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BackgroundParticulate matter (PM) < 2.5 μm (PM2.5) or fine PM is a serious public health concern. It affects DNA methylation and heightens carcinogenesis. Deleted in lung and esophageal cancer 1 (DLEC1) is a tumor suppressor gene. However, aberrant methylation of the gene is associated with several cancers. We evaluated the association between PM2.5and DLEC1 promoter methylation in Taiwanese adults based on regular outdoor exercise.MethodsWe obtained DNA methylation and exercise data of 496 participants (aged between 30 and 70 years) from the Taiwan Biobank (TWB) database. We also extracted PM2.5data from the Air Quality Monitoring Database (AQMD) and estimated participants’ exposure using residential addresses.ResultsDLEC1 methylation and PM2.5were positively associated: beta coefficient (β) = 0.114 × 10−3;pvalue = 0.046. The test for interaction between exercise and PM2.5on DLEC1 methylation was significant (pvalue = 0.036). After stratification by exercise habits, PM2.5and DLEC1 methylation remained significantly associated only among those who exercised regularly (β= 0.237 × 10−3;pvalue = 0.007). PM2.5quartile-stratified analyses revealed an inverse association between regular exercise and DLEC1 methylation at PM2.5< 27.37 μg/m3(β= − 5.280 × 10−3;pvalue = 0.009). After combining exercise habits and PM2.5quartiles, one stratum (i.e., regular exercise and PM2.5< 27.37 μg/m3) was inversely associated with DLEC1 methylation (β= -5.160 × 10−3,pvalue = 0.007).ConclusionsWe found significant positive associations between PM2.5and DLEC1 promoter methylation. Regular exercise at PM2.5< 27.37 μg/m3seemingly regulated DLEC1 promoter methylation.

Background Glycosylated hemoglobin (HbA1c) reflects the average blood sugar over the past eight to twelve weeks. Several demographic and lifestyle factors are known to affect HbA1c levels. We evaluated the association of HbA1c with aerobic and resistance exercise in non-diabetic Taiwanese adults based on the waist-hip ratio (WHR). Methods We conducted this study based on TWB data collected from 90,958 individuals between 2008 and 2019. We estimated the Beta (β) coefficient and 95% confidence intervals (CI) for HbA1c using multivariate regression models. Results Based on the multivariate analysis, lower HbA1c levels were associated with both resistance exercise (β-coefficient = -0.027, 95% CI -0.037 to -0.017) and aerobic exercise (β-coefficient = 0.018, 95% CI, -0.023 to -0.013). Higher HbA1c levels were associated with abnormal WHR compared to normal WHR (β-coefficient = 0.091, 95% CI, 0.086 to 0.096). We detected an interaction between exercise and WHR (p for interaction = 0.0181). To determine the magnitude of the interaction, we performed additional analyses (with the reference group being ’abnormal WHR with no exercise’) and observed substantial decreases in HbA1c regardless of the WHR and exercise category. However, the largest reduction occurred in the ’normal WHR and resistance exercise’ group (β = -0.121, 95% CI, -0.132 to -0.109). Conclusions We found that normal resistance exercise, coupled with a normal WHR was significantly associated with lower HbA1c levels among non-diabetic individuals in Taiwan.

Background and objectives: High-density lipoprotein cholesterol (HDL-C) is important for improving risk estimates of atherosclerotic cardiovascular disease. We investigated the effect of omnivore and diverse vegetarian diets in connection with exercise on HDL-C. Materials and Methods: Historical data of 9588 biobank participants (4025 exercisers and 5563 non-exercisers) aged 30&ndash, 70 years were categorized as omnivores (n = 8589), former vegetarians (n = 544), lacto-ovo vegetarians (n = 417), and strict vegetarians (n = 38). We used multiple linear regression for analyses. Results: HDL-C levels were higher in exercisers compared to non-exercisers. Compared with omnivores, strict vegetarians had decreased levels of HDL-C (&beta, = &minus, 5.705, p = 0.001) followed by lacto-ovo vegetarians (&beta, 3.900, p &lt, 0.001) and former vegetarians (&beta, 0.329, p = 0.475). The test for trend was significant (p &lt, 0.001). After categorization by exercise modalities, the &beta, value was &minus, 13.984 for strict vegetarians, &minus, 4.419 for lacto-ovo vegetarians, and &minus, 1.864 for former vegetarians, respectively (p &lt, 0.05). There was an interaction between diet and exercise (p = 0.009). Omnivores who exercised regularly had significantly higher HDL-C, whereas strict vegetarians who exercised regularly had significantly lower HDL-C. Conclusions: In summary, strict vegetarian diets in conjunction with regular exercise might not serve as healthful behaviors to be implemented in everyday life considering the negative impact on HDL-C.

Education, sex, and the APOE-rs405509 variant are associated with Alzheimer&rsquo, s disease and cognitive performance. We investigated if the rs405509 TT, TG, and GG genotypes modulate the effect of sex and education on cognitive impairment in Taiwanese adults. Data on cognitive health (defined by Mini-Mental State Examination (MMSE) scores) and rs405509 were from Taiwan Biobank. Participants included 2105 men and 2027 women with a mean age of 64 years. Education below university level was significantly associated with lower MMSE scores. The odds ratios (ORs) were 1.82, 95% confidence interval (CI) 1.38&ndash, 2.41 for senior high school, 3.39, 95% CI 2.50&ndash, 4.59 for junior high school, and 11.94, 95% CI 9.91&ndash, 15.50 for elementary school and below (p-trend &lt, 0.05). The association between MMSE score and sex was significant only in the lowest educational group (elementary and below), with lower odds of having a low MMSE score in men compared to women (OR = 0.51, 95% CI 0.34&ndash, 0.77). After stratification by rs405509 genotypes, this association was significant only among TT genotype carriers (OR = 0.481, CI = 0.253&ndash, 0.915). In conclusion, a significant association between MMSE score and sex was observed in the lowest educational group, especially among carriers of rs405509 TT genotypes.

The effects of genetic variants on the interaction between hyperlipidemia and sex have not been investigated among gout patients in Taiwan. Using Taiwan Biobank and the National Health Insurance Research Database (NHIRD), we examined hyperlipidemia, sex, and their relationship with gout among Taiwanese adults with the human leukocyte antigen B (HLA-B) genetic variants. Hyperlipidemia was present in 1437 patients with gout. Sex and hyperlipidemia had significant associations on gout risk, with hyperlipidemia showing a relatively stronger effect. Gout was present in men, with an odds ratio (OR) of 1.945 (95% confidence interval (CI) 1.568&ndash, 2.411) compared to women, and in hyperlipidemic (OR = 4.032, 95% CI: 3.581&ndash, 4.540) compared to non-hyperlipidemic patients. The interaction of sex and hyperlipidemia was significant for rs2523608 GG (p = 0.0402) and rs4713518 AA (p = 0.0003) genotypes. After stratification, hyperlipidemia remained a risk factor in women (OR = 4.735, 95% CI: 3.375&ndash, 6.643) and men (OR = 3.640, 95% CI: 2.916&ndash, 4.544) with rs2523608 GG genotype. The odds ratio in hyperlipidemic women and men with rs4713518 AA genotype was 7.454 (95% CI 5.103&ndash, 10.888) and 3.585 (95% CI 2.854&ndash, 4.503), respectively. Our study indicates that hyperlipidemia-sex interactions exist for gout risk in Taiwanese adults with rs2523608 GG and rs4713518 AA genotypes.

Background Both SOX2 promoter methylation and air pollution have been associated with lung cancer risk. However, little has been done to assess SOX2 promoter methylation in individuals living in air pollution areas. The aim of this study was to investigate SOX2 promoter methylation in non-smoking Taiwanese adults living in areas with different levels of air pollution especially particulate matter with diameter

Background DNA methylation is associated with cancer, metabolic, neurological, and autoimmune disorders. Hypomethylation of aryl hydrocarbon receptor repressor (AHRR) especially at cg05575921 is associated with smoking and lung cancer. Studies on the association between AHRR methylation at cg05575921 and sources of polycyclic aromatic hydrocarbon (PAH) other than smoking are limited. The aim of our study was to assess the pattern of blood DNA methylation at cg05575921 in non-smoking Taiwanese adults living in areas with different PM2.5 levels. Methods Data on blood DNA methylation, smoking, and residence were retrieved from the Taiwan Biobank dataset (2008–2015). Current and former smokers, as well as individuals with incomplete information were excluded from the current study. The final analysis included 708 participants (279 men and 429 women) aged 30–70 years. PM2.5 levels have been shown to increase as one moves from the northern through central towards southern Taiwan. Based on this trend, the study areas were categorized into northern, north-central, central, and southern regions. Results Living in PM2.5 areas was associated with lower methylation levels: compared with the northern area (reference area), living in north-central, central, and southern areas was associated with lower methylation levels at cg05575921. However, only methylation levels in those living in central and southern areas were significant (β = − 0.01003, P = 0.009 and β = − 0.01480, P < 0.001, respectively. Even though methylation levels in those living in the north-central area were not statistically significant, the test for linear trend was significant (P < 0.001). When PM2.5 was included in the regression model, a unit increase in PM2.5 was associated with 0.00115 (P < 0.001) lower cg05575921 methylation levels. Conclusion Living in PM2.5 areas was inversely associated with blood AHRR methylation levels at cg05575921. The methylation levels were lowest in participants residing in southern followed by central and north-central areas. Moreover, when PM2.5 was included in the regression model, it was inversely associated with methylation levels at cg05575921. Blood methylation at cg05575921 (AHRR) in non-smokers might indicate different exposures to PM2.5 and lung cancer which is a PM2.5-related disease. Electronic supplementary material The online version of this article (10.1186/s13148-019-0662-9) contains supplementary material, which is available to authorized users.

BACKGROUND: This study compares the fertilization rate and embryonic development of oocytes randomly inseminated by conventional IVF or ICSI in patients with polycystic ovarian syndrome (PCOS) and normozoospermic semen during IVF cycles. METHODS: Sibling oocytes were randomized to be inseminated either by ICSI or IVF. Fertilization rate (two pronuclei/COC), day 2 embryonic morphology and rate of development were assessed. RESULTS: A total of 1089 cumulus-oocyte complexes (COC) were collected in 60 cycles (mean+/-SD, 18.2 +/- 7.2). Totals of 541 and 548 COC were inseminated by IVF and ICSI respectively, with a significantly higher fertilization rate in the ICSI group (ICSI versus IVF, 72.3 +/- 15.5 versus 44.8 +/- 25.1%). No fertilization failure occurred in the group of oocytes inseminated by ICSI, whereas the COC in nine patients (15%) inseminated by IVF had complete fertilization failure. The day 2 embryonic morphology and rate of development were not different regardless of the insemination method. CONCLUSIONS: Our results suggested that another randomized controlled study, randomizing patients instead of sibling oocytes, should be undertaken to compare the pregnancy rate per started cycle and to see whether ICSI should be performed on all, or at least on a portion of, oocytes for patients with PCOS undergoing IVF cycles.

Background: To assess the characteristics of progesterone (Prog) changes in women with a subtle Prog rise in recombinant follicle-stimulating hormone (r-FSH) and GnRH antagonist cycles. Methods: We enrolled 233 patients undergoing controlled ovarian hyperstimulation with r-FSH and GnRH antagonist for IVF or ICSI. A subtle Prog rise 1 day before hCG administration was defined as a Prog value of ≧1.2 ng/ml. Results: 100 of 233 cycles (42.9%) showed a subtle Prog rise in this study. The mean serum Prog levels and area under curve (AUC) in the group with Prog ≧1.2 ng/ml was significantly higher than that in the Prog Conclusion: A subtle Prog rise may occur as early as cycle day 8 in r-FSH/GnRH antagonist cycles.

A subtle rise in serum progesterone during the late follicular phase in patients undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) cycles is a frequent event that can decrease implantation and pregnancy rates in controlled ovarian hyperstimulation (COH) protocols that use a gonadotropin-releasing hormone (GnRH) antagonist. The aim of the present study was to evaluate the prevalence and effect of the subtle progesterone rise during COH with single-dose GnRH antagonist in combination with clomiphene citrate (CC) and human menopausal gonadotropins (hMG) in IVF or ICSI cycles. Ninety-five women undergoing COH with CC, hMG and a single 2.5 mg dose of the GnRH antagonist, cetrorelix, were enrolled in the study. Patients were grouped according to serum progesterone level on the day of human chorionic gonadotropin (hCG) administration (P1.2 ng/ml or P/= 1.2 ng/ml). The incidence of a subtle progesterone rise was 54.7% (52/95). The group with P/= 1.2 ng/ml had significantly higher serum levels of luteinizing hormone (p = 0.002) and estradiol (p0.001) on the day of hCG injection than the group with P1.2 ng/ml, and more oocytes were retrieved (p = 0.001). However, there was no significant difference in fertilization, clinical pregnancy or implantation rate between the two groups. In conclusion, a subtle progesterone rise during the late follicular phase is common but not associated with pregnancy outcome.

To investigate if the combination of clomiphene citrate, hMG, and cetrorelix (CC/hMG/cetrorelix protocol) can be applied to patients who had excessive response to GnRHa long protocol.Fifty patients who coasted and failed to conceive in their first cycles stimulated with GnRHa long protocol were stimulated with CC/hMG/cetrorelix protocol. The peak serum estradiol levels, the need of coasting and prolonged coasting (/=4 days), and the incidences of OHSS were compared.The peak estradiol level was significantly lower with CC/hMG/cetrorelix protocol compared to GnRHa long protocol. With CC/hMG/cetrorelix protocol, only four patients (8%) needed coasting and no one coasted/=4 days. In contrast, in the first cycles, 11 patients (22%) needed coasting/=4 days. The incidence of moderate OHSS was significantly lower with CC/hMG/cetrorelix protocol.The CC/hMG/cetrorelix protocol is an acceptable alternative protocol for patients who had excessive response to GnRHa long protocol.

Ectopic pregnancy situated in a Caesarean section scar is a rare but potentially life-threatening event. Because of its rarity, there are no universal treatment guidelines to manage this condition. We report a case of IVF-induced triplet heterotopic pregnancy of early gestational age that included one Caesarean scar pregnancy diagnosed as early as 6 weeks gestation. Treatment with embryo aspiration under vaginal ultrasonography for selective embryo reduction was given and the concurrent intrauterine twin pregnancy was preserved successfully.

BACKGROUND: The purpose of this study was to determine if there is any additional benefit from FSH priming in addition to hCG priming on in-vitro maturation (IVM) programmes. METHODS: Sixty women with polycystic ovary syndrome (PCOS) who underwent 68 IVM cycles were randomized by computer-generated numbers to receive FSH stimulation or not. Thirty-five cycles were pretreated with 75 IU rFSH for 6 days, and 33 cycles were not. Every cycle was given hCG 10 000 IU 36 h before oocyte retrieval. Immature oocytes were matured in vitro and fertilized by ICSI, and the resulting embryos were replaced on day 2 or 3. RESULTS: A total of 1528 immature oocytes were recovered. The overall maturation and fertilization rates were 74.2 and 72.8% respectively. After embryo transfer, 23 pregnancies resulted (33.8%). The oocyte numbers and endometrial thickness were similar between FSH-primed and non-FSH-primed groups. Serum estradiol level on the day of hCG injection was significantly higher in the FSH-primed group than in the non-FSH-primed group (377.2 pmol/l versus 143.8 pmol/l, P = 0.001). The maturation rate, fertilization rate and pregnancy rate were 76.5, 75.8 and 31.4% respectively for FSH-primed group, and 71.9, 69.5 and 36.4% respectively for non-FSH-primed group (all not significant). CONCLUSIONS: IVM is a feasible treatment for women with PCOS. FSH priming has no additional beneficial effect on IVM.

BACKGROUND: The introduction of GnRH antagonists such as cetrorelix acetate has made possible the simplification of ovarian stimulation. However, the most effective protocol for their administration has not yet been clearly defined. METHODS: Forty women with male-factor infertility undergoing 40 ICSI cycles were included in the study. Clomiphene citrate at 100 mg a day was given from cycle day 3 through day 7. hMG at 150 IU was given on cycle days 4, 6 and 8, and was adjusted from day 9 according to the follicular and hormone responses. Cetrorelix acetate at 2.5 mg was administered when the leading follicle reached 14 mm. The remaining 0.5 mg was divided into two 0.25 mg injections for possible later use. Serum FSH, LH, estradiol and progesterone levels were measured daily from the day of cetrorelix acetate injection until hCG was given. RESULTS: Serum LH level was suppressed effectively for 4 days. Four patients (10%) needed one or two additional injections of 0.25 mg cetrorelix acetate. No premature LH surge was detected in any of the women treated. Sixteen women became pregnant (40%), of which 14 pregnancies (35%) were ongoing at the time of writing. CONCLUSIONS: This study demonstrates that this new protocol is feasible for couples with male-factor infertility undergoing ICSI.