Predicting responses to omalizumab in antihistamine-refractory chronic urticaria: A real-world longitudinal study.

Background: Treating chronic urticaria (CU) that is unresponsive to H1-antihistamines (H1AHs) is challenging, and the real-world effectiveness of omalizumab remains unclear. Objective: Our aim was to evaluate the real-world effectiveness of omalizumab, optimal response assessment timing, and predictive factors. Methods: Initially, 5535 patients with CU who were receiving at least 20 mg of loratadine daily for at least 6 months (January 2007-August 2021) were screened. Ultimately, 386 patients who had been receiving omalizumab add-on treatment for >6 months were followed-up for more than 2 years. Predictors of treatment response to omalizumab add-on therapy for patients with antihistamine-refractory CU were identified by using a generalized linear model. Results: In our retrospective cohort, omalizumab treatment showed cumulative response rates of 55.2% at 3 months, 71.0% at 6 months, and 81.4% at 9 months for patients with H1AH-refractory CU. Analysis of longitudinal responses to omalizumab treatment revealed 3 distinct clusters: favorable (cluster 1 [n = 158]), intermediate (cluster 2 [n =1 43]), and poor responses (cluster 3 [n = 85]). Subjects were categorized on the basis of whether they had achieved a complete response within 3 months; 213 early responders, 117 late responders, and 56 nonresponders were identified. The initial dose of omalizumab differed significantly among the 3 clusters. Low total IgE level (<40 kU/L) predicted nonresponse (odds ratio [OR] = 3.10 [P = .018]). Early responders were associated with a higher initial omalizumab dose (≥300 mg) (OR = 2.07 [P = .016]), higher basophil counts (OR = 2.0 [P = .014]), total IgE levels exceeding 798 kU/L (OR = 0.37 [P = .047]), and lower platelet-to-lymphocyte ratio (OR = 0.50 [P = .050]). Conclusion: Real-world data reveal 3 distinct clusters for response to omalizumab treatment; confirm low serum total IgE level (<40 kU/L) as a predictor of nonresponse; and identify potential biomarkers, including IgE level, basophil count, and PLR, for early responders.

Decadal Trends in Physical Activity Adherence Among Korean Older Adults: An Analysis of National Survey of Older Korean Data, 2011-2020.

BACKGROUND/OBJECTIVES: This study investigated adherence to physical activity (PA) guidelines and associated sociodemographic factors among older Koreans from 2011 to 2020. METHODS: Utilizing four public data sets from the National Survey of Older Koreans, the study included the data on 40,993 older adults 65 years and older in South Korea, collected between 2011 and 2020. Adherence to PA guidelines and sociodemographic factors were assessed through self-reported questionnaires. The data were analyzed using a two-way analysis of variance and post hoc tests. RESULTS: Overall adherence increased from 39.1% in 2011 to 48.2% in 2017, then decreased to 37.6% in 2020 (p < .001). Men had higher adherence than women (p < .001). Age-related adherence peaked in the young-older group (65-74 years old) and was lowest in the oldest-old group (85+ years old) (p < .001). Marital status, education, and income were also significantly related to PA adherence (p < .001) across the years. CONCLUSION: Although continuous increase in adherence to PA among Koreans 65 years and older was observed, the decline in PA levels during the COVID era underscored the need for targeted interventions and well-informed health care policies to address demographic challenges. Still, considering that data were collected during the recommended social distancing period, a cautions interpretation of these findings is warranted. Significance/Implications: Health policies aiming to improve adherence to PA guidelines should prioritize Korean older adults who are female, belong to the oldest-old group, are single, and have low education and income levels, with the goal of enhancing health equity.

Evaluation on the Nutrition Quotient Scores of Elderly People Living Alone in Korea.

As the Korean society is aging rapidly, the issues on physical, social, economic, and mental disabilities of single-person households aged 65 years or older has also increased. This study aimed to investigate the nutrition-related dietary conditions of elderly people living alone and determine their dietary behavior by calculating the nutrition quotient for elderly (NQ-E). One hundred and three elderly people living alone who were basic living recipients were recruited from six senior welfare centers in Seoul, and the data were collected using a questionnaire from 19 July 2016 to 17 August 2016, with a 1:1 in-depth interview using the modified version of the NQ-E questionnaire. The data were analyzed using SPSS 27.0 for Mac (IBM Corp., Armonk, NY, USA); a p value of <0.05 was considered significant. The nutrition-related dietary conditions of the elderly living alone were limited, and many of them received support from the government, which helped improve their diet. The nutrition quotient score of the elderly living alone was 50.14, which was lower than the NQ-E mean score (57.6) of the Korean elderly and the NQ-E (62 points), which is the top 25% of the national survey subjects according to the criteria value presented by the Korean Nutrition Society. Elderly people living alone often have poor dietary habits and nutritional status. The NQ-E presented in this study can be used to evaluate the dietary conditions of the elderly and is expected to be used as an indicator for developing community programs for health promotion and evaluating their effectiveness.

Intraoperative sudden arrhythmias in cervical spine surgery adjacent to the stellate ganglion: A case report.

BACKGROUND: Atrial arrhythmias such as paroxysmal supraventricular tachycardia (PSVT) and atrial flutter (AF) are common in the perioperative setting. They commonly resolve spontaneously. However, occasionally, they may continually progress to fatal arrhythmias or cause complications. Therefore, prompt and appropriate management is important. CASE SUMMARY: A 46-year-old female patient diagnosed with cervical C6-7 radiculopathy characterized by decreased sensation in the right third, fourth and fifth fingers underwent C6-7 anterior cervical disc fusion surgery. Electrocardiography showed PSVT and ventricular tachycardia during C6-7 disc retraction. However, the patient remained stable. Initial treatment with esmolol and lidocaine for ventricular tachycardia was ineffective. Carotid massage and Valsalva maneuver were attempted but PSVT did not resolve. The surgery was paused, and the patient's fraction of inspired oxygen was set to 100%. Adenosine was administered for pharmacological management of PSVT. The arrhythmia temporarily resolved. However, it then transformed into AF. Diltiazem was administered, which briefly decreased blood pressure, which immediately recovered. Surgery resumed while the patient was in normal sinus rhythm. She was discharged safely on postoperative day 6 without complications or abnormalities. Currently, she is living a healthy life without arrhythmia recurrence. CONCLUSION: Ganglia associated with cardiac arrhythmias in the surgical site should be identified during cervical spine surgery.

The effect of using vapocoolant spray for pain reduction in arteriovenous fistula cannulation among patients undergoing hemodialysis: A randomized control trial.

AIM: The aim of this study was to assess the effects of alkane vapocoolant spray in reducing pain during arteriovenous access cannulation in adult patients undergoing hemodialysis. BACKGROUND: Developing and applying various approaches for pain relief remain important responsibility for nurses. METHODS: This study was designed as an experimental study with a cross-over design. Thirty-eight patients on hemodialysis volunteered to undergo cannulation of their arteriovenous access, after the application of vapocoolant or placebo spray or no intervention. Subjective and objective pain levels were assessed, along with various physiological parameters pre- and post-cannulation. RESULTS: Statistically significant between-group differences were observed in subjective pain at the venous (F = 4.97, p = 0.009) and arterial (F = 6.91, p = 0.001) puncture sites. The mean arterial site subjective pain scores were 4.45 ± 1.31 (no treatment), 4.04 ± 1.82 (placebo), and 2.98 ± 1.53 (vapocoolant spray). Significant between-group differences were observed in objective pain scores during arteriovenous fistula puncture (F = 5.13, p = 0.007). The mean objective pain scores after arteriovenous fistula puncture were 3.25 ± 2.66 (no treatment), 2.17 ± 1.76 (placebo), and 1.78 ± 1.66 (vapocoolant spray). Post-hoc test results indicated vapocoolant spray application was associated with significantly lower pain scores than no treatment or placebo. Patient blood pressure and heart rate recordings did not differ among the interventions. CONCLUSION: Vapocoolant application was significantly more effective than the placebo or no treatment in reducing the pain of cannulation in adult patients undergoing hemodialysis.

Transverse myelitis caused by herpes zoster following COVID-19 vaccination: A case report.

BACKGROUND: Transverse myelitis (TM) is characterized by sudden lower extremity progressive weakness and sensory impairment, and most patients have a history of advanced viral infection symptoms. A variety of disorders can cause TM in association with viral or nonviral infection, vascular, neoplasia, collagen vascular, and iatrogenic, such as vaccination. Vaccination has become common through the global implementation against coronavirus disease 2019 (COVID-19) and reported complications like herpes zoster (HZ) activation has increased. CASE SUMMARY: This is a 68-year-old woman who developed multiple pustules and scabs at the T6-T9 dermatome site 1 wk after vaccination with the COVID-19 vaccine (Oxford/AstraZeneca ([ChAdOx1S{recombinant}]). The patient had a paraplegia aggravation 3 wk after HZ symptoms started. Spinal magnetic resonance imaging (MRI) showed transverse myelitis at the T6-T9 Level. Treatment was acyclovir with steroids combined with physical therapy. Her neurological function was slowly restored by Day 17. CONCLUSION: HZ developed after COVID-19 vaccination, which may lead to more severe complications. Therefore, HZ treatment itself should not be delayed. If neurological complications worsen after appropriate management, an immediate diagnostic procedure, such as magnetic resonance imaging and laboratory tests, will start and should treat the neurological complications.

Three Clinical Clusters Identified through Hierarchical Cluster Analysis Using Initial Laboratory Findings in Korean Patients with Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a heterogeneous disorder with diverse clinical manifestations. This study classified patients by combining laboratory values at SLE diagnosis via hierarchical cluster analysis. Linear discriminant analysis was performed to construct a model for predicting clusters. Cluster analysis using data from 389 patients with SLE yielded three clusters with different laboratory characteristics. Cluster 1 had the youngest age at diagnosis and showed significantly lower lymphocyte and platelet counts and hemoglobin and complement levels and the highest erythrocyte sedimentation rate (ESR) and anti-double-stranded DNA (dsDNA) antibody level. Cluster 2 showed higher white blood cell (WBC), lymphocyte, and platelet counts and lower ESR and anti-dsDNA antibody level. Cluster 3 showed the highest anti-nuclear antibody titer and lower WBC and lymphocyte counts. Within approximately 171 months, Cluster 1 showed higher SLE Disease Activity Index scores and number of cumulative manifestations, including malar rash, alopecia, arthritis, and renal disease, than did Clusters 2 and 3. However, the damage index and mortality rate did not differ significantly between them. In conclusion, the cluster analysis using the initial laboratory findings of the patients with SLE identified three clusters. While disease activities, organ involvements, and management patterns differed between the clusters, damages and mortalities did not.

No-ozone cold plasma can kill oral pathogenic microbes in H2O2-dependent and independent manner.

To apply the sterilisation effect of low-temperature plasma to the oral cavity, the issue of ozone from plasma must be addressed. In this study, a new technology for generating cold plasma with almost no ozone is developed and is named Nozone (no-ozone) Cold Plasma (NCP) technology. The antimicrobial efficacy of the NCP against four oral pathogens is tested, and its specific mechanism is elucidated. The treatment of NCP on oral pathogenic microbes on a solid medium generated a growth inhibition zone. When NCP is applied to oral pathogens in a liquid medium, the growth of microbes decreased by more than 105 colony forming units, and the bactericidal effect of NCP remained after the installation of dental tips. The bactericidal effect of NCP in the liquid medium is due to the increase in hydrogen peroxide levels in the medium. However, the bactericidal effect of NCP in the solid medium depends on the charged elements of the NCP. Furthermore, the surface bactericidal efficiency of the dental-tip-installed NCP is proportional to the pore size of the tips and inversely proportional to the length of the tips. Overall, we expect this NCP device to be widely used in dentistry in the near future.

Arsenite-induced cytotoxicity is regulated by p38-SQSTM1/p62 and JNK-BNIP3L/Nix signaling in lung cancer cells.

Arsenic is a potent carcinogen in humans. However, the molecular mechanisms underlying its toxicity in lung cancer remain unclear. Here, we report that arsenite-induced cytotoxicity is regulated by SQSTM1/p62 and BNIP3L/Nix signaling in non-small-cell lung cancer H460 cells. Arsenite exposure resulted in dose-dependent growth inhibition, which was associated with apoptosis, as demonstrated by depolarized mitochondrial membrane potential and cleavage of caspase-8, caspase-3, PARP-1, and Bax. The autophagy adaptor p62 was detected in the monomeric and multiple high-molecular-weight (HMW) forms, and protein levels were upregulated depending on both arsenite concentrations (≤45 µM) and exposure times (<24 h). LC3-II, an autophagy marker, was upregulated as early as 1 h after arsenite treatment. Expression of Nix, a mitochondrial outer membrane protein, continued to increase with arsenite concentration and exposure time; it was detected in the monomeric and multiple HMW forms. Soon after arsenite exposure, p62 colocalized with Nix in the cytoplasm, and p62 knockdown reduced the Nix levels and increased the LC3-II levels. In contrast, Nix knockdown did not affect the p62 and LC3-II levels but reduced caspase-8, caspase-3, and Bax cleavage, indicating that Nix accumulation resulted from its reduced autophagic degradation and promoted apoptosis. p38 inhibition markedly increased arsenite-induced Nix protein and reduced p62 protein levels, resulting in increased autophagy and apoptosis. Furthermore, c-Jun NH2-terminal kinase inhibition reduced Nix and Bax cleavage, and both signaling pathways were suppressed by N-acetylcysteine treatment. Our results suggest that arsenite-induced cytotoxicity is modulated by the coordinated action of p62 and Nix through MAPK.

In vitro modulatory effects of ginsenoside compound K, 20(S)-protopanaxadiol and 20(S)-protopanaxatriol on uridine 5'-diphospho-glucuronosyltransferase activity and expression.

We explored the inhibitory effect of ginsenoside compound K (CK), 20(S)-protopanaxadiol (PPD), and 20(S)-protopanaxatriol (PPT) on six uridine 5'-diphospho-glucuronosyltransferase (UGT) enzyme (UGT1A1, 1A3, 1A4, 1A6, 1A9, and 2B7) activities in human liver microsomes (HLMs) and 10 UGT enzyme (UGT1A1, 1A3, 1A4, 1A6, 1A9, 2B4, 2B7, 2B10, 2B15, and 2B17) activities in recombinant UGT isoforms.PPD was a potent inhibitor of UGT1A3 activity with half-maximal inhibitory concentration values of 5.62 and 3.38 µM in HLMs and recombinant UGT1A3, respectively. UGT1A3 inhibition by CK and PPD was competitive with inhibitory constant (Ki) values of 17.4 and 1.21 µM, respectively, and inhibition by PPT was non-competitive with a Ki value of 8.07 µM in HLMs. PPD exhibited more than 3.4-fold selectivity for UGT1A3 inhibition compared with other UGT isoforms inhibition, while CK and PPT showed more than 2.16- and 2.21-fold selectivity, respectively.PPD did not significantly increase the mRNA expression of UGT1A1, 1A3, 1A4, 1A9, and 2B7 in hepatocytes.Given the low plasma concentrations of PPD in healthy human subjects and the absence of induction potential on UGT isoforms, we conclude that PPD cause no pharmacokinetic interactions with other co-administered drugs metabolised by UGT1A3.

Non-thermal atmospheric pressure plasma activates Wnt/ß-catenin signaling in dermal papilla cells.

There is an unmet need for novel, non-pharmacological therapeutics to treat alopecia. Recent studies have shown the potential biological benefits of non-thermal atmospheric pressure plasma (NTAPP), including wound healing, angiogenesis, and the proliferation of stem cells. We hypothesized that NTAPP might have a stimulatory effect on hair growth or regeneration. We designed an NTAPP-generating apparatus which is applicable to in vitro and in vivo experiments. The human dermal papilla (DP) cells, isolated fresh hair follicles, and mouse back skin were exposed with the NTAPP. Biological outcomes were measured using RNA-sequencing, RT-PCR, Western blots, and immunostaining. The NTAPP treatment increased the expression levels of Wnt/ß-catenin pathway-related genes (AMER3, CCND1, LEF1, and LRG1) and proteins (ß-catenin, p-GSK3ß, and cyclin D1) in human DP cells. In contrast, inhibitors of Wnt/ß-catenin signaling, endo-IWR1 and IWP2, attenuated the levels of cyclin D1, p-GSK3ß, and ß-catenin proteins induced by NTAPP. Furthermore, we observed that NTAPP induced the activation of ß-catenin in DP cells of hair follicles and the mRNA levels of target genes of the ß-catenin signaling pathway (CCND1, LEF1, and TCF4). NTAPP-treated mice exhibited markedly increased anagen induction, hair growth, and the protein levels of ß-catenin, p-GSK3ß, p-AKT, and cyclin D1. NTAPP stimulates hair growth via activation of the Wnt/ß-catenin signaling pathway in DP cells. These findings collectively suggest that NTAPP may be a potentially safe and non-pharmacological therapeutic intervention for alopecia.

Cefaclor-induced hypersensitivity: Differences in the incidence of anaphylaxis relative to other 2nd and 3rd generation cephalosporins.

Cefaclor, a second-generation oral cephalosporin, is the most frequently prescribed cephalosporin in Korea. Studies, however, have yet to analyze the incidence of cefaclor-associated adverse drug reactions (ADRs), including hypersensitivity (HS), according to total national usage rates. This study aimed to investigate the incidence rates and clinical features of cefaclor ADRs reported to the Korean Adverse Event Reporting System (KAERS) and Health Insurance Review and Assessment Service (HIRA) database for the most recent 5 years. Reviewing the HIRA database, which contains information on all insurance claims, including prescribed medications and patient demographics, we identified the total number of individuals who had been prescribed cefaclor and other cephalosporins including 2nd generation without cefaclor and 3rd generation antibiotics from January 2014 to December 2018. Additionally, we retrospectively analyzed all ADRs reported to the KAERS for these drugs over the same study period. Incidence rates for ADRs, HS, and anaphylaxis to cefaclor were 1.92/10,000 persons, 1.17/10,000 persons, and 0.38/10,000 persons, respectively, lower than those to other 2nd and 3rd cephalosporins. Among all ADRs, HS (60.9% vs. 43.6% vs. 44.8%, P <0.001) and anaphylaxis (19.8% vs. 4.6% vs. 4.7%, P <0.001) were more common for cefaclor than for other 2nd and 3rd cephalosporins. Females, individuals under 65 years of age, concomitant use of drugs, and serious ADRs were more strongly associated with HS to cefaclor than with HS to other 2nd and 3rd cephalosporins. In a nationwide database for the Korean population, the incidence of cefaclor-induced ADRs, particularly HS and anaphylaxis, was high. Female sex, age younger than 65 years, and concomitant use of drugs may be associated with HS to cefaclor.

Autophagy-mediated cytoplasmic accumulation of p53 leads to apoptosis through DRAM-BAX in cadmium-exposed human proximal tubular cells.

The tumor suppressor p53 is involved in cadmium (Cd)-induced apoptosis and autophagy. However, the regulatory mechanisms of p53 in Cd-induced kidney injury are not well established. Here, we report the role of autophagy in Cd-induced p53 induction in human proximal tubular cells (HK-2). HK-2 cells treated with Cd induced the expression of p53, DNA damage autophagy modulator (DRAM), and Bcl-2-associated X protein (BAX), as well as caused poly [ADP-ribose] polymerase 1 (PARP-1) cleavage. Cd exposure also induced autophagy with the accumulation of monomeric p62 and multiple high molecular weight form (HMW)-p62. The expression levels of p53, p62, microtubule-associated protein 1A/1B-light chain 3 (LC3)-1, and LC3-II were similar in the sense that they increased up to 12 h and then gradually decreased. DRAM and BAX levels began to increase post autophagy induction and continued to increase, indicating that autophagy preceded apoptosis. While the genetic knockdown of p53 downregulated HWM-p62, DRAM, and BAX, the expression levels of these proteins were upregulated by p53 overexpression. The genetic knockdown of p62 downregulated p53, autophagy, DRAM, and BAX. The inhibition of autophagy through pharmacological and genetic knockdown reduced p53 and inhibited Cd-induced apoptosis. Collectively, Cd induces apoptosis through p53-mediated DRAM-BAX signaling, which can be regulated by autophagy.

A highly intuitive and ergonomic redundant joint master device for four-degrees of freedom flexible endoscopic surgery robot.

BACKGROUND: Studies have been conducted on slave-specific master devices with a similar kinematic structure to the slave to enhance intuitiveness. However, for the four-degrees of freedom (DOFs) slave of a flexible endoscopic surgery robot, only four DOFs in the master device causes low ergonomic performance. METHODS: To enhance ergonomic performance, a second yaw joint was added as a redundant joint after considering the range of wrist motion and the workspace shape. Three experiments were performed to compare the intuitiveness and ergonomic performance of the proposed device with four-DOFs slave-specific and six-DOFs general-purpose master devices. RESULTS: Significant differences were observed in terms of intuitiveness performance between the slave-specific and the general-purposed master device. On the other hand, there was no significant difference in ergonomic performance between the master devices with redundant joint. CONCLUSIONS: Compared with a general-purpose master device, the proposed one exhibited noticeably improved intuitiveness performance and comparable ergonomic performance.

Addition of Partial Envelope Domain II into Envelope Domain III of Dengue Virus Antigen Potentiates the Induction of Virus-Neutralizing Antibodies and Induces Protective Immunity.

Dengue virus (DENV) comprises four serotypes in the family Flaviviridae and is a causative agent of dengue-related diseases, including dengue fever. Dengue fever is generally a self-limited febrile illness. However, secondary infection of patients with a suboptimal antibody (Ab) response provokes life-threatening severe dengue hemorrhagic fever or dengue shock syndrome. To develop a potent candidate subunit vaccine against DENV infection, we developed the EDII-cEDIII antigen, which contains partial envelope domain II (EDII) including the fusion loop and BC loop epitopes together with consensus envelope domain III (cEDIII) of all four serotypes of DENV. We purified Ab from mice after immunization with EDII-cEDIII or cEDIII and compared their virus neutralization and Ab-dependent enhancement of DENV infection. Anti-EDII-cEDIII Ab showed stronger neutralizing activity and lower Ab-dependent peak enhancement of DENV infection compared with anti-cEDIII Ab. Following injection of Ab-treated DENV into AG129 mice, anti-EDII-cEDIII Ab ameliorated DENV infection in tissues with primary and secondary infection more effectively than anti-cEDIII Ab. In addition, anti-EDII-cEDIII Ab protected against DENV1, 2, and 4 challenge. We conclude that EDII-cEDIII induces neutralizing and protective Abs, and thus, shows promise as a candidate subunit vaccine for DENV infection.

Association between primary immunodeficiency and asthma exacerbation in adult asthmatics.

BACKGROUND/AIMS: Primary immunodef iciency (PID) is a serious comorbid condition in adult asthmatics that have frequent exacerbations, which requires monthly replacement of intravenous immunoglobulin (IVIG). However, the prevalence and clinical significance of PID in adult asthmatics in Korea have not yet been reported. The aim of this study is to assess the prevalence of PID and its association with asthma exacerbation in Korean adult asthmatics. METHODS: A total of 2,866 adult asthmatics were enrolled in this study. The PID group was defined as subjects who had lower levels of immunoglobulin G (IgG)/ A/M and/or IgG subclass presenting with recurrent respiratory infections. Serum samples were assayed for total IgG/A/M by immunoturbidimetry, and IgG subclasses by nephelometry. RESULTS: Of the 2,866 asthmatic patients enrolled, 157 (5.49%) had PID (classified as the PID group), while those without PID was classified as the non-PID group. IgG subclass deficiency (58%) is most prevalent, among which IgG3 subclass deficiency was most common (58%). The relative risk of asthma exacerbation was 1.70 times higher in the PID group compared to the non-PID group (1.696; 95% confidence interval, 1.284 to 2.239; p < 0.001); the prevalence of severe asthma was significantly higher in the PID group than in the non-PID group (32.48% vs. 13.00%, p < 0.001). Thirty-five among 157 patients in the PID group d maintained IVIG to prevent asthma exacerbation. CONCLUSION: It is suggested that PID, especially IgG3 subclass deficiency, is a significant risk factor for asthma exacerbation. Screening of IgG subclass levels and IVIG replacement should be considered in the management in adult asthmatics.

Ginsenoside Rc Is a New Selective UGT1A9 Inhibitor in Human Liver Microsomes and Recombinant Human UGT Isoforms.

Ginseng is known to have inhibitory effects on UGT1A9 activity. However, little is known about the inhibitory effects of ginsenosides, the major active compounds in ginseng, on UGT1A9 activity. In vitro investigation of UGT1A9 inhibition by ginsenosides was carried out using human liver microsomes (HLMs). Among 10 ginsenosides, ginsenoside Rc was the strongest inhibitor of UGT1A9-mediated mycophenolic acid glucuronidase activity. Further inhibition kinetic studies using HLMs suggested that ginsenoside Rc competitively and noncompetitively inhibited UGT1A9-mediated propofol and mycophenolic acid glucuronidation activities, with K i values of 2.83 and 3.31 µM, respectively. Next, to investigate whether the inhibitory effect of ginsenoside Rc is specific to the UGT1A9 isoform, we studied the inhibitory potency of ginsenoside Rc on nine human uridine diphospho-glucuronosyltransferase (UGT) activities using recombinant human UGT isoforms. Ginsenoside Rc exhibited a 12.9-fold selectivity (which was similar to niflumic acid at 12.5-fold) for UGT1A9 inhibition. Ginsenoside Rc at 50 µM also inhibited none of the other UGT isoform-specific activities above 12.0%, except for UGT1A9 (>91.5%) in HLMs, indicating that ginsenoside Rc might be used as a selective UGT1A9 inhibitor in reaction phenotyping studies of new chemical entities. Considering lower plasma concentrations (0.01 µM) of ginsenoside Rc in healthy subjects and no induction potential on UGT isoforms, ginsenoside Rc does not cause pharmacokinetic drug interactions with other coadministered drugs metabolized by UGT1A9. SIGNIFICANCE STATEMENT: Ginsenoside Rc selectively inhibited UGT1A9-mediated propofol and mycophenolic acid glucuronidation activities in human liver microsomes and recombinant uridine diphospho-glucuronosyltransferase (UGT) isoforms. It exhibited a 12.9-fold selectivity for UGT1A9 inhibition. Therefore, ginsenoside Rc might be used as a selective UGT1A9 inhibitor in reaction phenotyping studies of new chemical entities, such as niflumic acid.

Development of accurate dose evaluation technique of X-ray inspection for quality assurance of semiconductor with Monte Carlo simulation.

Since higher dose delivered to a semiconductor leads to more functional loss to the device, accurate dose evaluation of the semiconductor is very important to reduce the defect rate during x-ray inspection. The aim of this study is to develop the technique to accurately evaluate the absorbed dose to the semiconductor using the Monte Carlo method. The x-ray radiographic system was modeled based on the Geant4 Monte Carlo tool-kit. The Monte Carlo commissioning was performed by comparing the energy spectrum between the simulation and measurement. The dose evaluation technique for the semiconductor was developed, and the dose delivered to the semiconductor device was evaluated according to various x-ray energies. The energy spectrum of the x-ray beam simulated with Geant4 was validated with the experiment using the CdTe detector for various x-ray beams. The accurate dose to the semiconductor component was assessed according to various x-ray energies. The x-rays of 25 keV energy delivered the highest dose to the silicon die, while the 67.5 keV showed the minimum dose to the die. It was observed that the higher energy over about 70 keV also increased the dose with the scattered photons produced in the solder ball and circuit board. The technique to accurately determine the absorbed dose in the semiconductor was suggested and the x-ray energy deliver the high dose to the semiconductor die was assessed. These results could be fundamentally used to reduce the dose in semiconductor and defect rate in x-ray inspection.

Body mass index and glucocorticoid dose contribute to subclinical atherosclerosis in Korean patients with systemic lupus erythematosus: A prospective 4 year follow-up study.

AIM: Patients with systemic lupus erythematosus (SLE) have an increased risk of cardiovascular disease owing to an immunological abnormality, along with traditional risk factors. We found that carotid artery intima-media thickness (cIMT) and plaque were associated with age, body mass index (BMI) and disease activity in a previous study 4 years ago. Our aim was to identify risk factors associated with progression of subclinical atherosclerosis in SLE. METHODS: We assessed cIMT and plaque using Doppler ultrasonography in 61 Korean women with SLE who were enrolled in the previous study 4 years ago. RESULTS: The mean cIMT of the patients was 0.39 ± 0.09 mm; 11 patients had carotid plaques, which was similar to the results of the previous study. Twenty-one patients had increased cIMT, and new carotid plaque had developed in seven patients. Patients with increased cIMT had a lower BMI and took fewer non-steroidal anti-inflammatory drugs and higher 4 year cumulative glucocorticoid dose than patients without increased cIMT. The 4 year cumulative glucocorticoid dose was higher in patients with carotid plaque than in those without. On multivariate regression analysis, BMI (odds ratio [OR] = 0.67, P = 0.034) was associated with increased cIMT, and the 4 year cumulative glucocorticoid dose was associated with increased cIMT (OR = 6.994, P = 0.025) and carotid plaque (OR = 5.651, P = 0.031). CONCLUSION: This prospective follow-up study on cIMT and plaque in patients with SLE showed that low BMI and 4 year cumulative glucocorticoid dose were associated with the progression of subclinical atherosclerosis.

Effect of Fibroblast Growth Factor-2 and its Receptor Gene Polymorphisms on the Survival of Patients With Hepatitis B Virus-associated Hepatocellular Carcinoma.

BACKGROUND/AIM: Fibroblast growth factor (FGF), vascular endothelial growth factor, and hepatocyte growth factor play a critical role in the pathogenesis of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: We assessed nine single nucleotide polymorphisms (SNPs) in the FGF1, FGF2, FGF receptor (FGFR)-2, Flt-1, and c-MET genes in 245 HCC patients and 483 chronic hepatitis B virus (HBV) carriers without HCC. RESULTS: Kaplan-Meier analysis showed that patients with the FGF2 rs308447 TT genotype had shorter overall survival than patients with the CC or CT genotype (p=0.016) and that FGF2 rs308379 A allele carriers had shorter overall survival than patients with the TT genotype (p=0.020). CONCLUSION: Multivariate Cox proportional analysis revealed that the FGF2 rs308379 A allele (hazard ratio(HR)=1.663, p=0.004) and advanced tumor stage (HR=3.430, p<0.001) were independent prognostic factors for overall survival in patients with HCC.