Global untargeted and individual targeted plasma metabolomics of breast cancer recurrence modified by hormone receptors.

BACKGROUND: Breast cancer is a heterogeneous and complex etiological disease. Understanding perturbations of circulating metabolites could improve prognosis. METHODS: We recruited breast cancer patients from Kaohsiung Medical University (KMU) to perform untargeted (case-control design) and targeted (patient cohort) metabolomics analyses in the discovery and validation phases to evaluate interaction effects between clinical factors and plasma metabolites using multivariable Cox proportional hazards model. RESULTS: In the discovery phase, partial least squares-discriminant analysis (PLS-DA) showed that plasma metabolites were significantly different between recurrent and non-recurrent breast cancer patients. Metabolite set enrichment analysis (MSEA) and metabolomic pathway analysis (MetPA) showed that valine, leucine, and isoleucine degradation was the significant pathway, and volcano plot showed significant ten upregulated and two downregulated metabolites between recurrent and non-recurrent cases. Combined with receiver operating characteristic (ROC) curve and biological significance, creatine, valine, methionine, and mannose were selected for the validation phase. In this patient cohort with 41 new-recurrent vs. 248 non-recurrent breast cancer cases, followed for 720.49 person-years, compared with low level of valine, high valine level was significantly negatively associated with recurrent breast cancer (aHR: 0.36, 95% CI: 0.18-0.72, P = 0.004), especially in ER-negative and PR-negative status. There were interaction effects between valine and ER (Pinteraction = 0.006) as well as PR (Pinteraction = 0.002) on recurrent breast cancer. After Bonferroni correction, stratification effects between valine and hormone receptors were still significant. CONCLUSION: Our study revealed that plasma metabolites were significantly different between recurrent and non-recurrent patients, proposing therapeutic insights for breast cancer prognosis.

Association of blood lipid profiles and asthma: A bidirectional two-sample Mendelian randomization study.

BACKGROUND: Observational studies and meta-analyses have indicated associations between blood lipid profiles and asthma. However, the causal association is unknown. Therefore, this study investigated the causal relationship between blood lipid profiles and asthma using bidirectional Mendelian randomization analysis. METHODS AND MATERIALS: Our analyses were performed using individual data from the Taiwan Biobank and summary statistics from the Asian Genetic Epidemiology Network (AGEN). The causal estimates between all genetic variants, exposures of interest and asthma were calculated using an inverse-variance weighted method based on Taiwan Biobank data from 24,853 participants (mean age, 48.8 years; 49.8% women). Sensitivity analyses, including the weighted median, MR Egger regression, MR-PRESSO, mode-based estimate, contamination mixture methods, and leave-one-out analysis, were applied to validate the results and detect pleiotropy. RESULTS: In the inverse-variance weighted (IVW) analyses, we found evidence of a significant causal effect of an increased level of low-density lipoprotein cholesterol on asthma risk (ßIVW = 1.338, p = 0.001). A genetically decreased level of high-density lipoprotein cholesterol was also associated with asthma risk (ßIVW = -0.338, p = 0.01). We also found that an increased level of total cholesterol was associated with an increased risk of asthma (ßIVW = 1.343, p = 0.001). Several sensitivity analyses generated consistent findings. We did not find evidence to support the causality between asthma and blood lipid profiles in either direction. CONCLUSION: Our results supported the causal relationship between higher levels of LDL cholesterol and total cholesterol and lower levels of HDL cholesterol with an increased risk of asthma.

Cluster analysis of phenotypes, job exposure, and inflammatory patterns in elderly and nonelderly asthma patients.

BACKGROUND: Asthma has been identified as different phenotypes due to various risk factors. Age differences may have potential effects on asthma phenotypes. Our study aimed to identify potential asthma phenotypes among adults divided by age as either younger or older than 65 years. We also compared differences in blood granulocyte patterns, occupational asthmagens, and asthma control-related outcomes among patient phenotype clusters. METHODS: We recruited nonelderly (<65 years old) (n = 726) and elderly adults (≥65 years old) (n = 201) with mild-to-severe asthma. We conducted a factor analysis to select 17 variables. A two-step cluster analysis was used to classify subjects with asthma phenotypes, and a discriminant analysis was used to verify the classification of cluster results. RESULTS: There were three clusters with different characteristics identified in both the nonelderly and elderly asthmatic adults. In the nonelderly patient group, cluster 2 (obese, neutrophilic phenotypes) had a 1.85-fold significantly increased risk of asthma exacerbations. Cluster 3 (early-onset, atopy, and smoker with an eosinophil-predominant pattern) had a 2.37-fold risk of asthma exacerbations and higher oral corticosteroid (OCS) use than cluster 1 (late-onset and LMW exposure with paucigranulocytic blood pattern). Among elderly patients, cluster 2 had poor lung function and more ex-smokers. Cluster 3 (early-onset, long asthma duration) had the lowest paucigranulocytic blood pattern percentages in the elderly group. CONCLUSIONS: The novelty of the clusters was found in age-dependent clusters. We identified three distinct phenotypes with heterogeneous characteristics, asthma exacerbations and medicine use in nonelderly and elderly asthmatic patients, respectively. Classification of age-stratified asthma phenotypes may lead to precise identification of patients, which provides personalized disease management.

Lifestyle Factors and Energy Intakes with Risks of Breast Cancer among Pre- and Post- Menopausal Women in Taiwan.

Although the incidence of invasive breast cancer (BC) among women in Asian is generally lower than that in Western countries, the incidence of BC has been on the rise in the past three decades in Asian countries. This hospital-based case-control study aimed to explore the relationship between dietary and metabolic factors and BC risk in pre- and post-menopausal women. We enrolled 285 patients with newly diagnosed BC at the National Taiwan University Hospital and 297 controls from the local community and hospital staff. Before receiving anticancer therapy, all patients with BC and control participants completed a 57-question semi-quantitative Food Frequency Questionnaire. For pre-menopausal women, plant-based factor scores rich in seeds and nuts, soy, fruits, and seaweeds correlated significantly with reduced BC risks, whereas menarche occurring at <12 years of age, reduced physical activity, and high-density lipoprotein <40 mg/dL were associated with increased BC risks. For post-menopausal women, plant-based dietary factor scores were also associated with reduced risks, whereas increased body mass index and energy intake levels correlated with increased BC risks. Diets rich in plant-based dietary patterns are protective against BC risk, regardless of menopausal status. Habitual physical activity is protective against BC risk among pre-menopausal Taiwanese women. Maintaining optimal weight and caloric intake is beneficial for reducing post-menopausal BC risk.

Body composition modify the association between ambient particulate matter and lung function among asthma patients.

The effect of ambient PM10 and PM2.5 on lung function modified by body muscle and adipose tissue is not fully understood at present. Our aims were to investigate the association between seasonal average air pollutants and lung function in asthmatic patients modified by body composition indicators. In this cross-sectional study, we recruited 914 doctor-diagnosed asthmatic patients, and performed interaction and stratified analysis using the median values of total body muscle (TBM), total body fat (TBF), and percentage body fat (PBF) as well as body mass index (BMI) =25 as the cutoff points of the high/low body composition groups. The adjusted R2 values of the developed LUR models of PM2.5 and PM10 were 91.4% and 90.5% and also verified by cross-validation, respectively. After adjusting for confounding factors, we found that TBM significantly modified the association between PM10 and lung function among asthma patients (interaction P value <0.05). In the low TBM group, seasonal average concentrations of PM10 estimated by the LUR model increased by 10 µg/m3, and negative associations with lung function indicators were observed. For obese patients with BMI>25 and high TBF, the increase in PM10 was associated with the decrease in lung function. The asthma patients with obesity and low total body muscle were more susceptible to adverse effects of PM10 on lung function.

Phthalate derivative DEHP disturbs the antiproliferative effect of camptothecin in human lung cancer cells by attenuating DNA damage and activating Akt/NF-κB signaling pathway.

Plasticizers/phthalates play a facilitating role in the development of cancer and help the tumor to grow and metastasize. Camptothecin (CPT) and its derivatives are known to have anticancer properties of inhibiting cell growth, promoting cell apoptosis, and increasing autophagy. Therefore, in this study, we investigated whether the presence of di(2-ethylhexyl) phthalate (DEHP) could hinder apoptosis and autophagy caused by CPT in non-small cell lung cancer (NSCLC) cells. We found that DEHP interferes with CPT-induced apoptosis and autophagy and increases the prosurvival pathway by reducing the DNA damage marker γ-H2AX and activating the Akt and NF-κB pathways. Furthermore, we also confirmed that combining DEHP with 3-MA has additive effects in inhibiting autophagy and apoptosis in NSCLC cells. Taken together, our findings show that DEHP could affect CPT-induced anticancer treatment and provide evidence to show that DEHP induces chemoresistance in CPT-based chemotherapy.

Depression, Diabetes Mellitus and Mortality in Older Adults: A National Cohort Study in Taiwan.

Purpose: Diabetes mellitus (DM) increases the risk of cardiovascular and all-cause mortality. The coexistence of depression and DM is associated with an increased risk of DM complications and functional morbidity. The independent effect of depression on mortality in patients with DM is unclear, and relevant Asian studies have provided inconsistent results. Accordingly, this study assessed the independent and additive effects of DM and depression on mortality in a nationally representative cohort of older adults in Taiwan over a 10-year observation period. Patients and Methods: A total of 5041 participants aged 50 years or older were observed between 1996 and 2007. We defined depression as a score of ≥8 on the 10-item Center for Epidemiologic Studies Depression (CES-D 10) scale. Additionally, we defined participants as having type 2 DM if they had received a diagnosis of type 2 DM from a health-care provider. Cox proportional hazard models were applied to analyze predictors of mortality in depression and DM comorbidity groups. Results: During the 10-year follow-up period, 1637 deaths were documented. After adjustment for potential confounders, the hazard ratios for mortality in participants with both depression and DM, DM only, and depression only were 2.47 (95% confidence interval [CI]: 2.02-3.03), 1.95 (95% CI: 1.63-2.32), and 1.23 (95% CI: 1.09-1.39), respectively. Conclusion: The co-occurrence of depression with DM in Asian adults increased overall mortality rates. Our results indicate that the increased mortality hazard in individuals with DM and depression was independent of sex.

Association of early-onset breast cancer with body mass index, menarche, and menopause in Taiwan.

BACKGROUND: The trend of women suffering from early-onset breast cancer is increasing in Taiwan. The association of early-onset breast cancer with body mass index (BMI), menarche, and menopausal status has focused interest on the field of cancer epidemiology; however, few studies have explored the interaction of these factors on early-onset risk. This study aimed to estimate the interaction effects of BMI, menarche, and menopausal status on 40-year-old early-onset breast cancer. METHODS: Breast cancer patients were recruited from Kaohsiung Medical University Chung-Ho Memorial Hospital from 2013 to 2020. Multivariable logistic regression was used to estimate odds ratios (ORs) for early-onset breast cancer risk associated with menarcheal age stratified by sociodemographic factors and for the interaction between BMI and menopausal status on early-onset risk. RESULTS: A total of 775 participants were divided into 131 early-onset cases (≤ 40 years) and 644 late-onset cases (> 40 years). Compared to the age of 13 years at menarche, the age ≤ 11 years was significantly positively associated (OR: 2.62, 95% CI: 1.38-4.97) and ≥ 16 years was negatively associated (OR: 0.13, 95% CI: 0.03-0.53) with 40-year-old early-onset breast cancer respectively. In an adjusted model, the status of BMI < 24 and premenopause had 1.76- and 4.59-fold risk of early-onset breast cancer respectively. Especially in BMI < 24 status, premenopause also had a 6.47-fold early-onset risk and the early-onset risk increased by a significant amount per one year younger at menarche (aOR: 1.26, 95% CI: 1.03-1.55). There was also a positive interaction effect on an additive scale between BMI and menopausal status on early-onset breast cancer (RERIOR = 4.62, Pinteraction = 0.057). Compared to both BMI ≥ 24 and peri-/postmenopausal status, both the status of BMI < 24 and premenopause were associated with early-onset breast cancer (aOR: 7.16, 95% CI: 3.87-13.25). CONCLUSIONS: This study suggests that the status of BMI < 24 and premenopause were associated with an increased risk of early-onset breast cancer and there was a positive interaction on an additive scale. Understanding how obesity and menopausal status affect early-onset breast cancer is important for drafting preventive measures for early-onset breast cancer in Taiwan.

Association between recurrent breast cancer and phthalate exposure modified by hormone receptors and body mass index.

The association between phthalate exposure and breast cancer remains controversial. We performed a prospective patient cohort design to explore the interaction between creatinine-corrected urinary phthalate metabolites and hormone receptors as well as body mass index (BMI) on recurrent breast cancer. In this follow-up study, 636 female breast cancer patients and 45 new recurrent cases diagnosed for a total of 1576.68 person-years of follow-up were recruited. Mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP) was negatively associated with breast cancer recurrence, with adjusted hazard ratio (aHR) 3rd vs. 1st quartile of 0.15 (95% CI 0.04-0.51). The MEOHP presented as a non-monotonic dose-response (NMDR) curve, being U-shaped. In the stratification of hormone receptors, MEOHP still exhibited a U-shaped dose-response curve. The third quartile of MEOHP showed significant lowest recurrent risk in the status of ER-positive (aHR 0.18, 95% CI 0.05-0.66), PR-negative (aHR 0.14, 95% CI 0.03-0.63), and HER2-negative (aHR 0.24, 95% CI 0.08-0.76). Whether in BMI < 25 or in BMI ≥ 25, the third quartile of MEOHP was negatively associated with recurrent breast cancer, and there was a negative interaction on an additive scale between MEOHP and BMI (pinteraction = 0.042). The association between MEOHP and recurrent breast cancer was modified by hormone receptors and BMI.

Asthma and early smoking associated with high risk of panic disorder in adolescents and young adults.

PURPOSE: Studies have reported a strong link between asthma and panic disorder. We conducted a 17-year community-based large cohort study to examine the relationship between asthma, early smoking initiation, and panic disorder during adolescence and early adulthood. METHODS: A total of 162,766 participants aged 11-16 years were categorized into asthma and nonasthma groups at baseline and compared within the observation period. Covariates during late childhood or adolescence included parental education, cigarette smoking by family members of participants, and participant's gender, age, alcohol consumption, smoking, and exercise habits. Data for urbanicity, prednisone use, allergic comorbidity, and Charlson comorbidity index were acquired from the National Health Insurance Research Database. The Cox proportional-hazards model was used to evaluate the association between asthma and panic disorder. RESULTS: Our findings revealed that asthma increased the risk of panic disorder after adjustment for key confounders in the Cox proportional hazard regression model (adjusted HR: 1.70, 95% CI 1.28-2.26). Hospitalizations or visits to the emergency department for asthma exhibited a dose-response effect on the panic disorder (adjusted HR: 2.07, 95% CI 1.30-3.29). Patients with asthma with onset before 20 years of age who smoked during late childhood or adolescence had the greatest risk for panic disorder (adjusted HR: 4.95, 95% CI 1.23-19.90). CONCLUSIONS: Patients newly diagnosed with asthma had a 1.7-times higher risk of developing panic disorder. Smoking during late childhood or adolescence increased the risk for developing the panic disorder in patients with asthma.

DEHP mediates drug resistance by directly targeting AhR in human breast cancer.

Resistance to chemotherapy and hormonal therapy is a major clinical problem in breast cancer medicine, especially for cancer metastasis and recurrence. Di(2-ethylhexyl)phthalate (DEHP) affects drug resistance by an unknown mechanism of action. Here we analyzed breast cancer patients (N = 457) and found that Σ4MEHP (the sum of MEHP, MEHHP, MECPP and MEOHP concentrations) in urine was significantly higher (P = 0.018) in the recurrent breast cancer group compared with non-recurrent patients. Σ4MEHP-High was positively and significantly correlated with tumor stage (P = 0.005), lymph node status (P = 0.001), estrogen receptor status (P = 0.010), Her2/Neu status (P = 0.004), recurrence (P = 0.000) and tumor size (P = 0.002), as well as an independent prognostic marker (OR = 1.868; 95% CI = 1.424-2.451; P < 0.000) associated with poor survival rates based on a positive Her2/Neu status (P = 0.035). In addition, we found that DEHP inhibited paclitaxel and doxorubicin effects in breast cancer cell lines MCF-7 and MDA-MB-231 and in zebrafish and mouse tumor initiation models. DEHP induced trefoil factor 3 (TFF3) expression through the vinculin/aryl hydrocarbon receptor (AhR)/ERK signaling pathway and induced CYP2D6, CYP2C8 and CYP3A4 expression through the AhR genomic pathway to increase the epithelial-mesenchymal transition (EMT) and doxorubicin metabolism, respectably. DEHP mediated AhR-related alterations in estrogen receptor expression through the ubiquitination system, which decreased tamoxifen effects in AhR knockout mice. These findings suggest a novel therapeutic avenue by targeting AhR in drug-resistant and recurrent breast cancer.

Adequacy of prescribed caloric and protein intake and reduction of mortality in critically ill patients with body mass indices <30 kg/m2.

OBJECTIVE: Although the provision of nutrition helps minimize adverse outcomes in most patients in intensive care units (ICUs), little is known about the relative effect of energy and protein delivered on mortality in ICU patients with different ranges of body mass index (BMI). The aim of this study was to examine the relationships between adequacy of dietary energy and protein intakes separately and simultaneously, and short-term mortality in medical ICU patients across four BMI categories. METHODS: We enrolled 1693 patients admitted to a medical center ICU in Taiwan during the period of 2005 to 2011, subcategorizing them by BMI levels: <18.5(n = 418), 18.5-24.9 (n = 889), 25-29.9 (n = 289), and ≥30 kg/m2 (n = 97). Dietary energy and protein intake (DEI and DPI) were defined by the percent of prescribed dosages that each patient actually received: highly adequate (>80%), moderately adequate (60-80%), and inadequate (<60%), during the first 10 d in the ICU. RESULTS: Mean DEI was 1237 kcal/d and DPI 47 g protein/d. Analyzed separately in our multiple regression models, moderately and highly adequate DEI (Ptrends = 0.003-0.026) and DPI (Ptrends = 0.001-0.004) were both significantly correlated with reduced mortality in patients with BMI <18.5, 18.5-24.9, and 25-29.9 kg/m2 but not in those with BMI levels ≥30 kg/m2. With DEI and DPI analyzed simultaneously, only APACHE II scores and DPI levels remained significantly related to reduced mortality in patients with BMI <30 kg/m2. CONCLUSION: Although the adequacy of delivery of prescribed DEI or DPI dosages appeared to be important for reduced risks for mortality in ICU patients with BMI <30 kg/m2 when analyzed separately, DPI had a stronger effect on decreases in ICU mortality when the two were analyzed simultaneously. Further investigation may be needed to study the role of increased protein in improving clinical outcomes.

The Long-Term DEHP Exposure Confers Multidrug Resistance of Triple-Negative Breast Cancer Cells through ABC Transporters and Intracellular ROS.

The characteristics of phthalates had been thought to be similar to endocrine disruptors, which increases cancer risk. The role of phthalates in acquired drug resistance remains unclear. In this study, we investigated the effect of di-(2-ethylhexyl) phthalate (DEHP) on acquired drug resistance in breast cancer. MCF7 and MDA-MB-231 breast cancer cells were exposed to long-term physiological concentration of DEHP for more than three months. Long-exposure DEHP permanently attenuated the anti-proliferative effect of doxorubicin with estrogen receptor-independent activity even after withdrawal of DEHP. Long term DEHP exposure significantly reduced ROS (O2-) level in MDA-MB-231 cells while increased in MCF7 cells. ATP-binding cassette (ABC) transporters possess a widely recognized mechanism of drug resistance and are considered a target for drug therapy. Upregulation of ABC family proteins, ABCB-1 and ABCC-1 observed in DEHP-exposed clones compared to doxorubicin-resistant (DoxR) and parental MDA-MB-231 cells. A viability assay showed enhanced multidrug resistance in DEHP-exposed clones against Dox, topotecan, and irinotecan. Inhibition of ABC transporters with tariquidar, enhanced drug cytotoxicity through increased drug accumulation reversing acquired multidrug resistance in MDA-MB-231 breast cancer cells. Tariquidar enhanced Dox cytotoxicity by increasing intracellular ROS production leading to caspase-3 mediated apoptosis. Activation of PI3K/Akt signaling enhanced proliferation and growth of DEHP-exposed MDA-MB-231 cells. Overall, long-term DEHP exposure resulted in acquired multidrug resistance by upregulating ABCB-1 and ABCC1; apart from proliferation PI3K/Akt may be responsible for acquired drug resistance through ABC transporter upregulation. Targeting ABCB1 and ABCC1 with tariquidar may be a promising strategy for reversing the acquired multidrug resistance of triple-negative breast cancer cells.

Disrupted Expression of Circadian Clock Genes in Patients with Bronchial Asthma.

PURPOSE: Circadian clock is synchronized to the 24-hour day by the daily light-dark cycle and proper function of circadian rhythm is essential for many physiological processes. Disruption of circadian rhythm can affect disease processes and influence disease severity, treatment responses, and even survivorship. In this retrospective case-controlled study, we tried to explore whether expression of circadian clock genes was disturbed in patients with bronchial asthma. PATIENTS AND METHODS: We performed real-time quantitative reverse transcriptase-polymerase chain reactions to examine the expression of the nine core circadian clock genes (BMAL1, CK1ε, CLOCK, CRY1, CRY2, PER1, PER2, PER3, and TIM) in total leukocytes of peripheral blood collected at chest clinics from 120 patients with asthma and 60 health individuals. RESULTS: Expression levels of the nine circadian clock genes were significantly different between patients and healthy individuals, but not associated with the asthma control status. We also noted the difference of PER3 expression in asthmatic patients with and without nocturnal symptoms. In well-controlled asthmatics, expression of BMAL1, CK1ε, CLOCK, CRY1, CRY2, and PER1 was significantly lower in patients with nocturnal symptoms than those without nocturnal symptoms. However, in not well-controlled asthmatics, expression of only BMAL1, CK1ε, PER1, and PER2 was significantly different between patients with and without nocturnal symptoms. Binary logistic regression analysis selected BMAL1, CKIε, PER3, and TIM as independent factors for bronchial asthma and ROC curves showed the combined expression of these four genes enhanced the capability of predicting asthma (AUC=0.924; 95% CI=0.875-0.958; P<0.001). CONCLUSION: Our results showed altered expression of circadian clock genes in patients with bronchial asthma and down-regulated PER3 in patients with nocturnal symptoms. Altered expression of circadian clock genes was also observed in asthmatics with or without nocturnal symptoms in well- or not well-controlled subgroups. Combined expression of BMAL1, CKIε, PER3, and TIM could be a potential predictor for bronchial asthma.

Incidence of nontuberculous mycobacterial disease and coinfection with tuberculosis in a tuberculosis-endemic region: A population-based retrospective cohort study.

ABSTRACT: Nontuberculous mycobacteria (NTM) infection may interfere in the diagnosis and treatment of tuberculosis (TB) in TB-endemic regions. However, the population-based incidence of NTM disease and NTM-TB coinfection remains unclear.We used Taiwan's National Health Insurance Research Database to identify new diagnoses of NTM disease and TB from 2005 to 2013 and calculated the incidence rate and the proportion of NTM-TB coinfection. The patients with NTM disease or TB were determined by the use of disease codes from International Classification of Diseases, Ninth Revision, Clinical Modification, laboratory mycobacterium examination codes, and antimycobacterial therapy receipts.From 2005 to 2013, the age-adjusted incidence rate of NTM disease increased from 5.3 to 14.8 per 100,000 people per year and the age-adjusted incidence rate of NTM-TB coinfection was around 1.2 to 2.2 per 100,000 people per year. The proportion of NTM-TB coinfection among patients with confirmed TB was 2.8%. Male and older patients had a significantly higher incidence of NTM disease. The effects of urbanization and socioeconomic status (SES) on the incidences of TB and NTM disease were different. Rural living and lower SES were significantly associated with increasing the incidence of confirmed TB but not with that of NTM disease. For NTM disease, those living in the least urbanized area had significantly lower incidence rate ratio than in the highest urbanized area. The incidence of NTM-TB coinfection was higher in older patients and compared with patients aged < 45 years, the incidence rate ratio of the patients aged> 74 years was 12.5.In TB-endemic Taiwan, the incidence of NTM disease increased from 2005 to 2013. Male gender and old age were risk factors for high incidence of NTM disease. SES did not have a significant effect on the incidence of NTM disease, but rural living was associated with lower incidence of NTM disease. In TB-endemic areas, NTM-TB coinfection could disturb the diagnosis of TB and treatment, especially in elderly patients.

Visceral obesity and cell cycle pathways serve as links in the association between bisphenol A exposure and breast cancer.

It has been identified that bisphenol A (BPA) exposure causes developmental toxicity in breast cells. However, the exact molecular mechanisms underlying the association between exposure to BPA and breast cancer remain unclear. The aim of the present study was to investigate the BPA-regulated signaling pathways associated with the aggressiveness and the development of breast cancer. Microarray technology and functional gene set analyses were used to evaluate BPA and breast cancer-associated biomarkers and pathways in a discovery-driven manner. Using individual dataset analyses, it was indicated that two BPA-associated gene sets, the visceral obesity pathway, involved in visceral fat deposits and the metabolic syndrome, and the cell cycle pathway, involved in cyclins and cell cycle regulation, were significantly associated with a high grade of aggressiveness and the development of estrogen receptor (ER)-positive breast cancer (between P<0.05 and 0.0001). The pooled analysis indicated that the most significant pathway was G1/S checkpoint regulation, and the cyclin and cell cycle regulation pathway for BPA-associated ER-positive cancer. Cancer cell signaling pathways were associated with healthy breast cells developing into breast cancer. The visceral obesity and the cell cycle pathways were indicated to link BPA exposure to breast cancer. The results of the present study demonstrate a significant association between breast cancer and BPA-regulated gene pathways.

Household airborne endotoxin associated with asthma and allergy in elementary school-age children: a case-control study in Kaohsiung, Taiwan.

To evaluate the association between the presence of asthma and allergy, and airborne endotoxin in homes of school-age children in Kaohsiung City, Taiwan, with a case-control study design by matching the age and class exposure. Data collection of home visits included an interviewer-administered questionnaire and air sampling of participants' homes for endotoxin, bacteria, and fungi, as well as temperature and relative humidity measurements. Endotoxin was detected in all air samples with a median value of 0.67 EU m-3. In the adjusted logistic regression model, household airborne endotoxin was associated with higher prevalence of asthma and allergy; OR = 4.88 (95% CI 1.16-20.55) for Q3 (between 0.67 and 1.97 EU m -3) vs. Q1 (< 0.31 EU m -3), with statistical significance. Airborne fungi were associated with higher prevalence of asthma and allergy; OR = 4.47 (95% CI 1.13-17.69) for Q3 (between 314 and 699 CFU m -3) vs. Q1 (< 159 CFU m -3) in adjusted logistic regression models. Airborne endotoxin and fungi were significantly associated with children's asthma and allergy.

Canned food intake and urinary bisphenol a concentrations: a randomized crossover intervention study.

Bisphenol A (BPA) is an endocrine disruptor. To evaluate the effect of canned food consumption on internal BPA dose, urinary BPA concentrations were measured before and after intake of canned foods. This study applied a randomized crossover design, recruited 20 healthy volunteers, and divided them into two groups. One group consumed canned food; the other group consumed fresh food. After a 1-day washout, the dietary interventions were reversed. In each period, urine samples were collected immediately before meals and then 2 h, 4 h, and 6 h after meals. A mixed-effects model was used to assess BPA changes over time. Our results showed urinary BPA concentrations increased after consumption of canned food. Specifically, urinary BPA concentrations significantly differed between consumption of canned food and fresh food at 2 h, 4 h, and 6 h after intake (p values of 0.001, < 0.001, and < 0.001, respectively). Mean BPA concentrations at 2 h, 4 h, and 6 h after meals were 152%, 206%, and 79% higher, respectively, than mean BPA concentrations before meals. Urine concentration profiles of canned food intake showed that peaks were at 4 h, the increase diminished at 6 h, and returned to baseline levels at 24 h after intake. Therefore, dietary intervention and a 1-day washout period are effective for limiting internal BPA burden. This study provides convincing evidence of a human exposure route to BPA and a basis for designing interventions to mitigate exposure.

Allergic rhinitis increases the risk of incident panic disorder among young individuals: A nationwide population-based cohort study in Taiwan.

BACKGROUND: Studies have reported an association between allergy and panic disorder. However, few studies have explored the relationship between allergic rhinitis and panic disorder. Previous studies were limited by cross-sectional study designs, self-reported symptoms, absence of matched controls, and lack of consideration of the influence of steroid and comorbidities. This study aimed to explore the longitudinal association between allergic rhinitis and panic disorder in a large population-based cohort of young people. METHODS: In this study, 79,917 new cases of allergic rhinitis between 1998 and 2012 in individuals younger than 20 years were identified from Taiwan's National Health Insurance Research Database. One control (nonallergic rhinitis) per case (allergic rhinitis) was randomly selected from the remaining sample, matching for age, sex, residence, and insurance premium. Both groups were followed until the end of 2013 for incidence of panic disorder. Cox regression analysis was performed, adjusting for sex, age, residence, insurance premium, systemic steroids, asthma, atopic dermatitis, allergic conjunctivitis, attention deficit hyperactivity disorder, depression, and Charlson index. RESULTS: Allergic rhinitis was associated with a 2-fold increase in risk for panic disorder after adjustment for other variables. Additional independent risk factor of panic disorders were female sex, older age group, and depression. LIMITATIONS: Lifestyle, substance use, smoking by the patient or family members, and psychosocial stressors were not evaluated. CONCLUSIONS: Allergic rhinitis was associated with increased risk of panic disorder. Assessment and intervention of allergy rhinitis among young people with panic disorder are critical.