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Zusammenfassung„One Health“ bezeichnet ein Konzept, das die Gesundheit von Menschen, Tieren und der Umwelt miteinander verbindet. In Deutschland gibt es umfangreiche Daten zur Antibiotikaresistenz (AMR) und multiresistenten Erregern (MRE) in der Human- und Veterinärmedizin sowie aus Untersuchungen in verschiedenen Umweltkompartimenten (Boden, Wasser, Abwasser). Die Erhebung erfolgt nach unterschiedlichen Vorgaben und Standards, was den Vergleich von Daten erschwert. Ein Fokus auf humantherapeutisch wichtige AMR und MRE ist hilfreich, um eine gewisse Orientierung vorzugeben. Die meisten Daten liegen sektorübergreifend zu Methicillin-resistenten Staphylococcus aureus und multiresistenten Enterobacterales wie Escherichia coli und Klebsiella pneumoniae vor. Hier sind die Trends der Resistenzen heterogen. Der Einsatz von Antibiotika führt zur Selektion von MRE, was gut dokumentiert ist. Erfolge bei der Minimierung des Antibiotikaeinsatzes konnten in zurückliegenden Jahren für einzelne Sektoren dargestellt und z. T. mit Erfolgen in der Eindämmung von AMR und MRE korreliert werden (Rückgang MRSA in der Humanmedizin). Auch sektorspezifische Maßnahmen zur Senkung der Last durch MRE und AMR sind notwendig, da Resistenzprobleme nicht generell eine Verknüpfung mit anderen Sektoren aufweisen. Carbapenemresistenzen sind vor allem bei pathogenen Erregern vom Menschen nachweisbar. Colistinresistenzen kommen in verschiedenen Sektoren vor, zeigen aber dort jeweils verschiedene Mechanismen. Resistenzen gegen Reservesubstanzen wie Linezolid sind in Deutschland selten, sie zeigen aber einen konkreten One-Health-Bezug. Bestrebungen zur Harmonisierung von Methoden, z. B. im Bereich der antimikrobiellen Empfindlichkeitstestung und genombasierten Erreger- und AMR-Surveillance, sind ein wichtiger erster Schritt zu einer Vergleichbarkeit der verschiedenen Datenerhebungen.

Purpose Acute poisonings of workers handling shipping containers by fumigants and other harmful chemicals off-gassed from cargo have been reported but (sub)-chronic neuropsychological effects have not been well studied. Methods This cross-sectional study assessed, using standardised questionnaires, current (past 3-months) neuropsychological symptoms in 274 container handlers, 38 retail workers, 35 fumigators, and 18 log workers, all potentially exposed to fumigants and off-gassed chemicals, and a reference group of 206 construction workers. Prevalence odds ratios (OR), adjusted for age, ethnicity, smoking, alcohol consumption, education, personality traits and BMI, were calculated to assess associations with the total number of symptoms (≥ 3, ≥ 5 or ≥ 10) and specific symptom domains (neurological, psychosomatic, mood, memory/concentration, fatigue, and sleep). Results Compared to the reference group, exposed workers were more likely to report ≥ 10 symptoms, statistically significant only for retail workers (OR 6.8, 95% CI 1.9–24.3) who also reported more fatigue (OR 10.7, 95% CI 2.7–42.7). Container handlers with the highest exposure-duration were more likely to report ≥ 10 symptoms, both when compared with reference workers (OR 4.0, 95% CI 1.4–11.7) and with container handlers with shorter exposure duration (OR 7.5, 95% CI 1.7–32.8). The duration of container handling was particularly associated with symptoms in the memory/concentration domain, again both when compared to reference workers (OR 8.8, 95% CI 2.5–31.4) and workers with the lowest exposure-duration (OR 6.8, 95% CI 1.5–30.3). Conclusion Container handlers may have an increased risk of neuropsychological symptoms, especially in the memory/concentration domain. Retail workers may also be at risk, but this requires confirmation in a larger study.

Review the most recent evidence on the role of sedentary behavior in the prevention of cardiovascular disease (CVD).Prospective cohort studies continue to suggest a relationship between sedentary behavior and CVD, but the dose-response association, and the implications of sedentary pattern (vs. total volume) and context on CVD risk require further investigation. Most recent evidence suggests that physical activity influences the association between sedentary time and CVD risk, and that replacing sedentary time with other movement behaviors yields cardiometabolic benefits. Short-term intervention studies have further demonstrated that interrupting prolonged sitting with bouts of physical activity can elicit acute improvements on cardiometabolic biomarkers and vascular function relative to prolonged, uninterrupted sitting, albeit limited evidence exists on the long-term effects. More conclusive evidence regarding the implications of sedentary time on CVD risk is warranted before the optimal sedentary behavior reduction prescription for the prevention of CVD can be elucidated.

Deep venous thrombosis and residual thrombus burden correlates with circulating IL-6 levels in humans. To investigate the cellular source and role of IL-6 in thrombus resolution, Wild type C57BL/6J (WT), and IL-6−/− mice underwent induction of VT via inferior vena cava (IVC) stenosis or stasis. Vein wall (VW) and thrombus were analyzed by western blot, immunohistochemistry, and flow cytometry. Adoptive transfer of WT bone marrow derived monocytes was performed into IL6-/- mice to assess for rescue. Cultured BMDMs from WT and IL-6−/− mice underwent quantitative real time PCR and immunoblotting for fibrinolytic factors and matrix metalloproteinase activity. No differences in baseline coagulation function or platelet function were found between WT and IL-6−/− mice. VW and thrombus IL-6 and IL-6 leukocyte-specific receptor CD126 were elevated in a time-dependent fashion in both VT models. Ly6Clo Mo/MØ were the predominant leukocyte source of IL-6. IL-6−/− mice demonstrated larger, non-resolving stasis thrombi with less neovascularization, despite a similar number of monocytes/macrophages (Mo/MØ). Adoptive transfer of WT BMDM into IL-6−/− mice undergoing stasis VT resulted in phenotype rescue. Human specimens of endophlebectomized tissue showed co-staining of Monocyte and IL-6 receptor. Thrombosis matrix analysis revealed significantly increased thrombus fibronectin and collagen in IL-6−/− mice. MMP9 activity in vitro depended on endogenous IL-6 expression in Mo/MØ, and IL-6−/− mice exhibited stunted matrix metalloproteinase activity. Lack of IL-6 signaling impairs thrombus resolution potentially via dysregulation of MMP-9 leading to impaired thrombus recanalization and resolution. Restoring or augmenting monocyte-mediated IL-6 signaling in IL-6 deficient or normal subjects, respectively, may represent a non-anticoagulant target to improve thrombus resolution.

Background Rural Latino children have higher rates of obesity compared to non-Latino Whites. Schools are in a unique position to address rural childhood obesity through policies. While evidence exists on factors that promote or impede school-based physical activity (PA) and nutrition policies, only a fraction has been in rural communities. This study seeks to understand 1) the knowledge and perceptions of school nutrition and PA policies and 2) barriers and facilitators to their implementation among rural school stakeholders from Washington State. Methods We conducted 20 semi-structured, in-depth interviews with school stakeholders (e.g., principals and school nutrition directors) from four K–12 school districts in the Lower Yakima Valley of Eastern Washington State. Thematic analysis was conducted using inductive, constant comparison approach to identify themes around knowledge and perceptions of policies and barriers and facilitators of policy implementation. Results Three main themes were identified: perceptions and knowledge of school PA and nutrition policies, barriers to policy implementation, and facilitators of policy implementation. The majority of stakeholders were supportive of school-based policies promoting PA and a healthy diet, even when lacking a specific understanding of these policies. Four subthemes were identified as barriers to policy implementation: viewing PA as a low priority, misuse of recess time, funding constraints, and lack of strong leadership. Facilitators of implementation included strong leadership at the district level, creating healthy norms through school-community linkages and pooling community resources to improve nutrition and PA among children. Conclusions Schools provide a unique setting to promote healthy diet and PA behaviors among children and their families. Study findings show that while knowledge of specific nutrition and PA policies may vary, support for such policies were high among rural stakeholders. Study findings can inform policy development and support strategies for policy implementation in rural settings. Future studies may want to examine whether implementation of strategies addressing the barriers and enhancing facilitators lead to success in rural school settings.

Background Few real-world examples exist of how best to select and adapt implementation strategies that promote sustainability. We used a collaborative care (CC) use case to describe a novel, theory-informed, stakeholder engaged process for operationalizing strategies for sustainability using a behavioral lens. Methods Informed by the Dynamic Sustainability Framework, we applied the Behaviour Change Wheel to our prior mixed methods to identify key sustainability behaviors and determinants of sustainability before specifying corresponding intervention functions, behavior change techniques, and implementation strategies that would be acceptable, equitable and promote key tenets of sustainability (i.e., continued improvement, education). Drawing on user-centered design principles, we enlisted 22 national and local stakeholders to operationalize and adapt (e.g., content, functionality, workflow) a multi-level, multi-component implementation strategy to maximally target behavioral and contextual determinants of sustainability. Results After reviewing the long-term impact of early implementation strategies (i.e., external technical support, quality monitoring, and reimbursement), we identified ongoing care manager CC delivery, provider treatment optimization, and patient enrollment as key sustainability behaviors. The most acceptable, equitable, and feasible intervention functions that would facilitate ongoing improvement included environmental restructuring, education, training, modeling, persuasion, and enablement. We determined that a waiting room delivered shared decision-making and psychoeducation patient tool (DepCare), the results of which are delivered to providers, as well as ongoing problem-solving meetings/local technical assistance with care managers would be the most acceptable and equitable multi-level strategy in diverse settings seeking to sustain CC programs. Key adaptations in response to dynamic contextual factors included expanding the DepCare tool to incorporate anxiety/suicide screening, triage support, multi-modal delivery, and patient activation (vs. shared decision making) (patient); pairing summary reports with decisional support and yearly onboarding/motivational educational videos (provider); incorporating behavioral health providers into problem-solving meetings and shifting from billing support to quality improvement and triage (system). Conclusion We provide a roadmap for designing behavioral theory-informed, implementation strategies that promote sustainability and employing user-centered design principles to adapt strategies to changing mental health landscapes.

Objectives To evaluate the disease activity before and after COVID-19 and risk factors associated with outcomes, including hospitalization, intensive care unit (ICU) admission, mechanical ventilation (MV) and death in patients with spondylarthritis (SpA). Methods ReumaCoV Brazil is a multicenter prospective cohort of immune-mediated rheumatic diseases (IMRD) patients with COVID-19 (case group), compared to a control group of IMRD patients without COVID-19. SpA patients enrolled were grouped as axial SpA (axSpA), psoriatic arthritis (PsA) and enteropathic arthritis, according to usual classification criteria. Results 353 SpA patients were included, of whom 229 (64.9%) were axSpA, 118 (33.4%) PsA and 6 enteropathic arthritis (1.7%). No significant difference was observed in disease activity before the study inclusion comparing cases and controls, as well no worsening of disease activity after COVID-19. The risk factors associated with hospitalization were age over 60 years (OR = 3.71; 95% CI 1.62–8.47, p = 0.001); one or more comorbidities (OR = 2.28; 95% CI 1.02–5.08, p = 0.001) and leflunomide treatment (OR = 4.46; 95% CI 1.33–24.9, p = 0.008). Not having comorbidities (OR = 0.11; 95% CI 0.02–0.50, p = 0.001) played a protective role for hospitalization. In multivariate analysis, leflunomide treatment (OR = 8.69; CI = 95% 1.41–53.64; p = 0.023) was associated with hospitalization; teleconsultation (OR = 0.14; CI = 95% 0.03–0.71; p = 0.01) and no comorbidities (OR = 0.14; CI = 95% 0.02–0.76; p = 0.02) remained at final model as protective factor. Conclusions Our results showed no association between pre-COVID disease activity or that SARS-CoV-2 infection could trigger disease activity in patients with SpA. Teleconsultation and no comorbidities were associated with a lower hospitalization risk. Leflunomide remained significantly associated with higher risk of hospitalization after multiple adjustments.

Let $S$ be the first degeneracy locus of a morphism of vector bundles corresponding to a general matrix of linear forms in $\mathbb{P}^s$. We prove that, under certain positivity conditions, its Hilbert square $\mathrm{Hilb}^2(S)$ is isomorphic to the zero locus of a global section of an irreducible homogeneous vector bundle on a product of Grassmannians. Our construction involves a naturally associated Fano variety, and an explicit description of the isomorphism., Comment: 20 pages, comments welcome!

Interactions between a T cell receptor (TCR) and a peptide-major histocompatibility complex (pMHC) ligand are typically mediated by noncovalent bonds. By studying T cells expressing natural or engineered TCRs, here we describe covalent TCR-pMHC interactions that involve a cysteine-cysteine disulfide bond between the TCR and the peptide. By introducing cysteines into a known TCR-pMHC combination, we demonstrate that disulfide bond formation does not require structural rearrangement of the TCR or the peptide. We further show these disulfide bonds still form even when the initial affinity of the TCR-pMHC interaction is low. Accordingly, TCR-peptide disulfide bonds facilitate T cell activation by pMHC ligands with a wide spectrum of affinities for the TCR. Physiologically, this mechanism induces strong Zap70-dependent TCR signaling, which triggers T cell deletion or agonist selection in the thymus cortex. Covalent TCR-pMHC interactions may thus underlie a physiological T cell activation mechanism that has applications in basic immunology and potentially in immunotherapy.

20 Pág. Departamento de Medio Ambiente y Agronomía​, Restoration of degraded drylands is urgently needed to mitigate climate change, reverse desertification and secure livelihoods for the two billion people who live in these areas. Bold global targets have been set for dryland restoration to restore millions of hectares of degraded land. These targets have been questioned as overly ambitious, but without a global evaluation of successes and failures it is impossible to gauge feasibility. Here we examine restoration seeding outcomes across 174 sites on six continents, encompassing 594,065 observations of 671 plant species. Our findings suggest reasons for optimism. Seeding had a positive impact on species presence: in almost a third of all treatments, 100% of species seeded were growing at first monitoring. However, dryland restoration is risky: 17% of projects failed, with no establishment of any seeded species, and consistent declines were found in seeded species as projects matured. Across projects, higher seeding rates and larger seed sizes resulted in a greater probability of recruitment, with further influences on species success including site aridity, taxonomic identity and species life form. Our findings suggest that investigations examining these predictive factors will yield more effective and informed restoration decision-making., We would like to thank the supporters of the Global Arid Zone Project. The intellectual and energetic input of the network participants made this work possible. We also acknowledge the many employers and funding agencies that supported projects and the authors’ time in preparing this work and contributing data to the GAZP database. Please note that any use of trade, firm or product names is for descriptive purposes only and does not imply endorsement by the US Government

We prove that, given integers $m\geq 3$, $r\geq 1$ and $n\geq 0$, the moduli space of torsion free sheaves on $\mathbb P^m$ with Chern character $(r,0,\ldots,0,-n)$ that are trivial along a hyperplane $D \subset \mathbb P^m$ is isomorphic to the Quot scheme $\mathrm{Quot}_{\mathbb A^m}(\mathscr O^{\oplus r},n)$ of $0$-dimensional length $n$ quotients of the free sheaf $\mathscr O^{\oplus r}$ on $\mathbb A^m$., Minor improvements. Final version

Brain atlases have proven to be valuable neuroscience tools for localizing regions of interest and performing statistical inferences on populations. Although many human brain atlases exist, most do not contain information about white matter structures, often neglecting them completely or labelling all white matter as a single homogenous substrate. While few white matter atlases do exist based on diffusion MRI fiber tractography, they are often limited to descriptions of white matter as spatially separate “regions” rather than as white matter “bundles” or fascicles, which are well-known to overlap throughout the brain. Additional limitations include small sample sizes, few white matter pathways, and the use of outdated diffusion models and techniques. Here, we present a new population-based collection of white matter atlases represented in both volumetric and surface coordinates in a standard space. These atlases are based on 2443 subjects, and include 216 white matter bundles derived from 6 different state-of-the-art tractography techniques. This atlas is freely available and will be a useful resource for parcellation and segmentation.

The cross-stressor adaptation hypothesis of exercise training has not been investigated under real-life conditions. Using ecological momentary assessment (EMA), we tested whether usual exercise level moderates the relationship of self-reported anxiety to concurrent ambulatory heart rate (HR) and systolic/diastolic blood pressure (SBP/DBP). Participants (N=832) completed 24-hour ambulatory monitoring of HR/BP, using a brachial BP cuff that took readings at 28-minute intervals. Anxiety levels were concurrently reported on a visual analog scale (VAS) using a Palm Pilot. Usual exercise behavior was assessed by a self-report questionnaire. Random coefficients linear regression models predicting momentary HR/BP readings from time-matched anxiety scores were estimated, yielding the average within-person effect (slope) of anxiety. The interaction of exercise level (i.e., no weekly exercise, 1–149, and ≥150 minutes/week; a between-person factor) with anxiety was added to the model in order to estimate the average anxiety slope for participants in each exercise category. The relationship of HR/BP to anxiety did not differ significantly among exercise categories, hence not providing evidence for the cross-stressor hypothesis. In an exploratory analysis of the difference in HR/BP between occasions when anxiety was in the top versus bottom person-specific quintiles of responses, the difference in HR (but not SBP or DBP) varied significantly by exercise level (F(2,625)=4.92, p=0.008). Though our pre-specified analysis did not support the hypothesis, we provide some post-hoc evidence supporting the cross-stressor hypothesis of exercise training for the HR response to anxiety.

Introduction: We used data from MOBI-Kids, a 14-country international collaborative case-control study of brain tumors (BTs), to study clinical characteristics of the tumors in older children (10 years or older), adolescents and young adults (up to the age of 24). Methods: Information from clinical records was obtained for 899 BT cases, including signs and symptoms, symptom onset, diagnosis date, tumor type and location. Results: Overall, 64% of all tumors were low-grade, 76% were neuroepithelial tumors and 62% gliomas. There were more males than females among neuroepithelial and embryonal tumor cases, but more females with meningeal tumors. The most frequent locations were cerebellum (22%) and frontal (16%) lobe. The most frequent symptom was headaches (60%), overall, as well as for gliomas, embryonal and 'non-neuroepithelial' tumors; it was convulsions/seizures for neuroepithelial tumors other than glioma, and visual signs and symptoms for meningiomas. A cluster analysis showed that headaches and nausea/vomiting was the only combination of symptoms that exceeded a cutoff of 50%, with a joint occurrence of 67%. Overall, the median time from first symptom to diagnosis was 1.42 months (IQR 0.53-4.80); it exceeded 1 year in 12% of cases, though no particular symptom was associated with exceptionally long or short delays.Conclusions: This is the largest clinical epidemiology study of BT in young people conducted so far. Many signs and symptoms were identified, dominated by headaches and nausea/vomiting. Diagnosis was generally rapid but in 12% diagnostic delay exceeded 1 year with none of the symptoms been associated with a distinctly long time until diagnosis. This work was supported by the MOBI-Kids study and the work in this study was obtained from the European Community's Seventh Framework Programme under Grant Agreements Number 226873—the MOBI-Kids Project—and 603794—the GERoNiMO project. Additional funds for the coordination of MOBI-Kids were obtained from the Spanish Ministry of Science and Innovation (MINECO), while complementary funds for the conduct of MOBI-Kids in Spain were obtained from the Spanish Health Research Fund (FIS) of the National Institute for Health Carlos III. Italian participation is partially supported by a Ministry of Health grant (RF-2009-1546284). In Canada, funding was provided by a grant from the Canadian Institutes for Health Research under a peer-reviewed university-industry partnership program that involved the Canadian Wireless Telecommunications Association, who provided technical data on wireless telecommunications practices in Canada. The German study centre received additional support by the Federal Office for Radiation Protection (BfS). Japanese participation in MOBI-Kids was supported by the Ministry of Internal Affairs and Communications. New Zealand participation was supported by Health Research Council and Cure Kids. In France, this study received funds from the French National Agency for Sanitary Safety of Food, Environment and Labour (ANSES, contract FSRF2008-3), French National Cancer Institute (INCa), Pfizer Foundation and League against cancer. India received funding from Board of Research in Nuclear Sciences (BRNS). The funding sources had no role in: the study design; the collection, analysis, and interpretation of data; the writing of the report; and the decision to submit the article for publication.

Venous thromboembolism (VTE) is a significant cause of mortality1, yet its genetic determinants remain incompletely defined. We performed a discovery genome-wide association study in the Million Veteran Program and UK Biobank testing ~13 million DNA sequence variants for association with VTE (26,066 cases; 624,053 controls) and meta-analyzed both studies, followed by independent replication with up to 17,672 VTE cases and 167,295 controls. We identified 22 novel loci, bringing the total number of VTE-associated loci to 33 and subsequently fine-mapped these associations. We developed a genome-wide polygenic risk score for VTE that identifies 5% of the population at equivalent incident VTE risk to carriers of the established F5 Leiden (p.R506Q) and prothrombin G20210A mutations. Our data provide new mechanistic insights into the genetic epidemiology of VTE and suggest a greater overlap among venous and arterial cardiovascular disease than previously suggested., Editorial summary Genome-wide analysis of venous thromboembolism identifies 22 new risk loci and facilitates construction of a polygenic risk score. Comparison to arterial vascular disease highlights shared pathophysiology and potential therapeutic strategies.

Background Pediatric acute kidney injury (AKI) is associated with long-term morbidity and mortality; however, outcomes improve when AKI is detected earlier. Current definitions of AKI use baseline creatinine; community-acquired AKI (CA-AKI) is difficult to define and detect in the pediatric emergency department (ED) when no baseline creatinine is available. Our objective was to compare age- and gender-based creatinine norms to the traditional baseline (lowest creatinine in previous 3 months) to diagnose CA-AKI. Methods This was a retrospective cross-sectional study conducted in children 1 month-18 years of age seen in the pediatric ED in whom a creatinine was obtained. Results Per the Kidney Disease Improving Global Outcomes AKI definition in encounters with baseline creatinine available, 343/2338 (14.7%) had CA-AKI. When the upper limit of the age- and gender-based creatinine norm was applied as a surrogate baseline creatinine, CA-AKI was diagnosed in 1.5% of encounters (239/15,486). Additionally, CA-AKI was diagnosed in 178 cases using the upper limit of age- and gender-based creatinine norms only, as these cases did not have a baseline creatinine. Conclusions Age- and gender-based creatinine norms can be applied as a surrogate baseline to detect CA-AKI in all children regardless of whether baseline creatinine is available, potentially detecting it earlier.

Assessment of treating metastatic ileal neuroendocrine tumors (NETs) with complete resection of primary tumor, nodal and liver metastases, plus administration of long-acting somatostatin analogues (SSAs). A prospective database was queried for patients with ileal or pancreatic NETs with pathology-confirmed liver metastases and tumor somatostatin receptors. Patients did not have MEN-1 and had no previous treatment. The impacts of SSA treatment on the primary outcome of survival and secondary outcome of progression-free survival were assessed with Kaplan–Meier analysis. Log rank test was used to compare overall and progression-free survival among groups. Seventeen ileal NET patients and 36 pancreatic NET patients who underwent surgical resection between 2001 and 2018, who had pathology-confirmed liver metastases and confirmed tumor somatostatin receptors, did not have MEN-1, and had no previous treatment were identified. Median follow-up for patients with ileal NETs was 80 months (range 0–197 months) and 32 months (range 1–182 months) for pancreatic NETs. Five-year survival was 93% and 72% for ileal and pancreatic NET, respectively. Progression-free 5-year survival was 70% and 36% for ileal and pancreatic NET, respectively. Overall 5-year survival for pNETs was greater in those patients treated with SSA (79%) compared to those who underwent surgery alone (34%, p

Myocardin is a potent transcriptional coactivator protein, which functions as the master regulator of vascular smooth muscle cell differentiation. The cofactor activity of myocardin is mediated by its physical interaction with serum response factor, a ubiquitously expressed transactivator that binds to CArG boxes in genes encoding smooth muscle-restricted proteins. Purine-rich element binding protein B (Purβ) represses the transcription of the smooth muscle α-actin gene (Acta2) in fibroblasts and smooth muscle cells by interacting with single-stranded DNA sequences flanking two 5' CArG boxes in the Acta2 promoter. In this study, the ability of Purβ to modulate the cofactor activity of myocardin was investigated using a combination of cellular and biochemical approaches. Results of smooth muscle gene promoter-reporter assays indicated that Purβ specifically inhibits the coactivator function of myocardin in a manner requiring the presence of all three single-stranded DNA binding domains in the Purβ homodimer. DNA binding analyses demonstrated that Purβ interacts with CArG-containing DNA elements with a much lower affinity compared to other purine-rich target sequences present in the Acta2 promoter. Co-immunoprecipitation and DNA pull-down assays revealed that Purβ associates with myocardin and serum response factor when free or bound to duplex DNA containing one or more CArG boxes. Functional analysis of engineered Purβ point mutants identified several amino acid residues essential for suppression of myocardin activity. Collectively, these findings suggest an inhibitory mechanism involving direct protein-protein interaction between the homodimeric Purβ repressor and the myocardin-serum response factor-CArG complex.

Adolescents are disproportionately affected by sexually transmitted infections (STIs). Failure to diagnose and treat STIs in a timely manner may result in serious sequelae. Adolescents frequently access the emergency department (ED) for care. Although ED-based STI screening is acceptable to both patients and clinicians, understanding how best to implement STI screening processes into the ED clinical workflow without compromising patient safety or efficiency is critical. The objective of this study was to conduct direct observations documenting current workflow processes and tasks during patient visits at six Pediatric Emergency Care Applied Research Network (PECARN) EDs for site-specific integration of STI electronically-enhanced screening processes. Workflow observations were captured via TaskTracker, a time and motion electronic data collection application that allows researchers to categorize general work processes and record multitasking by providing a timestamp of when tasks began and ended. Workflow was captured during 118 patient visits across six PECARN EDs. The average time to initial assessment by the most senior provider was 76 min (range 59– 106 min, SD = 43 min). Care teams were consistent across sites, and included attending physicians, advanced practice providers, nurses, registration clerks, technicians, and students. A timeline belt comparison was performed. Across most sites, the most promising implementation of a STI screening tool was in the patient examination room following the initial patient assessment by the nurse.