Lysenin, a pore-forming protein extracted from the coelomic fluid of the earthworm Eisenia foetida, manifests cytolytic activity by inserting large conductance pores in host membranes containing sphingomyelin. In the present study, we found that adenosine phosphates control the biological activity of lysenin channels inserted into planar lipid membranes with respect to their macroscopic conductance and voltage-induced gating. Addition of ATP, ADP, or AMP decreased the macroscopic conductance of lysenin channels in a concentration-dependent manner, with ATP being the most potent inhibitor and AMP the least. ATP removal from the bulk solutions by buffer exchange quickly reinstated the macroscopic conductance and demonstrated reversibility. Singlechannel experiments pointed to an inhibition mechanism that most probably relies on electrostatic binding and partial occlusion of the channel-conducting pathway, rather than ligand gating induced by the highly charged phosphates. The Hill analysis of the changes in macroscopic conduction as a function of the inhibitor concentration suggested cooperative binding as descriptive of the inhibition process. Ionic screening significantly reduced the ATP inhibitory efficacy, in support of the electrostatic binding hypothesis. In addition to conductance modulation, purinergic control over the biological activity of lysenin channels has also been observed to manifest as changes of the voltage-induced gating profile. Our analysis strongly suggests that not only the inhibitor's charge but also its ability to adopt a folded conformation may explain the differences in the observed influence of ATP, ADP, and AMP on lysenin's biological activity.

Abstinence-contingent incentives improved cessation outcomes among financially disadvantaged smokers with mental illness receiving tobacco treatment at community mental health centers.

Significance: Young adults with schizophrenia, bipolar disorder and other severe mental illnesses (SMI) have high rates of smoking, but little research has evaluated predictors of cessation activity and treatment utilization in this group. Methods: We assessed attitudes, beliefs, social norms, perceived behavioral control, intention, quit attempts, treatment utilization, and cessation among 58 smokers with SMI, age 18-30, enrolled in a randomized pilot study comparing a brief interactive/motivational vs. a static/ educational computerized intervention. Subjects were assessed at baseline, post intervention, and 3-month follow-up. Results: Over follow-up, one-third of participants self-reported quit attempts. Baseline measures indicating lower breath CO, greater intention to quit, higher perceptions of stigma, psychological benefits of smoking, and symptom distress were associated with quit attempts, whereas gender, diagnosis, social support, attitudes about smoking, and use of cessation treatment were not. In the multivariate analysis, lower breath CO, higher intention to quit and symptom distress were significantly related to quit attempts. Only 5% of participants utilized verified cessation treatment during followup. Consistent with the Theory of Planned Behavior, attitudes, social norms and perceived behavioral control regarding cessation treatments correlated significantly with intention to use treatment. Norms and beliefs about treatment were somewhat positive and some improved after intervention, with a pattern

Purpose: The purpose of this report is to assess the efficacy and adverse event profile of photon-based stereotactic radiosurgery (SRS) compared with fractionated stereotactic radiotherapy (fSRT) for the treatment of uveal melanoma. Primary outcomes include incidence proportions of local control, enucleation, metastatic progression, disease-specific, and overall mortality. Treatment-related toxicities such as incidence proportions of radiation retinopathy, neovascular glaucoma, optic neuropathy, and cataract formation were examined as secondary outcomes. Five-year survival and 5-year local control rates were also assessed. Materials and Methods: PubMed, Embase, Web of Science, Scopus, and 2 Cochrane databases were searched up to December 31, 2018. Random effects models were used to calculate pooled incidence proportions of outcome measures. Meta-regression was carried out to explore the potential impact of dose per fraction on local control. Results: Twenty-four articles with a total of 1745 patients were included in the meta-analysis. There were no statistically significant differences between photon-based fSRT and SRS for all primary, secondary and 5-year outcome measures, including local control (P=0.28), enucleation (P=0.51), and neovascular glaucoma (P=0.40). The 5-year local control rate was 90% (95% confidence interval: 76%, 96%) for fSRT and 89% (70%, 97%) for SRS. Conclusions: Our meta-analysis showed no difference in tumor control, survival and toxicities, as defined in this paper, between SRS and fSRT for uveal melanoma. Confounding biases remain an expected limitation in this study of novel treatment modalities deployed in rare tumors. Further investigation is needed to validate outcomes and compare stereotactic treatment techniques.

The purpose of our study is to assess the impact of COVID-19 on the clinical responsibilities, training, and wellness of US radiation oncology residents. An anonymous cross-sectional survey was sent to all 91 radiation oncology residency programs in the USA. The survey included questions related to demographics, changes in clinical duties and training, job prospects, and wellness indicators. Univariate and multivariate logistic regression analyses were used to evaluate factors associated with residents endorsing high satisfaction with their departments’ response to COVID-19. A total of 96 residents completed the survey from 67 US radiation oncology programs. In the multivariate logistic regression model, remote contouring (OR: 3.91 (95% CI: 1.11, 13.80), p = 0.03) and belief that one will be adequately trained to independently practice after completing residency (OR: 4.68 (1.12, 19.47), p = 0.03) were significantly associated with high resident satisfaction with their department’s response to COVID-19. Most residents indicated that hypofractionation was encouraged to a greater extent ( n = 79, 82.3%), patients were triaged by disease risk ( n = 67, 69.8%), and most agreed/strongly agreed that they have been provided with adequate personal protective equipment (PPE) ( n = 85, 88.5%). The COVID-19 pandemic has affected the training and wellness of radiation oncology residents. Our analysis suggests that radiation oncology programs might increase resident satisfaction with their department’s response to COVID-19 by enabling remote contouring and working with residents to identity and remedy possible concerns regarding their ability to independently practice post residency. Supplementary Information The online version contains supplementary material available at 10.1007/s13187-021-01993-5.