Single-Operator Left atrial appendage Occlusion utilizing Conscious sedation TEE, Lack of Outpatient pre-imaging, and Same-day Expedited discharge (SOLO-CLOSE): A comparison with conventional approach.

BACKGROUND: Left atrial appendage occlusion (LAAO) with WATCHMAN currently requires preprocedural imaging, general anesthesia, and inpatient overnight admission. We sought to facilitate simplification of LAAO. AIMS: We describe and compare SOLO-CLOSE (single-operator LAA occlusion utilizing conscious sedation TEE, lack of outpatient pre-imaging, and same-day expedited discharge) with the conventional approach (CA). METHODS: A single-center retrospective analysis of 163 patients undergoing LAAO between January 2017 and April 2022 was conducted. The SOLO-CLOSE protocol was enacted on December 1, 2020. Before this date, we utilized the CA. The primary efficacy endpoint was defined as successful LAAO with ≤5 mm peri-device leak at time of closure. The primary safety endpoint was the composite incidence of all-cause deaths, any cerebrovascular accident (CVA), device embolization, pericardial effusion, or major postprocedure bleeding within 7 days of the index procedure. Procedure times, 7-day readmission rates, and cost analytics were collected as well. RESULTS: Baseline characteristics were similar in both cohorts. Congestive heart failure (37.5% vs. 11.1%) and malignancy (28.8% vs. 12.5%) were higher in SOLO-CLOSE. Median CHA2D2SVASc score was 5 in both cohorts. The primary efficacy endpoint was met 100% in both cohorts. Primary safety endpoint was similar between cohorts (p = 0.078). Mean procedure time was 30 min shorter in SOLO-CLOSE (p < 0.01). Seven-day readmissions for SOLO-CLOSE was zero. After SOLO-CLOSE implementation, there was a 188% increase in positive contribution margin per case. CONCLUSIONS: The SOLO-CLOSE methodology offers similar efficacy and safety when compared to the CA, while improving clinical efficiency, reducing procedural times, and increasing economic benefit.

Isradipine augmentation of virtual reality cue exposure therapy for tobacco craving: a triple-blind randomized controlled trial.

Preclinical research with rodents suggests that the L-type calcium channel blocker isradipine can enhance long-term extinction of conditioned place preference for addictive substances when it is administered in conjunction with extinction training. Although isradipine alone, which is FDA-approved for hypertension, has not shown a direct effect on craving in human drug users, its potential to augment behavioral treatments designed to reduce craving remains unknown. We conducted a triple-blind, randomized placebo-controlled pilot clinical trial of isradipine combined with a novel virtual reality cue exposure therapy (VR-CET) approach with multimodal cues that targeted craving. After 24 hours of abstinence, 78 adults with an ongoing history of daily cigarette use received isradipine (n = 40) or placebo (n = 38) and reported craving levels after each of 10 trials of VR-CET. Consistent with pre-registered hypotheses, the isradipine group had significantly lower mean craving across cue exposure trials at the medication-free 24-hour follow-up (d = -0.42, p = 0.046). There were no serious adverse events; however, side effects such as headache and dizziness occurred more frequently in the isradipine group. The findings of the current study support follow-up clinical trials that specifically test the efficacy of isradipine-augmented VR-CET for reducing smoking relapse rates after an initial quit attempt. clinicaltrials.gov: NCT03083353.

Efficacy and implementation of exercise-based smoking cessation treatment for adults with high anxiety sensitivity (STEP): Study protocol for a randomized controlled trial.

Anxiety sensitivity (AS), reflecting the fear of bodily sensations, is a transdiagnostic vulnerability factor that underpins both affective psychopathology and smoking. Phase II research supports the efficacy of a 15-week community-based intervention (STEP) that combines high-intensity exercise offered by the YMCA with standard smoking cessation treatment (tobacco quitline and nicotine replacement therapy) for sedentary smokers with elevated AS. This Phase III study aims to enroll 360 adults to evaluate whether STEP efficacy for achieving smoking abstinence generalizes to Black and Hispanic smokers with elevated AS.

[Current diagnostics and treatment of ankle sprains in German]. / Aktuelle Diagnostik und Behandlung der Sprunggelenks-Distorsion in Deutschland.

BACKGROUND: Ankle sprains are one of the most frequent injuries of the musculoskeletal system. The injury pattern determines the treatment and are crucial for the outcome. Nonoperative treatment is commonly recommended for isolated injuries of the lateral ligaments but no standard strategy exists in combined ankle ligament injuries. The goal of this national survey was to achieve an overview about the current diagnostic strategies and common treatment concepts in Germany. MATERIAL AND METHODS: All members of the German Society for Orthopaedics and Trauma Surgery (DGOU) were invited to participate in an anonymous survey about the diagnostic and therapeutic approach in cases of ankle sprains. The online survey consisted of 20 questions. Besides questions about the speciality and scope of activities the participants were ask to depict their diagnostic and therapeutic strategy. RESULTS: A total of 806 participants completed the survey. Most of them were orthopedic trauma surgeons and worked in a hospital. During the first presentation the anterior drawer test (89.5%) and the inversion/eversion test (81.6%) were most commonly used, 88.1% always make an X­ray examination and 26.5% an ultrasonography examination. Isolated injuries of the anterior fibulotalar ligament (LFTA) were treated nonoperatively by 99.7% of the participants, 78.8% recommend full weight bearing in an orthesis, 78.8% treat the complete rupture of the lateral ligaments without operation whereas 30.1% stated that they would treat a combined lateral ligaments rupture with an injury of the syndesmosis nonoperatively. DISCUSSION: Due to the heterogeneity of injury patterns after ankle sprain no consistent recommendations for diagnostics and treatment exist. The Ottawa ankle rules and ultrasonography were not often utilized despite of the good evidence. The isolated rupture of the LFTA is diagnosed and treated according to the national guidelines by most of the participants. In cases of combined injuries of the lateral and medial ankle ligaments the majority choose a nonoperative treatment strategy which is justified by the guidelines with a low level of evidence. Combined injuries of the syndesmosis and the lateral ankle ligaments were treated operatively, which also correlates with the recommendations in the literature. The standard care of ankle sprain in Germany is in accordance with the recommendations from the current literature.

A Study on the Epidemiological-Molecular Role of Staphylococcus aureus Strains in the Development of Ventilator-Associated Pneumonia in a Tertiary Hospital in Brazil.

This study aimed to explore the molecular epidemiology of Staphylococcus aureus isolated from patients on mechanical ventilation and the participation of virulence factors in the development of ventilator-associated pneumonia (VAP). A prospective cohort study was conducted on patients under mechanical ventilation, with periodic visits for the collection of tracheal aspirates and clinical data. The S. aureus isolates were analyzed regarding resistance profile, virulence, expression of protein A and alpha-toxin using Western blot, clonal profile using PFGE, sequence type using MLST, and characterization and quantification of phenol-soluble modulins. Among the 270 patients in the study, 51 S. aureus strains were isolated from 47 patients. The incidence density of S. aureus and MRSA VAP was 2.35/1000 and 1.96/1000 ventilator days, respectively; of these, 45% (n = 5) were resistant to oxacillin, with 100% (n = 5) harboring SCCmec types II and IV. The most frequent among the tested virulence factors were icaA, hla, and hld. The clonal profile showed a predominance of sequence types originating from the community. Risk factors for VAP were the presence of solid tumors and the sea gene. In conclusion, patient-related risk factors, together with microbiological factors, are involved in the development of S. aureus VAP, which is caused by the patient's own strains.

Two transporters cooperate to secrete amphipathic peptides from the cytoplasmic and membranous milieus.

Diverse organisms secrete amphipathic biomolecules for competitive gains. However, how cells cope with producing these membrane-permeabilizing molecules is unclear. We focused on the PSM family of secreted amphipathic peptides in the pathogen Staphylococcus aureus that uses two ABC transporters, PmtCD and AbcA, to export peptides across the bacterial cell membrane. We found that increased peptide hydrophobicity favors PSM secretion through PmtCD over AbcA and that only PmtCD protected cells against amphipathic peptides. We propose a two-system model in which PmtCD and AbcA independently export PSMs from either membrane or cytosolic environments, respectively. Our model provides a rationale for the encoding of multiple transport systems on diverse biosynthetic gene clusters used to produce distinct amphipathic molecules. In addition, our data serve as a guide for selectively blocking PSM secretion to achieve antimicrobial or antivirulence approaches and to disrupt established roles of PSM-mediated virulence.

Initial assessment of the feasibility and efficacy of a scalable digital CBT for generalized anxiety and associated health behaviors in a cardiovascular disease population.

Generalized anxiety disorder (GAD) is a significant yet modifiable risk factor for worse cardiovascular disease (CVD) outcomes. The treatment of GAD in an accessible manner represents an unmet need in CVD, given that patients with CVD experience numerous barriers to in-person treatment engagement. This paper presents the rationale and design for an investigation of a strategy to enhance care for patients with CVD by introducing a scalable, affordable, and system-friendly digital intervention that targets a prominent modifiable risk factor (generalized anxiety and associated worry) for negative health behaviors in CVD. In the context of a randomized clinical trial design, we describe an experimental medicine approach for evaluating the degree to which a digital cognitive behavior therapy (dCBT), relative to a waitlist control group, engages anxiety and worry outcomes in a sample of 90 adults who have experienced an acute CVD event and who have comorbid GAD symptoms. We also investigate the degree to which dCBT leads to greater changes in GAD symptoms compared to the control condition and whether reductions in these symptoms are associated with corresponding reductions in cardiac anxiety and cardiac health behaviors (including smoking, physical activity, heart-healthy diet, and medication adherence). We propose that by targeting GAD symptoms in CVD in a way that does not tax ongoing medical care provision, we have the potential to improve the uptake of effective care and address both GAD and associated health behaviors.

An investigation of racial and ethnic differences in e-cigarette beliefs and use characteristics.

In this study we provide information on e-cigarette use characteristics in relation to racial and ethnic characteristics in a sample of 535 adult e-cigarette users. We also evaluated how anxiety sensitivity (AS; fear of anxiety) interacted with race/ethnicity to predict vaping outcomes. We found an association between greater AS and higher e-cigarette dependence for White, but not Black, participants. A similar trend was observed for level of risk perception. Also, Hispanic status was associated with higher perception of e-cigarette benefits. Overall, the present study contributes to the understanding of factors linked to e-cigarette use.

Characterization and immunomodulatory activity of sulfated galactan from the red seaweed Gracilaria fisheri.

Polysaccharides from the red seaweed Gracilaria fisheri possess many functions, which include antioxidant, antiviral, and antibacterial activities. However, detailed data on their immunomodulatory activities are scarce. Here, we isolated sulfated galactans (SG) from G. fisheri. We found that the predominant SG from G. fisheri, termed SG-1, had an estimated molecular mass of 100 kDa and activated murine J774A.1 macrophages via the dectin-1 signaling pathway. Furthermore, we observed enhancement of nitric oxide (NO) secretion, increased expression of inducible nitric oxide synthase (iNOS) mRNA, and increased mRNA levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukins IL-1ß and IL-6 by SG-1 in macrophages. Moreover, there was higher expression of intercellular adhesion molecule 1 (ICAM-1) and co-stimulatory molecules (B7-1 and B7-2) mRNA. Treatment with G. fisheri SG-1 at 50 µg/mL generally achieved or exceeded the pro-inflammatory activities of 100 ng/mL lipopolysaccharide. Our study demonstrates immune-stimulatory activities of G. fisheri SG that may be of value for immune-potentiating treatment in humans or livestock.

Do Pain-Related Anxiety and Difficulties With Emotion Regulation Impact Abstinence Expectancies or Motivation to Quit E-Cigarette Use?

OBJECTIVE: Pain-related anxiety is a psychologically based construct that is associated with tobacco dependence and may have important relevance to e-cigarette use. Difficulties with emotion regulation, a relevant construct in motives for cigarette smoking, may interact with pain-related anxiety to yield worsened clinical outcomes among e-cigarette users. We evaluated whether pain-related anxiety and difficulties with emotion regulation independently and in interaction predict e-cigarette users' expectancies surrounding abstinence and their motivation to stop using e-cigarettes. METHOD: Daily e-cigarette users (n = 290, mean age= 35.5, SD = 10.9, 56.6% male) completed an online survey about e-cigarette use. We conducted hierarchical multiple regression analyses to evaluate the main and interactive influence of pain-related anxiety and difficulties with emotion regulation on our outcomes. RESULTS: Increased pain-related anxiety independently predicted negative abstinence expectancies and increased motivation to quit e-cigarette use (ps < .001). Increased difficulties with emotion regulation predicted only negative abstinence expectancies (ps < .01) when pain-related anxiety was included in the model. The interaction between pain-related anxiety and difficulties with emotion regulation was not significant. CONCLUSIONS: As hypothesized, increased pain-related anxiety was associated with both negative expectancies of abstinence and increased motivation to quit e-cigarette use, but contrary to our hypothesis, difficulties with emotion regulation were not significantly associated with increased motivation to quit e-cigarette use when evaluated with pain-related anxiety in the model. These findings may elucidate processes influencing abstinence expectancies and motivation to quit in a sample of e-cigarette users, although replication in a larger, more diverse sample is warranted.

Community-based smoking cessation treatment for adults with high anxiety sensitivity: a randomized clinical trial.

BACKGROUND AND AIMS: People with anxiety disorders are more likely to smoke and less likely to succeed when they try to quit. Anxiety sensitivity may underlie both phenomena, such that people with high anxiety sensitivity react to interoceptive distress by avoidance. This study aimed to test the efficacy of an exercise program that induced interoceptive distress and thereby created tolerance to this distress in a safe environment. DESIGN, SETTING AND PARTICIPANTS: Randomized clinical trial at four YMCA branches in Austin, Texas, USA. Participants [n = 150; 130 (86.7%) white; 101 (67.3%) female; meanage  = 38.6, standard deviation (SD)age  = 10.4] were adult, daily smokers with high anxiety sensitivity motivated to quit smoking, who reported no regular moderate-intensity exercise. INTERVENTIONS: Participants were assigned a YMCA personal trainer who guided them through a 15-week intervention aerobic exercise program. Participants assigned to the personalized intervention trained at 60-85% of their heart rate reserve (HRR), whereas participants assigned to the control intervention trained at 20-40% of their HRR. Participants in both groups received standard behavioral support and nicotine replacement therapy. MEASUREMENTS: The primary outcome was biologically verified 7-day point prevalence abstinence (PPA) at 6-month follow-up. FINDINGS: Sixty-one per cent of participants were available at the 6-month follow-up. PPA at 6 months was higher in the personalized intervention than the control intervention [27.6 versus 14.8%; odds ratio (OR) = 2.20, 95% confidence interval (CI) = 1.28, 3.80, P = 0.005], assuming missing at random. Anxiety sensitivity declined in both groups with no evidence that this differed between groups. CONCLUSIONS: An exercise program of high intensity increased abstinence from smoking in people with high anxiety sensitivity, but may not have done so by reducing anxiety sensitivity.

The role of fear of COVID-19 in motivation to quit smoking and reductions in cigarette smoking: a preliminary investigation of at-risk cigarette smokers.

Preliminary data suggest that cigarette smokers could have an increased mortality risk from the novel coronavirus (SARS-CoV-2), and that certain factors (e.g., increased age, medical comorbidities) can also increase risk of poor coronavirus disease (COVID-19) outcomes. Between April 30th, 2020 and May 28th, 2020, we evaluated self-reported changes in recent smoking patterns and motivation to quit smoking among current daily cigarette smokers (N = 103) on Amazon Mechanical Turk. We also assessed the relationship of these outcomes to age, medical comorbidity status, and fear of COVID-19. Most participants (68.9%) reported smoking less frequently than usual in the last 28 days. Among daily smokers, increased fear of COVID-19 predicted increased motivation to quit smoking and actual smoking reductions (ps < .05). Endorsement of one or more medical comorbidities, but not increased age, predicted increased motivation to quit smoking (p < .05). These data suggest the potentially greater relevance of psychological factors (e.g., fear of COVID-19) over external risk factors (e.g., medical comorbidity, increased age) on motivation to quit smoking and actual reductions in smoking patterns, and may reflect that the pandemic is a suitable time for offering smoking cessation intervention.

Affective Vulnerability Across Non-Daily and Daily Electronic Cigarette Users.

Electronic cigarette (e-cigarette) use has risen exponentially since its initial introduction. The widespread and growing use of these novel products has prompted increased research to evaluate use from a nuanced perspective that considers patterns and antecedents of use. Specifically, research has identified sociodemographic characteristics related to varying levels of e-cigarette use frequency. Yet, limited research has investigated broad-based psychological factors related to frequent and infrequent e-cigarette use. The current study sought to address this clinically relevant research gap within a cross sectional design. Several affective vulnerability states were evaluated, including anxiety sensitivity, anxious arousal, general distress, and anhedonia across 566 (51.1% female, Mage = 35.3 years, SD = 10.1) non-daily and daily past month, adult e-cigarette users. Results demonstrated that in comparison to non-daily e-cigarette users, daily users evinced significantly higher levels of anxiety sensitivity, anxiety sensitivity cognitive concerns, anxiety sensitivity social concerns, anxiety sensitivity physical concerns, anxious arousal, and general distress. No significant differences were found for anhedonic depression. Overall, the current study provides initial and novel empirical evidence that certain affective vulnerability constructs related to anxiety may be more strongly endorsed by daily e-cigarette users. Importantly, this work adds to evolving, but underdeveloped, e-cigarette models by highlighting the need to consider anxiety-related constructs when evaluating e-cigarette use patterns and behavior.

A randomized controlled trial protocol for engaging distress tolerance and working memory to aid smoking cessation in low socioeconomic status (SES) adults.

Low income and low educational attainment are among the strongest predictors of both smoking prevalence and lapse (i.e., return) to smoking after cessation attempts. Treatment refinement is limited by inadequate knowledge of the specific lapse- or relapse-relevant vulnerabilities characteristic of populations that should be the target of treatment. In the context of a randomized clinical trial design, we describe an experimental medicine approach for evaluating the role of 2 specific lapse-relevant targets relative to the higher stress characteristic of low-socioeconomic contexts: low distress tolerance and low working memory capacity. Furthermore, we use an innovative approach for understanding risk of smoking lapse in smokers undergoing a quit attempt to examine candidate mechanistic targets assessed not only during nicotine use, but also during the conditions smokers will face upon a cessation attempt-during stressful nicotine-deprivation windows. This study is designed to show the incremental value of assessments during deprivation windows, in part because of the way in which specific vulnerabilities are modified by, and interact with, the heightened stress and withdrawal symptoms inherent to nicotine-deprivation states. Specifically, the study is designed to evaluate whether a novel mindfulness intervention (mindfulness combined with interoceptive exposure) can improve upon existing mindfulness interventions and extend therapeutic gains to the modification of mechanistic targets assessed in high-stress or negative affectivity contexts. The overall goal is to validate mechanistic targets and associated interventions for the purpose of expanding treatment options for at-risk smokers. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Age and pre quit-day attrition during smoking cessation treatment.

The present study aimed to replicate the finding that younger age predicts higher pre quit-day attrition. Our second aim was to explain this relation by examining empirically and theoretically informed age-related risk factors for low smoking cessation treatment engagement. 136 participants (Mage = 44.2 years, SD = 11.3 years; age = 22-64 years) were randomized to 15-weeks of either 1) an exercise intervention (n = 72) or 2) a wellness education control condition (n = 64). First, a logistic regression analysis was employed to test whether younger adults were more likely than older adults to drop prior to quit date. Next, we assessed whether smoking related health concerns, social expectancies, and/or perceived severity of craving affected the strength of the relation between age and attrition, by adding these three variables to the logistic regression along with age. The logistic regression model indicated that younger age and treatment condition were significantly related to the odds of dropping from treatment prior to the scheduled quit date. Further, health concerns, social expectancies, and/or perceived severity of cravings did not account for the effect of age on pre quit-day attrition. These findings highlight the importance of identifying empirically and theoretically informed variables associated with the pre quit-day attrition problem of young smokers.

Isradipine enhancement of virtual reality cue exposure for smoking cessation: Rationale and study protocol for a double-blind randomized controlled trial.

Cigarette smoking remains a leading cause of preventable death in the United States, contributing to over 480,000 deaths each year. Although significant strides have been made in the development of effective smoking cessation treatments, most established interventions are associated with high relapse rates. One avenue for increasing the effectiveness of smoking cessation interventions is to design focused, efficient, and rigorous experiments testing engagement of well-defined mechanistic targets. Toward this aim, the current protocol will apply a pharmacologic augmentation strategy informed by basic research in animal models of addiction. Our goal is to evaluate the enhancing effect of isradipine, an FDA-approved calcium channel blocker, on the extinction of craving-a key mechanism of drug relapse after periods of abstinence. To activate craving robustly in human participants, we will use multimodal smoking cues including novel 360° video environments developed for this project and delivered through consumer virtual reality headsets. Adult smokers will take either isradipine or placebo and complete the cue exposure protocol in a double-blind randomized control trial. In order to test the hypothesis that isradipine will enhance retention of craving extinction, participants will repeat cue exposure 24 h later without the administration of isradipine or placebo. The study will be implemented in a primary care setting where adult smokers receive healthcare, and smoking behavior will be tracked throughout the trial with ecological momentary assessment.

Enhancing panic and smoking reduction treatment with D-Cycloserine: A pilot randomized clinical trial.

In this placebo-controlled randomized clinical trial, we examined the efficacy of 250 mg d-cycloserine (DCS) for enhancing the effects of cognitive behavior therapy targeting anxiety sensitivity reduction in the context of smoking cessation treatment among adults with a history of panic attacks. We hypothesized that DCS would enhance treatment of our mechanistic targets-anxiety sensitivity and panic and related symptoms-and result in greater smoking abstinence. A total of 53 smokers were randomized to a 7-week integrated treatment and received study medication (DCS or placebo) prior to sessions 3-5; these sessions emphasized interoceptive exposure practice. Nicotine replacement therapy was initiated at session 5 (quit date). We found that DCS augmentation led to greater reductions of one (anxiety sensitivity) of two of our mechanistic targets at early but not late assessments, and that engaging that target predicted better smoking outcomes. However, there was no evidence of group (DCS vs. placebo) differences in smoking cessation success at treatment endpoint or follow-up evaluations. Hence, although we found that DCS can enhance treatment targeting a smoking maintaining factor, additional strategies appear to be needed to significantly affect smoking outcomes.

Targeting cognitive and emotional regulatory skills for smoking prevention in low-SES youth: A randomized trial of mindfulness and working memory interventions.

Research to date provides striking evidence that youth from low socio-economic status (SES) households are at an increased risk for smoking. Converging evidence from developmental studies, psychopathology studies, intervention studies, and basic research on self-control abilities have identified working memory and distress tolerance as potential crucial modifiable risk factors to prevent smoking onset in this cohort. To confirm the value of these mechanistic targets, this randomized trial was designed to evaluate the influence of working memory and distress tolerance interventions on risk of smoking initiation. Recruiting primarily from low-income community afternoon programs, we randomized 93 adolescents to one of three intervention conditions, all of which were a prelude to a smoking-prevention informational intervention: (1) a working memory intervention, (2) a mindfulness training intervention to target distress tolerance, and (3) a wellness-focused control condition. Despite a number of adherence efforts, engagement in treatment was limited, and under these conditions no significant evidence was found either for differential efficacy for smoking prevention or for intervention effects on mechanistic targets. However, working memory capacity and distress tolerance were found to be negatively related to smoking propensity. As such, our mechanistic targets-working memory and distress tolerance--may well be processes undergirding smoking, despite the fact that our interventions did not adequately engage these targets.

Differential Effects of Anxiety Sensitivity on E-Cigarettes Processes: The Importance of E-Cigarette Quit Attempt History.

BACKGROUND AND OBJECTIVES: Electronic cigarettes (e-cigarettes) are recognized as a prevalent form of substance use among adults in the United States. The rise in e-cigarette use has motivated research to identify subgroups of the population that may be particularly vulnerable to e-cigarette use and its associated harm. Individuals with elevated psychological vulnerability are one such group more at risk for being a lifetime or current e-cigarette user. Yet, little is known about how factors of psychological vulnerability relate to perceptions of e-cigarette use within the context of e-cigarette quit attempts. The current study evaluated the differential relations of anxiety sensitivity (AS), a core affective vulnerability factor, on several relevant e-cigarette processes across those with and without a previous attempt to quit using e-cigarettes. METHODS: Our sample consisted of 547 current e-cigarette users (51% female, Mage = 35.38 years, SD = 10.1). RESULTS: Results indicated that AS significantly related to greater perceived risks, benefits, and positive outcome expectancies of e-cigarette use among current e-cigarette users who reported at least one attempt to quit e-cigarettes but was unrelated among those who had never attempted to quit. DISCUSSION AND CONCLUSIONS: Findings identify e-cigarette users who fail to quit as a potential vulnerable subgroup of users who experience more strongly held perceptions about e-cigarettes because of increased AS. SCIENTIFIC SIGNIFICANCE: This work provides initial evidence for a conceptual model in which levels of AS and e-cigarette processes are strengthened by and differ across e-cigarette quit attempt history. (Am J Addict 2019;28:390-397).

Staphylococcus aureus induces DNA damage in host cell.

Staphylococcus aureus causes serious medical problems in human and animals. Here we show that S. aureus can compromise host genomic integrity as indicated by bacteria-induced histone H2AX phosphorylation, a marker of DNA double strand breaks (DSBs), in human cervix cancer HeLa and osteoblast-like MG-63 cells. This DNA damage is mediated by alpha phenol-soluble modulins (PSMα1-4), while a specific class of lipoproteins (Lpls), encoded on a pathogenicity island in S. aureus, dampens the H2AX phosphorylation thus counteracting the DNA damage. This DNA damage is mediated by reactive oxygen species (ROS), which promotes oxidation of guanine forming 7,8-dihydro-8-oxoguanine (8-oxoG). DNA damage is followed by the induction of DNA repair that involves the ATM kinase-signaling pathway. An examination of S. aureus strains, isolated from the same patient during acute initial and recurrent bone and joint infections (BJI), showed that recurrent strains produce lower amounts of Lpls, induce stronger DNA-damage and prompt the G2/M transition delay to a greater extent that suggest an involvement of these mechanisms in adaptive processes of bacteria during chronicization. Our findings redefine our understanding of mechanisms of S. aureus-host interaction and suggest that the balance between the levels of PSMα and Lpls expression impacts the persistence of the infection.