The risk relationships between alcohol consumption, alcohol use disorder and alcohol use disorder mortality: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Increasing levels of alcohol use are associated with a risk of developing an alcohol use disorder (AUD), which, in turn, is associated with considerable burden. Our aim was to estimate the risk relationships between alcohol consumption and AUD incidence and mortality. METHOD: A systematic literature search was conducted, using Medline, Embase, PsycINFO and Web of Science for case-control or cohort studies published between 1 January 2000 and 8 July 2022. These were required to report alcohol consumption, AUD incidence and/or AUD mortality (including 100% alcohol-attributable deaths). The protocol was registered with PROSPERO (CRD42022343201). Dose-response and random-effects meta-analyses were used to determine the risk relationships between alcohol consumption and AUD incidence and mortality and mortality rates in AUD patients, respectively. RESULTS: Of the 5904 reports identified, seven and three studies from high-income countries and Brazil met the inclusion criteria for quantitative and qualitative syntheses, respectively. In addition, two primary US data sources were analyzed. Higher levels of alcohol consumption increased the risk of developing or dying from an AUD exponentially. At an average consumption of four standard drinks (assuming 10 g of pure alcohol/standard drink) per day, the risk of developing an AUD was increased sevenfold [relative risk (RR) = 7.14, 95% confidence interval (CI) = 5.13-9.93] and the risk of dying fourfold (RR = 3.94, 95% CI = 3.53-4.40) compared with current non-drinkers. The mortality rate in AUD patients was 3.13 (95% CI = 1.07-9.13) per 1000 person-years. CONCLUSIONS: There are exponential positive risk relationships between alcohol use and both alcohol use disorder incidence and mortality. Even at an average consumption of 20 g/day (about one large beer), the risk of developing an alcohol use disorder (AUD) is nearly threefold that of current non-drinkers and the risk of dying from an AUD is approximately double that of current non-drinkers.

CRISPR/CasΦ2-mediated gene editing in wheat and rye.

The compact CRISPR/CasΦ2 system provides a complementary genome engineering tool for efficient gene editing including cytosine and adenosine base editing in wheat and rye with high specificity, efficient use of the protospacer-adjacent motif TTN, and an alternative base-editing window.

Alcoholic beverage types consumed by population subgroups in the United States: Implications for alcohol policy to address health disparities.

INTRODUCTION: We aimed to identify alcoholic beverage types more likely to be consumed by demographic subgroups with greater alcohol-related health risk than others, mainly individuals with low socio-economic status, racial/ethnic minority status and high drinking levels. METHODS: Fractional logit modelling was performed using a nationally representative sample of US adult drinkers (analytic N = 37,657) from the National Epidemiologic Survey on Alcohol and Related Conditions Waves 2 (2004-2005) and 3 (2012-2013). The outcomes were the proportions of pure alcohol consumed as beer, wine, liquor and coolers (defined as wine-/malt-/liquor-based coolers, hard lemonade, hard cider and any prepackaged cocktails of alcohol and mixer). RESULTS: Adults with lower education and low or medium income were more likely to drink beer, liquor and coolers, while those with a 4-year college/advanced degree and those with high income preferred wine. Excepting Asian adults, racial/ethnic minority adults were more likely to drink beer (Hispanics) and liquor (Blacks), compared with White adults. High- or very-high-level drinkers were more likely to consume liquor and beer and less likely to consume wine (and coolers), compared with low-level drinkers. High-level and very-high-level drinkers, who were less than 10% of all drinkers, consumed over half of the total volume of beer, liquor and coolers consumed by all adults. DISCUSSION AND CONCLUSIONS: Individuals with low socio-economic status, racial/ethnic minority status or high drinking level prefer liquor and beer. As alcohol taxes, sales and marketing practices all are beverage-specific, targeted approaches to reduce consumption of these beverages, particularly among individuals with these profiles, are warranted.

Associations between simultaneous use of alcohol and cannabis and cannabis-related problems in 2014-2016: evidence from the Washington panel survey.

BACKGROUND: To address the research question of how simultaneous users of alcohol and cannabis differ from concurrent users in risk of cannabis use problems after the recreational marijuana legalization in Washington State. METHODS: We used generalized estimating equations with a Poisson distribution to analyze the association between simultaneous use of alcohol and marijuana (SAM) and cannabis-related problems compared to concurrent use. The data is a longitudinal sample of drinkers and cannabis users (n = 257, 47% female) aged 18 years and older from Washington State in 2014-2016. We adjusted for survey weights to account for differential probability of selection and response rates. The primary outcome is the past-six-month CUDIT problem subscale (ranging from 0 to 28), which is the total score for seven CUDIT problem items, after excluding the three items that covered marijuana use frequency. Covariates include marijuana use frequency (daily/near daily use, regular use, or infrequent use), marijuana daily quantity, alcohol daily volume, panel survey cycle, medical marijuana recommendation, driving time to nearest marijuana outlet, age of marijuana use onset, and other demographics. RESULTS: After adjusting for covariates, we found that compared to concurrent use, SAM was significantly positively associated with CUDIT problem subscale (IRR = 1.68, 95% CI: 1.25-2.27, p < 0.001); daily/near daily use of marijuana was strongly significantly associated with CUDIT problem subscale compared with infrequent use (IRR = 5.1, 2.71-9.57, p < 0.001) or regular use (IRR = 3.05, 1.91-4.85, p < 0.001). Secondary analyses using CUDIT total score as the outcome also showed a significant positive association with SAM compared to concurrent use (IRR = 1.17, 1.02-1.34, p < 0.05). CONCLUSIONS: This study highlighted the importance of SAM, in addition to cannabis use frequency for predicting cannabis-related problems.

Differential Associations of Alcohol Use With Ischemic Heart Disease Mortality by Socioeconomic Status in the US, 1997-2018.

Importance: People with low socioeconomic status (SES) experience greater burden from alcohol-attributable health conditions and mortality at equal levels of alcohol consumption compared with those with high SES. A U-shaped association has been established between alcohol use and ischemic heart disease (IHD), but no study has explored how such an association differs by SES in the US. Objective: To investigate how the association of alcohol use with ischemic heart disease mortality differs by SES in the general US population. Design, Setting, and Participants: This cohort study used record-linked, cross-sectional National Health Interview Survey data for US adults aged 25 years and older, covering 1997 to 2018 with mortality follow-up until 2019. Data analysis was performed from March to June 2023. Exposures: SES (operationalized using education attainment) and alcohol consumption were obtained from self-reported questionnaires. Main Outcomes and Measures: The outcome was time to IHD mortality or last presumed alive by December 31, 2019. Cox proportional hazard models were applied to evaluate the interaction of SES and alcohol use on IHD mortality, with age as the time scale. Sex-stratified analyses were performed, adjusting for race and ethnicity, marital status, smoking, body mass index, physical activity, and survey year. Fine-Gray subdistribution models were applied to account for competing risks. Results: This cohort study of 524 035 participants (mean [SD] age at baseline, 50.3 [16.2] years; 290 492 women [51.5%]) found a statistically significantly greater protective association of drinking less than 20 g per day (vs lifetime abstinence) with IHD mortality in the high-SES group compared with the low-SES group (interaction term hazard ratio [HR], 1.22 [95% CI, 1.02-1.45] in men; HR, 1.35 [95% CI, 1.09-1.67] in women). In addition, the differential associations of drinking less than 20 g per day with IHD mortality by SES were observed only among people with less than monthly heavy episodic drinking (HED) (interaction term, HR, 1.20 [95% CI, 1.01-1.43] in men; HR, 1.34 [95% CI, 1.08-1.67] in women); no difference was found in people with at least monthly HED. Among women there was a greater protective association of drinking less than 20 g per day with IHD mortality in the high-SES group than the middle-SES group (interaction term, HR, 1.35 [95% CI, 1.06-1.72]). Among men, the harmful association of drinking more than 60 g per day with IHD mortality in the low-SES group was largely explained by other behavioral risk factors (ie, smoking, body mass index, and physical activity). Conclusions and Relevance: This cohort study found a greater protective association between drinking less than 20 g per day with less than monthly HED and IHD mortality in the high-SES group compared with the low-SES group, in both sexes even after adjusting for key covariables and behavioral risk factors. The findings suggest that public health interventions on alcohol use should account for different socioeconomic backgrounds when assessing the level of risk related to alcohol exposure, bearing in mind that levels of consumption deemed safe regarding a specific outcome such as IHD may indeed be less safe or not safe across all sociodemographic groups.

Potential Effects of Long-Term Exposure to Air Pollution on Dementia: A Longitudinal Analysis in American Indians Aged 55 Years and Older.

(1) Background: American Indians are disproportionately affected by air pollution, an important risk factor for dementia. However, few studies have investigated the effects of air pollution on the risk of dementia among American Indians. (2) Methods: This retrospective cohort study included a total of 26,871 American Indians who were 55+ years old in 2007, with an average follow-up of 3.67 years. County-level average air pollution data were downloaded from land-use regression models. All-cause dementia was identified using ICD-9 diagnostic codes from the Indian Health Service's (IHS) National Data Warehouse and related administrative databases. Cox models were employed to examine the association of air pollution with dementia incidence, adjusting for co-exposures and potential confounders. (3) Results: The average PM2.5 levels in the IHS counties were lower than those in all US counties, while the mean O3 levels in the IHS counties were higher than the US counties. Multivariable Cox regressions revealed a positive association between dementia and county-level O3 with a hazard ratio of 1.24 (95% CI: 1.02-1.50) per 1 ppb standardized O3. PM2.5 and NO2 were not associated with dementia risk after adjusting for all covariates. (4) Conclusions: O3 is associated with a higher risk of dementia among American Indians.

Life-course Accumulated Cannabis Use and Recent Cannabis-related Problems in the Washington Panel Survey.

BACKGROUND: Previous studies have only investigated the short-term association of recent cannabis use with cannabis-related problems, without accounting for the onset, duration, and variations in frequency of use in the life-course. METHODS: We obtained data from the Washington panel survey during 2014-2016. We constructed accumulated lifetime exposure to cannabis use, heavy drinking (5+ drinks on one occasion), and cigarette pack-years from age of onset based on a series of decades-based questions on cannabis use and heavy drinking, and tobacco use history. We used Generalized Estimating Equation with Poisson distribution to investigate the association between accumulated cannabis use and the past-6-month CUDIT score. We adjusted for accumulated heavy drinking and cigarette pack-years, substance co-use variables, demographics, and applied survey weights. RESULTS: We found strong and statistically significant correlations for the lifetime measures across the four panel surveys, indicating that the life-course measures of cannabis use and heavy drinking were largely reliable. We found a statistically significant relationship between the lifetime accumulated exposure to cannabis and CUDIT. The results were robust to the inconsistencies in reported frequencies and onset age across panel surveys. CONCLUSIONS: This study established the relationship between lifetime exposure to cannabis and cannabis-related problems in a representative sample of drinkers and marijuana users in Washington state. We have also provided test-retest validity and question details for the decades-based cannabis and heavy drinking measures to facilitate their use in future studies of cannabis and alcohol-related outcomes.

How does alcohol use impact morbidity and mortality of liver cirrhosis? A systematic review and dose-response meta-analysis.

BACKGROUND: Alcohol consumption is the most important risk factor responsible for the disease burden of liver cirrhosis (LC). Estimates of risk relationships available usually neither distinguish between different causes such as alcohol-related LC or hepatitis-related LC, nor differentiate between morbidity and mortality as outcome. We aimed to address this research gap and identify dose-response relationships between alcohol consumption and LC, by cause and outcome. METHODS: A systematic review using PubMed/Medline and Embase was conducted, identifying studies that reported an association between level of alcohol use and LC. Meta-regression models were used to estimate the dose-response relationships and control for heterogeneity. RESULTS: Totally, 44 studies, and 1 secondary data source, with a total of 5,122,534 participants and 15,150 cases were included. Non-linear dose-response relationships were identified, attenuated for higher levels of consumption. For morbidity, drinking 25 g/day was associated with a RR of 1.81 (95% CI 1.68-1.94) compared to lifetime abstention; 50 g/day and 100 g/day corresponded to 3.54 (95% CI 3.29-3.81) and 8.15 (95% CI 7.46-8.91), respectively. For mortality, for 25 g/day, a RR of 2.65 (95% CI 2.22-3.16); for 50 g/day, a RR of 6.83 (95% CI 5.84-7.97); for 100 g/day, a RR of 16.38 (95% CI 13.81-19.42) were identified. A higher risk for alcohol-related and all-cause LC as compared to hepatitis C-related LC was found. CONCLUSION: Our results demonstrated higher acceleration for mortality compared to morbidity. The current findings will inform the way we quantify the burden due to LC attributable to alcohol use.

Evaluation of the risk relationship between average alcohol volume consumed and suicide: An analysis of mortality linked cohort data.

Objective: To evaluate the relationship between average alcohol volume consumed per day and suicide. Methods: Data from the annual, cross-sectional US National Health Interview Survey, 1997-2018, was obtained, and linked to the 2019 National Death Index. The association between average alcohol volume consumed in grams per day (g/day) and suicide was quantified using Cox proportional hazards model (multiplicative) and Aalen's additive hazard model. All analyses were stratified by sex, and adjusted for education, marital status, race/ethnicity, and survey year. Results: On the multiplicative scale, for males, former drinkers and those who consumed on average (40, 60] g/day had about 53% (HR=1.53, 95% CI: 1.10, 2.13) and 77% (HR=1.77, 95% CI: 1.17, 2.66) greater risk of dying by suicide, compared to lifetime abstainers, respectively. There was no significant association found for former or current drinkers among females, on the multiplicative scale. On the additive scale, for males and females, being a former drinker was associated with 11.4 (95% CI: 2.3, 20.4) and 5.6 (95% CI: 0.8, 10.4) additional deaths per 100,000 person years, compared to lifetime abstainers. For males only, drinking (40, 60] g/day on average was associated with 23.2 (95% CI: 6.7, 39.7) additional deaths per 100,000 person years. Level of education was not found to modify the focal relationship for males or females. Conclusions: The findings suggest that the relationship between average alcohol volume consumed per day and suicide is nuanced. Additional research on the respective relationship is needed, including repeated measures of average alcohol consumption over time.

The Relationship Between Alcohol Consumption, BMI, and Type 2 Diabetes: A Systematic Review and Dose-Response Meta-analysis.

BACKGROUND: Moderate alcohol use may be associated with lower risk of type 2 diabetes mellitus (T2DM). Previous reviews have reached mixed conclusions. PURPOSE: To quantify the dose-response relationship between alcohol consumption and T2DM, accounting for differential effects by sex and BMI. DATA SOURCES: Medline, Embase, Web of Science, and one secondary data source. STUDY SELECTION: Cohort studies on the relationship between alcohol use and T2DM. DATA EXTRACTION: Fifty-five studies, and one secondary data source, were included with a combined sample size of 1,363,355 men and 1,290,628 women, with 89,983 and 57,974 individuals, respectively, diagnosed with T2DM. DATA SYNTHESIS: Multivariate dose-response meta-analytic random-effect models were used. For women, a J-shaped relationship was found with a maximum risk reduction of 31% (relative risk [RR] 0.69, 95% CI 0.64-0.74) at an intake of 16 g of pure alcohol per day compared with lifetime abstainers. The protective association ceased above 49 g per day (RR 0.82, 95% CI 0.68-0.99). For men, no statistically significant relationship was identified. When results were stratified by BMI, the protective association was only found in overweight and obese women. LIMITATIONS: Our analysis relied on aggregate data. We included some articles that determined exposure and cases via self-report, and the studies did not account for temporal variations in alcohol use. CONCLUSIONS: The observed reduced risk seems to be specific to women in general and women with a BMI ≥25 kg/m2. Our findings allow for a more precise prediction of the sex-specific relationship between T2DM and alcohol use, as our results differ from those of previous studies.

Can lifestyle factors explain racial and ethnic inequalities in all-cause mortality among US adults?

BACKGROUND: Racial and ethnic inequalities in all-cause mortality exist, and individual-level lifestyle factors have been proposed to contribute to these inequalities. In this study, we evaluate the extent to which the association between race and ethnicity and all-cause mortality can be explained by differences in the exposure and vulnerability to harmful effects of different lifestyle factors. METHODS: The 1997-2014 cross-sectional, annual US National Health Interview Survey (NHIS) linked to the 2015 National Death Index was used. NHIS reported on race and ethnicity (non-Hispanic White, non-Hispanic Black, and Hispanic/Latinx), lifestyle factors (alcohol use, smoking, body mass index, physical activity), and covariates (sex, age, education, marital status, survey year). Causal mediation using an additive hazard and marginal structural approach was used. RESULTS: 465,073 adults (18-85 years) were followed 8.9 years (SD: 5.3); 49,804 deaths were observed. Relative to White adults, Black adults experienced 21.7 (men; 95%CI: 19.9, 23.5) and 11.5 (women; 95%CI: 10.1, 12.9) additional deaths per 10,000 person-years whereas Hispanic/Latinx women experienced 9.3 (95%CI: 8.1, 10.5) fewer deaths per 10,000 person-years; no statistically significant differences were identified between White and Hispanic/Latinx men. Notably, these differences in mortality were partially explained by both differential exposure and differential vulnerability to the lifestyle factors among Black women, while different effects of individual lifestyle factors canceled each other out among Black men and Hispanic/Latinx women. CONCLUSIONS: Lifestyle factors provide some explanation for racial and ethnic inequalities in all-cause mortality. Greater attention to structural, life course, healthcare, and other factors is needed to understand determinants of inequalities in mortality and to advance health equity.

Can lifestyle factors explain racial and ethnic inequalities in all-cause mortality among US adults?

Background: Racial and ethnic inequalities in all-cause mortality exist, and individual-level lifestyle factors have been proposed to contribute to these inequalities. In this study, we evaluate the extent to which the association between race and ethnicity and all-cause mortality can be explained by differences in the exposure and vulnerability to harmful effects of different lifestyle factors. Methods: The 1997-2014 cross-sectional, annual US National Health Interview Survey (NHIS) linked to the 2015 National Death Index was used. NHIS reported on race and ethnicity (non-Hispanic White, non-Hispanic Black, and Hispanic/Latinx), lifestyle factors (alcohol use, smoking, body mass index, physical inactivity), and covariates (sex, age, education, marital status, survey year). Causal mediation using an additive hazard and marginal structural approach was used. Results: 465,073 adults (18-85 years) were followed 8.9 years (SD:5.3); 49,804 deaths were observed. Relative to White adults, Black adults experienced 21.7 (men; 95%CI: 19.9, 23.5) and 11.5 (women; 95%CI: 10.1, 12.9) additional deaths per 10,000 person-years whereas Hispanic/Latinx women experienced 9.3 (95%CI: 8.1, 10.5) fewer deaths per 10,000 person-years; no statistically significant differences were identified between White and Hispanic/Latinx men. Notably, these differences in mortality were partially explained by both differential exposure and differential vulnerability to these lifestyle factors among Black women, while different effects of individual lifestyle factors canceled each other out among Black men and Hispanic/Latinx women. Conclusions: Lifestyle factors provide some explanation for racial and ethnic inequalities in all-cause mortality. Greater attention to structural, life course, healthcare, and other factors is needed to understand determinants of inequalities in mortality and advance health equity.

Per- and polyfluoroalkyl substances in drinking water and hypertensive disorders of pregnancy in the United States during 2013-2015.

Background: Per- and polyfluoroalkyl substances (PFAS) widely exist in the environment and human bodies. Contaminated drinking water is one of the major exposure pathways for humans. Previous studies found weak or moderate associations between PFAS and hypertensive disorders of pregnancy (HDP). Methods: We obtained the number of births and counts of HDP cases for singleton births multiply stratified by county, maternal age, race, education, smoking status, and parity from CDC WONDER, and PFAS water concentrations from EPA UCMR3 data in the United States during 2013-2015. We used binomial regression on the multiply stratified HDP data to produce equal effect estimates and standard errors to those that would be derived from using individual-level data on binary HDP status and demographic covariates in logistic regression. Results: After adjusting for demographic covariates, we found small but statistically significant positive associations between HDP and population-weighted average water concentrations (ng/L) of all four PFAS: Odds ratio (OR) = 1.009, 95% CI = (1.001, 1.016) per IQR increase in perfluorooctanoic acid (PFOA); 1.030, 95% CI = (1.021, 1.040) per IQR increase in perfluorooctane sulfonate (PFOS); 1.008, 95% CI = (1.005, 1.011) per IQR increase in perfluoroheptanoic acid (PFHpA); 1.007, 95% CI = (1.004, 1.010) per IQR increase in perfluorohexane sulfonic acid (PFHxS), and 1.032, 95% CI = (1.022, 1.042) per IQR increase in the sum of four PFAS. Further adjustment for coexposures reversed the effect of PFOA from positive to inverse, and attenuated the effects of PFOS and PFHxS toward the null. After drinking water to serum concentration conversions, our effect estimates for PFOA, PFOS, and PFHxS are similar to previous studies. Conclusions: We found a weak positive association between the PFAS mixture and HDP, although the generalizability is subject to inherent limitations of the public-available datasets.

Retrospective exposure reconstruction using approximate Bayesian computation: A case study on perfluorooctanoic acid and preeclampsia.

BACKGROUND: In environmental epidemiology, measurements of toxicants in biological samples are often used as individual exposure assignments. It is common to obtain only one or a few exposure biomarkers per person and use those measurements to represent each person's relevant toxicant exposure for a given health outcome, even though most exposure biomarkers can fluctuate over time. When the timing of the exposure reflected by the biomarker measurement is misaligned with disease development especially if it occurs after the disease outcome, results could be subject to reverse causality or exposure measurement error. OBJECTIVE: This study aimed to use an approximate Bayesian computation (ABC) method to improve PFOA exposure estimates and characterize the effects of PFOA on preeclampsia in the C8 Studies. METHODS: Serum PFOA concentrations were measured in blood samples collected during 2005-2006 in West Virginia and Ohio (the C8 Studies), and residential and water use histories and pregnancy outcomes were obtained from self-reports. Our previous results may have been influenced by the choice of methods for characterizing PFOA exposures. Here we use an ABC method to combine measured PFOA serum concentrations and environmentally modeled PFOA concentrations to reconstruct historical PFOA exposures. We also expanded our previous work by assuming more realistic lognormal distributions for key input parameters in the exposure and pharmacokinetic models. RESULTS: Compared to using fixed values of model parameters and Monte Carlo simulations, ABC produced similar Spearman correlations between estimated and measured serum PFOA concentrations, yet substantially reduced the mean squared error by over 50%. Based on ABC, compared to previous studies, we found a similar adjusted odds ratio (AOR) for the association between PFOA and preeclampsia. CONCLUSIONS: Bayesian combination of modeled exposure and measured biomarker concentrations can reduce exposure measurement error compared to modeled exposure.

Household low pile carpet usage was associated with increased serum PFAS concentrations in 2005-2006.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are ubiquitous in the serum of the general US population. Food, drinking water, consumer products, dust, and air have been assessed as PFAS exposure sources for humans. The effects of various types of carpeting on serum PFAS concentrations have been less studied, despite the known use of PFAS in stain-resistant carpet treatments. OBJECTIVE: This study aimed to examine the associations between serum PFAS concentrations and type of residential flooring among the general US population aged 12 years and older using the 2005-2006 National Health and Nutrition Examination Survey (NHANES). METHODS: We used multiple linear regressions adjusted for complex survey design and relevant covariates to analyze the relations between serum PFAS concentrations and type of floor covering (smooth surface, low pile carpet, medium to high pile carpet, and combination of carpet and smooth surface), as well as other potential exposure factors. We used multiple imputation to address missing values. RESULTS: We found significantly higher serum concentrations of perfluorohexane sulfonic acid (PFHxS) and 2-(N-methyl-perfluorooctane sulfonamido) acetic acid (MeFOSAA) in US residents residing in homes with low pile carpeting compared with those residing in homes with smooth surface. We concluded that among US residents aged 12 years and older residing in homes with low pile carpeting in the home in 2005-2006, on average 24% and 19% of the PFHxS and MeFOSAA body burdens, respectively, could be attributed to carpeting. We found associations between other types of floor covering (medium to high pile carpet, combination of carpet and smooth surface) and some PFAS concentrations compared with the smooth surface, but these results were less consistent and generally not statistically significant. Additionally, a group Wald Chi-squared test showed a significant result for PFOS, indicating different contributions of various types of flooring to PFOS serum concentration. SIGNIFICANCE: Our results are representative of the general US population at the time of the survey, and potentially informative regarding ongoing PFAS exposure from a variety of sources including carpeting.

Per- and polyfluoroalkyl substances in drinking water and birthweight in the US: A county-level study.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are ubiquitous in the serum of the general US population, and were detected in public water systems serving approximately 16.5 million US residents during 2013-2015. Low birthweight was associated with PFAS exposures in previous studies. METHODS: Birthweights for singleton births during 2013-2015 were obtained from CDC WONDER, multiply stratified by county, maternal age, race, education, smoking status, and parity. PFAS water concentrations were obtained from EPA UCMR3 database and aggregated by county. Multiple regression weighted by inverse variance was used to produce effect estimates equivalent to those that would be obtained from individual-level data on birthweight and confounders. RESULTS: Adjusting for stratification demographic confounders (maternal age, race, education, smoking status, and parity), we found an average change in birthweight of 0.9 g (95% confidence interval [CI] = -0.5, 2.2), -1.3 g (-1.6, -0.9), -3.8 g (-4.9, -2.7), and -3.8 g (-4.3, -3.3) per ng/L increase in the population-weighted average perfluorooctanoic acid, perfluorooctane sulfonate, perfluoroheptanoic acid, and perfluorohexane sulfonic acid in public water supplies by county, respectively. We found an average change in birthweight of -1.0 g (95% CI = -1.2, -0.8) per ng/L increase in the sum of perfluorooctanoic acid, perfluorooctane sulfonate, perfluoroheptanoic acid, and perfluorohexane sulfonic acid concentrations in public water supplies. CONCLUSIONS: The direction and magnitude of association between PFAS and birthweight varied by PFAS chemical in this study. Conclusions are tempered by inherent limitations of the 2 public-use datasets, and by the sensitivity of our results to alternative methods such as mutual adjustment for co-exposures.

Molecular cloning and expression analysis of MyD88 and TRAF6 in Qihe crucian carp Carassius auratus.

Myeloid differentiation factor 88 (MyD88) and tumor necrosis factor receptor-associated factor 6 (TRAF6) are two critical signal transducers in toll-like receptor (TLR) pathway. In the present study, we identified and characterized the homologues of MyD88 and TRAF6 in Qihe crucian carp Carassius auratus, termed as CaMyD88 and CaTRAF6, respectively, and examined their roles during pathogenic infection. Full-length cDNA of CaMyD88 was 2463 bp, including a 191 bp 5'-untranslated region (UTR), a 1417 bp 3'-UTR, and an 855 bp open reading frame (ORF) encoding for a putative protein with 284 amino acids. Full-length cDNA of CaTRAF6 was identified to be 2555 bp, consisting of a 52 bp 5'-UTR, an 871 bp 3'-UTR, and a 1632 bp ORF encoding a protein of 543 amino acids. Deduced amino acid sequences of CaMyD88 and CaTRAF6 contained the typical domains (CaMyD88: death domain and TIR domain; CaTRAF6: one RING-type zinc finger domain, two TRAF-type zinc finger domains, one coiled-coil region, and one conserved C-terminal meprin and TRAF homology domain) as in other fish. Quantitative Real-Time PCR (qRT-PCR) analysis revealed that both CaMyD88 and CaTRAF6 were ubiquitously expressed throughout the development stages and appeared to be developmentally regulated. In addition, CaMyD88 and CaTRAF6 had a broadly distribution of expression in all examined eleven tissues of healthy fish, although the transcript levels varied among the different tissues. Moreover, it was found that mRNA expressions of CaMyD88 and CaTRAF6 were generally up-regulated after stimulation by polyI:C, flagellin, and Aeromonas hydrophila in spite of the down-regulation appeared at some time points or tissues. These results indicated that CaMyD88 and CaTRAF6 play the critical roles in the immune defense of Qihe crucian carp against pathogenic invasion. The present findings will provide the valuable information for understanding the innate immune responses of Qihe crucian carp and contribute to develop the preventive way against pathogens.