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Objective: Two methods for scaling up an evidence-based occupational sun protection program were compared., Methods: Regional districts (n = 138) in 21 state Departments of Transportation throughout the United States were randomized to receive the Go Sun Smart at Work program via in-person or digital scalability methods in 2019-2022 in 1:2 ratio. Managers completed pretest and posttest surveys and employees completed posttest surveys. Due to the COVID pandemic, only posttest measures were analyzed (n = 255 managers; n = 1387 employees)., Results: After scale-up, more employees reported training (b = 0.381, p = 0.021) and communication (b = 0.112, p = 0.049) at workplaces in in-person rather than digital strategy. There were no differences in managers' reports of sun protection training, communication, or actions by scalability method (p > 0.05)., Conclusions: Occupational sun protection was implemented during program scale up and employees recalled training/communication more in the in-person than digital strategy., Competing Interests: Conflict of Interest for All Authors: D. Buller receives a salary from Klein Buendel, Inc. And his spouse is an owner of Klein Buendel, Inc. M.K. Buller receives a salary from Klein Buendel, Inc. And she is an owner of Klein Buendel, Inc. G. Cutter Board membership, advisory board fees from Alexion, Antisense Therapeutics, Avotres, Biogen, Clene Nanomedicine, Clinical Trial Solutions LLC, Endra Life Sciences, Cognito Therapeutics, Entelexo Biotherapeutics, Inc., Genzyme, Genentech, GW Pharmaceuticals, Hoya Corporation, Immunic, Immunosis Pty Ltd, Klein Buendel Inc., Linical, Merck/Serono, Novartis, Perception Neurosciences, Protalix Biotherapeutics, Regeneron, Roche, SAB Biotherapeutics, and Sapience Therapeutics., and data and safety monitoring board fees from Applied Therapeutics, AI therapeutics, AMO Pharma, Astra-Zeneca, Avexis Pharmaceuticals, Bristol Meyers Squibb/Celgene, CSL Behring, Cynata Therapeutics, Diametica Therapeutics, Horizon Pharmaceuticals, Immunic, Karuna Therapeutics, Kezar Life Sciences, Medtronic, Mapi Pharmaceuticals LTD, Medtronic, Merck, Mitsubishi Tanabe Pharma Holdings, Opko Biologics, Prothena Biosciences, Novartis, Pipeline Therapeutics, Regeneron, Sanofi-Aventis, Reata Pharmaceuticals, Teva Pharmaceuticals, United BioSource LLC, University of Texas Southwestern, University of Pennsylvania, and Visioneering Technologies, Inc. outside the submitted work. J. Berteletti, A. Kinsey, I. Adjei, and N. Chirico receive a salary from Klein Buendel, Inc. R. Meenan and K. Henry report None Declared., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American College of Occupational and Environmental Medicine.)

Bolivia has one of the highest burdens of Chagas disease in the world. Vertical transmission from mother to infant accounts for a growing number of cases. We performed a systematic review of articles assessing the prevalence of Chagas disease in pregnant women and rates of vertical transmission to infants in Bolivia. Studies were not excluded based on year of publication or language. Random-effects analyses were performed to estimate a pooled prevalence of maternal Chagas disease and pooled vertical transmission rate. Our search yielded 21 articles describing over 400,000 cases of Chagas disease among pregnant women in Bolivia. The reported prevalence of maternal Chagas disease ranged from 17.3% to 64.5%, with a pooled prevalence of 33.0% (95% CI, 27.4-38.7%). The prevalence of maternal Chagas disease trended down over time (P = 0.006), decreasing by approximately 25% to 30% over the last 40 years. Vertical transmission rates ranged from 2.0% to 13% with a pooled average of 6.2% (95% CI, 4.4-7.5%); rates did not significantly change over time. Our study is the first systematic review and meta-analysis of Chagas disease maternal prevalence and vertical transmission in Bolivia. Our findings indicate that maternal Chagas disease has fallen in prevalence but still affects 20% to 30% of pregnant women and poses a considerable risk of vertical transmission. Pregnant women and infants are an important target for public health interventions to limit the mortality and morbidity of Chagas disease and to reduce intergenerational spread.

A 1.7 Å structure is presented for an active form of the virulence factor ScpB, the C5a peptidase from Streptococcus agalactiae. The previously reported structure of the ScpB active site mutant exhibited a large separation (~20 Å) between the catalytic His and Ser residues. Significant differences are observed in the catalytic domain between the current and mutant ScpB structures resulting with a high RMSD Cα (4.6 Å). The fold of the active form of ScpB is nearly identical to ScpA (RMSD Cα 0.2 Å), the C5a-peptidase from Streptococcus pyogenes. Both ScpA and ScpB have comparable activity against human C5a, indicating neither enzyme require host proteins for C5a-ase activity. These studies are a first step in resolving reported differences in the specificities of these enzymes., (© 2023 The Authors. Proteins: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC.)

Sensing the shape of continuum soft robots without obstructing their movements and modifying their natural softness requires innovative solutions. This letter proposes to use magnetic sensors fully integrated into the robot to achieve proprioception. Magnetic sensors are compact, sensitive, and easy to integrate into a soft robot. We also propose a neural architecture to make sense of the highly nonlinear relationship between the perceived intensity of the magnetic field and the shape of the robot. By injecting a priori knowledge from the kinematic model, we obtain an effective yet data-efficient learning strategy. We first demonstrate in simulation the value of this kinematic prior by investigating the proprioception behavior when varying the sensor configuration, which does not require us to re-train the neural network. We validate our approach in experiments involving one soft segment containing a cylindrical magnet and three magnetoresistive sensors. During the experiments, we achieve mean relative errors of 4.5%.

This study aims to assess the identification rates in a developmental monitoring system (i.e., preventive child healthcare, PCH system) regarding identification of emotional, behavioral (EB) problems, cognitive developmental and family problems in children, and the contribution of such a system to referral to (specialized) mental health and social care services. Over a predetermined period of 6 months, we retrieved data from a random sample of 1370 children aged 0 to 18 years from the registries of two PCH organizations in the Netherlands. We assessed the degree to which PCH professionals identify EB and cognitive developmental and family problems and invite children with these problems for follow-up PCH assessments or refer them to (specialized) mental health and social care services. Among preschool-aged children, we identified 22% with EB problems, cognitive developmental and/or family problems (mainly EB and family problems). Among school-aged children, numbers varied from 10 to 14% (mainly EB). PCH invited 3 to 10%, varying in proportions of child age, for a follow-up assessment, and referred 0 to 4% of the children to external services., Conclusion: A developmental monitoring system with only preventive tasks may help to identify children with EB, cognitive developmental, and/or family problems. This can lead to early support for most of these children, with low referral rates to (more specialized) mental health and social care services. Our findings deserve validation in comparable settings and in other countries., What Is Known: • Well-child care requires monitoring of the health and development of children for timely identification of problems and subsequent intervention. • The Dutch Preventive Child Healthcare system is an example of a developmental monitoring system with only preventive tasks., What Is New: • A developmental monitoring system with only preventive tasks may help to identify children with problems, resulting in early support for the majority. • This may reduce referral rates to (more specialized) mental/social health services., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Reducing exposure to ultraviolet radiation (UV) is crucial for preventing UV-induced diseases of the skin and eyes. Shade may offer significant protection from UV. More empirical research to quantify the UV protection offered from built shade is needed to guide disease prevention practices and confidence in investment in shade. This study quantified UV levels under built-shade relative to unshaded passive recreation areas (PRAs) over summer months in parks in two cities. In a randomized controlled trial, n = 1144 UV measurements were conducted at the center and periphery of PRAs in a total sample of 144 public parks as part of pretest and posttest measures of use of the PRAs by park visitors for three recruitment waves per city during 2010 to 2014. Following pretest, 36 PRAs received built-shade and 108 did not. Regression analyses modelled pre-post change in UV (Standard Erythemal Dose (SED) per 30 min) at PRAs; and environmental predictors. Mean UV at the center of built-shade PRAs decreased from pretest to posttest (x¯ = 3.39, x¯ = 0.93 SED), a change of x¯ = -3.47 SED relative to control PRAs ( p < 0.001) adjusting for the covariates of ambient SED, (cosine) solar elevation and cloud cover. Clouds decreased and solar elevation increased UV levels under shade. No significant differences in UV by shade design occurred. A substantial reduction in exposure to UV can be achieved using built-shade with shade cloth designs, offering considerable protection for shade users. Supplementary sun protection is recommended for extended periods of shade use during clear sky days.

Objective: Uncoupling protein 1 (UCP1) catalyses mitochondrial proton leak in brown adipose tissue to facilitate nutrient oxidation for heat production, and may combat metabolic disease if activated in humans. During the adrenergic stimulation of brown adipocytes, free fatty acids generated from lipolysis activate UCP1 via an unclear interaction. Here, we set out to characterise activator binding to purified UCP1 to clarify the activation process, discern novel activators and the potential to target UCP1., Methods: We assessed ligand binding to purified UCP1 by protein thermostability shift analysis, which unlike many conventional approaches can inform on the binding of hydrophobic ligands to membrane proteins. A detailed activator interaction analysis and screening approach was carried out, supported by investigations of UCP1 activity in liposomes, isolated brown fat mitochondria and UCP1 expression-controlled cell lines., Results: We reveal that fatty acids and other activators influence UCP1 through a specific destabilising interaction, behaving as transport substrates that shift the protein to a less stable conformation of a transport cycle. Through the detection of specific stability shifts in screens, we identify novel activators, including the over-the-counter drug ibuprofen, where ligand analysis indicates that UCP1 has a relatively wide structural specificity for interacting molecules. Ibuprofen successfully induced UCP1 activity in liposomes, isolated brown fat mitochondria and UCP1-expressing HEK293 cells but not in cultured brown adipocytes, suggesting drug delivery differs in each cell type., Conclusions: These findings clarify the nature of the activator-UCP1 interaction and demonstrate that the targeting of UCP1 in cells by approved drugs is in principle achievable as a therapeutic avenue, but requires variants with more effective delivery in brown adipocytes., (Copyright © 2022 The Authors. Published by Elsevier GmbH.. All rights reserved.)

The consumption of functional foods, such as mushrooms, apparently influences Gestational Diabetes Mellitus (GDM), and brings benefits to maternal-fetal health. Ganoderma lucidum contains a variety of bioactive compounds, such as polysaccharides, proteins and polyphenols that are able to control blood glucose and be used in anti-cancer therapy. We aimed to evaluate the effects of the consumption of Ganoderma lucidum (Gl) on maternal-fetal outcomes in streptozotocin-induced GDM (GDM-STZ). Pregnant rats were exposed to Gl (100 mg/kg/day) before and after the induction of GDM-STZ (single dose 40 mg/kg) on the eighth pregnancy day. Biochemical and oxidative stress parameters, reproductive performance and morphometry of fetuses were assessed. Gl reduced the glycemic response in the oral glucose tolerance test. Moreover, Gl decreased AST and ALT activities. GDM increased lipid peroxidation, which was reverted by Gl. Catalase and glutathione peroxidase activities were decreased in GDM and the administered Gl after the fetus implantation increased catalase activity. Measurements of the fetal head, thorax, craniocaudal and tail showed greater values in fetuses from rats exposed to Gl compared to GDM. Ganoderma lucidum has an encouraging nutritional and medicinal potential against GDM, since it modifies glucose metabolism, reduces lipid peroxidation, and has protective effects in fetuses born from GDM dams.

Radiation is the standard of care for dogs with nasal tumours. The addition of another therapy that could improve outcome without increasing toxicity is attractive. Medical therapy that could offer better outcome than maximally tolerated dose chemotherapy when radiation therapy (RT) is not possible or is declined is also attractive. This article reports the findings from a prospective, multi-centre, non-randomized, Veterinary Radiation Therapy Oncology Group clinical trial designed to evaluate whether toceranib phosphate (toceranib) has primary activity and if the addition of toceranib to RT could positively impact outcome. Owner's discretion determined enrolment in toceranib alone or toceranib + RT arm. Historical controls for radiation alone were selected from patients treated with identical RT and imaging protocols. Responses were evaluated with pre-treatment and week-16 CT scans. RT total dose of 42 Gy was completed in 10 fractions. Sixty-three dogs enrolled from 10 study sites. Overall response rates (CR + PR) were significantly improved in the toceranib + RT (79.4%) and RT alone (68.9%) arms over toceranib alone (22%) (p = .011). Clinical benefit rates (CR + PR + SD) were significantly improved in the toceranib + RT arm over the RT alone arm at 97.3% and 79.2% respectively (p = .036). Treatment with toceranib alone, toceranib + RT and RT alone resulted in median survival times of 298, 615 and 368 days respectively, but were not statistically significantly different (p = .0502). Adverse events associated with toceranib administration did not potentiate the RT side effect profile. Toceranib appears to have primary activity against nasal carcinoma., (© 2021 John Wiley & Sons Ltd.)

Background: Students who are targets of bullying and who witness bullying are at high risk for negative mental health outcomes. Bystander training is essential to reduce bullying and the negative associated consequences for targets and bystanders. Resources necessary for program delivery, however, pose significant barriers for schools, particularly those in rural, low-income communities. Technology-based programs can reduce health disparities for students in these communities through cost-effective, easy-to-disseminate programming., Objective: The aim of this study is to conduct usability testing of a bystander bullying web app prototype, STAC-T (technology-based STAC, which stands for the 4 bystander strategies Stealing the Show, Turning it Over, Accompanying Others, and Coaching Compassion) as an initial step in the development of a full-scale STAC-T intervention. Objectives include assessing usability and acceptability of the STAC-T prototype, understanding school needs and barriers to program implementation, and assessing differences in usability between school personnel and students., Methods: A sample of 16 participants, including school personnel and students recruited from 3 middle schools in rural, low-income communities, completed usability testing followed by a qualitative interview. Descriptive statistics, 2-tailed independent sample t tests, and consensual qualitative research were used to assess usability and program satisfaction and to extract themes related to acceptability, feasibility, needs, barriers, and feedback for intervention development., Results: Usability testing indicated that the app was easy to use, acceptable, and feasible. Both school personnel (mean rating 89.6, SD 5.1) and students (mean rating 91.8, SD 7.0) rated the app well above the standard cutoff score for above-average usability (ie, 68), and both school personnel (mean rating 5.83, SD 0.41) and students (mean rating 6.10, SD 0.57) gave the app high user-friendliness ratings (0-7 scale, with 7 as high user-friendliness). The overall ratings also suggested that school personnel and students were satisfied with the program. Of the 6 school personnel who said they would recommend the program, 1 (17%), 4 (66%), and 1 (17%) rated the program as 3, 4, and 5 stars, respectively; 80% (8/10) of students said they would recommend the program; and 60% (6/10) and 40% (4/10) rated the program as 4 stars and 5 stars, respectively. Qualitative data revealed that school personnel and students found the STAC-T app to be useful, user-friendly, and relevant, while providing feedback related to the importance of digital learning activities that engage the user. Data from school personnel also indicated positive perceptions regarding program feasibility and probability of program adoption, with the most significant barrier being cost, suggesting the importance of considering the financial resources available to schools in rural, low-income communities when setting the price point for the full-scale STAC-T intervention., Conclusions: This study provides support for the full-scale development of the STAC-T app and provides key information for revision to enhance used engagement., Trial Registration: ClinicalTrials.gov NCT04681495; https://clinicaltrials.gov/ct2/show/NCT04681495., (©Diana M Doumas, Aida Midgett, Valerie Myers, Mary Klein Buller. Originally published in JMIR Formative Research (https://formative.jmir.org), 26.10.2021.)

Background: Healthy dietary intake reduces the risk of complications of diabetes mellitus. Using assessment methods helps to understand these circumstances, and an electronic application may optimize this practice., Objective: In this study, we aimed to (1) assess the dietary intake and health status of elderly patients with type 2 diabetes mellitus (T2DM) in primary care, (2) use a mobile app as a tool for data collection and analysis in the context of primary care, and (3) verify the perceptions of multidisciplinary health professionals regarding app use., Methods: First, we developed a mobile app comprised of the questions of the Food and Nutrition Surveillance System (SISVAN) of Brazil, which includes a food frequency questionnaire of food categories with a recall of the previous 7 days. Thereafter, we used the app to collect data on the health status and dietary intake of 154 participants, aged 60-96 years, diagnosed with T2DM, and under treatment in primary care centers in the northern region of Rio Grande do Sul, Brazil. We also collected participants' demographic, anthropometric, biochemical, and lifestyle variables. The associations between dietary intake and other variables were tested using chi-square tests with a 5% significance level. Regarding the app, we assessed usability and acceptance with 20 health professionals., Results: Between August 2018 and December 2018, participants had an intake in line with recommended guidelines for raw salads (57.1%), fruits (76.6%), milk products (68.2%), fried foods (72.7%), savory biscuits (60.4%), cookies or sweets (72.1%), and sugary drinks (92.9%) Meanwhile, the consumption of beans (59.7%), pulses and cooked vegetables (73.4%), and processed meat products (59.7%) was not in line with the guidelines. There were statistically significant differences in meeting the recommended guidelines among participants of different genders (P=.006 and P=.035 for the intake of fried foods and sugary drinks, respectively), place of residence (P=.034 for the intake of cookies and sweets), family history of diabetes (P<.001 for the intake of beans), physical activity engagement (P=.003 for the intake fresh fruits), history of smoking (P=.001 for the intake of raw salads), and presence of coronary disease (P=.050 for the intake of pulses and cooked vegetables). The assessment of usability resulted in a mean score of 71.75 points. Similarly, the assessment of the 15 acceptance questions revealed high scores, and the qualitative questions revealed positive perceptions., Conclusions: We identified that most participants complied with recommended intake guidelines for 7 of 10 categories in the SISVAN guidelines. However, most participants were overweight and had nutritional and clinical disorders, which justifies further investigations in this population. The app was well-rated by health professionals and considered a useful and promising tool for collecting and analyzing data in primary care settings., (©Joane Diomara Coleone, Ericles Andrei Bellei, Mateus Klein Roman, Vanessa Ramos Kirsten, Ana Carolina Bertoletti De Marchi. Originally published in JMIR Formative Research (https://formative.jmir.org), 27.08.2021.)

Background: Occupational sun protection is recommended by government health authorities. Sun safety policies and predictors of managers' reports of sun safety actions were assessed., Methods: Written policies from 21 state departments of transportation (DOTs) enrolled in a randomized trial to test methods for scaling-up an occupational sun safety intervention were coded for sun safety content at baseline. Managers (n = 1113) supervising outdoor workers reported on sun safety actions in a baseline survey., Results: Twenty state DOTs (95.2%) have a policy with at least one sun protection component. Sun safety training was increased at workplaces with a written sun safety policy (p < 0.001) and unwritten standard procedures on sun protection (p < 0.001). Reported sun safety actions were highest where there was a written sun safety policy (p < 0.001) and unwritten standard procedures on sun protection (p < 0.001)., Conclusions: Policies are essential for the implementation of employee sun safety. There is room for improvement in existing policies of state DOTs., (© 2021 Wiley Periodicals LLC.)

Objective: An online training in responsible marijuana vendor (RMV) practices was evaluated for effects on compliance with ID checking regulations., Method: A random sample of state-licensed recreational marijuana stores (n = 175) in Colorado and Washington State was selected in 2016-2017 and was enrolled in a randomized pretest-posttest controlled design. After baseline assessment, 75 stores were randomly assigned to a usual and customary training control group, stratified by state and region. The remaining stores (n = 100) were invited to use the RMV training. Stores were posttested at 3 and 9 months postrandomization. The primary outcome was refusal of sale measured with pseudo-underage patrons who attempted to enter stores and purchase cannabis without a state-approved ID., Results: There was no difference by treatment group in refusal of pseudo-underage patron buyers (baseline: 92.5% intervention vs. 94.7% control; 3-month posttest 94.8% vs. 97.5%; 9-month posttest 97.5% vs. 97.1%, p = .286 [one tailed, adjusted for covariates]). The use of training increased refusals at store entry (trained: 65.9% baseline 82.5%, 3 months 79.9%, 9 months; not trained: 82.6%, 83.1%, 84.5%, p = .020 [two tailed, adjusted for covariates]). This difference was especially evident in Washington State (trained: 40.3%, 65.1%, 60.4%; not trained: 57.9%, 68.5%, 72.3%) but not in Colorado (trained: 95.2%, 101.0%, 101.4; not trained: 95.7%, 98.6%, 99.2%, p = .033 [two tailed, adjusted for covariates])., Conclusions: When used by store personnel, online RMV training increased refusal of buyers who appeared young and did not provide a state-approved ID. However, it did not improve refusal rates overall. Stores that had lower refusals at baseline and used the training may have benefited from it.

We aimed to obtain reliable reference charts for sleep duration, estimate the prevalence of sleep complaints across the lifespan and identify risk indicators of poor sleep. Studies were identified through systematic literature search in Embase, Medline and Web of Science (9 August 2019) and through personal contacts. Eligible studies had to be published between 2000 and 2017 with data on sleep assessed with questionnaires including ≥100 participants from the general population. We assembled individual participant data from 200,358 people (aged 1-100 years, 55% female) from 36 studies from the Netherlands, 471,759 people (40-69 years, 55.5% female) from the United Kingdom and 409,617 people (≥18 years, 55.8% female) from the United States. One in four people slept less than age-specific recommendations, but only 5.8% slept outside of the 'acceptable' sleep duration. Among teenagers, 51.5% reported total sleep times (TST) of less than the recommended 8-10 h and 18% report daytime sleepiness. In adults (≥18 years), poor sleep quality (13.3%) and insomnia symptoms (9.6-19.4%) were more prevalent than short sleep duration (6.5% with TST < 6 h). Insomnia symptoms were most frequent in people spending ≥9 h in bed, whereas poor sleep quality was more frequent in those spending <6 h in bed. TST was similar across countries, but insomnia symptoms were 1.5-2.9 times higher in the United States. Women (≥41 years) reported sleeping shorter times or slightly less efficiently than men, whereas with actigraphy they were estimated to sleep longer and more efficiently than man. This study provides age- and sex-specific population reference charts for sleep duration and efficiency which can help guide personalized advice on sleep length and preventive practices.

Background: Successful methods for scaling-up evidence-based programs are needed to prevent skin cancer among adults who work outdoors in the sun., Methods: A randomized trial is being conducted comparing two methods of scaling-up the Sun Safe Workplaces (SSW) intervention. Departments of transportation (DOTs) from 21 U.S. states are participating and their 138 regional districts were randomized following baseline assessment. In districts assigned to the in-person method (n = 46), project staff meets personally with managers, conducts trainings for employees, and provides printed materials. In districts assigned to the digital method (n = 92), project staff conduct these same activities virtually, using conferencing technology, online training, and electronic materials. Delivery of SSW in both groups was tailored to managers' readiness to adopt occupational sun safety. Posttesting will assess manager's support for and use of SSW and employees' sun safety. An economic evaluation will explore whether the method that uses digital technology results in lower implementation of SSW but is more cost-effective relative to the in-person method., Results: The state DOTs range in size from 997 to 18,415 employees. At baseline, 1113 managers (49.0%) completed the pretest (91.5% male, 91.1% white, 19.77 years on the job, 66.5% worked outdoors; and 24.4% had high-risk skin types). They were generally supportive of occupational sun safety. A minority reported that the employer had a written policy, half reported training, and two-thirds, messaging on sun protection., Conclusions: Digital methods are available that may make scale-up of SSW cost-effective in a national distribution to nearly half of the state DOTs., Trial Registration: The ClinicalTrials.gov registration number is NCT03278340., (Copyright © 2020. Published by Elsevier Inc.)

Background: People have insufficient knowledge and many misconceptions about the blood donation process, which hampers donors recruitment. Therefore, novel strategies and resources are needed to provide information and improve these circumstances., Objective: We aimed at an interactive conversational agent to explain about blood donation., Methods: We used the Dialogflow framework to develop a conversational agent and deployed it publicly. Afterward, we conducted an assessment of user experience (UX) with 50 participants who interacted with the agent. We analyzed participants' opinions, the different UX scales, and their association with participants' demographic variables., Results: The conversational agent is available on the Google Assistant platform in Brazil. It is capable of responding to utterances related to 30 common questions and concerns about donating blood. The user can interact and explore freely and in any order by typing, speaking and selecting interface elements. The agent responds by speaking and displaying visual information, some multimedia content, and suggestions for continuing the dialogue. It enables a conversational sequence in which knowledge is imparted to the user in stages as the dialogue evolves. The overall UX assessed was very satisfactory, and people with specific demographic characteristics were more likely to have better UX. All participants had positive opinions and attitudes towards the conversational agent., Conclusions: A conversational agent is a creative and captivating strategy of imparting knowledge and engage people regarding blood donation. The findings reaffirm the potential of using this technology for information outreach, especially for socially relevant purposes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Noncompressible torso hemorrhage accounts for a significant portion of preventable trauma deaths. We report here on the development of injectable, targeted supramolecular nanotherapeutics based on peptide amphiphile (PA) molecules that are designed to target tissue factor (TF) and, therefore, selectively localize to sites of injury to slow hemorrhage. Eight TF-targeting sequences were identified, synthesized into PA molecules, coassembled with nontargeted backbone PA at various weight percentages, and characterized via circular dichroism spectroscopy, transmission electron microscopy, and X-ray scattering. Following intravenous injection in a rat liver hemorrhage model, two of these PA nanofiber coassemblies exhibited the most specific localization to the site of injury compared to controls ( p < 0.05), as quantified using immunofluorescence imaging of injured liver and uninjured organs. To determine if the nanofibers were targeting TF in vivo , a mouse saphenous vein laser injury model was performed and showed that TF-targeted nanofibers colocalized with fibrin, demonstrating increased levels of nanofiber at TF-rich sites. Thromboelastograms obtained using samples of heparinized rat whole blood containing TF demonstrated that no clots were formed in the absence of TF-targeted nanofibers. Lastly, both PA nanofiber coassemblies decreased blood loss in comparison to sham and backbone nanofiber controls by 35-59% ( p < 0.05). These data demonstrate an optimal TF-targeted nanofiber that localizes selectively to sites of injury and TF exposure, and, interestingly, reduces blood loss. This research represents a promising initial phase in the development of a TF-targeted injectable therapeutic to reduce preventable deaths from hemorrhage.

Malaria-associated acute respiratory distress syndrome (ARDS) is an inflammatory disease causing alveolar-pulmonary barrier lesion and increased vascular permeability characterized by severe hypoxemia. Computed tomography (CT), among other imaging techniques, allows the morphological and quantitative identification of lung lesions during ARDS. This study aims to identify the onset of malaria-associated ARDS development in an experimental model by imaging diagnosis. Our results demonstrated that ARDS-developing mice presented decreased gaseous exchange and pulmonary insufficiency, as shown by the SPECT/CT technique. The pulmonary aeration disturbance in ARDS-developing mice on the 5th day post infection was characterized by aerated tissues decrease and nonaerated tissue accumulation, demonstrating increased vascular permeability and pleural effusion. The SPECT/CT technique allowed the early diagnosis in the experimental model, as well as the identification of the pulmonary aeration. Notwithstanding, despite the fact that this study contributes to better understand lung lesions during malaria-associated ARDS, further imaging studies are needed., Competing Interests: The authors have declared that no competing interests exist.

Background: The aim of this review was to describe emerging therapies that could serve as a prehospital intervention to slow or stop noncompressible torso hemorrhage in the civilian and military settings. Hemorrhage accounts for 90% of potentially survivable military deaths and 30%-40% of trauma deaths. There is a great need to develop novel therapies to slow or stop noncompressible torso hemorrhage at the scene of the injury., Methods: A comprehensive literature search was performed using PubMed (1966 to present) for therapies not approved by the Food and Drug Administration for noncompressible torso hemorrhage in the prehospital setting. Therapies were divided into compressive versus intravascular injectable therapies. Ease of administration, skill required to use the therapy, safety profile, stability, shelf-life, mortality benefit, and efficacy were reviewed., Results: Multiple potential therapies for noncompressible torso hemorrhage are currently under active investigation. These include (1) tamponade therapies, such as gas insufflation and polyurethane foam injection; (2) freeze-dried blood products and alternatives such as lyophilized platelets; (3) nanoscale injectable therapies such as polyethylene glycol nanospheres, polyethylenimine nanoparticles, SynthoPlate, and tissue factor-targeted nanofibers; and (4) other injectable therapies such as polySTAT and adenosine, lidocaine, and magnesium. Although each of these therapies shows great promise at slowing or stopping hemorrhage in animal models of noncompressible hemorrhage, further research is needed to ensure safety and efficacy in humans., Conclusions: Multiple novel therapies are currently under active investigation to slow or stop noncompressible torso hemorrhage in the prehospital setting and show promising results., (Published by Elsevier Inc.)

Objective: This retrospective observational study examined the implementation of antibiotic stewardship (ABS) on the surgical intensive care unit (SICU) of a specialized academic teaching hospital., Methods: Application density of antimicrobial agents (ADA), substance class change, development of resistance, and clinical outcomes were investigated with reference to ABS in three intervals over a 10-year period: the pre-intervention phase (2008-2010), the intervention phase (2011-2014), and the post-intervention phase (2015-2017)., Results: Following the introduction of ABS, ADA was reduced from 89.3 recommended daily doses/100 patient days (RDD/100 PD) at the pre-intervention phase to 68.0 RDD/100 PD at the post-intervention phase. The antibiotic ADA (AB-ADA) similarly showed a significant decrease from 83.3 to 62.0 RDD/100 PD (p < 0.0001). The case mix index (CMI), which describes the average case severity across patients and mortality on the SICU was not significantly different comparing intervention and post-intervention phase. It was also possible to achieve a substance class change following the introduction of ABS. There was no obvious change in bacterial resistance rates., Conclusion: The study demonstrates a sustainable effect of the implementation of ABS, which was sustained through the post-intervention phase.

Background: Chronic noncommunicable diseases such as arterial hypertension have a high impact in the context of public health. Previous studies have shown improvements in blood pressure due to simple lifestyle changes, which were supported by electronic health (eHealth) solutions., Objective: The aim of this study is to develop an eHealth platform and assess the effects of its use on the health conditions of patients with hypertension, with assistance from health professionals in the public health system of a Brazilian city., Methods: The platform will include a server that centralizes all the data and business rules, a website dashboard for health professionals, and a mobile app for patients. We will analyze the effects of its use through a controlled, nonrandomized, nonblind, prospective, monocentric clinical trial. We will enroll 68 participants diagnosed with arterial hypertension and under medical follow-up and categorize them into two groups. The participants of the intervention group will use the platform as a monitoring method, whereas the participants of the control group will use conventional methods. In both groups, we will assess and compare the evolution of blood pressure and treatment adherence before, during, and after the intervention., Results: The project was funded at the end of 2018. We have been developing the software since 2019 with plans to complete it in 2020, and we will enroll patients between 2020 and 2021. We expect to submit the first results for publication in 2020., Conclusions: For the primary outcome, we expect a reduction and stabilization of blood pressure. For the secondary outcomes, we hope to see improvements in treatment adherence, physical activities and dietary practices, and acceptance of the eHealth platform. In public health, the technology that favors disease control also helps reduce complications and, consequently, treatment costs. The platform might encourage the adaptation of medical assistance to incorporate this technology into patient monitoring., International Registered Report Identifier (irrid): PRR1-10.2196/15299., (©Ana Carolina Bertoletti De Marchi, Ana Luisa Sant' Anna Alves, Carla Beatrice Crivellaro Gonçalves, Cristiano Roberto Cervi, Daiana Biduski, Ericles Andrei Bellei, Guilherme Afonso Madalozzo, Ivana Beatrice Mânica Da Cruz, Jeangrei Emanoelli Veiga, João Pedro Mazuco Rodriguez, Luciano Rodrigo Ferretto, Luiz Carlos Pereira Bin, Marcelo Trindade Rebonatto, Marilene Rodrigues Portella, Mateus Klein Roman, Nathália Pinto Cechetti, Rafael Rieder, Raquel Debon, Simiane Salete Volpi. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 20.01.2020.)

The severity of Plasmodium falciparum malaria is associated with parasite cytoadherence, but there is limited knowledge about the effect of parasite cytoadherence in malaria-associated acute respiratory distress syndrome (ARDS). Our objective was to evaluate the cytoadherence of infected red blood cells (iRBCs) in a murine model of ARDS and to appraise a potential function of endothelial protein C receptor (EPCR) in ARDS pathogenesis. DBA/2 mice infected with P. berghei ANKA were classified as ARDS- or hyperparasitemia- (HP-) developing mice according to respiratory parameters and parasitemia. Lungs, blood, and bronchoalveolar lavage were collected for gene expression or protein analyses. Primary cultures of microvascular lung endothelial cells from DBA/2 mice were analyzed for iRBC interactions. Lungs from ARDS-developing mice showed evidence of iRBC accumulation along with an increase in EPCR and TNF concentrations. Furthermore, TNF increased iRBC adherence in vitro . Dexamethasone-treated infected mice showed low levels of TNF and EPCR mRNA expression and, finally, decreased vascular permeability, thus protecting mice from ARDS. In conclusion, we identified that increased iRBC cytoadherence in the lungs underlies malaria-associated ARDS in DBA/2-infected mice and that inflammation increased cytoadherence capacity, suggesting a participation of EPCR and a conceivable target for drug development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2019 Luana dos Santos Ortolan et al.)

Background: Outdoor workers experience chronic exposure to harmful ultraviolet radiation (UV) elevating their risk for skin cancer., Methods: A controlled randomized trial promoted the adoption of workplace sun safety policy and employee education at 98 public organizations in Colorado. A 2-year follow-up study with 68 organizations assessed the association of senior manager awareness of sun safety policies and implementation of sun safety actions., Results: Senior managers' awareness of existing sun safety policies, but not their personal sun protection behaviors, predicted implementation of sun safety actions including the number of sun protection messages and sun protection items in the workplace and increased communication about sun safety to employees., Conclusions: Organizational adoption of sun safety policy must include efforts to broadly inform a workplace's senior management to ensure the policies are actually implemented and provide support for sun protection behaviors by outdoor workers to reduce UV exposure and skin cancer risk., (© 2019 Wiley Periodicals, Inc.)

Background: In 1993, the Family and Medical Leave Act (FMLA) mandated 12 weeks of unpaid, job-protected leave. The current impact of taking 12 weeks of leave during residency has not been evaluated., Methods: We examined the 2018 Accreditation Council for Graduate Medical Education (n = 24) specialty leave policies to determine the impact of 6- and 12-week leave on residency training, board eligibility, and fellowship training. We compared our findings with a 2006 study., Results: In 2018, five (21%) specialties had policy language regarding parental leave during residency, and four (16%) had language regarding medical leave. Median leave allowed was 4 weeks (IQR 4-6). Six specialties (25%) decreased the number of weeks allowed for leave from 2006 to 2018. In 2006, a 6-week leave would cause a 1-year delay in board eligibility in six specialties; in 2018, it would not cause delayed board eligibility in any specialty. In 2018, a 12-week (FMLA) leave would extend training by a median of 6 weeks (mean 4.1, range 0-8), would delay board eligibility by 6-12 months in three programs (mean 2.25, range 0-12), and would delay fellowship training by at least 1 year in 17 specialties (71%). The impact of a 12-week leave was similar between medical and surgical specialties., Conclusions: While leave policies have improved since 2006, most specialties allow for 6 weeks of leave, less than half of what is mandated by the FMLA. Moreover, a 12-week, FMLA-mandated leave would cause significant delays in board certification and entry into fellowship for most residency programs., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Implementation of employer sun safety actions was assessed in a 2-year follow-up to an occupational sun protection policy intervention., Design: Two-year follow-up assessment in a randomized pretest-posttest controlled design., Setting: Local government organizations with workers in public safety, public works, and parks and recreation., Participants: Sixty-three local government organizations (participation = 64%) and 330 frontline supervisors and 1454 workers., Intervention: Sun Safe Workplaces (SSW) intervention promoting occupational sun safety policy and education., Measures: Observations of SSW messages and sun safety items and surveys on organizations' communication and actions on sun safety., Analysis: Comparison between SSW and control groups was conducted using regression models and adjusted for clustering where appropriate, with α criterion set at P = .05 (2-tailed)., Results: At intervention worksites, more SSW messages ( P < .001) and sun safety items ( P = .025) were observed; more frontline supervisors reported organizations provided free/reduced price sunscreen ( P = .005) and communicated about sun safety ( P < .001); and more workers recalled receiving sun safety messages ( P < .001) and sun safety training ( P <.001) compared to control organizations. Implementation was greater at larger than smaller intervention organizations for wide-brimmed hats ( P = .009), long work pants ( P = .017), and shade structures ( P = .036). Older workers received the most written messages ( P = .015)., Conclusions: Sun Safe Workplaces appeared to produce actions by organizations to support employee sun safety. Large organizations may have processes, communication channels, and slack resources to achieve more implementation.

Context: Six US states have implemented retail sales of recreational marijuana. Training in responsible sales practices has been effective in the alcohol market. An online responsible marijuana vendor (RMV) training was produced and implemented with stores in a randomized trial., Program: An online RMV training was developed through meetings with state regulators and local law enforcement personnel, curriculum standards published by the Colorado Marijuana Enforcement Division in May 2015, interviews with recreational marijuana store personnel (n = 15), and usability testing of a prototype training with store personnel (n = 19) in Colorado and Washington State. The training contained 5 modules: state laws and regulations, ID checking, health effects of marijuana, customer service practices including recognizing intoxicated patrons, and rules of the trade., Implementation: A randomized controlled trial testing the training enrolled a random sample of state-licensed retail recreational marijuana stores (n = 225) in Colorado, Oregon, and Washington State. In total, 125 stores were randomly assigned to receive the RMV training. A total of 420 store employees completed the online training between June 2017 and February 2018 (43.5% female, 88.4% younger than 40 years, and 74.1% non-Hispanic white)., Evaluation: Responses to posttraining surveys showed that most trainees found the training user-friendly (78.4%), were satisfied (68.8%), and would recommend it to another employee (91.1%). The training improved trainees' ability to check IDs (pretraining mean = 3.91 [SD = 1.36], posttraining mean = 4.58 [SD = 0.66], t387,388 = 8.68, P < .001) and their confidence to use the state's inventory tracking system (pretraining mean = 2.52 [SD = 0.65], posttraining mean = 2.85 [SD = 0.39], t387, 388 = 10.89, P < .001) and spot intoxicated customers (pretraining mean = 2.79 [SD = 0.41], posttraining mean = 2.94 [SD = 0.25], t387,388 = 6.87, P < .001)., Discussion: Online RMV training was acceptable to retail recreational marijuana personnel and potentially improved responsible sales practices. Responsible vendor training has been successful under certain conditions in the alcohol market and should be considered for the recreational marijuana market.

Competing Interests: Competing interests: The authors have no conflicts of interest to disclose.

Background: Chemotherapeutic options for the treatment of canine lymphoma have not changed in several decades necessitating the identification of new therapeutics to improve patient outcome. KPT-335 (verdinexor) is a novel orally bioavailable selective inhibitor of nuclear export (SINE) that exhibited anti-tumor activity against non-Hodgkin lymphoma in a prior phase I study. The objective of this phase II study was to expand upon the initial findings and assess the activity and safety in a larger population of dogs with lymphoma., Results: Fifty-eight dogs with naïve or progressive B-cell and T-cell lymphoma were enrolled in this clinical trial. KPT-335 was administered orally in one of three dosing groups, based on the previously established biologically active dose of 1.5 mg/kg three times weekly. Treatment with single-agent, orally administered KPT-335 resulted in an objective response rate (ORR) of 37%, of which dogs with T-cell lymphoma had an ORR of 71%. KPT-335 was well tolerated in all dose groups with grade 1-2 anorexia being the most common adverse event. Anorexia was responsive to symptomatic and supportive medications, including prednisone., Conclusions: These data demonstrate that KPT-335 has biologic activity in canine lymphoma, and support continued evaluation of SINE compounds such as KPT-335 in combination with standard chemotherapeutics in canine lymphoma.

Purpose: To evaluate an intervention promoting adoption of occupational sun protection policies by employers in a randomized trial., Design: A randomized pretest-posttest controlled design with 2-year follow-up was conducted in 2010 to 2013., Setting: Local government organizations in Colorado who had outdoor workers in public works, public safety, and/or parks and recreation., Participants: Ninety-eight local government organizations (n = 51 municipalities, 10 counties, and 37 special districts)., Intervention: Organizations were randomly assigned to receive a policy and education intervention comprised of personal contacts and theory-based training and materials or to an attention control group., Measures: Occupational policy documents were coded for sun safety content by a trained research assistant blind to condition., Analysis: Policy scores were analyzed with logistic and Poisson regression models using imputation., Results: At posttest, more organizations in the intervention group had a sun protection policy than in the control group (odds ratio [OR] = 4.91, P < .05; intent to treat: OR = 5.95, P < .05) and policies were more extensive (χ 2 = 31.29, P < .01; intent to treat: χ 2 =73.79, P < .01) and stronger (χ 2 = 24.50, P < .01; intent to treat: χ 2 = 51.95, P < .01). Policy adoption was higher when the number of contacts and trainings increased ( P < .05)., Conclusion: The intervention had a large effect on adoption of formal sun protection policies, perhaps because of its fit with legal requirements to maintain safe workplaces. Personal contacts with managers were influential on adoption of occupational policy even in this age of communication technology and social media.

Objective: Obsessive-compulsive symptoms (OCS) co-occur frequently with anxiety and depressive disorders, but the nature of their relationship and their impact on severity of anxiety and depressive disorders is poorly understood. In a large sample of patients with anxiety and depressive disorders, we assessed the frequency of OCS, defined as a Young Adult Self-Report Scale-obsessive-compulsive symptoms score >7. The associations between OCS and severity of anxiety and/or depressive disorders were examined, and it was investigated whether OCS predict onset, relapse, and persistence of anxiety and depressive disorders., Methods: Data were obtained from the third (at 2-year follow-up) and fourth wave (at 4-year follow-up) of data collection in the Netherlands Study of Anxiety and Depression cohort, including 469 healthy controls, 909 participants with a remitted disorder, and 747 participants with a current anxiety and/or depressive disorder., Results: OCS were present in 23.6% of the total sample, most notably in those with current combined anxiety and depressive disorders. In patients with a current disorder, OCS were associated with severity of this disorder. Moreover, OCS predicted (1) first onset of anxiety and/or depressive disorders in healthy controls (odds ratio [OR], 5.79; 95% confidence interval [CI], 1.15 to 29.14), (2) relapse in those with remitted anxiety and/or depressive disorders (OR, 2.31; 95% CI, 1.55 to 3.46), and (3) persistence in patients with the combination of current anxiety and depressive disorders (OR, 4.42; 95% CI, 2.54 to 7.70) within the 2-year follow-up period Conclusions: OCS are closely related to both the presence and severity of anxiety and depressive disorders and affect their course trajectories. Hence, OCS might be regarded as a course specifier signaling unfavorable outcomes. This specifier may be useful in clinical care to adapt and intensify treatment in individual patients.

Introduction: Policy is a key aspect of school-based efforts to prevent skin cancer. We explored the extent and accuracy of knowledge among principals and teachers in California public school districts about the elements specified in their district's written sun safety policy., Methods: The sample consisted of California public school districts that subscribed to the California School Boards Association, had an elementary school, adopted Board Policy 5141.7 for sun safety, and posted it online. The content of each policy was coded. Principals (n = 118) and teachers (n = 113) in elementary schools were recruited from September 2013 through December 2015 and completed a survey on sun protection policies and practices from January 2014 through April 2016., Results: Only 38 of 117 principals (32.5%) were aware that their school district had a sun protection policy. A smaller percentage of teachers (13 of 109; 11.9%) than principals were aware of the policy (F 108 = 12.76, P < .001). We found greater awareness of the policy among principals and teachers who had more years of experience working in public education (odds ratio [OR] = 1.05, F 106 = 4.71, P = .03) and worked in schools with more non-Hispanic white students (OR = 7.65, F 109 = 8.61, P = .004) and fewer Hispanic students (OR = 0.28, F 109 = 4.27, P = .04)., Conclusion: Policy adoption is an important step in implementing sun safety practices in schools, but districts may need more effective means of informing school principals and teachers of sun safety policies. Implementation will lag without clear understanding of the policy's content by school personnel.

Objectives: To test whether shade sails will increase the use of passive recreation areas (PRAs)., Methods: We conducted a stratified randomized pretest-posttest controlled design study in Melbourne, Australia, and Denver, Colorado, in 2010 to 2014. We randomized a sample of 144 public parks with 2 PRAs in full sun in a 1:3 ratio to treatment or control. Shade sails were built at 1 PRA per treatment park. The outcome was any use of the study PRA (n = 576 pretest and n = 576 posttest observations; 100% follow-up)., Results: Compared with control PRAs (adjusted probability of use: pretest = 0.14, posttest = 0.17), use of treatment PRAs (pretest = 0.10, posttest = 0.32) was higher at posttest (odds ratio [OR] = 3.91; 95% confidence interval [CI] = 1.71, 8.94). Shade increased use of PRAs in Denver (control: pretest = 0.18, posttest = 0.19; treatment: pretest = 0.16, posttest = 0.47) more than Melbourne (control: pretest = 0.11, posttest = 0.14; shaded: pretest = 0.06, posttest = 0.19; OR = 2.98; 95% CI = 1.09, 8.14)., Conclusions: Public investment in shade is warranted for skin cancer prevention and may be especially useful in the United States., Trial Registration: Clinicaltrials.gov identifier NCT02971709.

Objective: The purpose of this study was to measure compliance with age and personal ID regulations by state-licensed recreational marijuana stores in two states., Method: Recreational marijuana stores (N = 175) in Colorado and Washington State were each visited twice by pseudo-buyer assessment teams in September 2016 to April 2017. The observer entered the store first, performed an environmental scan, and observed the buyer's purchase behavior. In both Washington State visits and in the first visit in Colorado, a young-adult buyer attempted to enter the store and purchase marijuana without showing a state-approved ID (i.e., valid driver's license). In the second Colorado visit, a buyer age 18-20 showed an underage driver's license and attempted to enter the store and purchase marijuana., Results: All stores (100%) requested an ID. Stores refused buyers in 73.6% of visits at the entrance, 88.3% cumulative before the counter, and 92.6% by the time of a purchase attempt. Refusal was lower in Washington State (at entry, 53.1%; before the counter, 80.5%; and at purchase attempt, 86.6%) than in Colorado (at entry, 95.3%, p < .01; before the counter, 96.5%, p < .01; and at purchase attempt, 98.8%, p < .01), but it did not differ by buyer protocol (p > .05)., Conclusions: Compliance with laws restricting marijuana sales to individuals 21 or older with a valid ID was high. Compliance in Washington State might be improved by having store personnel check IDs at the store entry. Although recreational stores may not be selling marijuana directly to youth, no information was collected on straw purchases.

Purpose/background: D-cycloserine (DCS) is a partial N-methyl-D-aspartate receptor agonist that potentially augments response to exposure therapy in anxiety disorders by enhancing extinction learning. This randomized, double-blinded, placebo-controlled augmentation trial examined (1) the effectiveness of adding 125 mg of DCS to exposure therapy (before or directly after the first 6 treatment sessions) in patients with panic disorder with agoraphobia and (2) the effectiveness of DCS augmentation preceding exposure relative to DCS augmentation directly postexposure., Methods/procedures: Fifty-seven patients were allocated to 1 of 3 medication conditions (placebo and pre-exposure and postexposure DCS) as an addition to 6 exposure sessions within a 12-session exposure and response prevention protocol. The primary outcome measure was the mean score on the "alone" subscale of the Mobility Inventory (MI)., Findings/results: No differences were found in treatment outcome between DCS and placebo, administered either pre-exposure or postexposure therapy, although at 3-month follow-up, the DCS postexposure group compared with DCS pre-exposure, exhibited greater symptom reduction on the MI-alone subscale. Ancillary analyses in specific subgroups (responders vs nonresponders, early vs late responders, severely vs mildly affected patients) did not reveal any between-group DCS versus placebo differences. Finally, the study did not find an effect of DCS relative to placebo to be specific for successful exposure sessions., Implications/conclusions: This study does not find an effect of augmentation with DCS in patients with severe panic disorder and agoraphobia administered either pretreatment or directly posttreatment sessions. Moreover, no preferential effects are revealed in specific subgroups nor in successful exposure sessions. Yet, a small effect of DCS administration postexposure therapy cannot be ruled out, given the relatively small sample size of this study.

Background: Standard of care treatment for multicentric lymphoma in dogs remains doxorubicin (DOX)-based combination chemotherapy, but owners may hesitate to commit the time and financial resources to complete such a protocol, typically requiring 12-16 visits. Rabacfosadine (RAB), a double prodrug of the nucleotide analog 9-(2-phosphonylmethoxyethyl) guanine, has substantial single-agent activity in dogs with lymphoma, and a different mechanism of action than DOX., Hypothesis/objectives: Our objective was to evaluate the efficacy and adverse effect (AE) profile of alternating doses of RAB and DOX in dogs with naïve multicentric lymphoma., Animals: Fifty-four dogs with previously untreated lymphoma., Methods: Open-label, multicenter prospective clinical trial. Dogs received alternating RAB (1.0 mg/kg IV weeks 0, 6, 12) and DOX (30 mg/m 2 IV weeks 3, 9, 15). Dogs that achieved complete response (CR) were followed by monthly evaluations. Complete clinicopathological evaluation and assessment of remission and AEs were performed every 21 days., Results: The overall response rate was 84% (68%; CR; 16%; partial response [PR)]. The overall median progression-free interval (PFI) was 194 days (216 for CR and 63 for PR). Most AEs were mild and self-limiting: gastrointestinal and hematologic AEs were most common. Thirteen dogs experienced dermatologic AEs, and 2 dogs developed grade 5 pulmonary fibrosis., Conclusions and Clinical Importance: Alternating RAB/DOX generally was well tolerated and resulted in PFIs comparable to standard DOX-based multi-agent protocols, with fewer treatment visits. Most adverse events were mild or moderate and self-limiting. Further studies are warranted to explore long-term outcome and other RAB chemotherapy combinations., (Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.)

Environments can be structured to reduce solar ultraviolet radiation (UV) exposure to prevent skin cancer. A prospective randomized trial is being conducted to test whether introducing shade sails in passive recreation areas (PRAs) in public parks will increase use and decrease UV exposure in the shaded compared to unshaded PRAs. Shade effects will be compared between Melbourne, Australia and Denver, USA. The trial enrolled 145 public parks with PRAs suitable for shade construction and randomized parks to intervention or control in a 1:3 ratio. Use of PRAs and UV levels were recorded at each park by trained observers during 30-minute periods on four weekend days in each of two summers (pretest and posttest). Shade sails were constructed between the summers. Given low numbers of users at pretest, the outcome measure was modified to use of the PRA (use vs. no use) and unit of analysis to the individual observation. Observations (n=580) occurred on average 29days from the summer solstice and 55min from solar noon in warm weather (mean=26.2°C) with some cloud cover but only slight or no wind. Typically, PRAs had benches and picnic tables and were located near playgrounds. PRAs were in use during 13.3% of observations (mean=0.41 users). UV over 30-minutes at the PRA boundary (mean=3.2 standard erythemal dose [SED]) and center (mean=3.3 SED) was high. Shade for skin cancer prevention has been understudied. This study will address this gap by determining whether purpose-built shade structures promote greater use of shaded areas within public parks., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Gradients of biomolecules on synthetic, solid substrates can efficiently mimic the natural, graded variation of properties of the extracellular matrix (ECM). Such gradients represent accessible study platforms for the understanding of cellular activities, and they also provide functional supports for tissue engineering (TE). This review describes the most relevant methods to produce 2-dimensional (2D) as well as 3-dimensional (3D) gradient supports for cell manipulations, and also addresses the response of cells from different origins when seeded on these constructs. The fabrication strategies summarized encompass the combination of polymer and surface chemistries, micro- and nano-engineering construction strategies and biotechnological approaches. This multidisciplinary scheme has enabled the design and realization of diverse, synthetic supports as cellular environments, spanning from the first gradient self-assembled monolayer (SAM) to multilayers, and hybrid constructs mimicking the complexity of natural tissue environments. The standing challenge is bringing these advances in the fabrication of supports to a dynamic functioning in space and time, towards the successful imitation of the most complex bio-chemical system ever studied: our body.

Phylogenies within Toxoplasmatinae have been widely investigated with different molecular markers. Here, we studied molecular phylogenies of the Toxoplasmatinae subfamily based on apicoplast and mitochondrial genes. Partial sequences of apicoplast genes coding for caseinolytic protease (clpC) and beta subunit of RNA polymerase (rpoB), and mitochondrial gene coding for cytochrome B (cytB) were analyzed. Laboratory-adapted strains of the closely related parasites Sarcocystis falcatula and Sarcocystis neurona were investigated, along with Neospora caninum, Neospora hughesi, Toxoplasma gondii (strains RH, CTG and PTG), Besnoitia akodoni, Hammondia hammondiand two genetically divergent lineages of Hammondia heydorni. The molecular analysis based on organellar genes did not clearly differentiate between N. caninum and N. hughesi, but the two lineages of H. heydorni were confirmed. Slight differences between the strains of S. falcatula and S. neurona were encountered in all markers. In conclusion, congruent phylogenies were inferred from the three different genes and they might be used for screening undescribed sarcocystid parasites in order to ascertain their phylogenetic relationships with organisms of the family Sarcocystidae. The evolutionary studies based on organelar genes confirm that the genus Hammondia is paraphyletic. The primers used for amplification of clpC and rpoB were able to amplify genetic sequences of organisms of the genus Sarcocystisand organisms of the subfamily Toxoplasmatinae as well.

Importance: Skin cancer prevention remains a national priority. Reducing chronic UV radiation exposure for outdoor workers through sun-safety practices is an important step to help reduce the incidence of skin cancer., Objective: To determine the presence of occupational sun-safety policies at local government organizations in a single state., Design, Setting, and Participants: Of 571 potentially eligible local government organizations of Colorado cities, counties, and special tax districts, we enrolled 98 in a randomized pretest-posttest controlled experiment starting August 15, 2010, that evaluated an intervention to promote the adoption of sun-safety policies. We used a policy-coding protocol to evaluate personal sun-protection practices, environmental and administrative controls, and policy directives for sun safety starting February 10, 2011. We report the baseline assessment of the occupational sun-protection policies of these organizations., Main Outcomes and Measures: The presence of an occupational sun-safety policy., Results: Overall, 85 local government organizations (87%) had policies that required personal sun-protection practices, including the use of eyewear, hats, and protective clothing. However, of the 98 responding organizations, only 8 hat policies (8%), 10 eyewear policies (10%), and 7 clothing policies (7%) mentioned sun protection as the intent of the policy. Only cosmopoliteness, operationalized as proximity to an urban area, was associated with the presence of a sun-safety policy (odds ratio, 0.99 [95% CI, 0.98-1.00]; P = .02)., Conclusions and Relevance: Outdoor workers are at increased risk for skin cancer because of long-term exposure to solar UV radiation. Although organizational policies have the potential to increase sun protection in occupational settings, occupational sun-safety policies were uncommon among local governments. Opportunities exist for dermatologists and other physicians to influence occupational sun-safety practices and policies, which are consistent with other safety procedures and could easily be integrated into existing workplace practices.

Background: Spenic hemangiosarcoma (HSA) in dogs treated with surgery alone is associated with short survival times, and the addition of doxorubicin (DOX) chemotherapy only modestly improves outcome. The purpose of this study was to evaluate the impact of toceranib administration on progression free survival in dogs with stage I or II HSA following splenectomy and single agent DOX chemotherapy. We hypothesized that dogs with splenic HSA treated with adjuvant DOX followed by toceranib would have prolonged disease-free interval (DFI) and overall survival time (OS) when compared to historical dogs treated with DOX-based chemotherapy alone., Results: Dogs with stage I or II splenic HSA were administered 5 cycles of single-agent DOX every 2 weeks beginning within 14 days of splenectomy. Dogs were restaged 2 weeks after completing DOX, and those without evidence of metastatic disease began toceranib therapy at 3.25 mg/kg every other day. Forty-three dogs were enrolled in this clinical trial. Seven dogs had evidence of metastatic disease either before or at re-staging, and an additional 3 dogs were found to have metastatic disease within 1 week of toceranib administration. Therefore 31 dogs went on to receive toceranib following completion of doxorubicin treatment. Twenty-five dogs that received toceranib developed metastatic disease. The median disease free interval for all dogs enrolled in this study (n = 43) was 138 days, and the median disease free interval for those dogs that went on to receive toceranib (n = 31) was 161 days. The median survival time for all dogs enrolled in this study was 169 days, and the median survival time for those dogs that went on to receive toceranib was 172 days., Conclusions: The use of toceranib following DOX chemotherapy does not improve either disease free interval or overall survival in dogs with stage I or II HSA.

Coupling of rapid prototyping techniques and surface-confined polymerizations allows the fabrication of 3D multidirectional gradients of biomolecules within microporous scaffolds. The compositional gradients can be tailored by polymer-brush-assisted diffusion of protein solutions. This technique allows spatial control over stem cells manipulation within 3D environments., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Animal flight performance has been studied using models developed for man-made aircraft. For an aeroplane with fixed wings, the energetic cost as a function of flight speed can be expressed in terms of weight, wing span, wing area and body area, where more details are included in proportionality coefficients. Flying animals flap their wings to produce thrust. Adopting the fixed wing flight model implicitly incorporates the effects of wing flapping in the coefficients. However, in practice, these effects have been ignored. In this paper, the effects of reciprocating wing motion on the coefficients of the fixed wing aerodynamic power model for forward flight are explicitly formulated in terms of thrust requirement, wingbeat frequency and stroke-plane angle, for optimized wingbeat amplitudes. The expressions are obtained by simulating flights over a large parameter range using an optimal vortex wake method combined with a low-level blade element method. The results imply that previously assumed acceptable values for the induced power factor might be strongly underestimated. The results also show the dependence of profile power on wing kinematics. The expressions introduced in this paper can be used to significantly improve animal flight models.

Importance: Mobile smartphones are rapidly emerging as an effective means of communicating with many Americans. Using mobile applications (apps), they can access remote databases, track time and location, and integrate user input to provide tailored health information., Objective: A smartphone mobile app providing personalized, real-time sun protection advice was evaluated in a randomized clinical trial., Design, Setting, and Participants: The trial was conducted in 2012 and had a randomized pretest-posttest controlled design with a 10-week follow-up. Data were collected from a nationwide population-based survey panel. A sample of 604 non-Hispanic and Hispanic adults from the Knowledge Panel 18 years or older who owned an Android smartphone were enrolled., Interventions: The mobile app provided advice on sun protection (ie, protection practices and risk of sunburn) and alerts (to apply or reapply sunscreen and get out of the sun), hourly UV Index, and vitamin D production based on the forecast UV Index, the phone's time and location, and user input., Main Outcomes and Measures: Percentage of days using sun protection and time spent outdoors (days and minutes) in the midday sun and number of sunburns in the past 3 months were collected., Results: Individuals in the treatment group reported more shade use (mean days staying in the shade, 41.0% vs 33.7%; P = .03) but less sunscreen use (mean days, 28.6% vs 34.5%; P = .048) than controls. There was no significant difference in number of sunburns in the past 3 months (mean, 0.60 in the treatment group vs 0.62 for controls; P = .87). Those who used the mobile app reported spending less time in the sun (mean days keeping time in the sun to a minimum, 60.4% for app users vs 49.3% for nonusers; P = .04) and using all protection behaviors combined more (mean days, 39.4% vs 33.8%; P = .04)., Conclusions and Relevance: The mobile app improved some sun protection. Use of the mobile app was lower than expected but associated with increased sun protection. Providing personalized advice when and where people are in the sun may help reduce sun exposure.

Importance: Mobile applications on smartphones can communicate a large amount of personalized, real-time health information, including advice on skin cancer prevention, but their effectiveness may be affected by whether recipients can be convinced to use them., Objective: To evaluate a smartphone mobile application (Solar Cell) delivering real-time advice about sun protection for a second time in a randomized clinical trial., Design, Setting, and Participants: A previous trial conducted in 2012 used a randomized pretest-posttest design. For the present trial, we collected data from a volunteer sample of 202 adults 18 years or older who owned a smartphone. Participants were recruited nationwide through online promotions. Screening procedures and a 3-week run-in period were added to increase the use of the mobile application. We conducted follow-ups at 3 and 8 weeks after randomization to examine the immediate and the longer-term effects of the intervention., Interventions: Use of the mobile application. The application gave feedback on sun protection (ie, sun-safety practices and the risk for sunburn) and alerted users to apply or to reapply sunscreen and to get out of the sun. The application also displayed the hourly UV Index and vitamin D production based on the forecast UV Index, time, and location., Main Outcomes and Measures: Percentage of days with the use of sun protection, time spent outdoors in the midday sun (days and hours), and the number of sunburns in the last 3 months., Results: Participants in the intervention group used wide-brimmed hats more at 7 weeks than control participants (23.8% vs 17.4%; F = 4.07; P = .045). Women who used the mobile application reported using all sun protection combined more than men (46.4% vs 43.3%; F = 1.49; P = .04), whereas men and older individuals reported less use of sunscreen (32.7% vs 35.5%; F = 5.36; P = .02) and hats (15.6% vs 17.9%; F = 4.72; P = .03)., Conclusions and Relevance: The mobile application initially appeared to confer weak improvement of sun protection. Use of the mobile application was greater than in a previous trial and was associated with greater sun protection, especially among women. Strategies to increase the use of the mobile application are needed if the application is to be deployed effectively to the general adult population.

Background: We hypothesized that the addition of toceranib to metronomic cyclophosphamide/piroxicam therapy would significantly improve disease-free interval (DFI) and overall survival (OS) in dogs with appendicular osteosarcoma (OSA) following amputation and carboplatin chemotherapy., Methods and Findings: This was a randomized, prospective clinical trial in which dogs with OSA free of gross metastatic disease (n = 126) received carboplatin chemotherapy (4 doses) following amputation. On study entry, dogs were randomized to receive piroxicam/cyclophosphamide with or without toceranib (n = 63 each) after completing chemotherapy. Patient demographics were not significantly different between both groups. During or immediately following carboplatin chemotherapy, 32 dogs (n = 13 toceranib; n = 19 control) developed metastatic disease, and 13 dogs left the study due to other medical conditions or owner preference. Following carboplatin chemotherapy, 81 dogs (n = 46 toceranib; n = 35 control) received the metronomic treatment; 35 dogs (n = 20 toceranib; n = 15 control) developed metastatic disease during the maintenance therapy, and 26 dogs left the study due to other medical conditions or owner preference. Nine toceranib-treated and 11 control dogs completed the study without evidence of metastatic disease 1-year following amputation. Toceranib-treated dogs experienced more episodes of diarrhea, neutropenia and weight loss than control dogs, although these toxicities were low-grade and typically resolved with supportive care. More toceranib-treated dogs (n = 8) were removed from the study for therapy-associated adverse events compared to control dogs (n = 1). The median DFI for control and toceranib treated dogs was 215 and 233 days, respectively (p = 0.274); the median OS for control and toceranib treated dogs was 242 and 318 days, respectively (p = 0.08). The one year survival rate for control dogs was 35% compared to 38% for dogs receiving toceranib., Conclusions: The addition of toceranib to metronomic piroxicam/cyclophosphamide therapy following amputation and carboplatin chemotherapy did not improve median DFI, OS or the 1-year survival rate in dogs with OSA.

For several decades, nonaqueous dispersions of PMMA particles have played an important role in colloid research. They have found application as colloidal model systems, which are used to probe glassy dynamics or to explore crystal nucleation. To date, most research has focused on spherical particles, in which only translational motion can be investigated. Recently, however, there has been a surge of interest in analyzing also rotational dynamics. In this contribution, we introduce a new class of core-shell particles, which can be used as rotational probes. The colloids described herein are composed of shape anisotropic, fluorescent cores covered with nonfluorescent PMMA shells. The core-shell particles are built up in four steps. In a first step, we produce fluorescent and photo-cross-linkable PMMA colloids. In the second step, these particles are thermomechanically elongated and fixed in defined ellipsoidal shapes by photo-cross-linking. Subsequently, we cover the cross-linked, fluorescent core with a nonfluorescent PMMA shell. The shape of the resulting core-shell colloids is tunable between the initial anisotropic and perfect spherical shape. For shaping, we apply a simple solvent swelling procedure. As one option, this method yields perfect PMMA spheres with ellipsoidal, fluorescent centers. We also report morphological particle characterization using various fluorescence microscopy techniques. Finally, we demonstrate that the rotational dynamics of individual colloids can be tracked and analyzed.

Unlabelled: Population aging is associated with a higher prevalence of chronic health conditions. Previous studies have shown that older persons, specifically those with chronic conditions, often lack sufficient knowledge about their condition and thus frequently have poor self-care skills. Efforts to increase general health screenings and improve access to chronic condition management resources are hampered by a lack of disease and health awareness. Self-Care for Older People (SCOPE) study, a cluster randomized controlled trial in Singapore, was designed to evaluate the impact of a self-care program for chronic disease awareness and management of specific health measures and quality of life of older people over eighteen months. SCOPE provided self-care education targeted at older people with low income and low education in order to improve health-related knowledge. A total of 378 low-income older people with no or minimal disability, defined as having difficulty in one or more activities of daily living (ADL), were recruited from senior activity centers. The measurements taken included self-reported health conditions, health and disease knowledge questions, and biomarkers (HbA1c, blood pressure, peak expiratory flow, lipid panel, albumin, and creatinine). SCOPE was also designed to provide information for policy makers on chronic disease burden and healthcare facility utilization among community-dwelling older adults., Trial Registration Number: NCT01672177., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Colloidal polymer particles are an important class of materials finding use in both everyday and basic research applications. Tailoring their composition, shape, and functionality is of key importance. In this article, we describe a new class of shape-tunable core-shell microparticles. They are composed of a cross-linked polystyrene (PS) core and a poly(methyl methacrylate) (PMMA) shell of varying thickness. In the first step, we prepared highly cross-linked PS cores, which are subsequently transferred into a nonpolar dispersant. They serve as the seed dispersion for a nonaqueous dispersion polymerization to generate the PMMA shell. The shape of the particles can subsequently be manipulated. After the shell growth stage, the spherical PS/PMMA core-shell colloids exhibit an uneven and wrinkled surface. An additional tempering procedure allows for smoothing the surface of the core-shell colloids. This results in polymer core-shell particles with a perfectly spherical shape. In addition to this thermal smoothing of the PMMA shell, we generated a selection of shape-anisotropic core-shell particles using a thermomechanical stretching procedure. Because of the unique constitution, we can selectively interrogate molecular vibrations in the PS core or the PMMA shell of the colloids using nonlinear optical microscopy techniques. This is of great interest because no photobleaching occurs, such that the particles can be tracked in real space over long times.