Non-canonical role of Hippo tumor suppressor serine/threonine kinase 3 STK3 in prostate cancer

1. Download : Download high-res image (207KB)
2. Download : Download full-size image

     

Motivational interviewing for maternal Immunizations: Intervention development

Background and ObjectiveVaccine uptake during pregnancy remains low. Our objectives were to describe 1) development and adaptation of a clinician communication training intervention for maternal immunizations and 2) obstetrics and gynecology (ob-gyn) clinician and staff perspectives on the intervention and fit for the prenatal care context.MethodsDesign of the Motivational Interviewing for Maternal Immunizations (MI4MI) intervention was based on similar communication training interventions for pediatric settings and included presumptive initiation of vaccine recommendations (“You’re due for two vaccines today”) combined with motivational interviewing (MI) for hesitant patients. Interviews and focus group discussions were conducted with ob-gyn clinicians and staff in five Colorado clinics including settings with obstetric physicians, certified nurse midwives (CNMs), and clinician-trainees. Participants were asked about adapting training to the ob-gyn setting and their implementation experiences. Feedback was incorporated through iterative changes to training components.ResultsInterview and focus group discussion results from participants before (n = 3), during (n = 11) and after (n = 25) implementation guided intervention development and adaptation. Three virtual, asynchronous training components were created: a video and two interactive modules. This virtual format was favored due to challenges attending group meetings; however, participants noted opportunities to practice skills through role-play were lacking. Training modules were adapted to include common challenging vaccine conversations and live-action videos. Participants liked interactive training components and use of adult learning strategies. Some participants initially resisted the presumptive approach but later found it useful after applying it in their practices. Overall, participants reported that MI4MI training fit well with the prenatal context and recommended more inclusion of non-clinician staff.ConclusionsMI4MI training was viewed as relevant and useful for ob-gyn clinicians and staff. Suggestions included making training more interactive, and including more complex scenarios and non-clinician staff.     

外泌体在肿瘤细胞与TAMs之间相互作用中“桥梁”和调控作用的研究进展北大核心

外泌体是一类直径为30~100 nm的圆盘囊泡,其内包含许多组分,诸如复杂RNA和蛋白质等,主要参与细胞间的信号转导。肿瘤相关巨噬细胞(tumor-associated macrophages,TAMs)是肿瘤微环境中普遍存在的巨噬细胞,通过对肿瘤生长、免疫逃逸、侵袭和转移、耐药性等多方面的作用影响肿瘤进程。外泌体在肿瘤相关巨噬细胞的招募、极化及抗肿瘤免疫调控等方面发挥着重要的调节功能。同时,TAMs以外泌体为媒介作用于肿瘤细胞,从而构成了外泌体、TAMs与肿瘤细胞之间相互作用的调控通路。综上所述,本文旨在阐明肿瘤细胞与TAMs之间,以外泌体为“桥梁”相互影响的潜在机制,以及靶向肿瘤细胞和TAMs来源的外泌体在恶性肿瘤治疗中的展望。     

Survival analysis of crown margin repair: A retrospective study in a dental school setting

BackgroundRepairing crowns with defective margins is minimally invasive and cost-effective compared with replacement. The authors’ objectives were to examine the survival trajectory of crown margin repairs and to determine the factors associated with survival.MethodsRecords of adult patients from January 2008 through August 2019 were reviewed for crown margin repairs completed at University of Iowa College of Dentistry. A total of 1,002 crown margin repairs were found. Each repair was followed through the end of study in 2019 or until an event (for example, additional repair, endodontic treatment, crown replacement, or extraction). A Cox proportional hazards model was used to study the relationship between selected covariates and time to event.ResultsDuring the follow-up period, 32.8% of the repairs needed reintervention. In the final model, repair material was the only significant covariate. No difference was found between the survival of repairs done with resin-modified glass ionomer and amalgam. However, the repairs done with resin-based composite and conventional glass ionomer were more likely (1.5 times: 95% CI, 1.02 to 2.10 times; and 2 times: 95% CI, 1.40 to 2.73 times, respectively) to need reintervention than were those done with amalgam.ConclusionsMedian survival time of crown margin repairs was 5.1 years (95% CI, 4.48 to 5.72 years). Median survival times for amalgam, resin-modified glass ionomer, resin-based composite, and glass ionomer repair materials were 5.7 years (95% CI, 4.80 to 6.25 years), 5.3 years (95% CI, 4.73 to 6.34 years), 3.2 years (95% CI, 2.51 to 6.19 years), and 3.0 years (95% CI, 2.53 to 3.62 years), respectively.Practical ImplicationsWhen considering crown margin repairs, resin-modified glass ionomer or amalgam is preferable to resin-based composite or glass ionomer.     

Phase 1/2 clinical trial of COVID-19 vaccine in Japanese participants: A report of interim findings

We initiated a randomized, placebo-controlled, phase 1/2 trial to evaluate the safety and immunogenicity of the S-268019-b recombinant protein vaccine, scheduled as 2 intramuscular injections given 21 days apart, in 60 randomized healthy Japanese adults. We evaluated 2 regimens of the S-910823 antigen (5 μg [n = 24] and 10 μg [n = 24]) with an oil-in-water emulsion formulation and compared against placebo (n = 12). Reactogenicity was mild in most participants. No serious adverse events were noted. For both regimens, vaccination resulted in robust IgG and neutralizing antibody production at days 36 and 50 and predominant T-helper 1-mediated immune reaction, as evident through antigen-specific polyfunctional CD4+ T-cell responses with IFN-γ, IL-2, and IL-4 production on spike protein peptides stimulation. Based on the interim analysis, the S-268019-b vaccine is safe, produces neutralizing antibodies titer comparable with that in convalescent serum from COVID-19-recovered patients. However, further evaluation of the vaccine in a large clinical trial is warranted.     

Nanotherapy: New Approach for Impeding Hepatic Cancer Microenvironment via Targeting Multiple Molecular Pathways

Objective: Hepatocellular carcinoma (HCC) microenvironment has been recognized as a key contributor for cancer progression, metastasis, and drug resistance. The crosstalk between tumor cells, the vascular endothelial growth factor (VEGF), and the chemokine (C-C motif) ligand 2 (CCL2) signaling networks mediates immunoinhibitory impact and facilitates tumor angiogenesis. The current investigation aimed at exploring the potent anti-cancer activity of the newly designed nano-based anti-cancer therapy comprising anti-VEGF drug, avastin (AV), and CCR2 antagonist (CR) to counteract HCC and tracking its mode of action in vivo. Methods: The prepared AV, CR, and AVCR nanoprototypes were characterized by nanoscale characterization techniques in our previous work. Here, they are applied for unearthing their anti-cancer properties / mechanisms in hepatic cancer-induced rats via analyzing protein levels and genetic expression of the elements incorporated in the angiogenesis, apoptosis, and metastasis signalling pathways. Results: The present results revealed a significant down-regulation in the angiogenesis, survival and metastasis indices along with up-regulation in the pro-apoptotic mediators upon treatment of hepatic cancer-bearing rats with the novel synthesized nanomaterials when compared with the untreated counterparts. We showed across HCC model that anti-VEGF in combination with CCR2 antagonism therapy leads to sensitization and enhanced tumor response over anti-VEGF or CCR2 antagonism monotherapy, particularly in its nanoscale formulation. Conclusion: The present approach provides new mechanistic insights into the powerful anti-hepatic cancer advantage of the novel nanoprototypes which is correlated with modulating critical signal transduction pathways implicated in tumor microenviroment such as angiogenesis, apoptosis and metastasis. This research work presents a substantial foundation for future studies focused on prohibiting cancer progression and recovery by targeting tumor microenviroment.     

Robotic-assisted central pancreatectomy: A minimally invasive approach for benign and low-grade lesions

BackgroundCentrally located pancreatic lesions are often treated with extended pancreaticoduodenectomy or distal pancreatectomy resulting in loss of healthy parenchyma and a high risk of diabetes and exocrine insufficiency. Robotic central pancreatectomy (RCP) is a parenchyma sparring alternative that has been shown safe and feasible [[1], [2]].MethodsIn this article, we describe our operative technique and the perioperative outcomes of a series of RCP for low-grade or benign pancreatic tumors.ResultsSix patients (5 female and 1 man) with a median age of 51.5 (44–68) years underwent a RCP for 2 serous cystadenomas, 2 mucinous cystic tumors, 1 neuroendocrine tumor, and 1 autoimmune pancreatitis. There were no conversions, intraoperative complications, or perioperative transfusions. Median operative time and was 240 (230–291) minutes and median blood loss was 100 (100–400) ml. The median hospital stay was 8 (5–27) days. There were no mortalities, reoperations, or readmissions. One patient developed a grade B pancreatic fistula which was successfully managed conservatively. All resections had free margins and the median tumor size was 2.5 (1.5–3.5) cm. After a mean follow-up of 46 months, no patients presented new-onset diabetes or exocrine insufficiency.ConclusionsRCP represents the least invasive option for both the patient and the pancreatic parenchyma. With a standardized technique, RCP results in low postoperative morbidity and excellent long-term pancreatic function. Although our results are excellent, POPF still represents the main complication of central pancreatectomy with an incidence ranging from 0 to 80% depending on multiple factors such as the surgeon, technique, and pancreatic texture.