Autism in patients with eosinophilic gastrointestinal disease: A systematic review with meta-analysis.

PURPOSE: Neurodevelopmental disorders, such as autism spectrum disorder (ASD), have been increasingly associated with eosinophilic gastrointestinal disorders (EGID). However, the relationship between these diseases remains unclear. We performed a systematic review with meta-analysis to address this issue. METHODS: The search was performed according to the PRISMA guidelines using descriptors for ASD and EGIDs from the MEDLINE, Embase, PsycInfo, LILACS, and Web of Science databases. Observational studies with the prevalence of ASD in any EGID were included. The study protocol was registered on the PROSPERO platform under the number CRD42023455177. RESULTS: The total dataset comprised 766,082 participants. The result of the single-arm meta-analysis showed an overall prevalence of ASD in the population with EGID of 21.59% (95% CI: 10.73-38.67). There was an association between EGID and ASD (OR: 3.44; 95% CI: 1.25-2.21), also significant when restricted only to EoE (OR: 3.70; 95% CI: 2.71-5.70). DISCUSSION: Recent studies have implicated the influence of an inadequate epithelial barrier integrity in the pathogenesis of several diseases. The role of this mechanism can be extended to situations beyond allergic reactions, including other conditions with underlying immunological mechanisms. Several diseases are potentially related to the systemic effect of bacterial translocation in tissues with defective epithelial barriers. CONCLUSION: Our meta-analysis provides evidence that supports the consideration of EGID in patients with ASD and ASD in patients with EGID. Despite its limitations, the results should also be validated by future studies, preferably using multicenter prospective designs in populations with low referral bias.

Non-smokers' and smokers' support for smoke-free legislation in 14 indoor and outdoor settings across 12 European countries.

BACKGROUND: European countries differ considerably in the scope and the extent of their policies to protect people from the harms of secondhand smoke exposure. Public opinion may have a substantial influence on several stages of policy development, implementation, and compliance. For this reason, we aimed to evaluate the population level of support for smoke-free policies and its correlates. METHODS: We used data from the TackSHS Survey (2017-2018), a cross-sectional study with representative samples of the general population aged ≥15 years from 12 European countries. We described the proportion of non-smokers' and smokers' support for the implementation of smoke-free legislation in 14 indoor and outdoor settings and the country-level characteristics associated with it. RESULTS: In the total sample (n = 11,902), support for smoke-free legislation were the lowest for restaurants/bar patios (non-smokers = 53.0%; smokers = 29.2%) and the highest for workplaces (non-smokers = 78.5%; smokers = 66.5%). In the country-level analysis, the highest support among non-smokers was for workplaces in Bulgaria (93.1%) and the lowest for restaurants/bars patios in Greece (39.4%). Among smokers, the corresponding estimates were for children's playgrounds in Latvia (88.9%) and for cars in Portugal (21%). For most settings, support for smoke-free legislation was directly related with the countries' prevalence of secondhand smoke presence and reported smoking in each setting. DISCUSSION: Our results show that the majority of European adults (including a large proportion of smokers) are supportive of implementing smoke-free legislation in indoor settings and extending it to selected outdoor settings. Such expressive support can be seen as an opportunity to advance legislation and protect the European population from secondhand smoke exposure.

Secondhand Smoke Exposure in European Countries With Different Smoke-Free Legislation: Findings From the EUREST-PLUS ITC Europe Surveys.

INTRODUCTION: Exposure to secondhand smoke (SHS) poses serious and extensive health and economic-related consequences to European society and worldwide. Smoking bans are a key measure to reducing SHS exposure but have been implemented with varying levels of success. We assessed changes in the prevalence of self-reported SHS exposure and smoking behavior in public places among smokers in six European countries and the influence of the country's type of smoking ban (partial or total ban) on such exposure and smoking behavior. AIMS AND METHODS: The EUREST-PLUS ITC Europe Surveys were conducted among adult smokers in Germany, Greece, Hungary, Poland, Romania, and Spain in 2016 (Wave 1, n = 6011) and 2018 (Wave 2, n = 6027). We used generalized estimating equations models to assess changes between Waves 1 and 2 and to test the interaction between the type of smoking ban and (1) self-reported SHS exposure, (2) self-reported smoking in several public places. RESULTS: A significant decrease in self-reported SHS exposure was observed in workplaces, from 19.1% in 2016 to 14.0% in 2018 (-5.1%; 95% CI: -8.0%; -2.2%). Self-reported smoking did not change significantly inside bars (22.7% in Wave 2), restaurants (13.2% in Wave 2) and discos/nightclubs (34.0% in W2). SHS exposure in public places was significantly less likely (adjusted odds ratio = 0.35; 95% CI: 0.26-0.47) in the countries with total bans as compared to those countries with partial bans. CONCLUSION: The inverse association between smoking in public places and smoking bans indicates an opportunity for strengthening smoke-free legislation and protecting bystanders from exposure to SHS in public places. IMPLICATIONS: Prevalence of smokers engaging in and being exposed to smoking in public places varied by type of smoke-free legislation across six European Union countries in our study; those with total smoke bans reported significantly less exposure to SHS than those with partial or no bans. Our results indicate room for improvement, not only to decrease the prevalence of exposure to SHS in Europe but also to diminish the variability between countries through common, more restrictive smoke-free legislation, and importantly, strong and sustained enforcement.

Tool to monitor tobacco control policy implementation: the Tobacco Control Scale in Latin America. Adaptation process and pilot study.

BACKGROUND: Monitoring tobacco control policy implementation is one of the keys for tobacco consumption reduction in Latin America (LA). This study reports on the adaptation of the Tobacco Control Scale (TCS) for use in LA countries and the level of tobacco control policy implementation in this region according to the scale. METHODS: Ecological cross-sectional survey. The questionnaire to measure tobacco control policies was a translated (into Spanish and Portuguese) and adapted version of the last TCS as used in Europe. The resulting TCS-LA maintains the same structure as the original TCS, with eight policy domains and 100 points (pts) as maximum score; however, four policy domains were adapted because the exact same rationale could not be applied. At least two non-governmental tobacco control experts were contacted per country to answer the TCS-LA. RESULTS: Informants from 17 out of 18 countries completed the questionnaire. Using the TCS-LA, Panama (70 pts), Uruguay (68 pts) and Ecuador (61 pts) exhibited the strongest tobacco control policies, while Guatemala (32 pts), Bolivia (30 pts) and Dominican Republic (29 pts) have implemented a lower number of tobacco control policies. Eight countries reached 50% of the TCS-LA total possible score, indicating a relatively good implementation level of tobacco control policies. CONCLUSIONS: Panama, Uruguay and Ecuador are the tobacco control policy leaders in LA; however, tobacco control in the region has room for improvement since nine countries have a total score under 50 pts. The TCS is a feasible and adaptable tool to monitor tobacco control in other WHO regions beyond Europe.

Beyond the European Union Tobacco Products Directive: smokers' and recent quitters' support for further tobacco control measures (2016-2018).

BACKGROUND: Several measures recommended by the WHO Framework Convention on Tobacco Control have not been implemented in the European Union, despite changes in the legislation such as the Tobacco Products Directive (TPD). This study aims to understand smokers' and recent quitters' levels of support for tobacco control measures that go beyond the TPD during and after its implementation. METHODS: Data from wave 1 (2016, n=6011) and wave 2 (2018, n=6027) of the EUREST-PLUS International Tobacco Control Policy Evaluation Project Six European Countries Survey, a cohort of adult smokers in Germany, Greece, Hungary, Poland, Romania, Spain were used to estimate the level of support for seven different tobacco control measures, overall and by country. RESULTS: In 2018, the highest support was for implementing measures to further regulate tobacco products (50.5%) and for holding tobacco companies accountable for the harm caused by smoking (48.8%). Additionally, in 2018, 40% of smokers and recent quitters supported a total ban on cigarettes and other tobacco products within ten years, if assistance to quit smoking is provided. Overall, support for tobacco control measures among smokers and recent quitters after the implementation of the TPD remained stable over time. CONCLUSION: There is considerable support among smokers and recent quitters for tobacco control measures that go beyond the current measures implemented. A significant percentage of smokers would support a ban on tobacco products in the future if the government provided assistance to quit smoking. This highlights the importance of implementing measures to increase smoking cessation in conjunction with other policies.

The Relationship Between Childhood Physical and Sexual Abuse and Adolescent Cannabis Use: A Systematic Review.

Background: Among adolescents, cannabis use is a health concern due to associations with drug addiction and mental health disorders across the life course. It has been shown that childhood maltreatment is associated with drug addiction in adulthood. However, a better understanding of the relationship between maltreatment and drug use may improve targeted prevention and interventions. The aim of this systematic review is to describe the association between exposure to childhood maltreatment, specifically physical and sexual abuse, with adolescent cannabis use. Methods: A systematic search strategy was applied to Embase, PsycINFO, and Ovid MEDLINE(R) databases. Methods followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Abstract and title screening was performed to identify papers which reported an estimate of the association between childhood physical or sexual abuse and adolescent cannabis use. Full text screening of each paper was performed, and data were extracted and study quality assessed. Weighted means meta-analysis was performed on studies reporting odds ratios as effect estimates. Results: Of 8,780 screened articles, 13 were identified for inclusion. Eight papers received a quality rating score indicating lower risk of bias. Eleven papers reported the relationship between childhood sexual abuse and adolescent cannabis use; effect estimates ranged from AOR 0.53-AOR 2.18 (weighted mean OR 1.29, 95% CI 1.08-1.49). The relationship between childhood physical abuse and adolescent cannabis use was reported in 7 papers; effect estimates ranged from AOR 1.25-AOR 1.87 (weighted mean OR 1.39, 95% CI 1.12-1.66). Differences in the strength of the evidence were observed by the method of exposure ascertainment, and there was some evidence of differences in association by gender, age of cannabis initiation, and the severity of the abuse. Conclusions: This systematic review indicates childhood physical or sexual abuse may increase risk of adolescent-onset cannabis use. Few studies considered variation in timing of onset, or by gender. Adolescent cannabis use precedes is strongly associated with increased risk of negative mental health outcomes; further exploration of adolescent cannabis use's place on the causal pathway between childhood abuse and adult mental health problems is warranted to improve intervention.

HLA-DRB1 allelic epitopes that associate with autoimmune disease risk or protection activate reciprocal macrophage polarization.

Associations between particular human leukocyte antigen (HLA) alleles and susceptibility to-or protection from-autoimmune diseases have been long observed. Allele-specific antigen presentation (AP) has been widely proposed as a culprit, but it is unclear whether HLA molecules might also have non-AP, disease-modulating effects. Here we demonstrate differential macrophage activation by HLA-DRB1 alleles known to associate with autoimmune disease risk or protection with resultant polarization of pro-inflammatory ("M1") versus anti-inflammatory ("M2") macrophages, respectively. RNA-sequencing analyses of in vitro-polarized macrophages in the presence of AP-incompetent short synthetic peptides corresponding to the third allelic hypervariable regions coded by those two HLA-DRB1 alleles showed reciprocal activation of pro- versus anti-inflammatory transcriptomes, with implication of corresponding gene ontologies and upstream regulators. These results identify a previously unrecognized mechanism of differential immune modulation by short HLA-DRB1-coded allelic epitopes independent of AP, and could shed new light on the mechanistic basis of HLA-disease association.

Do smokers want to protect non-smokers from the harms of second-hand smoke in cars? Findings from the EUREST-PLUS ITC Europe Surveys.

BACKGROUND: There is currently no comprehensive legislation protecting non-smokers and children from second-hand smoke (SHS) exposure in private cars at the European Union (EU) level. This study aims to assess smokers' support for smoke-free cars legislation in six EU countries. METHODS: Data come from the EUREST-PLUS ITC Europe Surveys: Wave 1 (2016, n = 6011) and Wave 2 (2018, n = 6027) conducted in Germany, Greece, Hungary, Poland, Romania and Spain. Support for smoke-free cars carrying pre-school children and non-smokers and voluntary implementation of smoke-free cars were assessed among adult smokers. Generalized estimating equations models were used to assess changes in support between waves. RESULTS: In 2018, 96.3% [95% confidence interval (CI) 95.4-97.0%] of the overall sample supported smoke-free legislation for cars carrying pre-school children, representing an increase of 2.4 percentage points in comparison to 2016. Smoke-free legislation for cars transporting non-smokers was supported by 85.2% (95% CI 83.1-87.1%) of smokers' in 2016 and 90.2% (95% CI 88.6-91.7%) in 2018. Among smokers who owned cars, there was a significant 7.2 percentage points increase in voluntary implementation of smoke-free cars carrying children from 2016 (60.7%, 95% CI 57.2-64.0%) to 2018 (67.9%, 95% CI 65.1-70.5%). All sociodemographic groups of smokers reported support higher than 80% in 2018. CONCLUSION: The vast majority of smokers in all six EU countries support smoke-free legislation for cars carrying pre-school children and non-smokers. This almost universal support across countries and sociodemographic groups is a clear indicator of a window of opportunity for the introduction of comprehensive legislation to protect non-smokers and children from SHS exposure in cars.

Effectiveness of tobacco warning labels before and after implementation of the European Tobacco Products Directive-findings from the longitudinal EUREST-PLUS ITC Europe surveys.

BACKGROUND: Tobacco product packaging is a key part of marketing efforts to make tobacco use appealing. In contrast, large, prominent health warnings are intended to inform individuals about the risks of smoking. In the European Union, since May 2016, the Tobacco Products Directive 2014/40/EU (TPD2) requires tobacco product packages to carry combined health warnings consisting of a picture, a text warning and information on stop smoking services, covering 65% of the front and back of the packages. METHODS: Key measures of warning label effectiveness (salience, cognitive reactions and behavioural reaction) before and after implementation of the TPD2, determinants of warning labels' effectiveness and country differences were examined in a longitudinal sample of 6011 adult smokers from Germany, Greece, Hungary, Poland, Romania and Spain (EUREST-PLUS Project) using longitudinal Generalized Estimating Equations (GEE) models. RESULTS: In the pooled sample, the warning labels' effectiveness increased significantly over time in terms of salience (adjusted OR = 1.18; 95% CI: 1.03-1.35), while cognitive and behavioural reactions did not show clear increases. Generally, among women, more highly educated smokers and less addicted smokers, the effectiveness of warning labels tended to be higher. CONCLUSION: We found an increase in salience, but no clear increases for cognitive and behavioural reactions to the new warning labels as required by the TPD2. While it is likely that our study underestimated the impact of the new pictorial warning labels, it provides evidence that health messages on tobacco packaging are more salient when supported by large pictures.

Shared epitope-aryl hydrocarbon receptor crosstalk underlies the mechanism of gene-environment interaction in autoimmune arthritis.

The susceptibility to autoimmune diseases is affected by genetic and environmental factors. In rheumatoid arthritis (RA), the shared epitope (SE), a five-amino acid sequence motif encoded by RA-associated HLA-DRB1 alleles, is the single most significant genetic risk factor. The risk conferred by the SE is increased in a multiplicative way by exposure to various environmental pollutants, such as cigarette smoke. The mechanism of this synergistic interaction is unknown. It is worth noting that the SE has recently been found to act as a signal transduction ligand that facilitates differentiation of Th17 cells and osteoclasts in vitro and in vivo. Intriguingly, the aryl hydrocarbon receptor (AhR), a transcription factor that mediates the xenobiotic effects of many pollutants, including tobacco combustion products, has been found to activate similar biologic effects. Prompted by these similarities, we sought to determine whether the SE and AhR signaling pathways interact in autoimmune arthritis. Here we uncovered a nuclear factor kappa B-mediated synergistic interaction between the SE and AhR pathways that leads to markedly enhanced osteoclast differentiation and Th17 polarization in vitro. Administration of AhR pathway agonists to transgenic mice carrying human SE-coding alleles resulted in a robust increase in arthritis severity, bone destruction, overabundance of osteoclasts, and IL17-expressing cells in the inflamed joints and draining lymph nodes of arthritic mice. Thus, this study identifies a previously unrecognized mechanism of gene-environment interaction that could provide insights into the well-described but poorly understood amplification of the genetic risk for RA upon exposure to environmental pollutants.

Impact of anti-smoking advertising on health-risk knowledge and quit attempts across 6 European countries from the EUREST-PLUS ITC Europe Survey.

INTRODUCTION: Exposure to anti-smoking advertising and its effects differ across countries. This study examines the reported exposure to anti-smoking advertising among smokers and its relation to knowledge of smoking harms and quit attempts in six European countries. METHODS: Data come from Wave 1 of the International Tobacco Control (ITC) 6 European Country (6E) Survey (Germany, Greece, Hungary, Poland, Romania, Spain) carried out among smokers between June and September 2016 (n=6011). Key measures included whether participants had noticed anti-smoking advertising in the last six months in 6 different channels, their knowledge of 13 adverse smoking/second-hand smoking health effects and if they had made at least one quit attempt in the last 12 months. Multivariate logistic regression models were used in the analysis. RESULTS: Across the six countries, only 35.2% of smokers reported being exposed to any anti-smoking advertising. Television was the most common channel identified (25.7%), followed by newspapers and magazines (13.8%), while social media were the least reported (9.5%). Participants 18-24 years old were significantly more likely to have noticed advertisements on the Internet than participants >55 years old (24.3% vs 4.9%; OR=5.15). Participants exposed to anti-smoking advertising in all six channels were twice more likely to have a higher knowledge of smoking risks than those not exposed (2.4% vs 97.6%, respectively; OR=2.49). The likelihood of making a quit attempt was increased by 10% for each additional channel through which smokers were exposed to anti-smoking advertising. CONCLUSIONS: Knowledge of health risks of smoking tended to be higher in countries that aired a campaign in recent years. Exposure to anti-smoking advertising, in the six channels combined, was related to higher smoking knowledge of risks and to more quit attempts. Future anti-smoking mass media campaigns should consider advertising in all dissemination channels to increase the awareness of the dangers of smoking.

Knowledge of the health risks of smoking and impact of cigarette warning labels among tobacco users in six European countries: Findings from the EUREST-PLUS ITC Europe Surveys.

INTRODUCTION: The aim of this study was to examine knowledge of health effects of smoking and the impact of cigarette package warnings among tobacco users from six European Union (EU) Member States (MS) immediately prior to the introduction of the EU Tobacco Products Directive (TPD) in 2016 and to explore the interrelationship between these two factors. METHODS: Cross-sectional data were collected via face-to-face interviews with adult smokers (n=6011) from six EU MS (Germany, Greece, Hungary, Poland, Romania, Spain) between June-September 2016. Sociodemographic variables and knowledge of health risks of smoking (KHR) were assessed. Warning salience, thoughts of harm, thoughts of quitting and foregoing of cigarettes as a result of health warnings were assessed. The Label Impact Index (LII) was used as a composite measure of warning effects. Linear and logistic regression analyses were used to examine sociodemographic predictors of KHR and LII and the inter-relationship between knowledge and LII scores. RESULTS: The KHR index was highest in Romania and Greece and lowest in Hungary and Germany. While the majority of smokers knew that smoking increases the risk for heart diseases, lung and throat cancer, there was lower awareness that tobacco use caused mouth cancer, pulmonary diseases, stroke, and there were very low levels of knowledge that it was also associated with impotence and blindness, in all six countries. Knowledge regarding the health risks of passive smoking was moderate in most countries. The LII was highest in Romania and Poland, followed by Spain and Greece, and lowest in Germany and Hungary. In almost all countries, there was a positive association between LII scores and higher KHR scores after controlling for sociodemographic variables. Several sociodemographic factors were associated with KHR and LII, with differences in these associations documented across countries. CONCLUSIONS: These data provide evidence to support the need for stronger educational efforts and policies that can enhance the effectiveness of health warnings in communicating health risks and promoting quit attempts. Data will serve as a baseline for examining the impact of the TPD.

Cigarette brand loyalty among smokers in six European countries: Findings from the EUREST-PLUS ITC Europe Surveys.

INTRODUCTION: This study aims to describe the degree of smokers' loyalty to a specific brand of tobacco products and the variables related to choosing a specific brand among smokers in six European countries. METHODS: A cross-sectional analysis was conducted for a representative sample of adult smokers from Germany, Greece, Hungary, Poland, Romania, and Spain (approximately 1000 smokers per country). The prevalence of smokers' having a usual brand of cigarettes smoked (factory-made or roll-yourown cigarettes), the brand of choice, the factors for choosing a specific brand and the degree of loyalty to that brand (not at all, a little, somewhat and a lot) were assessed by country, sociodemographics and smoking-related variables. RESULTS: In total, 86.6% of the smokers reported having a usual brand. In three out of the six countries, one brand holds the loyalty of between 17.8% and 24.5% of the smokers that reported having a usual brand for factory-made cigarettes. Most participants reported being loyal 'a lot' to their brand of choice (44.4%). The reasons most reported for choosing a cigarette brand were the taste (83.2%) and the price (51.7%). CONCLUSIONS: Brand loyalty is high among factory-made and roll-your-own cigarette smokers in six European countries. Future research on longitudinal trends of brand loyalty to evaluate the effect of tobacco control policies in these European countries is warranted.

Secondhand exposure to e-cigarette aerosols among smokers: A cross-sectional study in six European countries of the EUREST-PLUS ITC Europe Surveys.

INTRODUCTION: Electronic cigarette (e-cigarette) use has grown significantly in some European Union (EU) Member States (MS). A better understanding of the exposure to secondhand e-cigarette aerosols (SHA) is necessary to develop and implement comprehensive regulations on e-cigarette use in public places. This study aims to assess the observation of e-cigarette use in public places, the self-reported exposure to SHA, and the level of users' comfort using e-cigarettes in the presence of others. METHODS: This is a cross-sectional study of the Wave 1 International Tobacco Control 6 European Countries Survey recruiting adult smokers (n=6011) across six EU MS: Germany, Greece, Hungary, Poland, Romania, and Spain, within the EURESTPLUS Project. A descriptive analysis was conducted to estimate the prevalence (%) of observed e-cigarette use in different places, frequency of self-reported exposure to SHA, and level of comfort using e-cigarettes in the presence of others. RESULTS: In all, 31.0% of smokers observed others using e-cigarette in public places, 19.7% in indoor places where smoking is banned, and 14.5% indoors at work. Almost 37% of smokers reported to be ever exposed to SHA, ranging from 17.7% in Spain to 63.3% in Greece. The higher prevalence of observed e-cigarette use and passive exposure to SHA was reported by smokers of younger age, of higher educational level and those being current or former e-cigarette users. Part (8.8%) of the smokers who were also e-cigarette users reported feeling uncomfortable using e-cigarettes in the presence of others. CONCLUSIONS: A third of smokers from six EU MS reported being exposed to SHA. Prevalence differences were observed among the countries. In the context of scarce evidence on long-term health effects of exposure to SHA, precautionary regulations protecting bystanders from involuntary exposure should be developed.

Effect of Different Levels of Peep on Oxygenation during Non-Invasive Ventilation in Patients Submitted to CABG Surgery: Randomized Clinical Trial.

INTRODUCTION: During and after coronary artery bypass grafting, a decline in multifactor lung function is observed. Due to this fact, some patients may benefit from non-invasive ventilation after extubation targeting lung expansion and consequently improved oxygenation. OBJECTIVE: To test the hypothesis that higher levels of positive end expiration pressure during non-invasive ventilation improves oxygenation in patients undergoing coronary artery bypass grafting. METHODS: A randomized clinical trial was conducted at Instituto Nobre de Cardiologia in Feira de Santana. On the first day after surgery, the patients were randomized: Group PEEP 10, Group PEEP 12 and Group PEEP 15 who underwent non-invasive ventilation with positive end expiration pressure level. All patients were submitted to analysis blood pressure oxygen (PaO2), arterial oxygen saturation (SaO2) and oxygenation index (PaO2/FiO2). RESULTS: Thirty patients were analyzed, 10 in each group, with 63.3% men with a mean age of 61.1±12.2 years. Mean pulmonary expansion pre-therapy PaO2 was generally 121.9±21.6 to 136.1±17.6 without statistical significance in the evaluation among the groups. This was also present in PaO2/FiO2 and SaO2. Statistical significance was only present in pre and post PEEP 15 when assessing the PaO2 and SaO2 (P=0.02). CONCLUSION: Based on the findings of this study, non-invasive ventilation with PEEP 15 represented an improvement in oxygenation levels of patients undergoing coronary artery bypass grafting.

Effect of different levels of peep on oxygenation during non-invasive ventilation in patients submitted to cabg surgery: randomized clinical trial

Abstract Introduction: During and after coronary artery bypass grafting, a decline in multifactor lung function is observed. Due to this fact, some patients may benefit from non-invasive ventilation after extubation targeting lung expansion and consequently improved oxygenation. Objective: To test the hypothesis that higher levels of positive end expiration pressure during non-invasive ventilation improves oxygenation in patients undergoing coronary artery bypass grafting. Methods: A randomized clinical trial was conducted at Instituto Nobre de Cardiologia in Feira de Santana. On the first day after surgery, the patients were randomized: Group PEEP 10, Group PEEP 12 and Group PEEP 15 who underwent non-invasive ventilation with positive end expiration pressure level. All patients were submitted to analysis blood pressure oxygen (PaO2), arterial oxygen saturation (SaO2) and oxygenation index (PaO2/FiO2). Results: Thirty patients were analyzed, 10 in each group, with 63.3% men with a mean age of 61.1±12.2 years. Mean pulmonary expansion pre-therapy PaO2 was generally 121.9±21.6 to 136.1±17.6 without statistical significance in the evaluation among the groups. This was also present in PaO2/FiO2 and SaO2. Statistical significance was only present in pre and post PEEP 15 when assessing the PaO2 and SaO2 (P=0.02). Conclusion: Based on the findings of this study, non-invasive ventilation with PEEP 15 represented an improvement in oxygenation levels of patients undergoing coronary artery bypass grafting.

The Use of Cannabis as a Predictor of Early Onset of Bipolar Disorder and Suicide Attempts.

Introduction. Bipolar disorder (BD) implies risk of suicide. The age at onset (AAO) of BD carries prognostic significance. Substance abuse may precede the onset of BD and cannabis is the most common illicit drug used. The main goal of this study is to review the association of cannabis use as a risk factor for early onset of BD and for suicide attempts. Materials and Methods. PubMed database was searched for articles using key words "bipolar disorder," "suicide attempts," "cannabis," "marijuana," "early age at onset," and "early onset." Results. The following percentages in bipolar patients were found: suicide attempts 3.6-42%; suicide attempts and substance use 5-60%; suicide attempts and cannabis use 15-42%. An early AAO was associated with cannabis misuse. The mean age of the first manic episode in individuals with and without BD and cannabis use disorder (CUD) was 19.5 and 25.1 years, respectively. The first depressive episode was at 18.5 and 24.4 years, respectively. Individuals misusing cannabis showed increased risk of suicide. Discussion. Cannabis use is associated with increased risk of suicide attempts and with early AAO. However, the effect of cannabis at the AAO and suicide attempts is not clear.

A new recombinant BCG vaccine induces specific Th17 and Th1 effector cells with higher protective efficacy against tuberculosis.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb) that is a major public health problem. The vaccine used for TB prevention is Mycobacterium bovis bacillus Calmette-Guérin (BCG), which provides variable efficacy in protecting against pulmonary TB among adults. Consequently, several groups have pursued the development of a new vaccine with a superior protective capacity to that of BCG. Here we constructed a new recombinant BCG (rBCG) vaccine expressing a fusion protein (CMX) composed of immune dominant epitopes from Ag85C, MPT51, and HspX and evaluated its immunogenicity and protection in a murine model of infection. The stability of the vaccine in vivo was maintained for up to 20 days post-vaccination. rBCG-CMX was efficiently phagocytized by peritoneal macrophages and induced nitric oxide (NO) production. Following mouse immunization, this vaccine induced a specific immune response in cells from lungs and spleen to the fusion protein and to each of the component recombinant proteins by themselves. Vaccinated mice presented higher amounts of Th1, Th17, and polyfunctional specific T cells. rBCG-CMX vaccination reduced the extension of lung lesions caused by challenge with Mtb as well as the lung bacterial load. In addition, when this vaccine was used in a prime-boost strategy together with rCMX, the lung bacterial load was lower than the result observed by BCG vaccination. This study describes the creation of a new promising vaccine for TB that we hope will be used in further studies to address its safety before proceeding to clinical trials.

Recombinant BCG: Innovations on an Old Vaccine. Scope of BCG Strains and Strategies to Improve Long-Lasting Memory.

Bacille Calmette-Guérin (BCG), an attenuated vaccine derived from Mycobacterium bovis, is the current vaccine of choice against tuberculosis (TB). Despite its protection against active TB in children, BCG has failed to protect adults against TB infection and active disease development, especially in developing countries where the disease is endemic. Currently, there is a significant effort toward the development of a new TB vaccine. This review article aims to address publications on recombinant BCG (rBCG) published in the last 5 years, to highlight the strategies used to develop rBCG, with a focus on the criteria used to improve immunological memory and protection compared with BCG. The literature review was done in April 2013, using the key words TB, rBCG vaccine, and memory. This review discusses the BCG strains and strategies currently used for the modification of BCG, including: overexpression of Mycobacterium tuberculosis (Mtb) immunodominant antigens already present in BCG; gene insertion of immunodominant antigens from Mtb absent in the BCG vaccine; combination of introduction and overexpression of genes that are lost during the attenuation process of BCG; BCG modifications for the induction of CD8+ T-cell immune responses and cytokines expressing rBCG. Among the vaccines discussed, VPM1002, also called rBCGΔureC:hly, is currently in human clinical trials. Much progress has been made in the effort to improve BCG, with some promising candidates, but considerable work is still required to address functional long-lasting memory.

Leptospira interrogans enolase is secreted extracellularly and interacts with plasminogen.

Leptospira interrogans is the agent for leptospirosis, an important zoonosis in humans and animals across the globe. Surface proteins of invading pathogens, such as L. interrogans, are thought to be responsible for successful microbial persistence in vivo via interaction with specific host components. In particular, a number of invasive infectious agents exploit host proteolytic pathways, such as one involving plasminogen (Pg), which aid in efficient pathogen dissemination within the host. Here we show that L. interrogans serovar Lai binds host Pg and that the leptospiral gene product LA1951, annotated as enolase, is involved in this interaction. Interestingly, unlike in related pathogenic Spirochetes, such as Borrelia burgdorferi, LA1951 is not readily detectable in the L. interrogans outer membrane. We show that the antigen is indeed secreted extracellularly; however, it can reassociate with the pathogen surface, where it displays Pg-binding and measurable enzymatic activity. Hamsters infected with L. interrogans also develop readily detectable antibody responses against enolase. Taken together, our results suggest that the L. interrogans enolase has evolved to play a role in pathogen interaction with host molecules, which may contribute to the pathogenesis of leptospirosis.