Nationwide and long-term epidemiological research of snakebite envenomation in Taiwan during 2002-2014 based on the use of snake antivenoms: A study utilizing National Health Insurance Database.

INTRODUCTION: In Taiwan, six venomous snake species with medical importance have been found; however, long-term epidemiological data of snakebite envenomation (SBE) is lacking. This study aimed to explore the epidemiology of SBE based on the distribution and use of different antivenoms in different parts of Taiwan to facilitate the development of prevention strategies and resource allocation. METHODS AND RESULTS: This retrospective study was conducted using the Taiwan National Health Insurance Research Database from 2002 to 2014. A total of 12,542 patients were treated with antivenoms. The directly standardized cumulative incidence was 3.6 cases per 100,000 individuals based on the 2000 World Standard Population. The incidence of SBEs peaked in the summer (35.9%). The relative risk (RR) of male patients versus female patients was 2.5 (p < 0.0001). The RRs of patients aged 18-64 and ≥65 years versus those aged <18 years were 6.0 (p < 0.0001) and 14.3 (p < 0.0001), respectively. Furthermore, the RR of eastern Taiwan versus northern Taiwan was 6.8 (p < 0.0001). The RR of agricultural workers versus laborers was 5.5 (p < 0.0001). Compared with patients envenomed by Trimeresurus stejnegeri stejnegeri or Protobothrops mucrosquamatus, those envenomed by Naja atra or Bungarus multicinctus multicinctus were more likely to occur in central (adjusted odds ratio [aOR] = 2.6, p < 0.0001) or southern (aOR = 3.2, p < 0.0001) Taiwan, but less frequently among agricultural workers (aOR = 0.6, p < 0.0001). The overall case-fatality rate was 0.11%. CONCLUSIONS: Among Asian countries, Taiwan had low incidence and case-fatality rates of SBE. Risk factors included male gender, old age, summer season, being in eastern Taiwan, and being an agricultural worker. Differences of the epidemiological findings between snake species should be focused on when developing strategies for snakebite prevention.

Factors Deciding Conservative or Intervention Treatment for Prostate Abscess: A Retrospective Case-Control Study.

Prostate abscess (PA) can lead to severe urosepsis and septic shock if not treated promptly. However, early diagnosis can be hindered by the declining incidence of PA, especially in developing countries and high-risk patients. Despite the prevalence of PA, there is currently a lack of well-established contemporary guidelines or treatment algorithms. This study aimed to review the etiology, pathophysiology, diagnosis, and treatment options for PA, as well as analyze the characteristics, background profiles of patients, and clinical course. Ultimately, the goal was to develop a personalized treatment strategy for patients with PA. This retrospective study examined 44 patients diagnosed with PA at a tertiary medical center between 2010 and 2020. The patients were divided into two groups based on their treatment: conservative treatment or intervention (transurethral resection of the prostate [TURP] or transurethral prostate drainage [TPD]). The study evaluated various factors, including patients' background profiles, comorbidities, laboratory data, and PA size and volume. Complications of the interventions were also analyzed. No significant differences were found in basic data between the conservative treatment group (19 patients) and intervention group (25 patients; 20 for TURP, 5 for TPD). However, it was observed that single abscesses, size <2.2 cm, and prostate volume <48 cm3, may be suitable for conservative treatment. Patients with diabetes mellitus and human immunodeficiency virus should be monitored for thrombotic events. In addition, there was a significant difference in white blood count between the two groups (12.1 ± 7.0 vs. 17.6 ± 9.7 × 109/L, p < 0.05). A subgroup analysis of the intervention group showed no significant difference in the risk of complications between TPD and TURP. Patients with poorly controlled diabetes mellitus and immunodeficiency are at a high risk of PA but are not indicated for surgical treatment. The PA profile, including number, size, volume, and percentage to prostate volume, should be considered when deciding on surgical intervention for patients with PA. Patients with higher leukocytosis may require surgical treatment. Overall, these findings can help guide the development of a personalized treatment strategy for patients with PA.

Transcriptome-wide analyses of piRNA binding sites suggest distinct mechanisms regulate piRNA binding and silencing in C. elegans.

PIWI-interacting RNAs (piRNAs) protect genome integrity by silencing transposon mRNAs and some endogenous mRNAs in various animals. However, C. elegans piRNAs only trigger gene silencing at select predicted targeting sites, suggesting additional cellular mechanisms regulate piRNA silencing. To gain insight into possible mechanisms, we compared the transcriptome-wide predicted piRNA targeting sites to the in vivo piRNA binding sites. Surprisingly, while sequence-based predicted piRNA targeting sites are enriched in 3' UTRs, we found that C. elegans piRNAs preferentially bind to coding regions (CDS) of target mRNAs, leading to preferential production of secondary silencing small RNAs in the CDS. However, our analyses suggest that this CDS binding preference cannot be explained by the action of antisilencing Argonaute CSR-1. Instead, our analyses imply that CSR-1 protects mRNAs from piRNA silencing through two distinct mechanisms-by inhibiting piRNA binding across the entire CSR-1 targeted transcript, and by inhibiting secondary silencing small RNA production locally at CSR-1 bound sites. Together, our work identifies the CDS as the critical region that is uniquely competent for piRNA binding in C. elegans. We speculate the CDS binding preference may have evolved to allow the piRNA pathway to maintain robust recognition of RNA targets in spite of genetic drift. Together, our analyses revealed that distinct mechanisms are responsible for restricting piRNA binding and silencing to achieve proper transcriptome surveillance.

Sodium-Glucose Transport Protein 2 Inhibitor Use for Type 2 Diabetes and the Incidence of Acute Kidney Injury in Taiwan.

Importance: The association between sodium-glucose transport protein 2 inhibitor (SGLT2i) use and the incidence of acute kidney injury (AKI) remains controversial. The benefits of SGLT2i use in patients to reduce AKI requiring dialysis (AKI-D) and concomitant diseases with AKI as well as improve AKI prognosis have not yet been established. Objective: To investigate the association between SGLT2i use and AKI incidence in patients with type 2 diabetes (T2D). Design, Setting, and Participants: This nationwide retrospective cohort study used the National Health Insurance Research Database in Taiwan. The study analyzed a propensity score-matched population of 104 462 patients with T2D treated with SGLT2is or dipeptidyl peptidase 4 inhibitors (DPP4is) between May 2016 and December 2018. All participants were followed up from the index date until the occurrence of outcomes of interest, death, or the end of the study, whichever was earliest. Analysis was conducted between October 15, 2021, and January 30, 2022. Main Outcomes and Measures: The primary outcome was the incidence of AKI and AKI-D during the study period. AKI was diagnosed using International Classification of Diseases diagnostic codes, and AKI-D was determined using the diagnostic codes and dialysis treatment during the same hospitalization. Conditional Cox proportional hazard models assessed the associations between SGLT2i use and the risks of AKI and AKI-D. The concomitant diseases with AKI and its 90-day prognosis, ie, the occurrence of advanced chronic kidney disease (CKD stage 4 and 5), end-stage kidney disease, or death, were considered when exploring the outcomes of SGLT2i use. Results: In a total of 104 462 patients, 46 065 (44.1%) were female patients, and the mean (SD) age was 58 (12) years. After a follow-up of approximately 2.50 years, 856 participants (0.8%) had AKI and 102 (<0.1%) had AKI-D. SGLT2i users had a 0.66-fold risk for AKI (95% CI, 0.57-0.75; P < .001) and 0.56-fold risk of AKI-D (95% CI, 0.37-0.84; P = .005) compared with DPP4i users. The numbers of patients with AKI with heart disease, sepsis, respiratory failure, and shock were 80 (22.73%), 83 (23.58%), 23 (6.53%), and 10 (2.84%), respectively. SGLT2i use was associated with lower risk of AKI with respiratory failure (hazard ratio [HR], 0.42; 95% CI, 0.26-0.69; P < .001) and shock (HR, 0.48; 95% CI, 0.23-0.99; P = .048) but not AKI with heart disease (HR, 0.79; 95% CI, 0.58-1.07; P = .13) and sepsis (HR, 0.77; 95% CI, 0.58-1.03; P = .08). The 90-day AKI prognosis for the risk of advanced CKD indicated a 6.53% (23 of 352 patients) lower incidence in SGLT2i users than in DPP4i users (P = .045). Conclusions and Relevance: The study findings suggest that patients with T2D who receive SGLT2i may have lower risk of AKI and AKI-D compared with those who receive DPP4i.

Determination of potential sources of heavy metals in patients with urothelial carcinoma in central Taiwan: a biomonitoring case-control study.

The clarification of possible exposure sources of multiple metals to identify associations between metal doses and urothelial carcinoma (UC) risk is currently limited in the literature. We sought to identify the exposure sources of 10 metals (Vanadium, chromium, manganese, cobalt, nickel, copper, zinc, arsenic, cadmium, and lead) using principal component analysis (PCA) and then linked various principal component (PC) scores with environmental characteristics, including smoking-related indices, PM2.5, and distance to the nearest bus station. In addition, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and DNA hypomethylation markers (5-methyl-2'-deoxycytidine levels; %5-MedC) were investigated in combination with UC risks. We conducted this hospital-based case control study in 359 UC patients with histologically confirmed disease and 718 controls. All data were collected from face-to-face interviews and medical records. Approximately 6 mL blood was collected from participants for analysis of multiple heavy metal and DNA methylation in leukocyte DNA. Further, a 20 mL urine sample was collected to measure urinary cotinine and 8-OHdG levels. In addition, average values for PM2.5 for individual resident were calculated using the hybrid kriging/land-use regression model. In UC patients, significantly higher cobalt, nickel, copper, arsenic, and cadmium (µg/L) levels were observed in blood when compared with controls. Three PCs with eigenvalues > 1 accounted for 24.3, 15.8, and 10.7% of UC patients, and 26.9, 16.7, and 11.1% of controls, respectively. Environmental metal sources in major clusters were potentially associated with industrial activities and traffic emissions (PC1), smoking (PC2), and food consumption, including vitamin supplements (PC3). Multiple metal doses were linked with incremental urinary 8-OHdG and DNA hypomethylation biomarkers. For individuals with high PC1 and PC2 scores, both displayed an approximate 1.2-fold risk for UC with DNA hypomethylation.In conclusion, we provide a foundation for health education and risk communication strategies to limit metal exposure in environment, so that UC risks can be improved potentially.

APOE-ε4 Alleles Modify the Decline of MMSE Scores Associated With Time-Dependent PM2.5 Exposure: Findings From a Community-Based Longitudinal Cohort Study.

OBJECTIVE: Limited research has explored the long-term effect of reduced PM2.5 exposure on cognitive function. This study aimed to investigate the effects of time-dependent PM2.5 exposure and the interactions of PM2.5 and aging on declines in Mini-Mental State Examination (MMSE) scores, in carriers and non-carriers of the APOE-ε4 allele. METHODS: Participants aged over 60 were recruited for this cohort study, undergoing MMSE tests twice from the Taiwan Biobank Program from 2008 to 2020. Participants with dementia or baseline MMSE scores <24 were excluded. Annual PM2.5 levels were estimated using a hybrid kriging/land use regression model with extreme gradient boosting, treated as a time-dependent variable. Generalized estimating equations were used to assess the impacts of repeated PM2.5 on MMSE decline, further stratified by the presence of APOE-ε4 alleles. RESULTS: After follow-up, 290 participants out of the overall 7,000 community residents in the Biobank dataset demonstrated incidences of MMSE declines (<24), with an average MMSE score decline of 1.11 per year. Participants with ε4/ε4 alleles in the APOE gene had significantly 3.68-fold risks of MMSE decline. High levels of PM2.5 across all visits were significantly associated with worsening of scores on the overall MMSE. As annual levels of PM2.5 decreased over time, the impact of PM2.5 on MMSE decline also slowly diminished. CONCLUSION: Long-term PM2.5 exposure may be associated with increased risk of MMSE decline, despite improvements in ambient PM2.5 levels over time. Validation of these results necessitates a large-scale prospective cohort study with more concise cognitive screening tools.

METTL4-mediated nuclear N6-deoxyadenosine methylation promotes metastasis through activating multiple metastasis-inducing targets.

BACKGROUND: DNA N6-methyldeoxyadenosine (6mA) is rarely present in mammalian cells and its nuclear role remains elusive. RESULTS: Here we show that hypoxia induces nuclear 6mA modification through a DNA methyltransferase, METTL4, in hypoxia-induced epithelial-mesenchymal transition (EMT) and tumor metastasis. Co-expression of METTL4 and 6mA represents a prognosis marker for upper tract urothelial cancer patients. By RNA sequencing and 6mA chromatin immunoprecipitation-exonuclease digestion followed by sequencing, we identify lncRNA RP11-390F4.3 and one novel HIF-1α co-activator, ZMIZ1, that are co-regulated by hypoxia and METTL4. Other genes involved in hypoxia-mediated phenotypes are also regulated by 6mA modification. Quantitative chromatin isolation by RNA purification assay shows the occupancy of lncRNA RP11-390F4.3 on the promoters of multiple EMT regulators, indicating lncRNA-chromatin interaction. Knockdown of lncRNA RP11-390F4.3 abolishes METTL4-mediated tumor metastasis. We demonstrate that ZMIZ1 is an essential co-activator of HIF-1α. CONCLUSIONS: We show that hypoxia results in enriched 6mA levels in mammalian tumor cells through METTL4. This METTL4-mediated nuclear 6mA deposition induces tumor metastasis through activating multiple metastasis-inducing genes. METTL4 is characterized as a potential therapeutic target in hypoxic tumors.

Long-term exposure to air pollutants and increased risk of chronic kidney disease in a community-based population using a fuzzy logic inference model.

Background: Fuzzy inference systems (FISs) based on fuzzy theory in mathematics were previously applied to infer supplementary points for the limited number of monitoring sites and improve the uncertainty of spatial data. Therefore we adopted the FIS method to simulate spatiotemporal levels of air pollutants [particulate matter <2.5 µm (PM2.5), sulfur dioxide (SO2) and (NO2)] and investigated the association of levels of air pollutants with the community-based prevalence of chronic kidney disease (CKD). Methods: A Complex Health Screening program was launched during 2012-2013 and a total of 8284 community residents in Chiayi County, which is located in southwestern Taiwan, received a series of standard physical examinations, including measurement of estimated glomerular filtration rate (eGFR). CKD cases were defined as eGFR <60 mL/min/1.73 m2 and were matched for age and gender in a 1:4 ratio of cases:controls. Data on air pollutants were collected from air quality monitoring stations during 2006-2016. The longitude, latitude and recruitment month of the individual case were entered into the trained FIS. The defuzzification process was performed based on the proper membership functions and fuzzy logic rules to infer the concentrations of air pollutants. In addition, we used conditional logistic regression and the distributed lag nonlinear model to calculate the prevalence ratios of CKD and the 95% confidence interval. Confounders including Framingham Risk Score (FRS), diabetes, gout, arthritis, heart disease, metabolic syndrome and vegetables consumption were adjusted in the models. Results: Participants with a high FRS (>10%), diabetes, heart disease, gout, arthritis or metabolic syndrome had significantly increased CKD prevalence. After adjustment for confounders, PM2.5 levels were significantly increased in CKD cases in both single- and two-pollutant models (prevalence ratio 1.31-1.34). There was a positive association with CKD in the two-pollutant models for NO2. However, similar results were not observed for SO2. Conclusions: FIS may be helpful to reduce uncertainty with better interpolation for limited monitoring stations. Meanwhile, long-term exposure to ambient PM2.5 appears to be associated with an increased prevalence of CKD, based on a FIS model.

Association of SGLT2 inhibitors with lower incidence of death in type 2 diabetes mellitus and causes of death analysis.

Sodium-glucose cotransporter 2 inhibitor (SGLT2i) potentially decrease all-cause and cardiovascular death, however, associations with non-cardiovascular death remain unclear. Therefore, we investigated SGLT2i associations with death and the cause of death. We used the Taiwanese National Health Institutes Research database linked to the National Register of Deaths (NRD). Incident type 2 diabetes mellitus (T2DM) patients and propensity score matched T2DM SGLT2i and Dipeptidyl peptidase 4 inhibitor (DPP4i) users were investigated. The index year was the SGLT2i or DPP4i prescription date from May 2016. Patients were followed-up until death or December 2018. Deaths verified by the NRD and grouped accordingly. Multiple Cox proportional hazards models were used. In total, 261,211 patients were included in the population; 47% of the patients were female and the average age was 62 years. The overall incidence of all-cause death was 8.67/1000 patient-years for SGLT2i and 12.41 for DPP4i users during follow-up. After adjusting for potential risk factors in the propensity score matched population, SGLT2i users were associated with lower risks of all-cause death, cardiovascular death, cancer death, and non-cancer, non-vascular death compared with DPP4i-users. For specific death causes, significantly lower death risks from heart disease, cerebrovascular disease, and accidents were associated with SGLT2i-use. SGLT2i benefits for T2DM patients were not different across subgroups. Compared with DPP4i-use, SGLT2i-use for T2DM was associated with lower disease and death risk.

Long-Term Exposure to Fine Particulate Matter and the Deterioration of Estimated Glomerular Filtration Rate: A Cohort Study in Patients With Pre-End-Stage Renal Disease.

Limited literature has explored the effect of air pollutants on chronic kidney disease (CKD) progression, especially for patients with pre-end-stage renal disease (pre-ESRD). In this study, we reported the linear and nonlinear relationships of air pollutants of particles with diameter <2.5 µm (PM2.5) and nitrogen dioxide (NO2) with estimated glomerular filtration rate (eGFR) deterioration after adjusting for smoking status and other traditional clinical factors. This study adopted a retrospective cohort of patients with stage 3b to stage 5 CKD (N = 11,479) from Taichung Veterans General Hospital during January 2006 to December 2020. The eGFR deterioration was defined as a decline in eGFR > 5 ml/min/1.73 m2/year. Hybrid kriging/land-use regression models were used to estimate the individual exposure levels of PM2.5 and NO2. The relationships of air pollutants with eGFR deterioration were evaluated using Cox proportional hazard models. After adjusting for smoking status, baseline eGFR stages, and other traditional clinical factors, the risk of eGFR deterioration was found to increase with increasing PM2.5 and NO2 level (p < 0.0001 and p = 0.041, respectively), especially for those exposed to PM2.5 ≥ 31.44 µg/m3 or NO2 ≥ 15.00 ppb. Similar results were also found in the two-pollutant models. Nonlinear dose-response relationships of eGFR deterioration were observed for concentrations of 26.11 µg/m3 for PM2.5 and 15.06 ppb for NO2. In conclusion, linear and nonlinear associations between PM2.5 and NO2 levels and the incidence risk of eGFR deterioration were observed in patients with pre-ESRD.

Association and mediation analyses among multiple metals exposure, plasma folate, and community-based impaired estimated glomerular filtration rate in central Taiwan.

BACKGROUND: Chronic kidney disease (CKD) is increasing, with heavy metal exposure an important risk factor. Additionally, the antioxidant folic acid has been studied for reducing blood arsenic levels and related tissue damage. Therefore, we explored the association and mediation effects among various heavy metal levels in blood, plasma folate, other CKD risk factors, and impaired estimated glomerular filtration rate (eGFR). METHODS: We constructed a community-based cross-sectional study from the Human Biomonitoring and Environmental Health Program in central Taiwan. A total of 1643 participants had lived locally for > 5 years, > 40 years old, and completely received health examinations and biospecimen collections. Impaired eGFR was defined as one single eGFR < 60 mL/min/1.73 m2. Plasma folate and metal levels in blood were determined, as well as urinary 8-hydroxy-2'-deoxyguanosine as an oxidative stress marker. Generalized weighted quantile sum (WQS) regression analysis was used to calculate a WQS score, reflecting overall body-burden of multiple metals (arsenic, cadmium, chromium, nickel, and lead) in blood. RESULTS: Impaired eGFR was identified in 225 participants. Participants with high WQS scores had increased risk of impaired eGFR (odds ratio = 1.67; 95% confidence interval [CI]: 1.34, 2.07). Of five metals, arsenic, lead, and cadmium were weighted highly in impaired eGFR. Participants with high WQS and folate insufficiency (< 6 ng/mL) had 2.38-fold risk of impaired eGFR compared to those with low WQS and high folate (≥6 ng/mL) (95% CI: 1.55, 5.17). Similar increased 4.16-fold risk of impaired eGFR was shown in participants with high WQS and uric acid levels (95% CI: 2.63, 6.58). However, there were no significant WQS-folate (p = 0.87) or WQS-uric acid (p = 0.38) interactions on impaired eGFR risk. As a mediator, uric acid contributed 24% of the association between WQS score and impaired eGFR risk (p < 0.0001). However, no mediation effect of plasma folate was observed. CONCLUSION: WQS analysis could be applied to evaluate the joint effects of multiple metals exposure. High WQS scores may influence impaired eGFR risk through increased uric acid levels. A large-scale and prospective cohort study is necessary to validate these results and demonstrate any causal relationship.

Relationships of multiple metals exposure, global DNA methylation, and urothelial carcinoma in central Taiwan.

The relationship between heavy metal exposure and human health has been investigated mostly for individual metals, failing to consider their potential interactions. In this study, we assessed the joint effects of multiple metals using generalized weighted quantile sum (WQS) regression on the risk of urothelial carcinoma (UC). Also, we performed mediation analysis to evaluate the mediator %5-MedC in DNA involved in the mechanism of urothelial carcinogenesis. We conducted a hospital-based case-control study of 355 UC patients and 710 controls, where diagnosis of UC was histologically confirmed. All data were collected from face-to-face interviews and medical records. Also, we measured six metals and 8-OHdG in urine samples along with %5-MedC in peripheral blood. Ni and Pb levels increased with UC risk in single-pollutant analysis using traditional logistic regression, and similar results were obtained in multi-pollutant analysis, where all metals analyzed were considered. In WQS analysis, the weights of Ni (27%), Pb (20%), Cr (18%), and Co (16%) predominated in the metal mixture index. WQS score and UC risk showed odds ratios of 1.65 (95%CI: 1.26, 2.15) and 1.43 (95%CI: 1.00, 2.05) for a linear and non-linear relationship, respectively. Finally, we did not observe a natural indirect effect of %5-MedC in DNA; however, a marginal effect of WQS score and natural direct effect were still found after considering a natural indirect effect. In conclusion, positive associations between WQS scores and increased risk of UC were observed. Interactions of multiple metals should be considered in assessing human health risk.

Impact of peritoneal dialysis-related peritonitis on PD discontinuation and mortality: A population-based national cohort study.

BACKGROUND: The impact of peritoneal dialysis-associated peritonitis (PD peritonitis) on long-term outcomes is uncertain. This nationwide retrospective study was conducted in Taiwan to understand the incidence, risk factors and long-term outcomes of PD peritonitis. METHODS: A total of 11,202 incident adult peritoneal dialysis (PD) patients from 2000 to 2010 were collected from a Longitudinal Health Insurance Database and followed up until the end of 2011. Definition of peritonitis, the primary outcome, simultaneously met the diagnosis of peritonitis (International Classification of Diseases, Ninth Revision, Clinical Modification 567) and antibiotic use. Secondary outcomes included the impact of peritonitis on PD discontinuation and survival. Cox proportional hazards models with and without time-dependent variables were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS: There were 7634 peritonitis episodes in 4245 patients during the follow-up period. The overall incidence of peritonitis was 0.18 episodes per patient-year. Peritonitis-associated risk factors included older age, female gender, chronic heart failure, cerebrovascular disease, liver cirrhosis and lower monthly income. In an adjusted Cox hazard proportional regression with the time-dependent model, peritonitis patients had a higher risk of PD discontinuation (HR 2.71, 95% CI 2.52-2.92) and mortality (HR 1.68, 95% CI 1.57-1.81) compared to patients without peritonitis. The adjusted HRs for mortality increased with each prior episode: one episode, two episodes and more than two episodes (all p < 0.05). The adjusted HRs for PD discontinuation also increased with the frequency of peritonitis. These negative effects were greatest during the first year and persisted significantly after 5 years. In a sensitivity analysis in which peritonitis within 30 days of death or PD discontinuation was excluded, peritonitis patients still had significantly increased risk of PD discontinuation and mortality compared to patients without peritonitis. CONCLUSIONS: Although peritonitis incidence was low, our findings reveal that peritonitis carried acute and long-term sequelae of higher PD discontinuation and lower patient survival.

The combined effects of nucleotide-binding domain-like receptor protein 3 polymorphisms and levels of blood lead on developmental delays in preschool children.

Nucleotide-binding domain-like receptors protein 3 (NLRP3) inflammasomes are associated with neuroinflammation and multiple NLRP3 genes regulate NLRP3 expression. Our study aimed to investigate the association of NLRP3 polymorphisms with developmental delay in preschool children. We also explored whether NLRP3 polymorphisms modified the effects of total urinary arsenic and blood cadmium and lead to developmental delays. A total of 178 children with developmental delays and 88 healthy children were analyzed for urinary arsenic concentrations and red blood cell lead and cadmium concentrations. We examined the genotypes of fifteen common single-nucleotide polymorphisms in NLRP3. We observed that levels of total urinary arsenic and blood lead were significantly associated with developmental delay. The NLRP3rs10754555 CG versus CC/GG, NLRP3rs12048215 AG versus AA/GG, and NLRP3rs12137901 TC/TT versus CC genotype showed a lower odds of developmental delay, with the odds ratio (OR) and 95% confidence interval (CI) = 0.38 (0.19-0.75), 0.52 (0.27-0.99), and 0.33 (0.12-0.90), respectively. Children with the NLRP3rs10754555 CC/GG genotype and high blood lead levels had a significant multiplicative interaction with developmental delay [OR (95% CI) = 9.74 (3.59-26.45)]. This study found evidence that suggested the joint effects of NLRP3rs10754555 CC/GG genotype and high blood lead levels on developmental delays.

Exploring the factors related to adolescent health literacy, health-promoting lifestyle profile, and health status.

BACKGROUND: Health literacy has been concerned a key factor for determining the use of health information and promoting health. The study aimed to explore adolescent health literacy, health-promoting lifestyle profile, and health status and related factors. METHODS: A cross-sectional study design was used; 918 first year junior college students were recruited in Taiwan. The measurements were the Chinese Health Literacy Survey Questionnaire (HLS-C-Q), the Chinese Health-Promoting Lifestyle Profile (HPLP-S), and the Health Status Questionnaire. RESULTS: The mean score for health literacy was 36.15 (±6.21), with 30.17% of the participants having insufficient or problematic health literacy. Further, 19.9% of participants were obese and 11.2% experienced emotional instability. Health literacy and health-promoting lifestyle profile showed significant positive and negative correlations with perceived health status and depression, respectively (p < 0.05). An exercise frequency of ≥3 times/week was a predictor of health literacy, health-promoting lifestyle profile, and emotional stability. CONCLUSIONS: Adolescent health literacy, health-promoting lifestyle profile, and health status require careful consideration. In adolescents, developing regular exercise may increase health literacy, thereby developing healthy lifestyle profiles and ameliorating obesity and depression-related issues.

Ethnic disparity in metabolic syndrome and related obesity and health behavior: a community study in Taiwan.

BACKGROUND: As studies on ethnic disparities in metabolic syndrome and its risk factors in Taiwan are still rare, the aims of this study were: (1) to detect the differences in the rates of metabolic syndrome, obesity and health behaviors between two ethnic groups (indigenous Tsou and nonindigenous Han) living in the same area and with similar age and sex distributions; (2) to examine whether ethnicity per se plays a significant role in the occurrence of metabolic syndrome, while taking other risk factors including sociodemographic characteristics, obesity and health behaviors into consideration. METHODS: This is a cross-sectional study using data from a community survey conducted in Chiayi County in southwestern Taiwan. A frequency matching strategy by age and sex with a ratio of 1 (Tsou) to 3 (Han) was applied to select a comparable sample between both ethnic groups (667 Tsou and 2001 Han) from among the survey participants. Furthermore, participants with cardiometabolic diseases diagnosed before the surveyed day were excluded to avoid confounding any associated risk factors for developing metabolic syndrome (MS). A final analytic sample of 1482 remained. The used information included sociodemographic characteristics, medical histories, health behaviors, and the concentrations of triglycerides, cholesterol, and glucose. RESULTS: Indigenous Tsou had significantly higher rates of metabolic syndromes, obesity and unhealthy behaviors than their Han counterparts (MS: 54.0% vs. 29.1%, obesity: 54.0% vs. 23.2%, drinking alcohol: 17.5% vs. 13.6%, and higher intake of fried food: 6.4% vs. 4.4%), even though they were similar in age and sex distributions. The significant risk factors for subsequently developing MS included being indigenous Tsou (adjusted POR = 2.62, P < 0.001), older, single, and obese. Stratified analyses on the risk factors for developing MS by health behaviors and by obese problems also indicated increased risks of being indigenous Tsou. CONCLUSIONS: There existed ethnic differences in the rates of metabolic syndrome, obesity, and health behaviors. Ethnicity per se did play a significant role in developing MS; in particular indigenous Tsou people had increased risks, suggesting possible biological reasons rooted in their origins that need further exploration. In addition, unhealthy behaviors may potentially have an indirect effect on developing MS via their effect on obesity.

Association of Sodium-Glucose Transport Protein 2 Inhibitor Use for Type 2 Diabetes and Incidence of Gout in Taiwan.

Importance: The use of sodium-glucose transport protein 2 (SGLT2) inhibitors is currently a standard intervention in patients with type 2 diabetes (T2DM) and exerts favorable pleiotropic effects to consistently lower blood urate levels. However, to date, no association between SGLT2 inhibitor use and the incidence of gout have been established. Objective: To investigate whether prescribed SGLT2 inhibitors are associated with lower gout incidence in patients with T2DM. Design, Setting, and Participants: In a cohort study, all patients with incident T2DM in Taiwan National Health Institution databases between May 1, 2016, and December 31, 2018, were retrospectively analyzed. As a comparator, patients using dipeptidyl peptidase 4 (DPP4) inhibitors were included. A total of 47 905 individuals receiving an SGLT2 inhibitor and 183 303 receiving a DPP4 inhibitor were evaluated, along with 47 405 pairs of patients using an SGLT2 inhibitor or DPP4 inhibitor in 1:1 propensity score-matched analyses. Data analysis was conducted from April 1 to June 30, 2021. Main Outcomes and Measures: A gout diagnosis was based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) and the International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM). Multiple Cox proportional hazards regression models were used to calculate hazard ratios (HRs) and 95% CIs. Results: In total, 231 208 patients with T2DM were included in the population; 113 812 individuals (49.22%) were women, and the mean (SD) age was 61.53 (12.86) years. The overall gout incidence was 20.26 per 1000 patient-years for SGLT2 inhibitor users and 24.30 per 1000 patient-years for DPP4 inhibitor users. When potential risk factors were adjusted in the propensity score-matched population, use of SGLT2 inhibitors was associated with a lower risk of gout (HR, 0.89; 95% CI, 0.82-0.96) compared with DPP4 inhibitors, particularly for patients receiving dapagliflozin (HR, 0.86; 95% CI, 0.78-0.95). A sensitivity analysis, performed when a gout diagnosis was ascertained using the ICD-9-CM or ICD-10-CM code with gout-related medication, also showed a significantly lower risk for gout incidence of 15% with SGLT2 inhibitors (HR, 0.85; 95% CI, 0.74-0.97). Subgroup analysis indicated that SGLT2 inhibitor benefits in patients with T2DM to achieve a lower gout risk were not different across subgroups. Conclusions and Relevance: The findings of this study suggest that patients with T2DM who are receiving SGLT2 inhibitors may have a lower risk for gout compared with those receiving DPP4 inhibitors.

The effects of traffic-related air pollutants on chronic obstructive pulmonary disease in the community-based general population.

BACKGROUND: Previous studies have shown inconsistent results regarding the impact of traffic pollution on the prevalence of chronic obstructive pulmonary disease (COPD). Therefore, using frequency matching and propensity scores, we explored the association between traffic pollution and COPD in a cohort of 8284 residents in a major agricultural county in Taiwan. METHODS: All subjects completed a structured questionnaire interview and health checkups. Subjects with COPD were identified using Taiwan National Health Insurance Research Databases. A hybrid kriging/LUR model was used to identify levels of traffic-related air pollutants (PM2.5 and O3). Multiple logistic regression models were used to calculate the prevalence ratios (PRs) of COPD and evaluate the role played by traffic-related indices between air pollutants and COPD. The distributed lag nonlinear model was applied in the analysis; we excluded current or ever smokers to perform the sensitivity analysis. RESULTS: Increased PRs of COPD per SD increment of PM2.5 were 1.10 (95% CI 1.05-1.15) and 1.25 (95% CI 1.13-1.40) in the population with age and sex matching as well as propensity-score matching, respectively. The results of the sensitivity analysis were similar between the single and two pollutant models. PM2.5 concentrations were significantly associated with traffic flow including sedans, buses, and trucks (p < 0.01). The higher road area and the higher PM2.5 concentrations near the subject's residence correlated with a greater risk of developing COPD (p for interaction < 0.01). CONCLUSIONS: Our results suggest that long-term exposure to traffic-related air pollution may be positively associated with the prevalence of COPD.

Exposure to Ambient NO2 Increases the Risk of Dry Eye Syndrome in Females: An 11-Year Population-Based Study.

Previous studies have indicated that women suffer from dry eye syndrome (DES) more significantly than men. Therefore, we specifically explore the associations between air pollutant levels and the risks of DES for women. The study obtained 27,605 participants from the 29 recruitment centers of the Taiwan Biobank, which was established in October 2012. A large scale cross-sectional study involving DES sufferers and age- and education-matched control groups without DES was designed. Based on the municipality of residence, the predicted concentration levels of various air pollutants, including PM2.5, sulfur dioxide (SO2), ozone (O3), and nitrogen dioxide (NO2) were estimated by using hybrid kriging/LUR model. Multiple logistic regressions were applied to estimate the prevalence ratios (PR) of DES and 95% confidence interval. Hormone supplementations, DBP, allergies, and arthritis were considered as important comorbidities for increased PR risk of DES. In addition, with each standard deviation (SD) increment of PM2.5 and temperature, women had significant increases in PRs of DES of 1.09- and 1.07-fold, respectively; conversely, each SD increment of relative humidity (RH) had a protective effect against the risk of DES. After considering hormone supplementation, arthritis, and allergy, the SD increment of NO2 and temperature were associated with the PRs of DES. In conclusion, significant associations of ambient NO2 concentration, RH and temperature with DES indicated the importance of increased environmental protection in the female population. Female exposure to high levels of NO2 when receiving hormone supplementation, or suffering with allergies or arthritis, had significantly increased risk of DES.

Primary aldosteronism is associated with risk of urinary bladder stones in a nationwide cohort study.

We analyzed database from the Taiwan National Health Insurance to investigate whether primary aldosteronism (PA) increases the risk of bladder stones. This retrospective nationwide population-based cohort study during the period of 1998-2011 compared patients with and without PA extracted by propensity score matching. Cox proportional hazard models and competing death risk model were used to estimate the hazard ratios (HRs), sub-hazard ratios (SHRs) and corresponding 95% confidence intervals (CIs). There were 3442 patients with PA and 3442 patients without PA. The incidence rate of bladder stones was 5.36 and 3.76 per 1000 person-years for both groups, respectively. In adjusted Cox hazard proportional regression models, the HR of bladder stones was 1.68 (95% CI 1.20-2.34) for patients with PA compared to individuals without PA. Considering the competing risk of death, the SHR of bladder stones still indicates a higher risk for PA than a comparison cohort (SHR, 1.79; 95% CI 1.30-2.44). PA, age, sex, and fracture number were the variables significantly contributing to the formation of bladder stones. In conclusion, PA is significantly associated with risk of bladder stones.