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Floral traits, including floral display and nutritional rewards from pollen and nectar, drive pollinator visitation. Even within a single plant species, environmental factors can influence the quality and quantity of floral resources. Yet, the ecological interactions driving this variation in floral resources, especially those belowground, remain unknown. Here, we investigate how soil microbial community composition and nutrient availability, specifically distinct arbuscular mycorrhizal fungi (AMF) species and phosphorus (P) supply, affect plant growth, AMF traits, floral traits, and how that, in turn, affects bee visitation. We found that increased AMF richness of functional diversity enhanced floral display (flower size and number) and rewards (nectar volume and pollen protein) and increased bee visitation. Using structural equation modeling, we found that AMF associations could boost bee visitation by enhancing flower size. However, trade-offs occur; flower size correlates negatively with root colonization but positively with hyphal length, suggesting that AMF traits drive the effects of AMF on flower growth. Overall, the effect of AMF on floral traits and bee visitation was not homogenous; instead, AMF trait differences interact with P supply, resulting in varying effects on floral traits and subsequently bee foraging dynamics. These results highlight that focusing on beneficial belowground interactions could provide an opportunity to bolster bee visitation.

BACKGROUND: Uptake of mobile phone surveys (MPS) is increasing in many low- and middle-income countries, particularly within the context of data collection on non-communicable diseases (NCDs) behavioural risk factors. One barrier to collecting representative data through MPS is capturing data from older participants.Respondent driven sampling (RDS) consists of chain-referral strategies where existing study subjects recruit follow-up participants purposively based on predefined eligibility criteria. Adapting RDS strategies to MPS efforts could, theoretically, yield higher rates of participation for that age group. OBJECTIVE: To investigate factors that influence the perceived acceptability of a RDS recruitment method for MPS involving people over 45 years of age living in Colombia. METHODS: An MPS recruitment strategy deploying RDS techniques was piloted to increase participation of older populations. We conducted a qualitative study that drew from surveys with open and closed-ended items, semi-structured interviews for feedback, and focus group discussions to explore perceptions of the strategy and barriers to its application amongst MPS participants. RESULTS: The strategys success is affected by factors such as cultural adaptation, institutional credibility and public trust, data protection, and challenges with mobile phone technology. These factors are relevant to individuals willingness to facilitate RDS efforts targeting hard-to-reach people. Recruitment strategies are valuable in part because hard-to-reach populations are often most accessible through their contacts within their social network who can serve as trust liaisons and drive engagement. CONCLUSIONS: These findings may inform future studies where similar interventions are being considered to improve access to mobile phone-based data collection amongst hard-to-reach groups.

White matter hyperintensities of presumed vascular origin (WMH) are associated with cognitive impairment and are a key imaging marker in evaluating brain health. However, WMH volume alone does not fully account for the extent of cognitive deficits and the mechanisms linking WMH to these deficits remain unclear. Lesion network mapping (LNM) enables us to infer if brain networks are connected to lesions and could be a promising technique for enhancing our understanding of the role of WMH in cognitive disorders. Our study employed LNM to test the following hypotheses: (i) LNM-informed markers surpass WMH volumes in predicting cognitive performance; and (ii) WMH contributing to cognitive impairment map to specific brain networks. We analysed cross-sectional data of 3485 patients from 10 memory clinic cohorts within the Meta VCI Map Consortium, using harmonized test results in four cognitive domains and WMH segmentations. WMH segmentations were registered to a standard space and mapped onto existing normative structural and functional brain connectome data. We employed LNM to quantify WMH connectivity to 480 atlas-based grey and white matter regions of interest (ROI), resulting in ROI-level structural and functional LNM scores. We compared the capacity of total and regional WMH volumes and LNM scores in predicting cognitive function using ridge regression models in a nested cross-validation. LNM scores predicted performance in three cognitive domains (attention/executive function, information processing speed, and verbal memory) significantly better than WMH volumes. LNM scores did not improve prediction for language functions. ROI-level analysis revealed that higher LNM scores, representing greater connectivity to WMH, in grey and white matter regions of the dorsal and ventral attention networks were associated with lower cognitive performance. Measures of WMH-related brain network connectivity significantly improve the prediction of current cognitive performance in memory clinic patients compared to WMH volume as a traditional imaging marker of cerebrovascular disease. This highlights the crucial role of network integrity, particularly in attention-related brain regions, improving our understanding of vascular contributions to cognitive impairment. Moving forward, refining WMH information with connectivity data could contribute to patient-tailored therapeutic interventions and facilitate the identification of subgroups at risk of cognitive disorders.

RNA-Puzzles is a collective endeavor dedicated to the advancement and improvement of RNA three-dimensional structure prediction. With agreement from structural biologists, RNA structures are predicted by modeling groups before publication of the experimental structures. We report a large-scale set of predictions by 18 groups for 23 RNA-Puzzles: 4 RNA elements, 2 Aptamers, 4 Viral elements, 5 Ribozymes and 8 Riboswitches. We describe automatic assessment protocols for comparisons between prediction and experiment. Our analyses reveal some critical steps to be overcome to achieve good accuracy in modeling RNA structures: identification of helix-forming pairs and of non-Watson-Crick modules, correct coaxial stacking between helices and avoidance of entanglements. Three of the top four modeling groups in this round also ranked among the top four in the CASP15 contest.

INTRODUCTION: The Alzheimers Disease Neuroimaging Initiative-4 (ADNI-4) Engagement Core was launched to advance Alzheimers disease (AD) and AD-related dementia (ADRD) health equity research in underrepresented populations (URPs). We describe our evidence-based, scalable culturally informed, community-engaged research (CI-CER) model and demonstrate its preliminary success in increasing URP enrollment. METHODS: URPs include ethnoculturally minoritized, lower education (≤ 12 years), and rural populations. The CI-CER model includes: (1) culturally informed methodology (e.g., less restrictive inclusion/exclusion criteria, sociocultural measures, financial compensation, results disclosure, Spanish Language Capacity Workgroup) and (2) inclusive engagement methods (e.g., the Engagement Core team; Hub Sites; Community-Science Partnership Board). RESULTS: As of April 2024, 60% of ADNI-4 new in-clinic enrollees were from ethnoculturally or educationally URPs. This exceeds ADNI-4s ≥ 50% URP representation goal for new enrollees but may not represent final enrollment. DISCUSSION: Findings show a CI-CER model increases URP enrollment in AD/ADRD clinical research and has important implications for clinical trials to advance health equity. HIGHLIGHTS: The Alzheimers Disease Neuroimaging Initiative-4 (ADNI-4) uses a culturally informed, community-engaged research (CI-CER) approach. The CI-CER approach is scalable and sustainable for broad, multisite implementation. ADNI-4 is currently exceeding its inclusion goals for underrepresented populations.

Background/Objectives: This study aims to develop and validate a Glaucoma Health Score (GHS) that incorporates multiple individual glaucoma risk factors to enhance glaucoma detection in screening environments. Methods: The GHS was developed using a retrospective dataset from two clinical sites, including both eyes of glaucoma patients and controls. The model incorporated age, central corneal thickness, intraocular pressure, pattern standard deviation from a visual field threshold 24-2 test, and two parameters from an optical coherence tomography (OCT) test: the average circumpapillary retinal nerve fiber layer thickness and the minimum thickness of the six sectors of the macular ganglion cell plus the inner plexiform layer. The GHS was then validated in two independent datasets: one from primary care sites using Maestro OCT data (test dataset 1) and another from an academic center using DRI OCT Triton (test dataset 2). Results: Both eyes of 51 glaucoma patients and 67 controls were included in the development dataset. Setting the GHS cutoff at 75 points out of 100, test dataset 1, which comprised 41 subjects with glaucoma and 41 healthy controls, achieved an area under the receiver operating characteristic curve (AUROC) of 0.98, with a sensitivity of 71% and specificity of 98%; test dataset 2, which included 53 patients with glaucoma and 53 healthy controls, resulted in an AUROC of 0.95, with a sensitivity of 75% and specificity of 96%. A decision curve analysis across all datasets demonstrated a higher net benefit for the GHS model compared to individual OCT parameters. Conclusions: The GHS offers a feasible, standardized approach for early detection of glaucoma, providing strong specificity and acceptable sensitivity, with clear decision-making benefits in screening settings.

Indigenous peoples have cultivated biodiverse agroecosystems since time immemorial. The rise of metagenomics and high-throughput sequencing technologies in biodiversity studies has rapidly expanded the scale of data collection from these lands. A respectful approach to the data life cycle grounded in the sovereignty of indigenous communities is imperative to not perpetuate harm. In this paper, we operationalize an indigenous data sovereignty (IDS) framework to outline realistic considerations for genomic data that span data collection, governance, and communication. As a case study for this framework, we use arthropod genomic data collected from diversified and simplified farm sites close to and far from natural habitats within a historic Kānaka Ōiwi (Indigenous Hawaiian) agroecosystem. Diversified sites had the highest Operational Taxonomic Unit (OTU) richness for native and introduced arthropods. There may be a significant spillover effect between forest and farm sites, as farm sites near a natural habitat had higher OTU richness than those farther away. We also provide evidence that management factors such as the number of Polynesian crops cultivated may drive arthropod community composition. Through this case study, we emphasize the context-dependent opportunities and challenges for operationalizing IDS by utilizing participatory research methods, expanding novel data management tools through the Local Contexts Hub, and developing and nurturing community partnerships-all while highlighting the potential of agroecosystems for arthropod conservation. Overall, the workflow and the example presented here can help researchers take tangible steps to achieve IDS, which often seems elusive with the expanding use of genomic data.

There is an urgent need for strategies to reduce the negative impacts of a warming climate on human health. Cooling urban neighborhoods by planting trees and vegetation and increasing albedo of roofs, pavements, and walls can mitigate urban heat. We used synoptic climatology to examine how different tree cover and albedo scenarios would affect heat-related morbidity in Los Angeles, CA, USA, as measured by emergency room (ER) visits. We classified daily meteorological data for historical summer heat events into discrete air mass types. We analyzed those classifications against historical ER visit data to determine both heat-related and excess morbidity. We used the Weather Research and Forecasting model to examine the impacts of varied tree cover and albedo scenarios on meteorological outcomes and used these results with standardized morbidity data algorithms to estimate potential reductions in ER visits. We tested three urban modification scenarios of low, medium, and high increases of tree cover and albedo and compared these against baseline conditions. We found that avoiding 25% to 50% of ER visits during heat events would be a common outcome if the urban environment had more tree cover and higher albedo, with the greatest benefits occurring under heat events that are moderate and those that are particularly hot and dry. We conducted these analyses at the county level and compared results to a heat-vulnerable, working-class Los Angeles community with a high concentration of people of color, and found that reductions in the rate of ER visits would be even greater at the community level compared to the county.

Patterns of transcriptional activity are encoded in our genome through regulatory elements such as promoters or enhancers that, paradoxically, contain similar assortments of sequence-specific transcription factor (TF) binding sites1-3. Knowledge of how these sequence motifs encode multiple, often overlapping, gene expression programs is central to understanding gene regulation and how mutations in non-coding DNA manifest in disease4,5. Here, by studying gene regulation from the perspective of individual transcription start sites (TSSs), using natural genetic variation, perturbation of endogenous TF protein levels and massively parallel analysis of natural and synthetic regulatory elements, we show that the effect of TF binding on transcription initiation is position dependent. Analysing TF-binding-site occurrences relative to the TSS, we identified several motifs with highly preferential positioning. We show that these patterns are a combination of a TF's distinct functional profiles-many TFs, including canonical activators such as NRF1, NFY and Sp1, activate or repress transcription initiation depending on their precise position relative to the TSS. As such, TFs and their spacing collectively guide the site and frequency of transcription initiation. More broadly, these findings reveal how similar assortments of TF binding sites can generate distinct gene regulatory outcomes depending on their spatial configuration and how DNA sequence polymorphisms may contribute to transcription variation and disease and underscore a critical role for TSS data in decoding the regulatory information of our genome.

Maintenance of water homeostasis is a fundamental cellular process required by all living organisms. Here, we use the single-celled green alga Chlamydomonas reinhardtii to establish a foundational understanding of osmotic-stress signaling pathways through transcriptomics, phosphoproteomics, and functional genomics approaches. Comparison of pathways identified through these analyses with yeast and Arabidopsis allows us to infer their evolutionary conservation and divergence across these lineages. 76 genes, acting across diverse cellular compartments, were found to be important for osmotic-stress tolerance in Chlamydomonas through their functions in cytoskeletal organization, potassium transport, vesicle trafficking, mitogen-activated protein kinase and chloroplast signaling. We show that homologs for five of these genes have conserved functions in stress tolerance in Arabidopsis and reveal a novel PROFILIN-dependent stage of acclimation affecting the actin cytoskeleton that ensures tissue integrity upon osmotic stress. This study highlights the conservation of the stress response in algae and land plants, and establishes Chlamydomonas as a unicellular plant model system to dissect the osmotic stress signaling pathway.

During the pandemic, many older adults felt out of place in their home, work, and community spaces with potentially long-term consequences for health and wellbeing. Using national data from the COVID-19 Coping Study, thematic analysis of online long-answer responses (n = 1171; mean age 68 years; 71% female; 93% non-Hispanic White; 86% with at least a 4-year college degree; data collected April-June 2022) identified four themes regarding why particular places are challenging since the pandemic onset: (1) viral exposure fears, (2) frustrating regulations, (3) uncomfortable and hostile social dynamics, and (4) out of place negative emotions. Participants also shared how they continuously address or adapt to place-based challenges through lifestyle adjustments and coping strategies. Novel findings may inform multi-scalar policymaking and interventions to support wellbeing in later life in times of stress and instability.

The SARS-CoV-2 virus that led to COVID-19 is associated with significant and long-lasting neurologic symptoms in many patients, with an increased mortality risk for people with Alzheimer's disease (AD) and/or Down syndrome (DS). However, few studies have evaluated the neuropathological and inflammatory sequelae in postmortem brain tissue obtained from AD and people with DS with severe SARS-CoV-2 infections. We examined tau, beta-amyloid (Aβ), inflammatory markers and SARS-CoV-2 nucleoprotein in DS, AD, and healthy non-demented controls with COVID-19 and compared with non-infected brain tissue from each disease group (total n = 24). A nested ANOVA was used to determine regional effects of the COVID-19 infection on arborization of astrocytes (Sholl analysis) and percent-stained area of Iba-1 and TMEM 119. SARS-CoV-2 antibodies labeled neurons and glial cells in the frontal cortex of all subjects with COVID-19, and in the hippocampus of two of the three DS COVID-19 cases. SARS-CoV-2-related alterations were observed in peri-vascular astrocytes and microglial cells in the gray matter of the frontal cortex, hippocampus, and para-hippocampal gyrus. Bright field microscopy revealed scattered intracellular and diffuse extracellular Aβ deposits in the hippocampus of controls with confirmed SARS-CoV-2 infections. Overall, the present preliminary findings suggest that SARS-CoV-2 infections induce abnormal inflammatory responses in Down syndrome.

Defects in tRNA biogenesis are associated with multiple neurological disorders, yet our understanding of these diseases has been hampered by an inability to determine tRNA expression in individual cell types within a complex tissue. Here, we developed a mouse model in which RNA polymerase III is conditionally epitope tagged in a Cre-dependent manner, allowing us to accurately profile tRNA expression in any cell type in vivo. We investigated tRNA expression in diverse nervous system cell types, revealing dramatic heterogeneity in the expression of tRNA genes between populations. We found that while maintenance of levels of tRNA isoacceptor families is critical for cellular homeostasis, neurons are differentially vulnerable to insults to distinct tRNA isoacceptor families. Cell-type-specific translatome analysis suggests that the balance between tRNA availability and codon demand may underlie such differential resilience. Our work provides a platform for investigating the complexities of mRNA translation and tRNA biology in the brain.

Pediatric COVID-19 vaccination is effective in preventing COVID-19-related hospitalization, but duration of protection of the original monovalent vaccine during SARS-CoV-2 Omicron predominance merits evaluation, particularly given low coverage with updated COVID-19 vaccines. During December 19, 2021-October 29, 2023, the Overcoming COVID-19 Network evaluated vaccine effectiveness (VE) of ≥2 original monovalent COVID-19 mRNA vaccine doses against COVID-19-related hospitalization and critical illness among U.S. children and adolescents aged 5-18 years, using a case-control design. Too few children and adolescents received bivalent or updated monovalent vaccines to separately evaluate their effectiveness. Most case-patients (persons with a positive SARS-CoV-2 test result) were unvaccinated, despite the high frequency of reported underlying conditions associated with severe COVID-19. VE of the original monovalent vaccine against COVID-19-related hospitalizations was 52% (95% CI = 33%-66%) when the most recent dose was administered

To describe the race and ethnicity, gender, and financial status of students who remain interested in (retention), become interested in (recruitment), or lose interest in (attrition) OBGYN from matriculation to graduation.

The dynamic response of surface ligands on nanoparticles (NPs) to external stimuli critically determines the functionality of NP–ligand systems. For example, in electrocatalysis the collective dissociation of ligands on NP surfaces can lead to the creation of an NP/ordered-ligand interlayer, a microenvironment that is highly active and selective for CO2-to-CO conversion. However, the lack of in situ characterization techniques with high spatial resolution hampers a comprehensive molecular-level understanding of the mechanism of interlayer formation. Here we utilize in situ infrared nanospectroscopy and surface-enhanced Raman spectroscopy, unveiling an electrochemical bias-induced consecutive bond cleavage mechanism of surface ligands leading to formation of the NP/ordered-ligand interlayer. This real-time molecular insight could influence the design of confined localized fields in multiple catalytic systems. Moreover, the demonstrated capability of capturing nanometre-resolved, dynamic molecular-scale events holds promise for the advancement of using controlled local molecular behaviour to achieve desired functionalities across multiple research domains in nanoscience. (Figure presented.).

AimsQuantile regression is an alternate type of regression analysis that has been shown to have numerous advantages over standard linear regression. Unlike linear regression, which uses the mean to fit a linear model, quantile regression uses a data set's quantiles (or percentiles), which leads to a more comprehensive analysis of the data. However, while relatively common in other scientific fields such as economic and environmental modeling, it is infrequently used to understand biological and microbiological systems.Methods and resultsWe analyzed a set of bacterial growth rates using quantile regression analysis to better understand the effects of antibiotics on bacterial fitness. Using a bacterial model system containing 16 variant genotypes of the TEM β-lactamase enzyme, we compared our quantile regression analysis to a previously published study that uses the Tukey's range test, or Tukey honestly significantly difference (HSD) test. We find that trends in the distribution of bacterial growth rate data, as viewed through the lens of quantile regression, can distinguish between novel genotypes and ones that have been clinically isolated from patients. Quantile regression also identified certain combinations of genotypes and antibiotics that resulted in bacterial populations growing faster as the antibiotic concentration increased-the opposite of what was expected. These analyses can provide new insights into the relationships between enzymatic efficacy and antibiotic concentration.ConclusionsQuantile regression analysis enhances our understanding of the impacts of sublethal antibiotic concentrations on enzymatic (TEM β-lactamase) efficacy and bacterial fitness. We illustrate that quantile regression analysis can link patterns in growth rates with clinically relevant mutations and provides an understanding of how increasing sub-lethal antibiotic concentrations, like those found in our modern environment, can affect bacterial growth rates, and provide insight into the genetic basis for varied resistance.

ObjectiveThe objective of this study is to compare drilling variables and torsional mechanical properties of rabbit femora after bicortical drilling with a 1.5-mm standard surgical drill bit, acrylic drill bit, and K-wire.Samples24 pairs of rabbit femora.MethodsAfter drilling under controlled axial displacement rate, each bone was biaxially loaded in compression followed by rapid external torsion to failure. Maximum axial thrust force, maximum drill torque, integral of force and displacement, change in temperature, maximum power spectral density of the torque signal, torque vibration, and torque and angle at the yield and failure points were collected. Pre- and postyield stiffness, yield and failure energies, and postyield energy were calculated.ResultsThe work required to drill through the cis- and transcortices (integral of force and displacement) was greater for the K-wire, followed by the acrylic and then standard drill bits, respectively. The K-wire demonstrated higher maximum torque than the drill bits at the ciscortex, and the force of drilling was significantly greater. The vibration data was greater with the acrylic and standard drill bits than the K-wire. There was no difference in torsional strength between drilling types.Clinical relevanceMechanical differences exist between different drill bits and K-wire and demonstrate that the K-wire is overall more damaging than the surgical drill bit.

University brings many changes and challenges in students inducing a great amount of emotion fluctuation. During these times of emotion fluctuation, students can experience a drop off in academic performance and a rise in stress levels. In these times, effective emotion regulation has demonstrated to be a valuable tool correlated with improving academic performance and lowering stress. Music and light/color have been shown to be effective aspects of a smart environment for emotion regulation. Combining this knowledge along with physiological signal analysis correlating with emotions, we set out to develop a smart environment system set to aid students with emotion regulation. Our goal is to develop a low-cost accessible tool for university students that enhances student performance, emotional self understanding, and positive emotion regulation habits.Faculty Advisor: Professor Dang

PurposeWe evaluate the efficacy and safety profiles of currently available conservative management options for penile and urethral lichen sclerosus.Materials and methodsA systematic review of existing literature on lichen sclerosus was conducted utilizing the PubMed, Embase, and Web of Science databases. References were assessed for relevance to nonsurgical management of male genital lichen sclerosus by title and abstract by 3 independent reviewers, then reviewed in full and in duplicate by 5 independent reviewers.ResultsSeventeen studies describing conservative management of histologically confirmed penile and urethral lichen sclerosus in male patients were included in the final review. We present available evidence supporting the use of 4 major treatment modalities represented in the existing literature: topical corticosteroids, tacrolimus, platelet-rich plasma, and CO2 laser. We also briefly discuss the limited studies on the use of oral acitretin and polydeoxyribonucleotide injections. Outcomes assessed include symptoms, clinical appearance, quality of life, sexual satisfaction, adverse effects, and long-term efficacy of treatment.ConclusionsTopical corticosteroids remain the mainstay of conservative management of penile and urethral lichen sclerosus, with current literature supporting the use of other therapies such as tacrolimus and platelet-rich plasma as alternatives or adjuvant treatments when escalation of treatment is necessary. Future research should further explore the efficacy and safety of newer therapies through additional controlled clinical trials in the targeted population.

BACKGROUND AND OBJECTIVES: In June 2022, the mRNA COVID-19 vaccination was recommended for young children. We examined clinical characteristics and factors associated with vaccination status among vaccine-eligible young children hospitalized for acute COVID-19. METHODS: We enrolled inpatients 8 months to

Individuals with Down syndrome (DS) have a partial or complete trisomy of chromosome 21, resulting in an increased risk for early-onset Alzheimer's disease (AD)-type dementia by early midlife. Despite ongoing clinical trials to treat late-onset AD, individuals with DS are often excluded. Furthermore, timely diagnosis or management is often not available. Of the genetic causes of AD, people with DS represent the largest cohort. Currently, there is a knowledge gap regarding the underlying neurobiological mechanisms of DS-related AD (DS-AD), partly due to limited access to well-characterized brain tissue and biomaterials for research. To address this challenge, we created an international consortium of brain banks focused on collecting and disseminating brain tissue from persons with DS throughout their lifespan, named the Down Syndrome Biobank Consortium (DSBC) consisting of 11 biobanking sites located in Europe, India, and the USA. This perspective describes the DSBC harmonized protocols and tissue dissemination goals.

PURPOSE: Meningiomas are the most common primary brain tumors in adults with management varying widely based on World Health Organization (WHO) grade. However, there are limited datasets available for researchers to develop and validate radiomic models. The purpose of our manuscript is to report on the first dataset of meningiomas in The Cancer Imaging Archive (TCIA). ACQUISITION AND VALIDATION METHODS: The dataset consists of pre-operative MRIs from 96 patients with meningiomas who underwent resection from 2010-2019 and include axial T1post and T2-FLAIR sequences-55 grade 1 and 41 grade 2. Meningioma grade was confirmed based on the 2016 WHO Bluebook classification guideline by two neuropathologists and one neuropathology fellow. The hyperintense T1post tumor and hyperintense T2-FLAIR regions were manually contoured on both sequences and resampled to an isotropic resolution of 1 × 1 × 1 mm3 . The entire dataset was reviewed by a certified medical physicist. DATA FORMAT AND USAGE NOTES: The data was imported into TCIA for storage and can be accessed at https://doi.org/10.7937/0TKV-1A36. The total size of the dataset is 8.8GB, with 47 519 individual Digital Imaging and Communications in Medicine (DICOM) files consisting of 384 image series, and 192 structures. POTENTIAL APPLICATIONS: Grade 1 and 2 meningiomas have different treatment paradigms and are often treated based on radiologic diagnosis alone. Therefore, predicting grade prior to treatment is essential in clinical decision-making. This dataset will allow researchers to create models to auto-differentiate grade 1 and 2 meningiomas as well as evaluate for other pathologic features including mitotic index, brain invasion, and atypical features. Limitations of this study are the small sample size and inclusion of only two MRI sequences. However, there are no meningioma datasets on TCIA and limited datasets elsewhere although meningiomas are the most common intracranial tumor in adults.

Fog/cloud drops and aerosol liquid water are important sites for the transformations of atmospheric species, largely through reactions with photoformed oxidants such as the hydroxyl radical (OH), singlet molecular oxygen (1O2 -), and oxidizing triplet excited states of organic matter (3C -). Despite their importance, few studies have measured these oxidants or their seasonal variations. To address this gap, we collected ambient PM2.5 from Davis, California, over the course of a year and measured photooxidant concentrations and light absorption in dilute aqueous extracts. Mass absorption coefficients (MACs) normalized by dissolved organic carbon range from 0.4-3.8 m2 per gram C at 300 nm. Concentrations of OH, 1O2 -, and 3C - in the extracts range from (0.2-4.7) × 10-15 M, (0.7-45) × 10-13 M, and (0.03-7.9) × 10-13 M, respectively, with biomass burning brown carbon playing a major role in light absorption and the formation of 1O2 - and 3C -. Extrapolating photooxidant kinetics from our dilute particle extracts to concentrated aerosol liquid water (ALW) conditions gives an estimated OH concentration of 7 × 10-15 M and ranges for 1O2 - and 3C - of (0.6-7) × 10-12 M and (0.2-1) × 10-12 M, respectively. Compared to the results in Kaur et al. (2019), our ALW predictions show roughly 10 times higher OH, up to 5 times higher 3C, and 1O2 - concentrations that are lower by factors of 20-100. These concentrations suggest that 3C - and 1O2 - in ALW dominate the processing of organic compounds that react quickly with these oxidants (e.g., phenols and furans, respectively), while OH is more important for less reactive organics.

Roof rats (Rattus rattus) are a successful invasive species worldwide because of their ability to exploit their commensal relationship with humans. They are opportunistic feeders that use a wide range of natural and anthropogenic food sources. Because some rodent control methods, such as traps and rodenticides, threaten non-target wildlife species, understanding the diets of roof rats can help develop targeted approaches to better control these pests. Our aim is to use stable isotope analysis and stomach contents analysis to determine the diets of roof rats collected in agricultural, urban, and suburban areas in California. We hypothesized that diets of roof rats trapped in agricultural areas would contain crop plants and food resources associated with the agricultural environ­ment (arthropods, mollusks), whereas those from urban and suburban areas, e.g., schools, residential zones, would consume a broader range of food sources, including anthropogenic foods such as pet food, trash, and produce from gardens and fruit trees. To date, we have obtained roof rat carcasses from control efforts across the state, including our own trapping in southern California. Rats were frozen until they could be dissected in the lab. From each rat, we removed the gastrointestinal tract and took a small sample of ear tissue for stable isotope analysis; all tissues were stored in 95% ethanol. Ear tissue samples were dried, cut into small pieces, and weighed before sending them to the UC Davis Stable Isotope Facility for stable carbon (C) and nitrogen (N) isotope analysis. Stomachs were dissected under a dissecting microscope and food items were identified using reference keys. Preliminary analyses of stomach contents revealed significant amounts of what appears to be plant material, seeds, arthropod parts, and rodenticide bait, as well as many roundworms. Isotopic analysis of ear tissue of 64 rats from four Central Valley counties and urban/suburban rats from three southern California counties (n = 65) and Yolo County (n = 14) showed that δ13C values of rats from urban settings were significantly enriched compared to rural rats (Figure 1; F = 4.52, d.f. = 1, 141, P = 0.053), which is consistent with an urban diet containing more anthropogenic foods. δ13C values of urban roof rats were also much more variable (coefficient-of-variation, CV = 8.7%) than that of rats from agricultural areas (CV = 3.6%), which showed remarkably little variation within a site, indicative of feeding on a concentrated, shared resource. δ15N of rats differed significantly between agricultural counties (F = 195.9, d.f. = 3, 60, P

This report serves as one of five individual documents developed over the course of Phase II of the Urban Forest Equity Collective. This document provides an overview of the Sylmar pilot neighborhood assessment, engagement, and tree planting implementation process. It is intended to provide a transparent view into the decisions, points of analysis and key themes derived over the course of this phase.

This report serves as one of five individual documents developed over the course of Phase II of the Urban Forest Equity Collective. This document provides an overview of the Central Alameda pilot neighborhood assessment, engagement, and tree planting implementation process. It is intended to provide a transparent view into the decisions, points of analysis, and key themes derived over the course of this phase.

The Urban Forest Equity Collective (UFEC) is a consortium of forestry experts, Los Angeles (LA) City staff, community-based organizations, researchers, and consultants aiming to create holistic strategies to advance urban forest equity in the lowest-canopied neighborhoods. By conducting a holistic analysis and creating strategies to advance urban forest equity in LA, UFEC presents methods to address decades of systemic disinvestment and planning decisions that have resulted in poor public health outcomes, limited access to green spaces, and a host of related consequences ranging from heat exposure and poor air quality, to food insecurity and reduced ecosystem services.

Introduction: People without reliable access to healthcare are more likely to be diagnosed with late-stage cancer that could have been treated more effectively if diagnosed earlier. Emergency departments (ED) may be a novel place for cancer screening education for underserved patients. In this study we sought to determine patient characteristics and barriers to cancer screening for those patients who presented to a large, academic safety-net ED and were overdue for breast, cervical, and colorectal cancer screening since the coronavirus 2019 (COVID-19) pandemic.Methods: Adult ED patients eligible for at least one cancer screening based on US Preventive Serivces Task Force guidelines completed a web-based survey. We examined the association of demographic characteristics and having a personal physician with being overdue on screening using chi-square or the Fisher exact test for categorical variables and t-tests for continuous variables.Results: Of 221 participants, 144 were eligible for colorectal, 96 for cervical, and 55 for breast cancer screening. Of eligible patients, 46% (25/55) were overdue for breast cancer screening, 43% (62/144) for colorectal, and 40% (38/96) for cervical cancer screening. There were no significant characteristics associated with breast cancer screening. Being overdue for cervical cancer screening was significantly more likely for patients who were of Asian race (P = 0.02), had less than a high school diploma (P = 0.01), and were without a routine checkup within the prior five years (P = 0.01). Overdue for colorectal cancer screening was associated with patients not having insurance (P = 0.04), being in their 40s (P = 0.03), being Hispanic (P = 0.01), and not having a primary care physician (P = 0.01). Of 97 patients overdue for at least one screening, the most common barriers were cost (37%), lack of time (37%), and lack of knowledge of screening recommendations (34%). Only 8.3% reported that the COVID-19 pandemic delayed their screening.Conclusion: The ED may be a novel setting to target patients for cancer screening education. Future work that refers patients to free screening programs and primary care physicians mayhelp improve disparities in cancer screening and cancer mortality rates for underserved populations.

BackgroundEnvironmental contamination is suspected to play an important role in Candida auris transmission. Understanding speed and risks of contamination after room disinfection could inform environmental cleaning recommendations.MethodsWe conducted a prospective multicenter study of environmental contamination associated with C. auris colonization at six ventilator-capable skilled nursing facilities and one acute-care hospital in Illinois and California. Known C. auris carriers were sampled at five body-sites followed by sampling of nearby room surfaces before disinfection and at 0, 4, 8, and 12-hours post-disinfection. Samples were cultured for C. auris and bacterial multidrug-resistant organisms (MDROs). Odds of surface contamination after disinfection were analyzed using multilevel generalized estimating equations.ResultsAmong 41 known C. auris carriers, colonization was detected most frequently on palms/fingertips (76%) and nares (71%). C. auris contamination was detected on 32.2% (66/205) of room surfaces pre-disinfection and 20.5% (39/190) of room surfaces by 4-hours post-disinfection. A higher number of C. auris-colonized body sites was associated with higher odds of environmental contamination at every time point following disinfection, adjusting for facility of residence. In the rooms of 38 (93%) C. auris carriers co-colonized with a bacterial MDRO, 2%-24% of surfaces were additionally contaminated with the same MDRO by 4-hours post-disinfection.ConclusionsC. auris can contaminate the healthcare environment rapidly after disinfection, highlighting the challenges associated with environmental disinfection. Future research should investigate long-acting disinfectants, antimicrobial surfaces, and more effective patient skin antisepsis to reduce the environmental reservoir of C. auris and bacterial MDROs in healthcare settings.

Most studies projecting human survivability limits to extreme heat with climate change use a 35 °C wet-bulb temperature (Tw) threshold without integrating variations in human physiology. This study applies physiological and biophysical principles for young and older adults, in sun or shade, to improve current estimates of survivability and introduce liveability (maximum safe, sustained activity) under current and future climates. Our physiology-based survival limits show a vast underestimation of risks by the 35 °C Tw model in hot-dry conditions. Updated survivability limits correspond to Tw~25.8-34.1 °C (young) and ~21.9-33.7 °C (old)-0.9-13.1 °C lower than Tw = 35 °C. For older female adults, estimates are ~7.2-13.1 °C lower than 35 °C in dry conditions. Liveability declines with sun exposure and humidity, yet most dramatically with age (2.5-3.0 METs lower for older adults). Reductions in safe activity for younger and older adults between the present and future indicate a stronger impact from aging than warming.

Pediatric and adult autoimmune encephalitis (AE) are often associated with Abs to the NR1 subunit of the N-methyl-d-aspartate (NMDA) receptor (NMDAR). Very little is known regarding the cerebrospinal fluid humoral immune profile and Ab genetics associated with pediatric anti-NMDAR-AE. Using a combination of cellular, molecular, and immunogenetics tools, we collected cerebrospinal fluid from pediatric subjects and generated 1) flow cytometry data to calculate the frequency of B cell subtypes in the cerebrospinal fluid of pediatric subjects with anti-NMDAR-AE and controls, 2) a panel of recombinant human Abs from a pediatric case of anti-NMDAR-AE that was refractory to treatment, and 3) a detailed analysis of the Ab genes that bound the NR1 subunit of the NMDAR. Ag-experienced B cells including memory cells, plasmablasts, and Ab-secreting cells were expanded in the pediatric anti-NMDAR-AE cohort, but not in the controls. These Ag-experienced B cells in the cerebrospinal fluid of a pediatric case of NMDAR-AE that was refractory to treatment had expanded use of variable H chain family 2 (VH2) genes with high somatic hypermutation that all bound to the NR1 subunit of the NMDAR. A CDR3 motif was identified in this refractory case that likely drove early stage activation and expansion of naive B cells to Ab-secreting cells, facilitating autoimmunity associated with pediatric anti-NMDAR-AE through the production of Abs that bind NR1. These features of humoral immune responses in the cerebrospinal fluid of pediatric anti-NMDAR-AE patients may be relevant for clinical diagnosis and treatment.

Noncoding genetic variation drives phenotypic diversity, but underlying mechanisms and affected cell types are incompletely understood. Here, investigation of effects of natural genetic variation on the epigenomes and transcriptomes of Kupffer cells derived from inbred mouse strains identified strain-specific environmental factors influencing Kupffer cell phenotypes, including leptin signaling in Kupffer cells from a steatohepatitis-resistant strain. Cell-autonomous and non-cell-autonomous effects of genetic variation were resolved by analysis of F1 hybrid mice and cells engrafted into an immunodeficient host. During homeostasis, non-cell-autonomous trans effects of genetic variation dominated control of Kupffer cells, while strain-specific responses to acute lipopolysaccharide injection were dominated by actions of cis-acting effects modifying response elements for lineage-determining and signal-dependent transcription factors. These findings demonstrate that epigenetic landscapes report on trans effects of genetic variation and serve as a resource for deeper analyses into genetic control of transcription in Kupffer cells and macrophages in vitro.

BackgroundPublic health pandemics, such as COVID-19, not only impact the physical health and wellbeing of communities but also often have far-reaching effects on their social, psychological, environmental, and economic welfare. The coronavirus pandemic has highlighted the significant inequities experienced among those who are Black, Indigenous, and People of Color (BIPOC), especially in the areas of housing instability, unemployment, and debt accrual. This study investigates the socioeconomic impacts of COVID-19 on residents of the Canal neighborhood ("The Canal"), a low-income Latinx community in Marin County, California. This study also uplifts mitigation strategies already underway to facilitate post-pandemic recovery efforts.MethodsThis study utilized a mixed-methods, community participatory approach in which community leaders from a local nonprofit, Canal Alliance, administered a survey assessing the impact of COVID-19 on Canal residents. Additionally, community stakeholders including nonprofits, small businesses, and public officials were interviewed, and their field notes were analyzed through exploratory open coding.ResultsOn a macro level, the data showed that Canal residents were severely impacted by COVID-19 in the form of massive job loss (61.2% of respondents were unemployed or underemployed) as well as financial stress related to eviction, housing instability, and debt accrual (78.8% of respondents struggled to cover rent and often had to borrow money from friends and family).ConclusionsIn spite of the severe socioeconomic impacts of COVID-19 on The Canal, there is a significant opportunity for recovery and growth because of an overwhelming investment by residents, community-based organizations, and public officials to support those who have been financially impacted by the pandemic. Some key areas of policy focus include expansion of affordable housing, pandemic-resistant workforce development, and restructuring of social services to increase accessibility. This report will explore recommendations related to strategic funding of community-based programs as well as short-term and long-term solutions for economic recovery.

ObjectiveTo systematically compare success, cure and complication rates of urethral sling surgeries in stress urinary incontinence patients with and without a history of pelvic radiotherapy (RT).Materials and methodsWe searched PUBMED, EMBASE, and Web of Science to identify relevant articles. The primary outcomes were the success and cure rates. The secondary outcomes included the rates of infection, urethral erosion, total complications, explantation, and satisfaction. Outcomes were analyzed using a random-effects model to calculate the unadjusted odds ratio (OR) in patients with a history of RT compared with those without prior RT.ResultsOn pooled analysis, we found significantly lower odds of success (OR 0.68; 95% confidence interval [CI] 0.53-0.87, P

INTRODUCTION: Latinas in the United States have higher mortality from breast cancer, but longitudinal studies of mammography ordering (a crucial initial step towards screening) in primary care are lacking. METHODS: We conducted an analysis of mammography order rates in Latinas (by language preference) and non-Latina white women (N = 181,755) over a > 10 year period in a multi-state network of community health centers (CHCs). We evaluated two outcomes (ever having a mammogram order and annual rate of mammography orders) using generalized estimating equation modeling. RESULTS: Approximately one-third of all patients had ever had a mammogram order. Among those receiving mammogram orders, English-preferring Latinas had lower mammogram order rates than non-Hispanic white women (RR = 0.92, 95% CI = 0.89-0.95). Spanish-preferring Latinas had higher odds of ever having a mammogram ordered than non-Hispanic whites (odds ratio = 2.12, 95% CI = 2.06-2.18) and, if ever ordered, had a higher rate of annual mammogram orders (rate ratio = 1.53, 95% CI = 1.50-1.56). CONCLUSION: These findings suggest that breast cancer detection barriers in low-income Latinas may not stem from a lack of orders in primary care, but in the subsequent accessibility of receiving ordered services.

The neural crest is a stem cell population that originates from the ectoderm during the initial steps of nervous system development. Neural crest cells delaminate from the neuroepithelium by undergoing a spatiotemporally regulated epithelial-mesenchymal transition (EMT) that proceeds in a coordinated wave head-to-tail to exit from the neural tube. While much is known about the transcriptional programs and membrane changes that promote EMT, there are additional levels of gene expression control that neural crest cells exert at the level of RNA to control EMT and migration. Yet, the role of post-transcriptional regulation, and how it drives and contributes to neural crest EMT, is not well understood. In this mini-review, we explore recent advances in our understanding of the role of post-transcriptional regulation during neural crest EMT.

Advances in electrocatalysis research rely heavily on building a thorough mechanistic understanding of catalyst active sites under realistic operating conditions. Only recently have techniques emerged that enable sensitive spectroscopic data collection to distinguish catalytically relevant surface sites from the underlying bulk material under applied potential in the presence of an electrolyte layer. Here, we demonstrate that operando high-energy-resolution fluorescence detected X-ray absorption spectroscopy (HERFD-XAS) is a powerful spectroscopic method which offers critical surface chemistry insights in CO2 electroreduction with sub-electronvolt energy resolution using hard X-rays. Combined with the high surface area-to-volume ratio of 5 nm copper nanoparticles, operando HERFD-XAS allows us to observe with clear evidence the breaking of chemical bonds between the ligands and the Cu surface as part of the ligand desorption process occurring under electrochemical potentials relevant for the CO2 reduction reaction (CO2RR). In addition, the dynamic evolution of oxidation state and coordination number throughout the operation of the nanocatalyst was continuously tracked. With these results in hand, undercoordinated metallic copper nanograins are proposed to be the real active sites in the CO2RR. This work emphasizes the importance of HERFD-XAS compared to routine XAS in catalyst characterization and mechanism exploration, especially in the complicated electrochemical CO2RR.

Cardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing-induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre-procedure evaluation and preparation, implant procedure management, follow-up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified.

Cis-regulatory elements (CREs) can be classified by the shapes of their transcription start site (TSS) profiles, which are indicative of distinct regulatory mechanisms. Massively parallel reporter assays (MPRAs) are increasingly being used to study CRE regulatory mechanisms, yet the degree to which MPRAs replicate individual endogenous TSS profiles has not been determined. Here, we present a new low-input MPRA protocol (TSS-MPRA) that enables measuring TSS profiles of episomal reporters as well as after lentiviral reporter chromatinization. To sensitively compare MPRA and endogenous TSS profiles, we developed a novel dissimilarity scoring algorithm (WIP score) that outperforms the frequently used earth mover's distance on experimental data. Using TSS-MPRA and WIP scoring on 500 unique reporter inserts, we found that short (153 bp) MPRA promoter inserts replicate the endogenous TSS patterns of ∼60% of promoters. Lentiviral reporter chromatinization did not improve fidelity of TSS-MPRA initiation patterns, and increasing insert size frequently led to activation of extraneous TSS in the MPRA that are not active in vivo. We discuss the implications of our findings, which highlight important caveats when using MPRAs to study transcription mechanisms. Finally, we illustrate how TSS-MPRA and WIP scoring can provide novel insights into the impact of transcription factor motif mutations and genetic variants on TSS patterns and transcription levels.

Autosomal dominant Alzheimers disease (ADAD) is genetically determined, but variability in age of symptom onset suggests additional factors may influence cognitive trajectories. Although apolipoprotein E (APOE) genotype and educational attainment both influence dementia onset in sporadic AD, evidence for these effects in ADAD is limited. To investigate the effects of APOE and educational attainment on age-related cognitive trajectories in ADAD, we analyzed data from 675 Presenilin-1 E280A mutation carriers and 594 non-carriers. Here we show that age-related cognitive decline is accelerated in ADAD mutation carriers who also have an APOE e4 allele compared to those who do not and delayed in mutation carriers who also have an APOE e2 allele compared to those who do not. Educational attainment is protective and moderates the effect of APOE on cognition. Despite ADAD mutation carriers being genetically determined to develop dementia, age-related cognitive decline may be influenced by other genetic and environmental factors.

Digital adherence technologies (DATs) have emerged as an alternative to directly observed therapy (DOT) for supervisions of tuberculosis (TB) treatment. We conducted a meta-analysis of implementation feedback obtained from people with TB and health care workers (HCWs) involved in TB REACH Wave 6-funded DAT evaluation projects. Projects administered standardized post-implementation surveys based on the Capability, Opportunity, Motivation, Behavior (COM-B) model to people with TB and their health care workers. The surveys included questions on demographics and technology use, Likert scale questions to assess capability, opportunity, and motivation to use DAT and open-ended feedback. We summarized demographic and technology use data descriptively, generated pooled estimates of responses to Likert scale questions within each COM-B category for people with TB and health care workers using random effects models, and performed qualitative analysis of open-ended feedback using a modified framework analysis approach. The analysis included surveys administered to 1290 people with TB and 90 HCWs across 6 TB REACH-funded projects. People with TB and HCWs had an overall positive impression of DATs with pooled estimates between 4·0 to 4·8 out of 5 across COM-B categories. However, 44% of people with TB reported taking TB medications without reporting dosing via DATs and 23% reported missing a dose of medication. Common reasons included problems with electricity, network coverage, and technical issues with the DAT platform. DATs were overall perceived to reduce visits to clinics, decrease cost, increase social support, and decrease workload of HCWs. DATs were acceptable in a wide variety of settings. However, there were challenges related to the feasibility of using current DAT platforms. Implementation efforts should concentrate on ensuring access, anticipating, and addressing technical challenges, and minimizing additional cost to people with TB.

Considerable racial/ethnic disparities persist in exposure to life stressors and socioeconomic resources that can directly affect threat neurocircuitry, particularly the amygdala, that partially mediates susceptibility to adverse posttraumatic outcomes. Limited work to date, however, has investigated potential racial/ethnic variability in amygdala reactivity or connectivity that may in turn be related to outcomes such as post-traumatic stress disorder (PTSD). Participants from the AURORA study (n = 283), a multisite longitudinal study of trauma outcomes, completed functional magnetic resonance imaging and psychophysiology within approximately two-weeks of trauma exposure. Seed-based amygdala connectivity and amygdala reactivity during passive viewing of fearful and neutral faces were assessed during fMRI. Physiological activity was assessed during Pavlovian threat conditioning. Participants also reported the severity of posttraumatic symptoms 3 and 6 months after trauma. Black individuals showed lower baseline skin conductance levels and startle compared to White individuals, but no differences were observed in physiological reactions to threat. Further, Hispanic and Black participants showed greater amygdala connectivity to regions including the dorsolateral prefrontal cortex (PFC), dorsal anterior cingulate cortex, insula, and cerebellum compared to White participants. No differences were observed in amygdala reactivity to threat. Amygdala connectivity was associated with 3-month PTSD symptoms, but the associations differed by racial/ethnic group and were partly driven by group differences in structural inequities. The present findings suggest variability in tonic neurophysiological arousal in the early aftermath of trauma between racial/ethnic groups, driven by structural inequality, impacts neural processes that mediate susceptibility to later PTSD symptoms.

Fragment antigen-binding domains of antibodies (Fabs) are powerful probes of structure-function relationships of assembly line polyketide synthases (PKSs). We report the discovery and characterization of Fabs interrogating the structure and function of the ketosynthase-acyltransferase (KS-AT) core of Module 2 of the 6-deoxyerythronolide B synthase (DEBS). Two Fabs (AC2 and BB1) were identified to potently inhibit the catalytic activity of Module 2. Both AC2 and BB1 were found to modulate ACP-mediated reactions catalyzed by this module, albeit by distinct mechanisms. AC2 primarily affects the rate (kcat), whereas BB1 increases the KM of an ACP-mediated reaction. A third Fab, AA5, binds to the KS-AT fragment of DEBS Module 2 without altering either parameter; it is phenotypically reminiscent of a previously characterized Fab, 1B2, shown to principally recognize the N-terminal helical docking domain of DEBS Module 3. Crystal structures of AA5 and 1B2 bound to the KS-AT fragment of Module 2 were solved to 2.70 and 2.65 Å resolution, respectively, and revealed entirely distinct recognition features of the two antibodies. The new tools and insights reported here pave the way toward advancing our understanding of the structure-function relationships of DEBS Module 2, arguably the most well-studied module of an assembly line PKS.

99DOTS is a low-cost digital adherence technology that allows people with tuberculosis (TB) to self-report treatment adherence. There are limited data on its implementation, feasibility, and acceptability from sub-Saharan Africa. We conducted a longitudinal analysis and cross-sectional surveys nested within a stepped-wedge randomized trial at 18 health facilities in Uganda between December 2018 and January 2020. The longitudinal analysis assessed implementation of key components of a 99DOTS-based intervention, including self-reporting of TB medication adherence via toll-free phone calls, automated text message reminders and support actions by health workers monitoring adherence data. Cross-sectional surveys administered to a subset of people with TB and health workers assessed 99DOTS feasibility and acceptability. Composite scores for capability, opportunity, and motivation to use 99DOTS were estimated as mean Likert scale responses. Among 462 people with pulmonary TB enrolled on 99DOTS, median adherence was 58.4% (inter-quartile range [IQR] 38.7-75.6) as confirmed by self-reporting dosing via phone calls and 99.4% (IQR 96.4-100) when also including doses confirmed by health workers. Phone call-confirmed adherence declined over the treatment period and was lower among people with HIV (median 50.6% vs. 63.7%, p3 consecutive doses. Surveys were completed by 83 people with TB and 22 health workers. Composite scores for capability, opportunity, and motivation were high; among people with TB, composite scores did not differ by gender or HIV status. Barriers to using 99DOTS included technical issues (phone access, charging, and network connection) and concerns regarding disclosure. 99DOTS was feasible to implement and highly acceptable to people with TB and their health workers. National TB Programs should offer 99DOTS as an option for TB treatment supervision.

While most detailed analyses of antibiotic resistance plasmids focus on those found in clinical isolates, less is known about the vast environmental reservoir of mobile genetic elements and the resistance and virulence factors they encode. We selectively isolated three strains of cefotaxime-resistant Escherichia coli from a wastewater-impacted coastal wetland. The cefotaxime-resistant phenotype was transmissible to a lab strain of E. coli after one hour, with frequencies as high as 10-3 transconjugants per recipient. Two of the plasmids also transferred cefotaxime resistance to Pseudomonas putida, but these were unable to back-transfer this resistance from P. putida to E. coli. In addition to the cephalosporins, E. coli transconjugants inherited resistance to at least seven distinct classes of antibiotics. Complete nucleotide sequences revealed large IncF-type plasmids with globally distributed replicon sequence types F31:A4:B1 and F18:B1:C4 carrying diverse antibiotic resistance and virulence genes. The plasmids encoded extended-spectrum β-lactamases blaCTX-M-15 or blaCTX-M-55, each associated with the insertion sequence ISEc9, although in different local arrangements. Despite similar resistance profiles, the plasmids shared only one resistance gene in common, the aminoglycoside acetyltransferase aac(3)-IIe. Plasmid accessory cargo also included virulence factors involved in iron acquisition and defense against host immunity. Despite their sequence similarities, several large-scale recombination events were detected, including rearrangements and inversions. In conclusion, selection with a single antibiotic, cefotaxime, yielded conjugative plasmids conferring multiple resistance and virulence factors. Clearly, efforts to limit the spread of antibiotic resistance and virulence among bacteria must include a greater understanding of mobile elements in the natural and human-impacted environments.

Reaction of MBr2 with 3 equiv of [K(18-crown-6)][O2N2CPh3] generates the trityl diazeniumdiolate complexes [K(18-crown-6)][M(O2N2CPh3)3] (M = Co, 2; Fe, 3) in good yields. Irradiation of 2 and 3 using 371 nm light led to NO formation in 10 and 1% yields (calculated assuming a maximum of 6 equiv of NO produced per complex), respectively. N2O was also formed during the photolysis of 2, in 63% yield, whereas photolysis of 3 led to the formation of N2O, as well as Ph3CN(H)OCPh3, in 37 and 5% yields, respectively. These products are indicative of diazeniumdiolate fragmentation via both C-N and N-N bond cleavage pathways. In contrast, oxidation of complexes 2 and 3 with 1.2 equiv of [Ag(MeCN)4][PF6] led to N2O formation but no NO formation, suggesting that diazeniumdiolate fragmentation occurs exclusively via C-N bond cleavage under these conditions. While the photolytic yields of NO are modest, they represent a 10- to 100-fold increase compared to the previously reported Zn congener, suggesting that the presence of a redox-active metal center favors NO formation upon trityl diazeniumdiolate fragmentation.