The validation of Chinese version of workplace PERMA-profiler and the association between workplace well-being and fatigue.

BACKGROUND: Well-being is an important issue in workplace. One of these assessment tools of well-being, Workplace PERMA Profiler, is based on Seligman's five dimensions well-being. Prolonged fatigue may last for a long time, leading a great impact on both employees and enterprises. However, rare studies about the association between well-being and fatigue had been investigated. Our aim is to establish the Chinese version Profiler, and to discovery the association between workplace well-being and fatigue. METHODS: The Chinese version was established according to International Society of Pharmacoeconomics and Outcomes Research (ISPOR) task force guidelines. In the study, researchers employed simple random sampling by approaching individuals undergoing health checkups or receiving workplace health services, inviting them to participate in a questionnaire-based interview. Prolonged Fatigue was evaluated by Checklist Individual Strength (CIS). The reliability was evaluated by Cronbach's alphas, Intra-class Correlation Coefficients (ICCs), and measurement errors. Moreover, confirmatory factor analysis and correlational analyses were assessed for the validity. RESULTS: The analyses included 312 Chinese workers. Cronbach's alphas of the Chinese version ranged from 0.69 to 0.93, while the ICC ranged from 0.70 to 0.92. The 5-factor model of confirmatory factor analysis revealed a nearly appropriate fit (χ2 (82) = 346.560, Comparative Fit Index [CFI] = 0.887, Tucker-Lewis Index [TLI] = 0.855, Root Mean Square Error of Approximation [RMSEA] = 0.114, Standardized Root Mean Square Residual [SRMR] = 0.060). Moreover, the CIS and its four dimensions were significantly and negatively associated with the Positive Emotion, while they are positively associated with Engagement dimension except CIS-Motivation dimension. CONCLUSION: The Chinese version Workplace PERMA-Profiler indicate nice reliability and validity. Furthermore, all CIS dimensions were negatively influenced by Positive Emotion, while commonly positively associated with Engagement.

Performance of nonalcoholic fatty liver fibrosis score in estimating atherosclerotic cardiovascular disease risk.

BACKGROUND AND AIMS: It is currently unclear whether the nonalcoholic fatty liver disease (NAFLD) fibrosis score, when compared to major anthropometric indices, is useful in estimating the risk of atherosclerotic cardiovascular disease (ASCVD). METHODS AND RESULTS: This study included 3886 adults undergoing a health checkup. An elevated risk of ASCVD was determined as a 10-year ASCVD risk ≥7.5% using Pooled Cohort Equations. NAFLD was diagnosed with abdominal ultrasonography. Receiver operating characteristic curves were used to evaluate the performance of estimating an elevated ASCVD risk. Among study participants, 521 (13.4%) had an elevated ASCVD risk and 1473 (37.9%) had NAFLD. Subjects with NAFLD had a significantly higher rate of ASCVD risk ≥7.5% (p < 0.001) compared to those without NAFLD. After adjusting for cardiometabolic risk factors, NAFLD (OR = 1.49, 95% CI: 1.10-2.00, p = 0.009) in all participants and NAFLD fibrosis score >0.676 (OR = 1.95, 95% CI: 1.30-2.92, p = 0.001) in individuals with NAFLD were significantly associated with an elevated risk of ASCVD. When compared to different anthropometric indices, NAFLD fibrosis score exhibited the largest area under the curve (AUC) in individuals with NAFLD (AUC = 0.750) in estimating an elevated ASCVD risk. Furthermore, NAFLD fibrosis score displayed the best predictive performance for identifying an elevated ASCVD risk in male participants with NAFLD (AUC = 0.737). CONCLUSION: NAFLD was a significant risk factor for elevated ASCVD risk. NAFLD fibrosis score >0.676 was associated with increased ASCVD risk in individuals with NAFLD. Compared with anthropometric indices, NAFLD fibrosis score demonstrated the best performance in estimating elevated ASCVD risk among those with NAFLD.

Exploring the association of metal mixture in blood to the kidney function and tumor necrosis factor alpha using machine learning methods.

This research aimed to approach relationships between metal mixture in blood and kidney function, tumor necrosis factor alpha (TNF-α) by machine learning. Metals levels were measured by Inductively Couple Plasma Mass Spectrometry in blood from 421 participants. We applied K Nearest Neighbor (KNN), Naive Bayes classifier (NB), Support Vector Machines (SVM), random forest (RF), Gradient Boosting Decision Tree (GBDT), Categorical boosting (CatBoost), eXtreme Gradient Boosting (XGBoost), Whale Optimization-based XGBoost (WXGBoost) to identify the effect of plasma metals, TNF-α, and estimated glomerular filtration rate (eGFR by CKD-EPI equation). We conducted not only toxic metals, lead (Pb), arsenic (As), cadmium (Cd) but also included trace essential metals, selenium (Se), copper (Cu), zinc (Zn), cobalt (Co), to predict the interaction of TNF-α, TNF-α/white blood count, and eGFR. The high average TNF-α level group was observed among subjects with higher Pb, As, Cd, Cu, and Zn levels in blood. No associations were shown between the low and high TNF-α level group in blood Se and Co levels. Those with lower eGFR group had high Pb, As, Cd, Co, Cu, and Zn levels. The crucial predictor of TNF-α level in metals was blood Pb, and then Cd, As, Cu, Se, Zn and Co. The machine learning revealed that As was the major role among predictors of eGFR after feature selection. The levels of kidney function and TNF-α were modified by co-exposure metals. We were able to acquire highest accuracy of over 85% in the multi-metals exposure model. The higher Pb and Zn levels had strongest interaction with declined eGFR. In addition, As and Cd had synergistic with prediction model of TNF-α. We explored the potential of machine learning approaches for predicting health outcomes with multi-metal exposure. XGBoost model added SHAP could give an explicit explanation of individualized and precision risk prediction and insight of the interaction of key features in the multi-metal exposure.

What is the association between secondhand smoke (SHS) and possible obstructive sleep apnea: a meta-analysis.

BACKGROUND: Association between smoking and sleep apnea is well-known from previous studies. However, the influence of secondhand smoke (SHS), which is a potential risk factor of obstructive sleep apnea (OSA), remains unclear. Our aim was to investigate the relationship between SHS and OSA using a meta-analysis. MATERIALS AND METHODS: For the meta-analysis, searches were performed in MEDLINE, EMBASE, and Web of Science databases on January 10, 2022, by combining various keywords including "SHS exposure" and "OSA". Data were extracted using defined inclusion and exclusion criteria. Fixed-effects model meta-analyses were used to pool risk ratio (RR) estimates with their 95% confidence intervals (CI). I2 was used to assess heterogeneity. Moreover, we performed subgroup meta-analyses of children-adults, and smoker fathers and mothers. RESULTS: In total, 267 articles were obtained through an electronic search. Twenty-six articles were included in our analysis according to the inclusion and exclusion criteria. We found evidence of an association between SHS exposure and possible OSA (RR 1.64, 95% CI 1.44-1.88). The results of the subgroup analyses showed that children passive smokers (RR 1.84, 95% CI 1.60-2.13) were at greater risks of possible OSA than adult passive smokers (RR 1.35, 95% CI 1.21-1.50). Also, significant differences were observed in mothers with smoking exposure (RR 2.61, 95% CI 1.62-4.21, p < 0.0001), as well as in fathers with smoking exposure (RR 2.15, 95% CI 0.98-4.72, p = 0.06). SHORT CONCLUSION: Our meta-analysis confirmed that SHS exposure is significantly associated with OSA. In the subgroup analyses, the association of SHS and possible OSA was significant in both children and adults, as well as in smoker mothers and fathers.

Association between secondhand smoke and peripheral arterial disease: a meta-analysis of cross-sectional studies.

PURPOSE: The association between secondhand smoke (SHS) and peripheral arterial disease (PAD) was inconsistent and the studies were relatively scarce, hence, we conducted a meta-analysis of the association between SHS and PAD. MATERIALS AND METHODS: We systematically searched three electronic databases (PubMed, EMBASE, and Web of Science), and calculated the pooled prevalence risk ratio (RR) and estimated standard error by random effect model from the meta-analysis. Furthermore, we performed a subgroup meta-analysis according to the location of SHS exposure. RESULTS: We initially identified 502 articles from the electronic database, and 6 articles, cross-sectional data from 4 cross-sectional studies and 2 prospective cohort studies, were included in the meta-analysis. Among these six articles, two studies showed a significant correlation between SHS exposure and PAD, whereas no study showed a negative correlation between SHS exposure and PAD. In the meta-analysis, pooled prevalence showed a significant association between SHS exposure and PAD (RR = 1.23; 95% confidence interval [CI] 1.08-1.41; z = 3.02, p = 0.003). In the subgroup analysis based on location of SHS exposure, the prevalence RR of PAD at home was 1.30 (95% CI 1.14-1.49, Z-3.99, p < 0.0001). The prevalence RR in the subgroup of SHS exposure at work was not significant (RR = 0.89; 95% CI 0.55-1.44; z = 0.48, p = 0.63). CONCLUSION: Exposure to SHS was significantly and positively associated with PAD. Moreover, we found a significant association between exposure to SHS and PAD at home, but the association was not significant at work.

Smartphone addiction and victimization predicts sleep problems and depression among children.

BACKGROUND: In this study we examined the phenomena of smartphone addiction, online harassment, and school bullying/victimization to predict the prospective influence these could have on the onset and persistence of sleep problems and depression among children. METHODS: Responses from 2155 fifth-grade children recruited from 30 primary schools in Taipei were assessed, and a follow-up was performed in the 6th grade. Self-administered questionnaires were collected for each year. FINDINGS: Children who reported smartphone addictions, online harassment, and school bullying/victimization coupled with an increase in those factors were more likely to experience the onset and persistence of sleep problems. In addition, children who reported smartphone addiction, online harassment, school bullying/victimization, and poor sleep quality were more likely to experience the onset and persistence of depression. IMPLICATIONS: School nurses or pediatric nurses should be able to assess children's Internet use and risks to understand potential influences on sleep quality and mental status and provide recommendations for children, parents and schools.

Higher NAFLD fibrosis score is associated with impaired eGFR.

BACKGROUND/PURPOSE: Chronic kidney disease (CKD) has become a worldwide health problem, leading to high morbidity and mortality, and non-alcoholic fatty liver disease (NAFLD) is considered a risk factor for CKD. The aim of this study was to explore the relationship between NAFLD fibrosis score (NFS) and the estimated glomerular filtration rate (eGFR), and identify possible risk factors related to the NFS among Taiwanese subjects. METHODS: Subjects were enrolled from the database of the Department of Preventive Medicine of Kaohsiung Municipal Hsiao-Kang Hospital. The eGFR was calculated according to the Taiwanese Modification of Diet in Renal Disease (TMDRD) equation, and the NFS was employed to evaluate the fibrotic level. RESULTS: In total, 11,376 subjects were enrolled in this study, with a mean age of 52.0 ± 6.81 years, including 4529 (39.8%) males. A fasting sugar level ≥100 mg/dL (OR = 1.70, 95% CI = 1.52-1.87) and an abnormal waist circumference (OR = 1.81, 95% CI = 1.65-1.99) were significant factors associated with NFS (p < 0.05). Trends of a decreasing TMDRD score and an increasing NFS with increasing age were noted (p < 0.05). The NFS was significantly negatively correlated with the TMDRD score (standard coefficients: -0.067, p < 0.001). CONCLUSION: A higher NFS is associated with an impaired eGFR in Taiwanese subjects. Controlling risk factors, especially fasting sugar level and waist circumference, may be useful in preventing NFS deterioration, which is negatively correlated with the eGFR.

Peroxisome Proliferator-Activated Receptor γ Coactivator 1α Activates Vascular Endothelial Growth Factor That Protects Against Neuronal Cell Death Following Status Epilepticus through PI3K/AKT and MEK/ERK Signaling.

Status epilepticus may cause molecular and cellular events, leading to hippocampal neuronal cell death. Peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α) is an important regulator of vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2), also known as fetal liver kinase receptor 1 (Flk-1). Resveratrol is an activator of PGC-1α. It has been suggested to provide neuroprotective effects in epilepsy, stroke, and neurodegenerative diseases. In the present study, we used microinjection of kainic acid into the left hippocampal CA3 region in Sprague Dawley rats to induce bilateral prolonged seizure activity. Upregulating the PGC-1α pathway will increase VEGF/VEGFR2 (Flk-1) signaling and further activate some survival signaling that includes the mitogen activated protein kinase kinase (MEK)/mitogen activated protein kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathways and offer neuroprotection as a consequence of apoptosis in the hippocampal neurons following status epilepticus. Otherwise, downregulation of PGC-1α by siRNA against pgc-1α will inhibit VEGF/VEGFR2 (Flk-1) signaling and suppress pro-survival PI3K/AKT and MEK/ERK pathways that are also accompanied by hippocampal CA3 neuronal cell apoptosis. These results may indicate that the PGC-1α induced VEGF/VEGFR2 pathway may trigger the neuronal survival signaling, and the PI3K/AKT and MEK/ERK signaling pathways. Thus, the axis of PGC-1α/VEGF/VEGFR2 (Flk-1) and the triggering of downstream PI3K/AKT and MEK/ERK signaling could be considered an endogenous neuroprotective effect against apoptosis in the hippocampus following status epilepticus.

Utility of human leukocyte antigen-B*58: 01 genotyping and patient outcomes.

AIM: Human leukocyte antigen (HLA-B*58:01) allele screening before allopurinol administration is recommended to prevent gene-mediated severe cutaneous adverse reactions (SCARs). The objective of the analysis was to examine the clinical utility and effects of HLA-B*58:01 genotyping on patient's outcomes in a practice setting. PATIENTS AND METHODS: The electronic medical records covering diagnosis, laboratory results, and prescription dispensing for patients who were newly treated with allopurinol or tested for HLA-B*58:01 were obtained from a large medical organization in Taiwan between 2010 and 2014. The uptake of HLA-B*58:01 testing, incidence of allopurinol-associated SCAR, and changes in urate-lowering agent utilization were assessed. RESULTS: A total of 17 532 allopurinol new users were identified from 2010 to 2014, and the HLA-B*58:01 test was ordered for 2844 (21.76%) of 13 069 new users when available between 2011 and 2014 in the study. The allopurinol-related SCAR events decreased from 0.21% (22/4460) to 0 (0/2167) after the introduction of HLA-B*58:01 testing, accompanied by a gradual increase from 8% (326/4207) to 31% (674/2167) in genotype testing rate. However, the HLA-B*58:01 testing performed before allopurinol prescription was 60.34%, and ~40% of patients were tested after already taking allopurinol. A shift from allopurinol to other urate-lowering agent regimens appeared among new allopurinol users. CONCLUSION: HLA-B*58:01 test was associated with the prevention of allopurinol-induced SCAR. The clinical utility of genotype testing may not be consistent with recommendations for testing, and treatment alternatives are a competitive intervention associated with effective implications in a real-world setting.

Use of Genetic Algorithm Combinational Single-nucleotide Polymorphisms Could Modify the Association of Blood Lead Levels and Bone Matrix Density.

BACKGROUND: Previous studies have not explored the relationship between a single gene and a single disease. Our study aims to investigate the association of multiple genotypes with blood lead levels and bone matrix density (BMD) by using genetic algorithms. METHODS: Our research focused on 506 employees (245 males and 261 females) of a lead battery factory in Taiwan. We collected data on their BMD, blood lead level, and 6 SNPs (ACE, alpha-adducin, Bsm, Tag, Apa, and ALAD); these factors were analyzed using discrete binary particle swarm optimization (DBPSO) and logistic regression analysis. RESULTS: We found no association between blood lead level and bone density, which may be due to the relatively young age of this population (mean age = 45.1 years). However, the genotype that contained both Bsm type bb and ALAD type 1-1 may play an important role in protecting against lower bone density among these employees. CONCLUSIONS: In conclusion, this study found that the Bsm and ALAD genes influence bone density among lead workers. However, the mechanism and exact relationship between these two genes and bone density require further investigation.

Toxic Metals Increase Serum Tumor Necrosis Factor-α Levels, Modified by Essential Elements and Different Types of Tumor Necrosis Factor-α Promoter Single-nucleotide Polymorphisms.

BACKGROUND: Lead (Pb), cadmium (Cd), and arsenic (As) could cause health issues through oxidative stress that is indicated in the elevated tumor necrosis factor-alpha (TNF-α). However, some of the essential elements-selenium (Se), zinc (Zn), cobalt (Co), and copper (Cu)-are cofactors or structural components of antioxidant enzymes. It is suggested that single-nucleotide polymorphisms (SNPs) in the TNF-α gene have different TNF-α responses. This study aims to evaluate the effect of serum TNF-α levels through the interactions between toxic metals and essential elements and how the interactions between the toxic metals and TNF-α SNPs (-1031 T > C, -863 C > A, -857 C > T, -308 G > A, -238 G > A) influence serum TNF-α levels. METHODS: Blood samples were collected from 455 workers who carried out annual health examinations and multielements determined by inductively coupled plasma mass spectrometry (ICP-MS). TNF-α levels were detected by enzyme-linked immunosorbent assay (ELISA). TNF-α promoter SNPs were analyzed by specific primer probes using real-time polymerase chain reaction (PCR) methods. RESULTS: Increasing blood Pb, Cd, and As levels were associated with elevated TNF-α levels. The interaction between Pb and Cu decreased TNF-α levels and so did the interaction between Cd and Se. In the interaction between Pb and SNPs, individuals with AA/AG (-308 G > A) and AA/AG (-238 G > A) had higher serum TNF-α levels. However, lower TNF-α levels were noted in those individuals with AA/CA (-863 C > A). In the interaction between As and SNPs, workers with AA/AG (-238 G > A) had synergic effect with As and induced higher serum TNF-α levels. CONCLUSIONS: Blood Cu and Se were antagonists of toxic metals (Pb, As, and Cd) through lower serum TNF-α levels. Variant types of TNF-α SNPs (-308 G > A, -238 G > A) and wild type of -863 CC would be more susceptible to toxic metals.

Vocational rehabilitation for enhancing return-to-work in workers with traumatic upper limb injuries.

BACKGROUND: Traumatic upper limb injury is a leading cause of work-related disability. After return-to-work (RTW), many survivors of injuries are able to regain a quality of life (QoL) comparable with the normal population. Since RTW plays an important role in economic productivity and regaining health-related QoL, enhancing RTW in workers with traumatic limb injuries is the primary goal of rehabilitation. Vocational rehabilitation has been commonly employed in the field of occupational safety and health to increase the number of injured people returning to the labour market, prevent illness, increase well-being, and reduce disability. OBJECTIVES: To assess the effects of vocational rehabilitation programmes for enhancing RTW in workers with traumatic upper limb injuries. SEARCH METHODS: This is an update of a Cochrane review previously published in 2013. We updated our searches of the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 2017, Issue 9), MEDLINE (to 30 August 2017), EMBASE (to 3 September 2017), CINAHL (to 6 September 2017), and PsycINFO (to 6 September 2017), and we handsearched the references lists of relevant review articles. SELECTION CRITERIA: We aimed to include all randomised controlled trials (RCTs) comparing vocational rehabilitation with an alternative (control) intervention such as standard rehabilitation, a limited form of the vocational rehabilitation intervention (such as advice on RTW, referral information, or liaison with employer), or waiting-list controls. DATA COLLECTION AND ANALYSIS: Two authors independently inspected abstracts, and we obtained full papers when necessary. When the two authors disagreed about the inclusion of a study, we resolved disagreements by discussion. A third author arbitrated when necessary. MAIN RESULTS: Our updated search identified 466 citations. Based on assessments of their titles and abstracts, we decided to evaluate the full texts of five records; however, none met our inclusion criteria. AUTHORS' CONCLUSIONS: There is currently no high-quality evidence to support or refute the efficacy of vocational rehabilitation for enhancing RTW in workers with traumatic upper limb injuries. Since injured people in occupational settings frequently receive vocational rehabilitation with the aim of decreasing work disability, enhancing RTW, increasing productivity, and containing the welfare cost, further high-quality RCTs assessing the efficacy of vocational rehabilitation for workers with traumatic upper limb injury are needed to fill this gap in knowledge.

Compliance with risk management plan recommendations on laboratory monitoring of antitumor necrosis factor-α therapy in clinical practice.

BACKGROUND/PURPOSE: A risk management plan (RMP) was introduced to monitor the association between initiation of antitumor necrosis factor-α (anti-TNF-α) therapy and tuberculosis (TB) and viral hepatitis infections. The aim of this study was to assess adherence and predictors of laboratory-testing rates among patients treated with anti-TNF-α therapy. METHODS: Data on patients receiving anti-TNF-α therapy between January 1, 2005, and November 31, 2013, were retrieved from a large medical organization in Taiwan. Newly-treated patients were categorized into pre- and post-RMP groups. Laboratory testing for TB and hepatitis B and C was ascertained and the proportion of new users receiving the test was compared between the pre- and post-RMP groups. Patient characteristics and concomitant medications used were investigated using multivariate logistic regression to determine the impact of each factor on laboratory testing. RESULTS: Among 1128 new users, the initial testing rate of chest X-ray (CXR) for latent TB infection increased from 60.26% before RMP to 76.38% after RMP implementation; hepatitis B surface antigen (HBsAg) increased from 31.13% to 51.42%; and hepatitis C virus antibody (HCVAb) increased from 32.2% to 54.10%. CXR was significantly associated with age >60 years, higher Quan-Charlson comorbidity index score, psoriasis, and use of prednisolone (≥7.5 mg/d). Patients aged 40-60 years and with prednisolone doses of ≥7.5 mg/d and history of cancer were more likely to receive HBsAg or HCVAb tests than their counterparts. CONCLUSION: The rate of laboratory test monitoring for anti-TNF-α therapy increased after RMP implementation. A strategy that integrates efforts from patient's education, health profession, and regulatory agencies is needed to improve safety screening and access to laboratory resources for the at-risk group of patients.

Prevalence and risk factors of asymptomatic colorectal diverticulosis in Taiwan.

BACKGROUND: To investigate the prevalence and risk factors of asymptomatic colorectal diverticulosis in Taiwanese general population. METHODS: From January 2009 to December 2011, consecutive asymptomatic subjects undergoing a health check-up were evaluated by colonoscopy. The colorectal diverticulosis was assessed, and a medical history and demographic data were obtained from each subject. Logistic regression analysis was conducted to search the risk factors of colorectal diverticulosis. RESULTS: Of the 1899 asymptomatic subjects, the prevalence of colorectal diverticulosis was 13.5%. On univariate logistic regression analysis, age over 60 years old, male, adenomatous polyp, current smoking and heavy alcohol consumption were significantly associated with diverticulosis. Multivariate logistic regression analysis revealed that age over 60 years old (relative risk [RR], 2.57; 95% confidence interval [CI], 1.64-6.47), adenomatous polyps (RR, 2.18; 95% CI, 1.18-4.61) and heavy alcohol consumption (RR, 1.82; 95% CI, 1.04-3.08) were independent predictors for colorectal diverticulosis. CONCLUSIONS: The prevalence of asymptomatic colorectal diverticulosis was 13.5% in Taiwan. Age over 60 years old, adenomatous polyp and heavy alcohol consumption may affect the risk of development of the disease.

Pb²âº induced IL-8 gene expression by extracellular signal-regulated kinases and the transcription factor, activator protein 1, in human gastric carcinoma cells.

Divalent lead (Pb(2+) ) is a common industrial pollutant epidemiologically associated with gastric cancers. Pb(2+) was found to promote tumorigenesis, which may include interleukin (IL)-8, a pro-inflammatory chemokine that promotes angiogenesis and tumor metastasis. Given that the gastrointestinal tract is a major route of Pb(2+) exposure, we investigated the ability of Pb(2+) to induce IL-8 expression in gastric carcinoma cells and its underlying mechanism. At a concentration of 0.1 µM, Pb(2+) induced IL-8 gene activation in gastric carcinoma AGS cells. Using a IL-8 promoter-deletion analysis, transcription factor activator protein 1 (AP-1) was identified as a necessary component of Pb(2+) -induced IL-8 gene activation. Upregulation of the IL-8 gene was abrogated by the MEK inhibitor, PD98059, and partially suppressed by the epidermal growth factor receptor inhibitors, AG1478 and PD153035. Furthermore, c-Jun protein expression was induced in cells treated with Pb(2+) , and overexpression of c-Jun enhanced Pb(2+) -induced IL-8 activation. Collectively, our findings highlight the pivotal roles of AP-1 and extracellular signal-regulated kinase in signal transduction of Pb(2+) -induced IL-8 gene activation. These molecules may be potential therapeutic targets for Pb(2+) -related inflammation leading to stomach carcinogenesis. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 315-322, 2015.

Pb2+ induces gastrin gene expression by extracellular signal-regulated kinases 1/2 and transcription factor activator protein 1 in human gastric carcinoma cells.

Divalent lead ions (Pb(2+) ) are toxic environmental pollutants known to cause serious health problems in humans and animals. Absorption of Pb(2+) from air, water, and food takes place in the respiratory and digestive tracts. The ways in which absorbed Pb(2+) affects cell physiology are just beginning to be understood at the molecular level. Here, we used reverse transcription PCR and Western blotting to analyze cultures of human gastric carcinoma cells exposed to 10 µM lead nitrate. We found that Pb(2+) induces gastrin hormone gene transcription and translation in a time-dependent manner. Promoter deletion analysis revealed that activator protein 1 (AP1) was necessary for gastrin gene transcription in cells exposed to Pb(2+) . MitogIen-activated protein kinase (MAPK)/ERK kinase inhibitor PD98059 suppressed the Pb(2+) -induced increase in messenger RNA. Epidermal growth factor receptor (EGFR) inhibitors AG1478 and PD153035 reduced both transcription and phosphorylation by extracellular signal-regulated kinase (ERK1/2). Cells exposed to Pb(2+) also increased production of c-Jun protein, a component of AP1, and over-expression of c-Jun enhanced activation of the gastrin promoter. In sum, the findings suggest the EGFR-ERK1/2-AP1 pathway mediates the effects of Pb(2+) on gastrin gene activity in cell culture.

Cirrhosis as a risk factor for tuberculosis infection--a nationwide longitudinal study in Taiwan.

Tuberculosis (TB) and cirrhosis of the liver are both endemic in many regions of the world. However, the risk of TB in cirrhotic patients has rarely been investigated. A nationwide cohort study was conducted to elucidate and characterize the association between cirrhosis and TB in Taiwan. The study included 41,076 cirrhotic patients and 204,244 noncirrhotic controls from 1998 through 2007. Cirrhotic and noncirrhotic subjects were matched 1:5 on age and sex. A total of 957 of 41,076 (2.32%) cirrhotic patients developed TB, yielding a rate that was significantly higher than that of the 955 of 204,244 (0.46%) noncirrhotic patients (P < 0.001). In a Cox regression model adjusted for age, sex, and underlying medical disorders, a significantly higher active TB rate was maintained for cirrhotic patients compared with their noncirrhotic counterparts (adjusted hazard ratio = 3.55, 95% confidence interval (CI): 3.08, 4.09; P < 0.001). Alcoholism and hepatitis C infection were associated with significantly higher TB risk with adjust hazard ratios of 2.18 (95% CI: 1.86, 4.09; P < 0.001) and 1.18 (95% CI: 1.02, 1.30; P < 0.001), respectively. Cirrhotic patients have a greater risk of TB than noncirrhotic patients, particularly those with alcoholism and hepatitis C infection.

Determining delayed admission to intensive care unit for mechanically ventilated patients in the emergency department.

INTRODUCTION: The adverse effects of delayed admission to the intensive care unit (ICU) have been recognized in previous studies. However, the definitions of delayed admission varies across studies. This study proposed a model to define "delayed admission", and explored the effect of ICU-waiting time on patients' outcome. METHODS: This retrospective cohort study included non-traumatic adult patients on mechanical ventilation in the emergency department (ED), from July 2009 to June 2010. The primary outcomes measures were 21-ventilator-day mortality and prolonged hospital stays (over 30 days). Models of Cox regression and logistic regression were used for multivariate analysis. The non-delayed ICU-waiting was defined as a period in which the time effect on mortality was not statistically significant in a Cox regression model. To identify a suitable cut-off point between "delayed" and "non-delayed", subsets from the overall data were made based on ICU-waiting time and the hazard ratio of ICU-waiting hour in each subset was iteratively calculated. The cut-off time was then used to evaluate the impact of delayed ICU admission on mortality and prolonged length of hospital stay. RESULTS: The final analysis included 1,242 patients. The time effect on mortality emerged after 4 hours, thus we deduced ICU-waiting time in ED > 4 hours as delayed. By logistic regression analysis, delayed ICU admission affected the outcomes of 21 ventilator-days mortality and prolonged hospital stay, with odds ratio of 1.41 (95% confidence interval, 1.05 to 1.89) and 1.56 (95% confidence interval, 1.07 to 2.27) respectively. CONCLUSIONS: For patients on mechanical ventilation at the ED, delayed ICU admission is associated with higher probability of mortality and additional resource expenditure. A benchmark waiting time of no more than 4 hours for ICU admission is recommended.

Association of Decreased Bone Density and Hyperlipidemia in a Taiwanese Older Adult Population.

Objective: This study aimed to determine if a combination of 2 abnormal lipid profiles revealed a stronger association with low bone mass than a single blood lipid abnormality alone. Methods: This study enrolled 1373 participants who had received a dual-energy x-ray absorptiometry scan from January 2016 to December 2016 in a medical center in southern Taiwan. Logistic regression was used to examine association between lipid profiles and osteopenia or osteoporosis after adjusting for covariates. Results: Compared to people with total cholesterol (TC) < 200 mg/dL, those with TC ≥ 240 mg/dL tended to have osteopenia or osteoporosis (OR 2.61; 95% CI, 1.44-4.71). Compared to people with low-density lipoprotein cholesterol (LDL-C) < 130 mg/dL, those with LDL-C ≥ 160 mg/dL tended to develop osteopenia or osteoporosis (OR 2.13; 95% CI, 1.21-3.74). The association of increased triglyceride and decreased bone mass was similar, although not statistically significant. Those with the combination of TG ≥ 200 mg/dL and TC ≥ 240 mg/dL had a stronger tendency to have osteopenia or osteoporosis (OR 3.51; 95% CI, 1.11-11.13) than people with only one blood lipid abnormality. Similarly, people with TG ≥ 200 mg/dL and LDL-C ≥ 160 mg/dL had a stronger tendency to have osteopenia or osteoporosis (OR 9.31; 95% CI, 1.15-75.42) than people with only one blood lipid abnormality, after adjustment for the same covariates. Conclusion: Blood levels of TC, LDL-C, and TG were associated with osteopenia or osteoporosis. Results indicate that individuals aged older than 50 years with abnormal lipid profiles should be urged to participate in a bone density survey to exclude osteopenia or osteoporosis.

Physical frailty identification using machine learning to explore the 5-item FRAIL scale, Cardiovascular Health Study index, and Study of Osteoporotic Fractures index.

Background: Physical frailty is an important issue in aging societies. Three models of physical frailty assessment, the 5-Item fatigue, resistance, ambulation, illness and loss of weight (FRAIL); Cardiovascular Health Study (CHS); and Study of Osteoporotic Fractures (SOF) indices, have been regularly used in clinical and research studies. However, no previous studies have investigated the predictive ability of machine learning (ML) for physical frailty assessment. The aim was to use two ML algorithms, random forest (RF) and extreme gradient boosting (XGBoost), to predict these three physical frailty assessment models. Materials and methods: Questionnaires regarding demographic characteristics, lifestyle habits, living environment, and physical frailty assessment were answered by 445 participants aged 60 years and above. The RF and XGBoost algorithms were used to assess their scores for the three physical frailty indices. Furthermore, feature importance and Shapley additive explanations (SHAP) were used to determine the important physical frailty factors. Results: The XGBoost algorithm obtained higher accuracy for predicting the three physical frailty indices; the areas under the curve obtained by the XGBoost algorithm for the 5-Item FRAIL, CHS, and SOF indices were 0.84. 0.79, and 0.69, respectively. The feature importance and SHAP of the XGBoost algorithm revealed that systolic blood pressure, diastolic blood pressure, age, and body mass index play important roles in all three physical frailty models. Conclusion: The XGBoost algorithm has a more accurate predictive rate than RF across all three physical frailty assessments. Thus, ML can be a useful tool for the early detection of physical frailty.