Importance of self-weighing to avoid post-cessation weight gain: A secondary analysis of the fit and quit randomized trial.

Background: Smoking cessation is associated with weight gain, and the risk of weight gain is a common deterrent to quitting smoking. Thus, the identification of strategies for reducing post-smoking cessation weight gain is critical. Objective: Conduct secondary analysis of data from the Fit & Quit trial to determine if greater frequency of self-weighing is associated with less weight gain in the context of smoking cessation. Methods: Participants (N = 305) were randomized to one of three 2-month weight interventions (i.e., Stability, Loss, Bibliotherapy), followed by a smoking cessation intervention. Stability and Loss conditions received different types of self-weighing feedback. All participants received e-scales at baseline, to capture daily self-weighing data over 12 months. General linear models were applied to test the main objective. Results: Frequency of self-weighing was (mean ± SD) 2.67 ± 1.84 days/week. The Stability condition had significantly higher self-weighing frequency (3.18 ± 1.72 days/week) compared to the Loss (2.51 ± 1.99 days/week) and the Bibliotherapy conditions (2.22 ± 1.63 days/week). Adjusting for baseline weight and treatment condition, self-weighing 3-4 days/week was associated with weight stability (-0.77 kg, 95% CI: -2.2946, 0.7474, p = 0.3175), and self-weighing 5 or more days/week was associated with 2.26 kg weight loss (95% CI: -3.9249, -0.5953, p = 0.0080). Conclusions: Self-weighing may serve as a useful tool for weight gain prevention after smoking cessation. Feedback received about self-weighing behaviors and weight trajectory (similar to the feedback Stability participants received) might enhance adherence.

A Single Surface-Exposed Amino Acid Determines Differential Neutralization of AAV1 and AAV6 by Human Alpha-Defensins.

Adeno-associated viruses (AAVs) are being developed as gene therapy vectors due to their low pathogenicity and tissue tropism properties. However, the efficacy of these vectors is impeded by interactions with the host immune system. One potential immune barrier to vector transduction is innate immune host defense peptides, such as alpha-defensins, which are potent antiviral agents against other nonenveloped viruses. To investigate the interaction between AAVs and alpha-defensins, we utilized two closely related AAV serotypes, AAV1 and AAV6. Although their capsids differ by only six residues, these two serotypes exhibit markedly different tissue tropisms and transduction efficiencies. Using two abundant human alpha-defensins, enteric human defensin 5 (HD5) and myeloid human neutrophil peptide 1 (HNP1), we found both serotype-specific and defensin-specific effects on AAV infection. AAV6 infection was uniformly neutralized by both defensins at low micromolar concentrations; however, inhibition of AAV1 infection was profoundly influenced by the timing of defensin exposure to the virus relative to viral attachment to the cell. Remarkably, these differences in the defensin-dependent infection phenotype between the viruses are completely dictated by the identity of a single, surface-exposed amino acid (position 531) that varies between the two serotypes. These findings reveal a determinant for defensin activity against a virus with unprecedented precision. Furthermore, they provide a rationale for the investigation of other AAV serotypes not only to understand the mechanism of neutralization of defensins against AAVs but also to design more efficient vectors. IMPORTANCE The ability of adeno-associated viruses (AAVs) to infect and deliver genetic material to a range of cell types makes them favorable gene therapy vectors. However, AAV vectors encounter a wide variety of host immune factors throughout the body, which can impede efficient gene delivery. One such group of factors is the alpha-defensins, which are a key component of the innate immune system that can directly block viral infection. By studying the impact that alpha-defensins have on AAV infection, we found that two similar AAV serotypes (AAV1 and AAV6) have different sensitivities to inhibition. We also identified a single amino acid (position 531) that differs between the two AAV serotypes and is responsible for mediating their defensin sensitivity. By investigating the effects that host immune factors have on AAV infection, more efficient vectors may be developed to evade intervention by the immune system prior to gene delivery.

Patient-Centered Insights and Biases Regarding Cardiologists Via Online Review Platform Analysis.

Background Online cardiologist reviews, such as those on the Yelp website, are a frequently used method for patients to find a cardiologist. It remains unknown how bias may influence such reviews. Our objectives for this study were to (1) determine which cardiologist- or practice-related factors influence the overall rating of cardiologists and patient satisfaction and (2) discover any associations between sex and race with the overall rating of cardiologists or with cardiologist- or practice-related factors. Methods and Results Cardiologist Yelp reviews from practices in the United States from 2007 to 2020 were analyzed. A total of 563 reviews were coded for positive and negative themes. Binary logistic regression was used to determine whether certain factors increased the likelihood of high ratings. Chi-squared tests were used to determine associations between sex and race with certain factors and overall cardiologist ratings. Cardiologists were more likely to receive higher ratings when reviewers noted the characteristics of competency/knowledge base and thoroughness, positive interactions with staff, and when the cardiologist's name was mentioned in the review. Negative interactions with staff were associated with lower ratings. Female cardiologists received lower ratings and more negative mentions of cardiologist-patient communication than expected. White and Black cardiologists received lower ratings than expected compared with other racial groups. Conclusions Patient-perceived cardiologist competency, thoroughness, and positive staff interactions were associated with positive reviews in online assessments. Sex and racial differences were also found. Further research must be done to confirm these findings and to understand the association of online reviews with clinical care and patient outcomes.

Mechanical competition triggered by innate immune signaling drives the collective extrusion of bacterially infected epithelial cells.

Intracellular pathogens alter their host cells' mechanics to promote dissemination through tissues. Conversely, host cells may respond to the presence of pathogens by altering their mechanics to limit infection. Here, we monitored epithelial cell monolayers infected with intracellular bacterial pathogens, Listeria monocytogenes or Rickettsia parkeri, over days. Under conditions in which these pathogens trigger innate immune signaling through NF-κB and use actin-based motility to spread non-lytically intercellularly, we found that infected cell domains formed three-dimensional mounds. These mounds resulted from uninfected cells moving toward the infection site, collectively squeezing the softer and less contractile infected cells upward and ejecting them from the monolayer. Bacteria in mounds were less able to spread laterally in the monolayer, limiting the growth of the infection focus, while extruded infected cells underwent cell death. Thus, the coordinated forceful action of uninfected cells actively eliminates large domains of infected cells, consistent with this collective cell response representing an innate immunity-driven process.