Risks of occupational mental disorders in Korean civil servants (2009-18).

BACKGROUND: Previous studies have suggested that firefighters, police officers and civil servants in the education sector, particularly in Western countries, are vulnerable to mental stress and disorders; however, evidence for this association in South Korea is lacking. AIMS: This study aimed to identify whether firefighters, police officers and teachers are at a higher risk for occupational mental health disorders. METHODS: We used workers' compensation claims from civil servants (2009-18). Our target population comprised 46 209 civil servants (9009 civil servants in administrative and technical positions, 23 107 police officers, 4417 firefighters and 8676 civil servants in the educational sector). Occupational and environmental medicine physicians and medical doctors defined and confirmed mental disorders. We conducted Cox proportional hazards regression analyses to evaluate civil servants' risk of occupational mental health disorders. RESULTS: Compared with the civil servants in administrative and technical positions, civil servants in the education sector (hazard ratio [HR] = 2.16; 95% confidence interval [CI]:1.65-2.84) showed a statistically significant increased risk of mental disorders; conversely, firefighters did not (HR = 0.80; 95% CI 0.51-1.27). Police officers had a significantly decreased mental disorder risk compared with civil servants in administrative and technical positions (HR = 0.17; 95% CI 0.11-0.25). CONCLUSIONS: The risk of occupational mental health disorders was higher in civil servants in the education sector but lower in police officers and firefighters than civil servants in administrative and technical positions. Further studies on civil servants' mental health awareness are required to confirm our results.

BLZ8 activates a plastidial peroxiredoxin and a ferredoxin to protect Chlamydomonas reinhardtii against oxidative stress.

Reactive oxygen species (ROS) cause damage to various cellular processes in almost all organisms, in particular photosynthetic organisms that depend on the electron transfer chain for CO2 fixation. However, the detoxifying process to mitigate ROS damage has not been studied intensively in microalgae. Here, we characterized the ROS detoxifying role of a bZIP transcription factor, BLZ8, in Chlamydomonas reinhardtii. To identify downstream targets of BLZ8, we carried out comparative genome-wide transcriptomic profiling of BLZ8 OX and its parental CC-4533 under oxidative stress conditions. Luciferase reporter activity assays and RT-qPCR were performed to test whether BLZ8 regulates downstream genes. We performed an in silico functional gene network analysis and an in vivo immunoprecipitation assay to identify the interaction between downstream targets of BLZ8. Comparative transcriptomic analysis and RT-qPCR revealed that overexpression of BLZ8 increased the expression levels of plastid peroxiredoxin1 (PRX1) and ferredoxin-5 (FDX5) under oxidative stress conditions. BLZ8 alone could activate the transcriptional activity of FDX5 and required bZIP2 to activate transcriptional activity of PRX1. Functional gene network analysis using FDX5 and PRX1 orthologs in A. thaliana suggested that these two genes were functionally associated. Indeed, our immunoprecipitation assay revealed the physical interaction between PRX1 and FDX5. Furthermore, the complemented strain, fdx5 (FDX5), recovered growth retardation of the fdx5 mutant under oxidative stress conditions, indicating that FDX5 contributes to oxidative stress tolerance. These results suggest that BLZ8 activates PRX1 and FDX5 expression, resulting in the detoxification of ROS to confer oxidative stress tolerance in microalgae.

High reproduction number of Middle East respiratory syndrome coronavirus in nosocomial outbreaks: mathematical modelling in Saudi Arabia and South Korea.

BACKGROUND: Effective countermeasures against emerging infectious diseases require an understanding of transmission rate and basic reproduction number (R0). R0 for severe acute respiratory syndrome is generally considered to be >1, whereas that for Middle East respiratory syndrome (MERS) is considered to be <1. However, this does not explain the large-scale outbreaks of MERS that occurred in Kingdom of Saudi Arabia (KSA) and South Korean hospitals. AIM: To estimate R0 in nosocomial outbreaks of MERS. METHODS: R0 was estimated using the incidence decay with an exponential adjustment model. The KSA and Korean outbreaks were compared using a line listing of MERS cases compiled using publicly available sources. Serial intervals to estimate R0 were assumed to be six to eight days. Study parameters [R0 and countermeasures (d)] were estimated by fitting a model to the cumulative incidence epidemic curves using Matlab. FINDINGS: The estimated R0 in Korea was 3.9 in the best-fit model, with a serial interval of six days. The first outbreak cluster in a hospital in Pyeongtaek had an R0 of 4.04, and the largest outbreak cluster in a hospital in Samsung had an R0 of 5.0. Assuming a six-day serial interval, the KSA outbreaks in Jeddah and Riyadh had R0 values of 3.9 and 1.9, respectively. CONCLUSION: R0 for the nosocomial MERS outbreaks in KSA and South Korea was estimated to be in the range of 2-5, which is significantly higher than the previous estimate of <1. Therefore, more comprehensive countermeasures are needed to address these infections.

Acetylcholine precursor, citicoline (cytidine 5'-diphosphocholine), reduces hypoglycaemia-induced neuronal death in rats.

Citicoline (cytidine 5'-diphosphocholine) is an important precursor for the synthesis of neuronal plasma membrane phospholipids, mainly phosphatidylcholine. The administration of citicoline serves as a choline donor for the synthesis of acetylcholine. Citicoline has been shown to reduce the neuronal injury in animal models with cerebral ischaemia and in clinical trials of stroke patients. Citicoline is currently being investigated in a multicentre clinical trial. However, citicoline has not yet been examined the context of hypoglycaemia-induced neuronal death. To clarify the therapeutic impact of citicoline in hypoglycaemia-induced neuronal death, we used a rat model with insulin-induced hypoglycaemia. Acute hypoglycaemia was induced by i.p. injection of regular insulin (10 U kg-1 ) after overnight fasting, after which iso-electricity was maintained for 30 minutes. Citicoline injections (500 mg/kg, i.p.) were started immediately after glucose reperfusion. We found that post-treatment of citicoline resulted in significantly reduced neuronal death, oxidative injury and microglial activation in the hippocampus compared to vehicle-treated control groups at 7 days after induced hypoglycaemia. Citicoline administration after hypoglycaemia decreased immunoglobulin leakage via blood-brain barrier disruption in the hippocampus compared to the vehicle group. Citicoline increased choline acetyltransferase expression for phosphatidylcholine synthesis after hypoglycaemia. Altogether, the present findings suggest that neuronal membrane stabilisation by citicoline administration can save neurones from the degeneration process after hypoglycaemia, as seen in several studies of ischaemia. Therefore, the results suggest that citicoline may have therapeutic potential to reduce hypoglycaemia-induced neuronal death.

Dietary total, animal, vegetable calcium and type 2 diabetes incidence among Korean adults: The Korean Multi-Rural Communities Cohort (MRCohort).

BACKGROUND AND AIMS: Although a possible mechanism for developing type 2 diabetes in relation to calcium intake has been suggested, there is currently little epidemiological evidence on the association between dietary calcium and type 2 diabetes (T2D). This study aimed to evaluate the prospective association between dietary calcium and T2D incidence among adults 40 years of age or over, from the Multi-rural Communities Cohort (MRCohort), South Korea. METHODS AND RESULTS: In total, 8313 participants (3033 men and 5280 women) who did not have diabetes at baseline were recruited between 2005 and 2013. The incidence rate ratio (IRR) was estimated using a modified Poisson regression model with a robust error estimator. During follow-up (31,570 person-years), 322 T2D cases were newly diagnosed. Dietary calcium (total and vegetable calcium) were inversely associated with the risk of T2D incidence among women (IRR = 0.61, 95% CI = 0.43-0.86, P for trend = 0.007 in third tertile of baseline total calcium intake comparing to the first tertile; IRR = 0.57, 95% CI = 0.39-0.84, P for trend = 0.006 for baseline vegetable calcium intake), not for men. The tendency of those inverse associations remained in both the normal fasting blood glucose group and the impaired fasting blood glucose group and were independent of obesity, smoking, and magnesium intake. CONCLUSIONS: Total and vegetable calcium may be inversely associated with T2D incidence among women, regardless of impaired fasting blood glucose group or normal group. The associations may be potentially dose-responsive. Moderate dietary calcium may be related to lower risk of T2D incidence comparing to low intake group among women.

The long-term relationship between dietary pantothenic acid (vitamin B5) intake and C-reactive protein concentration in adults aged 40 years and older.

BACKGROUND AND AIMS: Low-grade inflammation, represented by minor C-reactive protein (CRP) elevation, has a critical role in the early stages of atherosclerosis, and pantothenic acid (PA) may have an antioxidant effect in inflammatory process. However, the long-term relationship between PA intake and CRP has not yet been studied. The objective of the present study was to evaluate the long-term relationship of PA intake to CRP concentration in healthy adults aged 40 years or older living in a rural area of South Korea. METHODS AND RESULTS: A total of 908 subjects (349 men, 559 women) with repeated data on dietary PA intake and CRP concentration were included in the final analysis. To represent the long-term effect of PA intake, both PA intake at the baseline and average PA intake were used as the exposure, and CRP concentration at the third visit and its change from the baseline to the third visit were used as the outcome. After adjustment for potential confounders, a significant inverse relationship between PA intake and CRP concentration at the third visit was observed (P for trend = 0.001, ß = -0.07 (P-value = 0.001) for PA baseline; P for trend = <0.0001, ß = -0.11 (P-value = 0.0004) for PA average (baseline, 2nd, 3rd)). Higher PA intake was significantly related to lower or attenuated increase in CRP concentration (P for trend = 0.002, ß = -0.24 (P-value = 0.002) for PA baseline; P for trend = 0.001, ß = -0.35 (P-value = 0.001) for PA average (baseline, 2nd, 3rd)). CONCLUSIONS: In conclusion, dietary PA intake was inversely related to subsequent CRP concentration in both men and women aged 40 years or older in South Korea.

RAC-LATS1/2 signaling regulates YAP activity by switching between the YAP-binding partners TEAD4 and RUNX3.

The tumor-suppressor RUNX3 has a critical role in a lineage determination, cell cycle arrest and apoptosis. Lozenge (Lz), a Drosophila homolog of mammalian RUNX family members, has integral roles in these processes and specifically in eye cell fate determination. To elucidate the genetic modifiers of Lz/RUNX3, we performed a large-scale functional screen in a fly mutant library. The screen revealed genetic interactions between the Lz, Rac and Hippo pathways. Analysis of interactions among these genes revealed that the defective phenotype resulting from activation of Yki, an end point effector of the Hippo pathway, was suppressed by Lz and enhanced by Rac-Trio. Molecular biological analysis using mammalian homologs reveled that LATS1/2-mediated YAP phosphorylation-facilitated dissociation of the YAP-TEAD4 complex and association of the YAP-RUNX3 complex. When cells were stimulated to proliferate, activated RAC-TRIO signaling inhibited LATS1/2-mediated YAP phosphorylation; consequently, YAP dissociated from RUNX3 and associated with TEAD, thereby replacing the YAP-RUNX3 complex with YAP-TEAD. RUNX3 contributed to both association and dissociation of YAP-TEAD complex, most likely through the formation of the YAP-TEAD-RUNX3 ternary complex. Ectopic expression of RUNX3 in MKN28 gastric cancer cells reduced tumorigenicity, and the tumor-suppressive activity of RUNX3 was associated with its ability to interact with YAP. These results identify a novel regulatory mechanism, mediated by the Hippo and RAC-TRIO pathways, that changes the binding partner of YAP.

Vertigo and nystagmus in orthostatic hypotension.

BACKGROUND AND PURPOSE: Generalized cerebral ischaemia from cardiovascular dysfunction usually leads to presyncopal dizziness, but several studies reported a higher frequency of rotatory vertigo in cardiovascular patients. Whether generalized cerebral ischaemia due to cardiovascular disorders may produce objective vestibular dysfunction was investigated. METHODS: Thirty-three patients with orthostatic dizziness/vertigo due to profound orthostatic hypotension and 30 controls were recruited. All participants underwent recording of eye movements during two orthostatic challenging tests: the Schellong and the squatting-standing tests. Most patients had neuroimaging, and patients with abnormal eye movements were subjected to follow-up evaluations. RESULTS: Symptoms associated with orthostatic dizziness/vertigo included blurred vision, fainting and tinnitus. Ten (30%) of 33 patients developed rotatory vertigo and nystagmus during the Schellong (n = 5) or squatting-standing test (n = 5). Four of them showed pure downbeat nystagmus whilst five had downbeat and horizontal nystagmus with or without torsional component. Patients with orthostatic nystagmus had shorter duration of orthostatic intolerance than those without nystagmus (1.0 ± 1.6 vs. 11.0 ± 9.7 months, P < 0.001). In two patients, orthostatic nystagmus disappeared during follow-up despite the persistence of profound orthostatic hypotension. CONCLUSIONS: Generalized cerebral ischaemia caused by orthostatic hypotension induces rotatory vertigo due to objective vestibular dysfunction. The presence of orthostatic vertigo and nystagmus has an association with the duration of orthostatic intolerance.

Characteristics of pleural effusions in systemic lupus erythematosus: differential diagnosis of lupus pleuritis.

We investigated the clinical characteristics of pleural effusion in systemic lupus erythematosus (SLE). A prospective analysis of 17 SLE patients with pleural effusion (seven lupus pleuritis, eight transudative effusions and two parapneumonic effusions) was performed. Thirty non-SLE patients with pleural effusion were recruited as controls. A pleural fluid ANA titer ≥1:160 was found in 8/17 (47.1%) SLE patients and none of the 30 non-SLE patients (p = 0.0001). Pleural fluid to serum C3 ratios were significantly lower in SLE than in non-SLE (median (minimum-maximum) 0.29 (0.03-0.43) versus 0.52 (0.26-0.73), p = 0.0002). Among SLE patients, pleural fluid ANA titers ≥1:160 were more frequently found in patients with lupus pleuritis than in those with pleural effusion from causes other than lupus itself (85.7% versus 20.0%, p = 0.0152). Serum CRP levels were significantly increased in patients with lupus pleuritis compared with SLE patients with transudative pleural effusion (2.30 (0.30-5.66) versus 0.7 (0.12-1.47) mg/dl, p = 0.0062). In conclusion, pleural fluid ANA titer and serum CRP levels are significantly increased in lupus pleuritis.

The association of radiographic progression with serum R-spondin 1 (RSPO1) levels or Dickkopf-1 (DKK1)/RSPO1 ratios in rheumatoid arthritis patients: clinical evidence for reciprocal inhibition between DKK1 and RSPO1.

OBJECTIVES: To investigate the clinical implications of serum levels of R-spondin 1 (RSPO1), a natural antagonist for Dickkopf-1 (DKK1), and of DKK1/RSPO1 ratios in rheumatoid arthritis (RA) patients. METHOD: Serum DKK1 and RSPO1 levels were measured in 102 RA patients and 39 age- and gender-matched healthy controls. In addition, DKK1 and RSPO1 levels were determined prior to and 3 months after anti-tumour necrosis factor alpha (anti-TNF-α) therapy in 15 RA patients. Clinical and laboratory data and baseline radiographs of the hands and feet were obtained. Serial radiographs were evaluated in 83 RA patients. Radiographic joint damage was assessed by the modified Sharp/van der Heijde score (SHS). RESULTS: Serum RSPO1 levels were significantly reduced whereas serum DKK1 levels and DKK1/RSPO1 ratios were significantly increased in RA patients compared with controls (all p < 0.0001). Anti-TNF-α treatment significantly suppressed DKK1/RSPO1 ratios (p < 0.01). In contrast to DKK1 or RSPO1 levels, the ratios were significantly associated with erosive disease, elevated acute phase reactants, Disease Activity Score in 28 joints (DAS28) > 3.2, and radiographic progression rate (all p < 0.05). Although the RA patients with radiographic progression exhibited significantly increased DKK1 and reduced RSPO1 levels (p < 0.05), only the DKK1/RSPO1 ratio (log-transformed) was found to be a significant predictor of subsequent radiographic progression [odds ratio (OR) 2.07, p < 0.01]. CONCLUSIONS: In this study, the presence of RSPO1 in the circulation was shown for the first time. Our results suggest that the serum DKK1/RSPO1 ratio represents a better predictor of structural progression than either DKK1 or RSPO1 levels alone in RA patients.

Harmful and beneficial relationships between alcohol consumption and subclinical atherosclerosis.

BACKGROUND AND AIMS: Arterial stiffness and increased intima-media wall thickness are two of the main predictors of cardiovascular disease (CVD). We evaluated whether brachial-ankle pulse wave velocity (baPWV) and common carotid artery intima-media wall thickness (CCA-IMT) are correlated with alcohol consumption in a cross-sectional study among Korean men and women aged 40 years and over. METHODS AND RESULTS: All 5539 subjects (2121 men and 3418 women) were participants in the Multi-Rural Communities cohort (MRcohort) study, a part of the Korean Genome Epidemiology Study (KoGES). The baPWV was positively correlated with alcohol consumption in men (p for trend <0.0001). Age (middle-aged versus elderly) modified the effect of alcohol consumption on PWV. On the other hand CCA-IMT decreased with alcohol consumption in men. There was no favorable zone of alcohol consumption in terms of baPWV and CCA-IMT. Adjustment for lipid profiles substantially attenuated the relationship between alcohol consumption and CCA-IMT. There was no clear relation between alcohol consumption and baPWV/CCA-IMT in women. CONCLUSIONS: Along with a linear harmful relationship between alcohol consumption and arterial stiffness in men there may also be a beneficial relationship between alcohol consumption and carotid intima-wall thickness. The effect of alcohol on arterial stiffness may be slightly stronger in elderly men, and the effect of alcohol on CCA-IMT may be mediated by lipid factors.

Costs of illness and quality of life in patients with systemic lupus erythematosus in South Korea.

OBJECTIVE: To assess the costs of illness, health-related quality of life (HRQOL) and their associated factors in patients with systemic lupus erythematosus (SLE) in South Korea. METHOD: Two hundred and one patients with SLE were enrolled at the Rheumatology clinic of Seoul National University Hospital. Direct, indirect and total costs and HRQOL were measured using hospital electronic data and face-to-face interview. Socio-demographic and clinical factors associated with cost of illness and HRQOL were analyzed using multiple regression and multivariate logistic regression. RESULTS: The average total cost of illness was estimated to be KRW 9.82 million (US $ 8993) per year, of which 41.6% was accounted for by direct costs and 58.4% by indirect costs. In multivariate regression, patients with renal involvement and those with depression incurred an average increment in annual total costs of 37.6% (p = 0.050) and 49.1% (p = 0.024), respectively, and an average increment in annual direct costs of 26.4% (p = 0.050) and 43.3% (p = 0.002), respectively, compared with patients without renal involvement and depression, respectively. In addition, disease damage was positively associated with an average increment in annual total and direct costs (55.3%, p = 0.006; 33.3%, p = 0.013, respectively), and the occurrence of indirect costs (OR 2.21, 1.09-4.88). There was no significant difference in HRQOL between patients with and without renal involvement (0.655 vs. 0.693, p = 0.203) CONCLUSION: Renal involvement, depression, and disease damage were major factors associated with higher total and medical costs for patients with SLE in South Korea. Effective treatment of renal disorders and depression may reduce the high economic burden of SLE.

A cross-sectional analysis of the relationship between daily alcohol consumption and serum adiponectin levels among adults aged 40 years or more in a rural area of Korea.

BACKGROUND/OBJECTIVES: Light-to-moderate alcohol consumption has been proposed to raise serum adiponectin levels, but this view is controversial. There is little information on the effect of heavy drinking. The aim of this study was to examine the relationship between alcohol consumption and serum adiponectin levels in healthy Koreans. SUBJECTS/METHODS: The design of the study was cross-sectional, using data from the Korean Multi-Rural Communities Cohort Study (MRCohort), which is a part of the Korean Genome Epidemiology Study (KoGES). The subjects were 1542 individuals (635 men and 907 women) aged ≥ 40 years who were recruited in Yangpyeong-Gun, Kyunggi province, South Korea, in 2005 and 2006. Daily alcohol consumption was calculated from average frequency of alcohol consumption and the amount of alcohol consumed per occasion using a structured questionnaire and serum adiponectin levels were measured. RESULTS: Although adiponectin levels appeared to be higher in those consuming moderate levels of alcohol than in nondrinkers, the difference was not statistically significant. Heavy drinking (≥ 90.0 g/day) was significantly related to reduced serum adiponectin levels (P=0.003), although the significance of the relationship was reduced after adjusting for potential confounders (P=0.061) such as age, waist/hip ratio, blood pressure, fasting blood glucose, current smoker, higher education, protein intake, vitamin C intake and vitamin E intake in men. The relation seemed to be stronger in individuals consuming alcohol in the form of takju (Korean rice wine; P=0.022). CONCLUSIONS: Heavy alcohol drinking (≥ 90.0 g/day) may be related to lower serum adiponectin levels in Korean men.

Association of genetic variation in FTO with risk of obesity and type 2 diabetes with data from 96,551 East and South Asians.

AIMS/HYPOTHESIS: FTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians. METHODS: All studies published on the association between FTO-rs9939609 (or proxy [r (2) > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes. RESULTS: The FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10(-19)), overweight by 1.13-fold/allele (p = 1.0 × 10(-11)) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10(-8)). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10(-5)). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m(2) per allele (p = 2.8 × 10(-17)), WHR by 0.003/allele (p = 1.2 × 10(-6)), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12-20%) than South Asians (30-33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations. CONCLUSIONS/INTERPRETATION: FTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI.

Population attributable fraction of infection-related cancers in Korea.

BACKGROUND: A number of infectious agents have been classified as human carcinogens. The purpose of the current study was to provide an evidence-based assessment of the burden of infection-related cancers in the Korean population. MATERIALS AND METHODS: The population attributable fraction was calculated using infection prevalence data from 1990 or earlier, relative risk estimates from meta-analyses using mainly Korean studies and national data on cancer incidence and mortality for the year 2007. RESULTS: The fractions of all cancers attributable to infection were 25.1% and 16.8% for cancer incidence in men and women, and 25.8% and 22.7% of cancer mortality in men and women, respectively. Among infection-related cancers, Helicobacter pylori was responsible for 56.5% of cases and 45.1% of deaths, followed by hepatitis B virus (HBV) (23.9% of cases and 37.5% of deaths) and human papillomavirus (HPV) (11.3% of cases and 6% of deaths) and then by hepatitis C virus (HCV) (6% of cases and 9% of deaths). Over 97% of infection-related cancers were attributable to infection with H. pylori, HBV, HCV and HPV. CONCLUSION: Up to one-quarter of cancer cases and deaths would be preventable through appropriate control of infectious agents in Korea.

Segregation of enlarged vestibular aqueducts in families with non-diagnostic SLC26A4 genotypes.

BACKGROUND: Hearing loss with enlarged vestibular aqueduct (EVA) can be inherited as an autosomal recessive trait caused by bi-allelic mutations of SLC26A4. However, many EVA patients have non-diagnostic SLC26A4 genotypes with only one or no detectable mutant alleles. METHODS AND RESULTS: In this study, the authors were unable to detect occult SLC26A4 mutations in EVA patients with non-diagnostic genotypes by custom comparative genomic hybridisation (CGH) microarray analysis or by sequence analysis of conserved non-coding regions. The authors sought to compare the segregation of EVA among 71 families with two (M2), one (M1) or no (M0) detectable mutant alleles of SLC26A4. The segregation ratios of EVA in the M1 and M2 groups were similar, but the segregation ratio for M1 was significantly higher than in the M0 group. Haplotype analyses of SLC26A4-linked STR markers in M0 and M1 families revealed discordant segregation of EVA with these markers in eight of 24 M0 families. CONCLUSION: The results support the hypothesis of a second, undetected SLC26A4 mutation that accounts for EVA in the M1 patients, in contrast to non-genetic factors, complex inheritance, or aetiologic heterogeneity in the M0 group of patients. These results will be helpful for counselling EVA families with non-diagnostic SLC26A4 genotypes.

Identities and frequencies of mutations of the otoferlin gene (OTOF) causing DFNB9 deafness in Pakistan.

Mutations in OTOF, encoding otoferlin, cause non-syndromic recessive hearing loss. The goal of our study was to define the identities and frequencies of OTOF mutations in a model population. We screened a cohort of 557 large consanguineous Pakistani families segregating recessive, severe-to-profound, prelingual-onset deafness for linkage to DFNB9. There were 13 families segregating deafness consistent with linkage to markers for DFNB9. We analyzed the genomic nucleotide sequence of OTOF and detected probable pathogenic sequence variants among all 13 families. These include the previously reported nonsense mutation p.R708X and 10 novel variants: 3 nonsense mutations (p.R425X, p.W536X, and p.Y1603X), 1 frameshift (c.1103_1104delinsC), 1 single amino acid deletion (p.E766del) and 5 missense substitutions of conserved residues (p.L573R, p.A1090E, p.E1733K, p.R1856Q and p.R1939W). OTOF mutations thus account for deafness in 13 (2.3%) of 557 Pakistani families. This overall prevalence is similar, but the mutation spectrum is different from those for Western populations. In addition, we demonstrate the existence of an alternative splice isoform of OTOF expressed in the human cochlea. This isoform must be required for human hearing because it encodes a unique alternative C-terminus affected by some DFNB9 mutations.

Pesticide residue monitoring in Korean agricultural products, 2003-05.

Between 2003 and 2005, a total of 11,716 samples were collected and analysed to determine the level of pesticides residues. Multi-residue methods (MRMs) capable of simultaneously determining 250 pesticides were used. Of the 11,716 samples, 89.1% had no detectable residues and 1.7% had violative residues. The detection rates by commodity group were 11.4, 8.6, 0.3, and 0.02% for vegetables, fruit, grain, mushrooms, and the others, respectively. Agricultural products with pesticide residues were pepper, Perilla frutescens, leafy lettuce and spinach in decreasing order. Of the 250 pesticides that were monitored, 70 pesticides were actually found. Procymidone, endosulfan, chlorfenapyr, metalaxyl, and diethofencarb were frequently detected. Of the samples, parsley, Petasites hybridus, Aster scaber and leek had high violative rates of 23.1, 12.6, 8.2, and 7.9%, respectively. From violative samples, procymidone, endosulfan, metalaxyl, diazinon and chlorpyrifos were frequently detected. The violation rates were 1.71, 1.68, and 1.76% in 2003, 2004 and 2005, respectively, and the detection rates were 8.5, 12.0, and 13.3% in 2003, 2004, and 2005, respectively.

Relationship between the change in overweight status from childhood to adolescence and metabolic syndrome phenotypes: a 9-year retrospective study.

OBJECTIVE: To evaluate how the changes in overweight status from childhood to adolescence are related to metabolic syndrome phenotypes in adolescents. SUBJECTS AND METHODS: A total 375 adolescents aged 16 years. The overweight status from childhood to adolescence (from 7 years of age to 16 years) was determined by body mass index (BMI, kg/m(2)) calculated from records of the School Physical Examination data. The change in body weight was classified into four groups: normal weight to normal weight (NW-NW); overweight to normal (OW-NW); normal to overweight (NW-OW); overweight to overweight (OW-OW). Metabolic syndrome phenotypes were examined from a cross-sectional survey. RESULTS: The mean values of all phenotypes except for body fatness (BMI and waist) and the cluster score of phenotypes at 16 years of age were not different between the NW-NW group and the OW-NW group, nor between the NW-OW group and the OW-OW group. However, the score as well as the level of body fatness and blood glucose were significantly different between current overweight and normal adolescents regardless of overweight status during childhood (P<0.05). CONCLUSION: There was a linear relationship between overweight status during childhood and metabolic syndrome phenotypes in adolescence but current overweight status (adolescence overweight) was more closely related to the adolescent risk of metabolic syndrome than childhood overweight status.

Lack of association between LTA and LGALS2 polymorphisms and myocardial infarction in Japanese and Korean populations.

To investigate the recently reported associations of polymorphisms in lymphotoxin-alpha (LTA) and galectin-2 (LGALS2) with myocardial infarction (MI), we analyzed a single nucleotide polymorphism of LTA (LTA 252A>G in LTA intron 1) and that of LGALS2 (LGALS2 3279C>T in LGALS2 intron 1) in Japanese and Korean populations. Although significant associations with MI were not observed in either population, we found that LTA 252GG was significantly associated with the severity of the disease for both the Japanese and Korean populations (P=0.017 and P=0.001, respectively). On the other hand, the polymorphism of LGALS2 was not associated with the severity of coronary atherosclerosis. These observations showed that, while the LTA 252GG genotype might modify the development of coronary atherosclerosis, the relation of LTA and LGALS2 to MI itself remained much less certain.