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In higher education institutions, many faculty members are hired because they are experts in their field of study, but not necessarily individuals who are trained in how to teach. This quantitative quasi-experimental study examined college faculty member's level of methodology training in relation to student satisfaction, current course performance, attendance, the belief in the need for training, and a faculty member's sense of efficacy in teaching. In other words, does having a college professor trained in how to teach matter? The researcher found statistically significant results for student satisfaction, current course performance, and attendance. The faculty member's belief in the need for teaching methodology training showed that 96% (n = 87) of the faculty surveyed felt there was a need to be trained to teach at the college level. Faculty members want to be trained and great things can happen when faculty members develop the skills in "how to teach."

In occupational therapy practice, critical thinking is a foundational skill for the delivery of effective care; however, there is limited evidence on the development of critical thinking skills in occupational therapy education. The purpose of this study was to explore the effects and student perceptions of concept mapping on critical thinking skills in occupational therapy education. This study used a quasiexperimental design with a retrospective pre-post assessment after two teaching conditions: (a) traditional lecture and (b) concept mapping. The same convenience sample of students was used for each condition. Additional outcome measures included assessment of student concept maps using a scoring rubric and a survey of students' perceptions on the use of concept mapping. Results of the retrospective pre-post assessment indicated significant gains in student knowledge (p<0.001) following both the concept mapping activity (n=39) and traditional lecture (n=46). Assessment of the concept maps along with the results of the student survey indicated that concept mapping supported student use of key critical thinking skills including interpreting knowledge, understanding relationships, communicating their rationale, and reflecting on their thinking. Overall, students reported strong affective acceptance of concept mapping and found concept mapping easy to use. Given these findings, occupational therapy educators need to consider incorporating concept mapping as a form of active, student-centered learning to support enhanced knowledge of content and higher-level thinking.

Extensive reading (ER) provides young English language learners (YELLs) many benefits, including the sustainable development of writing (e.g., the reading-writing relationship). However, this area is underresearched. To address this, this quasi-experimental study investigated the effect of ER on YELLs' second language writing achievement using an enhanced ER treatment. Pre- and post-Cambridge Primary English Test (PET) samples were collected and evaluated via the PET analytic rubric total band and subscales scores (Content, Communicative Achievement, Organization, Language). The results indicated that the EG outperformed the CG in total band score and three subscale bands (Content, Organization, Language), and the EG and CG performed comparably well in the fourth (Communicative Achievement). As prior research specific to ER's effect on YELLs' writing achievement in the Vietnam context is noticeably understudied, this study offers a starting point for future investigations.

Abstract Background Children with disabilities worldwide experience disparities in oral health. Parents and children encounter challenges in accessing quality dental care. Similar challenges are experienced in Saudi Arabia. This study aimed to explore the barriers and facilitators of oral healthcare for children with disabilities in Saudi Arabia. Methods This was an ethnographic study. The sample size was 25 participants, comprising of 12 pediatric dentists and 13 parents of children with disabilities. Data were collected through in-depth interviews, employing a topic guide. A pre-defined analytical framework was developed from the study objectives and framework analysis used to analyse data. Results The study identified significant barriers and facilitators to oral healthcare for children with disabilities. Barriers included long travel distances, inadequate clinic facilities, a shortage of specialist pediatric dentists, inefficiencies in referral systems, and financial constraints. Other challenges were related to physical barriers in clinics, cultural norms, and socioeconomic inequalities. Facilitators, though fewer, included personal connections, specialized disability friendly clinics, and the Priority Card Program, albeit with limited effectiveness. Suggestions for improvement highlighted the need for better training for dental professionals, enhanced clinic accessibility, and greater financial support for families. Conclusion Accessibility of dental care for children with disabilities in Saudi Arabia remains a significant challenge due to systemic barriers and individual-level obstacles. The study underscores the need for policy reforms, enhanced professional training, and the improvement of physical and financial accessibility to dental services. Addressing these issues through comprehensive educational programs and targeted interventions is essential for reducing oral health disparities and improving care for children with disabilities.

This study investigated what features undergraduate EFL learners perceive as affecting the difficulty of model paragraphs. Four hundred and seventy-five Vietnamese undergraduates participated in a partial least squares structural equation model design. They ranked five paragraphs from easiest to most difficult and responded to a 10-point Likert questionnaire regarding 11 features (titles, paragraph length, vocabulary, vocabulary in context, rhetorical organization, paragraph structure, sentence length, punctuation, signal words, interest, background knowledge). The results showed that eight variables (titles, vocabulary, vocabulary in context, sentence length, rhetorical organization, paragraph structure, interest, background knowledge) had a significant direct effect and four variables (vocabulary, sentence length, rhetorical organization, background knowledge) had mediating effects. The model accounted for 0.508 R[superscript 2] of students' perceptions, with a moderate to high predictive relevance (Q[superscript 2] = 0.35). The paper also discusses the results' implications for those in writing studies and the publishing industry. Suggestions for future study are also presented.

Abstract We describe the geographical variation in tree species composition across Amazonian forests and show how environmental conditions are associated with species turnover. Our analyses are based on 2023 forest inventory plots (1 ha) that provide abundance data for a total of 5188 tree species. Within-plot species composition reflected both local environmental conditions (especially soil nutrients and hydrology) and geographical regions. A broader-scale view of species turnover was obtained by interpolating the relative tree species abundances over Amazonia into 47,441 0.1-degree grid cells. Two main dimensions of spatial change in tree species composition were identified. The first was a gradient between western Amazonia at the Andean forelands (with young geology and relatively nutrient-rich soils) and central–eastern Amazonia associated with the Guiana and Brazilian Shields (with more ancient geology and poor soils). The second gradient was between the wet forests of the northwest and the drier forests in southern Amazonia. Isolines linking cells of similar composition crossed major Amazonian rivers, suggesting that tree species distributions are not limited by rivers. Even though some areas of relatively sharp species turnover were identified, mostly the tree species composition changed gradually over large extents, which does not support delimiting clear discrete biogeographic regions within Amazonia.

Abstract The intricate network of protein-chaperone interactions is crucial for maintaining cellular function. Recent discoveries have unveiled the existence of specialized chaperone assemblies, known as epichaperomes, which serve as scaffolding platforms that orchestrate the reconfiguration of protein-protein interaction networks, thereby enhancing cellular adaptability and proliferation. This study explores the structural and regulatory aspects of epichaperomes, with a particular focus on the role of post-translational modifications (PTMs) in their formation and function. A key finding is the identification of specific PTMs on HSP90, particularly at residues Ser226 and Ser255 within an intrinsically disordered region, as critical determinants of epichaperome assembly. Our data demonstrate that phosphorylation of these serine residues enhances HSP90’s interactions with other chaperones and co-chaperones, creating a microenvironment conducive to epichaperome formation. Moreover, we establish a direct link between epichaperome function and cellular physiology, particularly in contexts where robust proliferation and adaptive behavior are essential, such as in cancer and pluripotent stem cell maintenance. These findings not only provide mechanistic insights but also hold promise for the development of novel therapeutic strategies targeting chaperone assemblies in diseases characterized by epichaperome dysregulation, thereby bridging the gap between fundamental research and precision medicine.

Abstract Background Children with disabilities experience poorer oral health and frequently have complex needs. The accessibility of oral health care services for children with disabilities is crucial for promoting oral health and overall well-being. This study aimed to systematically review the literature to identify the barriers and facilitators to oral health care services for children with disabilities, and to propose priority research areas for the planning and provision of dental services to meet their needs. Methods This was a mixed methods systematic review. Multiple databases searched included MEDLINE, Scopus, PsycINFO, EMBASE, and CINAHL. The search strategy included Medical Subject Heading (MeSH) terms related to children, disabilities, and access to oral health. Eligibility criteria focused on studies about children with disabilities, discussing the accessibility of oral health care. Results Using Levesque’s framework for access identified barriers such as professional unwillingness, fear of the dentist, cost of treatment, and inadequate dental facilities. Facilitators of access offered insight into strategies for improving access to oral health care for children with disabilities. Conclusion There is a positive benefit to using Levesque’s framework of access or other established frameworks to carry out research on oral healthcare access, or implementations of dental public health interventions in order to identify gaps, enhance awareness and promote better oral health practices. The evidence suggests that including people with disabilities in co-developing service provision improves accessibility, alongside using tailored approaches and interventions which promote understanding of the importance of dental care and increases awareness for professionals, caregivers and children with disabilities. Trial registration Protocol has been registered online on the PROSPERO database with an ID CRD42023433172 on June 9, 2023.

Early childhood aggression is a ubiquitous and developmentally normal behavior; however, different report sources (e.g., child self-report vs. teacher) often yield markedly different interpretations. The current study examined how typical demographic and cognitive factors that have been previously found to explain child behavior (e.g., SES, inhibitory control) differentially explain child aggression and prosociality as a function of the informant. Preschool-age children (N = 121) completed several cognitive tasks (PPVT, Theory of Mind battery, Day/Night Stroop, moral judgment) as well as a dual-puppet self-report behavior interview. Parents reported demographics. Teachers completed the Preschool Proactive and Reactive Aggression-Teacher Report. As expected, teachers' and children's reports differed considerably and corresponded with different aspects of child development--teachers' reports of aggression were largely explained by demographic variables (i.e., fathers' education level), whereas children's self-reports of aggression were explained by cognitive maturation (i.e., PPVT and moral understanding). These findings support the continued position that studies of early childhood psychopathology should employ multiple mixed methods of reporting, and considers the strengths and weaknesses of each approach.

The idea that reading model essays facilitates better writing is generally accepted in second language writing literature. As such, anthologies of model essays are often selected for inclusion in writing centre self-access library shelves. When selecting these texts, readability is often considered via the application of quantitative readability formulae (e.g. the Lexile Readability Formula). Unfortunately, such formulae only measure two (i.e. semantic, syntactic) of the many features that impact readability, leaving other features that require qualitative consideration (e.g. signal words, SWs) unexplored. To address this, this article reports the findings of a sequential, mixed-methods study conducted in a Taiwanese university writing centre context that explored how SWs affect post-secondary English language learners' perceptions of ease and difficulty when reading model essays excerpted from anthologies. The inferential statistics showed that the informants (students who visited the writing centre) ranked the essays' ease and difficulty significantly differently than the Lexile Formula. The qualitative exploration found that SWs (e.g. students' awareness of SWs) contributed to this ranking. The study also suggests that writing studies professionals (teachers, writing centre staff) and the publishing industry include signal words as part of a hybrid (quantitative-qualitative) exploration when considering the difficulty of model essays in anthologies.

Research highlights the many benefits of study abroad in higher education with emerging scholarship on study abroad in K-12 education. This paper focuses on how leading study abroad fosters a collaborative, cosmopolitan-oriented, professional environment for secondary teachers in Washington, D.C. Public Schools (DCPS). Theoretically we apply frameworks related to the development of cosmopolitan capital and the formation of collaborative professional communities. Using a qualitative case study approach, we draw on data from interviews, written materials, observations of pre-departure meetings and training, and post-program survey responses. Analysis illustrates several emergent themes: First, educators with previous international experience tend to seek out globally oriented in-service teacher education experience. Second, the majority of participating teachers report leading study abroad experience as beneficial to them. Third, findings show the importance of forming professional communities among global educators. Together these findings signal the unique benefits of study abroad in teacher education and professional development settings.

Parental support or resistance has been widely recognised as an important factor that enables or constrains the implementation of quality Relationships and Sexuality Education (RSE). This paper analyses parental experiences of involvement and engagement with Gender Equality Matters (GEM), an educational programme focused on raising awareness, building confidence and enhancing capacity levels among children to tackle gender inequality and promote LGBTQI inclusion. The paper focuses on qualitative data from participating parents in the Irish primary school context. Pre- and post-questionnaires (n = 162) and semi-structured interviews (n = 3) were utilised to gain insight into the parents' experience of participating in GEM. Using thematic analysis, the analysis explores three themes: 1) positive parental partnerships; 2) naturalistic at-home conversations; and 3) resistance and disengagement. The study highlights the key role of parental partnerships with school curricula, whilst critically reflecting on potential sites for resistance and providing a successful model for future educational programmes to adopt.

Telehealth was widely adopted in pediatric occupational therapy practice during the COVID-19 pandemic; however, there is limited knowledge on telehealth use post-pandemic. This study collected 132 responses to a mixed-methods survey from March-October 2023 to explore pediatric occupational therapists’ current use and perceptions on telehealth. Results indicated that over half of respondents continue to use telehealth. Frequency of use was differentiated by setting, with a significantly lower proportion of school-based respondents using telehealth compared to outpatient (p

Reviewing the literature is an important part of academic work, as it helps readers see what has come before, what has and has not worked, and situates the author's place in the ongoing discussion. Accepting this view, extensive reading literature often points to Day and Bamford (1988) as identifying Kelly (1969) as crediting Palmer (1921) as the first to apply the term extensive reading (ER) in L2 pedagogy. At the time of Day and Bamford and Kelly's publications, a reference to Palmer was a worthy seminal identification as literature searches were not aided by today's more powerful electronic databases. Utilizing more modern search tools (Archive.org, Google Books, JSTOR, Project Gutenberg, Google Books) and the archival works they provide, we extend the discussion by offering a more complete history of the term for researchers to draw from. Specifically, we (a) explore early L1 uses of the term and (b) point to three new L2 seminal benchmarks: the earliest (1) use of the term (2) intensive/extensive distinction; and (3) definition found to date. We then (c) continue our discussion up through today's modern definitions of the term. Directions for future studies are also discussed.

ABSTRACT: Introduction: Oral diseases affect a significant proportion of the world's population, yet international comparisons involving oral health outcomes have often been limited due to differences in the way country-level primary data are collected. In response to this, the World Dental Federation (FDI) Oral Health Observatory project was launched with the goal of collecting and producing standardised international data on oral health across countries. The aim of this descriptive cross-sectional study was to examine associations between self-reported general health and a range of factors (sociodemographics, oral health–related behaviours, oral impacts, clinical variables) using these standardised international datasets. Methods: Dentists within FDI member National Dental Associations who chose to take part in the project were selected using a multistage sampling method. The number of dentists in each cluster was set according to the proportion of the national population living in the area, and 50 patients per dentist were systematically approached to take part. Patients and dentists completed 2 separate questionnaires on a mobile app. Ordinal logistic regression (conducted in December 2022) was used to analyse the linked patient and dentist data from 6 countries: China (n = 2242); Colombia (n = 1029); India (n = 999); Italy (n = 711); Japan (n = 1271); and Lebanon (n = 798). Self-reported general health was the dependent variable, with age, sex, education, self-reported oral health–related behaviours, self-reported oral impacts, and clinical variables acting as the independent variables. Results: The results demonstrated a different pattern of associations in the different countries. Better self-reported general health was associated with degree-level education in all 6 countries and with reporting no oral impact and no sensitive teeth in 4 countries. Several country-specific patterns were also found, including the importance of tooth brushing in Colombia, periodontal health in Italy, and differing associations with sugary drinks consumption in India and Japan. Conclusions: These descriptive findings provide a basis for further research and, importantly, for advocacy in identifying patient oral health care needs according to both person-reported and clinical aspects. This can facilitate optimisation of service provision and potentially influence policy and investments.

Abstract Acute kidney injury (AKI) is a systemic disease that affects energy metabolism in various remote organs in murine models of ischemic AKI. However, AKI-mediated effects in the liver have not been comprehensively assessed. After inducing ischemic AKI in 8–10-week-old, male C57BL/6 mice, mass spectrometry metabolomics revealed that the liver had the most distinct phenotype 24 h after AKI versus 4 h and 7 days. Follow up studies with in vivo [13C6]-glucose tracing on liver and kidney 24 h after AKI revealed 4 major findings: (1) increased flux through glycolysis and the tricarboxylic (TCA) cycle in both kidney and liver; (2) depleted hepatic glutathione levels and its intermediates despite unchanged level of reactive oxygen species, suggesting glutathione consumption exceeds production due to systemic oxidative stress after AKI; (3) hepatic ATP depletion despite unchanged rate of mitochondrial respiration, suggesting increased ATP consumption relative to production; (4) increased hepatic and renal urea cycle intermediates suggesting hypercatabolism and upregulation of the urea cycle independent of impaired renal clearance of nitrogenous waste. Taken together, this is the first study to describe the hepatic metabolome after ischemic AKI in a murine model and demonstrates that there is significant liver-kidney crosstalk after AKI.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a human pathogenic virus that encodes for a helicase (SC2Hel) that is essential for viral replication. SC2Hel has the ability to unravel dsRNA or dsDNA in an NTP-dependent manner from the 5′ to 3′ directionality. The standard helicase assay from studies involving SARS-CoV and SARS-CoV-2 have relied on the concept of fluorescence resonance energy transfer. Adding to the collection of helicase assays, herein, we have developed a novel tetrazolium-based colorimetric assay system for the detection of ADP that is produced via SC2Hel activity. This SC2Hel assay combines three enzyme-coupled steps involving the ADP-dependent Thermococcus litoralis glucokinase (TlGlcK), Leuconostoc mesenteroides glucose-6-phosphate dehydrogenase (LmG6PDH), and Clostridium kluyveri diaphorase (CkDIA). Iodonitrotetrazolium chloride (INT), a colorimetric tetrazolium reagent, was used in the final step of the assay that converted into INT-formazan during reduction. INT-formazan in the assay’s buffered solution at pH 7.6 exhibited an intense colorimetric response at a wavelength maximum of 505 nm. The assay exhibited excellent performance characteristics as it revealed a Z’ factor of 0.87 and it has the potential to be further adopted into high-throughput screening studies for therapeutic drug discovery research.

Like many forage fish species, Pacific sand lance (Ammodytes personatus) play a key role in nearshore marine ecosystems as an important prey source for a diverse array of predators in the northeastern Pacific. However, the primary threats to Pacific sand lance and their habitat are poorly defined due to a lack of systematic data. Crucial information needed to assess their population status is also lacking including basic knowledge of their local and regional abundance and distribution. Sand lance are currently listed as ‘not evaluated’ under the IUCN red list and they have not been assessed by US and Canadian agencies. This hampers management and policy efforts focused on their conservation. To address this knowledge gap, we conducted a three-part, structured expert elicitation to assess the vulnerability of Salish Sea sand lance populations. Experts were asked to list and rank key threats to Salish Sea sand lance and/or their habitat, to further quantify the vulnerability of sand lance to identified threats using a vulnerability matrix, and to predict the population trajectory in 25 years from today. Impacts associated with climate change (e.g. sea level rise, sea temperature rise, ocean acidification, and extreme weather) consistently ranked high as threats of concern in the ranking exercise and quantified vulnerability scores. Nearly every expert predicted the population will have declined from current levels in 25 years. These results suggest sand lance face numerous threats and may be in decline under current conditions. This research provides vital information about which threats pose the greatest risk to the long-term health of sand lance populations and their habitat. Managers can use this information to prioritize which threats to address. Future research to reliably quantify population size, better understand the roles of natural and anthropogenic impacts, and to identify the most cost-effective actions to mitigate multiple threats, is recommended.

Abstract The Afrotropics are experiencing some of the fastest urbanisation rates on the planet but the impact of city growth on their rich and unique biodiversity remains understudied, especially compared to natural baselines. Little is also known about how introduced species influence β‐diversity in these contexts, and how patterns coincide with native ranges of species. Here we investigated how tree assemblages of the endemic‐rich Afrotropical island of São Tomé differed between urban, rural and natural zones. These were primarily characterised by urban greenspaces, shade plantations, and old‐growth forests, respectively. Based on 81 transects, we assessed biodiversity metrics of endemic, native and introduced species. Tree abundance and species richness were highest in the natural zone, where the composition was most different from the urban zone. The tree community of the rural zone was the most uneven and had the least variation among transects, representing the lowest β‐diversity. The urban zone was dominated by introduced species (57.7%), while the natural zone hosted almost exclusively native species (93.3%), including many endemics (26.1%). The biogeographic realms that species originated from were particularly diverse in the urban zone, with few species from the Afrotropics. In contrast to native and endemic trees, introduced trees were clearly associated with urban and rural expansion, as they were much more abundant and species‐rich in these zones than in the natural zone, facilitating biotic homogenisation. These findings highlight how urban and rural environments are affecting the native tree flora of São Tomé, and the need for conservation measures geared towards globally threatened and endemic tree species. Importantly, these require the protection of natural forests, despite the rising land demands for settlements and agriculture. Ultimately, such action to conserve endemic trees will contribute to global efforts to prevent further biodiversity declines.

Abstract Background In recent years, stimulant use has increased among persons who use opioids in the rural U.S., leading to high rates of overdose and death. We sought to understand motivations and contexts for stimulant use among persons who use opioids in a large, geographically diverse sample of persons who use drugs (PWUD) in the rural settings. Methods We conducted semi-structured individual interviews with PWUD at 8 U.S. sites spanning 10 states and 65 counties. Content areas included general substance use, injection drug use, changes in drug use, and harm reduction practices. We used an iterative open-coding process to comprehensively itemize and categorize content shared by participants related to concurrent use. Results We interviewed 349 PWUD (64% male, mean age 36). Of those discussing current use of stimulants in the context of opioid use (n = 137, 39%), the stimulant most used was methamphetamine (78%) followed by cocaine/crack (26%). Motivations for co-use included: 1) change in drug markets and cost considerations; 2) recreational goals, e.g., seeking stronger effects after heightened opioid tolerance; 3) practical goals, such as a desire to balance or alleviate the effects of the other drug, including the use of stimulants to avoid/reverse opioid overdose, and/or control symptoms of opioid withdrawal; and 4) functional goals, such as being simultaneously energized and pain-free in order to remain productive for employment. Conclusion In a rural U.S. cohort of PWUD, use of both stimulants and opioids was highly prevalent. Reasons for dual use found in the rural context compared to urban studies included changes in drug availability, functional/productivity goals, and the use of methamphetamine to offset opioid overdose. Education efforts and harm reduction services and treatment, such as access to naloxone, fentanyl test strips, and accessible drug treatment for combined opioid and stimulant use, are urgently needed in the rural U.S. to reduce overdose and other adverse outcomes.

Abstract One of the major consequences of the COVID-19 pandemic has been the significant incidence of persistent fatigue following resolution of an acute infection (i.e. post-COVID fatigue). We have shown previously that, in comparison to healthy controls, those suffering from post-COVID fatigue exhibit changes in muscle physiology, cortical circuitry, and autonomic function. Whether these changes preceded infection, potentially predisposing people to developing post-COVID fatigue, or whether the changes were a consequence of infection was unclear. Here we present results of a 12-month longitudinal study of 18 participants from the same cohort of post-COVID fatigue sufferers to investigate these correlates of fatigue over time. We report improvements in self-perception of the impact of fatigue via questionnaires, as well as significant improvements in objective measures of peripheral muscle fatigue and autonomic function, bringing them closer to healthy controls. Additionally, we found reductions in muscle twitch tension rise times, becoming faster than controls, suggesting that the improvement in muscle fatigability might be due to a process of adaptation rather than simply a return to baseline function.

Abstract English as a foreign language (EFL) learners often read at rates below recommended reading speeds needed for reading fluency. Two methods are often employed to facilitate reading rates: unassisted repeated reading (UARR) and audio-assisted repeated reading (AARR). Both approaches have demonstrated significant gains. However, the two methods’ effects have not been explored and compared in the course of one investigation. To address this, an experimental design was employed with undergraduate EFL learners (N = 50) at a university in Southern Vietnam. The results indicated that both procedures produced significant positive gains; however, the AARR showed a significantly higher effect than UARR (77.27, 44.72, p

Lipid II is an essential glycolipid found in bacteria. Accessing this valuable cell wall precursor is important both for studying cell wall synthesis and for studying/identifying novel antimicrobial compounds. Herein, we describe optimizations to the modular chemical synthesis of lipid II and unnatural analogues. In particular, the glycosylation step, a critical step in the formation of the central disaccharide unit (GlcNAc-MurNAc), was optimized. This was achieved by employing the use of glycosyl donors with diverse leaving groups. The key advantage of this approach lies in its adaptability, allowing for the generation of a wide array of analogues through the incorporation of alternative building blocks at different stages of synthesis.

Summary: Retinoic acid (RA), controls the immunoregulatory functions of many immune cells, including dendritic cells (DCs), and is important for mucosal immunity. In DCs, RA regulates the expression of pattern recognition receptors and stimulates interferon production. Here, we investigated the role of RA in DCs in mounting immunity to respiratory syncytial virus (RSV). To abolish RA signaling in DCs, we used mice expressing a dominant negative form of retinoic acid receptor-α (RARα) under the CD11c promoter (CD11c-dnRARα). Paradoxically, upon RSV challenge, these animals had lower viral burden, reduced pathology, and greater Th1 polarized immunity than wild-type (WT) mice. Moreover, CD11c-dnRARα DCs infected with RSV showed enhancement in innate and adaptive immunity genes, while genes associated with viral replication were downregulated. These findings suggest that the absence of RA signaling in DCs enhances innate immunity against RSV infection leading to decreased viral load and reduced pathogenicity.

We previously reported on the interaction of 10-chloro-7H-benzo[de]benzo[4,5]imidazo[2,1-a]isoquinolin-7-one (10-Cl-BBQ) with the Aryl hydrocarbon Receptor (AhR) and selective growth inhibition in breast cancer cell lines. We now report on a library of BBQ analogues with substituents on the phenyl and naphthyl rings for biological screening. Herein, we show that absence of the phenyl Cl of 10-Cl-BBQ to produce the simple BBQ molecule substantially enhanced the growth inhibitory effect with GI50 values of 0.001–2.1 μM in select breast cancer cell lines MCF-7, T47D, ZR-75-1, SKBR3, MDA-MB-468, BT20, BT474 cells, while having modest effects of 2.1–7 μM in other cell lines including HT29, U87, SJ-G2, A2780, DU145, BE2-C, MIA, MDA-MB-231 or normal breast cells, MCF10A (3.2 μM). The most potent growth inhibitory effect of BBQ was observed in the triple negative cell line, MDA-MB-468 with a GI50 value of 0.001 μM, presenting a 3,200-fold greater response than in the normal MCF10A breast cells. Additions of Cl, CH3, CN to the phenyl ring and ring expansion from benzoimidazole to dihydroquinazoline hindered the growth inhibitory potency of the BBQ analogues by blocking potential sites of CYP1 oxidative metabolism, while addition of Cl or NO2 to the naphthyl rings restored potency. In a cell-based reporter assay all analogues induced 1.2 to 10-fold AhR transcription activation. Gene expression analysis confirmed the induction of CYP1 oxygenases by BBQ. The CYP1 inhibitor α-naphthoflavone, and the SULT1A1 inhibitor quercetin significantly reduced the growth inhibitory effect of BBQ, confirming the importance of both phase I and II metabolic activation for growth inhibition. Conventional molecular modelling/docking revealed no significant differences between the binding poses of the most and least active analogues. More detailed DFT analysis at the DSD-PBEP86/Def-TZVPP level of theory could not identify significant geometric or electronic changes which would account for this varied AhR activation. Generation of Fukui functions at the same level of theory showed that CYP1 metabolism will primarily occur at the phenyl head group of the analogues, and substituents within this ring lead to lower cytotoxicity.

Introduction Understanding the interplay of immune mediators in relation to clinical outcomes during acute infection has the potential to highlight immune networks critical to symptom recovery. The objective of the present study was to elucidate the immune networks critical to early symptom resolution following severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Methods In a community-based randomised clinical trial comparing inhaled budesonide against usual care in 139 participants with early onset SARS-CoV-2 (the STOIC study; clinicaltrials.gov identifier NCT04416399), significant clinical deterioration (reported need for urgent care, emergency department visit, hospitalisation: the primary outcome), self-reported symptom severity (Influenza Patient-Reported Outcome questionnaire) and immune mediator networks were assessed. Immune mediator networks were determined using pre-defined mathematical modelling of immune mediators, determined by the Meso Scale Discovery U-Plex platform, within the first 7 days of SARS-CoV-2 infection compared to 22 healthy controls. Results Interferon- and chemokine-dominant networks were associated with high viral burden. Elevated levels of the mucosal network (chemokine (C-C motif) ligand (CCL)13, CCL17, interleukin (IL)-33, IL-5, IL-4, CCL26, IL-2, IL-12 and granulocyte–macrophage colony-stimulating factor) was associated with a mean 3.7-day quicker recovery time, with no primary outcome events, irrespective of treatment arm. This mucosal network was associated with initial nasal and throat symptoms at day 0. Conclusion A nasal immune network is critical to accelerated recovery and improved patient outcomes in community-acquired viral infections. Overall, early prognostication and treatments aimed at inducing epithelial responses may prove clinically beneficial in enhancing early host response to virus.

Claims that Herodotus reveals himself as a proto-biographer are not yet widely accepted. To advance this claim, I review his recount of Kleomenes of Sparta (c. 540–c. 490), who finds his kingdom caught in the periphery of the Greco-Persian conflict, and whose activities over a thirty-year reign are recorded in the Histories. It is to Heraclitus to whom we attribute the maxim—character is human destiny. It is the truth of this maxim—which implies effective human agency—that makes Herodotus’ creation of historical narrative possible. He is often read for his off-topic vignettes, which color-in the character of the individuals depicted without necessarily advancing his narrative. But by leapfrogging through five of the nine books of the Histories, we can assemble a largely continuous narrative for this remarkable Spartan ruler. This narrative permits us to attribute both credit and moral responsibility for his actions. Arguably, this implied causation demonstrates that Herodotus’ writings include much that amounts to proto-biography.

Abstract Social dominance encompasses winning dyadic contests and gaining priority access to resources and reproduction. Dominance is influenced by environmental factors, particularly during early postnatal life and adolescence. A disinhibitory medial prefrontal cortex (mPFC) microcircuit has been implicated in the expression of dominance in the “tube test” social competition paradigm in mice, but the neuroplasticity underlying dominance is not known. We previously reported that male pups raised by physically active (wheel-running, as opposed to sedentary) dams exhibit tube test dominance and increased reproductive fitness, and here we show that social isolation from weaning also increases dominance. By using single cell transcriptomics, we tested if increased dominance in these models is associated with a specific transcriptional profile in one or more cell-types in the mPFC. The preweaning maternal effect, but not postweaning social isolation, caused gene expression changes in pyramidal neurons. However, both the effect of maternal exercise and social isolation induced the coordinated downregulation of synaptic channel, receptor, and adhesion genes in parvalbumin positive (PV) interneurons, suggesting that development of dominance is accompanied by impaired PV interneuron-mediated inhibition of pyramidal cells. This study may help understand environmentally induced transcriptional plasticity in the PFC and its relationship to tube test dominance.

Abstract Using 2.046 botanically-inventoried tree plots across the largest tropical forest on Earth, we mapped tree species-diversity and tree species-richness at 0.1-degree resolution, and investigated drivers for diversity and richness. Using only location, stratified by forest type, as predictor, our spatial model, to the best of our knowledge, provides the most accurate map of tree diversity in Amazonia to date, explaining approximately 70% of the tree diversity and species-richness. Large soil-forest combinations determine a significant percentage of the variation in tree species-richness and tree alpha-diversity in Amazonian forest-plots. We suggest that the size and fragmentation of these systems drive their large-scale diversity patterns and hence local diversity. A model not using location but cumulative water deficit, tree density, and temperature seasonality explains 47% of the tree species-richness in the terra-firme forest in Amazonia. Over large areas across Amazonia, residuals of this relationship are small and poorly spatially structured, suggesting that much of the residual variation may be local. The Guyana Shield area has consistently negative residuals, showing that this area has lower tree species-richness than expected by our models. We provide extensive plot meta-data, including tree density, tree alpha-diversity and tree species-richness results and gridded maps at 0.1-degree resolution.

Background: Research has demonstrated that the loss of one or more natural teeth can be an emotionally traumatic experience that mirrors processes associated with bereavement. There remains scant literature examining the role of emotions in dental encounters. One such exception is the literature on the idea of the ‘treatment alliance’ in dental encounters. The aim of this paper is to explore the role of the ‘treatment alliance’ in dentist–patient encounters. Methods: Data were collected from clinical observations, semi-structured interviews and focus groups exploring the experience of tooth loss and how the treatment alliance shaped the patient journey. Data analysis was conducted using the grounded theory method influenced by phenomenology. Coding was conducted using NVIVO and the unit of analysis was the treatment alliance. Results: Twenty participants took part in the interviews (eleven male; nine female; 22–86 years; mean age = 58.9 years). Observations were carried out with a further fourteen participants (seven male; seven female; 50–101 years; mean age = 62.2 years). The paper draws on four cases taken from the observational data to illustrate important dynamics underpinning how the treatment alliance varied. These case studies are then used as the basis for a critical discussion of the importance of the treatment alliance in dentistry. Conclusions: The treatment alliance acted as an important moderator in the clinical encounter, helping to influence successful outcomes. An important foundational component of the treatment alliance was the degree of emotional work the dental team conducted when ‘getting to know’ unfamiliar patients. Whilst emotions were an important factor in dental encounters, their acknowledgement and management were not essential to all successful outcomes. Much more research is therefore needed into the role of emotional labour in dental encounters.

Lead (Pb) is a well-known neurotoxin with established adverse effects on the neurological functions of children and younger adults, including motor, learning, and memory abilities. However, its potential impact on older adults has received less attention. Using the zebrafish model, our study aims to characterize the dose–response relationship between environmentally relevant Pb exposure levels and their effects on changes in behavior and transcriptomics during the geriatric periods. We exposed two-year-old zebrafish to waterborne lead acetate (1, 10, 100, 1000, or 10,000 µg/L) or a vehicle (DMSO) for 5 days. While lower concentrations (1–100 µg/L) reflect environmentally relevant Pb levels, higher concentrations (1000–10,000 µg/L) were included to assess acute toxicity under extreme exposure scenarios. We conducted adult behavior assessment to evaluate the locomotor activity following exposure. The same individual fish were subsequently sacrificed for brain dissection after a day of recovery in the aquatic system. RNA extraction and sequencing were then performed to evaluate the Pb-induced transcriptomic changes. Higher (1000–10,000 ug/L) Pb levels induced hyperactive locomotor patterns in aged zebrafish, while lower (10–100 ug/L) Pb levels resulted in the lowest locomotor activity compared to the control group. Exposure to 100 µg/L led to the highest number of differentially expressed genes (DEGs), while 10,000 µg/L induced larger fold changes in both directions. The neurological pathways impacted by Pb exposure include functions related to neurotransmission, such as cytoskeletal regulation and synaptogenesis, and oxidative stress response, such as mitochondrial dysfunction and downregulation of heat shock protein genes. These findings emphasize a U-shape dose–response relationship with Pb concentrations in locomotor activity and transcriptomic changes in the aging brain.

SARS-CoV-2 antibody kinetics based on immunologic history is not fully understood. We analyzed anti-spike and anti-nucleocapsid antibody responses following acute infection in a cohort of Indigenous persons. The models of peak concentrations and decay rates estimated that one year after infection, participants would serorevert for anti-nucleocapsid antibodies and remain seropositive for anti-spike antibodies. The peak anti-spike concentrations were higher for individuals vaccinated prior to infection, but the decay rates were similar across immunologic status groups. Children had significantly lower peak anti-spike concentrations than adults. This study affirms the importance of continued vaccination to maintain high levels of immunity in the face of waning immunity.

Claims that Herodotus reveals himself as a proto-biographer are not yet widely accepted. To advance this claim, I have selected two men, Miltiades the Elder and his nephew, Miltiades the Younger whose activities are recounted in the Histories. It is the latter, one of only a few Athenians with any battle experience, who taking refuge back in Athens, finds himself in a leadership role during the first Persian invasion of Greece. It is to a near contemporary to whom we attribute the maxim—character is human destiny. It is the truth of this maxim—which implies effective human agency—that makes Herodotus’ creation of historical narrative possible. He is often read for his off-topic vignettes, which color-in the character of the individuals depicted without necessarily advancing his narrative. But by leap frogging through two of the nine books of the Histories, we can assemble a largely continuous narrative for these two remarkable individuals. This narrative permits us to attribute both credit and moral responsibility for their actions. Arguably, this implied causation demonstrates that Herodotus’ writings include much that amounts to proto-biography.

Background: The Oral Health Observatory (OHO), launched in 2014 by FDI World Dental Federation, aims to provide a coordinated approach to international oral health data collection. A feasibility project involving 12 countries tested the implementation of the methodology and data collection tools and assessed data quality from 6 countries. Methods: National dental associations (NDAs) recruited dentists following a standardised sampling method. Dentists and patients completed paired questionnaires (N = 7907) about patients’ demographics, dental attendance, oral health–related behaviours, oral impacts, and clinical measures using a mobile app. In addition, participating dentists (n = 93) completed an evaluation survey, and NDAs completed a survey and participated in workshops to assess implementation feasibility. Results: Feasibility data are presented from the 12 participating countries. In addition, the 6 countries most advanced with data collection as of July 2020 (China, Colombia, India, Italy, Japan, and Lebanon) were included in the assessment of data quality and qualitative evaluation of implementation feasibility. All NDAs in these 6 countries reported interest in collecting standardised, international data for policy and communication activities and to understand service use and needs. Eighty-two percent of dentists (n = 76) reported a patient response rate of between 80% and 100%. More than 70% (n = 71) of dentists were either satisfied or very satisfied with the patient recruitment and data collection methods. There were variations in patient oral health and behaviours across countries, such as self-reporting twice-daily brushing which ranged from 45% in India to 83% in Colombia. Conclusions: OHO provides a feasible model for collecting international standardised data in dental practices. Reducing time implications, ensuring mobile app reliability, and allowing practitioners to access patient-reported outcomes to inform practice may enhance implementation.

Summary: Background: The principal barrier to an HIV cure is the presence of the latent viral reservoir (LVR), which has been understudied in African populations. From 2018 to 2019, Uganda instituted a nationwide rollout of ART consisting of Dolutegravir (DTG) with two NRTI, which replaced the previous regimen of one NNRTI and the same two NRTI. Methods: Changes in the inducible replication-competent LVR (RC-LVR) of ART-suppressed Ugandans with HIV (n = 88) from 2015 to 2020 were examined using the quantitative viral outgrowth assay. Outgrowth viruses were examined for viral evolution. Changes in the RC-LVR were analyzed using three versions of a Bayesian model that estimated the decay rate over time as a single, linear rate (model A), or allowing for a change at time of DTG initiation (model B&C). Findings: Model A estimated the slope of RC-LVR change as a non-significant positive increase, which was due to a temporary spike in the RC-LVR that occurred 0–12 months post-DTG initiation (p

IntroductionThere have been few controlled evaluations of Social Prescribing (SP), in which link workers support lonely individuals to engage with community-based social activities. This study reports early outcomes of a trial comparing General Practitioner treatment-as-usual (TAU) with TAU combined with Social Prescribing (SP) in adults experiencing loneliness in Queensland.MethodsParticipants were 114 individuals who were non-randomly assigned to one of two conditions (SP, n = 63; TAU, n = 51) and assessed at baseline and 8 weeks, on primary outcomes (loneliness, well-being, health service use in past 2 months) and secondary outcomes (social anxiety, psychological distress, social trust).ResultsRetention was high (79.4%) in the SP condition. Time × condition interaction effects were found for loneliness and social trust, with improvement observed only in SP participants over the 8-week period. SP participants reported significant improvement on all other outcomes with small-to-moderate effect sizes (ULS-8 loneliness, wellbeing, psychological distress, social anxiety). However, interaction effects did not reach significance.DiscussionSocial prescribing effects were small to moderate at the 8-week follow up. Group-based activities are available in communities across Australia, however, further research using well-matched control samples and longer-term follow ups are required to provide robust evidence to support a wider roll out.

Abstract The Hikurangi Margin east of New Zealand's North Island hosts an extensive gas hydrate province with numerous gas hydrate accumulations related to the faulted structure of the accretionary wedge. One such hydrate feature occurs in a small perched upper‐slope basin known as Urutī Basin. We investigated this hydrate accumulation by combining a long‐offset seismic line (10‐km‐long receiver array) with a grid of high‐resolution seismic lines acquired with a 600‐m‐long hydrophone streamer. The long‐offset data enable quantitative velocity analysis, while the high‐resolution data constrain the three‐dimensional geometry of the hydrate accumulation. The sediments in Urutī Basin dip landward due to ongoing deformation of the accretionary wedge. These strata are clearly imaged in seismic data where they cross a distinct bottom simulating reflection (BSR) that dips counterintuitively in the opposite direction to the regional dip of the seafloor. BSR‐derived heat flow estimates reveal a distinct heat flow anomaly that coincides spatially with the upper extent of a landward‐verging thrust fault. We present a conceptual model of this gas hydrate system that highlights the roles of fault‐controlled fluid flow at depth merging into strata‐controlled fluid flow into the hydrate stability zone. The result is a layer‐constrained accumulation of concentrated gas hydrate in the dipping strata. Our study provides new insight into the interplay between deep faulting, fluid flow and gas hydrate formation within an active accretionary margin.

Non-invasive vagus nerve stimulation (nVNS) is an established neurostimulation therapy used in the treatment of epilepsy, migraine and cluster headache. In this randomized, double-blind, sham-controlled trial we explored the role of nVNS in the treatment of gait and other motor symptoms in Parkinson’s disease (PD) patients. In a subgroup of patients, we measured selected neurotrophins, inflammatory markers and markers of oxidative stress in serum. Thirty-three PD patients with freezing of gait (FOG) were randomized to either active nVNS or sham nVNS. After baseline assessments, patients were instructed to deliver six 2 min stimulations (12 min/day) of the active nVNS/sham nVNS device for 1 month at home. Patients were then re-assessed. After a one-month washout period, they were allocated to the alternate treatment arm and the same process was followed. Significant improvements in key gait parameters (speed, stance time and step length) were observed with active nVNS. While serum tumor necrosis factor- α decreased, glutathione and brain-derived neurotrophic factor levels increased significantly (p

Abstract Chemical probes have reached a prominent role in biomedical research, but their impact is governed by experimental design. To gain insight into the use of chemical probes, we conducted a systematic review of 662 publications, understood here as primary research articles, employing eight different chemical probes in cell-based research. We summarised (i) concentration(s) at which chemical probes were used in cell-based assays, (ii) inclusion of structurally matched target-inactive control compounds and (iii) orthogonal chemical probes. Here, we show that only 4% of analysed eligible publications used chemical probes within the recommended concentration range and included inactive compounds as well as orthogonal chemical probes. These findings indicate that the best practice with chemical probes is yet to be implemented in biomedical research. To achieve this, we propose ‘the rule of two’: At least two chemical probes (either orthogonal target-engaging probes, and/or a pair of a chemical probe and matched target-inactive compound) to be employed at recommended concentrations in every study.

Abstract Multiple FDA-approved SARS-CoV-2 vaccines currently provide excellent protection against severe disease. Despite this, immunity can wane relatively fast, particularly in the elderly and novel viral variants capable of evading infection- and vaccination-induced immunity continue to emerge. Intranasal (IN) vaccination more effectively induces mucosal immune responses than parenteral vaccines, which would improve protection and reduce viral transmission. Here, we developed a rationally designed IN adjuvant consisting of a combined nanoemulsion (NE)-based adjuvant and an RNA-based RIG-I agonist (IVT DI) to drive more robust, broadly protective antibody and T cell responses. We previously demonstrated this combination adjuvant (NE/IVT) potently induces protective immunity through synergistic activation of an array of innate receptors. We now demonstrate that NE/IVT with the SARS-CoV-2 receptor binding domain (RBD), induces robust and durable humoral, mucosal, and cellular immune responses of equivalent magnitude and quality in young and aged mice. This contrasted with the MF59-like intramuscular adjuvant, Addavax, which showed a decrease in immunogenicity with age. Robust antigen-specific IFN-γ/IL-2/TNF-α was induced in both young and aged NE/IVT-immunized animals, which is significant as their reduced production is associated with suboptimal protective immunity in the elderly. These findings highlight the potential of adjuvanted mucosal vaccines for improving protection against COVID-19.

Combining genomic and geospatial data can be useful for understanding Mycobacterium tuberculosis transmission in high-burden tuberculosis (TB) settings. We performed whole-genome sequencing on M. tuberculosis DNA extracted from sputum cultures from a population-based TB study conducted in Gaborone, Botswana, during 2012–2016. We determined spatial distribution of cases on the basis of shared genotypes among isolates. We considered clusters of isolates with ≤5 single-nucleotide polymorphisms identified by whole-genome sequencing to indicate recent transmission and clusters of ≥10 persons to be outbreaks. We obtained both molecular and geospatial data for 946/1,449 (65%) participants with culture-confirmed TB; 62 persons belonged to 5 outbreaks of 10–19 persons each. We detected geospatial clustering in just 2 of those 5 outbreaks, suggesting heterogeneous spatial patterns. Our findings indicate that targeted interventions applied in smaller geographic areas of high-burden TB identified using integrated genomic and geospatial data might help interrupt TB transmission during outbreaks.

Link worker social prescribing programs are gaining recognition in Australia for addressing health and social needs outside routine medical care. The evaluation of these programs is essential for informing future social prescribing programs, research and evolving policy. However, diverse outcome evaluation measures present challenges for benchmarking across link worker social prescribing programs. An integrative review was conducted to identify and describe outcome domains and measures, and the methodological approaches and evaluation designs of link worker social prescribing programs in Australia. Comprehensive searches of the literature on link worker social prescribing programs in Australia were conducted across 14 electronic databases. In order to reduce the risk of bias, study selection and data extraction were conducted independently by multiple authors, and included studies underwent quality and risk of bias assessment using the standardised Mixed Methods Appraisal Tool. Six studies met the inclusion criteria. Outcome domains were categorised into 'person-level', 'system-level' and 'program implementation' domains. Despite the variation in participant groups, the 'person-level' domains of global well-being and social well-being were consistently evaluated. While measurement tools varied significantly, the WHO Quality of Life Brief Assessment and short-form UCLA Loneliness Scale were most commonly applied. At the system level, health service utilisation was primarily evaluated. This integrative review reports on the current state of evidence in Australia, with the potential to track changes and trends over time. Developing a core outcome set, incorporating stakeholder and consumer contributions for benchmarking aligned with the healthcare landscape is recommended. The findings may guide the refining of social prescribing initiatives and future research, ensuring methodological robustness and alignment with individual and community needs.

ABSTRACT Early COVID-19 convalescent plasma (CCP) transfusion to outpatients with COVID-19 decreases progression to hospitalization, but the mechanism of how CCP reduces severity is unknown. Among 882 COVID-19 participants transfused with CCP or control plasma in a randomized controlled trial, 21 cytokines and chemokines were measured using electrochemiluminescence assays. Wilcoxon rank sum tests were used to evaluate the difference between early (transfused within 5 days of symptom onset) CCP vs early control plasma and late (transfused 6–9 days after symptom onset) CCP vs late control plasma at each visit. Linear mixed-effect models were used to assess the difference in the slope of cytokine change. Median cytokine and chemokine levels were similar between the early CCP and early control groups pre-transfusion. At the day 14 visit, only the median IL-6 (P = 0.014) and IL-16 (P = 0.036) levels were lower in the early CCP group compared to the early control group, but these differences were not statistically significant after correcting for multiple comparisons (requiring P < 0.0024). IL-6 levels decreased significantly faster in the early CCP group from screening to the day 14 visit compared to the early control group (P < 0.001). No difference was observed in the slope of cytokine change from screening to day 90 between early CCP and early control groups. Late control and late CCP arms showed similar cytokine and chemokine levels through study follow-up. One mechanism by which early CCP transfusion reduces hospitalization may be by decreasing IL-6 levels, as the reduction is associated with better recovery from COVID-19. IMPORTANCE This study examined the role that cytokines may have played in the beneficial outcomes found when outpatient individuals infected with SARS-CoV-2 were transfused with COVID-19 convalescent plasma (CCP) early in their infection. We found that the pro-inflammatory cytokine IL-6 decreased significantly faster in patients treated early with CCP. Participants with COVID-19 treated with CCP later in the infection did not have the same effect. This decrease in IL-6 levels after early CCP treatment suggests a possible role of inflammation in COVID-19 progression. The evidence of IL-6 involvement brings insight into the possible mechanisms involved in CCP treatment mitigating SARS-CoV-2 severity.

Abstract Beneficial effects on health outcomes have been observed from exposure to spaces with substantial green vegetation (“greenspace”). This includes studies of greenspace exposure on birth outcomes; however, these have been conducted largely in urban regions. We characterized residential exposure to greenspace and land cover diversity during pregnancy in rural northern New England, USA, investigating whether variation in greenspace or diversity related to newborn outcomes. Five landscape variables (greenspace land cover, land cover diversity, impervious surface area, tree canopy cover, and the Normalized Difference Vegetation Index) were aggregated within six circular zones of radii from 100 to 3,000 m around residential addresses, and distance to conservation land was measured, providing a total of 31 greenspace and diversity metrics. Four birth outcomes along with potentially confounding variables were obtained from 1,440 participants in the New Hampshire Birth Cohort Study. Higher greenspace land cover up to 3,000 m was associated with larger newborn head circumference, while impervious surface area (non‐greenspace) had the opposite association. Further, birth length was positively associated with land cover diversity. These findings support beneficial health impacts of greenspace exposure observed in urban regions for certain health outcomes, such as newborn head circumference and length but not others such as birthweight and gestational age. Further our results indicate that larger radius buffer zones may be needed to characterize the rural landscape. Vegetation indices may not be interchangeable with other greenspace metrics such as land cover and impervious surface area in rural landscapes.

We present a case report of a 48-year-old male marathon runner who was seen for initial evaluation in August of 2022 with a 3-day history of significant right arch pain limiting ambulation without a history of a traumatic event or inciting incident. Subsequent work-up with magnetic resonance imaging [MRI] without contrast revealed a plantar vein thrombosis [PVT]. The patient was placed on Eliquis [Apixaban] 5mg for 4 months with full resolution of his symptoms. With the use of oral anticoagulant therapy, the patient was able to compete in and complete 5 marathons over an 18-month period without return of the PVT.