Concurrent Use of Cigarettes and Smokeless Tobacco in Minnesota

Cigarette smokers are being encouraged to use smokeless tobacco (SLT) in locations where smoking is banned. We examined state-wide data from Minnesota to measure changes over time in the use of SLT and concurrent use of cigarettes and SLT. The Minnesota Adult Tobacco Survey was conducted four times between 1999 and 2010 and has provided state-wide estimates of cigarette smoking, SLT use and concurrent use of SLT by smokers. The prevalence of SLT was essentially unchanged through 2007, then increased significantly between 2007 and 2010 (3.1% versus 4.3%, P < 0.05). Similarly, the prevalence of cigarette smokers who reported using SLT was stable then increased between 2007 and 2010 (4.4% versus 9.6%, P < 0.05). The finding of higher SLT use by smokers could indicate that smokers in Minnesota are in an experimental phase of testing alternative products as they adjust to recent public policies restricting smoking in public places. The findings are suggestive that some Minnesota smokers are switching to concurrent use of cigarettes and SLT. Future surveillance reports will be necessary to confirm the results

The First Human Epitope Map of the Alphaviral E1 and E2 Proteins Reveals a New E2 Epitope with Significant Virus Neutralizing Activity

Although the murine immune response to Venezuelan equine encephalitis virus (VEEV) is well-characterized, little is known about the human antibody response to VEEV. In this study we used phage display technology to isolate a panel of 11 VEEV-specfic Fabs from two human donors. Seven E2-specific and four E1-specific Fabs were identified and mapped to five E2 epitopes and three E1 epitopes. Two neutralizing Fabs were isolated, E2-specific F5 and E1-specific L1A7, although the neutralizing capacity of L1A7 was 300-fold lower than F5. F5 Fab was expressed as a complete IgG1 molecule, F5 native (n) IgG. Neutralization-escape VEEV variants for F5 nIgG were isolated and their structural genes were sequenced to determine the theoretical binding site of F5. Based on this sequence analysis as well as the ability of F5 to neutralize four neutralization-escape variants of anti-VEEV murine monoclonal antibodies (mapped to E2 amino acids 182–207), a unique neutralization domain on E2 was identified and mapped to E2 amino acids 115–119

Suono e Spettacolo. Athanasius Kircher, un percorso nelle Immagini sonore.

The Society of Jesus made great propaganda efforts throughout the seventeenth century and chose the images and the play as a privileged means to communicate and persuade. Athanasius Kircher, a key figure of the seventeenth century, he decided to dominate the wild nature of sound through Phonurgia Nova, which includes a gallery of powerful symbolic images for Baroque aesthetics. The essay, through the grant of the images from the Library of the Department of Mathematics "Guido Castelnuovo" Sapienza University of Rome, aims to understand, through the pictures offered by Kircher, the sound phenomenon and the spectacle that this produces. In Phonurgia Nova a process of dramatization sound effects takes place, often through machines and "visions" applied to the theatrical reality, as experimental and astonishing environment beloved in baroque. Kircher illustrates the sound through explanatory figures, so to dominate the sound through the eyes. Sound is seen, admired and represented: its spectacle not only takes place through the implementation of sound machines or the "wonders" applied to the theater, but even through images, creating create a sense of wonder in in the erudite person of the seventeenth century

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