Comparison of dermal and inhalation routes of entry for organic chemicals

The quantitative comparison of the chemical concentration inside the body as the result of a dermal exposure versus an inhalation exposure is useful for assessing human health risks and deciding on an appropriate protective posture. In order to describe the relationship between dermal and inhalation routes of exposure, a variety of organic chemicals were evaluated. The types of chemicals chosen for the study were halogenated hydrocarbons, aromatic compounds, non-polar hydrocarbons and inhalation anesthetics. Both dermal and inhalation exposures were conducted in rats and the chemicals were in the form of vapors. Prior to the dermal exposure, rat fur was closely clipped and during the exposure rats were provided fresh breathing air through latex masks. Blood samples were taken during 4-hour exposures and analyzed for the chemical of interest. A physiologically based pharmacokinetic model was used to predict permeability constants (cm/hr) consistent with the observed blood concentrations of the chemical. The ratio of dermal exposure to inhalation exposure required to achieve the same internal dose of chemical was calculated for each test chemical. The calculated ratio in humans ranged from 18 for styrene to 1180 for isoflurane. This methodology can be used to estimate the dermal exposure required to reach the internal dose achieved by a specific inhalation exposure. Such extrapolation is important since allowable exposure standards are often set for inhalation exposures, but occupational exposures may be dermal

Cachimbos europeus de cerâmica branca, séculos XVI ao XIX: parâmetros básicos para análise arqueológica

O tabaco foi introduzido na Europa no final do século XV. Desde então, uma das formas mais comuns para o seu consumo foi o cachimbo, além do rapé, do tabaco de mascar, do charuto e, mais recentemente, dos cigarros. Os cachimbos de cerâmica branca, largamente produzidos e utilizados na Europa desde o século XV, são encontrados em sítios arqueológicos históricos ao redor do mundo, incluindo no Brasil, em decorrência do comércio internacional, que gradualmente se intensificou após o início da conquista europeia. Eles funcionam como excelentes elementos para datação de sítios e estratos arqueológicos, tendo sido estudados em vários países a partir dessa abordagem. Ainda, esse tipo de artefato, mais que fornecer datações, permite identificar redes comerciais entre nações e desenvolver discussões de cunho social e cultural. Contudo, eles foram pouco estudados no Brasil. Visando contribuir com os estudos nacionais dessa categoria material, este artigo oferece uma revisão da literatura internacional acerca do histórico da produção dos cachimbos europeus de caulim, incluindo apresentação dos principais centros produtores; da morfologia e decoração desses produtos, considerando a cronologia do fabrico; e dos métodos de análise dos diferentes cachimbos de caulim no âmbito da arqueologia histórica.Tobacco was introduced in Europe at the end of the 15th century. Since then, one of the most traditional means for its use has been the pipe, next to the powder version, chewing, cigars, and, more recently, cigarettes. White clay tobacco pipes, widely produced and used in Europe since the 15th century, are found in historical archaeological sites around the world, including Brazil, due to international trade, which gradually intensified with the European conquest of the New World. They are excellent guides for dating archaeological sites and layers. In addition, this type of artifact, more than a dating tool, permits identifying trading networks between nations and developing discussions of cultural and social nature. These pipes, however, have been understudied in Brazil. In order to contribute to studies of this type of artifact in our country, this paper offers a revision of the international literature on the history of clay pipe production in Europe, including the presentation of main production centers; morphology and decoration of these products, considering issues of fabrication chronology; and the methods used in Historical Archaeology for analyzing clay tobacco pipes

Proceedings of the 13th annual conference of INEBRIA

CITATION: Watson, R., et al. 2016. Proceedings of the 13th annual conference of INEBRIA. Addiction Science & Clinical Practice, 11:13, doi:10.1186/s13722-016-0062-9.The original publication is available at https://ascpjournal.biomedcentral.comENGLISH SUMMARY : Meeting abstracts.https://ascpjournal.biomedcentral.com/articles/10.1186/s13722-016-0062-9Publisher's versio

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

A systematic review of alcohol screening and assessment measures for young people

CITATION: Watson, R., et al. 2016. Proceedings of the 13th annual conference of INEBRIA. Addiction Science & Clinical Practice, 11:13, doi:10.1186/s13722-016-0062-9.The original publication is available at https://ascpjournal.biomedcentral.comENGLISH SUMMARY : Meeting abstracts.https://ascpjournal.biomedcentral.com/articles/10.1186/s13722-016-0062-9Publisher's versio