Anatomical and volumetric description of the guiana dolphin (Sotalia guianensis) brain from an ultra-high-field magnetic resonance imaging.

The Guiana dolphin (Sotalia guianensis) is a common species along Central and South American coastal waters. Although much effort has been made to understand its behavioral ecology and evolution, very little is known about its brain. The use of ultra-high field MRI in anatomical descriptions of cetacean brains is a very promising approach that is still uncommon. In this study, we present for the first time a full anatomical description of the Guiana dolphin's brain based on high-resolution ultra-high-field magnetic resonance imaging, providing an exceptional level of brain anatomical details, and enriching our understanding of the species. Brain structures were labeled and volumetric measurements were delineated for many distinguishable structures, including the gray matter and white matter of the cerebral cortex, amygdala, hippocampus, superior and inferior colliculi, thalamus, corpus callosum, ventricles, brainstem and cerebellum. Additionally, we provide the surface anatomy of the Guiana dolphin brain, including the labeling of main sulci and gyri as well as the calculation of its gyrification index. These neuroanatomical data, absent from the literature to date, will help disentangle the history behind cetacean brain evolution and consequently, mammalian evolution, representing a significant new source for future comparative studies.

Unveiling the Strong Black Woman Schema-Evolution and Impact: A Systematic Review.

The Strong Black Woman (SBW) schema is described as a statue of unrelenting strength, resilience, and self-sufficiency, serving as a shield of protection and cultural adaptation to suppress and control manifestations of racial and gender oppression. Stemming from superwoman syndrome, a conceptual model exploring the multifactorial roles women hold and their impact, the SBW extends beyond gender roles to the sociopolitical context of the Black woman's lived experience. Endorsement of the SBW posits risk for health disparities including stress, anxiety, depression, and obesity. This review was conducted to explore the SBW schema and experiences of Black women who endorse it, to delineate how Black women describe themselves in relation to the SBW persona, and to inform further inquiry, nursing practice, and clinical approaches to improving health outcomes of this population. A systematic review of qualitative studies was conducted with a literature search from CINAHL, APA PsycINFO, MEDLINE, PubMed, and SocINDEX databases yielding seven relevant papers for this analysis. Studies using the superwoman schema and the SBW schema with participants who identified as Black women were included in the review. Consistent with the SBW phenomenon, many participants described examples and consequences of being an SBW. While most women identified with SBW, not all endorsed the persona entirely, challenging its ideal and reinforcing positive self-care. Themes include (a) Strength by nature, not choice, (b) Suppressed emotion, (c) Success over everything, and (d) Prioritizing others over self. Additional emerging themes are also included. Black women increasingly recognize the negative impacts of the SBW schema, pinpointing how their internal feelings manifest in their external world. The conceptual framework itself is an anomaly, incongruently impacting both the mental and physical health of Black women, further contributing to the long-term health and sociopolitical disparities that Black women experience. Simply acknowledging and understanding these experiences by healthcare practitioners are not enough to prevent or eliminate the risks involved with the endorsement of the SBW schema but rather intentionally addressing these as a contributing social determinant of health that predisposes them to long-term chronic conditions.

A Qualitative Analysis of Knowledge Levels, Perceived Susceptibility, and Perceived Severity Surrounding Anal Cancer and Human Papillomavirus.

INTRODUCTION: When examining health literacy and disease specific knowledge levels across ethnicities and communities, ethnic minority groups are known to be at a higher risk of being below the average health literacy threshold which is a factor linked to poor health status and higher mortality rates. This study examined disease specific knowledge levels, perceived severity, and perceived susceptibility surrounding anal cancer and HPV-related screening behaviors. METHODS: The following research questions were explored: (1) "What are the common themes and/or beliefs when asked about anal cancer, HPV, and preventive screening?" and (2) "What are the common themes and beliefs surrounding the severity and susceptibility of contracting anal cancer?". This study utilized a cross-sectional design to survey 26 individuals regarding their knowledge level and perspectives regarding anal cancer and HPV. An 8-question survey was developed de novo based on an application of the Health Belief Model (HBM) elements. This study employed thematic analysis to explore critical themes to construct a model to understand knowledge levels, attitudes, and risk perceptions regarding anal cancer and intention to participate in preventive screenings. The fundamental attitudes and themes related to anal cancer risk and intention to participate in preventative screenings were elicited using a qualitative descriptive technique. Coded data was utilized to analyze themes based on (1) knowledge and (2) perceived risk, both severity and susceptibility. RESULTS: Overall, the findings indicate very low levels of knowledge regarding screening, anal cancer, and HPV across all genders. The low levels of anal cancer and HPV knowledge were seen in 13 coded segments (50% of surveys) which showed no familiarity with or comprehension of HPV, and 4 coded segments indicated no familiarity with anal cancer. In addition, 15 respondents (57%) had low or no preventive or screening-related knowledge. While some respondents (46%) illustrated high perceived severity for anal cancer, only 23% indicated high perceived susceptibility for anal cancer. CONCLUSION: The results from this study may be used to inform practitioners, providers, and policymakers in developing interventions addressing low levels of understanding and disease specific knowledge surrounding anal cancer in support of creating a standardized health screening procedure.

Free and Charitable Clinic Perspectives on the Implementation and Utilization of Telehealth Services During the COVID-19 Pandemic.

BACKGROUND: The onset of the COVID-19 pandemic challenged healthcare providers to adapt their models of care and leverage technology to continue to provide necessary care while reducing the likelihood of exposure. One setting that faced a unique set of challenges and opportunities was free and charitable clinics. In response to the emerging pandemic, The North Carolina Association for Free and Charitable Clinics (NCAFCC) offered their 66 member clinics access to a telehealth platform, free of charge. OBJECTIVE: This paper explores the varied perspectives of leaders in the NCAFCC member clinics regarding the implementation of telehealth services to facilitate continuity of care for patients during the height of the pandemic. DESIGN: This qualitative study is part of a broader research effort to understand and contextualize the experience of implementing and using telehealth services by North Carolina free and charitable clinics during and after the COVID-19 pandemic. The research team conducted 13 key informant interviews and employed thematic analysis and grounded theory to explore critical themes and construct a model based on the CFIR to describe the use of telehealth in free and charitable clinics. RESULTS: Twelve clinic managers and executive directors from free and charitable clinics across the state participated in the key informant interviews providing their unique perspective on the experience of implementing telehealth services in a free and charitable clinic environment during the COVID-19 pandemic. When examined within the lens of the consolidated framework for implementation research (CFIR), 3 key themes emerged from the key informant interviews: mission driven patient centered care, resilience and resourcefulness, and immediate implementation. CONCLUSIONS: This study aligns with existing literature regarding telehealth implementation across other safety net provider settings and highlights the key implementation factors, organizational elements, provider perspectives, and patient needs that must collectively be considered when implementing new technologies, especially in a low-resource, high need healthcare setting. The study showcases the implementation climate, resourcefulness, and mission driven approach that allowed many NCAFCC clinics to respond to an emergent situation by adopting and implementing a telehealth platform in a period of 2 weeks or less.

Free and Charitable Clinic Telehealth Adoption and Utilization During the COVID-19 Era: The North Carolina Experience.

Purpose: The emergence of the COVID-19 pandemic led health care systems and providers worldwide to rapidly adopt telehealth solutions to minimize risk and comply with isolation mandates. This article explores telehealth utilization trends in North Carolina (NC) free and charitable clinics-an ambulatory health care delivery setting where traditional third-party reimbursement policies are not a primary consideration. Methods: We surveyed NC free and charitable clinic administrators regarding clinic decisions to adopt an externally sponsored telehealth system, what services are provided by telehealth, clinic implementation processes, which populations used telehealth, how telehealth was incorporated into current clinic workflows, and perceptions of telehealth outcomes. Findings: Telehealth was rapidly adopted among free and charitable clinics after the COVID-19 outbreak. Reasons for implementing telehealth included the ability to continue providing services during a public health emergency and to increase access to patients. However, clinics report that telehealth utilization has dropped significantly since the initial pandemic surge. Patient and provider preferences for in-person services are a common reason cited for this drop. Free and charitable clinics report a strong interest in continuing to deliver services through telehealth. The majority reported continuing to offer telehealth services, but primarily as a supplement to in-person visits rather than as a replacement. They perceive that implementing telehealth has increased access to care but are less certain about the impact on cost of care and patient satisfaction. However, clinic administrators believe improvements in interoperability with other data systems, workflows, scheduling, and care delivery approaches are needed to achieve telehealth's fullest utilization. Conclusion: Telehealth can play a significant role in expanding access to services in the free and charitable clinic setting. However, continued refinements in the technology to facilitate integration with other systems and workflow processes are needed to reach its full potential.

Asian American nursing students' experiences of racial microaggressions amid the COVID-19 pandemic: Focus group discussions.

AIM: This study aimed to explore the thoughts and feelings of Asian American nursing students regarding Anti-Asian racism that they might anticipate or experience during their clinical training. BACKGROUND: Asian Americans have long been viewed as perpetual foreigners and coronavirus disease 2019 has reinforced that negative view. Asian American nursing students may anticipate and experience racial discrimination during their clinical training, which could negatively affect their mental health. DESIGN: This is a qualitative research study using focus group discussions. METHOD: Focus group discussions were conducted over Zoom and audiotaped. The audiotapes were transcribed and validated for accuracy. A thematic analysis was performed using NVivo10. Emerging themes and subthemes were compared and discussed until agreements were made. RESULTS: Nineteen students participated in four focus group meetings, of which, 13 (68 %) had clinical training and six (32 %) were preclinical students. Four major themes emerged: (a) looking forward to hands-on learning opportunities, (b) enduring racial microaggressions, (c) maintaining professionalism in the face of racial microaggressions and (d) standing up for oneself and other Asian American healthcare workers. Preclinical students were anxiously waiting for clinical training so that they could have hands-on learning experiences. They anticipated that anti-Asian racism in clinical settings would be similar to what they had experienced on the streets and therefore, they were not afraid of it. Students who had clinical training reported experiencing a variety of racial microaggressions that varied from "side-eyes" to "verbal assault" and occurred at three levels: patients, nurses and clinical instructors. They reported that most of the microaggressions were familiar to them, but some, especially coming from their clinical instructors, were unique to clinical settings. CONCLUSION: Asian American nursing students experienced racial microaggressions during their clinical training which came from patients, nurses on the unit and their clinical instructors. Nevertheless, the students strove to maintain professionalism and stand up for themselves and other Asian healthcare workers as they gained confidence in clinical knowledge and skills.

High-resolution Spatiotemporal Dynamics of Harmful Algae in the Indian River Lagoon (Florida)-A Case Study of Aureoumbra lagunensis, Pyrodinium bahamense, and Pseudo-nitzschia.

The Indian River Lagoon (IRL), located on the east coast of Florida, is a complex estuarine ecosystem that is negatively affected by recurring harmful algal blooms (HABs) from distinct taxonomic/functional groups. Enhanced monitoring was established to facilitate rapid quantification of three recurrent bloom taxa, Aureoumbra lagunensis, Pyrodinium bahamense, and Pseudo-nitzschia spp., and included corroborating techniques to improve the identification of small-celled nanoplankton (<10 µm in diameter). Identification and enumeration of these target taxa were conducted during 2015-2020 using a combination of light microscopy and species-specific approaches, specifically immunofluorescence flow cytometry as well as a newly developed qPCR assay for A. lagunensis presented here for the first time. An annual bloom index (ABI) was established for each taxon based on occurrence and abundance data. Blooms of A. lagunensis (>2×108 cells L-1) were observed in all six years sampled and across multiple seasons. In contrast, abundance of P. bahamense, largely driven by the annual temperature cycle that moderates life cycle transitions and growth, displayed a strong seasonal pattern with blooms (105-107 cells L-1) generally developing in early summer and subsiding in autumn. However, P. bahamense bloom development was delayed and abundance was significantly lower in years and locations with sustained A. lagunensis blooms. Pseudo-nitzschia spp. were broadly distributed with sporadic bloom concentrations (reaching 107 cells L-1), but with minimal concentrations of the toxin domoic acid detected (<0.02 µg L-1). In summer 2020, multiple monitoring tools characterized a novel nano-cyanobacterium bloom (reaching 109 cells L-1) that coincided with a decline in A. lagunensis and persisted into autumn. Statistical and time-series analyses of this spatiotemporally intensive dataset highlight prominent patterns in variability for some taxa, but also identifies challenges of characterizing mechanisms underlying more episodic yet persistent events. Nevertheless, the intersect of temperature and salinity as environmental proxies proved to be informative in delineating niche partitioning, not only in the case of taxa with long-standing data sets but also for seemingly unprecedented blooms of novel nanoplanktonic taxa.

Using spatial and temporal variability data to optimize sediment toxicity identification evaluation (TIE) study designs.

Toxicity tests are an important aspect of sediment quality assessments, but knowledge of the cause of toxicity is needed to determine effective management actions. Toxicity identification evaluation (TIE) methods were developed to meet this need. While TIE method manuals provide information on the procedures, little information on study design is presented. The level of variability associated with performing TIEs and how to account for it is also not addressed. The goal of this study was to collect data on both the spatial and temporal variability associated with sediment TIEs by use of the amphipod Eohaustorius estuarius 10-day survival test and then apply that information to make recommendations for designing future TIE studies. Ten stations were sampled at Consolidated Slip in Los Angeles Harbor, California, with samples collected 2 months apart. In the first stage, TIEs were conducted on whole sediment and pore water from 3 of the most toxic stations. In the second stage, focused TIEs were conducted on whole sediment from all stations. Chemical analysis for metals and organic contaminants was also performed. With a weight of evidence approach, it was determined that pyrethroid pesticides were the likely cause of toxicity, with a lesser contribution from polycyclic aromatic hydrocarbons (PAHs). Results of the individual TIEs fell into 3 broad categories: TIEs in which treatments for organic chemicals and pyrethroids were effective; TIEs in which the treatment for pyrethroids was not effective but the treatment for organic contaminants was effective; and TIEs in which the treatment for pyrethroids was effective but the treatment for organic contaminants was not. This variability was used to calculate that at least 3 TIEs were necessary to make a confident assessment of the cause of toxicity. There was not substantial temporal variability in the TIE outcomes. Other recommendations are made regarding effective TIE study design. Integr Environ Assess Manag 2019;15:248-258. © 2018 SETAC.

Magnitude of acute toxicity of marine sediments amended with conventional copper and nanocopper.

It is well known that copper (Cu) is toxic to marine organisms. We measured and compared the acute toxicity of several forms of Cu (including nanoCu) amended into a marine sediment with mysids and amphipods. For all the forms of Cu tested, toxicity, measured as the median lethal concentration, ranged from 708 to > 2400 mg Cu/kg (dry sediment) for mysids and 258 to 1070 mg Cu/kg (dry sediment) for amphipods. Environ Toxicol Chem 2018;37:2677-2681. © 2018 SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Towards Resolving the Pro- and Anti-Tumor Effects of the Aryl Hydrocarbon Receptor.

We have postulated that the aryl hydrocarbon receptor (AHR) drives the later, more lethal stages of some cancers when chronically activated by endogenous ligands. However, other studies have suggested that, under some circumstances, the AHR can oppose tumor aggression. Resolving this apparent contradiction is critical to the design of AHR-targeted cancer therapeutics. Molecular (siRNA, shRNA, AHR repressor, CRISPR-Cas9) and pharmacological (AHR inhibitors) approaches were used to confirm the hypothesis that AHR inhibition reduces human cancer cell invasion (irregular colony growth in 3D Matrigel cultures and Boyden chambers), migration (scratch wound assay) and metastasis (human cancer cell xenografts in zebrafish). Furthermore, these assays were used for a head-to-head comparison between AHR antagonists and agonists. AHR inhibition or knockdown/knockout consistently reduced human ER−/PR−/Her2− and inflammatory breast cancer cell invasion, migration, and metastasis. This was associated with a decrease in invasion-associated genes (e.g., Fibronectin, VCAM1, Thrombospondin, MMP1) and an increase in CDH1/E-cadherin, previously associated with decreased tumor aggression. Paradoxically, AHR agonists (2,3,7,8-tetrachlorodibenzo-p-dioxin and/or 3,3′-diindolylmethane) similarly inhibited irregular colony formation in Matrigel and blocked metastasis in vivo but accelerated migration. These data demonstrate the complexity of modulating AHR activity in cancer while suggesting that AHR inhibitors, and, under some circumstances, AHR agonists, may be useful as cancer therapeutics.

Assessing the release of copper from nanocopper-treated and conventional copper-treated lumber into marine waters II: Forms and bioavailability.

One application of nanocopper is as a wood-preserving pesticide in pressure-treated lumber. Recent research has shown that pressure-treated lumber amended with micronized copper azole (MCA), which contains nanosized copper, releases copper under estuarine and marine conditions. The form of copper released (i.e., ionic, nanocopper [1-100 nm in size]) is not fully understood but will affect the bioavailability and toxicity of the metal. In the present study, multiple lines of evidence, including size fractionation, ion-selective electrode electrochemistry, comparative toxicity, and copper speciation were used to determine the form of copper released from lumber blocks and sawdust. The results of all lines of evidence supported the hypothesis that ionic copper was released from MCA lumber and sawdust, with little evidence that nanocopper was released. For example, copper concentrations in size fractionations of lumber block aqueous leachates including unfiltered, 0.1 µm, and 3 kDa were not significantly different, suggesting that the form of copper released was in the size range operationally defined as dissolved. These results correlated with the ion-selective electrode data which detects only ionic copper. In addition, comparative toxicity testing resulted in a narrow range of median lethal concentrations (221-257 µg/L) for MCA lumber blocks and CuSO4 . We conclude that ionic copper was released from the nanocopper pressure-treated lumber under estuarine and marine conditions. Environ Toxicol Chem 2018;37:1969-1979. Published 2018 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Assessing the release of copper from nanocopper-treated and conventional copper-treated lumber into marine waters I: Concentrations and rates.

Little is known about the release of metal engineered nanomaterials (ENMs) from consumer goods, including lumber treated with micronized copper. Micronized copper is a recent form of antifouling wood preservative containing nanosized copper particles for use in pressure-treated lumber. The present study investigated the concentrations released and the release rate of total copper over the course of 133 d under freshwater, estuarine, and marine salinity conditions (0, 1, 10, and 30‰) for several commercially available pressure-treated lumbers: micronized copper azole (MCA) at 0.96 and 2.4 kg/m3 , alkaline copper quaternary (ACQ) at 0.30 and 9.6 kg/m3 , and chromated copper arsenate (CCA) at 40 kg/m3 . Lumber was tested as blocks and as sawdust. Overall, copper was released from all treated lumber samples. Under leaching conditions, total release ranged from 2 to 55% of the measured copper originally in the lumber, with release rate constants from the blocks of 0.03 to 2.71 (units per day). Generally, measured release and modeled equilibrium concentrations were significantly higher in the estuarine conditions compared with freshwater or marine salinities, whereas rate constants showed very limited differences between salinities. Furthermore, organic carbon was released during the leaching and demonstrated a significant relationship with released copper concentrations as a function of salinity. The results indicate that copper is released into estuarine/marine waters from multiple wood treatments including lumber amended with nanoparticle-sized copper. Environ Toxicol Chem 2018;37:1956-1968. Published 2018 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Effects of micronized and nano-copper azole on marine benthic communities.

The widespread use of copper nanomaterials (CuNMs) as antibacterial and antifouling agents in consumer products increases the risk for metal contamination and adverse effects in aquatic environments. Information gaps exist on the potential toxicity of CuNMs in marine environments. We exposed field-collected marine meio- and macrobenthic communities to sediments spiked with micronized copper azole (MCA) using a novel method that brings intact benthic cores into the laboratory and exposes the organisms via surface application of sediments. Treatments included field and laboratory controls, 3 spiked sediments: low-MCA (51.9 mg/kg sediment), high-MCA (519 mg/kg sediment), and CuSO4 (519 mg/kg sediment). In addition, single-species acute testing was performed with both MCA and CuSO4. Our results indicate that meio- and macrofaunal assemblages exposed to High-MCA and CuSO4 treatments differed significantly from both the laboratory control and the low-MCA treatments. Differences in macrofauna were driven by decreases in 3 Podocopa ostracod species, the bivalve Gemma gemma, and the polychaetes Exogone verugera and Prionospio heterobranchia relative to the laboratory control. Differences in the meiofaunal community are largely driven by nematodes. The benthic community test results were more sensitive than the single-species test results. Findings of this investigation indicate that CuNMs represent a source of risk to marine benthic communities comparable to that of dissolved Cu. Environ Toxicol Chem 2018;37:362-375. Published 2017 Wiley Periodicals Inc. on behalf of SETAC. This article is a US government work and, as such, is in the public domain in the United States of America.

Exceptional Evolutionary Expansion of Prefrontal Cortex in Great Apes and Humans.

One of the enduring questions that has driven neuroscientific enquiry in the last century has been the nature of differences in the prefrontal cortex of humans versus other animals [1]. The prefrontal cortex has drawn particular interest due to its role in a range of evolutionarily specialized cognitive capacities such as language [2], imagination [3], and complex decision making [4]. Both cytoarchitectonic [5] and comparative neuroimaging [6] studies have converged on the conclusion that the proportion of prefrontal cortex in the human brain is greatly increased relative to that of other primates. However, considering the tremendous overall expansion of the neocortex in human evolution, it has proven difficult to ascertain whether this extent of prefrontal enlargement follows general allometric growth patterns, or whether it is exceptional [1]. Species' adherence to a common allometric relationship suggests conservation through phenotypic integration, while species' deviations point toward the occurrence of shifts in genetic and/or developmental mechanisms. Here we investigate prefrontal cortex scaling across anthropoid primates and find that great ape and human prefrontal cortex expansion are non-allometrically derived features of cortical organization. This result aligns with evidence for a developmental heterochronic shift in human prefrontal growth [7, 8], suggesting an association between neurodevelopmental changes and cortical organization on a macroevolutionary scale. The evolutionary origin of non-allometric prefrontal enlargement is estimated to lie at the root of great apes (∼19-15 mya), indicating that selection for changes in executive cognitive functions characterized both great ape and human cortical organization.

Evaluating the Relationship between Equilibrium Passive Sampler Uptake and Aquatic Organism Bioaccumulation.

This Critcal Review evaluates passive sampler uptake of hydrophobic organic contaminants (HOCs) in water column and interstitial water exposures as a surrogate for organism bioaccumulation. Fifty-seven studies were found where both passive sampler uptake and organism bioaccumulation were measured and 19 of these investigations provided direct comparisons relating passive sampler uptake and organism bioaccumulation. Polymers compared included low-density polyethylene (LDPE), polyoxymethylene (POM), and polydimethylsiloxane (PDMS), and organisms ranged from polychaetes and oligochaetes to bivalves, aquatic insects, and gastropods. Regression equations correlating bioaccumulation (CL) and passive sampler uptake (CPS) were used to assess the strength of observed relationships. Passive sampling based concentrations resulted in log-log predictive relationships, most of which were within one to 2 orders of magnitude of measured bioaccumulation. Mean coefficients of determination (r2) for LDPE, PDMS, and POM were 0.68, 0.76, and 0.58, respectively. For the available raw, untransformed data, the mean ratio of CL and CPS was 10.8 ± 18.4 (n = 609). Using passive sampling as a surrogate for organism bioaccumulation is viable when biomonitoring organisms are not available. Passive sampling based estimates of bioaccumulation provide useful information for making informed decisions about the bioavailability of HOCs.

An Aryl Hydrocarbon Receptor-Mediated Amplification Loop That Enforces Cell Migration in ER-/PR-/Her2- Human Breast Cancer Cells.

The endogenous ligand-activated aryl hydrocarbon receptor (AHR) plays an important role in numerous biologic processes. As the known number of AHR-mediated processes grows, so too does the importance of determining what endogenous AHR ligands are produced, how their production is regulated, and what biologic consequences ensue. Consequently, our studies were designed primarily to determine whether ER-/PR-/Her2- breast cancer cells have the potential to produce endogenous AHR ligands and, if so, how production of these ligands is controlled. We postulated that: 1) malignant cells produce tryptophan-derived AHR ligand(s) through the kynurenine pathway; 2) these metabolites have the potential to drive AHR-dependent breast cancer migration; 3) the AHR controls expression of a rate-limiting kynurenine pathway enzyme(s) in a closed amplification loop; and 4) environmental AHR ligands mimic the effects of endogenous ligands. Data presented in this work indicate that primary human breast cancers, and their metastases, express high levels of AHR and tryptophan-2,3-dioxygenase (TDO); representative ER-/PR-/Her2- cell lines express TDO and produce sufficient intracellular kynurenine and xanthurenic acid concentrations to chronically activate the AHR. TDO overexpression, or excess kynurenine or xanthurenic acid, accelerates migration in an AHR-dependent fashion. Environmental AHR ligands 2,3,7,8-tetrachlorodibenzo[p]dioxin and benzo[a]pyrene mimic this effect. AHR knockdown or inhibition significantly reduces TDO2 expression. These studies identify, for the first time, a positive amplification loop in which AHR-dependent TDO2 expression contributes to endogenous AHR ligand production. The net biologic effect of AHR activation by endogenous ligands, which can be mimicked by environmental ligands, is an increase in tumor cell migration, a measure of tumor aggressiveness.

Rural Ambulatory Access for Semi-Urgent Care and the Relationship of Distance to an Emergency Department.

INTRODUCTION: Availability of timely access to ambulatory care for semi-urgent medical concerns in rural and suburban locales is unknown. Further distance to an emergency department (ED) may require rural clinics to serve as surrogate EDs in their region, and make it more likely for these clinics to offer timely appointments. We determined the availability of urgent (within 48 hours) access to ambulatory care for non-established visiting patients, and assessed the effect of insurance and ability to pay cash on a patient's success in scheduling an appointment in rural and suburban Eastern United States. We also assessed how proximity to EDs and urgent care (UC) facilities influenced access to semi-urgent ambulatory appointments at primary care facilities. METHODS: The Appalachian Trail, which runs from Georgia to Maine, was used as a transect to select 190 rural and suburban primary care clinics located along its entire length. We calculated their location and distance to the nearest hospital-based ED or UC via Google Earth. A sham patient representing a non-established visiting patient called each clinic over a four-month period (2013), requesting an appointment in the next 48 hours for one of three scripted clinical vignettes representing common semi-urgent ambulatory concerns. We randomized the scenarios and insurance statuses (insured vs. uninsured). Each clinic was contacted twice, once with the caller representing an insured patient, once with the caller representing an uninsured patient. When the caller was representing an uninsured patient, any required upfront payment was requested from each clinic. One hundred dollars was used as a cutoff between the uninsured as a distinction between those able to afford substantial upfront sums and those who could not. To determine if proximity to other sources of care impacted a clinic's ability to grant an appointment, distance to the nearest ED or UC was modeled as a dichotomous variable using 30 miles as the divider. RESULTS: Of 380 requests, 96 (25.3%) resulted in appointments within 48 hours. Insured patients and uninsured patients able to pay a substantial amount upfront (>$100) were more likely to book an appointment (p-value <0.001, OR 18, CI [5-154]). Of the 47 clinics that granted uninsured patients appointments 89.3% required some form of payment up front. Farther distances from an ED did not result in greater likelihood of an appointment (OR 1.7, CI [0.4-11.3]). Clinics located within 30 miles of an UC were more likely to grant an appointment (OR 2.45, CI [1.19-5.80]). CONCLUSION: Almost 75% of rural clinics were unable to grant a new appointment for a semi-urgent health complaint. Lack of insurance and large upfront charges appear to be significant barriers to rural ambulatory care appointments. Greater distance from an ED does not improve a clinic's ability to see semi-urgent appointments. Clinics located near an UC were more likely to grant an appointment than clinics without close alternative outpatient healthcare options.

Environmental biodegradability of [¹4C] single-walled carbon nanotubes by Trametes versicolor and natural microbial cultures found in New Bedford Harbor sediment and aerated wastewater treatment plant sludge.

Little is known about environmental biodegradability or biotransformations of single-walled carbon nanotubes (SWNT). Because of their strong association with aquatic organic matter, detailed knowledge of the ultimate fate and persistence of SWNT requires investigation of possible biotransformations (i.e., biodegradation) in environmental media. In the present study, [(14)C]SWNT were utilized to track biodegradation over 6 mo by pure liquid culture of the fungus Trametes versicolor and mixed bacterial isolates from field-collected sediment or aerated wastewater treatment plant sludge. The mixed cultures were chosen as more environmentally relevant media where SWNT will likely be deposited under both aerobic and anaerobic conditions. Activity of [(14)C] was assessed in solid, aqueous, and (14)CO2 gaseous phases to determine amounts of intact SWNT, partially soluble SWNT degradation products, and mineralized SWNT, respectively, during the 6 mo of the experiment. Mass balances based on radiocarbon activity were approximately 100% over 6 mo, and no significant degradation of SWNT was observed. Approximately 99% of the [(14)C] activity remained in the solid phase, 0.8% in the aqueous phase, and less than 0.1% was mineralized to (14)CO2, regardless of culture type. These results suggest that SWNT are not readily biodegraded by pure fungal cultures or environmental microbial communities, and are likely persistent in environmental media.

In silico identification of an aryl hydrocarbon receptor antagonist with biological activity in vitro and in vivo.

The aryl hydrocarbon receptor (AHR) is critically involved in several physiologic processes, including cancer progression and multiple immune system activities. We, and others, have hypothesized that AHR modulators represent an important new class of targeted therapeutics. Here, ligand shape-based virtual modeling techniques were used to identify novel AHR ligands on the basis of previously identified chemotypes. Four structurally unique compounds were identified. One lead compound, 2-((2-(5-bromofuran-2-yl)-4-oxo-4H-chromen-3-yl)oxy)acetamide (CB7993113), was further tested for its ability to block three AHR-dependent biologic activities: triple-negative breast cancer cell invasion or migration in vitro and AHR ligand-induced bone marrow toxicity in vivo. CB7993113 directly bound both murine and human AHR and inhibited polycyclic aromatic hydrocarbon (PAH)- and TCDD-induced reporter activity by 75% and 90% respectively. A novel homology model, comprehensive agonist and inhibitor titration experiments, and AHR localization studies were consistent with competitive antagonism and blockade of nuclear translocation as the primary mechanism of action. CB7993113 (IC50 3.3 × 10(-7) M) effectively reduced invasion of human breast cancer cells in three-dimensional cultures and blocked tumor cell migration in two-dimensional cultures without significantly affecting cell viability or proliferation. Finally, CB7993113 effectively inhibited the bone marrow ablative effects of 7,12-dimethylbenz[a]anthracene in vivo, demonstrating drug absorption and tissue distribution leading to pharmacological efficacy. These experiments suggest that AHR antagonists such as CB7993113 may represent a new class of targeted therapeutics for immunomodulation and/or cancer therapy.