Carbapenem resistance is an urgent public health threat. Wastewater surveillance could support antimicrobial resistance monitoring at long-term care facilities (LTCFs). Feasibility of wastewater sampling (via composite or passive sampler, and sewer biofilm swabs) for carbapenemase genes ( bla KPC , bla VIM , bla OXA-48-like , bla NDM , and bla IMP ) detected by qPCR or GeneXpert® Carba-R from a LTCF was assessed over 16 months and compared to clinical infections. bla KPC , bla OXA-48-like , and bla VIM were routinely detected in composite wastewater samples (6.4±0.8 log 10 gene copy (GC)/ml (100% of 61 samples), 5.5±0.8 (98%), and 5.9±1.3 (34%), respectively), passive samples (8.2±0.5 log 10 GC/g (31% of 55), 6.6±0.5 (96%), and 6.6±0.7 (31%)) and sewer biofilm (6.0±0.7 log 10 GC/cm 2 of pipe (100% of 17), 5.0±0.7 (100%), and 5.8±2.7 (24%)). Resistomes of wastewater and sewer biofilms differed, but both contained bla KPC, bla VIM, and bla IMP . Passive sampling may be a suitable alternative to composite sampling. Wastewater surveillance is a promising addition to carbapenemase monitoring.

ABSTRACT Sewer biofilms represent dynamic interfaces for exchange of bacteria and antibiotic resistance genes between biofilms and the overlying wastewater. Using inline, biofilm reactors, the movement of bacteria and 16S rRNA and carbapenemase genes ( bla KPC , bla VIM , bla NDM , bla OXA-48-like , and bla IMP ) between wastewater and sewer biofilms was investigated. Established, complex biofilms without these β-lactamase ( bla ) genes, absorbed resistant bacteria within two minutes of exposure to high concentrations of resistant cultures in lab settings. Carbapenem-resistant organisms from these high-concentration source biofilms transferred to downstream biofilms over 60 minutes of representative sewer shear flows. Mass balances of bacteria and genes in biofilms versus wastewater under representative shear flow showed that biofilms exposed to resistant cultures contributed more to the wastewater than to the downstream biofilms. In field studies, established, complex biofilms without target carbapenem-resistant bacteria and genes from wastewater within hours and then stabilized between 2 to 15 days, not varying by more than 0.5 MPN/cm 2 or 0.5 log gene copies (GC)/cm 2 . In contrast, metagenomic profiles of the bacterial community species continued to change up to 21 days. Established biofilms with resistant bacteria and genes exposed to tertiary-treated wastewater without target carbapenemase genes or meropenem antibiotics did not lose resistant genes or bacteria over nine days of exposure (i.e., < 1 log GC/cm 2 reduction). Results show that sewer biofilms contribute to the resistance-gene signal found in sewer wastewater by absorbing and releasing bacteria and genes. Consideration of sewer biofilm dynamics is essential for more accurately interpreting wastewater bacterial concentrations in wastewater-based epidemiology studies. GRAPHICAL ABSTRACT

The Centralized Health and Exposomic Resource (C-HER) project has identified, profiled, spatially indexed, and stored over 30 external exposomic datasets. The resulting analytic and AI-ready data (AAIRD) provides a significant opportunity to develop an integrated picture of the exposome for health research. The exposome is a conceptual framework designed to guide the study of the complex environmental and genetic factors that together shape human health. Few composite measures of the exposome exist due to the high dimensionality of exposure data, multimodal data sources, and varying spatiotemporal scales. We develop a data engineering solution that overcomes the challenges of spatio-temporal linkage in this field. We provide examples of how environmental data can be combined to characterize a region, model air pollution, or provide indicators for cancer research. The development of AAIRD will allow future studies to use ML and deep learning methods to generate spatial and contextual exposure data for disease prediction.

Wastewater surveillance (WWS) at healthcare facilities is a nascent field with knowledge gaps in the feasibility of conducting such surveillance at this specialized facility type, and for how to best implement and interpret wastewater (WW) data. WWS was piloted at skilled nursing facilities, including conducting tracer studies, optimization of a low-flow strainer for autosampler WW collection, and preliminary testing of a WW access survey. An expanded WW access survey with collaboration from additional partners was distributed to 16 post-acute/long-term care facilities. The lessons learned obtained through the pilot ‘use cases’ demonstrated minimal clogging and consistent collection of WW using a low-flow strainer (±0.36 L) and tracer studies highlighted the importance to confirm facility effluent source with an average visual dye detection between 1.5 and 2.5 min from the toilet flush. The expanded WW access survey assessed the feasibility of WWS regarding physical onsite manhole access, safety aspects, effluent flow, and other factors, where 75% (12 of 16) of surveyed facilities demonstrated feasibility. Healthcare facility-level WWS includes specialized methodological approaches prior to implementation to achieve the intended public health impact. These considerations support the continued overall goal of detecting emerging biological public health threats at healthcare facilities using WWS.

AIMS:The burden of Type 1 Diabetes Mellitus (DM, T1D) is growing and represents a major health care cost. This study investigated the relationship between ambient particulate matter (PM2.5) exposure and T1D complications. The research was motivated by the potential for air pollution's known inflammatory effects to exacerbate T1D's microvascular harms (i.e., damaged peripheral tissues from poor glucose control). METHODS:In a cohort of 12, 925 Utah participants, competing-risk Cox proportional hazards regression analyzed the increased risk of PM2.5 exposure and diabetic ketoacidosis (DKA), along with kidney, ophthalmic, and neurological complications. RESULTS:An interquartile range increase in one-year PM2.5 exposure was associated with increased risk of DKA by 28.8 % (95 % CI: 14.3, 45.2), ophthalmic complications by 33.5 % (95 % CI: 10.0, 62.0), and neurological complications by 35.1 % (95 % CI: 14.3, 59.6). No statistically significant effect was found for diabetic kidney complications. Acute exposures of 30, 60, and 90 days was also associated with increased risk of diabetic ketoacidosis, although less than one-year exposure. CONCLUSIONS:We hypothesize these effects stem from PM2.5-induced oxidative stress and systemic inflammation, which may exacerbate metabolic disruptions already present in hyperglycemic individuals. Clients and providers may want to consider environmental factors, like air pollution, in T1D management.

Animal models suggest that environmental exposures can impact future generations of offspring. Yet, there are limited human epidemiological studies of multigenerational environmental exposures, and even fewer such studies of maternal and paternal exposures. Leveraging a unique data resource in Utah (USA), we examine if offspring (F2, n = 6380) are at increased risk of intellectual disability (ID) if the mother or father (F1) were exposed to polluting industrial facilities while their own mothers (F0) were pregnant. We obtained historical data on polluting industry locations and calculated facility densities within 3 km and 5 km of each child's (F2) grandmothers' (F0) residential addresses at time of their mothers' and fathers' (F1) births as well as their mother's address at the time of their birth. We weighted those counts by pairing industry codes with national Risk-Screening Environmental Indicators health risk scores. One standard deviation (SD) increase in the density of facilities near the pregnant maternal grandmother was associated with 1.12 (1.03-1.22) and 1.09 (1.003-1.19) times greater odds of ID at 3 km and 5 km, respectively. Weighing these facility densities by risk, odds ratios associated with SD increases were 1.12 (1.04-1.20, 3 km) and 1.08 (1.003-1.17, 5 km). Associations with facility densities near the pregnant paternal grandmother were positive but weak. Associations with risk-weighted facility density near the pregnant paternal grandmother were stronger at 5 km (1.12, 1.02-1.22) than at 3 km. Results indicated that ancestral exposures, particularly when the maternal grandmother (F0) was pregnant with the mother (F1), may increase risks of developmental disabilities in the next generation (F2).

Typhoid fever poses a significant public health risk, particularly in low- and middle-income countries where access to clean water and improved sanitation may be limited. In Pakistan, this risk is especially serious given the emergence of an extensively drug-resistant (XDR) Salmonella Typhi strain, a strain attributed to S. Typhi acquisition of the blaCTX-M-15 gene. The now-dominant XDR S. Typhi strain, non-XDR S. Typhi, and blaCTX-M genes are readily disseminated via drinking water and wastewater in Pakistan and may also be present in biofilm associated with these environmental sources. This study investigates the presence of S. Typhi and blaCTX-M genes within these environmental compartments. Drinking water (n=35) or wastewater samples (n=35) and samples of their associated biofilms were collected in Karachi and Hyderabad, Pakistan. Samples were tested by PCR for S. Typhi and blaCTX-M group 1 genes as a proxy for blaCTX-M-15. Heterotrophic plate counts (HPC) were conducted to assess microbial load. S. Typhi was detected by PCR in one bulk wastewater sample and one drinking water biofilm. BlaCTX-M group 1 genes were detected in all sample types and were detected more frequently in bulk wastewater (n=13/35) than in drinking water (n=2/35) and more frequently overall in biofilm samples (n=22/70) versus bulk water (n=15/70). Detection of blaCTX-M in biofilm was not significantly associated with detection in the associated bulk water sample. This study marks the first detection of S. Typhi in drinking water biofilm and the first report of blaCTX-M genes in environmental biofilm in Pakistan. Environmental biofilm, particularly in drinking water systems, may serve as reservoirs for human exposure to S. Typhi and drug resistance genes. This study underscores the importance of expanding surveillance strategies to include biofilm sampling, providing valuable insights into pathogen dissemination in water systems, and informing targeted public health interventions to prevent waterborne diseases.

Abstract Background Antimicrobial resistance is a critical global concern. Pathogens may become resistant through acquisition of mobile genetic elements harboring antimicrobial resistance genes (ARGs). Environmental biofilms provide an excellent venue for ARG transfer via mobile elements. Mobile ARG dissemination pathways in the environment require a better understanding. Here we use proximity-ligation (Hi-C) and metagenomic sequencing to pair plasmids and ARGs to their bacterial hosts and present evidence of plasmid sharing between bacterial species. Methods Eight environmental biofilm swabs collected from water sources in Sindh Province, Pakistan were equally aliquoted for preparation by 1) DNA cross-linking for proximity ligation and Hi-C metagenomic sequencing, and 2) traditional shotgun metagenomic sequencing. Metagenomic Hi-C was used to analyze the proximity-ligation and shotgun sequencing data to construct metagenomic-assembled genomes, determine if ARGs were chromosomally- or plasmid-located, and associate mobile genetic elements and ARGs with their host cells. Results Actinomycetia, Gammaproteobacteria, and Alphaproteobacteria were the most frequently detected taxa in most samples, with Bacteroidia also being at higher numbers than other taxa in most samples. Multiple classes of ARGs in the sample were identified as being located on plasmids, including aminoglycoside ARGs (e.g. aph(3'), aph(6)), beta-lactam RGs (blaCTX-M-15, blaEC, blaTEM-1, blaOKP-A), macrolide RGs (ere(A), erm(X), mph(A), mef(C), mph(G)), quinolone RG qnrS1, sulfonamide RG sul1, and several tetracycline and metal ARGs. TetC, blaA2, and aac(3)I, were only found on bacterial chromosomes. Analysis of unique assembled ARG-bearing plasmids and taxonomic clusters revealed plasmid sharing between bacterial species, some of which were not closely related taxa. Conclusion Mobile ARGs are common in environmental biofilms. These ARGs have the potential to spread within biofilms between species, as evidenced by shared plasmid between different bacterial species. The environment should be considered an important source for mobile ARG dissemination between bacterial species. Disclosures All Authors: No reported disclosures

Measures of access to essential surgery in Mongolia have not accounted for natural barriers to movement, seasonality, and the modifiable areal unit problem scale effects. This physical accessibility analysis indicates natural barriers and seasonality threaten access to surgical care, shifting Mongolia from an attaining to a non-attaining country with estimates below the target population goal of 80%. Remote communities are particularly impacted, with access reduced by up to 6.1%. Spatial resolution of the input data influences the results by up to 14.2%. This highlights the importance of including natural barriers and seasonality in healthcare access scenarios using a fine spatial resolution.

BACKGROUND:Research demonstrates that chronic exposure to fine particulates (PM2.5) increases risks of neurodevelopmental conditions, such as intellectual disability (ID). Few studies have examined neurodevelopmental health impacts of pollution spikes exceeding 24-h (24-h) PM2.5 guidelines, despite relevance to the regulatory landscape. The current potential for regulatory changes to 24-h PM2.5 standards in the United States makes research on exceedances relevant. OBJECTIVE:To examine associations between 24-h PM2.5 exceedances and the risk of ID. METHODS:We conducted a retrospective case-control study of a sample of children in Utah, USA. We used generalized estimating equations to predict odds of ID based on the number of 24-h PM2.5 exceedance days during the preconception period and three trimesters of pregnancy. Exceedance days are defined as per current World Health Organization (WHO) [≥15 μg/m3] and current US Environmental Protection Agency (EPA) [≥35 μg/m3] 24-h guidelines. RESULTS:PM2.5 exceedances are associated with ID risk during the preconception and first trimester periods and not the second and third trimesters. During the preconception period, each day exceeding 15 μg/m3 or 35 μg/m3 was associated with a 1.023 (CI: 1.011-1.040) or 1.042 (CI: 1.026-1.059, p < 0.001) increase in odds of ID, respectively. During the first trimester, each day exceeding 15 μg/m3 or 35 μg/m3 was associated with a 1.032 (CI: 1.017-1.047) or 1.059 (CI: 1.030-1.088) increase in odds of ID, respectively. IMPACT STATEMENT:Potential regulatory movement on the US 24-h PM2.5 standard makes research that explicitly studies exceedances highly relevant. Yet few studies examine health effects of exceeding 24-h guidelines for any air pollutants. This study fills important gaps in the literature by examining associations between odds of intellectual disability and the count of days exceeding current 24-h PM2.5 guidelines, as established by the World Health Organization and US Environmental Protection Agency, during the prenatal period. We find that exceedances of both sets of guidelines, during the preconception and first trimester periods, are associated with ID risk.

Objectives. To examine whether a previously reported association between airborne lead exposure and children’s cognitive function replicates across a geographically diverse sample of the United States. Methods. Residential addresses of children (< 5 years) were spatially joined to the Risk-Screening Environmental Indicators model of relative airborne lead toxicity. Cognitive outcomes for children younger than 8 years were available for 1629 children with IQ data and 1476 with measures of executive function (EF; inhibitory control, cognitive flexibility). We used generalized linear models using generalized estimating equations to examine the associations of lead, scaled by interquartile range (IQR), accounting for individual- and area-level confounders. Results. An IQR increase in airborne lead was associated with a 0.74-point lower mean IQ score (b = −0.74; 95% confidence interval = −1.00, −0.48). The association between lead and EF was nonlinear and was modeled with a knot at the 97.5th percentile of lead in our sample. Lead was significantly associated with lower mean inhibitory control but not with cognitive flexibility. This effect was stronger among males for both IQ and inhibitory control. Conclusions. Early-life exposure to airborne lead is associated with lower cognitive functioning. ( Am J Public Health. 2024;114(3):309–318. https://doi.org/10.2105/AJPH.2023.307519 )

There are substantial challenges in studying human transgenerational epigenetic outcomes resulting from environmental conditions. The task requires specialized methods and tools that incorporate specific knowledge of multigenerational relationship combinations of probands and their ancestors, phenotype data for individuals, environmental information of ancestors and their descendants, which can span historical to present datasets, and informative environmental data that chronologically aligns with ancestors and descendants over space and time. As a result, there are few epidemiologic studies of potential transgenerational effects in human populations, thus limiting the knowledge of ancestral environmental conditions and the potential impacts we face with modern human health outcomes. In an effort to overcome some of the challenges in studying human transgenerational effects, we present two transgenerational study designs: transgenerational space-time cluster detection and transgenerational case-control study design. Like other epidemiological methods, these methods determine whether there are statistical associations between phenotypic outcomes (e.g., adverse health outcomes) among probands and the shared environments and environmental factors facing their ancestors. When the ancestor is a paternal grandparent, a statistically significant association provides some evidence that a transgenerational inheritable factor may be involved. Such results may generate useful hypotheses that can be explored using epigenomic data to establish conclusive evidence of transgenerational heritable effects. Both methods are proband-centric: They are designed around the phenotype of interest in the proband generation for case selection and family pedigree creation. In the examples provided, we incorporate at least three generations of paternal lineage in both methods to observe a potential transgenerational effect.

ABSTRACTBackgroundAnnual or biennial breast cancer screenings are recommended for women 40 and older. Women residing in rural areas have worse breast cancer survival rates than urban women, but no study has focused on rural versus urban residence in Utah regarding breast cancer screening and mortality.MethodsCases (n = 14,516) were women aged > 39 diagnosed with a first primary invasive breast cancer between 1998 and 2017 in Utah. Controls (n = 63,117) without a history of breast cancer were matched to cases by birth year and birth state. Mammography screening status was identified by Current Procedural Terminology (CPT) codes. Logistic regression was used to assess the odds of breast cancer diagnosis. The Cox proportional hazards model was used to assess survival outcomes for rural and urban breast cancer patients based on screening status.ResultsScreening mammography usage among rural patients diagnosed with breast cancer was lower (17.7%) than urban usage (20.7%). Usage of screening mammograms resulted in higher odds of breast cancer diagnosis at localized stage rather than at a regional and distant stage. Rural breast cancer cases had a higher proportion of deaths, and a lower proportion screened, than urban breast cancer cases. Hazard ratios showed that screening mammography usage was associated with better survival among both rural (HR = 0.50, 95% CI = 0.44–0.57) and urban (HR = 0.56, 95% CI = 0.39–0.82) breast cancer cases.ConclusionScreening mammography usage was associated with better overall survival regardless of place of residence. Removing barriers and improving information regarding breast cancer screenings are needed in both rural and urban settings in Utah to increase mammography usage, with the overall goal of increasing early detection and outcomes of breast cancer.