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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.

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: 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.)

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: 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.)

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.

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.

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.)

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.

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.

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.

The Leading Edge Vortex (LEV) is a universal mechanism enhancing lift in flying organisms. LEVs, generally illustrated as a single vortex attached to the wing throughout the downstroke, have not been studied quantitatively in freely flying insects. Previous findings are either qualitative or from flappers and tethered insects. We measure the flow above the wing of freely flying hawkmoths and find multiple simultaneous LEVs of varying strength and structure along the wingspan. At the inner wing there is a single, attached LEV, while at mid wing there are multiple LEVs, and towards the wingtip flow separates. At mid wing the LEV circulation is ~40% higher than in the wake, implying that the circulation unrelated to the LEV may reduce lift. The strong and complex LEV suggests relatively high flight power in hawmoths. The variable LEV structure may result in variable force production, influencing flight control in the animals.

Background: Evidence on the differential impacts of the global food crisis as it translates into chronic food insecurity locally is essential to design food security interventions targeting the most vulnerable population groups. There are no studies on the extent of chronic food insecurity or its predictors among adolescents in developing countries. In the context of increased food prices in Ethiopia, we hypothesized that adolescents in low income urban households are more likely to suffer from chronic food insecurity than those in the rural areas who may have direct access to agricultural products., Methods: This report is based on data from the first two rounds of the Jimma Longitudinal Family Survey of Youth (JLFSY). Both adolescents and households were selected using a stratified random sampling method. A total of 1911 adolescents aged 13-17 years were interviewed on their personal experiences of food insecurity both at baseline and at year two. Multivariable logistic regression analyses were used to compare chronic adolescent food insecurity by household income, household food insecurity, and socio-demographic variables after one year of follow-up., Results: Overall, 20.5% of adolescents were food insecure in the first round survey, while the proportion of adolescents with food insecurity increased to 48.4% one year later. During the one year follow up period, more than half (54.8%) of the youth encountered transient food insecurity - that is, either during the first or the second round survey. During the follow up period, 14.0% of adolescents had chronic food insecurity (i.e. were food insecure at both rounds). Multivariable logistic regression analysis showed that adolescents in the urban households with low (OR = 1.69, P = 0.008) and middle (OR = 1.80, P = 0.003) income tertiles were nearly twice as likely to suffer from chronic food insecurity compared with those in high income tertile, while this was not the case in rural and semi-urban households. Female sex of adolescents (P < 0.01), high dependency ratio (P < 0.05) and household food insecurity (P < 0.001) were independent predictors of chronic adolescent food insecurity in urban, semi-urban, and rural areas, while educational status of the adolescents was negatively associated with chronic food insecurity (OR = 0.047, P = 0.002) in urban areas., Conclusions: In the context of increased food prices, household income is an independent predictor of chronic food insecurity only among adolescents in the low income, urban households. Female gender, educational status of primary or less and being a member of households with high dependency ratio were independent predictors of chronic food insecurity in urban, semi-urban, and rural areas. The fact that the prevalence of chronic food insecurity increased among adolescents who are members of chronically food insecure urban households as income tertiles decreased suggests that the resilience of buffering is eroded when purchasing power diminishes and food resources are dwindling. Food security interventions should target urban low income households to reduce the level of chronic food insecurity and its consequences.

Objective: To evaluate the safety and efficacy of a vaccine containing plasmid DNA with an insert encoding human tyrosinase (ie, huTyr vaccine) as adjunctive treatment for oral malignant melanoma (MM) in dogs., Animals: 111 dogs (58 prospectively enrolled in a multicenter clinical trial and 53 historical controls) with stage II or III oral MM (modified World Health Organization staging scale, I to IV) in which locoregional disease control was achieved., Procedures: 58 dogs received an initial series of 4 injections of huTyr vaccine (102 μg of DNA/injection) administered transdermally by use of a needle-free IM vaccination device. Dogs were monitored for adverse reactions. Surviving dogs received booster injections at 6-month intervals thereafter. Survival time for vaccinates was compared with that of historical control dogs via Kaplan-Meier survival analysis for the outcome of death., Results: Kaplan-Meier analysis of survival time until death attributable to MM was determined to be significantly improved for dogs that received the huTyr vaccine, compared with that of historical controls. However, median survival time could not be determined for vaccinates because < 50% died of MM before the end of the observation period. No systemic reactions requiring veterinary intervention were associated with vaccination. Local reactions were primarily limited to acute wheal or hematoma formation, mild signs of pain at the injection site, and postvaccination bruising., Conclusions and Clinical Relevance: Results support the safety and efficacy of the huTyr DNA vaccine in dogs as adjunctive treatment for oral MM., Impact for Human Medicine: Response to DNA vaccination in dogs with oral MM may be useful in development of plasmid DNA vaccination protocols for human patients with similar disease.

Background: In prior work, children born to mothers who received neuraxial anesthesia for cesarean delivery had a lower incidence of subsequent learning disabilities compared with vaginal delivery. The authors speculated that neuraxial anesthesia may reduce stress responses to delivery, which could affect subsequent neurodevelopmental outcomes. To further explore this possibility, we examined the association between the use of neuraxial labor analgesia and development of childhood learning disabilities in a population-based birth cohort of children delivered vaginally., Methods: The educational and medical records of all children born to mothers residing in the area of 5 townships of Olmsted County, Minnesota from 1976 to 1982 and remaining in the community at age 5 years were reviewed to identify those with learning disabilities. Cox proportional hazards regression was used to compare the incidence of learning disabilities between children delivered vaginally with and without neuraxial labor analgesia, including analyses adjusted for factors of either potential clinical relevance or that differed between the 2 groups in univariate analysis., Results: Of the study cohort, 4684 mothers delivered children vaginally, with 1495 receiving neuraxial labor analgesia. The presence of childhood learning disabilities in the cohort was not associated with use of labor neuraxial analgesia (adjusted hazard ratio, 1.05; 95%confidence interval, 0.85-1.31; P = 0.63)., Conclusion: The use of neuraxial analgesia during labor and vaginal delivery was not independently associated with learning disabilities diagnosed before age 19 years. Future studies are needed to evaluate potential mechanisms of the previous finding indicating that the incidence of learning disabilities is lower in children born to mothers via cesarean delivery under neuraxial anesthesia compared with vaginal delivery.

The accurate assessment of risky sexual behaviors and barriers to condom use is essential to reduce the spread of HIV/AIDS. This study tests a new nonverbal response-card method for obtaining more accurate responses to sensitive questions in the context of face-to-face interviewer-administered questionnaires in a survey of 1,269 Ethiopian young people aged 13-24. Comparisons of responses between a control group that provided verbal responses and an experimental group that used the card indicate that the prevalence of nonmarital sexual intercourse may be two times higher and knowledge of condom access may be 22 percent lower in the study than typical population-survey methods suggest. These results suggest that our nonverbal response-card method yields less biased estimates of risky adolescent sexual behavior and perceived access to condoms than those derived from conventional face-to-face interviewer-administered surveys, and that this method provides an effective, easy-to-use, low-cost alternative.

Objective: To determine the response rate after administration of a single dose of doxorubicin in dogs with B-cell or T-cell multicentric or thymic lymphoma., Design: Retrospective case series., Animals: 41 client-owned dogs with lymphoma., Procedures: Medical records of dogs in which lymphoma was diagnosed between February 2006 and October 2008 were reviewed. Entry criteria included that dogs had a confirmed lymphoma that was immunophenotyped to be of B-cell or T-cell origin. Only dogs that received doxorubicin alone as their first chemotherapy treatment and were evaluated 1 week later were included in the study. Dogs were excluded when they had received prior treatment with corticosteroids. Medical records were reviewed to obtain signalment, stage and substage of lymphoma, and immunophenotype and to determine whether the dog had hypercalcemia at the time of diagnosis., Results: Dogs with T-cell lymphoma had a significantly lower response rate to doxorubicin than did dogs with B-cell lymphoma. Twenty-five of 29 (86.2%) dogs with B-cell lymphoma had a complete response, compared with 2 of 12 dogs in the T-cell group that had a complete response. The overall response rate of dogs with B-cell lymphoma was 100%, compared with a response rate of 50% in dogs with T-cell lymphoma., Conclusions and Clinical Relevance: Standard-of-care chemotherapy protocols for the treatment of dogs with lymphoma include doxorubicin. Many dogs with T-cell lymphoma did not respond to doxorubicin; therefore, multiagent protocols containing doxorubicin may not be optimal. Alternative protocols should be considered for dogs with T-cell lymphoma that do not respond to doxorubicin.

Purpose: The purpose of this study was to determine the objective response rate (ORR) following treatment of canine mast cell tumors (MCT) with toceranib phosphate (Palladia, SU11654), a kinase inhibitor with both antitumor and antiangiogenic activity through inhibition of KIT, vascular endothelial growth factor receptor 2, and PDGFRbeta. Secondary objectives were to determine biological response rate, time to tumor progression, duration of objective response, health-related quality of life, and safety of Palladia., Experimental Design: Dogs were randomized to receive oral Palladia 3.25 mg/kg or placebo every other day for 6 weeks in the blinded phase. Thereafter, eligible dogs received open-label Palladia., Results: The blinded phase ORR in Palladia-treated dogs (n = 86) was 37.2% (7 complete response, 25 partial response) versus 7.9% (5 partial response) in placebo-treated dogs (n = 63; P = 0.0004). Of 58 dogs that received Palladia following placebo-escape, 41.4% (8 complete response, 16 partial response) experienced objective response. The ORR for all 145 dogs receiving Palladia was 42.8% (21 complete response, 41 partial response); among the 62 responders, the median duration of objective response and time to tumor progression was 12.0 weeks and 18.1 weeks, respectively. Palladia-treated responders scored higher on health-related quality of life versus Palladia-treated nonresponders (P = 0.030). There was no significant difference in the number of dogs with grade 3/4 (of 4) adverse events; adverse events were generally manageable with dose modification and/or supportive care., Conclusions: Palladia has biological activity against canine MCTs and can be administered on a continuous schedule without need for routine planned treatment breaks. This clinical trial further shows that spontaneous tumors in dogs are good models to evaluate therapeutic index of targeted therapeutics in a clinical setting.

Ciliary beating of airway epithelial cells drives the removal of mucus and particles from the airways. Mucociliary transport and possibly airway epithelial development are governed by muscarinic acetylcholine receptors but the precise roles of the subtypes involved are unknown. This issue was addressed by determining cilia-driven particle transport, ciliary beat frequency, and the composition and ultrastructural morphology of the tracheal epithelium in M1-M5 muscarinic receptor gene-deficient mice. Knockout of M3 muscarinic receptors prevented an increase in particle transport speed and ciliary beat frequency in response to muscarine. Furthermore, the ATP response after application of muscarine was blunted. Pretreatment with atropine before application of muscarine restored the response to ATP. Additional knockout of the M2 receptor in these mice partially restored the muscarine effect, most likely through the M1 receptor, and normalised the ATP response. M1, M4 and M5 receptor-deficient mice exhibited normal responses to muscarine. None of the investigated mutant mouse strains had any impairment of epithelial cellular structure or composition. In conclusion, M3 receptors stimulate whereas M2 receptors inhibit cilia-driven particle transport. The M1 receptor increases cilia-driven particle transport if the M3 and M2 receptors are missing. None of the receptors is necessary for epithelial development.

Background: Feline nasal lymphoma (NLSA) is a condition for which no standard of care exists., Hypothesis: There is no difference in survival times of cats with NLSA treated with single or multimodality therapy., Animals: Records from 97 cats diagnosed with NLSA were examined., Methods: The purpose of this retrospective study was to compare the survival times of cats with NLSA treated with radiation therapy (RT) alone, chemotherapy alone, or RT + chemotherapy and identify potential prognostic variables that affected survival. Cats were grouped according to therapy: RT + chemotherapy (n = 60), RT alone (n = 19), or chemotherapy alone (n = 18)., Results: Survival was calculated with 2 methods. The 1st survival analysis (method A) included all cats, but counted only deaths caused by progressive NLSA. The median survival time (MST), regardless of therapy modality, was 536 days. The 2nd survival analysis (method B) also included all cats and counted all deaths, regardless of cause, as events. The overall MST calculated for all deaths was 172 days. A negative independent prognostic variable identified was anemia (P < .001), and positive independent prognostic variables were a complete response to therapy (P < .001) and total radiation dose >32 Gy (P= .03)., Conclusions and Clinical Importance: There were no significant differences in survival times among the 3 treatment groups but these results suggest that the addition of higher doses of RT to a cat's treatment protocol may control local disease and therefore influence survival.

In many sub-Saharan African countries, young women face decreasing educational opportunities, age asymmetries between sexual partners, and high prevalence of HIV infection. This study draws upon data from the 2002 Cameroon Adolescent Reproductive Health Survey to analyze the determinants of young women's perceived ability to refuse sex in urban Cameroon. Our findings are consistent with predictions of social exchange theory: young women's status characteristics predict their vulnerability differently under different circumstances, and, overall, young women report having a lower ability to refuse sex in their relationships with men who offer to pay their school fees than in their relationships with men in positions of power over them. The costs and benefits of sexual exchanges made in order to continue one's education increase simultaneously in a context of declining enrollments and spreading HIV infection. When educational aspirations exceed opportunities, policy supporting access to education could reduce young women's need to employ their sexual resources in order to invest in their future.

Objective: To evaluate safety and efficacy of LDI-100, a preparation containing human chorionic gonadotropin (hCG) and bacillus Calmette-Guerin (BCG), in the treatment of dogs with mast cell tumors and to compare results with those from a control group receiving single-agent vinblastine., Animals: 95 dogs with measurable grade II or III mast cell tumors., Procedures: Dogs were randomized to receive either LDI-100 (1.35 ng of BCG and 2 units of hCG, SC, q 24 h) or vinblastine (2 mg/m(2), IV, q 1 wk) for 6 weeks. Tumors were measured at baseline and day 42, and dogs were monitored for signs of toxicosis. Clinical performance scores were recorded at each visit. Differences in host factors (sex, weight, and age), clinical performance score, tumor response, and adverse events were analyzed., Results: 46 dogs received LDI-100, and 49 dogs received vinblastine. No significant differences were found between the 2 treatment groups with regard to host factors or clinical performance score. Tumor response (>or=50% reduction) rates were similar between the LDI-100 and vinblastine group (28.6% and 11.7%, respectively). Dogs in the LDI-100 group had significantly less neutropenia than the vinblastine group., Conclusions and Clinical Relevance: hCG and BCG have immunomodulatory and antitumor effects against a variety of malignancies in humans and dogs. In this study, LDI-100 provided clinical responses comparable to single-agent vinblastine chemotherapy but without myelosuppression. LDI-100 is a promising new agent that should be further investigated for multimodality therapy of mast cell tumors in dogs.

For individuals meeting Bethesda criteria for hereditary nonpolyposis colorectal cancer syndrome, the microsatellite instability (MSI) test is recommended as a screening evaluation before proceeding to genetic testing. The MSI test is new to the medical setting, but will be increasingly used to screen patients at high risk for hereditary nonpolyposis colorectal cancer. The main goals of this study were to examine knowledge about and exposure to the MSI test among individuals considering the test, to evaluate perceived benefits and barriers to undergoing the MSI test, and to identify the demographic, medical, and psychosocial correlates of the perceived benefits and barriers to undergoing the test. One hundred and twenty-five patients completed a survey after being offered the test, but prior to making the decision whether to pursue MSI testing. Results indicated low levels of knowledge about and previous exposure to the MSI test. Participants held positive attitudes about the potential benefits of the test and perceived few barriers to undergoing the test. Motivations were similar to those cited by individuals considering other genetic tests. Participants with nonmetastatic disease, with lower perceived risk for cancer recurrence, and who reported more self-efficacy endorsed more benefits from the test. Higher levels of cancer-specific psychological distress were associated with more perceived barriers to having the test. These findings suggest that individuals considering the MSI test know very little about it but hold positive attitudes about the test's utility. More distressed patients, patients who perceive themselves at higher risk for cancer recurrence, and patients with metastatic disease might be less motivated to have the MSI test.

Background: This study was designed to assess the efficacy of a matrix metalloproteinase inhibitor in prolonging posttreatment survival for dogs with appendicular osteosarcoma after treatment with amputation and doxorubicin chemotherapy., Hypothesis: Survival will be prolonged in dogs receiving BAY 12-9566., Animals: The study included 303 dogs with appendicular osteosarcoma., Methods: Dogs were treated with doxorubicin (30 mg/m2) every 2 weeks for 5 treatments starting 2 weeks after amputation. Dogs were randomly allocated to receive a novel nonpeptidic biphenyl inhibitor of matrix metalloproteinases (MMPs, BAY 12-9566; 4-[4-4-(chlorophenyl)phenyl]-4-oxo-2S-(phenylthiomethyl) butanoic acid) or placebo after doxorubicin chemotherapy., Results: Median survival for all 303 dogs was 8 months; and 1-year, 2-year, and 3-year survival rates were 35%, 17%, and 9%, respectively. Treatment with BAY 12-9566 did not influence survival. Multivariate analysis revealed that increasing age (P = .004), increasing weight (P = .006), high serum alkaline phosphatase (ALP) (P = .012) and high bone ALP (P < .001) were independently associated with shorter median survival times. Additional analyses on available data indicated that as the number of mitotic figures in the biopsy increased (P = .013), and as plasma active MMP-2 concentrations increased (P = .027), the risk of dying increased., Conclusions and Clinical Importance: Doxorubicin is an effective adjuvant to amputation in prolonging survival for dogs with appendicular osteosarcoma.

Age at first union is increasing throughout much of sub-Saharan Africa at the same time that not all couples are waiting for marriage before their first sexual intercourse. We assessed the effect of a premarital first birth on entrance into a first union in an urban area in East Africa -- Moshi, Tanzania. The data come from the Moshi Infertility Survey of 2002-2003. Women who spent less than a year in single motherhood were significantly more likely than childless women to enter into a first union, although the magnitude of this relationship was weaker for more recent cohorts. Women who had been single mothers for 5 or more years (about two-thirds of women with a premarital birth) were significantly less likely than women without children to enter into a first union.

Forty-eight dogs with histologically confirmed appendicular osteosarcoma (OSA) entered a prospective clinical trial evaluating treatment with amputation and up to 4 doses of carboplatin given every 21 days. The median disease-free interval (DFI) was 257 days, with 31.2% of the dogs disease-free at 1 year. The median survival time was 321 days, with 35.4% of the dogs alive at 1 year. Dogs with proximal humeral OSA had shorter DFI (P = .016) and survival (P = .037) times than dogs with OSA at other locations. Dogs with lower body weights ( < 40 kg) had longer DFI (P = .0056) and survival (P = .007) times than larger dogs. Survival times for dogs that received carboplatin were statistically longer than those previously reported for amputation alone (P < .001). DFI and survival times are similar to those previously reported for 2 to 4 doses of cisplatin. Carboplatin appears to be a well-tolerated chemotherapeutic drug that can be given safely every 21 days at a dose of 300 mg/m2. Neutropenia was the dose-limiting toxicity in this study.

Twenty-five dogs with naturally occurring mast cell tumors were treated with daily oral prednisone (1 mg/kg) for 28 days. Five dogs (20%) had reduction in tumor volume and were considered responders. Four of these underwent partial remission and one underwent complete remission. Survival times for the five responders were 3, 5, 6, 7.5, and greater than 28 months, respectively. We therefore conclude that prednisone is effective in some canine mast cell tumors. Further studies are indicated to determine the most effective dose of prednisone, the appropriate duration of treatment, and the efficacy in more benign mast cell tumors, and in combination with other forms of therapy.

Seventy-one dogs with histologically confirmed appendicular osteosarcoma were evaluated. Seventeen dogs were treated with amputation and two postoperative [corrected] doses of IV cisplatin given 21 days apart (group 1). Nineteen dogs were treated with IV cisplatin 21 days before amputation, with a second dose given immediately after amputation (group 2). Thirty-five dogs were treated by amputation of the affected limb with no chemotherapy (group 3). The median disease-free interval for group 1 was 226 days, and 177 days for group 2. This was not significantly different. The median survival time was 262 days for group 1, 282 days for group 2 and 119 days for group 3. Group 1 and 2 dogs had survival times that were significantly longer than for dogs in group 3. Two IV courses of cisplatin given before or after amputation appears to improve the survival of dogs with osteosarcoma.