Cardioprotective effects of sinomenine in myocardial ischemia/reperfusion injury in a rat model

BackgroundIschemia reperfusion (I/R) play an imperative role in the expansion of cardiovascular disease. Sinomenine (SM) has been exhibited to possess antioxidant, anticancer, anti-inflammatory, antiviral and anticarcinogenic properties. The aim of the study was scrutinized the cardioprotective effect of SM against I/R injury in rat.MethodsRat were randomly divided into normal control (NC), I/R control and I/R + SM (5, 10 and 20 mg/kg), respectively. Ventricular arrhythmias, body weight and heart weight were estimated. Antioxidant, inflammatory cytokines, inflammatory mediators and plasmin system indicator were accessed.ResultsPre-treated SM group rats exhibited the reduction in the duration and incidence of ventricular fibrillation, ventricular ectopic beat (VEB) and ventricular tachycardia along with suppression of arrhythmia score during the ischemia (30 and 120 min). SM treated rats significantly (P < 0.001) altered the level of antioxidant parameters. SM treatment significantly (P < 0.001) repressed the level of creatine kinase MB (CK-MB), creatine kinase (CK) and troponin I (Tnl). SM treated rats significantly (P < 0.001) repressed the tissue factor (TF), thromboxane B2 (TXB2), plasminogen activator inhibitor 1 (PAI-1) and plasma fibrinogen (Fbg) and inflammatory cytokines and inflammatory mediators.ConclusionOur result clearly indicated that SM plays anti-arrhythmia effect in I/R injury in the rats via alteration of oxidative stress and inflammatory reaction.     

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.     

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.     

Sickle cell nephropathy: A review of novel biomarkers and their potential roles in early detection of renal involvement

Whether the underlying mutations are homozygous, heterozygous, or co-inherited with other hemoglobinopathies, sickle cell disease is known to afflict the kidneys, leading to the clinical entity known as sickle cell nephropathy (SCN). Although common, SCN remains diagnostically elusive. Conventional studies performed in the context of renal disorders often fail to detect early stage SCN. This makes the quest for early diagnosis and treatment more challenging, and it increases the burden of chronic kidney disease-related morbidity among patients. Novel diagnostic tools have been employed to overcome this limitation. In this study, we discuss various biomarkers of SCN, including those employed in clinical practice and others recently identified in experimental settings, such as markers of vascular injury, endothelial dysfunction, tubulo-glomerular damage, and oxidative stress. These include kidney injury molecule-1, monocyte chemoattractant protein-1, N-acetyl-B-D-glucosaminidase, ceruloplasmin, orosomucoid, nephrin, and cation channels, among others. Furthermore, we explore the potential of novel biomarkers for refining diagnostic and therapeutic approaches and describe some obstacles that still need to be overcome. We highlight the importance of a collaborative approach to standardize the use of promising new biomarkers. Finally, we outline the limitations of conventional markers of renal damage as extensions of the pathogenic process occurring at the level of the organ and its functional subunits, with a discussion of the expected pattern of clinical and biochemical progression among patients with SCN.     

Process evaluation of implementation strategies to reduce potentially inappropriate medication prescribing in older population: A scoping review

ObjectivesSeveral implementation strategies can reduce potentially inappropriate medication (PIM) prescribing. Although use of PIMs has declined in recent years, it remains prevalent. Various strategies exist to improve the appropriateness of medication use. However, little is known about the processes of these different implementation strategies. This scoping review aims to investigate how the process evaluation of implementation strategies for reducing PIM prescribing in the older population has been studied.MethodsWe searched for process evaluations of implementation strategies for reducing PIM prescribing in PUBMED, SCOPUS and Web of Science published between January 2000 and November 2019 in English. We applied the following inclusion criteria: patients aged ≥65 years, validated PIM criteria, and implementation process evaluated. The review focuses on decision support for health care professionals. We described the findings of the process evaluations, and compared the authors’ concepts of process evaluation of the included publications to those of Proctor et al.( 2010).ResultOf 9131 publications screened, 29 met our inclusion criteria. Different process evaluation conceptualizations were identified. Most process evaluations took place in the initial stages of the process (acceptability, adoption, appropriateness, and feasibility) and sustainability and implementation costs were seldom evaluated. None of the included publications evaluated fidelity.Multifaceted interventions were the most studied implementation strategies. Medication review was more common in acceptability evaluations, multidisciplinary interventions in adoption evaluations, and computerized systems and educational interventions in feasibility evaluations. Process evaluations were studied from the health care professionals’ viewpoint in most of the included publications, but the management viewpoint was missing.DiscussionThe conceptualization of process evaluation in the field of PIM prescribing is indeterminate. There is also a current gap in the knowledge of sustainability and implementation costs. Clarifying the conceptualization of implementation process evaluation is essential in order to effectively translate research knowledge into practice.     

靶向MLL1-WDR5蛋白-蛋白相互作用抑制剂的研究进展

Mixed lineage leukemia 1(MLL1)是组蛋白甲基转移酶SET家族的成员之一。MLL1与WDR5、RbBP5、Ash2L和DPY-30组成MLL1甲基转移酶复合物调控组蛋白H3的第4位赖氨酸的甲基化水平，对造血系统的发育和血细胞的更新至关重要。部分白血病患者体内存在因MLL1基因易位而产生的致癌蛋白——MLL1融合蛋白，MLL1融合蛋白在发挥其致癌作用时需要功能完整的MLL1酶复合物，故靶向MLL1-WDR5的蛋白-蛋白相互作用成为治疗MLL1融合型白血病的潜在策略。本文对MLL1-WDR5蛋白-蛋白相互作用的生物学机制、结构信息以及抑制剂进行了系统的总结，并结合已报道数据对该领域进行了展望，以期为后续研究提供参考。