The cytosolic hyperoxidation-sensitive and -robust Leishmania peroxiredoxins cPRX1 and cPRX2 are both dispensable for parasite infectivity.

Typical two-cysteine peroxiredoxins (2-Cys-PRXs) are H2O2-metabolizing enzymes whose activity relies on two cysteine residues. Protists of the family Trypanosomatidae invariably express one cytosolic 2-Cys-PRX (cPRX1). However, the Leishmaniinae sub-family features an additional isoform (cPRX2), almost identical to cPRX1, except for the lack of an elongated C-terminus with a Tyr-Phe (YF) motif. Previously, cytosolic PRXs were considered vital components of the trypanosomatid antioxidant machinery. Here, we shed new light on the properties, functions and relevance of cPRXs from the human pathogen Leishmania infantum. We show first that LicPRX1 is sensitive to inactivation by hyperoxidation, mirroring other YF-containing PRXs participating in redox signaling. Using genetic fusion constructs with roGFP2, we establish that LicPRX1 and LicPRX2 can act as sensors for H2O2 and oxidize protein thiols with implications for signal transduction. Third, we show that while disrupting the LicPRX-encoding genes increases susceptibility of L. infantum promastigotes to external H2O2in vitro, both enzymes are dispensable for the parasites to endure the macrophage respiratory burst, differentiate into amastigotes and initiate in vivo infections. This study introduces a novel perspective on the functions of trypanosomatid cPRXs, exposing their dual roles as both peroxidases and redox sensors. Furthermore, the discovery that Leishmania can adapt to the absence of both enzymes has significant implications for our understanding of Leishmania infections and their treatment. Importantly, it questions the conventional notion that the oxidative response of macrophages during phagocytosis is a major barrier to infection and the suitability of cPRXs as drug targets for leishmaniasis.

Structure-Activity Relationship Studies of 9-Alkylamino-1,2,3,4-tetrahydroacridines against Leishmania (Leishmania) infantum Promastigotes.

Leishmaniasis is one of the most neglected diseases in modern times, mainly affecting people from developing countries of the tropics, subtropics and the Mediterranean basin, with approximately 350 million people considered at risk of developing this disease. The incidence of human leishmaniasis has increased over the past decades due to failing prevention and therapeutic measures-there are no vaccines and chemotherapy, which is problematic. Acridine derivatives constitute an interesting group of nitrogen-containing heterocyclic compounds associated with numerous bioactivities, with emphasis to their antileishmanial potential. The present work builds on computational studies focusing on a specific enzyme of the parasite, S-adenosylmethionine decarboxylase (AdoMet DC), with several 1,2,3,4-tetrahydro-acridines emerging as potential inhibitors, evidencing this scaffold as a promising building block for novel antileishmanial pharmaceuticals. Thus, several 1,2,3,4-tetrahydroacridine derivatives have been synthesized, their activity against Leishmania (Leishmania) infantum promastigotes evaluated and a structure-activity relationship (SAR) study was developed based on the results obtained. Even though the majority of the 1,2,3,4-tetrahydroacridines evaluated presented high levels of toxicity, the structural information gathered in this work allowed its application with another scaffold (quinoline), leading to the obtention of N1,N12-bis(7-chloroquinolin-4-yl)dodecane-1,12-diamine (12) as a promising novel antileishmanial agent (IC50 = 0.60 ± 0.11 µM, EC50 = 11.69 ± 3.96 µM and TI = 19.48).

Arguments used by proponents and opponents in Brazil's regulatory discussions of e-cigarettes and heated tobacco products.

OBJECTIVES: To identify proponents and opponents of the commercialisation and marketing of e-cigarettes and heated tobacco products (HTPs), identify the arguments used on both sides and compare how the arguments have changed over time, we analysed three policy discussions occurring in 2009, 2018 and 2019. METHODS: We conducted a content analysis of one document and six videos from these discussions, provided on the Brazilian Health Regulatory Agency website, or upon request. RESULTS: The arguments most used by tobacco companies were related to claims that the use of e-cigarettes and HTPs is less harmful than conventional tobacco. Unions that support its commercialisation also argued that lifting the ban would prevent smuggling and guarantee their quality. On the other side, universities, medical and anti-tobacco institutions argued that such devices may have health risks, including the risk of inducing cigarette smoking. In 2009, most arguments belonged to the 'health' theme, while in 2018 and 2019 economic arguments and those related to morals and ethics were frequently used. CONCLUSIONS: Those that supported the commercialisation and marketing of e-cigarettes and HTPs first focused on arguments of harm reduction, while 10 years later the right to access and potential economic consequences also became common. Public health agents and academics must gather evidence to effectively respond to these arguments and discuss these policies, and must prepare themselves to use and respond to arguments related to moral and economic themes.

School tobacco policies and adolescent smoking in six European cities in 2013 and 2016: A school-level longitudinal study.

Assessment of the effectiveness of school tobacco policies (STPs) in reducing adolescent smoking remains inconclusive. Previous studies took insufficient account of different dimensions of STPs, the different views of students and staff, and policy changes over time. This study assessed how a multidimensional STP, as perceived by students and staff, was associated with adolescent smoking over time in six European cities. The SILNE and SILNE-R surveys were conducted among students (n = 18,502) and staff (n = 438) in 38 schools in 2013 and 2016. Three dimensions (comprehensiveness, enforcement, and communication) were assessed and we calculated total STP scores. Multilevel logistic regressions estimated associations of STPs with adolescent smoking on and just outside school premises and with weekly smoking. Further analyses estimated associations between 2013 and 2016 STP changes and smoking outcomes in 2016, controlling for STP and smoking prevalence in 2013. On average, there were few increases in STP scores over time. Greater STP enforcement, as perceived by students, was associated with lower odds of weekly smoking (OR:0.93, 95%CI:0.89-0.97) and of smoking on school premises (OR:0.80, 95%CI:0.72-0.90). Higher total STP scores were associated with lower odds of smoking on school premises (OR:0.76, 95%CI:0.67-0.86), but not of smoking just outside premises or smoking weekly. Greater increases in STP scores over time were associated with lower odds of smoking on school premises in 2016 (OR:0.65, 95%CI:0.47-0.89). Well-enforced STPs may help reduce adolescent smoking at school. Schools should be supported in adopting comprehensive policies that also extend to the surroundings of their premises.

Cost of youth tobacco-control policies in seven European countries.

BACKGROUND: Tobacco-control policies have been suggested to reduce smoking among adolescents. However, there is limited evidence on the real-world costs of implementation in different settings. In this study, we aimed at estimating the costs of school smoking bans, school prevention programmes and non-school bans (smoking bans in non-educational public settings, bans on sales to minors and bans on point-of-sale advertising), implemented in Finland, Ireland, the Netherlands, Belgium, Germany, Italy and Portugal, for 2016. METHODS: We retrospectively collected costs related to the inspection, monitoring and sanctioning activities related to bans and educational activities related to smoking prevention programmes. We used an 'ingredients-based' approach, identifying each resource used, quantity and unit value for one full year, under the state perspective. Costs were measured at national, regional, local and school-level and were informed by data on how these activities were performed in reality. RESULTS: Purchasing power parities adjusted-costs varied between €0.02 and €0.74 (average €0.24) per person (pp) for bans implemented outside schools. Mean costs of school smoking bans ranged from €3.31 to €34.76 (average €20.60), and mean costs of school educational programmes from €0.75 to €4.65 (average €2.92). CONCLUSIONS: It is feasible to estimate costs of health policies as implemented in different settings. Costs of the tobacco control policies evaluated here depend mainly on the number of person-hours allocated to their implementation, and on the scale of intervention. Non-school bans presented the lowest costs, and the implementation of all policies cost up to €36 pp for 1 year.

Economic Evaluation of Five Tobacco Control Policies Across Seven European Countries.

INTRODUCTION: Economic evaluations of tobacco control policies targeting adolescents are scarce. Few take into account real-world, large-scale implementation costs; few compare cost-effectiveness of different policies across different countries. We assessed the cost-effectiveness of five tobacco control policies (nonschool bans, including bans on sales to minors, bans on smoking in public places, bans on advertising at points-of-sale, school smoke-free bans, and school education programs), implemented in 2016 in Finland, Ireland, the Netherlands, Belgium, Germany, Italy, and Portugal. METHODS: Cost-effectiveness estimates were calculated per country and per policy, from the State perspective. Costs were collected by combining quantitative questionnaires with semi-structured interviews on how policies were implemented in each setting, in real practice. Short-term effectiveness was based on the literature, and long-term effectiveness was modeled using the DYNAMO-HIA tool. Discount rates of 3.5% were used for costs and effectiveness. Sensitivity analyses considered 1%-50% short-term effectiveness estimates, highest cost estimates, and undiscounted effectiveness. FINDINGS: Nonschool bans cost up to €253.23 per healthy life year, school smoking bans up to €91.87 per healthy life year, and school education programs up to €481.35 per healthy life year. Cost-effectiveness depended on the costs of implementation, short-term effectiveness, initial smoking rates, dimension of the target population, and weight of smoking in overall mortality and morbidity. CONCLUSIONS: All five policies were highly cost-effective in all countries according to the World Health Organization thresholds for public health interventions. Cost-effectiveness was preserved even when using the highest costs and most conservative effectiveness estimates. IMPLICATIONS: Economic evaluations using real-world data on tobacco control policies implemented at a large scale are scarce, especially considering nonschool bans targeting adolescents. We assessed the cost-effectiveness of five tobacco control policies implemented in 2016 in Finland, Ireland, the Netherlands, Belgium, Germany, Italy, and Portugal. This study shows that all five policies were highly cost-effective considering the World Health Organization threshold, even when considering the highest costs and most conservative effectiveness estimates.

Adolescents' smoking environment under weak tobacco control: A mixed methods study for Portugal.

INTRODUCTION: Bans on smoking in public places and on sales to minors have been widely implemented across the globe. However, many countries have either adopted non-comprehensive (i.e., partial) bans and/or weakly enforce those bans. Little is known, from the adolescents' perspective, how this affects their smoking-related perceptions and behaviors. We studied the case of Portugal, where bans are partial and/or weakly enforced. We sought to understand how the bans affect adolescents' access to cigarettes from commercial sources, the visibility of smoking in public places, and smoking locations. MATERIAL AND METHODS: We used a mixed methods design on data gathered in 2016. Quantitative, cross-sectional surveys were conducted in six schools (n = 2,444) in Coimbra, Portugal. In two of these schools, qualitative data were collected in eight single-sex focus group interviews (n = 42). RESULTS: Ninety-five percent of the adolescents who tried to buy cigarettes were able to do so from commercial sources, through vending machines, or directly from the vendor. Bans on smoking on school premises and at enclosed public places did not prevent these adolescents from observing smoking outside school gates (84.0%), in cafes and restaurants (97%), or from smoking at cafes, bars, or nightclubs (72.9%). DISCUSSION: Partial and/or weakly enforced policies seem to not prevent adolescents from having access to cigarettes, frequently seeing smoking, and finding ample opportunities to smoke in public places. Adopting and enforcing comprehensive policies are necessary efforts to prevent unfavorable responses and more effectively reduce adolescents' smoking behavior.

The visibility of smoking in Europe and its relationship with youth's positive beliefs about smoking.

OBJECTIVES: To determine adolescent-reported visibility of smoking in different public and private spaces in Europe and associations between smoking visibility and beliefs about the benefits of smoking. METHODS: We used SILNE-R cross-sectional survey data (2016/2017) of 10,798 14-16-year-old students from 55 secondary schools in seven European cities. Respondents reported for private and public spaces whether they had seen others smoke there in the last 6 months. Beliefs about the benefits of smoking were measured on a 7-item scale; higher scores indicated more positive beliefs. Multilevel linear regression analyses determined associations while controlling for potential confounders and stratifying by smoking status. RESULTS: Most students reported observing others smoke in public spaces, especially at train/bus stations (84%). Positive beliefs about smoking of never smokers were positively associated with seeing others smoke in train/bus stations and leisure/sports facilities, but not at home, a friend's home, restaurants or bars, when fully adjusted. Associations were of similar magnitude for ever smokers. CONCLUSIONS: Smoking in several public places is highly visible to adolescents. Reducing this visibility might weaken positive beliefs that adolescents have about smoking.

Smoking and school absenteeism among 15- to 16-year-old adolescents: a cross-section analysis on 36 European countries.

BACKGROUND: Schools have a crucial role to play in preventing youth smoking. However, the well-known long-term health consequences of youth smoking may be insufficient to convince education stakeholders to devote efforts to implement school-based programmes. However, if youth smoking were to have short-term consequences, this evidence could prompt education stakeholders' action. In this article, we investigate the link between smoking and school absenteeism. METHODS: We used data from the 2011 wave of the European School Survey Project on Alcohol and Other Drugs, on adolescents aged 15-16. We applied logistic models to assess the risk of more than 3 missed school days, by cause, as function of smoking intensity, adjusting for age, sex, socioeconomic status, academic performance, parental involvement and other risk behaviours (alcohol and cannabis consumption). Consistency was assessed by replicating the analyses for each sex and age group and further adjusting for depression and self-esteem. RESULTS: Smoking more than five cigarettes per day was significantly linked to school absenteeism, with a 55% excess risk of missing more than 3 school days per month due to illness (OR = 1.55, 95% CI 1.46-1.64), and a more than two times excess risk due to skipping (OR = 2.29; 95% CI 2.16-2.43). These findings were consistent across age and sex groups. CONCLUSION: We observed an association between smoking intensity and absenteeism among youth in Europe. This implies that, to the extent that this association is causal, school tobacco control policies may reduce the short-term consequences of smoking on adolescents' education and health.

Public smoking ban and socioeconomic inequalities in smoking prevalence and cessation: a cross-sectional population-based study in Geneva, Switzerland (1995-2014).

INTRODUCTION: Smoking bans were suggested to reduce smoking prevalence and increase quit ratio but their equity impact remains unclear. We aimed to characterise the socioeconomic status (SES)-related inequalities in smoking prevalence and quit ratio before and after the implementation of a public smoking ban. METHODS: We included data from 17 544 participants in the population-based cross-sectional Bus Santé study in Geneva, Switzerland, between 1995 and 2014. We considered educational attainment (primary, secondary and tertiary) as a SES indicator. Outcomes were smoking prevalence (proportion of current smokers) and quit ratio (ex-smokers to ever-smokers ratio). We used segmented linear regression to assess the overall impact of smoking ban on outcome trends. We calculated the relative (RII) and slope (SII, absolute difference) indexes of inequality, quantifying disparities between educational groups in outcomes overall (1995-2014), before and after ban implementation (November 2009). RESULTS: Least educated participants displayed higher smoking prevalence (RII=2.04, P<0.001; SII=0.15, P<0.001) and lower quit ratio (RII=0.73, P<0.001; SII=-0.18, P<0.001). As in other studies, smoking ban implementation coincided with a temporary reduction of smoking prevalence (P=0.003) and increase in quit ratio (P=0.02), with a progressive return to preban levels. Inequalities increased (P<0.05) in relative terms for smoking prevalence (RIIbefore=1.84, P<0.001 and RIIafter=3.01, P<0.001) and absolute terms for both outcomes (smoking prevalence: SIIbefore=0.14, P<0.001 and SIIafter=0.19, P<0.001; quit ratio: SIIbefore=-0.15, P<0.001 and SIIafter=-0.27, P<0.001). CONCLUSIONS: Implementation of a public smoking ban coincided with a short-lived decrease in smoking prevalence and increase in quit ratio but also with a widening in SES inequalities in smoking-related outcomes.

Cost-effectiveness of tobacco control policies and programmes targeting adolescents: a systematic review.

Background: Consistent evidence shows the importance of preventing smoking at young ages, when health behaviours are formed, with long-term consequences on health and survival. Although tobacco control policies and programmes targeting adolescents are widely promoted, the cost-effectiveness of such interventions has not been systematically documented. We performed a systematic review on the cost-effectiveness of policies and programmes preventing tobacco consumption targeting adolescents. Methods: We systematically reviewed literature on the (i) cost and effectiveness of (ii) prevention policies targeting (iii) smoking by (iv) adolescents. PubMed, Web of Science, Cochrane, CEA-TUFTS, Health Economic Evaluations, Wiley Online Library, Centre for Reviews and Dissemination Database, the National Institute for Health and Care Excellence and Google Scholar databases were used, and Google search engine was used for other grey literature review. Results: We obtained 793 full-text papers and 19 grey literature documents, from which 16 studies fulfilled the inclusion criteria. Of these, only one was published in the last 5 years, and 15 were performed in high-income countries. Eight analyzed the cost-effectiveness of school-based programmes, five focused on media campaigns and three on legal bans. Policies and programmes were found to be cost-effective in all studies, and both effective and cost-saving in about half of the studies. Conclusions: Evidence is scarce and relatively obsolete, and rarely focused on the evaluation of legal bans. Moreover, no comparisons have been made between different interventions or across different contexts and implementation levels. However, all studies conclude that smoking prevention policies and programmes amongst adolescents are greatly worth their costs.

Violência contra crianças e adolescentes: estudo do processo de vitimização / Violence against children and adolescents: study of the process of victimization

Estudo qualitativo que visa aprofundar o conhecimento sobre a questão política e cultural da violência contra crianças e adolescentes no Brasil. Desta forma, pretende estudar e compreender o fenômeno da vitimização de crianças e os fatores culturais a ele associados. O trabalho de campo resumiu-se ao estudo de 3 casos de vitimização de crianças, sendo entrevistados os vitimizadores e as crianças. Em todos os casos os vitimizadores eram as próprias mães, o que significa dizer que a violência contra criança começa dentro do próprio lar. Por outro lado, as mães-vitimizadoras encaram seus atos como algo sem importância. Dados culturais e sociais da nossa sociedade como a Síndrome do Pequeno Poder reforçam este tipo de atitude por parte dos vitimizadores. Simultaneamente, associam-se grandes problemas da esfera macro-social, o que nos dá um panorama vitimizador da infância no Brasil. Por último, conclui-se que é necessário lutar pela formação de sujeitos sociais capazes de transformar a realidade da infância em nosso país.