Genetic assessment of pathogenic germline alterations in lysosomal genes among Asian patients with pancreatic ductal adenocarcinoma.

BACKGROUND: Lysosomes are closely linked to autophagic activity, which plays a vital role in pancreatic ductal adenocarcinoma (PDAC) biology. The survival of PDAC patients is still poor, and the identification of novel genetic factors for prognosis and treatment is highly required to prevent PDAC-related deaths. This study investigated the germline variants related to lysosomal dysfunction in patients with PDAC and to analyze whether they contribute to the development of PDAC. METHODS: The germline putative pathogenic variants (PPV) in genes involved in lysosomal storage disease (LSD) was compared between patients with PDAC (n = 418) and healthy controls (n = 845) using targeted panel and whole-exome sequencing. Furthermore, pancreatic organoids from wild-type and KrasG12D mice were used to evaluate the effect of lysosomal dysfunction on PDAC development. RNA sequencing (RNA-seq) analysis was performed with established PDAC patient-derived organoids (PDOs) according to the PPV status. RESULTS: The PPV in LSD-related genes was higher in patients with PDAC than in healthy controls (8.13 vs. 4.26%, Log2 OR = 1.65, P = 3.08 × 10-3). The PPV carriers of LSD-related genes with PDAC were significantly younger than the non-carriers (mean age 61.5 vs. 65.3 years, P = 0.031). We further studied a variant of the lysosomal enzyme, galactosylceramidase (GALC), which was the most frequently detected LSD variant in our cohort. Autophagolysosomal activity was hampered when GALC was downregulated, which was accompanied by paradoxically elevated autophagic flux. Furthermore, the number of proliferating Ki-67+ cells increased significantly in pancreatic organoids derived from Galc knockout KrasG12D mice. Moreover, GALC PPV carriers tended to show drug resistance in both PDAC cell line and PDAC PDO, and RNA-seq analysis revealed that various metabolism and gene repair pathways were upregulated in PDAC PDOs harboring a GALC variant. CONCLUSIONS: Genetically defined lysosomal dysfunction is frequently observed in patients with young-onset PDAC. This might contribute to PDAC development by altering metabolism and impairing autophagolysosomal activity, which could be potentially implicated in therapeutic applications for PDAC.

Work-related burn injuries and claims for post-traumatic stress disorder in Korea.

OBJECTIVE: The objective of this study is to broaden our understanding of psychiatric disorders due to work-related burn injury compensated by the Industrial Accident Compensation Insurance operated by the Korea Workers' Compensation and Welfare Service (KCOMWEL). METHODS: Using the KCOMWEL electronic database, we collected data on psychiatric disorders due to work-related burn injury based on workers' compensation records from 2005 to 2014 and analyzed the characteristics of the claims. RESULTS: The average number of claims per year for post-traumatic stress disorder was 67 and the approval rate from 2005 to 2014 was 53.6%. Regarding occupation, 63 workers were elementary workers involved in the performance of simple and routine tasks which may require the use of hand-held tools and considerable physical effort and 59 were electrical and electronic equipment fitters and repairers. Acute stress disorder, nonorganic insomnia, and sexual dysfunction were the most commonly approved psychiatric disorders associated with work-related burn injury, followed by mixed anxiety-depressive disorder. CONCLUSIONS: We analyzed the characteristics of the psychiatric disorders due to work-related burn injury for which compensation was received from 2005 to 2014 according to the approved results. To gain a long-term understanding of the management of workers' compensation status for psychiatric disorders due to work-related burn injuries, we should gather accurate information on the risk factors involved in order to achieve the needed systematic improvements.

Epidemiology of Trichomoniasis in South Korea and Increasing Trend in Incidence, Health Insurance Review and Assessment 2009-2014.

Trichomoniasis, which is caused by Trichomonas vaginalis, is one of the most common non-viral sexually transmitted infections; however, limited population-based data are available that describe patterns and trends of the disease. We summarized insurance claims of trichomoniasis cases reported during 2009-2014 to South Korea Health Insurance Review and Assessment Service. The average annual incidence in South Korea was 276.8 persons per 100,000 population, and a substantial sex-associated variation was observed. The incidence rate among female subjects trended upward over 6 years, that is, it increased from 501 in 2009 to 625.8 in 2014 per 100,000 female population, which indicates a 25% overall increase. This trend was sharpest in the ≥60 years group of female population. However, a 66% decrease in incidence rates was observed among male subjects (23.7 in 2009 to 15.7 in 2014 per 100,000 male population). Further, substantial decrease was observed in the ≥40 years groups of male population. The incidence of trichomoniasis varied across regions and was the highest in Jeju province of South Korea. Overall, as the incidence of trichomoniasis appears to have increased in South Korea during 2009-2014, the disease burden is increasing; hence, there is a need to better understand the disease transmission.