Risk of Developing Hypertension in Atopic Dermatitis Patients Receiving Long-term and Low-dose Cyclosporine: A Nationwide Population-based Cohort Study.

BACKGROUND: Cyclosporine (CS) is a first-line immunosuppressive agent used to manage moderate to severe atopic dermatitis (AD). To date, the risk of developing hypertension associated with the long-term use of low-dose CS in AD patients is understudied. OBJECTIVE: To determine the cumulative dose-dependent effect of CS on the risk of developing hypertension in patients with AD. METHODS: A nationwide population-based retrospective cohort with 1,844,009 AD patients was built from the Korean National Health Insurance System database from 2005 to 2009. A Cox proportional-hazard regression analysis was performed according to patients' CS treatment history adjusted for potential confounders. RESULTS: Current use of CS was associated with an increased risk of developing hypertension (adjusted hazard ratio, 4.442; 95% confidence interval, 3.761-5.247). Among the current CS users, a higher cumulative dose of CS (≥39,725 mg) or longer cumulative use of CS (≥182 days), was significantly associated with an increased risk of developing hypertension. CONCLUSION: The incidence of CS-associated hypertension is very low when using low-dose treatment regimens for AD. However, the current use or a high cumulative dose of CS for treating patients with AD increases the risk of developing hypertension. Precaution is needed when prescribing CS for long-term treatment of AD.

Psychological Burden and Willingness to Pay Among Korean Rosacea Patients and Their Association With Rosacea Phenotype and Severity: A Multi-Center Cross-Sectional Study.

BACKGROUND: Rosacea is a chronic inflammatory disorder that can adversely affect the patient's quality of life (QOL). However, few studies have examined the association between the psychological burden and willingness to pay (WTP) with rosacea features and severity. OBJECTIVES: The study aimed to determine the overall psychological burden and WTP among Korean rosacea patients and identify factors that may contribute, such as patient demographics, clinical features, and rosacea severity. METHODS: This prospective cross-sectional study recruited Koreans with rosacea. All were asked to complete a questionnaire on their demographics, rosacea-related symptoms, self-rated severity, dermatology life quality index (DLQI), and WTP. The clinical features were assessed by a board-certified dermatologist. The investigator's global assessment and global flushing severity score (GFSS) were used to determine the clinical severity of rosacea. Multiple regression analysis was conducted to identify factors contributing to the psychological burden and WTP. RESULTS: Out of 201 rosacea patients, 147 (73.1%) were female, and 54 (26.9%) males, with a median age of 50.1 years. Their median DLQI score was 8 (interquartile range [IQR]): 4.0-13.0). The median WTP per month for the control of rosacea was $100, with relative WTP (WTP/household income per month x 100) being 3.3%. According to the multiple regression model, phymatous change (ß = .153, p = .030), DLQI score (ß = .152, P = .045), and GFSS (ß = .154, P = .041) contributed most to the WTP. CONCLUSION: Rosacea patients experience substantial psychological and economic burdens. More vigorous treatment should be performed for those with phyma and severe flushing whose QOL is most severely affected.

Steam Trap Maintenance-Prioritizing Model Based on Big Data.

Steam traps in large facilities need continuous maintenance to prevent corrosion and other damage that could pose a considerable threat to a facility and its workers. However, a significant amount of human resources is required for the maintenance of steam traps. An automatic method to inform stakeholders regarding maintenance cycles will be beneficial for the maintenance process. Therefore, an optimal maintenance priority decision model is developed in this study to establish an efficient steam trap management system. First, the frequency of failures, installation locations, and specifications of steam traps were determined as parameters causing a failure. A relative score and conversion score are calculated for each parameter. The final conversion score is the sum of the conversion score multiplied by the corresponding steam trap data weight factor. Steam traps within the range requiring inspection are classified as high priority cases. Experimental results confirmed that the failure accuracy rate is approximately 95%, and the average failure error rate is within 3%. Additionally, the number of steam traps to be checked was reduced by 3616. The proposed model significantly reduces maintenance in commercial industries.

The Drosophila histone methyltransferase NSD is positively regulated by the DRE/DREF system.

The Drosophila nuclear receptor-binding SET domain protein (NSD) gene encodes the Drosophila ortholog of mammalian NSD family members that are important in many aspects of development and disease in humans. In this study, we observed that overexpression of Drosophila NSD in imaginal discs induces organ atrophy. Thus, to gain an understanding of the transcriptional regulation of the gene, we analyzed the NSD promoter region. First, we identified the presence of three putative DNA replication-related element (DRE) sequences in its promoter region, where DRE-binding factor (DREF) could bind for transcriptional activation. In the experiments with the fly GAL4-UAS system, we demonstrated that overexpressed DREF increased the endogenous NSD transcription. To confirm the role of DREF as a transcriptional activator on the NSD expression, we generated a series of luciferase reporter gene constructs containing deleted portions of the 5'-flanking regions as well as point mutations in the putative DRE sites. When transiently transfected into S2 cells, the deletion construct containing no DRE sites showed dramatic decrease in the NSD promoter activity, but only two sites near the transcriptional start site were important. Furthermore, we verified the direct interaction of DREF with the two positively cis-acting sequences on the NSD promoter by chromatin immunoprecipitation assay. Taken together, these results demonstrated that NSD is one of the downstream targets of the DRE/DREF pathway that is associated with various cellular processes in Drosophila, indicating that our findings may contribute to the understanding of molecular mechanisms in complex disorders associated with NSD family members in humans.

Overexpression of histone methyltransferase NSD in Drosophila induces apoptotic cell death via the Jun-N-terminal kinase pathway.

The nuclear receptor-binding SET domain protein gene (NSD) family encodes a group of highly conserved SET domain-containing histone lysine methyltransferases that are important in multiple aspects of development in various organisms. The association of NSD1 duplications has been reported with growth retardation diseases in humans. In this study, to gain insight into the molecular mechanisms by which the overexpression of NSD1 influences the disease progression, we analyzed the gain-of-function mutant phenotypes of the Drosophila NSD using the GAL4/UAS system. Ubiquitous overexpression of NSD in the fly caused developmental delay and reduced body size at the larval stage, resulting in pupal lethality. Moreover, targeted overexpression in various developing tissues led to significant phenotype alterations, and the gain-of-function phenotypes were rescued by NSD RNAi knockdown. We also demonstrated that NSD overexpression not only enhanced the transcription of pro-apoptotic genes but also activated caspase. The atrophied phenotype of NSD-overexpressing wing was strongly suppressed by a loss-of-function mutation in hemipterous, which encodes a Drosophila Jun N-terminal kinase. Taken together, our findings suggest that NSD induces apoptosis via the activation of JNK, and thus contributes to the understanding of the molecular mechanisms involved in NSD1-related diseases in humans.

In vitro antiviral activity of red alga, Polysiphonia morrowii extract and its bromophenols against fish pathogenic infectious hematopoietic necrosis virus and infectious pancreatic necrosis virus.

Our previous investigation revealed that 80% methanolic extract of the red alga Polysiphonia morrowii has significant antiviral activities against fish pathogenic viruses, infectious hematopoietic necrosis virus (IHNV) and infectious pancreatic necrosis virus (IPNV). The present study was conducted to identify compounds attributed for its antiviral activities and investigate their antiviral activities against IHNV and IPNV. Activity-guided fractionation for 80% methanolic extract of Polysiphonia morrowii using a cell-based assay measuring virus-induced cytopathic effect (CPE) on cells yielded a 90% methanolic fraction, which showed the highest antiviral activity against both viruses among fractions yielded from the extract. From the fraction, two bromophenols were isolated and identified as 3-bromo-4,5-dihydroxybenzyl methyl ether (1) and 3-bromo-4,5-dihydroxybenzaldehyde (2) based on spectroscopic analyses. For both compounds, the concentrations to inhibit 50% of flounder spleen cell (FSP cell) proliferation (CC(50)) and each viral replication (EC(50)) were measured. In the pretreatment test, 3-bromo-4,5-dihydroxybenzyl methyl ether (1) and 3-bromo-4,5-dihy-droxybenzaldehyde (2) exhibited significant antiviral activities showing selective index values (SI = CC(50)/EC(50)) of 20 to 42 against both IHNV and IPNV. In direct virucidal test, 3-bromo-4,5-dihydroxybenzyl methyl ether (1) showed significant antiviral activités against both viruses while 3-bromo-4,5-dihydroxybenzaldehyde (2) was significantly effective against only IHNV. Although antiviral efficacies of both compounds against IHNV and IPNV were lower than those of ribavirin used as a positive control, our findings suggested that the red alga Polysiphonia morrowii and isolated two bromophenols may have potential as a therapeutic agent against fish viral diseases.