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Proteus mirabilis, a Gram-negative uropathogen, is a major causative agent in catheter-associated urinary tract infections (CAUTI). Mannose-resistant Proteus-like fimbriae (MR/P) are crucially important for P. mirabilis infectivity and are required for biofilm formation and auto-aggregation, as well as for bladder and kidney colonization. Here, the X-ray crystal structure of the MR/P tip adhesin, MrpH, is reported. The structure has a fold not previously described and contains a transition metal center with Zn2+ coordinated by three conserved histidine residues and a ligand. Using biofilm assays, chelation, metal complementation, and site-directed mutagenesis of the three histidines, we show that an intact metal binding site occupied by zinc is essential for MR/P fimbria-mediated biofilm formation, and furthermore, that P. mirabilis biofilm formation is reversible in a zinc-dependent manner. Zinc is also required for MR/P-dependent agglutination of erythrocytes, and mutation of the metal binding site renders P. mirabilis unfit in a mouse model of UTI. The studies presented here provide important clues as to the mechanism of MR/P-mediated biofilm formation and serve as a starting point for identifying the physiological MR/P fimbrial receptor.

Brain aging is characterized by changes in both hemodynamic and neuronal responses, which may be influenced by the cardiorespiratory fitness of the individual. To investigate the relationship between neuronal and hemodynamic changes, we studied the brain activity elicited by visual stimulation (checkerboard reversals at different frequencies) in younger adults and in older adults varying in physical fitness. Four functional brain measures were used to compare neuronal and hemodynamic responses obtained from BA17: two reflecting neuronal activity (the event-related optical signal, EROS, and the C1 response of the ERP), and two reflecting functional hemodynamic changes (functional magnetic resonance imaging, fMRI, and near-infrared spectroscopy, NIRS). The results indicated that both younger and older adults exhibited a quadratic relationship between neuronal and hemodynamic effects, with reduced increases of the hemodynamic response at high levels of neuronal activity. Although older adults showed reduced activation, similar neurovascular coupling functions were observed in the two age groups when fMRI and deoxy-hemoglobin measures were used. However, the coupling between oxy- and deoxy-hemoglobin changes decreased with age and increased with increasing fitness. These data indicate that departures from linearity in neurovascular coupling may be present when using hemodynamic measures to study neuronal function. •Neurovascular coupling estimated in young and old adults varying in fitness level.•Measurements include neuronal (ERPs, EROS) and hemodynamic (fMRI, NIRS) methods.•Non-linear relationship was found between neuronal and hemodynamic measures.•Oxy-hemoglobin concentration changes were reduced in low-fit older adults.

The catheter-associated uropathogen Proteus mirabilis frequently causes urinary stones, but little has been known about the initial stages of bladder colonization and stone formation. We found that P. mirabilis rapidly invades the bladder urothelium, but generally fails to establish an intracellular niche. Instead, it forms extracellular clusters in the bladder lumen, which form foci of mineral deposition consistent with development of urinary stones. These clusters elicit a robust neutrophil response, and we present evidence of neutrophil extracellular trap generation during experimental urinary tract infection. We identified two virulence factors required for cluster development: urease, which is required for urolithiasis, and mannoseresistant Proteus-like fimbriae. The extracellular cluster formation by P. mirabilis stands in direct contrast to uropathogenic Escherichia coli, which readily formed intracellular bacterial communities but not luminal clusters or urinary stones. We propose that extracellular clusters are a key mechanism of P. mirabilis survival and virulence in the bladder.

Background: The widespread use of organophosphorus (OP) pesticides has led to frequent exposure in adults and children. Because such exposure may cause adverse health effects, particularly in children, the sources and patterns of exposure need to be studied further. Objectives: We assessed young urban/suburban children's longitudinal exposure to OP pesticides in the Children's Pesticide Exposure Study (CPES) conducted in the greater Seattle, Washington, area, and used a novel study design that allowed us to determine the contribution of dietary intake to the overall OP pesticide exposure. Methods: Twenty-three children 3-11 years of age who consumed only conventional diets were recruited for this 1-year study conducted in 2003-2004. Children switched to organic diets for 5 consecutive days in the summer and fall sampling seasons. We measured specific urinary metabolites for malathion, chlorpyrifos, and other OP pesticides in urine samples collected twice daily for a period of 7, 12, or 15 consecutive days during each of the four seasons. Results: By substituting organic fresh fruits and vegetables for corresponding conventional food items, the median urinary metabolite concentrations were reduced to nondetected or close to nondetected levels for malathion and chlorpyrifos at the end of the 5-day organic diet intervention period in both summer and fall seasons. We also observed a seasonal effect on the OP urinary metabolite concentrations, and this seasonality corresponds to the consumption of fresh produce throughout the year. Conclusions: The findings from this study demonstrate that dietary intake of OP pesticides represents the major source of exposure in young children.

The Michigan Polybrominated Biphenyl (PBB) Registry, followed since 1976, was created after a 1973 chemical manufacturing mistake. The flame retardant PBB was accidentally mixed into animal feed and distributed to Michigan farms for nearly a year, exposing farm residents and animal product consumers. We synthesized knowledge to date on health effects of PBB exposure within the Michigan PBB Registry and describe research findings in the context of literature on other persistent organic pollutants (POPs) and endocrine-disrupting chemicals (EDCs). We reviewed literature published from 1973 to 2025 on human health effects of PBB following the Michigan contamination, using PubMed and Thompson Reuters (ISI) Web of Science databases. We excluded studies not in English; studies on exposures besides PBB; animal studies; reviews, abstracts, or letters to the editor; studies without a health outcome; and studies outside of Michigan or unrelated to the 1973 contamination. For each article, two researchers performed title and abstract screening, full article review, and data extraction. We included 79 publications out of 601 identified and screened. Early studies did not find many health outcomes associated with PBB, possibly because of methodological limitations. More recent studies on long-term and multigenerational impacts found an increased breast cancer risk, accelerated pubertal development and earlier menarche for girls exposed , urogenital problems and slower pubertal development in boys exposed , lower estrone 3-glucuronide and follicle-stimulating hormone among women exposed in childhood, and increased miscarriage risk among daughters of exposed women. Epigenetic and metabolomic research reported altered pathways related to estrogenic effects and immune function as well as the epigenetic alterations of spermatogenic cells. This unique community-academic partnership has produced insights into multigenerational consequences of EDC/POP exposures across the life course. The findings from this cohort underscore the broader relevance of critical windows of vulnerability, particularly during fetal development and childhood. https://doi.org/10.1289/EHP15012.

Polybrominated biphenyls (PBB) and polychlorinated biphenyls (PCB) are persistent organic pollutants with potential endocrine-disrupting effects linked to adverse health outcomes. In this study, we utilize high-resolution metabolomics (HRM) to identify internal exposure and biological responses underlying PCB and multigenerational PBB exposure for participants enrolled in the Michigan PBB Registry. HRM profiling was conducted on plasma samples collected from 2013 to 2014 from a subset of participants enrolled in the Michigan PBB Registry, including 369 directly exposed individuals (F0) who were alive when PBB mixtures were accidentally introduced into the food chain and 129 participants exposed to PBB or through breastfeeding, if applicable (F1). Metabolome-wide association studies were performed for PBB-153 separately for each generation and (PCB-118, PCB-138, PCB-153, and PCB-180) in the two generations combined, as both had direct PCB exposure. Metabolite and metabolic pathway alterations were evaluated following a well-established untargeted HRM workflow. Mean levels were [standard deviation (SD): 13.9] for PBB-153 and (SD: 0.788) for . Sixty-two and 26 metabolic features were significantly associated with PBB-153 in F0 and F1 [false discovery rate (FDR) ], respectively. There were 2,861 features associated with (FDR ). Metabolic pathway enrichment analysis using a bioinformatics tool revealed perturbations associated with in numerous oxidative stress and inflammation pathways (e.g., carnitine shuttle, glycosphingolipid, and vitamin B9 metabolism). Metabolic perturbations associated with PBB-153 in F0 were related to oxidative stress (e.g., pentose phosphate and vitamin C metabolism) and in F1 were related to energy production (e.g., pyrimidine, amino sugars, and lysine metabolism). Using authentic chemical standards, we confirmed the chemical identity of 29 metabolites associated with levels (level 1 evidence). Our results demonstrate that serum PBB-153 is associated with alterations in inflammation and oxidative stress-related pathways, which differed when stratified by generation. We also found that was associated with the downregulation of important neurotransmitters, serotonin, and 4-aminobutanoate. These findings provide novel insights for future investigations of molecular mechanisms underlying PBB and PCB exposure on health. https://doi.org/10.1289/EHP12657.

Experts recommend reporting environmental exposure results back to research participants and communities, yet environmental health researchers need further guidance to improve the practice of reporting back. We present the results of a workshop developed to identify pertinent issues and areas for action in reporting back environmental health research results. Thirty-five attendees participated, brainstorming responses to the prompt: “What are some specific issues that are relevant to reporting back research results to individuals or the larger community?”, and then grouping responses by similarity and rating their importance. Based on a combined theoretical foundation of grounded theory and qualitative content analysis, we used concept mapping to develop a collective understanding of the issues. Visual maps of the participants’ responses were created using nonmetric multidimensional scaling and hierarchical cluster analysis. The resulting concept map provided a spatial depiction of five issue areas: Effective Communication Strategies, Community Knowledge and Concerns, Uncertainty, Empowering Action, and Institutional Review and Oversight (listed from highest to lowest rating). Through these efforts, we disentangled the complex issues affecting how and whether environmental health research results are reported back to participants and communities, by identifying five distinct themes to guide recommendations and action. Engaging community partners in the process of reporting back emerged as a unifying global theme, which could improve how researchers report back research results by understanding community context to develop effective communication methods and address uncertainty, the ability to act, and institutional concerns about beneficence and justice.

The HERCULES Exposome Research Center at Emory University uses an exposome approach to study the environment's effect on health and community well-being. HERCULES is guided by a Stakeholder Advisory Board (SAB) that includes representatives of neighborhoods, nonprofit organizations, government agencies, and academic institutions in the Atlanta metropolitan region. This region (and the SAB) has a large proportion of Black residents, many of whom live in areas experiencing environmental injustices. Historic and current racial injustices in Atlanta and public health research made it imperative to initiate dialogue and implement actions to address racism and power dynamics that may impact research and partnerships between affected communities and our institution.After initial discussion, the HERCULES Community Engagement Core and SAB members formed a workgroup to develop an internal anti-racism process. The workgroup drafted an Anti-Racism Commitment, hosted a Racism and Equity Dialogue Series, and initiated a strategic planning process to implement the resulting recommendations, which fell into the following categories: anti-racist guidance/policies and recommendations for research, community engagement, and the department. Center leadership and the SAB were engaged throughout the iterative process.This deliberate and ongoing process allows HERCULES to identify and begin implementing action items that go beyond a written proclamation to address racialized power imbalances and systemic inequities. HERCULES is committed to working collaboratively to earn community trust while addressing systemic issues, recognizing that these are essential to forming research partnerships that address health inequities.

Background This study is a long-term follow-up of individuals exposed to polybrominated biphenyls (PBBs). Widespread contamination of PBBs began in 1973 in Michigan when PBBs entered the food chain. PBBs are synthetic chemicals that were once used in industrial products. Their production in the United States ended following this incident. PBBs and other brominated flame retardants belong to a class of persistent organic pollutants that have been shown to affect human health. We conducted this study to investigate whether PBB exposure was associated with all-cause or cause-specific mortality risk. Methods We included cohort data from 1976 (when the study began) and linked to National Death Index data obtained through the early release of 2021. Serum PBB concentrations were measured at enrollment in the study. We used survival analysis to estimate sex-specific hazard ratios (HR) and 95% confidence intervals (CI), adjusting for age and other important risk factors. The mortality study included 3,954 individuals. Results In age-stratified analyses, higher PBB exposure was not associated with all-cause mortality risk in males or females. In cause-specific analyses conducted in the 16 or older group, we found no association between PBB exposure and circulatory system disease mortality. For all-cancer mortality, we found higher PBB exposure associated with increased risk of mortality in females (HR: 1.50, 95% CI: 1.02–2.22), which was inversed in males (HR: 0.68, 95% CI: 0.46–1.01). BMI appeared to modify the association between PBB exposure and all-cause mortality risk in males and all-cancer mortality risk in males and females. Conclusions This comprehensive study found that the association between PBB exposure and cancer mortality risk varied by sex. Further research is needed to understand these sex-specific differences.

The Michigan PBB Oral History Project documented community residents’ descriptions of a large-scale chemical contamination—the PBB contamination—that occurred in Michigan in 1973. These oral histories document residents’ and others’ experiences during and after the contamination. We conducted a grounded theory qualitative analysis of 31 oral histories to examine the experiences of community members, researchers, lawyers, and others who actively sought out and contributed essential information about the contamination and its impacts. Our findings highlight several challenges encountered in the development of this knowledge including four central themes—contested knowledge, community skills, inaction, and uncertainty. Integrating environmental health literacy, community capacity, and contested illness frameworks, we examine the contributions of community residents, scientists (from inside and outside the community), and others to the development of knowledge to inform decisions and sustain action regarding this large-scale contamination. We close with a discussion of lessons learned regarding efforts to build environmental health knowledge within uncertain and often contested contexts and for promoting environmental health and action related to large-scale chemical contaminations. Our findings suggest the importance of integrated frameworks for examining and promoting the critical role of community skills, leadership, participation, sense of community, and community power in promoting environmental health.