Expression of the Salmonella Spp. Virulence Factor SifA in Yeast Alters Rho1 Activity on Peroxisomes

SifA is a virulence protein required for assembly and tubulation of a modified phagosome that promotes Salmonella replication. We show that SifA expressed in yeast induces membrane invagination during peroxisome proliferation and requires functional Rho1p. This is consistent with SifA ability to interact with RhoA and the fact that it is a GEF structural homologue

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

The moderating role of smoking amount per day on the relations between anxiety sensitivity, smoking dependence, and cognitive–affective aspects of smoking among treatment seeking smokers

The current study examined the moderating effects of smoking amount per day on the relation between anxiety sensitivity and nicotine dependence, cigarette smoking outcome expectancies, and reasons for quitting smoking among 465 adult, treatment-seeking smokers (48% female, Mage = 36.6, SD = 13.5). Smoking amount per day moderated the relation between anxiety sensitivity and nicotine dependence, smoking expectancies for negative consequences and appetite control as well as intrinsic reasons for quitting. However, no moderating effect was evident for negative reinforcement expectancies. The form of the significant interactions indicated across dependent variables lower levels of smoking amount per day suppressed the relation between anxiety sensitivity and smoking related dependent variable, such that the positive relation of anxiety sensitivity to smoking dependence and cognitive–affective aspects of smoking is weaker in heavier smokers and more robust in lighter smokers

Treatment attrition: Associations with negative affect smoking motives and barriers to quitting among treatment-seeking smokers

Introduction: Pre-treatment attrition and perceived barriers for quitting are clinically important processes involved in early phases of quitting smoking. However, less is known about the constructs that may contribute to these processes such as negative affect reduction smoking motives. Method: The current study sought to evaluate the relation between negative affect reduction smoking motives with pre-treatment attrition and perceived barriers for quitting in a sample of 425 treatment-seeking smokers (48.5% female; Mage = 37.69; SD = 13.61) enrolled in a smoking cessation study examining the efficacy of a transdiagnostic panic-smoking cessation treatment relative to a standard smoking cessation treatment. Results: Results indicated that greater negative affect reduction smoking motives was associated with an increased likelihood of treatment initiation (Odds Ratio = 1.49, CI: 1.09, 2.04). Additionally, negative affect reduction smoking motives was associated with greater perceived barriers for cessation among pre-treatment drop-outs and treatment initiators. Conclusions: This initial investigation provides evidence for the possible clinical utility in addressing negative affect reduction smoking motives during early stages of quitting. Additionally, such findings could potentially inform the development of personalized, early stages of quitting interventions for smoking cessation

Typology of cannabis use among adults: A latent class approach to risk and protective factors

BACKGROUND: Cannabis is among the most widely used substances worldwide. The United States has seen an increase in the number of adult daily cannabis users and in the number of adults diagnosed with cannabis use disorder. However, little work has examined patterns of use or unique subgroups of adult cannabis users, which may be useful in developing targeted treatment interventions for problematic cannabis users. Therefore, the current study used latent profile analysis to identify whether cannabis users can be categorized across distinct subgroups of adult users. METHOD: The sample included 374 current cannabis using adults (64.2% Male; M = 32.6). Cannabis use frequency, quantity, and related problems were used to differentiate subgroups. Further, age, race, emotion dysregulation, affect, anxiety sensitivity, other substance use, and motives for cannabis use were examined as class correlates. RESULTS: Results supported five unique classes of cannabis users, generally ranging from light, infrequent users with few problems to heavy, frequent users with more problems. Additionally, race, negative affectivity, anxiety sensitivity, emotion regulation, cannabis use motives, and alcohol use emerged as unique predictors of class membership. The current findings substantiate past work for heterogeneous latent classes that underlie the larger cannabis using population, however, this study provides novel evidence for subgroups of adult users. CONCLUSION: The identification of different classes of cannabis users may inform future treatment interventions, and ultimately, lead to the development of personalized treatments for each class based on correlates of group membership