Risk of malignancy in patients with psoriasis: a 15-year nationwide population-based prospective cohort study in Korea.

BACKGROUND: The association between psoriasis and risk of malignancy has not been thoroughly evaluated in a large longitudinal cohort of Asian population. OBJECTIVE: To determine the long-term risk of malignancy in Korean adult patients with psoriasis. METHODS: We conducted a nationwide population-based prospective cohort study with a 15-year observational period. During the baseline period (1997-2000), total 1 773 786 Korean subjects who received health insurance from the National Health Insurance System were enrolled and 5788 subjects were defined as a psoriasis group. The number of new-onset malignancy was collected during the observational period (2001-2015). RESULTS: Patients with psoriasis had a higher adjusted hazard ratio (aHR) for development of overall malignancy [aHR 1.08, 95% confidence interval (CI) 1.00-1.18] and gastric cancer (aHR 1.31, 95% CI 1.08-1.58) compared to controls. The risks of non-Hodgkin lymphoma and non-melanoma skin cancer were significantly increased only in patients with psoriasis who received systemic treatments (aHR 2.86, 95% CI 1.07-7.61 and aHR 3.93, 95% CI 1.47-10.47, respectively). CONCLUSION: Psoriasis is associated with long-term risk for overall malignancy in Koreans, which was primarily driven by the increased risk of gastric cancer.

Diabetes mellitus and tuberculosis in Korean adults: impact on tuberculosis incidence, recurrence and mortality.

The prevalence of diabetes mellitus (DM) worldwide is increasing markedly, and many countries with rising rates also have a high incidence rate of tuberculosis (TB). To investigate the relationships of fasting serum glucose (FSG) and DM with TB incidence, recurrence and mortality risk in a prospective cohort study in South Korea. Our study comprised 1 267 564 Koreans who received health insurance from the National Health Insurance System, had an initial medical evaluation between 1997 and 2000 and were prospectively followed biennially. Participants with DM had a higher risk for incident TB (hazard ratio [HR] 1.81, 95%CI 1.71-1.91 in males, HR 1.33; 95%CI 1.20-1.47 in females) than those without DM. There was a strong positive trend for TB risk with rising FSG among males. The risk for recurrent TB among those with previous TB was significantly higher in males (HR 1.58, 95%CI 1.43-1.75) and in females with DM (HR 1.38, 95%CI 1.08-1.76). The increased risk of death from TB during follow-up was also significant in men (HR 1.91, 95%CI 1.87-1.95) and in women (HR 1.71, 95%CI 1.65-1.77). A diagnosis of DM is a risk factor for TB, TB recurrence and death from TB. Screening for TB should be considered among people living with DM in Korea, particularly those with severe DM. .

Topology of feather melanocyte progenitor niche allows complex pigment patterns to emerge.

Color patterns of bird plumage affect animal behavior and speciation. Diverse patterns are present in different species and within the individual. Here, we study the cellular and molecular basis of feather pigment pattern formation. Melanocyte progenitors are distributed as a horizontal ring in the proximal follicle, sending melanocytes vertically up into the epithelial cylinder, which gradually emerges as feathers grow. Different pigment patterns form by modulating the presence, arrangement, or differentiation of melanocytes. A layer of peripheral pulp further regulates pigmentation via patterned agouti expression. Lifetime feather cyclic regeneration resets pigment patterns for physiological needs. Thus, the evolution of stem cell niche topology allows complex pigment patterning through combinatorial co-option of simple regulatory mechanisms.

The association between pulse wave velocity and metabolic syndrome in Korean.

The objective of this study was to compare aortic (the common carotid to femoral artery) PWV, arm (the brachial to radial artery) PWV, and leg (the femoral to dorsalis pedis artery) PWV in people with or without component of the metabolic syndrome. We analyzed 3345 Korean subjects (1907 men, age 44.6 ± 8.5, 1438 women, age 43.3 ± 8.9). Unpaired t-test was used to compare mean values of various metabolic parameters between subjects with and without Metabolic Syndrome (MetS), and one-way analysis of variance was used to compare these variables among groups satisfying different numbers of the components of MetS. In addition, we compared of Pearson correlation coefficient between age and PWV (arotic PWV, arm PWV and leg PWV) levels of according to whether the subject had components of the metabolic syndrome or not. The present study shows that leg PWV level was found to be significantly associated with the features of the metabolic syndrome in Korean men and women. And, we confirmed that blood pressure is significantly associated with the PWV values at three locations. And, this study shows that Pearson correlation coefficient of arotic PWV and leg PWV were about 10% higher than without diabetes according to age. Further studies need to be performed to evaluate the optimal cut-off value of PWV for diabetes, hypertension, and MetS in Korean.

Association of human adenovirus-36 in overweight Korean adults.

BACKGROUND: Although human adenovirus-36 (Ad-36) has been reported to be associated with obesity in US adults and children, Korean children and the Italian population, the association has not been found in Dutch or Belgian populations or in US military subjects. Therefore, we examined whether Ad-36 infection is associated with obesity in Korean adults. METHODS: A total of 540 age- and sex-matched individuals, who were normal weight, overweight or obese, were selected from participants in routine health examinations at the Ewha Womans University Medical Center. Overweight participants were defined as those with a body mass index (BMI) of 23 ≤ BMI<25 kg m(-2) and obese subjects were those with BMI ≥ 25 kg m(-2), according to the International Obesity Task Force definition. Ad-36 antibody was measured using a serum neutralization assay. RESULTS: Although more overweight participants than normal or obese subjects tested positive for the Ad-36 antibody (40%, 32.8% and 30%, respectively), the differences were not significant. The participants who tested positive for Ad-36 antibody had lower levels of triglycerides (TG) in each of the three groups, higher total cholesterol (TC) in the obese group and higher high-density lipoprotein-cholesterol (HDL-C) in both the normal and obese groups. The odds ratio (OR) for Ad-36 antibody positivity was greater in overweight than in normal subjects (OR=2.03; 95% confidence interval (CI), 1.16-3.55) after adjusting for age, sex and waist circumference. However, this OR was non-significant in the obese group (OR=1.56; 95% CI, 0.67-3.67). CONCLUSION: Ad-36 seems to be strongly associated with overweight, but not obese, Korean adults.

HLA polymorphism among Chinese patients with chronic plaque psoriasis: subgroup analysis.

BACKGROUND: HLA-Cw*06 has a strong influence on the clinical features and the susceptibility to psoriasis in different ethnicities. It is also used as a biomarker to predict the therapeutic efficacy of biologics, with inconsistent results. Additionally, most Asian patients with psoriasis do not carry HLA-Cw*06. OBJECTIVES: To determine additional HLA alleles which confer susceptibility or affect the severity of psoriasis in Chinese Han individuals. In addition, the potential of using HLA to predict treatment outcomes was also investigated. METHODS: We conducted a case-control association study in 199 Chinese patients with psoriasis and 200 unrelated healthy controls. HLA-B and HLA-C genotyping was performed and correlated with the therapeutic efficacy of the biologics, including alefacept, efalizumab, etanercept and ustekinumab. Patients with psoriasis were divided into group A (high-need patients with moderate to severe psoriasis) and B (general patients with psoriasis). RESULTS: The frequencies of HLA-B*60, HLA-B*75, HLA-Cw*06 and HLA-Cw*10 were significantly increased in patients with psoriasis compared with the healthy controls. However, the prevalence of HLA-Cw*06 was lower in group A compared with group B (6% vs. 17%, Pc=0·04). HLA-B*46 was found to be strongly associated with group A but not with group B patients with psoriasis. HLA-Cw*01/HLA-B*46 was also identified as a risk haplotype for Chinese patients with psoriasis, compatible with the results in Thais. Significant differences in response to biologics were observed between HLA-Cw*01+ and HLA-Cw*01- individuals in the alefacept treatment group, and between HLA-B*37+ and HLA-B*37-, and HLA-B*58+ and HLA-B*58- individuals in the efalizumab treatment group. CONCLUSIONS: In addition to HLA-Cw*06, the HLA-Cw*01/HLA-B*46 haplotype was also increased in Chinese patients with psoriasis. High-need patients with psoriasis had a lower frequency of HLA-Cw*06 but a higher prevalence of HLA-B*46 compared with general patients with psoriasis in our population.

Narrowband ultraviolet B phototherapy for patients with refractory uraemic pruritus: a randomized controlled trial.

BACKGROUND: Pruritus is very common in uraemic patients, but the treatment remains challenging. Studies regarding narrowband ultraviolet B (NB-UVB) phototherapy for uraemic pruritus are rare. OBJECTIVES: To investigate whether or not NB-UVB phototherapy is an effective treatment for uraemic pruritus. METHODS: We conducted a single-blind, randomized, controlled trial for patients with refractory uraemic pruritus. The treatment group received NB-UVB phototherapy three times per week for 6 weeks. The dose of NB-UVB started from 210 mJ cm(-2) and was increased by 10% each time. The control group received time-matched exposures to long-wave UVA radiation. A visual analogue scale (VAS) score was evaluated weekly for pruritus intensity for 12 weeks. The characteristics of pruritus were also assessed by a questionnaire at baseline and after 6 weeks of phototherapy. RESULTS: Both the NB-UVB and control groups had significant and comparable improvement in the pruritus intensity VAS scores during the period of phototherapy and follow-up. Compared with the control group, the NB-UVB group showed a significant improvement in the involved body surface area affected by pruritus (P = 0·006), but not in sleep quality. More detailed regression and estimating analysis revealed that the patients in the NB-UVB group had lower pruritus intensity scores at week 6, week 10 and week 12. This may indicate a beneficial difference at certain time points, but the effect seems marginal. CONCLUSIONS: NB-UVB phototherapy does not show a significant effect in reducing pruritus intensity compared with a control group for refractory uraemic pruritus. Further studies are warranted.

Mid-life and late-life vascular risk factors and dementia in Korean men and women.

Dementia is one of the most important neurological disorders in the elderly population. The significance of vascular risk factors for dementia remains controversial. This study aimed to determine the effects of vascular risk factors, such as blood pressure, diabetes and smoking in the mid-life or the late-life on dementia risk. The data in this prospective cohort study came from 3252 dementia events occurring over 14 years among 848,505 Koreans aged 40-95 years insured by the National Health Insurance Corporation who had a biennial medical evaluation during 1992-1995. Data on clinical dementia during the period 1993-2006 were examined in relation to vascular risk factors. The age adjusted incidence per 100,000 was 31.9 for men and 45.0 for women, respectively. In multivariate Cox proportional hazard models, diabetes increased the risk of either dementia in Alzheimer's disease or vascular dementia in men and women, controlling for age, hypertension, total cholesterol, alcohol drinking, and smoking. Hypertension also increased vascular dementia in both men [Hazard ratio (HR)=2.6, 95% confidence interval (CI)=1.7-3.8] and women (HR=2.3, 95%CI=1.6-3.3). The association of hypertension or diabetes on risk of vascular dementia, however, among the group aged older than 65 was attenuated but remained as significant in men. There was no interaction between hypertension and diabetes on the risk of dementia. This study demonstrates that diabetes and hypertension increased the risk of vascular dementia. Treatment for these risk factors may reduce the risk of vascular dementia.

SLURP1 mutation-impaired T-cell activation in a family with mal de Meleda.

BACKGROUND: Mal de Meleda (MDM) is palmoplantar erythrokeratoderma with an autosomal recessive inheritance and is caused by a mutation in the gene encoding SLURP-1 (lymphocyte antigen 6/urokinase-type plasminogen activator receptor related protein-1). SLURP-1 is an allosteric agonist to the nicotinic acetylcholine receptor (nAchR) and it regulates epidermal homeostasis. In addition, murine studies have shown that nAchR signalling is important for the regulation of T-cell function. Among the family members, patients with the homozygous SLURP1 (previously known as ARS component B) mutation are prone to melanoma and viral infection, which might link to defective T-cell function as well as a derangement of epidermal homeostasis. OBJECTIVES: To investigate the association of the SLURP1 gene mutation with T-cell activation in a Taiwanese family with MDM. To test that SLURP-1 is essential for T-cell activation. METHODS: Human peripheral blood mononuclear cells (PBMCs) were isolated from a Taiwanese MDM family bearing the G to A substitution in nucleotide 256 in the SLURP1 gene, corresponding to a glycine to arginine substitution at amino acid 86 (G86R) in the SLURP-1 protein. PBMCs from homozygotes and wild-type controls were stimulated with anti-CD3/anti-CD28 antibodies and the level of T-cell activation was determined by the stimulation index. RESULTS: PBMCs with the heterozygous and homozygous SLURP-1 G86R mutation had defective T-cell activation. This was restored by the addition of 0·5 µg mL(-1) recombinant human SLURP-1 protein. CONCLUSIONS: Patients with MDM with the homozygous SLURP-1 G86R mutation may have an impaired T-cell activation. The presence of wild-type SLURP-1 is essential for normal T-cell activation.

Transformation of dissolved organic matter by oxidative polymerization with horseradish peroxidase.

Dissolved organic matter (DOM) has significant influence on the transport and fate of contaminants in multiple phases and it has potential hazard by acting as a precursor of disinfection by-products in water supply. The changes in DOM characteristics, especially by oxidative polymerization might result in different behaviour in the interaction with many contaminants. The aim of this work was to verify the catalytic effects of peroxidase on oxidative polymerization of humic and fulvic substances by examination of the structural characteristics. Transformation of humic acid (HA) and fulvic acid (FA) by oxidative polymerization catalyzed by horseradish peroxidase and hydrogen peroxide were investigated. Size exclusion chromatography, excitation-emission matrices spectra (EEMs), synchronous fluorescence spectra, and infrared spectroscopy was used to evaluate the structural transformation of HA and FA. Molecular weight of HA and FA was continuously changed and their weight-average molecular weight (MWw) reached maximum after 8 h. The MWw of HA and FA were proportionally increased with a dosage of horseradish peroxidase and hydrogen peroxide, indicating that HA and FA was transformed into larger and complex molecules. Spectroscopic results indicated that HA and FA structure contains strong polycyclic aromatic structures with more aromatic rings and a higher degree of conjugation.

Molecular characterization of dermatophytes of the Trichophyton mentagrophytes complex found in Taiwan with emphasis on their correlation with clinical observations.

BACKGROUND: Fungi of the Trichophyton mentagrophytes complex are important pathogenic dermatophytes capable of causing various human skin infections. There are many species and varieties involved in this complex. Due to morphological similarity and existing intermediate forms and variants, unequivocally separating these dermatophytes is not always straightforward, and sampling appropriate isolates for research is often troublesome. Communicating epidemiological statistics of these dermatophytes is greatly impeded because taxonomic schemes adopted by different research groups are inconsistent and hardly comparable. OBJECTIVES: To analyse the molecular types existing within isolates of the T. mentagrophytes complex in Taiwan and evaluate the applicability of the current taxonomy on these isolates. METHODS: Forty-eight isolates of the T. mentagrophytes complex were obtained from humans and animals (rabbit, guinea pig and hedgehog) in Taiwan. Sequences of ITS1-5.8S-ITS2 and b-tubulin gene regions of each isolate were used for molecular typing. RESULTS: Among the 48 isolates, 43 belonged to the T. interdigitale clade, including 21 of the anthropophilic strain and 22 of the zoophilic strain, and five belonged to the T. erinacei clade. No isolates of the T. mentagrophytes genotype were found. CONCLUSIONS: The isolates previously identified as T. mentagrophytes should be relabelled as T. interdigitale according to current taxonomy. Because the taxonomy is quite different from what it used to be, confusion in the nomenclature of the T. mentagrophytes complex is to be expected. The applicability of the current taxonomic concept may require further evaluation.

The association between pulse wave velocity and metabolic syndrome and adiponectin in patients with impaired fasting glucose: cardiovascular risks and adiponectin in IFG.

We aimed to assess how metabolic profiles, surrogate markers of insulin resistance, and subclinical atherosclerosis are interrelated in subjects with impaired fasting glucose (IFG) and investigate whether the diagnosis of metabolic syndrome (MetS) further increases the risk of cardiovascular disease among subjects already at risk. We analyzed 1739 Korean subjects with IFG. The parameters of MetS, plasma adiponectin level, and pulse wave velocity (PWV) were assessed. Subjects with MetS had unfavorable metabolic parameters, lower adiponectin level, and higher peripheral PWV compared to those without MetS. Adiponectin correlated with fasting glucose, waist circumference, triglyceride, HDL-cholesterol, BMI, HOMA-IR, and the number of MetS components. In addition to blood pressure, peripheral PWV was associated with triglyceride, waist circumference, and the number of MetS components while aortic PWV correlated positively with fasting plasma glucose. Multiple linear regression analysis revealed that adiponectin correlated with HDL-cholesterol, HOMA-IR, fasting glucose, waist circumference, and triglyceride, peripheral PWV with blood pressure, body mass index, waist circumference, and the number of MetS components, and aortic PWV with fasting plasma glucose. In subjects with IFG, concurrent MetS increases PWV and has an unfavorable effect on cardiovascular risks, and these risks were further increased by additional MetS components.

Neuro-mediators as predictors of paediatric atopic dermatitis.

BACKGROUND: Attempts to identify predictors of atopic dermatitis (AD) have focused on genetic and immunologic factors. However, the role of neuro-mediators remains to be elucidated. OBJECTIVE: To evaluate nerve growth factor (NGF) and vaso-active intestinal peptide (VIP) in predicting paediatric AD and assess their correlation with intrinsic and extrinsic types of AD. METHODS: We performed a nested case-control study in the prospective Taiwan birth panel cohort study. Cord and maternal plasma and questionnaires were gathered at birth. During follow-up, we identified 40 available AD cases, which were matched to 80 unaffected controls chosen from this cohort. The concentrations of IgE, NGF, and VIP in cord and maternal plasma of these subjects were performed by ELISA. Receiver-operating characteristic (ROC) curves were generated to see how well each biomarker could predict AD. RESULTS: The NGF levels were significantly higher in AD patients than controls (mean+/-SD: 65.47+/-44.45 vs. 49.21+/-12.18 pg/mL for cord plasma and 89.68+/-41.04 vs. 66.96+/-23.05 pg/mL for maternal plasma) (P<0.05). VIP levels were also higher but not statistically significant. Plasma NGF may be a better biomarker than IgE in detecting paediatric AD (area under the ROC curve=0.65 vs. 0.61 for cord plasma and 0.69 vs. 0.61 for maternal plasma). Maternal NGF levels were significantly higher in patients with both intrinsic (96.18+/-48.15 pg/mL) and extrinsic (86.18+/-37.23 pg/mL) types of AD compared with controls (66.96+/-23.05 pg/mL) (P<0.05). We assessed a significant correlation between self-reported stress during pregnancy and maternal NGF levels (r=0.22, P=0.02). CONCLUSION: Our results suggest that NGF is a good alternative biomarker in predicting children with a risk of AD.

An extension of the regression of offspring on mid-parent to test for association and estimate locus-specific heritability: the revised ROMP method.

The Regression of Offspring on Mid-Parent (ROMP) method is a test of association between a quantitative trait and a candidate locus. ROMP estimates the trait heritability and the heritability attributable to a locus and requires genotyping the offspring only. In this study, the theory underlying ROMP was revised (ROMP(rev)) and extended. Computer simulations were used to determine the type I error and power of the test of association, and the accuracy of the locus-specific heritability estimate. The ROMP(rev) test had good power at the 5% significance level with properly controlled type I error. Locus-specific heritability estimates were, on average, close to simulated values. For non-zero locus-specific heritability, the proposed standard error was downwardly biased, yielding reduced coverage of 95% confidence intervals. A bootstrap approach with proper coverage is suggested as a second step for loci of interest. ROMP(rev) was applied to a study of cardiovascular-related traits to illustrate its use. An association between polymorphisms within the fibrinogen gene cluster and plasma fibrinogen was detected (p < 0.005) that accounted for 29% of the estimated fibrinogen heritability. The ROMP(rev) method provides a computationally fast and simple way of testing for association and obtaining accurate estimates of locus-specific heritability while minimizing the genotyping required.

Involvement of matrix metalloproteinase-13 in stromal-cell-derived factor 1 alpha-directed invasion of human basal cell carcinoma cells.

Basal cell carcinoma (BCC) is one of the most common skin neoplasms in humans and is usually characterized by local aggressiveness with little metastatic potential, although deep invasion, recurrence, and regional and distant metastases may occur. Here, we studied the mechanism of BCC invasion. We found that human BCC tissues and a BCC cell line had significant expression of CXCR4, which was higher in invasive than non-invasive BCC types. Further, of 19 recurrent tumors among 390 BCCs diagnosed during the past 12 years, 17/19 (89.5%) had high CXCR4 expression. We found that the CXCR4 ligand, stromal-cell-derived factor 1alpha (SDF-1alpha), directed BCC invasion and that this was mediated by time-dependent upregulation of mRNA expression and gelatinase activity of matrix metalloproteinase-13 (MMP-13). The transcriptional regulation of MMP-13 by SDF-1alpha was mediated by phosphorylation of extracellular signal-related kinase 1/2 and activation of the AP-1 component c-Jun. Finally, CXCR4-transfected BCC cells injected into nude mice induced aggressive BCCs that co-expressed CXCR4 and MMP-13. The identification of SDF-1alpha/CXCR4 as an important factor in BCC invasiveness may contribute insight into mechanisms involved in the aggressive potential of human BCC and may improve therapy for invasive BCCs.