Proxy For Exposure Research Articles

Environmental Pollution and the Risk of Congenital Hypothyroidism: Insights from a French Nationwide Retrospective Ecological Cohort Study

ObjectiveTo assess the potential association between congenital hypothyroidism (CH) and third-trimester maternal exposure to nitrate and perchlorate in tap water and to particulate matter (PM) in outdoor air. MethodsUsing the French National Health Data System (SNDS), a retrospective ecological cohort was created, including all children born in France between 2014 and 2019. Ecological data for each child's municipality were used to examine associations, measured as odds ratios (OR), between mean exposure levels and CH in 1,417,402 newborns . Both single and multipollutant analyses were undertaken. To limit residual bias from the administrative nature of SNDS, analyses were conducted at both national and regional levels. The Benjamini-Hochberg approach was used to account for multiple testing. ResultsHigher exposure to nitrates was associated with a greater risk of permanent CH (OR [95%CI] = 1.017 [1.001;1.035] in the Nord-Pas-de-Calais region and 1.024 [1.001;1.048] for the Pays-de-la-Loire region). Higher exposure to PM2.5 or PM10 was associated with a lower risk of permanent CH (OR [95%CI] = 0.928 [0.873;0.982] for PM10 in the Nord-Pas-de-Calais). These findings were confirmed in multi-pollutant analyses. ConclusionsIn some French regions, prenatal exposure to nitrate ions in tap water was significantly associated with an elevated risk of permanent HC, while exposure to PM was significantly associated with a decreased risk. However, using municipal-level exposure proxies may introduce ecological bias, and results were not robust enough to draw firm conclusions about pollutant influence on CH risk.

Impact of Cannabis Legalization on Umbilical Cord Tetrahydrocannabinol (THC) Levels.

Impact of Cannabis Legalization on Umbilical Cord Tissue Tetrahydrocannabinol (THC) levels Objective: To assess the impact of cannabis legalization on both qualitative and quantitative umbilical cord tissue tetrahydrocannabinol (THC) rates and concentrations as a proxy for fetal exposure. This is a retrospective, observational study of umbilical cord tissue THC levels in a single center, comparing THC exposure rates and concentration levels before and after cannabis legalization in the state of Illinois, Epoch 1 (October 1,2018-June 30, 2019, pre-legalization) and Epoch 2 (July 1, 2019-August 31, 2021, post-legalization). 811 umbilical cords were analyzed during epoch 1 and 2170 during epoch 2. A higher percent of umbilical cord tissue tested positive for THC in Epoch 2 compared to Epoch 1 (46.2% vs. 40.6%; p<0.01). Mean THC levels were 51% higher in umbilical cord tissue in Epoch 2 vs. Epoch 1 (6.2ng/gm vs 4.1 ng/gm; p<0.001). Legalization of recreational cannabis was associated with more fetuses exposed to THC and in higher concentrations.

The Validity of Impressions as a Media Dose Metric in a Tobacco Public Education Campaign Evaluation: Observational Study.

Evaluation research increasingly needs alternatives to target or gross rating points to comprehensively measure total exposure to modern multichannel public education campaigns that use multiple channels, including TV, radio, digital video, and paid social media, among others. Ratings data typically only capture delivery of broadcast media (TV and radio) and excludes other channels. Studies are needed to validate objective cross-channel metrics such as impressions against self-reported exposure to campaign messages. This study aimed to examine whether higher a volume of total media campaign impressions is predictive of individual-level self-reported campaign exposure in California. We analyzed over 3 years of advertisement impressions from the California Tobacco Prevention Program's statewide tobacco education campaigns from August 2019 through December 2022. Impressions data varied across designated market areas (DMAs) and across time. These data were merged to individual respondents from 45 waves of panel survey data of Californians aged 18-55 years (N=151,649). Impressions were merged to respondents based on respondents' DMAs and time of survey completion. We used logistic regression to estimate the odds of respondents' campaign recall as a function of cumulative and past 3-month impressions delivered to each respondent's DMA. Cumulative impressions were positively and significantly associated with recall of each of the Flavors Hook Kids (odds ratio [OR] 1.15, P<.001), Dark Balloons and Apartment (OR 1.20, P<.001), We Are Not Profit (OR 1.36, P<.001), Tell Your Story (E-cigarette, or Vaping, product use Associated Lung Injury; OR 1.06, P<.05), and Thrown Away and Little Big Lies (OR 1.05, P<.01) campaigns. Impressions delivered in the past 3 months were associated with recall of the Flavors Hook Kids (OR 1.13, P<.001), Dark Balloons and Apartment (OR 1.08, P<.001), We Are Not Profit (OR 1.14, P<.001), and Thrown Away and Little Big Lies (OR 1.04, P<.001) campaigns. Past 3-month impressions were not significantly associated with Tell Your Story campaign recall. Overall, magnitudes of these associations were greater for cumulative impressions. We visualize recall based on postestimation predicted values from our multivariate logistic regression models. Variation in cumulative impressions for California Tobacco Prevention Program's long-term multichannel tobacco education campaign is predictive of increased self-reported campaign recall, suggesting that impressions may be a valid proxy for potential campaign exposure. The use of impressions for purposes of evaluating public education campaigns may help address current methodological limitations arising from the fragmented nature of modern multichannel media campaigns.

Exploring estrogen-related mechanisms in ovarian carcinogenesis: association between bone mineral density and ovarian cancer risk in a multivariable Mendelian randomization study.

Estrogen may play a role in epithelial ovarian cancer (EOC) carcinogenesis, with effects varying by EOC histotype. Measuring women's long-term exposure to estrogen is difficult, but bone mineral density (BMD) may be a reasonable proxy of longer-term exposure. We examined this relationship by assessing the association between genetic predisposition for higher BMD and risk of EOC by histotype. We used Mendelian randomization (MR) to assess associations between genetic markers for femoral neck and lumbar spine BMD and each EOC histotype. We used multivariable MR (MVMR) to adjust for probable pleiotropic traits, including body mass index, height, menarcheal age, menopausal age, smoking, alcohol intake, and vitamin D. Univariable analyses suggested greater BMD was associated with increased risk of endometrioid EOC (per standard deviation increase; lumbar spine OR = 1.21; 95% CI 0.93,1.57, femoral neck: OR = 1.25; 0.99,1.57), but sensitivity analyses indicated that pleiotropy was likely. Adjustment using MVMR reduced the magnitude of estimates slightly (lumbar spine: OR = 1.13; 95% CI 1.00,1.28, femoral neck: OR = 1.18; 1.03,1.36). Results for lumbar spine BMD and high-grade serous EOC were also suggestive of an association (univariable MR: OR = 1.16; 95% CI 1.03,1.30; MVMR: OR = 1.06; 0.99,1.14). Our study found associations between genetic predisposition to higher BMD, a proxy for long-term estrogen exposure, and risk of developing endometroid and high-grade serous EOC cancers. These findings add to existing evidence of the relationship between estrogen and increased risk of EOC for certain histotypes.

Regional differences in autism and intellectual disability risk associated with cesarean section delivery.

Prior epidemiological studies investigating the association between delivery mode (i.e., vaginal birth and cesarean section [C-section]) and autism spectrum disorder (ASD) and intellectual disability (ID) risk have reported mixed findings. This study examined ASD and ID risks associated with primary and repeat C-section within diverse US regions. During even years 2000-2016, 8-years-olds were identified with ASD and/or ID and matched to birth records [ASD only (N = 8566, 83.6% male), ASD + ID (N = 3445, 79.5% male), ID only (N = 6158, 60.8% male)] using the Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring Network methodology. The comparison birth cohort (N = 1,456,914, 51.1% male) comprised all births recorded in the National Center for Health Statistics corresponding to birth years and counties in which surveillance occurred. C-section rates in the birth cohort demonstrated significant regional variation with lowest rates in the West. Overall models demonstrate increased odds of disability associated with primary and repeat C-section. Adjusted models, stratified by region, identified significant variability in disability likelihood associated with repeat C-section: increased odds occurred for all case groups in the Southeast, for ASD only and ID only in the Mid-Atlantic, and no case groups in the West. Regional variability in disability risk associated with repeat C-section coincides with differences in birth cohorts' C-section rates. This suggests increased likelihood of disability is not incurred by the procedure itself, but rather C-section serves as a proxy for exposures with regional variability that influence fetal development and C-section rates.

HMGCR as a promising molecular target for therapeutic intervention in aortic aneurisms: a mendelian randomization study

BackgroundDespite the exploration of the connections between serum low-density lipoprotein cholesterol (LDL-C) levels and aneurisms in epidemiological studies, causality remains unclear. Therefore, this study aimed to assess the causal impact of LDL-C-lowering targets (HMGCR, PCSK9, NPC1L1, CETP, APOB, and LDLR) on various forms of aneurisms using Mendelian Randomization (MR) analysis.MethodsTwo genetic instruments acted as proxies for exposure to LDL-C-lowering drugs: expression quantitative trait loci of drug target genes and genetic variants linked to LDL-C near drug target genes. Summary-data-based MR (SMR), inverse-variance-weighted MR (IVW-MR), and multivariable MR (MVMR) methods were employed to compute the effect estimates.ResultsThe SMR analysis revealed substantial associations between increased HMGCR expression and a heightened risk of aortic aneurism (odds ratio [OR] = 1.603, 95% confidence interval [CI] = 1.209–2.124), thoracic aortic aneurism (OR = 1.666, 95% CI = 1.122–2.475), and abdominal aortic aneurism (OR = 1.910, 95% CI = 1.278–2.856). Likewise, IVW-MR analysis demonstrated positive correlations between HMGCR-mediated LDL-C and aortic aneurism (OR = 2.228, 95% CI = 1.702–2.918), thoracic aortic aneurism (OR = 1.751, 95% CI = 1.191–2.575), abdominal aortic aneurism (OR = 4.784, 95% CI = 3.257–7.028), and cerebral aneurism (OR = 1.993, 95% CI = 1.277–3.110). Furthermore, in the MVMR analysis, accounting for body mass index, smoking, and hypertension, a significant positive relationship was established between HMGCR-mediated LDL-C levels and the development of aortic aneurisms, encompassing both thoracic and abdominal subtypes. Similarly, consistent positive associations were observed for PCSK9 and CETP genes, as well as PCSK9-mediated and CETP-mediated LDL-C levels, with the occurrence of aortic aneurism and abdominal aortic aneurism. Nonetheless, the evidence for potential associations between APOB, NPC1L1 and LDLR with specific subtypes of aortic aneurisms lacked consistent support from both SMR and IVW-MR analyses.ConclusionsOur MR analysis offered compelling evidence of a plausible causal link between HMGCR and an increased risk of aortic aneurism, encompassing both thoracic and abdominal types. These groundbreaking findings further bolster the case for the deployment of HMGCR inhibitors in the treatment of aortic aneurisms, including both thoracic and abdominal variants.

Career duration and later-life health conditions among former professional American-style football players

ObjectivesCareer duration is often used as a metric of neurotrauma exposure in studies of elite athletes. However, as a proxy metric, career length may not accurately represent causal factors, and...

Internet-based surveillance to track trends in seasonal allergies across the United States.

Over a quarter of adults in the United States suffer from seasonal allergies, yet the broader spatiotemporal patterns in seasonal allergy trends remain poorly resolved. This knowledge gap persists due to difficulties in quantifying allergies as symptoms are seldom severe enough to warrant hospital visits. We show that we can use machine learning to extract relevant data from Twitter posts and Google searches to examine population-level trends in seasonal allergies at high spatial and temporal resolution, validating the approach against hospital record data obtained from selected counties in California, United States. After showing that internet-derived data can be used as a proxy for aeroallergen exposures, we demonstrate the utility of our approach by mapping seasonal allergy-related online activity across the 144 most populous US counties at daily time steps over an 8-year period, highlighting the spatial and temporal dynamics in allergy trends across the continental United States.

Horizontal and vertical foreign direct investment linkages, absorptive capacity and domestic investment: evidence from Indonesian plant-level data

PurposeThis study examines the effect of horizontal and vertical foreign direct investment (FDI) linkages on the investment decisions of domestic plants. It explores this link for plants in a developing country, where the dynamics of FDI spillovers on domestic investment choices are distinct from those in developed countries. It also adds to the literature by examining the role the absorptive capacity of plants plays in this nexus, enriching our understanding of the interaction between FDI and the investment choices of domestic plants and providing insights for policymakers and managers seeking to maximize the positive effects of FDI spillovers.Design/methodology/approachThis study specifies the dynamic investment equation using the Euler and Q models. This equation is estimated using the first-difference and system generalized method of moments GMM estimators, which allow us to address persistency, endogeneity and unobserved plant-specific effects. FDI exposure proxy, calculated by weighing the FDI engagement variable by firm size, captures the strength of foreign equity participation in an industry and time. Input–output (IO) tables are used to calculate the proxies for horizontal and vertical (backward and forward) FDI. Total factor productivity is calculated using a method advocated by Olley and Pakes (1996) that allows us to control for selection and simultaneity.FindingsWe find that FDI inflows into both the domestic plants’ own industry and the input-supplying industry significantly boost the capital accumulation of the average domestic plants. Differentiating plants based on their absorptive capacities reveals that the presence of foreign firms significantly increases capital deepening for domestic plants with high absorptive capacity within their own industry (horizontal linkage) and in industries that supply inputs to the FDI-exposed industry (backward linkage). However, it leads to a decrease in capital deepening for high absorptive capacity domestic plants in industries using inputs produced by the industry exposed to FDI (forward linkage).Research limitations/implicationsThese findings have implications for policymakers and managers who aim to design incentives to maximize the positive spillover effect of horizontal and vertical FDI linkages on the capital deepening of domestic plants. Exploring additional mechanisms that could play a role in this nexus, separately for plants in different industries (such as the industries in which the country has a comparative advantage), may be fruitful.Originality/valueTo our knowledge, the relationship between the investment behavior of the domestic plants and FDI linkages has not been examined for a developing country. It is useful to explore this link in developing countries, as the investment choices of plants in these nations may be impacted differently by FDI spillovers than those in advanced nations. This study further contributes to the literature by investigating whether the plants’ absorptive capacity affects the nexus between FDI linkages and investment decisions of the domestic plants. The findings are valuable for policymakers and managers who aim to increase plants’ capital accumulation in developing countries.

Urinary concentrations of non-essential and essential elements during weaning in infants from the NELA cohort in Spain

Infancy is a period of continuous growth and development, where inadequate intake of essential elements and exposure to non-essential elements may have lifelong health consequences. Thus, the aim of this study is to evaluate the urine concentration of essential and non-essential elements as a proxy for internal exposure during the weaning period, from 3 to 18 months of age. The Nutrition in Early Life and Asthma (NELA) birth cohort generated the data for this study. Sociodemographic, dietary, and urine concentration of essential (Co, Cu, Mo, I, Fe, Mn, Se, Zn, and Ni) and non-essential elements (Al, V, As, Cd, Sb, Tl, and Pb) data were available for 490 participants at 3 months of age and 216 participants at 18 months of age. Paired urine samples at both time periods were available for 175 infants. At 3 months of age, exclusively breastfed infants had lower urine concentrations of Al, V, Fe, Co, Se, Sb, and Tl. Notably, the concentration of Mo had a median (IQR) of 0.60 (0.40–2.10) μg/L compared to a median (IQR) of 39.80 (25.00–56.40) μg/L observed in infants exclusively fed with formula. When we analyzed the change in urine elements concentrations between 3 and 18 months of age, we observed increased As (0.75 vs. 18.60 μg/L), Co (0.05 vs. 0.24 μg/L), Mo (1.98 vs. 50.0 μg/L), Pb (0.15 vs. 0.69 μg/L), Se (11.3 vs. 23.1 μg/L), Tl (0.02 vs. 0.11 μg/L), and V (0.05 vs. 0.11 μg/L). For Cu, lower urine concentrations were observed at 18 months of age in comparison with concentrations at 3 months (5.77 vs. 4.41 μg/L). Among the main food items identified as driving the changes in urine concentration between 3 and 18 months of age were white fish, rice and pasta, potato chips, custard, small blue fish, and legumes. Exclusively breastfed infants showed lower exposure to non-essential elements compared to those who were fed with a mixture or formula. With the introduction of solid foods, the exposure to some non-essential elements increased drastically, as in the case of As and Pb. In addition, exposure to the essential metal Mo also increased substantially with the introduction of solid food.

Long-term exposure to air pollution at residential and workplace addresses and breast cancer risk: A case-control study nested in the French E3N-Générations cohort from 1990 to 2011

BackgroundAn increasing evidence links air pollution to breast cancer (BC) risk. Yet, pollutant exposure estimates at the workplace location in pollution exposure assessment have not been considered. ObjectivesThis study investigates the association between particulate matters (PM2·5, PM10) and nitrogen dioxide (NO2) atmospheric concentrations (1990–2011), at the women’s residential and workplace locations, and BC risk. MethodsThis case-control study of 2419 BC cases and 2984 controls, was nested in the French prospective E3N cohort. The annual mean PM2·5, PM10 and NO2 concentrations were estimated using a Land Use Regression model (50 m x 50 m resolution) and assigned to the women’s geocoded residential and workplace locations, from cohort recruitment to their index date (date of case diagnosis). Odds ratios (OR) and 95 % confidence intervals (CI) were estimated using multivariate logistic regression models. ResultsAn increased BC risk was observed for a 10 µg/m3 increase of the 1990–2011 average PM2·5 concentration estimates (OR=1·28; CI 1·00, 1·63). An increased risk was suggested for a 10 µg/m3 increase for PM10 (OR=1·09; CI 0·92, 1·30) and NO2 (OR=1·05; CI 0·97, 1·13). No effect modification by menopausal status, nor difference by hormone receptor status were observed. DiscussionThis study is the first to estimate BC risk and long-term air pollutant exposure from both, residential and workplace location histories. Results suggest that residential PM2·5, PM10 and NO2 concentrations are strongly correlated with workplace ones, indicating that residential data may serve as proxy for overall exposure. Future studies should consider exposure during commuting.

Rethinking Wear Rate Analysis: a New Dentin Exposure Proxy and its Applications to Ancient Chinese Populations

Assessing age through dentin exposure often leads to underestimated age due to assumptions of constant molar wear rate. New methods for age-related dentin exposure accrual could facilitate cross-population comparisons independent of dietary habits and sociocultural strategies. We analyzed 3D dentin exposure surfaces in four Chinese archaeological samples to reveal variations in dentin exposure rates linked to socioeconomic practices. Linear regression models of dentin exposure areas across molar rows showed significant correlations, with the first molars exhibiting steeper slopes and smaller intercepts compared to the second molars, which had intermediate values, and the third molars showing the highest intercepts and lowest slopes. The first molar contributed most to overall dentin exposure in the molar quadrant, while the second molar wore faster post-eruption. Among populations, Banlashan, predominantly agriculturalist; Houtaomuga, focused on fishing; and Jiayi, a nomadic hunting society, displayed similar wear rate patterns. In contrast, Dunping, a Bronze Age nomadic settlement situated on a high-altitude plateau, exhibited distinctively lower wear rates. These observed dentin exposure rates aligned with ecological and dietary constraints, enabling interpopulation comparisons using the proposed 3D dentin exposure proxy. Moreover, the statistical model allows for comparing wear rates across populations relative to dietary habits and potentially estimating age at death for isolated archaeological specimens, whether humans or animals. The precision of this physiological age estimation depends on the regression models used, necessitating further research with specimens of known age at death.

On the informative value of community-based indoor radon values in relation to lung cancer.

Radon is a radioactive gas and a major risk factor for lung cancer (LC). We investigated the dose-response relationship between radon and LC risk in the International Lung Cancer Consortium with 8927 cases and 5562 controls from Europe, North America, and Israel, conducted between 1992 and 2016. Spatial indoor radon exposure in the residential area (sIR) obtained from national surveys was linked to the participants' residential geolocation. Parametric linear and spline functions were fitted within a logistic regression framework. We observed a non-linear spatial-dose response relationship for sIR < 200 Bq/m3. The lowest risk was observed for areas of mean exposure of 58 Bq/m3 (95% CI: 56.1-59.2 Bq/m3). The relative risk of lung cancer increased to the same degree in areas averaging 25 Bq/m3 (OR = 1.31, 95% CI: 1.01-1.59) as in areas with a mean of 100 Bq/m3 (OR = 1.34, 95% CI: 1.20-1.45). The strongest association was observed for small cell lung cancer and the weakest for squamous cell carcinoma. A stronger association was also observed in men, but only at higher exposure levels. The non-linear association is primarily observed among the younger population (age < 69 years), but not in the older population, which can potentially represent different biological radiation responses. The sIR is useful as proxy of individual radon exposure in epidemiological studies on lung cancer. The usual assumption of a linear, no-threshold dose-response relationship, as can be made for individual radon exposures, may not be optimal for sIR values of less than 200 Bq/m3.

IMPACT OF REAL-LIFE ENVIRONMENTAL EXPOSURES ON REPRODUCTION: Evidence for reproductive health effects following exposure to hydraulic fracturing chemical mixtures.

Unconventional oil and natural gas (UOG) operations, particularly hydraulic fracturing, have revolutionized oil and gas production, using and containing complex mixtures of chemicals that may impact reproductive health. While there is growing evidence for effects on births in hydraulic fracturing/UOG regions and good mechanistic evidence for potential reproductive toxicity, there is much research still needed to make firm conclusions about these practices and reproductive health. Unconventional oil and natural gas (UOG) operations have emerged over the last four decades to transform oil and gas production in the United States and globally by unlocking previously inaccessible hydrocarbon deposits. UOG development utilizes many compounds associated with conventional oil and gas, as well as some specific to UOG extraction, particularly during hydraulic fracturing (HF). While research is increasing on UOG chemicals and their mixtures, this review discusses the current evidence for reproductive toxicity following exposures to UOG/HF mixtures. These complex chemical mixtures have been demonstrated to interact with numerous mechanisms known to influence reproductive health. A growing number of environmental and controlled laboratory testing studies have reported adverse reproductive health effects in animals exposed to various UOG chemical mixtures. An expanding body of epidemiological literature has assessed adverse birth outcomes, although none has directly examined reproductive measures such as time to pregnancy, semen quality, and other direct measures of fertility. The existing literature provides moderate evidence for decreased birth weights, increased risk of small for gestational age and/or preterm birth, increased congenital abnormalities, and increased infant mortality, though importantly, studies are widely variable in methods used. Most studies utilized distance from UOG operations as an exposure proxy and did not measure actual chemical exposures experienced by those living near these operations. As such, while there is growing evidence for effects on births in these regions and good mechanistic evidence for potential reproductive toxicity, there is much research still needed to make firm conclusions about UOG development and reproductive health.

Prenatal exposure to common infections and newborn DNA methylation: A prospective, population-based study

BackgroundInfections during pregnancy have been robustly associated with adverse mental and physical health outcomes in offspring, yet the underlying molecular pathways remain largely unknown. Here, we examined whether exposure to common infections in utero associates with DNA methylation (DNAm) patterns at birth and whether this in turn relates to offspring health outcomes in the general population. MethodsUsing data from 2,367 children from the Dutch population-based Generation R Study, we first performed an epigenome-wide association study to identify differentially methylated sites and regions at birth associated with prenatal infection exposure. We also examined the influence of infection timing by using self-reported cumulative infection scores for each trimester. Second, we sought to develop an aggregate methylation profile score (MPS) based on cord blood DNAm as an epigenetic proxy of prenatal infection exposure and tested whether this MPS prospectively associates with offspring health outcomes, including psychiatric symptoms, BMI, and asthma at ages 13–16 years. Third, we investigated whether prenatal infection exposure associates with offspring epigenetic age acceleration – a marker of biological aging. Across all analysis steps, we tested whether our findings replicate in 864 participants from an independent population-based cohort (ALSPAC, UK). ResultsWe observed no differentially methylated sites or regions in cord blood in relation to prenatal infection exposure, after multiple testing correction. 33 DNAm sites showed suggestive associations (p < 5e10 − 5; of which one was also nominally associated in ALSPAC), indicating potential links to genes associated with immune, neurodevelopmental, and cardiovascular pathways. While the MPS of prenatal infections associated with maternal reports of infections in the internal hold out sample in the Generation R Study (R2incremental = 0.049), it did not replicate in ALSPAC (R2incremental = 0.001), and it did not prospectively associate with offspring health outcomes in either cohort. Moreover, we observed no association between prenatal exposure to infections and epigenetic age acceleration across cohorts and clocks. ConclusionIn contrast to prior studies, which reported DNAm differences in offspring exposed to severe infections in utero, we do not find evidence for associations between self-reported clinically evident common infections during pregnancy and DNAm or epigenetic aging in cord blood within the general pediatric population. Future studies are needed to establish whether associations exist but are too subtle to be statistically meaningful with present sample sizes, whether they replicate in a cohort with a more similar infection score as our discovery cohort, whether they occur in different tissues than cord blood, and whether other biological pathways may be more relevant for mediating the effect of prenatal common infection exposure on downstream offspring health outcomes.

PON1 Status in Relation to Gulf War Illness: Evidence of Gene-Exposure Interactions from a Multisite Case-Control Study of 1990-1991 Gulf War Veterans.

Deployment-related neurotoxicant exposures are implicated in the etiology of Gulf War illness (GWI), the multisymptom condition associated with military service in the 1990-1991 Gulf War (GW). A Q/R polymorphism at position 192 of the paraoxonase (PON)-1 enzyme produce PON1192 variants with different capacities for neutralizing specific chemicals, including certain acetylcholinesterase inhibitors. We evaluated PON1192 status and GW exposures in 295 GWI cases and 103 GW veteran controls. Multivariable logistic regression determined independent associations of GWI with GW exposures overall and in PON1192 subgroups. Exact logistic regression explored effects of exposure combinations in PON1192 subgroups. Hearing chemical alarms (proxy for possible nerve agent exposure) was associated with GWI only among RR status veterans (OR = 8.60, p = 0.014). Deployment-related skin pesticide use was associated with GWI only among QQ (OR = 3.30, p = 0.010) and QR (OR = 4.22, p < 0.001) status veterans. Exploratory assessments indicated that chemical alarms were associated with GWI in the subgroup of RR status veterans who took pyridostigmine bromide (PB) (exact OR = 19.02, p = 0.009) but not RR veterans who did not take PB (exact OR = 0.97, p = 1.00). Similarly, skin pesticide use was associated with GWI among QQ status veterans who took PB (exact OR = 6.34, p = 0.001) but not QQ veterans who did not take PB (exact OR = 0.59, p = 0.782). Study results suggest a complex pattern of PON1192 exposures and exposure-exposure interactions in the development of GWI.

Assessing Normalized Difference Vegetation Index as a proxy of urban greenspace exposure

The Normalized Difference Vegetation Index (NDVI) is a popular proxy of urban greenspace (UGS). However, it’s unclear how NDVI approximates physical characteristics of UGS in the context of urban health studies, causing ambiguities in translating research findings to UGS management. Therefore, we collected data from Landsat and MODIS satellites and Lidar 3D scans in New York City as of circa 2013, and we evaluated linear and non-linear relationships between NDVI and UGS characteristics. We found that: (1) % UGS was the best predicted UGS characteristic by NDVI (R2: 0.35–0.90, varies by data source and unit of analysis), whereas average tree height was the worst (R2: 0.09–0.46). The predictive power on % canopy cover, tree density, and crown volume density was in a similar range (R2: 0.10–0.67). Prediction improved with finer-resolution NDVI sources and larger units of analysis at the cost of losing useful variations; (2) There was a saturation effect where a linear relationship underestimated UGS characteristics in areas of high NDVI. These areas typically had NAIP-NDVI greater than the range of 0.08–0.25, Landsat-NDVI greater than the range of 0.42–0.65, and MODIS-NDVI greater than the range of 0.49–0.75; (3) Smaller absolute errors from a linear NDVI-UGS relationship were often found in more developed locations. We therefore recommend NDVI as a reliable predictor of UGS coverage and its use in longitudinal studies. Future studies should also consider fine resolution land cover maps and Lidar, which are increasingly available to derive detailed UGS characteristics.

Gut Microbiota Composition Is Causally Linked to Multiple Sclerosis: A Mendelian Randomization Analysis.

Accumulating evidence links the microbial communities inhabiting the gut to the pathophysiological processes underlying multiple sclerosis (MS). However, most studies on the microbiome in MS are correlative in nature, thus being at risk of confounding and reverse causality. Mendelian randomization (MR) analyses allow the estimation of the causal relationship between a risk factor and an outcome of interest using genetic variants as proxies for environmental exposures. Here, we performed a two-sample MR to assess the causality between the gut microbiome and MS. We extracted genetic instruments from summary statistics from three large genome-wide association studies (GWASs) on the gut microbiome (18,340, 8959, and 7738 subjects). The exposure data were derived from the latest GWAS on MS susceptibility (47,429 patients and 68,374 controls). We pinpointed several microbial strains whose abundance is linked with enhanced MS risk (Actinobacteria class, Bifidobacteriaceae family, Lactobacillus genus) or protection (Prevotella spp., Lachnospiranaceae genus, Negativibacillus genus). The largest risk effect was seen for Ruminococcus Torques (OR, 2.89, 95% C.I. 1.67-5, p = 1.51 × 10-4), while Akkermansia municiphila emerged as strongly protective (OR, 0.43, 95% C.I. 0.32-0.57, p = 1.37 × 10-8). Our findings support a causal relationship between the gut microbiome and MS susceptibility, reinforcing the relevance of the microbiome-gut-brain axis in disease etiology, opening wider perspectives on host-environmental interactions for MS prevention.

The causal relationship between plasma protein-to-protein ratios and type 2 diabetes and its complications: Proteomics mendelian randomization study.

In recent years, proteomics research has surged, with numerous observational studies identifying associations between plasma proteins and type 2 diabetes. However, research specifically focusing on the ratios of plasma proteins in type 2 diabetes remains relatively scarce. This study primarily employed a two-sample, two-step Mendelian randomization (MR) approach, leveraging genetic data from several large, publicly accessible genome-wide association studies, wherein single nucleotide polymorphisms served as proxies for exposures and diseases. Within this framework, we applied two-sample MR to assess the associations between the 2821 plasma protein-to-protein ratios and type 2 diabetes along with its complications and utilized reverse MR to confirm the unidirectionality of these causal relationships. In addition, we employed two-step MR to investigate the potential mediating role of body mass index in these associations. To augment the robustness of our findings, we systematically implemented a series of sensitivity analyses. The results gleaned from the inverse-variance weighted method elucidated that a cumulative sum of 23 protein-to-protein ratios bore a causal nexus with type 2 diabetes across both sample cohorts. With each incremental elevation of 1 standard deviation in the genetically anticipated protein-to-protein ratio, the susceptibility to type 2 diabetes oscillated from 0.93 (95% confidence interval: 0.87, 1.00) for the CNTN3/NCSS1 protein level ratio to 1.13 (1.06, 1.22) for the DBNL/NCK2 protein level ratio. Moreover, a tally of eight protein-to-protein ratios correlated with a minimum of one complication linked to type 2 diabetes. Diverse sensitivity analyses corroborated the robustness of these observations. The outcomes of our investigation unveiled correlations between 23 plasma protein-to-protein ratios and type 2 diabetes, with eight of these ratios entwined with complications of type 2 diabetes. These discoveries offer novel perspectives on the diagnosis and management of type 2 diabetes and its associated complications.

The mediating role of systemic inflammation and moderating role of racialization in disparities in incident dementia

BackgroundExposure to systemic racism is linked to increased dementia burden. To assess systemic inflammation as a potential pathway linking exposure to racism and dementia disparities, we investigated the mediating role of C-reactive protein (CRP), a systemic inflammation marker, and the moderating role of the racialization process in incident dementia.MethodsIn the US Health and Retirement Study (n = 6,908), serum CRP was measured at baseline (2006, 2008 waves). Incident dementia was classified by cognitive tests over a six-year follow-up. Self-reported racialized categories were a proxy for exposure to the racialization process. We decomposed racialized disparities in dementia incidence (non-Hispanic Black and/or Hispanic vs. non-Hispanic white) into 1) the mediated effect of CRP, 2) the moderated portion attributable to the interaction between racialized group membership and CRP, and 3) the controlled direct effect (other pathways through which racism operates).ResultsThe 6-year cumulative incidence of dementia is 12%. Among minoritized participants (i.e., non-Hispanic Black and/or Hispanic), high CRP levels ( ≥ 75th percentile or 4.73μg/mL) are associated with 1.26 (95%CI: 0.98, 1.62) times greater risk of incident dementia than low CRP ( < 4.73μg/mL). Decomposition analysis comparing minoritized versus non-Hispanic white participants shows that the mediating effect of CRP accounts for 3% (95% CI: 0%, 6%) of the racial disparity, while the interaction effect between minoritized group status and high CRP accounts for 14% (95% CI: 1%, 27%) of the disparity. Findings are robust to potential violations of causal mediation assumptions.ConclusionsMinoritized group membership modifies the relationship between systemic inflammation and incident dementia.