Proteomics approach to identify serum biomarkers associated with the progression of diabetes in Korean patients with abdominal obesity.

Type 2 diabetes is a metabolic disease with a group of metabolic derangements and inflammatory reactants in the serum. Despite the substantial public health implications, markers of diabetes progression with abdominal obesity are still needed to facilitate early detection and treatment. In this study, we performed a proteomic approach to identify differential target proteins underlying diabetes progression in patients with abdominal obesity. Proteomic differences were investigated in the serum of controls and patients with prediabetes or diabetes with or without abdominal obesity by 2-DE combined with MALDI-TOF-MS. Proteomics data were validated by western blot analyses and major protein-protein interactions were assessed using a network analysis with String database. Among 245 matched protein spots, 36 exhibited marked differences in normal patients with abdominal obesity, prediabetes, and diabetes compared to levels in normal patients without abdominal obesity. Seven (Alpha-1-antichymotrypsin, Alpha-1-antitrypsin, Apolipoprotein A-I, haptoglobin, retinol-binding protein 4, transthyretin, and zinc-alpha2-glycoprotein) of these spots exhibited significant differences between normal and prediabetes/diabetes patients. After a network analysis, functional annotation using Gene Ontology indicated that most of the identified proteins were involved in lipid transport, lipid localization, and the regulation of serum lipoprotein particle levels. Our results indicated that variation in the levels of these identified protein biomarkers has been reported in normal, prediabetes and diabetic Assessment of the levels of these biomarkers may contribute to the development of biomarkers for not only early diagnosis but also in prognosis of diabetes mellitus type 2.

Plasma sphingomyelins increase in pre-diabetic Korean men with abdominal obesity.

Abdominal or visceral obesity is a well-known risk factor for metabolic diseases. However, whether abdominal obesity significantly affects plasma lipid profile during the development of type 2 diabetes has not been fully elucidated. We investigated the differences in plasma lipid concentrations in 63 participants categorized into six groups (middle-aged Korean men); Normal, Pre-diabetes (pre-DM), and Diabetes mellitus (DM) with or without abdominal obesity (AO or lean). The lipidomic profiles were determined by using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Sphingomyelin (SM) levels in plasma were significantly higher in the pre-DM with AO than in pre-DM with lean (p = 0.021). SM concentrations correlated positively with waist-to-hip ratio (WHR) (r = 0.256, p = 0.044), cholesteryl ester (CE) (r = 0.483, p < 0.0001), ceramide (r = 0.489, p < 0.0001) and plasmanyl phosphatidylcholine (PC) (r = 0.446, p < 0.0001). The present study found that pre-diabetic patients with AO were characterized by increased plasma concentrations of SM. Plasma SM levels in individuals with AO may be an early prognostic biomarker to better predict the progression toward type 2 diabetes and metabolic syndrome.

Spatial analysis between particulate matter and emergency room visits for conjunctivitis and keratitis.

BACKGROUND: The concentration of particulate matter in the air varies depending on the region because it is lightweight and generated from a variety of sources. To assess the relationship between particulate matter and eye disease, this study analyzes the concentration data obtained from spatial analysis of particulate matter and emergency visit data. METHODS: The study included 769 residents of Daegu, Korea who had visited an emergency room for the problem of conjunctivitis or keratitis. Concentrations of PM10 and other air pollutants were obtained from the Korean Ministry of the Environment. PM10 concentrations and the number of patients from each of 143 administrative dongs (sub-municipal level administrative units) of the city of Daegu were obtained using spatial analysis. The patient distribution and PM10 concentration were mapped for comparison, and their relationship was examined using scatter plot, regression analysis, and the independent sample t-test. RESULTS: The number of patients with conjunctivitis and keratitis was significantly higher in the regions of the top 20% areas than the bottom 20% areas in terms of PM10 concentration. The distribution of PM10 concentration and number of patients was visually similar on the map. The concentration of PM10 and the number of patients showed a dose-response relationship. When the concentrations of other air polluta9nts were controlled for, the numbers of conjunctivitis and keratitis patients were 0.04 per 1000 ER patients and 0.10 per 1000 ER patients, respectively. CONCLUSION: As PM10 is associated with the prevalence of conjunctivitis and keratitis, measures to reduce particulate matter through environmental methods are needed.

Relationship between postural instability and subcortical volume loss in Alzheimer's disease.

The relationship between postural instability and subcortical structure in AD has received less attention. The aims of this study were to assess whether there are differences in the ability to control balance between Alzheimer's disease (AD) and controls, and to investigate the association between subcortical gray matter volumes and postural instability in AD.We enrolled 107 consecutive AD patients and 37 controls. All participants underwent detailed neuropsychological evaluations, T1-weighted MRI at 3 T, and posture assessment using computerized dynamic posturography. We segmented the volumes of 6 subcortical structures of the amygdala, thalamus, caudate nucleus, putamen, globus pallidus and nucleus accumbens, and of hippocampus, using the FMRIBs integrated registration and segmentation tool.All subcortical structures, except for the globus pallidus, were smaller in AD compared with controls on adjusting for age and gender. Falling frequencies in unilateral stance test (UST) and composite scores in sensory organization test (SOT) were worse in AD than in controls. The motor control test did not reveal any differences between groups. On subgroup analyses in AD, the groups with poor performance in UST or SOT exhibited significantly reduced nucleus accumbens and putamen volumes, and nucleus accumbens volume, respectively. The smaller volume of the nucleus accumbens was associated with postural instability in AD (OR [95% CI] 17.847 [2.59-122.80] for UST, 42.827[6.06-302.47] for SOT, all P < .05).AD patients exhibited reduced ability to control balance compared with controls, and this postural instability was associated with nucleus accumbens volume loss. Furthermore, cognitive dysfunction was more prominent in the group with severe postural instability.

Effectiveness of participatory training for the promotion of work-related health and safety among Korean farmers.

This study was conducted to explore the effectiveness of participatory training for promoting farmer's health and reducing agricultural work-related injuries. Candidates for this study included 595 farmers in 8 rural villages of South Korea. The one-day course participatory training was administered to 217 (36.5%) farmers and included an action-checklist, a good example presentation, and group discussion. The follow-up visit to participants' houses and farms was performed after 1 to 3 months. A direct interview survey was administered pre- and post-trainings. The total number of proposed action plans for the improvement of working condition was 620. It was observed that 61.5% of action plans (72.2% of short term and 41.3% of long term plans) were completely implemented. In regards to health and safety indices, the proportion of current smokers was reduced from 29.8% to 25.3% in the group that underwent training. The pesticide intoxication was reduced from 16.1% to 4.8% in participants that underwent training. However, the agricultural injury rate was unchanged in both groups. This study reports significant beneficial effects of participatory training in the agriculture sector in Korea.

Discrepancy between frequency domain optical coherence tomography and intravascular ultrasound in human coronary arteries and in a phantom in vitro coronary model.

BACKGROUND: This purpose of this study is to evaluate, concomitantly with quantitative coronary angiography (QCA), the potential discrepancy between frequency domain optical coherence tomography (FD-OCT) and intravascular ultrasound (IVUS) measurements in a phantom coronary model and in human coronary arteries within and outside stented segments. METHODS: FD-OCT and IVUS images sequentially obtained from a phantom coronary model and 57 stented human coronary arteries were compared between each other and with QCA. RESULTS: Lumen area (LA) by IVUS was 10.1% larger (6.43±0.09mm(2)) while by FD-OCT was similar (5.78±0.09mm(2)) to actual phantom LA (5.72mm(2)); IVUS vs. FD-OCT stent area (SA) was 4.2% larger. In human coronary artery, diameter by QCA was smaller than by IVUS and OCT in reference (by 10.5% and 3.5%, both p<0.001) and stented (3.6%, p<0.001; and 1.7%, p=0.012) segments. IVUS vs. FD-OCT distal reference LA was significantly larger (6.19±2.18mm(2) vs. 5.49±2.49mm(2), p<0.001, respectively), and SA was numerically larger (7.42±2.28mm(2) vs. 7.22±2.48mm(2), p=0.059) with larger discrepancy in reference (11.3%) than stented (2.7%) segments. IVUS vs. FD-OCT correlation for diameter was significantly higher for stented than reference segments (R(2)=0.8670 vs. 0.7351, p=0.047), while numerically higher for area (R(2)=0.8663 vs. 0.7806, p=0.157). CONCLUSIONS: In phantom model and human coronary arteries, IVUS vs. FD-OCT measurements were larger, particularly in non-stented than stented segments, and diameter was smaller by QCA vs. IVUS or FD-OCT. Despite undefined clinical significance, said discrepancy warrants consideration.

Factors related to heart rate variability among firefighters.

OBJECTIVES: The aim of this study was to investigate factors associated with heart rate variability in firefighters working in a metropolitan city in South Korea. METHODS: Self-administered questionnaires including Korean Occupational Stress Scale (KOSS) as well as surveys collecting socio-demographic characteristics and work-related factors were given to 962 firefighters. After exclusion for missing data, 645 firefighters were included, and analysis of covaiance adjusted for the general risk factors and job characteristics were used to assess the relationship between heart rate variability and associated factors. RESULTS: SDNN and RMSSD and were decreased in the area of occupational climate of the group with high job stress (p = 0.027, p = 0.036). HF(ln) was decreased in the area of organizational system and occupational climate of the group with high stress that statistically significant level (p = 0.034, p = 0.043). CONCLUSIONS: Occupational climate and organizational system are associated with reduction of heart rate variability. Preventive medical care plans for cardiovascular disease of firefighters through the analysis and evaluation of job stress factors are needed.

Anti-cancer effect of N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2,3-dihydronaphtho[1,2-b]furan-2-carboxamide, a novel synthetic compound.

Naphthofuran compounds have been known to regulate HNF 4α which is associated with proliferation, progression and metastasis of HCC. In this study, we investigated whether N-(3,5-bis(trifluoromethyl)phenyl)-5-chloro-2,3-dihydronaphtho[1,2-b]furan-2-carboxamide (NHDC), a novel synthetic naphthofuran compound inhibits liver tumor growth through activation of HNF 4α. Treatment with different concentrations (1-10.8 µM) of NHDC for various periods (0-72 h) inhibited liver cancer cells (HepG2, Hep3B) growth as well as colony formation followed by induction of apoptosis in a concentration dependent manner. NHDC also induced expression of the apoptosis regulating genes as well as inhibiting the action of STAT3. These inhibitory effects were associated with enhancement of expression and DNA binding activity of HNF 4α. In vivo study confirmed that liver tumor growth was prevented with NHDC (5 mg/kg), and its effect was also related with inhibition of STAT3 pathway through enhancement of expression and DNA binding activity of HNF 4α. Moreover, siRNA of HNF 4α abolished NHDC-induced cell growth inhibition as well as DNA binding activity and phosphorylation of STAT3. Pull down assay docking prediction analysis proved that NHDC directly binds to hydrophobic fatty acid ligand binding site of HNF 4α. A novel naphthofuran compound, NHDC inhibited liver tumor growth by inactivating of STAT3 through direct biding to HNF 4α.

Minnesota multiphasic personality inventory as related factor for post traumatic stress disorder symptoms according to job stress level in experienced firefighters: 5-year study.

OBJECTIVES: As first responders to an increasing number of natural and manmade disasters, active-duty firefighters are at increased risk for physical and psychiatric impairment as reflected by high rates of posttraumatic stress disorder (PTSD). Because little is known about related factor with PTSD according to job stress level among firefighters, we assessed utility of the Minnesota Multiphasic Personality Inventory (MMPI) using 5-year medical surveillance. METHODS: Data were analyzed from 185 male firefighters without psychiatric disease history and who at assessments in 2006 and 2011 completed all questionnaires on personal behaviors (including exercise, drinking and smoking habits) and job history (including job duration and department). MMPI, Events Scale-Revised-Korean version (IES-R-K) and Korean Occupational Stress Scale-Short Form (KOSS-SF) were used to screen for personality trait, PTSD symptom presence and job stress level, respectively. IES-R-K subgroups were compared using two-sample t- and χ2 tests, and factors influencing IES-R-K according to KOSS-SF were determined using uni- and multivariate logistic regression. RESULTS: Mean age and job duration were higher in PTSD-positive than negative groups. In multivariate analysis, increased PTSD risk was associated with: job duration (Odds ratio (OR) = 1.064, 95 % CI 1.012-1.118) for firefighters overall; masculinity-femininity (OR = 5.304, 95 % CI 1.191-23.624) and job duration (OR = 1.126, 95 % CI 1.003-1.265) for lower job stress level; and social introversion (OR = 3.727, 95 % CI 1.096-12.673) for higher job stress level. CONCLUSIONS: MMPI relates with PTSD according to job stress level among experienced firefighters. Masculinity-femininity and social introversion were the strongest related factor for PTSD symptom development in low and high job stress levels, respectively.

Usefulness of combined intravascular ultrasound parameters to predict functional significance of coronary artery stenosis and determinants of mismatch.

AIMS: Efficacy of combined intravascular ultrasound (IVUS) parameters in functional significance prediction and discrepancy between IVUS and fractional flow reserve (FFR) have not been well defined. This study therefore aimed to: 1) evaluate the diagnostic accuracy of combined IVUS parameters, namely minimal lumen area (MLA) and percent plaque burden (%PB), in functional significance prediction of coronary artery stenosis; and 2) define factors that affect the relation between FFR value and IVUS parameters. METHODS AND RESULTS: At 11 international centres, IVUS and FFR measurements were concurrently performed in 945 major epicardial coronary artery lesions (886 patients). Functional significance was defined as FFR ≤0.8. MLA and FFR correlated weakly (r=0.289, p<0.001). Diagnostic accuracy of MLA ≤4.0 mm2, %PB >70% and their combination were 50%, 47% and 51%, respectively, with similar area under the curve (AUC) of 0.561, 0.511 and 0.516, respectively. The best cut-off values (BCV) were MLA ≤3.0 mm2 and %PB >75%, with accuracy of 60% for MLA, 50% for %PB and 56% for their combination, and AUC of 0.618, 0.511 and 0.533, respectively. MLA BCV ≤3.0 mm2 had higher predictive power than %PB BCV >75% or their combination. Independent predictors of functional significance were male gender (odds ratio 1.76 [95% confidence interval: 1.19-2.62]), left ventricular ejection fraction (LVEF, 0.98 [0.96-0.99]), LAD lesion (2.52 [1.73-3.67]), reference vessel diameter (0.60 [0.41-0.86]), lesion length (1.04 [1.02-1.06]) and MLA (0.79 [0.69-0.92]). False negative lesion incidence was 24.4% in association with race (for Asians, 0.391 [0.219-0.698]), LAD lesion (2.677 [1.709-4.191]) and LVEF (0.977 [0.957-0.997]). False positive lesion incidence was 17.0% in association with non-LAD lesion (2.444 [1.620-3.686]). CONCLUSIONS: Combined IVUS parameters did not improve the accuracy of functional significance prediction. Discrepancy between IVUS and FFR, which was not rare, should be taken into account in clinical decision making.

Characteristics of function-anatomy mismatch in patients with coronary artery disease.

BACKGROUND AND OBJECTIVES: Coronary lesions with mismatched functional and anatomical significance are not uncommon. We assessed the accuracy and predictors of mismatch between fractional flow reserve (FFR) and quantitative coronary angiography (QCA) analyses in patients with coronary lesions. SUBJECTS AND METHODS: A total of 643 lesions with pre-interventional FFR and QCA measurements were consecutively enrolled and divided into four groups using FFR ≤0.80 and percent diameter stenosis (%DS) ≥50% as cutoffs for functional and anatomical significance, respectively. Accordingly, FFR >0.80 and DS ≥50%, and FFR ≤0.80 and DS <50% defined false-positive (FP) and false-negative (FN) lesions, respectively. RESULTS: Overall, 40.4% (260/643) of the lesions were mismatched, and 51.7% (218/414) and 18.3% (42/229) were FP and FN lesions, respectively. In a multivariate analysis, independent predictors of FP were non-left anterior descending artery location {odds ratio (OR), 0.36; 95% confidence interval (CI), 0.28-0.56; p<0.001}, shorter lesion length (OR, 0.96; 95% CI, 0.95-0.98; p<0.001), multi-vessel disease (OR, 0.47; 95% CI, 0.30-0.75; p=0.001), and larger minimal lumen diameter by QCA (OR, 2.88; 95% CI,1.65-5.00; p<0.001). Independent predictors of FN were multi-vessel disease (OR, 1.82; 95% CI, 1.24-5.27; p=0.048), aging (OR, 0.96; 95% CI, 0.93-0.99; p=0.034), smoking (OR, 0.36; 95% CI, 0.14-0.93; p=0.034), and smaller reference vessel diameter by QCA (OR, 0.30; 95% CI, 0.10-0.87; p=0.026). CONCLUSION: A mismatch between FFR and angiographic lesion severity is not rare in patients with coronary artery disease; therefore, an angiography-guided evaluation could under- or over-estimate lesion severity in specific lesion subsets.

Long-term outcomes of simple crossover stenting from the left main to the left anterior descending coronary artery.

BACKGROUND/AIMS: Although complex bifurcation stenting in patients with non-left main (LM) bifurcation lesions has not yielded better clinical outcomes than simpler procedures, the utility of complex bifurcation stenting to treat LM bifurcation lesions has not yet been adequately explored. METHODS: In the present study, patients who underwent LM-to-left anterior descending (LAD) coronary artery simple crossover stenting to treat significant de novo distal LM or ostial LAD disease, in the absence of angiographically significant ostial left circumflex (LCX) coronary artery disease, were consecutively enrolled. The frequencies of 3-year major adverse cardiovascular events (MACEs; cardiac death, myocardial infarction, and target lesion revascularization), were analyzed. RESULTS: Of 105 eligible consecutive patients, only 12 (11.4%) required additional procedures to treat ostial LCX disease after main vessel stenting. The mean percentage diameter of ostial LCX stenosis increased from 22.5% ± 15.2% to 32.3% ± 16.3% (p < 0.001) after LM-to-LAD simple crossover stenting. The 3-year incidence of MACEs was 9.7% (cardiac death 2.2%; myocardial infarction 2.2%; target lesion revascularization 8.6%), and that of stent thrombosis 1.1%. Of seven cases (7.5%) requiring restenosis, pure ostial LCX-related repeat revascularization was required by only two. CONCLUSIONS: Simple crossover LM-to-LAD stenting without opening of a strut on the LCX ostium was associated with acceptable long-term clinical outcomes.

Preclinical efficacy and mechanisms of mesenchymal stem cells in animal models of autoimmune diseases.

Mesenchymal stem cells (MSCs) are present in diverse tissues and organs, including bone marrow, umbilical cord, adipose tissue, and placenta. MSCs can expand easily in vitro and have regenerative stem cell properties and potent immunoregulatory activity. They inhibit the functions of dendritic cells, B cells, and T cells, but enhance those of regulatory T cells by producing immunoregulatory molecules such as transforming growth factor-ß, hepatic growth factors, prostaglandin E2, interleukin-10, indolamine 2,3-dioxygenase, nitric oxide, heme oxygenase-1, and human leukocyte antigen-G. These properties make MSCs promising therapeutic candidates for the treatment of autoimmune diseases. Here, we review the preclinical studies of MSCs in animal models for systemic lupus erythematosus, rheumatoid arthritis, Crohn's disease, and experimental autoimmune encephalomyelitis, and summarize the underlying immunoregulatory mechanisms.

Pulmonary function decline in firefighters and non-firefighters in South Korea.

OBJECTIVES: The purpose of this study was to evaluate and compare changes to pulmonary function among firefighters and non-firefighters who were exposed to harmful substances in their work environments. METHODS: Firefighters (n = 322) and non-firefighters (n = 107) in Daegu who received a pulmonary function test in 2008 and 2011 as well as a regular health examination were included. Repeated measures ANOVA was performed to evaluate the pulmonary function of the two groups over the three-year period. RESULTS: After adjusting for age, height, body mass index, duration of exposure, physical activity, and smoking, which were statistically different between the two groups and known risk factors of pulmonary function, the forced expiratory volume in one s FEV1, forced vital capacity FVC, and FEV1/FVC% over the 3 year period were significantly lower among firefighters compared with non-firefighters. CONCLUSIONS: Evaluating the working environment of firefighters is difficult; however, our study revealed that pulmonary function declined in firefighters. Thus, more effort should be made to prevent and manage respiratory diseases early by preforming strict and consistent pulmonary function tests in firefighters.

Factors Related to Sleep Disorders among Male Firefighters.

OBJECTIVES: The aim of this study was to investigate factors associated with sleep disorders in male firefighters working in a metropolitan city in South Korea. METHODS: Self-administered questionnaires including the Nordic Musculoskeletal Questionnaire, Korean Occupational Stress Scale-Short Form, Psychosocial Well-Being Index-Short Form, Pittsburg Sleep Quality Index, and Beck-Depression Inventory-2 as well as surveys collecting socio-demographic characteristics and work-related factors were given to 730 male firefighters. After exclusion for missing data, 657 male firefighters were included, and logistic regression analysis adjusted for the work-related factors, psychosocial factors, and general risk factors were used to assess the relationship between sleep disorders and associated factors. RESULTS: The prevalence of sleep disorders was 48.7%. Shift work (adjusted OR 1.58, 95% CI = 1.02-2.45), musculoskeletal symptoms (adjusted OR 2.89, 95% CI = 2.02-4.14), and depression (adjusted OR 7.04 95% CI = 4.03-12.30) were associated with sleep disorders. CONCLUSIONS: Musculoskeletal symptoms, shift work, and depression are associated with sleep disorders. Integrated health management is needed to promote good sleep quality among firefighters.

Preclinical and clinical studies on cytokine-induced killer cells for the treatment of renal cell carcinoma.

Renal cell carcinoma (RCC) is the most common malignancy of adult human kidney, which accounts for more than 2 % of all cancers. RCC generally does not respond well to conventional chemotherapy and radiotherapy. Cytokine-induced killer (CIK) cells are ex vivo activated lymphocytes with potent activity against various tumors and minimal side effects. Here, we summarize the data on preclinical and clinical efficacy of CIK cells for RCC treatment. Our preclinical data show that CIK cells have potent anti-tumor activity in vitro and in an in vivo nude mouse xenograft model. Clinical studies for the treatment of RCC patients indicate that CIK cell therapy can induce favorable responses with no serious side effects. These studies suggest that CIK cells may become a valuable strategy for the treatment of patients with RCC.

Fever after primary percutaneous coronary intervention in ST-segment elevation myocardial infarction is associated with adverse outcomes.

BACKGROUND: Fever is a common finding after primary percutaneous coronary intervention (PPCI) in patients with ST-segment elevation myocardial infarction (STEMI). However, its prognostic value is not validated yet. OBJECTIVES: This study sought to evaluate the impact of fever after PPCI in STEMI on adverse clinical outcomes. METHODS: Five hundred fourteen consecutive patients who underwent PPCI due to STEMI were enrolled. Body temperature (BT) was checked every 6 h for 5 days after PPCI. Patients were divided into two groups according to the highest quartile of peak BT; peak BT≤37.6 °C (control group) and peak BT>37.6 °C (fever group). Rates of 1-year major adverse cardiovascular events (MACE; death, myocardial infarction, any revascularization) were compared. RESULTS: The prevalence of fever group (peak BT>37.6 °C) was 24.7% (127/514). White blood cell count, highly sensitive C-reactive protein and serum cardiac troponin I level were higher in fever group than control group (12,162±4199/µL vs. 10,614±3773/µL, p<0.001; 22.9±49.4 mg/L vs. 7.4±2.5 mg/L, p=0.001, 16.7±36.9 ng/dl vs. 8.70±26.2 ng/dl, p=0.027, respectively). The frequency of a history of previous myocardial infarction and left ventricular ejection fraction was lower in fever group (0.0% vs. 4.7%, p=0.010; 47±8 % vs. 49±9 %, p=0.002, respectively). There was no significant difference in angiographic characteristics between 2 groups. 1-year MACE rates were higher in fever group (11.0% vs. 4.7%, p=0.010). Multivariate analysis revealed fever (OR 2.358, 95% CI 1.113-4.998, p=0.025), diabetes mellitus as risk factor (2.227, 1.031-4.812, 0.042), and left anterior descending artery as infarct related artery (2.443, 1.114-5.361, 0.026) as independent predictors for 1-year MACE. CONCLUSIONS: Fever after PPCI in patients with STEMI is frequently developed and it can predict adverse clinical outcome.

Correlations between Janus kinase 2 V617F allele burdens and clinicohematologic parameters in myeloproliferative neoplasms.

BACKGROUND: This study evaluated potential correlations between the allele burden of the Janus kinase 2 (JAK2) V617F mutation and clinicohematologic characteristics in patients with myeloproliferative neoplasms (MPN). METHODS: Clinical and hematologic features were reviewed for 103 MPN patients, including patients with polycythemia vera (PV, 22 patients), essential thrombocythemia (ET, 64 patients), and primary myelofibrosis (PMF, 17 patients). JAK2 V617F allele status and allele burdens were measured by allele-specific PCR and pyrosequencing, respectively. RESULTS: The JAK2 V617F mutation was detected in 95.5%, 68.8%, and 52.9% of PV, ET, and PMF patients, respectively. JAK2 V617F-positive ET patients were significantly older and exhibited higher neutrophil fractions, a higher frequency of thrombotic events, and a higher myelofibrosis rate than JAK2 V617F-negative patients (P <0.05). PV patients carried the highest mean T allele burden (66.0%±24.9%) compared with ET (40.5%±25.2%) and PMF patients (31.5%±37.0%) (P =0.00). No significant correlations were detected between V617F allele burden and patient age, white blood cell count, Hb, Hct, or the platelet count for PV, ET, or PMF patients. ET patients with organomegaly had a higher JAK2 V617F allele burden (53.4%±23.7%) than patients without organomegaly (35.6%±24.3%) (P =0.03). CONCLUSIONS: The JAK2 V617F mutational status and its allele burden correlate with the clinicohematologic phenotypes of ET patients, including older age, higher neutrophil count, and greater rates of organomegaly, thrombotic events, and myelofibrosis. For PV and PMF patients, larger-scale studies involving more MPN patients are needed.

Hearing effects from intermittent and continuous noise exposure in a study of Korean factory workers and firefighters.

BACKGROUND: South Korea and surrounding countries in East Asia are believed to have the highest proportion in the world of high frequency hearing loss due to occupational noise exposure, yet there has been limited information published in international journals, and limited information for control of noise in local workplaces beyond strategies from western countries. We exploit medical surveillance information from two worker groups to enhance local knowledge about noise-induced hearing loss and explore the possible importance of shift work to risk. METHODS: Four-years of hearing data were evaluated for 81 male farm machine factory workers and 371 male firefighters who had successfully completed a health examination and questionnaires for the duration of the study period. The averages of hearing thresholds at 2, 3, and 4 kHz were used as the primary end-point for comparison. Repeat measure analysis adjusted for age, exposure duration and smoking status was used to measure the difference in hearing threshold between the two groups. RESULTS: Noise levels were measured in the factory at a mean of 82 dBA, with a range of 66-97. No concurrent measurements were taken for the firefighters, but historic comparison values showed a wider range but a similar mean of 76-79 dBA. Although losses during follow-up were negligible, the factory workers had significantly (P < 0.0001) more hearing loss at the baseline of the study than the firefighters in both ears at 2, 3, and 4 kHz, adjusted for age, duration of employment and smoking status. Among those with 10 years of employment, mean losses at these frequencies among the factory workers fell into the impairment range (> 25 dB loss). Firefighters also showed increased losses associated with longer exposure duration, but these were significantly less marked. Losses at lower frequencies (< or = 1 kHz) were negligible in both groups. CONCLUSIONS: Korean work environments with continuous noise exposure in the measured range should consider implementation of a hearing conservation program. Further evaluation of hearing loss in workers exposed to irregular or intermittent high noise levels, such as firefighters, is also warranted.

Functional SYNTAX score for risk assessment in multivessel coronary artery disease.

OBJECTIVES: This study was aimed at investigating whether a fractional flow reserve (FFR)-guided SYNTAX score (SS), termed "functional SYNTAX score" (FSS), would predict clinical outcome better than the classic SS in patients with multivessel coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). BACKGROUND: The SS is a purely anatomic score based on the coronary angiogram and predicts outcome after PCI in patients with multivessel CAD. FFR-guided PCI improves outcomes by adding functional information to the anatomic information obtained from the angiogram. METHODS: The SS was prospectively collected in 497 patients enrolled in the FAME (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) study. FSS was determined by only counting ischemia-producing lesions (FFR ≤ 0.80). The ability of each score to predict major adverse cardiac events (MACE) at 1 year was compared. RESULTS: The 497 patients were divided into tertiles of risk based on the SS. After determining the FSS for each patient, 32% moved to a lower-risk group as follows. MACE occurred in 9.0%, 11.3%, and 26.7% of patients in the low-, medium-, and high-FSS groups, respectively (p < 0.001). Only FSS and procedure time were independent predictors of 1-year MACE. FSS demonstrated a better predictive accuracy for MACE compared with SS (Harrell's C of FSS, 0.677 vs. SS, 0.630, p = 0.02; integrated discrimination improvement of 1.94%, p < 0.001). CONCLUSIONS: Recalculating SS by only incorporating ischemia-producing lesions as determined by FFR decreases the number of higher-risk patients and better discriminates risk for adverse events in patients with multivessel CAD undergoing PCI.