Differences in PARP Inhibitors for the Treatment of Ovarian Cancer: Mechanisms of Action,Pharmacology, Safety,and Efficacy

Poly(ADP-ribose) polymerases (PARP) are proteins responsible for DNA damage detection and signal transduction. PARP inhibitors (PARPi) are able to interact with the binding site for PARP cofactor (NAD+) and trapping PARP on the DNA. In this way, they inhibit single-strand DNA damage repair. These drugs have been approved in recent years for the treatment of ovarian cancer. Although they share some similarities, from the point of view of the chemical structure and pharmacodynamic, pharmacokinetic properties, these drugs also have some substantial differences. These differences may underlie the different safety profiles and activity of PARPi.     

The Age-Sensitive Efficacy of Calorie Restriction on Mitochondrial Biogenesis and mtDNA Damage in Rat Liver

Calorie restriction (CR) is the most efficacious treatment to delay the onset of age-related changes such as mitochondrial dysfunction. However, the sensitivity of mitochondrial markers to CR and the age-related boundaries of CR efficacy are not fully elucidated. We used liver samples from ad libitum-fed (AL) rats divided in: 18-month-old (AL-18), 28-month-old (AL-28), and 32-month-old (AL-32) groups, and from CR-treated (CR) 28-month-old (CR-28) and 32-month-old (CR-32) counterparts to assay the effect of CR on several mitochondrial markers. The age-related decreases in citrate synthase activity, in TFAM, MFN2, and DRP1 protein amounts and in the mtDNA content in the AL-28 group were prevented in CR-28 counterparts. Accordingly, CR reduced oxidative mtDNA damage assessed through the incidence of oxidized purines at specific mtDNA regions in CR-28 animals. These findings support the anti-aging effect of CR up to 28 months. Conversely, the protein amounts of LonP1, Cyt c, OGG1, and APE1 and the 4.8 Kb mtDNA deletion content were not affected in CR-28 rats. The absence of significant differences between the AL-32 values and the CR-32 counterparts suggests an age-related boundary of CR efficacy at this age. However, this only partially curtails the CR benefits in counteracting the generalized aging decline and the related mitochondrial involvement.     

Efficacy of alpha-cypermethrin and thiamethoxam against Trogoderma granarium Everts (Coleoptera: Dermestidae) and Tenebrio molitor L. (Coleoptera: Tenebrionidae) on concrete

Laboratory bioassays were conducted to evaluate alpha-cypermethrin and thiamethoxam for the control of adults, small larvae and large larvae of the khapra beetle Trogoderma granarium, and the yellow mealworm beetle Tenebrio molitor, on concrete. Factors such as dose (0.025 and 0.1 mg alpha-cypermethrin or thiamethoxam/cm²), exposure interval (1, 3 and 7 d), and formulation (alpha-cypermethrin SC and thiamethoxam WG) were evaluated. Apart from immediate assessment at end of exposure, an assessment of delayed mortality was performed with the survivors of the 7-d exposure by removing them from the treated substrate and keeping them on untreated surfaces for 7 more days. After the 7-d exposure, more T. granarium adults were dead on dishes treated with alpha-cypermethrin than with thiamethoxam. Small larvae were generally less susceptible than adults. After 7 d, small larval mortality reached 64.4% for alpha-cypermethrin, while for thiamethoxam it was <6%. Large T. granarium larvae were more tolerant than the small ones. Delayed mortality of T. granarium adults was generally high for both insecticides and doses, and ranged between 43.3 and 63.3% of those that were still alive immediately after the 7-d treatment. For both larval categories, delayed mortality was higher for larvae that had been previously exposed to alpha-cypermethrin, than with thiamethoxam. For T. molitor, after the 7-d exposure, significantly more adults were dead on dishes treated with alpha-cypermethrin than with thiamethoxam. For small larvae mortality was 38.9% at the lowest thiamethoxam dose, but in the other cases ranged between 88.9 and 95.6%. In the case of large larvae, the overall mortality was low in all tested combinations. Regarding delayed mortality of this species, it remained at low levels, for both adults and small larvae. Our results indicate that T. molitor was more susceptible than T. granarium in both insecticides tested, but alpha-cypermethrin was more effective than thiamethoxam.     

Human responses to high levels of carbon dioxide and air temperature

In this study, 30 subjects were exposed to different combinations of air temperature (T_a: 24, 27, and 30°C) and CO₂ level (8000, 10 000, and 12 000 ppm) in a high-humidity (RH: 85%) underground climate chamber. Subjective assessments, physiological responses, and cognitive performance were investigated. The results showed that as compared with exposure to T_a = 24°C, exposure to 30°C at all CO₂ levels caused subjects to feel uncomfortably warm and experience stronger odor intensity, while increased mental effort and greater intensity of acute health symptoms were reported. However, no significant effects of T_a on task performance or physiological responses were found. This indicated that subjects had to exert more effort to maintain their performance in an uncomfortably warm environment. Increasing CO₂ from 8000 to 12 000 ppm at all T_a caused subjects to report higher rates of headache, fatigue, agitation, and feeling depressed, although the results were statistically significant only at 24 and 27°C. The text typing performance and systolic blood pressure (SBP) decreased significantly at this exposure, whereas diastolic blood pressure (DBP) and thermal discomfort increased significantly. These effects suggest higher arousal/stress. No significant interaction effect of T_a and CO₂ concentration on human responses was identified.     

化妆品功效评价(Ⅵ)——化妆品人体功效评价的实验设计

概述了化妆品人体功效评价实验设计的概念、基本要素和基本原则,介绍了常用实验设计类型和实验设计要点,提供了人体功效评价实验方案设计的思路,有助于提高研究者制定实验设计方案的水平。     

人纤维蛋白原对急诊外伤致创伤性凝血病疗效及相关因素分析

目的:探讨人纤维蛋白原(fibrinogen，FIB)对急诊创伤性凝血病患者的临床疗效及相关因素。方法:将2015年6月至2018年6月本院收治的100例严重创伤患者纳入本研究，根据是否创伤性凝血病分为凝血病组(80例)和非凝血病组(20例)。比较凝血病组和非凝血病组患者收住后第1个24 h的急性生理和慢性健康评分(acute physiology and chronic health evaluation II，APACHE II)、创伤严重程度评分(injury severity score，ISS)、低体温及低灌注发生率等指标。采用Logistic多因素回归方法分析严重创伤患者发生创伤性凝血病的相关因素。将80例创伤性凝血病患者随机分为观察组(40例)和对照组(40例)。对照组按照常规诊疗措施治疗，观察组在对照组处理基础上给予人FIB，比较治疗前后观察组和对照组的凝血功能指标，及治疗后的临床用血量、住院时间及病死率。结果:与治疗前相比，治疗后观察组和对照组的凝血酶原时间(prothrombin time，PT)、活化部分凝血活酶时间(activated partial thromboplastin time，APTT)及D-二聚体水平降低(P<0.05)，FIB水平明显升高(P<0.05)。观察组的红细胞(red blood cell，RBC) 输注量、新鲜冰冻血浆(fresh frozen plasma，FFP)输注量、重症加强护理病房(intensive care unit，ICU)时间及病死率均明显低于对照组，差异具有统计学意义(P<0.05)。创伤性凝血病患者PT>18 s(r=0.623，P=0.024)、APTT>60 s(r=0.722，P=0.018)、凝血酶时间(thrombin time，TT)>15 s(r=0.719，P=0.033)与ISS评分呈正相关。碱缺失(base deficit，BD)≥6(OR=3.678，95%CI=1.065～9.417)、格拉斯哥评分(Glasgow coma scale，GCS)≤8(OR=5.299，95%CI=1.122～8.711)和血小板(platelet，PLT)计数(OR=0.982，95%CI=0.971～0.996)是严重创伤患者发生创伤性凝血病的独立预测因素。结论:人FIB可有效改善创伤性凝血病患者的凝血功能，降低病死率、缩短ICU时间，创伤性凝血病与创伤严重程度、合并休克、低体温和重型颅脑损伤存在一定的相关性。     

Improving storability,physiological disorders,and antioxidant properties of ‘Bartlett’ and ‘d’Anjou’ pears (Pyrus communis L.) by pre-harvest 1-methylcyclopropene spraying

Ethylene continues to be a major factor influencing quality of European pears during storage. Although research has been done on the effect of pre-harvest 1-methylcyclopropene (1-MCP) on physiological characteristics in pears, a full understanding of cultivar response and antioxidant metabolism remains elusive. Spraying 1-MCP on ‘Bartlett’ and ‘d’Anjou’ pears was studied with respect to physiology, storage and eating quality, disorders, and antioxidant properties at two harvest date (H1 and H2) during storage and ripening. Treatment with 1-MCP extended the harvest window of ‘Bartlett’ and ‘d’Anjou’ pears 3 and 4 days, respectively, without reducing storage or eating quality. Treatment with 1-MCP reduced ethylene production (EPR) and respiration rates (RR), maintained fruit firmness and green colour during storage and retarded development of desirable melting texture in both cultivars. Additionally, 1-MCP lowered the incidence of disorders by alleviating membrane lipid peroxidation, retaining high total flavonoids (TF) and antioxidant capacity, and enhancing superoxide dismutase (SOD), catalase (CAT) and ascorbate peroxidase (APX) activity in both cultivars. Overall, pre-harvest 1-MCP applications could extend storage time of ‘Bartlett’ and ‘d’Anjou’ pears to 5 and 6 months, respectively, at −1.1 ± 0.5 °C, by reducing ethylene synthesis and enhancing antioxidant metabolism.     

Reciprocal Relationships Between Collective Efficacy and Team Performance in Women's Ice Hockey.

This study examined reciprocal relationships between collective efficacy and team performance over a season of competition in women's intercollegiate ice hockey within weekends where the opponent was constant for 2 games. Collective efficacy beliefs within 12 teams were assessed prior to both games for at least 7 weekends. Team performance indexes produced an overall measure of performance for each game. The average influence of Saturday collective efficacy on Saturday performance was moderate and positive after controlling for Friday performance. The average influence of Friday performance on Saturday collective efficacy was small and positive after removing the influence of Friday collective efficacy from Friday performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

应用激光活化饵料藻种的研究

应用Nd:YAG激光(波长1.06μm,功率5w,照射时间0.5-3 min)和Ar+激光(波长488nm,功率70mw,照射时间5-15min)对长期保存的不同保存形式的塔胞藻(Pyramidomonassp.)进行辐照处理。研究了不同剂量激光辐照对藻体生长和叶绿素含量的影响。实验结果表明:照射剂量为60s的Nd:YAG激光及剂量为15min的Ar+激光对液体保存形式的藻种有较明显的促长效果,接种后这两种激光处理组的比生长速率分别较对照提高达53.33%和28.89%,叶绿素含量分别增加73.33%和65.69%。两种激光对液体保存藻种的活化效果均好于固体保存种。     

Sprinklered office fire tests

This paper presents data relating to the performance of sprinklers and detectors in real office fire situations. For sprinklers, these data are additional to that associated with the standardized testing used to determine the design delivery density and pressure requirements for various occupancy situations, and provide a useful insight into the effect of sprinklers on developing fires with various office situations. The data given in this paper include the times for activation of various types of sprinkler heads (normal and fast response), the efficacy of the systems as far as extinguishment is concerned, estimates of the maximum size of the fires prior to commencement of extinguishment and associated air temperatures at various locations within the office enclosures. Copyright © 2008 John Wiley & Sons, Ltd.