Anticonvulsant Activity of Enantiomeric N‐trans‐Cinnamoyl Derivatives of 2‐Aminopropan‐1‐ols and 2‐Aminobutan‐1‐ols

Epilepsy, one of the most frequent neurological disorders, is still insufficiently treated in about 30% of patients. As a consequence, identification of novel anticonvulsant agents is an important issue in medicinal chemistry. In the present article we report synthesis, physicochemical, and pharmacological evaluation of N‐trans‐cinnamoyl derivatives of R and S‐2‐aminopropan‐1‐ol, as well as R and S‐2‐aminobutan‐1‐ol. The structures were confirmed by spectroscopy and for derivatives of 2‐aminopropan‐1‐ols the configuration was evaluated by means of crystallography. The investigated compounds were tested in rodent models of seizures: maximal electroshock (MES) and subcutaneous pentetrazol test (scPTZ), and also in a rodent model of epileptogenesis: pilocarpine‐induced status prevention. Additionally, derivatives of 2‐aminopropan‐1‐ols were tested in benzodiazepine‐resistant electrographic status epilepticus rat model as well as in vitro for inhibition of isoenzymes of cytochrome P450. All of the tested compounds showed promising anticonvulsant activity in MES. For R(–)‐(2E)‐N‐(1‐hydroxypropan‐2‐yl)‐3‐phenylprop‐2‐enamide pharmacological parameters were found as follows: ED₅₀ = 76.7 (68.2–81.3) mg/kg (MES, mice i.p., time = 0.5 h), ED₅₀ = 127.2 (102.1–157.9) mg/kg (scPTZ, mice i.p., time = 0.25 h), TD₅₀ = 208.3 (151.4–230.6) mg/kg (rotarod, mice i.p., time = 0.25 h). Evaluation in pilocarpine status prevention proved that all of the reported compounds reduced spontaneous seizure activity and act as antiepileptogenic agents. Both enantiomers of 2‐aminopropan‐1‐ols did not influence cytochrome P450 isoenzymes activity in vitro and are likely not to interact with CYP substrates in vivo. Chirality 28:482–488, 2016. © 2016 Wiley Periodicals, Inc.     

The influence of digital filter type,amplitude normalisation method,and co-contraction algorithm on clinically relevant surface electromyography data during clinical movement assessments

There is a large and growing body of surface electromyography (sEMG) research using laboratory-specific signal processing procedures (i.e., digital filter type and amplitude normalisation protocols) and data analyses methods (i.e., co-contraction algorithms) to acquire practically meaningful information from these data. As a result, the ability to compare sEMG results between studies is, and continues to be challenging. The aim of this study was to determine if digital filter type, amplitude normalisation method, and co-contraction algorithm could influence the practical or clinical interpretation of processed sEMG data. Sixteen elite female athletes were recruited. During data collection, sEMG data was recorded from nine lower limb muscles while completing a series of calibration and clinical movement assessment trials (running and sidestepping). Three analyses were conducted: (1) signal processing with two different digital filter types (Butterworth or critically damped), (2) three amplitude normalisation methods, and (3) three co-contraction ratio algorithms. Results showed the choice of digital filter did not influence the clinical interpretation of sEMG; however, choice of amplitude normalisation method and co-contraction algorithm did influence the clinical interpretation of the running and sidestepping task. Care is recommended when choosing amplitude normalisation method and co-contraction algorithms if researchers/clinicians are interested in comparing sEMG data between studies.     

Rational targeting of population groups and residential areas for colorectal cancer screening

BackgroundSociodemographic and spatial disparities in incidence and mortality burden of colorectal cancer (CRC) are important to consider in the implementation of population screening, in order to achieve expected benefit and not increase health inequities. Analytic methods should be adapted to provide rational support for targeted interventions.MethodsCRC incidence rates by tumor stage (I-IV) and location (colon vs. rectum) were analyzed for the time period 2008–2016 within a screening-relevant age interval of 55–74 years for the population of South and West Sweden, where screening is planned for. The study population was stratified by sex, country of birth, educational level (for Swedish-born citizens) and residential area. We also estimated disparities in excess mortality from CRC across groups of patients accordant to relevant population groups.ResultsThe analyses were based on 8961 patients with a first CRC diagnosis. There were marked socioeconomic gradients in the stage II-IV CRC incidence rates among Swedish-born men and women. Compared to men with high educational level, the incidence rate ratios (IRRs) of stage II, III, and IV CRC in men with low educational level were 1.38 (95% confidence interval 1.18, 1.62), 1.09 (0.95, 1.26), and 1.18 (1.02, 1.37), respectively. In women, the corresponding figures were 1.26 (1.06, 1.51), 1.19 (1.01, 1.39), and 1.45 (1.20, 1.80). The groups of patients with low educational level showed relatively high excess mortality burdens from CRC.ConclusionsOur analytic approach provided rational support for targeted intervention when implementing CRC screening, aiming at optimizing participation in groups with low educational level.     

入侵植物马缨丹研究进展

马缨丹原产于热带美洲,现已扩散至世界热带和亚热带地区,并严重威胁入侵地本地植物的生长。马缨丹因具有观赏价值而被我国大量引进,但由于疏于管理,发展成为入侵杂草,对我国农业、畜牧业及生态环境造成严重危害。目前对马缨丹的入侵机制还没有全面系统的认识。本文从马缨丹的生物学特性、入侵机制、生态学效应、防治与应用等方面进行综述,总结其研究进展,以期为马缨丹的防治工作提供依据。研究结果显示:马缨丹成功入侵的关键因素源于其独特的生物学性征;对农林业造成的危害的原因主要为它的化感作用;马缨丹的防治方法主要包括物理、化学和生物防治;马缨丹在防虫除虫、污染修复、药用价值等方面有所应用。此外,分析当前研究中的不足后发现,今后应加强马缨丹在自然环境中的适应机制、应用潜力、防治方法等的研究。     

Association between hypertension and cutaneous melanoma,and the effect of aspirin: extended follow-up of a large randomised controlled trial

BackgroundThe association between hypertension and melanoma is unclear, and previous analyses of data from the ASPirin in Reducing Events in the Elderly (ASPREE) study demonstrated a reduced number of invasive melanoma events amongst aspirin-exposed hypertensive individuals.MethodsData from the ASPREE study which included (1) the intervention period with a median follow-up of 4.7 years, and (2) the observational period with an additional 2 years follow-up, were combined for this analysis. Logistic regression analyses examined the association between baseline hypertension and treatment status and past melanoma history. Survival analyses examined the association between hypertension and melanoma risk, and the effect of aspirin across hypertension groups. Cox proportional hazards models were used to compare incidence across groups.Results19,114 participants (median age of 74 years) were randomised to daily 100 mg aspirin or placebo. At baseline, hypertension and past melanoma history were recorded in 14,195 and 685 individuals, respectively. After adjustment for confounders, hypertension was significantly associated with past melanoma history (OR=1.34, 95%CI: 1.11–1.62). In a prospective analysis, baseline hypertension was not associated with melanoma risk. However, aspirin was associated with a reduced risk of incident melanoma amongst individuals with uncontrolled hypertension (blood pressure ≥140/90 mmHg; HR=0.63, 95%CI 0.44–0.89), but not in those with controlled hypertension (HR=1.04, 95%CI 0.74–1.46).ConclusionOur results support a reduced melanoma incidence amongst individuals with uncontrolled hypertension exposed to aspirin. Additional studies are required to confirm these findings.     

入侵植物筛选方法在我国口岸防控中的应用建议

入侵植物是生物入侵中数量最多的类群,给全世界造成了重大的经济和环境影响。植物入侵的预测研究是口岸防控工作中的重要技术环节之一。本文介绍了入侵植物筛选方法的概念,简述了与之相关的基础理论、研究情况以及3种植物入侵的预测方法。综合来看,入侵植物筛选方法主要采用植物自身的生物生态学特性作为评估指标来筛选外来植物,能快速可靠地将外来植物评判为严重入侵植物、非入侵植物以及介于二者之间的一般入侵植物,因此该方法能为我国口岸防范外来植物入侵的管理提供基础技术支撑。当前我国入侵植物筛选方法的研究和应用尚处起步阶段,通过本文的简述期望引起相关人员对此问题进行探讨,并为我国口岸入侵植物防控工作提供理论参考。     

Molecular simulation of protein aggregation

Computer simulation offers unique possibilities for investigating molecular-level phenomena difficult to probe experimentally. Drawing from a wealth of studies concerning protein folding, computational studies of protein aggregation are emerging. These studies have been successful in capturing aspects of aggregation known from experiment and are being used to refine experimental methods aimed at abating aggregation. Here we review molecular-simulation studies of protein aggregation conducted in our laboratory. Specific attention is devoted to issues with implications for biotechnology.     

Weight gain prevention among women

Objective: Women 25 to 45 years old are at risk for weight gain and future obesity. This trial was designed to evaluate the efficacy of two interventions relative to a control group in preventing weight gain among normal or overweight women and to identify demographic, behavioral, and psychosocial factors related to weight gain prevention. Research Methods and Procedures: Healthy women (N = 284), ages 25 to 44, with BMI < 30 were randomized to one of three intervention conditions: a clinic‐based group, a correspondence course, or an information‐only control. Intervention was provided over 2 years, with a follow‐up at Year 3. BMI and factors related to eating and weight were assessed yearly. Results: Over the 3‐year study period, 40% (n = 114) of the women remained at or below baseline body weight (±2 lbs), and 60% gained weight (>2 lbs). Intervention had no effect on weight over time. Independently of intervention, women who were older, not actively dieting to lose weight, and who reported less perceived hunger at baseline were more likely to be successful at weight maintenance. Weight maintenance also was associated with increasing dietary restraint (conscious thoughts and purposeful behaviors to control calorie intake) and decreasing dietary disinhibition (the tendency to lose control over eating) over time. Discussion: This study raises concern about the feasibility and efficacy of weight gain prevention interventions because most women were interested in weight loss, rather than weight gain prevention, and the interventions had no effect on weight stability. Novel approaches to the prevention of weight gain are needed.     

Designer schools: the role of school space and architecture in obesity prevention

Spatial features of obesogenic environments studied on a broad community level have been associated with childhood overweight and obesity, but little research has focused on the effects of the design of micro spaces, such as schools, on individual health behaviors. This article aims to generate thinking and research on the link between school space and architecture and obesity prevention by reviewing and synthesizing available literature in architecture, environmental psychology, and obesity research, in an effort to propose promising ideas for school space design and redesign. The school environment is defined through 5 dimensions: physical, legal, policy, social, and cultural domains. Theories underlying environmental interventions and documented associations between the environment and health behaviors and outcomes are reviewed to illustrate how existing environmental research could translate to obesity prevention. Design strategies aimed at promoting physical activity and healthful eating are proposed, with particular emphasis on the design of cafeterias, activity spaces, connectivity with the larger community, and student health centers.     

Interventions to prevent or treat obesity in preschool children: a review of evaluated programs

Objective: To identify effective programs to prevent or treat overweight among 2‐ to <6‐year‐old children. Research Methods and Procedures: We searched six databases to identify evaluated intervention programs assessing changes in weight status or body fat and systematically summarized study attributes and outcomes. Results: Four of the seven studies (two intervention, two prevention) documented significant reductions in weight status or body fat. Among these, three sustained reductions at 1 or 2 years after program initiation, three incorporated a framework/theory, two actively and one passively involved parents, three included multicomponent strategies, and all four monitored behavioral changes. Of the three (prevention) studies that did not show reduction in weight or fat status, all performed assessments between 4 and 9 months after program initiation, and one used a multicomponent strategy. Other significant changes reported were reductions in television viewing, cholesterol, and parental restriction of child feeding. Discussion: The paucity of studies limits our ability to generalize findings. Among the available studies, multicomponent programs with 1‐ to 2‐year follow‐up in clinics or child care settings were successful in their impact on weight; they were likely enhanced by parental involvement. Both treatment programs and two of five prevention programs reduced weight/fat status. Our review highlights the need to evaluate more programs, advocate for use of a framework/behavioral theory and objective behavioral measures, further examine the impact of involving parents and the impact of intervention duration and follow‐up time, strengthen prevention programs, and further evaluate successful programs in other settings and among other racial/ethnic groups.