Objective- Coronary artery thrombosis can occur in the absence of plaque rupture because of superficial erosion. Erosion-prone atheromata associate with more neutrophil extracellular traps (NETs) than lesions with stable or rupture-prone characteristics. The effects of NETs on endothelial cell (EC) inflammatory and thrombogenic properties remain unknown. We hypothesized that NETs alter EC functions related to erosion-associated thrombosis. Approach and Results- Exposure of human ECs to NETs increased VCAM-1 (vascular cell adhesion molecule 1) and ICAM-1 (intercellular adhesion molecule 1) mRNA and protein expression in a time- and concentration-dependent manner. THP-1 monocytoid cells and primary human monocytes bound more avidly to NET-treated human umbilical vein ECs than to unstimulated cells under flow. Treatment of human ECs with NETs augmented the expression of TF (tissue factor) mRNA, increased EC TF activity, and hastened clotting of recalcified plasma. Anti-TF-neutralizing antibody blocked NET-induced acceleration of clotting by ECs. NETs alone did not exhibit TF activity or acceleration of clotting in cell-free assays. Pretreatment of NETs with anti-interleukin (IL)-1α-neutralizing antibody or IL-1Ra (IL-1 receptor antagonist)-but not with anti-IL-1β-neutralizing antibody or control IgG-blocked NET-induced VCAM-1, ICAM-1, and TF expression. Inhibition of cathepsin G, a serine protease abundant in NETs, also limited the effect of NETs on EC activation. Cathepsin G potentiated the effect of IL-1α on ECs by cleaving the pro-IL-1α precursor and releasing the more potent mature IL-1α form. Conclusions- NETs promote EC activation and increased thrombogenicity through concerted action of IL-1α and cathepsin G. Thus, NETs may amplify and propagate EC dysfunction related to thrombosis because of superficial erosion.

BackgroundThe incidence of melanoma is increasing faster than any other major cancer both in Brazil and worldwide. Southeast Brazil has especially high incidences of melanoma, and early detection is low. Exposure to ultraviolet (UV) radiation is a primary risk factor for developing melanoma. Increasing attractiveness is a major motivation among adolescents for tanning. A medical student-delivered intervention that takes advantage of the broad availability of mobile phones and adolescents’ interest in their appearance indicated effectiveness in a recent study from Germany. However, the effect in a high-UV index country with a high melanoma prevalence and the capability of medical students to implement such an intervention remain unknown.ObjectiveIn this pilot study, our objective was to investigate the preliminary success and implementability of a photoaging intervention to prevent skin cancer in Brazilian adolescents.MethodsWe implemented a free photoaging mobile phone app (Sunface) in 15 secondary school classes in southeast Brazil. Medical students “mirrored” the pupils’ altered 3-dimensional (3D) selfies reacting to touch on tablets via a projector in front of their whole grade accompanied by a brief discussion of means of UV protection. An anonymous questionnaire capturing sociodemographic data and risk factors for melanoma measured the perceptions of the intervention on 5-point Likert scales among 356 pupils of both sexes (13-19 years old; median age 16 years) in grades 8 to 12 of 2 secondary schools in Brazil.ResultsWe measured more than 90% agreement in both items that measured motivation to reduce UV exposure and only 5.6% disagreement: 322 (90.5%) agreed or strongly agreed that their 3D selfie motivated them to avoid using a tanning bed, and 321 (90.2%) that it motivated them to improve their sun protection; 20 pupils (5.6%) disagreed with both items. The perceived effect on motivation was higher in female pupils in both tanning bed avoidance (n=198, 92.6% agreement in females vs n=123, 87.2% agreement in males) and increased use of sun protection (n=197, 92.1% agreement in females vs n=123, 87.2% agreement in males) and independent of age or skin type. All medical students involved filled in a process evaluation revealing that they all perceived the intervention as effective and unproblematic, and that all pupils tried the app in their presence.ConclusionsThe photoaging intervention was effective in changing behavioral predictors for UV protection in Brazilian adolescents. The predictors measured indicated an even higher prospective effectiveness in southeast Brazil than in Germany (>90% agreement in Brazil vs >60% agreement in Germany to both items that measured motivation to reduce UV exposure) in accordance with the theory of planned behavior. Medical students are capable of complete implementation. A randomized controlled trial measuring prospective effects in Brazil is planned as a result of this study.

IntroductionThe incidence of melanoma is increasing faster than any other major cancer both in Brazil and worldwide. The Southeast of Brazil has especially high incidences of melanoma, and early detection is low. Exposure to UV radiation represents a primary risk factor for developing melanoma. Increasing attractiveness is a major motivation for adolescents for tanning. A medical student-delivered intervention that harnesses the broad availability of mobile phones as well as adolescents’ interest in their appearance may represent a novel method to improve skin cancer prevention.Methods and analysisWe developed a free mobile app (Sunface), which will be implemented in at least 30 secondary school classes, each with 21 students (at least 30 classes with 21 students for control) in February 2018 in Southeast Brazil via a novel method called mirroring. In a 45 min classroom seminar, the students’ altered three-dimensional selfies on tablets are ‘mirrored’ via a projector in front of their entire class, showing the effects of unprotected UV exposure on their future faces. External block randomisation via computer is performed on the class level with a 1:1 allocation. Sociodemographic data, as well as skin type, ancestry, UV protection behaviour and its predictors are measured via a paper–pencil questionnaire before as well as at 3 and 6 months postintervention. The primary end point is the group difference in the 30-day prevalence of daily sunscreen use at a 6-month follow-up. Secondary end points include (1) the difference in daily sunscreen use at a 3-month follow-up, (2) if a self-skin examination in accordance with the ABCDE rule was performed within the 6-month follow-up and (3) the number of tanning sessions.Ethics and disseminationEthical approval was obtained from the ethics committee of the University of Itauna. Results will be disseminated at conferences and in peer-reviewed journals.Trial registration numberNCT03178240; Pre-results.

Background Smoking is the largest preventable cause of mortality in Brazil. Education Against Tobacco (EAT) is a network of more than 3500 medical students and physicians across 14 countries who volunteer for school-based smoking prevention programs. EAT educates 50,000 adolescents per year in the classroom setting. A recent quasi-experimental study conducted in Germany showed that EAT had significant short-term smoking cessation effects among adolescents aged 11 to 15 years. Objective The aim is to measure the long-term effectiveness of the most recent version of the EAT curriculum in Brazil. Methods A randomized controlled trial was conducted among 2348 adolescents aged 12 to 21 years (grades 7-11) at public secondary schools in Brazil. The prospective experimental design included measurements at baseline and at 6 and 12 months postintervention. The study groups comprised randomized classes receiving the standardized EAT intervention (90 minutes of mentoring in a classroom setting) and control classes in the same schools (no intervention). Data were collected on smoking status, gender, social aspects, and predictors of smoking. The primary endpoint was the difference in the change in smoking prevalence between the intervention group and the control group at 12-month follow-up. Results From baseline to 12 months, the smoking prevalence increased from 11.0% to 20.9% in the control group and from 14.1% to 15.6% in the intervention group. This difference was statistically significant ( P <.01). The effects were smaller for females (control 12.4% to 18.8% vs intervention 13.1% to 14.6%) than for males (control 9.1% to 23.6% vs intervention 15.3% to 16.8%). Increased quitting rates and prevented onset were responsible for the intervention effects. The differences in change in smoking prevalence from baseline to 12 months between the intervention and control groups were increased in students with low school performance. Conclusions To our knowledge, this is the first randomized trial on school-based tobacco prevention in Brazil that shows significant long-term favorable effects. The EAT program encourages quitting and prevents smoking onset, especially among males and students with low educational background. Trial Registration ClinicalTrials.gov NCT02725021; https://clinicaltrials.gov/ct2/show/NCT02725021 International Registered Report Identifier (IRRID) RR2-10.2196/resprot.7134

Because exposure to UV radiation early in life is an important risk factor for melanoma development, reducing UV exposure in children and adolescents is of paramount importance. New interventions are urgently required.OBJECTIVE To determine the effect of the free face-aging mobile app Sunface on the skin cancer protection behavior of adolescents.DESIGN, SETTING, AND PARTICIPANTS This cluster-randomized clinical trial included a single intervention and a 6-month follow-up from February 1 to November 30, 2018. Randomization was performed on the class level in 52 school classes within 8 public secondary schools (grades 9-12) in Itauna, Southeast Brazil. Data were analyzed from May 1 to October 10, 2019.INTERVENTIONS In a classroom seminar delivered by medical students, adolescents' selfies were altered by the app to show UV effects on their future faces and were shown in front of their class, accompanied by information about UV protection. Information about relevant parameters was collected via anonymous questionnaires before and 3 and 6 months after the intervention. MAIN OUTCOMES AND MEASURESThe primary end point of the study was the difference in daily sunscreen use at 6 months of follow-up. Secondary end points included the difference in daily sunscreen use at 3 months of follow-up, at least 1 skin self-examination within 6 months, and at least 1 tanning session in the preceding 30 days. All analyses were predefined and based on intention to treat. Cluster effects were taken into account. RESULTS Participants included 1573 pupils (812 girls [51.6%] and 761 boys [48.4%]; mean [SD] age, 15.9 [1.3] years) from 52 school classes. Daily sunscreen use increased from 110 of 734 pupils (15.0%) to 139 of 607 ( 22.9%; P < .001) at the 6-month follow-up in the intervention group. The proportion of pupils performing at least 1 skin self-examination in the intervention group rose from 184 of 734 (25.1%) to 300 of 607 (49.4%; P < .001). Use of tanning decreased from 138 of 734 pupils (18.8%) to 92 of 607 (15.2%; P = .04). No significant changes were observed in the control group. The intervention was more effective for female students (number needed to treat for the primary end point: 8 for girls and 31 for boys). CONCLUSIONS AND RELEVANCEThese findings suggest that interventions based on face-aging apps may increase skin cancer protection behavior in Brazilian adolescents. Further studies are required to maximize the effect and to investigate the generalizability of the effects.