Dosimetry of 18F-Labeled Tyrosine Kinase Inhibitor SKI-249380, a Dasatinib-Tracer for PET Imaging

Purpose  

To obtain estimates of human normal-organ radiation doses of ¹⁸F-SKI-249380, as a prerequisite step towards first-in-human trial. ¹⁸F-SKI-249380 is a first-of-its-kind PET tracer for imaging the in vivo pharmacokinetics of dasatinib, an investigational targeted therapy for solid malignancies.     

不同大小仿膀胱生理牵张力对膀胱平滑肌细胞生物学特性的影响

目的 探索不同牵张力对膀胱平滑肌细胞形态和增殖活性的影响. 方法 膀胱平滑肌细胞复合硅胶材料后对材料施加5％、10％、15％、20％及25％等不同大小的牵张力,共聚焦显微镜下观察细胞形态变化.CCK-8酶标法检测细胞增殖能力,流式细胞仪分析细胞周期并计算细胞增殖指数. 结果 在牵张力作用下膀胱平滑肌细胞呈现“收缩型”形态学改变,由无序的星形舒展状态向相对规则的纺锤状细胞形态迁移变化.CCK-8所测对照组吸光值度A为0.471 ±0.027,各牵张组分别增至1.320±0.094(5％组,P＜0.0001)、1.001±0.029(10％组,P＜0.0001)、0.821 ±0.032(15％组,P＜0.0001)、0.621 ±0.032(20％组,P=0.0004)及0.591±0.056(25％组,P=0.0268).与对照组(29.35±0.55)％相比,细胞增殖指数增加到(55.55±1.05)％(5％组,P＜0.0001),(47.70±0.20)％(10％组,P＜0.0001),(35.40 ±2.10)％(15％组,P＜0.0001),与20％组的(34.85±0.55)％(P =0.1372)和25％组的(30.35 ±0.45)％(P =0.5234)比较差异均无统计学意义. 结论 适当强度牵张力可以调节膀胱平滑肌细胞形态并促进细胞增殖活性,5％形变率的牵张力下细胞增殖最活跃.     

High Rates of Relationship Dissolution Among Heterosexual HIV-Serodiscordant Couples in Kenya

HIV-1 serodiscordant couples may experience increased risks of relationship dissolution; however, longitudinal stability of these relationships is poorly understood. We determined rates and correlates of separation among 469 serodiscordant couples in Nairobi and found that 113 (24 %) separated during 2 years of follow-up. Couples with a female HIV-1 infected partner (F+M?) and no income were more likely to separate than M+F? couples without income (HR = 5.0; 95 % CI 1.1–25.0), and F+M? and M+F? couples with income (HR = 2.4; 95 % CI 1.3–4.5 and HR = 2.3; 95 % CI 1.2–4.8, respectively). High separation rates may be important for couple support services and for conducting discordant couple studies.     

Three-Year Survival after Transcatheter Aortic Valve Replacement: Findings from the Marshfield Aortic Valve Experience (MAVE) Study

Background: Transcatheter aortic valve replacement (TAVR) is a rapidly evolving treatment for severe aortic stenosis. However, uncertainties exist for optimal valve selection as there are few long-term studies comparing patient survival by valve type.Objective: We hypothesized that self-expandable valves (SEV) would provide a survival advantage over balloon expandable valves (BEV), as SEV continue to expand and might better accommodate to the anatomy of the aortic valve over time.Methods: We examined outcomes according to valve type from a rural tertiary referral center between 2012 and 2017.Results: Out of 269 patients, 77 deaths (28.6%) occurred over the study period with 6 deaths by 1 month post-TAVR and 37 deaths by 1 year post-TAVR. The median observation time for survivors was 21.5 months. The probability of survival at 3 years was 60.7% and 61.9% for patients who underwent treatment with SEV and BEV, respectively. There was no statistically significant difference in overall patient survival with or without adjustment for factors such as age, sex, race, and aortic valve area. Additionally, in a secondary analysis restricted to those patients treated in later years (2015-2017) survival among patients with BEV appeared superior (HR=0.456, P=0.015).Conclusion: Patients who underwent TAVR at a rural medical center with SEV showed similar survival compared to those who received a BEV. Superior survival was observed among those who received BEV versus SEV between 2015 and 2017     

Superoxide dismutase 1 (SOD1) is a target for a small molecule identified in a screen for inhibitors of the growth of lung adenocarcinoma cell lines

We previously described four small molecules that reduced the growth of lung adenocarcinoma cell lines with either epidermal growth factor receptor (EGFR) or KRAS mutations in a high-throughout chemical screen. By combining affinity proteomics and gene expression analysis, we now propose superoxide dismutase 1 (SOD1) as the most likely target of one of these small molecules, referred to as lung cancer screen 1 (LCS-1). siRNAs against SOD1 slowed the growth of LCS-1 sensitive cell lines; conversely, expression of a SOD1 cDNA increased proliferation of H358 cells and reduced sensitivity of these cells to LCS-1. In addition, SOD1 enzymatic activity was inhibited in vitro by LCS-1 and two closely related analogs. These results suggest that SOD1 is an LCS-1-binding protein that may act in concert with mutant proteins, such as EGFR and KRAS, to promote cell growth, providing a therapeutic target for compounds like LCS-1.     

Non-cardiogenic pulmonary edema complicating electroconvulsive therapy: short review of the pathophysiology and diagnostic approach

Acute pulmonary edema complicating electroconvulsive therapy is an extremely uncommon event that has rarely been described in the literature. Different theories, including one suggesting a cardiogenic component, have been proposed to explain its genesis. The present report describes a classic presentation of this condition with review of its potential mechanisms and diagnostic approach. After successful completion of a session of electroconvulsive therapy, a 42-year-old woman with major depressive disorder developed acute systemic high blood pressure, shortness of breath, and hemoptysis. A chest radiograph demonstrated diffuse bilateral pulmonary infiltrates. Initially cardiogenic pulmonary edema was presumed, but an extensive diagnostic work-up demonstrated normal systolic and diastolic left ventricular function, and with only supportive measures, a complete clinical and radiographic recovery was achieved within 48 hours. The present case does not support any cardiogenic mechanism in the genesis of this condition.