Prognostic Molecular Biomarkers in Breast Cancer Lesions with Non-Mass Enhancement on MR.

Clustered ring enhancement (CRE) is a new lexicon for non-mass enhancement (NME) of breast MR in the 5th BIRADS, indicating a high suspicion of malignancy. We wonder if the presence of CRE correlates with expression of prognostic molecular biomarkers of breast cancer. A total of 58 breast lesions, which MRI reported with NME, were collected between July 2013 and December 2018. The patterns of enhancement including CRE were reviewed and the pathological results with expression of molecular biomarkers were collected. The association between MRI NME, pathological, and IHC stain findings were investigated under univariate analysis. A total of 58 breast lesions were pathologically proven to have breast cancer, comprising 31 lesions with CRE and 27 lesions without CRE on breast MRI. The expression of the estrogen receptor (ER) (p = 0.017) and the progesterone receptor (PR) (p = 0.017) was significantly lower in lesions with CRE as compared with those without CRE. The expression of Ki-67 (≥25%) was significantly higher in lesions with CRE (p = 0.046). The lesions with CRE had a lower expression ratio of ER (50.71 ± 45.39% vs. 74.26 ± 33.59%, p = 0.028). Our study indicated that lesions with CRE may possess different features from those without CRE in molecular expression, bearing a more aggressive behavior.

GARP Polymorphisms Associated with Susceptibility to House Dust Mite-Sensitized Persistent Allergic Rhinitis in a Chinese Population.

Background: Genetic variants in GARP (also known as LRRC32) have been reported to have significant associations with asthma and eczema in special populations, but little is known about allergic rhinitis. This study purposes to evaluate the association of single nucleotide polymorphisms (SNPs) in GARP with house dust mite (HDM)-sensitized persistent allergic rhinitis (PER) in a population of Han Chinese. Methods: In this hospital-based case-control study, 534 HDM-sensitized PER patients and 451 healthy controls were recruited from East China. In this population, six SNPs in GARP were identified. Serum total and specific IgE levels were measured with ImmunoCAP. Secondary structure and minimum free energy were predicted by RNAfold. Results: rs79525962 was associated with the risk of HDM-sensitized PER (P < 0.05). The individuals with CT+TT genotype demonstrated a higher risk of HDM-sensitized PER than those with CC genotype (adjusted OR = 1.393, 95% CI = 1.019-1.904). The homozygous genotype CC of rs3781699 rendered a lower risk of HDM-sensitized PER than the wild-type genotype AA (adjusted OR = 0.646, 95% CI = 0.427-0.976); however, the genotype and allele frequencies of rs3781699 demonstrated no associations with HDM-sensitized PER (P > 0.05). rs79525962 increased the risk of HDM-sensitized PER in the subgroup aged ≥16 years (adjusted OR = 1.745, 95% CI = 1.103-2.760), and this high risk was also found in the females (adjusted OR = 1.708, 95% CI = 1.021-2.856). The G-C haplotype of rs1320646-rs3781699 rendered a lower risk of HDM-sensitized PER than the common haplotype G-A (adjusted OR = 0.819, 95% CI = 0.676-0.993). The secondary structure of GARP altered in response to different genotypes of rs79525962 and rs3781699. Conclusion: SNP rs79525962 in the GARP gene marks a risk locus of HDM-sensitized PER in Chinese Hans.

TLR Signaling Pathway Gene Polymorphisms, Gene-Gene and Gene-Environment Interactions in Allergic Rhinitis.

Background: Allergic rhinitis (AR) is a nasal inflammatory disease resulting from a complex interplay between genetic and environmental factors. The association between Toll-like receptor (TLR) signaling pathway and environmental factors in AR pathogenesis remains to be explored. This study aims to assess the genetic association of AR with single nucleotide polymorphisms (SNPs) in TLR signaling pathway, and investigate the roles of gene-gene and gene-environment interactions in AR. Methods: A total of 452 AR patients and 495 healthy controls from eastern China were enrolled in this hospital-based case-control study. We evaluated putatively functional genetic polymorphisms in TLR2, TLR4 and CD14 genes for their association with susceptibility to AR and related clinical phenotypes. Interactions between environmental factors (such as traffic pollution, residence, pet keeping) and polymorphisms with AR were examined using logistic regression. Models were stratified by genotype and interaction terms, and tested for the significance of gene-gene and gene-environment interactions. Results: In the single-locus analysis, two SNPs in CD14, rs2563298 (A/C) and rs2569191 (C/T) were associated with a significantly decreased risk of AR. Compared with the GG genotype, the GT and GT/TT genotypes of TLR2 rs7656411 (G/T) were associated with a significantly increased risk of AR. Gene-gene interactions (eg, TLR2 rs7656411, TLR4 rs1927914, and CD14 rs2563298) was associated with AR. Gene-environment interactions (eg, TLR4 or CD14 polymorphisms and certain environmental exposures) were found in AR cases, but they were not significant after Bonferroni correction. Conclusion: The genetic polymorphisms of TLR2 and CD14 and gene-gene interactions in TLR signaling pathway were associated with susceptibility to AR in this Han Chinese population. However, the present results were limited to support the association between gene-environment interactions and AR.

Pyogenic Liver Abscess Risk in Patients With Newly Diagnosed Type 2 Diabetes Mellitus: A Nationwide, Population-Based Cohort Study.

Background: To date, no comprehensive epidemiological study exists on pyogenic liver abscess (PLA) risk in patients with newly diagnosed type 2 diabetes mellitus (T2DM) worldwide. Methods: We conducted a retrospective cohort study by using data from Taiwan National Health Insurance Research Database (NHIRD) to examine the association between newly diagnosed T2DM and PLA. The T2DM cohort included patients newly diagnosed as having T2DM (ICD-9-CM:250) from 2000 to 2009, with follow-up until December 31, 2011. The comparison cohort was then recruited through 1:4 random frequency matching with the T2DM cohort. Finally, the adjusted hazard ratios for PLA were compared between the T2DM and comparison cohorts, which included 44,728 patients with T2DM and 178,912 patients without DM respectively. Results: In T2DM cohort, 166 patients were diagnosed as having PLA (incidence rate = 5.87 per 10,000 person-years) and in comparison cohort, 238 patients were diagnosed as having PLA (incidence rate = 2.06 per 10,000 person-years). The T2DM cohort exhibited higher PLA risk than did the comparison cohort (hazard ratio = 2.83, 95% confidence interval = 2.32-3.46). Furthermore, the adjusted hazard ratio for PLA risk in T2DM cohort was the highest in those who were younger, man and with duration of DM <2 years. In the T2DM cohort, the most common PLA causative agent was Klebsiella pneumonia (KP). In addition, PLA risk was high in T2DM patients with gallstone and cholecystitis. Compared with comparison cohort, patients with T2DM prescribed acarbose has a lower PLA risk, however glyburide significantly increased PLA risk in T2DM cohort. Conclusion: In patients with newly diagnosed T2DM, PLA risk was high and acarbose might reduce PLA risk.

Polymorphisms in MicroRNA Target Sites of TGF-ß Signaling Pathway Genes and Susceptibility to Allergic Rhinitis.

BACKGROUND: The polymorphisms inside microRNA target sites locating in the 3'-UTR region may introduce the micro-RNA-binding changes, which may regulate the gene expression and correlate with the potential diseases. OBJECTIVES: We aimed to investigate whether the polymorphisms in microRNA target sites of transforming growth factor beta (TGF-ß) signaling pathway genes are associated with the susceptibility of mite-sensitized allergic rhinitis (AR) in a Han Chinese population. METHODS: In this case-control study, 454 AR patients and 448 healthy controls were recruited. Three HapMap single-nucleotide polymorphisms (SNPs) were mapped to putative microRNA recognition sites and genotyped by TaqMan allelic discrimination assay. RESULTS: The genotype and allele frequencies of 3 SNPs (rs1590 in TGFBR1; rs1434536 and rs17023107 in BMPR1B) showed lack of significant association with AR. However, in the subgroup analysis, the TG, GG, and TG/GG genotypes of rs1590 exhibited significantly increased risk of AR in the male subgroup (TG: adjusted OR = 1.57, 95% CI = 1.08-2.31; GG: adjusted OR = 1.76, 95% CI = 1.09-2.86; TG/GG: adjusted OR = 1.62, 95% CI = 1.13-2.33). The CT genotypes of rs17023107 might have potential to protect against AR in the patients age of <15 years (adjusted OR = 0.37, 95% CI = 0.14-0.95) and the males (adjusted OR = 0.48, 95% CI = 0.25-0.95). No significant association was found between SNPs and the total serum IgE level. CONCLUSIONS: In a Han Chinese population, stratified by age and gender, susceptibility to mite-sensitized AR may be associated with 2 SNPs (rs1590 and rs17023107) in microRNA target sites of TGF-ß signaling pathway genes.

Polymorphism -509C/T in TGFB1 Promoter Is Associated With Increased Risk and Severity of Persistent Allergic Rhinitis in a Chinese Population.

BACKGROUND: Polymorphism -509C/T in the promoter of transforming growth factor beta1 (TGFB1) gene is implicated in the pathogenesis of asthma. This polymorphism might also act to regulate the development of allergic rhinitis (AR). OBJECTIVES: To investigate whether -509C/T is associated with AR susceptibility and severity in a Han Chinese population. METHODS: The study enrolled 263 patients with persistent AR and 249 healthy controls. AR patients were classified as mild or moderate/severe AR groups according to the Allergic Rhinitis and its Impact on Asthma classification. TGFB1 gene polymorphism -509C/T was genotyped with polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum total Immunoglobulin E (IgE) and specific IgE levels were determined using an ImmunoCAP. RESULTS: Significant difference was found in the allele frequency of TGFB1 -509C/T between AR patients and healthy controls (P = .027) but not in the genotype frequency (P =.051). However, the genotype frequency of TGFB1 -509C/T showed significant difference between the mild AR group, the moderate/severe AR group, and the control group (P = .012); between the moderate/severe AR group and the control group (P =.036); between the mild AR group and the moderate/severe AR group (P = .038); but not between the mild AR group and the control group (P =.075). CONCLUSION: TGFB1 promoter polymorphism -509C/T may be associated with the susceptibility and the severity of persistent AR of Han Chinese, but the functional relationship still needs clarification.

Prolonged international normalized ratio and vascular injury at divisional level predict embolization failures of patients with iatrogenic renal vascular injuries.

Transcatheter arterial embolization (TAE), as an alternative to surgery for iatrogenic renal vascular injury (IRVI), may have unsatisfactory outcomes. Nonetheless, there is inadequate information regarding the predictors of TAE outcomes for IRVI in the literature. The aim of this retrospective study was to investigate the predictors of TAE outcomes for IRVI. Of 47 patients, none had major complications, 17 (36.2%) patients had minor complications, and none suffered significant renal function deterioration after TAE. Technical success and clinical success were 91.5% and 93.6%, respectively. Technical failure was associated with older age, thrombocytopenia, prolonged international normalized ratio (INR) and divisional IRVI. Clinical failure was associated with kidney failure, use of steroids, prolonged INR, and divisional IRVI. In addition, prolonged INR was a significant predictor of technical failure. This implies that aggressive measures to control the INR prior to TAE are warranted to facilitate technical success, and technical success could then be validated on post-TAE images. Furthermore, divisional IRVI was a predictor of clinical failure. Thus, divisional IRVI should undergo surgery first since TAE is prone to clinical failure. The avoidance of clinical failure is validated if divisional IRVI does not need further intervention.

Medical Monitoring for Occupational Asthma Among Toluene Diisocyanate Production Workers in the United States.

OBJECTIVE: The aim of this study was to describe a study of medical monitoring methods and lessons learned in detecting health outcomes in U.S. plants producing toluene diisocyanate (TDI). METHODS: A multidisciplinary team implemented a medical and environmental monitoring program in three TDI plants. RESULTS: Of 269 eligible workers, 197 (73%) participated and 42 (21%) met symptom and/or lung function criteria that would trigger evaluation for possible asthma over 5 years of data collection. Subsequent evaluation was delayed for most, and a web-based data collection system improved timeliness. CONCLUSION: Medical monitoring of TDI workers identified workers triggering further assessment per study protocol. Systems and/or personnel to ensure rapid follow-up are needed to highlight when triggering events represent potential cases of asthma needing further evaluation. Implementation of a research protocol requires resources and oversight beyond an occupational health program.

Incidence of Occupational Asthma and Exposure to Toluene Diisocyanate in the United States Toluene Diisocyanate Production Industry.

OBJECTIVE: This study examines asthma risk in facilities producing toluene diisocyanate (TDI). METHODS: A total of 197 workers were monitored from 2007 to 2012. TDI air concentrations were used to estimate exposures. RESULTS: The incidence of cases consistent with TDI-induced asthma was 0.009 per person-years (seven cases) or consistent with TDI-induced asthma or asthma indeterminate regarding work-relatedness was 0.012 (nine cases). Increased risk of cases consistent with TDI asthma was observed for cumulative (odds ratio [OR] = 2.08, 95% confidence interval [CI] 1.07 to 4.05) per logarithm parts per billion-years and peak TDI exposures (OR = 1.18, 95% CI 1.06 to 1.32) (logarithm parts per billion). There was a weak association with cumulative and peak exposures for decline of short-term forced expiratory volume in one second (FEV1). Asthma symptoms were associated with workers noticing an odor of TDI (OR 6.02; 95% CI 1.36 to 26.68). CONCLUSIONS: There is evidence that cumulative and peak exposures are associated with TDI-induced asthma.

Longitudinal and Cross-sectional Analyses of Lung Function in Toluene Diisocyanate Production Workers.

OBJECTIVE: The aim of this study was to investigate lung function among toluene diisocyanate (TDI) production workers. METHODS: One hundred ninety-seven U.S workers performed spirometry from 2006 through 2012. Results were compared within the study cohort and with U.S. population measures. A mixed-effects model assessed factors affecting repeated forced expiratory volume in 1 second (FEV1) measurements. RESULTS: The cohort's mean FEV1 and forced vital capacity (FVC) percent reference values, although greater than 90%, were significantly lower and the prevalence of abnormal spirometry (predominantly restrictive pattern) was significantly higher than in the U.S. POPULATION: Differences in lung function among workers with higher cumulative TDI exposure were in the direction of an exposure effect, but not significant. CONCLUSION: We found little evidence of an adverse effect of TDI exposure on longitudinal spirometry in these workers. The association between TDI exposure and the increasing prevalence of a restrictive pattern needs further exploration.

Suppression of Lipid Accumulation by Indole-3-Carbinol Is Associated with Increased Expression of the Aryl Hydrocarbon Receptor and CYP1B1 Proteins in Adipocytes and with Decreased Adipocyte-Stimulated Endothelial Tube Formation.

This study investigated the effects of indole-3-carbinol (I3C) on adipogenesis- and angiogenesis-associated factors in mature adipocytes. The cross-talk between mature adipocytes and endothelial cells (ECs) was also explored by cultivating ECs in a conditioned medium (CM) by using I3C-treated adipocytes. The results revealed that I3C significantly inhibited triglyceride accumulation in mature adipocytes in association with significantly increased expression of AhR and CYP1B1 proteins as well as slightly decreased nuclear factor erythroid-derived factor 2-related factor 2, hormone-sensitive lipase, and glycerol-3-phosphate dehydrogenase expression by mature adipocytes. Furthermore, I3C inhibited CM-stimulated endothelial tube formation, which was accompanied by the modulated secretion of angiogenic factors in adipocytes, including vascular endothelial growth factor, interleukin-6, matrix metalloproteinases, and nitric oxide. In conclusion, I3C reduced lipid droplet accumulation in adipocytes and suppressed adipocyte-stimulated angiogenesis in ECs, suggesting that I3C is a potential therapeutic agent for treating obesity and obesity-associated disorders.

Small Airway Dysfunction and Abnormal Exercise Responses. A Study in Coal Miners.

RATIONALE: Coal mine dust exposure can cause symptoms and loss of lung function from multiple mechanisms, but the roles of each disease process are not fully understood. OBJECTIVES: We investigated the implications of small airway dysfunction for exercise physiology among a group of workers exposed to coal mine dust. METHODS: Twenty coal miners performed spirometry, first breathing air and then helium-oxygen, single-breath diffusing capacity, and computerized chest tomography, and then completed cardiopulmonary exercise testing. MEASUREMENTS AND MAIN RESULTS: Six participants meeting criteria for small airway dysfunction were compared with 14 coal miners who did not. At submaximal workload, miners with small airway dysfunction used a higher proportion of their maximum voluntary ventilation and had higher ventilatory equivalents for both O2 and CO2. Regression modeling indicated that inefficient ventilation was significantly related to small airway dysfunction but not to FEV1 or diffusing capacity. At the end of exercise, miners with small airway dysfunction had 27% lower O2 consumption. CONCLUSIONS: Small airway abnormalities may be associated with important inefficiency of exercise ventilation. In dust-exposed individuals with only mild abnormalities on resting lung function tests or chest radiographs, cardiopulmonary exercise testing may be important in defining causes of exercise intolerance.

Association of VDR and CYP2R1 Polymorphisms with Mite-Sensitized Persistent Allergic Rhinitis in a Chinese Population.

As recent studies have described an association between vitamin D and allergic rhinitis, we hypothesized that vitamin D pathway-related genes may be candidate genes for susceptibility to allergic rhinitis. Thus, we sought to evaluate whether polymorphisms in the vitamin D receptor (VDR) and CYP2R1 genes are associated with mite-sensitized persistent allergic rhinitis (PER) in a Han Chinese population. A hospital-based case-control study consisting of 519 patients with mite-sensitized PER and 447 healthy controls was conducted. Five single nucleotide polymorphisms (SNPs) in VDR and CYP2R1 were selected for genotyping. The genotype and allele frequencies of rs9729, rs2228570, rs1544410, and rs731236 in VDR as well as rs2060793 in CYP2R1 were not significantly associated with susceptibility to mite-sensitized PER. After stratification analyses, however, both the CT and CT/TT genotypes of rs2228570 in VDR exhibited a significantly decreased risk (CT: adjusted odds ratio (OR)=0.58, 95% confidence intervals (CI)=0.37-0.91; CT/TT: adjusted OR=0.61, 95% CI=0.40-0.93) of mite-sensitized PER, while the AA genotype of rs2060793 in CYP2R1 exhibited a significantly increased risk (adjusted OR=1.85, 95% CI=1.03-3.34) of PER in the age subgroup of <16 years old. Both the AG and AG/GG genotypes of rs731236 in VDR exhibited a significantly decreased risk (AG: adjusted OR=0.43, 95% CI=0.21-0.89; AG/GG: adjusted OR=0.46, 95% CI=0.23-0.94) of PER in the female subgroup. Analysis of the locus-locus interactions of VDR and CYP2R1 revealed two models that involved combined SNPs of VDR and CYP2R1 were statistically significant (P<0.05). Our data suggest that age and gender may have an impact on the association of three SNPs (rs2228570, rs731236, and rs2060793) in genes of the vitamin D pathway with the risk of mite-sensitized PER in this Chinese population. The VDR and CYP2R1 variants may be involved in genetic interactions in the pathogenesis of PER.

α-Naphthoflavone Increases Lipid Accumulation in Mature Adipocytes and Enhances Adipocyte-Stimulated Endothelial Tube Formation.

The aryl hydrocarbon receptor (AhR) is a ligand-activated factor that regulates biological effects associated with obesity. The AhR agonists, such as environmental contaminants 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and ß-naphthoflavone (BNF), inhibit preadipocyte differentiation and interfere with the functions of adipose tissue, whereas the antagonist may have opposite or protective effects in obesity. This study investigated the effects of α-naphthoflavone (α-NF), an AhR antagonist, on adipogenesis- and angiogenesis-associated factors in mature adipocytes and on cross-talk of mature adipocytes with endothelial cells (ECs). Besides, the roles of the AhR on lipid accumulation and on secretion of vascular endothelial growth factor were also determined by introducing siRNA of AhR. Differentiated 3T3-L1 cells were treated with α-naphthoflavone (α-NF) (1-5 µM) for 16 h. Lipid accumulation and the expressions of AhR-associated factors in the cells were determined. The interaction between adipocytes and ECs was investigated by cultivating ECs with conditioned medium (CM) from α-NF-treated mature adipocytes, followed by the determination of endothelial tube formation. The results showed that α-NF significantly increased triglyceride (TG) accumulation in mature adipocytes, which was associated with increased expression of hormone-sensitive lipase (HSL), estrogen receptor (ER), as well as decreased expression of AhR, AhR nuclear translocator (ARNT), cytochrome P4501B1 (CYP1B1), and nuclear factor erythroid-2-related factor (NRF-2) proteins. In addition, CM stimulated formation of tube-like structures in ECs, and α-NF further enhanced such stimulation in association with modulated the secretions of various angiogenic mediators by mature adipocytes. Similarly, increased TG accumulation and vascular endothelial growth factor (VEGF) secretion were observed in AhR-knockout cells. In conclusion, α-NF increased TG accumulation in mature adipocytes and enhanced mature adipocyte-stimulated tube formation in ECs, suggesting that the AhR may suppress obesity-induced adverse effects, and α-NF abolished the protective effects of the AhR.

Small mine size is associated with lung function abnormality and pneumoconiosis among underground coal miners in Kentucky, Virginia and West Virginia.

OBJECTIVES: To describe the prevalence of lung function abnormality and coal workers' pneumoconiosis (CWP) by mine size among underground coal miners in Kentucky, Virginia and West Virginia. METHODS: During 2005-2012, 4491 miners completed spirometry and chest radiography as part of a health surveillance programme. Spirometry was interpreted according to American Thoracic Society and European Respiratory Society guidelines, and radiography per International Labour Office standards. Prevalence ratios (PR) were calculated for abnormal spirometry (obstructive, restrictive or mixed pattern using lower limits of normal derived from National Health and Nutrition Examination Survey (NHANES) III) and CWP among workers from small mines (≤50 miners) compared with those from large mines. RESULTS: Among 3771 eligible miners, those from small mines were more likely to have abnormal spirometry (18.5% vs 13.8%, p<0.01), CWP (10.8% vs 5.2%, p<0.01) and progressive massive fibrosis (2.4% vs 1.1%, p<0.01). In regression analysis, working in a small mine was associated with 37% higher prevalence of abnormal spirometry (PR 1.37, 95% CI 1.16 to 1.61) and 2.1 times higher prevalence of CWP (95% CI 1.68 to 2.70). CONCLUSIONS: More than one in four of these miners had evidence of CWP, abnormal lung function or both. Although 96% of miners in the study have worked exclusively under dust regulations implemented following the 1969 Federal Coal Mine Safety and Health Act, we observed high rates of respiratory disease including severe cases. The current approach to dust control and provision of safe work conditions for central Appalachian underground coal miners is not adequate to protect them from adverse respiratory health effects.

Association study on ADAM33 polymorphisms in mite-sensitized persistent allergic rhinitis in a Chinese population.

BACKGROUND: The ADAM33 gene has been identified as a potentially important asthma candidate gene and polymorphisms in this gene have been shown to be associated with asthma and seasonal allergic rhinitis. OBJECTIVE: To assess whether the ADAM33 polymorphisms are associated with persistent allergic rhinitis (PER) due to house dust mites in a Chinese population. METHODS: In a hospital-based case-control study of 515 patients with mite-sensitized PER and 495 healthy controls, we genotyped seven single nucleotide polymorphisms (SNPs) in ADAM33. Serum levels of eosinophil cationic protein, total IgE and allergen-specific IgE against Dermatophagoides pteronyssinus and Dermatophagoides farinae were measured by the ImmunoCAP assays. RESULTS: In the single-locus analysis, three polymorphisms, rs3918392 (F1), rs528557 (S2) and rs2787093, were significantly associated with mite-sensitized PER. SNP S2 was associated with significantly increased risk both of asthmatic and nonasthmatic mite-sensitized PER. In the combined genotypes analysis, individuals with 2-4 risk alleles had a significantly higher risk of mite-sensitized PER (adjusted OR = 1.99, 95% CI = 1.50-2.62) than those with 0-1 risk alleles. Haplotype-based association analysis revealed that the ACAGCCT haplotype might have potential to protect against mite-sensitized PER (adjusted OR = 0.67; 95% CI = 0.49-0.90). CONCLUSIONS: Polymorphisms in the ADAM33 gene may contribute to susceptibility of mite-sensitized PER in this Chinese population.

Lung-function impairment among US underground coal miners, 2005 to 2009: geographic patterns and association with coal workers' pneumoconiosis.

OBJECTIVE: To investigate contemporary geographic distributions of lung-function impairment and radiographic evidence of coal workers' pneumoconiosis (CWP) and their associations. METHODS: From 2005 to 2009, 6373 underground coal miners completed a health survey, including spirometry testing and chest radiography. Coal workers' pneumoconiosis and progressive massive fibrosis were determined by NIOSH B readers, using the International Labour Office classification. Prevalences of CWP and spirometry less than lower normal limits were mapped by county, and their association assessed. RESULTS: The prevalences of abnormal spirometry results and CWP were 13.1% and 4.0%, respectively. Counties with elevated prevalences for both the outcomes were located in contiguous areas of southeastern Kentucky, western Virginia, southern West Virginia, and eastern Pennsylvania. Prevalence of abnormal spirometry results increases with increasing category of simple CWP and progressive massive fibrosis. CONCLUSIONS: Abnormal spirometry in coal miners is associated with CWP; these two health outcomes have similar geographic distributions.

Rapid decline in lung function in coal miners: evidence of disease in small airways.

BACKGROUND: Coal mine dust exposure can cause both pneumoconiosis and chronic airflow limitation. The contributions of various pathophysiologic mechanisms to dust-related lung function decrements remain unclear. METHODS: Clinical and physiological findings were assessed for 15 underground coal miners who had demonstrated accelerated FEV1 losses (decliners) over 6-18 years. Decliners' findings were evaluated in comparison to a group of 11 miners who had shown relatively stable lung function (referents) during the same period. RESULTS: At follow-up examination, the decliners showed significantly greater mean airway resistance (10.47 vs. 6.78 cmH2 O/L/s; P = 0.05) and more air trapping (RV/TLC = 37.5 vs. 29.1%; P < 0.01) compared to the referents. Decliners also demonstrated more evidence of small airways dysfunction and tended to have more bronchospasm than the referent group. Total lung capacity, lung compliance, diffusing capacity, and chest radiography did not differ significantly between the two groups. After cessation of mine dust exposures, the decliners' mean rate of FEV1 loss normalized. CONCLUSION: In a series of working coal miners, accelerated lung function declines were associated with air trapping and evidence of small airways dysfunction. A preventive benefit from controlling dust exposures was suggested.

Application of the revised Tumour Node Metastasis (TNM) staging system of clear cell renal cell carcinoma in eastern China: advantages and limitations.

This study was designed to evaluate whether the revised 2010 Tumour Node Metastasis (TNM) staging system could lead to a more accurate prediction of the prognosis of renal cell carcinoma (RCC) patients. A total of 1216 patients who had undergone radical nephrectomy or partial nephrectomy for RCC from 2003 to 2011 were enrolled. All of the patients had pathologically confirmed clear cell RCC (ccRCC). All cases were staged by both the 2002 and 2010 TNM staging systems after pathological review, and survival data were collected. Univariate and multivariate Cox regression models were used to evaluate cancer-specific survival (CSS) and progression-free survival (PFS) after surgery. Continuous variables, such as age and tumour diameter, were calculated as mean values and standard deviations (s.d.) or as median values. Survival was calculated by the Kaplan-Meier method, and the log-rank test assessed differences between groups. Statistically significant differences in CSS and PFS were noted among patients in T3 subgroups using the new 2010 staging system. Therefore, the revised 2010 TNM staging system can lead to a more accurate prediction of the prognosis of ccRCC patients. However, when using the revised 2010 staging system, we found that more than 92% of patients (288/313) with T3 tumours were staged in the T3a subgroup, and their survival data were not significantly different from those of patients with T2b tumours. In addition, T2 subclassification failed to independently predict survival in RCC patients.

Antiangiogenic activity of indole-3-carbinol in endothelial cells stimulated with activated macrophages.

The effect of indole-3-carbinol (I3C), a major indolic metabolite in cruciferous vegetables, on lipopolysaccharide (LPS)-activated macrophage-induced tube formation and its associated factors in endothelial EA hy926 cells was investigated. LPS significantly enhanced the capillary-like structure of endothelial cells (ECs) co-cultured with macrophages, but no such effect was observed in single-cultured ECs. I3C, on the other hand, suppressed such enhancement in concert with decreased secretions of vascular endothelial growth factor (VEGF), nitric oxide (NO), interleukin-6 (IL-6), and matrix metalloproteinases (MMPs). The results obtained from cultivating ECs with conditioned medium (CM) collected from macrophages suggested that both ECs and macrophages were inactivated by I3C. These results indicate that I3C from cruciferous vegetables may possess potential roles in preventing inflammation-associated angiogenic diseases.