Non-melanoma skin cancer as a clinical marker for internal malignancies: a nationwide population-based cohort study.

INTRODUCTION: Non-melanoma skin cancers (NMSCs) are the most common cancers in the world, but the risk of internal malignancy in patients with NMSC has not been well investigated. OBJECTIVES: We aimed to assess the risk of internal malignancy in patients with NMSC compared with controls without NMSC in Korean population. METHODS: This nationwide cohort study, compared 27 259 NMSC patients with 54 518 matched controls without NMSC, 40 years or older using the data from Korea Health Insurance Review and Assessment Service from 2007 to 2016. The first 2 years were washout period, and we followed the patients for 8 years to observe the development of any internal malignancies after a diagnosis of NMSC. The Cox proportional hazard model was used to determine the hazard ratios (HRs) for developing internal malignancies. RESULTS: The overall risk of internal malignancies at all sites was 2727.7 and 1392.4 per 100 000 person-years for the patients with NMSC and controls, respectively. The risk was significantly higher in the patients with NMSC (HR 1.866, 95% confidence interval [CI] 1.768-1.970). Bone cancer showed the highest risk (HR 12.745, 95% CI 6.288-25.834), followed by nasal cavity and larynx (HR 10.279, 95% CI 6.178-7.103), oral cavity and pharynx (HR 10.211, 95% CI 7.375-14.137), anus and anal canal (HR 8.147, 95% CI 3.893-17.051) and cervical (HR 5.900, 95% CI 3.694-9.423) cancers with risks greater than fivefold higher in NMSC patients compared with the controls. The risks of cancers of the thorax, oesophagus, breast, lung, stomach, thyroid gland and non-Hodgkin's lymphoma were also statistically higher in the patients with NMSC. In contrast, the risks of cancers of the colon and rectum were found to be significantly decreased in the patients with NMSC (HR 0.765, 95% CI 0.657-0.890). CONCLUSION: Patients with NMSC require careful screening and follow-up for internal malignancy.

Cultural Stigma Manifested in Official Suicide Death in South Korea.

This article examines the cultural sources of underreported suicide deaths in South Korea. It analyzes two sets of suicide data compiled by two different government agencies. Noting the considerable undercounting of suicide deaths compiled by the National Statistical Office, it explores how the underreporting is linked to the Confucian norm of familism. Despite an effort to improve the quality of official suicide data, a reform in the death system is needed in order to gather accurate data for a better understanding of the increased suicides as well as for the development of more effective suicide prevention and intervention strategies.

Effects of dietary supplementation of bacteriophages against enterotoxigenic Escherichia coli (ETEC) K88 on clinical symptoms of post-weaning pigs challenged with the ETEC pathogen.

The present study was performed to investigate the effects of dietary supplementation of bacteriophages (phages) against enterotoxigenic Escherichia coli (ETEC) K88 as a therapy against the ETEC infection in post-weaning pigs. Two groups of post-weaning pigs aged 35 days, eight animals per group, were challenged with 3.0 × 1010 colony forming units of ETEC K88, a third group given the vehicle. The unchallenged group and one challenged group were fed a basal nursery diet for 14 days while the remaining challenged group was fed the basal diet supplemented with 1.0 × 107 plaque forming units of the phage per kg. Average daily gain (ADG), goblet cell density and villous height:crypt depth (VH:CD) ratio in the intestine were less in the challenged group than in the unchallenged group within the animals fed the basal diet (p < 0.05); the reverse was true for rectal temperature, faecal consistency score (FCS), E. coli adhesion score (EAS) in the intestine, serum interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α) concentrations and digesta pH in the stomach, caecum and colon. The ETEC infection symptom within the challenged animals was alleviated by the dietary phage supplementation (p < 0.05) in ADG, FCS, EAS in the jejunum, serum TNF-α concentration, digesta pH in the colon, goblet cell density in the ileum and colon and VH:CD ratio in the ileum. Moreover, the infection symptom tended to be alleviated (p < 0.10) by the phage supplementation in rectal temperature, EAS in the ileum and caecum, and VH:CD ratio in the duodenum and jejunum. However, EAS in the colon, digesta pH in the stomach and caecum, and goblet cell density in the jejunum did not change due to the dietary phage. Overall, results indicate that the phage therapy is effective for alleviation of acute ETEC K88 infection in post-weaning pigs.

Exogenous administration of DLK1 ameliorates hepatic steatosis and regulates gluconeogenesis via activation of AMPK.

BACKGROUND/OBJECTIVES: Activation of Notch signaling pathologically enhances lipogenesis and gluconeogenesis in the liver causing non-alcoholic fatty liver disease (NAFLD) and diabetes. Delta-like 1 homolog (DLK1), an imprinted gene that can modulate adipogenesis and muscle development in mice, was found as an inhibitory regulator of Notch signaling. Therefore, we investigated the metabolic effect of exogenous DLK1 in vitro and in vivo. SUBJECTS/METHODS: A soluble DLK1 peptide was generated with fusion between a human Fc fragment and extracellular domain of DLK1. Male db/db mice were randomly assigned to two groups: vehicle treated and DLK1-treated group (25 mg kg(-1), intraperitoneal injection, twice a week for 4 weeks). Primary mice hepatocytes and HepG2 cells were used for in vitro experiments. RESULTS: After 4 weeks of DLK1 administration, hepatic triglyceride content and lipid droplets in liver tissues, as well as serum levels of liver enzymes, were markedly decreased in db/db mice. DLK1 treatment induced phosphorylation of AMPK and ACC and suppressed nuclear expression of SREBP-1c in the mouse liver or hepatocytes, indicating regulation of fatty acid oxidation and synthesis pathways. Furthermore, DLK1-treated mice showed significantly lower levels of fasting and random glucose, with improved glucose and insulin tolerance compared with the vehicle-treated group. Macrophage infiltration and proinflammatory cytokine levels in the epididymal fat were decreased in DLK1-treated db/db mice. Moreover, DLK1 suppressed glucose production from hepatocytes, which was blocked after co-administration of an AMPK inhibitor, compound C. DLK1-treated hepatocytes and mouse liver tissues showed lower PEPCK and G6Pase expression. DLK1 triggered AKT phosphorylation followed by cytosolic translocation of FOXO1 from the nucleus in hepatocytes. CONCLUSIONS: The present study demonstrated that exogenous administration of DLK1 reduced hepatic steatosis and hyperglycemia via AMPK activation in the liver. This result suggests that DLK1 may be a novel therapeutic approach for treating NAFLD and diabetes.

Characteristics of nonbalding scalp zones of androgenetic alopecia in East Asians.

BACKGROUND: Hair is known to persist on the occipital and part of the temporal scalp in patients with androgenetic alopecia (AGA), but no quantified data about the follicular changes in such areas exist. AIM: To evaluate the hair characteristics in nonbalding scalp areas in East Asian patients with AGA. METHODS: In total, 265 participants [211 patients with AGA and 50 healthy controls (HCs)] were enrolled. The patients were divided by the Basic and Specific (BASP) classification [four basic types (L, M, C, and U) and two special types (V and F)], and the hair in the occipital region and two sites of the temporal region were analysed by computer-assisted phototrichography. Hair density, hair width, number of each follicular unit, ratio of single to compound hairs and ratio of terminal to vellus hairs were examined. RESULTS: In the temporal region, a statistically significant (P < 0.05) decrease in hair density was observed in patients with C, U or F subtypes, and a significant (P < 0.05) decrease in hair thickness was observed in patients with the U subtype compared with HCs. In the mastoid and occipital areas, both hair density and hair thickness was significantly (P < 0.05) decreased in patients with the U subtype compared with HCs. Within each classification, hairs became generally thinner as the hair loss progressed. CONCLUSIONS: Hair density and hair thickness of known nonbalding scalp regions showed some differences depending on the severity and the BASP subtypes in East Asian people with male pattern baldness.

Use of permanent marker to deposit a protection layer against FIB damage in TEM specimen preparation.

Permanent marker deposition (PMD), which creates permanent writing on an object with a permanent marker, was investigated as a method to deposit a protection layer against focused ion beam damage. PMD is a simple, fast and cheap process. Further, PMD is excellent in filling in narrow and deep trenches, enabling damage-free observation of high aspect ratio structures with atomic resolution in transmission electron microscopy (TEM). The microstructure, composition, gap filling ability and planarization of the PMD layer were studied using dual beam focused ion beam, transmission electron microscopy, energy dispersive X-ray spectroscopy and electron energy loss spectroscopy. It was found that a PMD layer is basically an amorphous carbon structure, and that such a layer should be at least 65 nm thick to protect a surface against 30 keV focused ion beam damage. We suggest that such a PMD layer can be an excellent protection layer to maintain a pristine sample structure against focused ion beam damage during transmission electron microscopy specimen preparation.

Rural and urban suicide in South Korea.

Suicide rates in 2005 in South Korea were higher in rural areas than in urban areas. Those in rural areas more often used pesticides and chemicals as a method for suicide, and there was a greater proportion of men and the elderly, both groups at higher risk for suicide in South Korea. These three factors may account for the high rural suicide rate in South Korea.

Suicide among foreign residents of Japan.

The suicide rate of Koreans living in Japan is twice as high as that of Koreans in South Korea. Reasons for this high suicide rate are discussed, including effects of economic crises and discrimination.

Clinical Features and Management of Stenotrophomonas Maltophilia Keratitis.

INTRODUCTION: Stenotrophomonas maltophilia keratitis is an uncommon infectious disease of the cornea. The clinical features, antibiotic susceptibility, and clinical outcomes of S. maltophilia keratitis were investigated in this study. METHODS: Between January 2015 and February 2020, the medical records of 16 patients with culture-proven S. maltophilia-associated infectious keratitis were retrospectively reviewed. Clinical data were analyzed regarding risk factors, clinical presentation, antibiotic susceptibility, and clinical outcomes. RESULTS: The average age of the patients was 56.24 ± 24.84 years. The most common risk factors for S. maltophilia keratitis were trauma (6/16, 37.5%), use of contact lenses (6/16, 37.5%), and herpes simplex virus keratitis (3/16, 18.8%), which caused ocular instability. Regarding the antibiotic sensitivities, most isolates (15/16, 93.8%) were susceptible to fluoroquinolones, 87.5% (14/16) of them to aminoglycosides, and 81.3% (13/16) of them to beta-lactams. Patients were classified into two groups according to the initial antibiotic eye drops, and there were significant differences in the final visual acuity between two groups: mixed fluoroquinolone, beta-lactam, aminoglycoside group, and mixed beta-lactam and aminoglycoside groups (p = 0.039). CONCLUSION: Ocular infection due to S. maltophilia is an opportunistic infection followed by instability of the ocular surface. In cases of S. maltophilia infection, mixed use of fluoroquinolone, beta-lactam, and aminoglycoside should be considered for treatment of choice.

Protest suicide among Korean students and laborers: a study of suicide notes.

Suicide notes from two groups of protest suicides in South Korea during the period 1975-2003 were compared: suicide notes from students (n =16) and suicide notes from workers (n = 15). The students appeared to be acting upon abstract ideals, including the oppression of the masses by the government and the American forces in Korea, and they typically urged the reunification of Korea. The workers were acting upon more local concerns, such as the oppression of their union by the government and the companies and the policies of their specific companies.

The effect of beta-cyclodextrin complexation on the bioavailability and hepatotoxicity of clotrimazole.

Clotrimazole, a poorly water-soluble antimycotic agent, is a promising therapeutic agent for various diseases including cancer and sickle cell anemia. The oral bioavailability and hepatic toxicity of clotrimazole were compared with its beta-cyclodextrin inclusion form which was prepared by the spray-drying method. The inclusion complex gave significantly higher initial plasma concentrations, Cmax and AUC than did clotrimazole alone, indicating that the drug from the inclusion compound could be more easily absorbed in rats. Furthermore, mice treated with the inclusion compound showed significantly higher GOT/GPT values compared to clotrimazole alone. The inclusion compound also induced hypertrophy of hepatic cells by fat accumulation and disappearance of hepatic sinusoids, indications of pathological changes of liver, suggesting that the inclusion compound could induce more severe tissue damage in the liver than clotrimazole alone. Thus, hepatotoxicity of clotrimazole seems to be correlated with the enhanced oral bioavailability by inclusion complexation. Our results suggest that, in the development of a novel oral product, appearance or enhancement of hepatic toxicity must be considered along with oral bioavailability.

Correlates of a Taoist orientation among Korean students.

Associations of .35 and -.34, respectively, were found for a measure of having a Taoist orientation to life with death anxiety and the perception that one's self is unified (versus fragmented) in samples of 41 Korean high school and 145 Korean university students.

Social integration and suicide in South Korea.

The increasing suicide rate in South Korea in recent decades was found to be associated with measures of social integration/regulation (birth and divorce rates).

Anti-invasive activity of ursolic acid correlates with the reduced expression of matrix metalloproteinase-9 (MMP-9) in HT1080 human fibrosarcoma cells.

We examined the anti-invasive activity of ursolic acid (UA) on the highly metastatic HT1080 human fibrosarcoma cell line. UA reduced tumor cell invasion through a reconstituted basement membrane in a transwell chamber. A significant down-regulation of matrix metalloproteinase-9 [MMP-9; Mr 92,000 gelatinase/type IV collagenase (gelatinase B)] by UA was detected by Northern blot analysis. However, MMP-2 [Mr 72,000 gelatinase/type IV collagenase (gelatinase A)] and membrane-type MMP were constantly expressed, and the expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 also was not changed after 3 and 6 days of treatment with UA. Quantitative gelatin-based zymography confirmed a markedly reduced expression of MMP-9 but not MMP-2 after treatment with UA. To confirm the UA-induced down-regulation of MMP-9 expression, we constructed a secreted alkaline phosphatase (SEAP) reporter vector including MMP-9 promoter. After transfection of MMP-9/SEAP reporter vector into HT1080 cells, reduced SEAP activity was detected after treatment with UA. These results suggest that down-regulation of MMP-9 contributes to the anti-invasive activity of UA in HT1080 cells.

Insulin-like growth factor II induced by hypoxia may contribute to angiogenesis of human hepatocellular carcinoma.

Insulin-like growth factor II (IGF-II) is highly expressed during hepatocarcinogenesis (P. Schirmacher et al., Cancer Res., 52: 2549-2556, 1992; B. C. Park et al., J. Hepatol., 22: 286-294, 1995). However, the mechanism of its enhanced expression is largely unknown. In this study, we show that IGF-II mRNA levels are increased within six h of exposing human hepatoma cell cultures to hypoxia, suggesting that hypoxia may be a strong stimulus for the induction of IGF-II expression in the process of hepatocarcinogenesis. This finding and the fact that hepatocellular carcinoma (HCC) is a typical hypervascular tumor (M. Mise et al., Hepatology, 23: 455-464, 1996) imply that IGF-II may play an important role in the development of neovascularization of HCC. Here we demonstrate that IGF-II substantially increases vascular endothelial growth factor (VEGF) mRNA and protein levels in a time-dependent manner in human hepatoma cells. The induction of VEGF by IGF-II was additively increased by hypoxia. Moreover, the direct angiogenic activity of IGF-II was observed in the quantitative chick chorioallantoic membrane assay (M. Nguyen et al., Microvasc. Res., 47: 31-40, 1994). These data suggest that IGF-II may be a hypoxia-inducible angiogenic factor in HCC.

Egr-1 mediates transcriptional activation of IGF-II gene in response to hypoxia.

We have previously reported that the exposure of human HepG2 cells to hypoxic conditions results in the overexpression of human insulin-like growth factor II (IGF-II) mRNA whose size is 6.0 kb. This particular size of IGF-II mRNA is transcribed under the control of the IGF-II P3 promoter. In the present study, to delineate the molecular mechanism for the activation of the IGF-II gene, we examined the induction of P3 promoter activity in HepG2 cells by hypoxia in the transient expression system. In this system, hypoxia induced a linear increase within 24 h in the expression of luciferase that was driven by the IGF-II P3 promoter. To further delineate which factors mediate this response, the expression pattern of regulators of the P3 promoter, Egr-1, Sp1, and WT1, were analyzed by reverse transcription-PCR and Northern blot analysis. We found that hypoxia increased the expression of Egr-1 but not of Sp1. In contrast, the level of WT1, a repressor of IGF-II expression, was markedly decreased during hypoxia. The mRNA stability assay revealed that the induction of transcription is the mechanism of underlying Egr-1 mRNA elevation. We then investigated the effects of hypoxia on the DNA binding activity of Egr-1. Both electrophoretic mobility shift assay and supershift assay demonstrated that the DNA binding activity of the Egr-1 protein was increased by hypoxia. In addition, the level of Egr-1 protein was also increased under the hypoxia as determined by Western blot analysis. Cotransfection of HepG2 cells with an Egr-1 expression vector and an IGF-II P3 promoter-luciferase reporter plasmid showed that the transcription of IGF-II was activated by Egr-1 in a dose-dependent manner. Moreover, the elevation of IGF-II P3 promoter activity was induced synergistically by the cotreatment of hypoxia with Egr-1 overexpression. Deletion of sequences in the IGF-II P3 promoter containing Egr-1 binding sites did not respond to hypoxic stress. Taken together, these data strongly indicate that hypoxia-induced IGF-II expression in HepG2 cells is due to the enhanced activity of Egr-1 on the IGF-II P3 promoter and that the Egr-1 binding site in the IGF-II P3 promoter is essential for the transcriptional regulation of IGF-II under hypoxic conditions.

Crystal structures of thermostable xylose isomerases from Thermus caldophilus and Thermus thermophilus: possible structural determinants of thermostability.

The crystal structures of highly thermostable xylose isomerases from Thermus thermophilus (TthXI) and Thermus caldophilus (TcaXI), both with the optimum reaction temperature of 90 degrees C, have been determined by X-ray crystallography. The model of TcaXI has been refined to an R-factor of 17.8 % for data extending to 2.3 A and that of TthXI to 17.1 % for data extending to 2.2 A. The tetrameric arrangement of subunits characterized by the 222-symmetry and the tertiary fold of each subunit in both TcaXI and TthXI are basically the same as in other xylose isomerases. Each monomer is composed of two domains. Domain I (residues 1 to 321) folds into the (beta/alpha)8-barrel. Domain II (residues 322 to 387), lacking beta-strands, makes extensive contacts with domain I of an adjacent subunit. Each monomer of TcaXI contains ten beta-strands, 15 alpha-helices, and six 310-helices, while that of TthXI contains ten beta-strands, 16 alpha-helices, and five 310-helices. Although the electron density does not indicate the presence of bound metal ions in the present models of both TcaXI and TthXI, the active site residues show the conserved structural features. In order to understand the structural basis for thermostability of these enzymes, their structures have been compared with less thermostable XIs from Arthrobacter B3728 and Actinoplanes missouriensis (AXI and AmiXI), with the optimum reaction temperatures of 80 degrees C and 75 degrees C, respectively. Analyses of various factors that may affect protein thermostability indicate that the possible structural determinants of the enhanced thermostability of TcaXI/TthXI over AXI/AmiXI are (i) an increase in ion pairs and ion-pair networks, (ii) a decrease in the large inter-subunit cavities, (iii) a removal of potential deamidation/isoaspartate formation sites, and (iv) a shortened loop.

The use of cementless expansion acetabular component and an alumina-polyethylene bearing in total hip arthroplasty for osteonecrosis.

We performed 114 consecutive primary total hip arthroplasties with a cementless expansion acetabular component in 101 patients for advanced osteonecrosis of the femoral head. The mean age of the patients at surgery was 51 years (36 to 62) and the mean length of follow-up was 110 months (84 to 129). The mean pre-operative Harris hip score of 47 points improved to 93 points at final follow-up. The polyethylene liner was exchanged in two hips during this period and one broken acetabular component was revised. The mean linear wear rate of polyethylene was 0.07 mm/year and peri-acetabular osteolysis was seen in two hips (1.9%). Kaplan-Meier analysis indicated that the survival of the acetabular component without revision was 97.8% (95% confidence interval 0.956 to 1.000) at ten years. Our study has shown that the results of THA with a cementless expansion acetabular component and an alumina-polyethylene bearing surface are good.