is a cellular communication network factor family protein involved in many cellular functions. The purpose of this study was to determine the effects of CTGF on the proliferation, osteogenic capacity, and mRNA expression of spheroids composed of gingiva-derived mesenchymal stem cells (GMSCs). Methods: CTGF was applied at final concentrations of 0, 25, 50, 100, and 200 ng/mL. Qualitative cell viability was determined using Live/Dead kit assay. Metabolic viability was determined with a colorimetric assay kit. Osteogenic activity was analyzed with alkaline phosphatase activity and Alizarin Red S staining. Quantitative polymerase chain reaction (qPCR) was used to assess the expression levels of RUNX2, BSP, OCN, and COL1A1. Results: In general, there was no significant difference in cell viability between the groups on Days 1, 4, and 7. Addition of CTGF produced an increase in Alizarin Red S staining. qPCR results demonstrated that the mRNA expression levels of RUNX2, BSP, OCN, and COL1A1 were significantly increased with the addition of CTGF. Conclusions: Based on these findings, we conclude that CTGF 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 < 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 < 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 < 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.