Placental Transfer of a Fully Human IgG2 Monoclonal Antibody in the Cynomolgus Monkey,Rat, and Rabbit: A Comparative Assessment from during Organogenesis to Late Gestation

Understanding species differences in the placental transfer of monoclonal antibodies is important to inform species selection for nonclinical safety assessment, interpret embryo‐fetal changes observed in these studies, and extrapolate their human relevance. Data presented here for a fully human immunoglobulin G2 monoclonal antibody (IgG2X) revealed that, during organogenesis, in both the cynomolgus monkey (gestation day 35 [gd35]) and the rat (gd10) the extent of IgG2X placental transfer (approximately 0.5% maternal plasma concentration, MPC) was similar to the limited published human data for endogenous IgG. At this early gestational stage, IgG2X placental transfer was approximately 6‐fold higher in the rabbit (gd10). By the end of organogenesis, rat embryonic plasma concentrations (gd16) exceeded those in the cynomolgus monkey (gd50) by approximately 3‐fold. These data suggest that relative to the cynomolgus monkey, the rabbit (and to a lesser extent the rat) may overestimate potential harmful effects to the human embryo during this critical period of development. Beyond organogenesis, fetal IgG2X plasma concentrations increased approximately 10‐fold early in the second trimester (gd50–70) in the cynomolgus monkey and remained relatively unchanged thereafter (at approximately 5% MPC). Late gestational assessment was precluded in rabbits due to immunogenicity, but in rats, fetal IgG2X plasma concentrations increased more than 6‐fold from gd16 to gd21 (reaching approximately 15% MPC). In rats, maternal exposure consistent with that achieved by ICH S6(R1) high‐dose selection criteria resulted in embryonic plasma concentrations, reaching pharmacologically relevant levels during organogenesis. Furthermore, dose proportional exposure in both mothers and embryos indicated that this was unlikely to occur at the lower therapeutic dose levels used in humans     

Strong influence of dietary intake and physical activity on body fatness in elderly Japanese men: age-associated loss of polygenic resistance against obesity

Genome-wide association studies identified single nucleotide polymorphisms (SNPs) associated with body mass index (BMI) in middle-aged populations; however, it is unclear whether these SNPs are associated with body fatness in elderly people. We examined the association between genetic risk score (GRS) from BMI-associated SNPs and body fatness in elderly Japanese men. We also examined the contribution of GRS, dietary macronutrient intake, and physical activity to body fatness by different age groups. GRS was calculated from 10 BMI-associated SNPs in 84 middle-aged (30–64 years) and 97 elderly (65–79 years) Japanese men; subjects were divided into low, middle, and high GRS groups. Dietary macronutrient intake was assessed using a questionnaire, and physical activity was evaluated using both a questionnaire and an accelerometer. The middle-aged individuals with a high GRS had greater BMI; waist circumference; and total abdominal fat, visceral fat, and subcutaneous fat areas than the middle-aged individuals with low GRS, whereas the indicators were not different between the GRS groups in elderly individuals. Multiple linear regression analysis showed that GRS was the strongest predictor of BMI, total abdominal fat, and visceral fat in the middle-aged group, whereas fat, alcohol, and protein intakes or vigorous-intensity physical activity were more strongly associated with these indicators than was GRS in the elderly group. These results suggest that GRS from BMI-associated SNPs is not predictive of body fatness in elderly Japanese men. The stronger contribution of dietary macronutrient intake and physical activity to body fatness may attenuate the genetic predisposition in elderly men.     

冠心病强化标准化药物治疗最新进展

冠状动脉粥样硬化性心脏病的患病人数呈逐年上升趋势,目前治疗冠心病的方法主要包括改善生活方式,药物治疗,经皮冠状动脉介入治疗（PCI）和外科冠状动脉旁路移植手术治疗（CABG）。虽然介入治疗在治疗阻塞性冠心病取得了显著的进展,但因支架再狭窄,晚期血栓形成,及未知的机制,其死亡率未见明显下降。冠状动脉旁路移植手术虽可降低死亡率,但因其为侵入性操作及手术费用的较高成本,不能为大部分患者接受。近几年来进行了一些全球多中心的临床试验研究,以评估不同诊疗方案对冠心病的预后及远期疗效。目前一些研究表明强化标准化药物治疗（optimal medical therapy,OMT）可与再血管化治疗同效。本文将针对冠心病强化标准化药物治疗方面的实验研究进展进行简要综述。     

三金排石汤对特发性钙结石患者24小时尿成石危险因素水平的影响

目的:分析三金排石汤对特发性钙结石患者24小时尿成石危险因素水平的影响,探讨其用于预防手术取石后的特发性钙结石患者结石复发的临床价值。方法:选择2009年9月~2013年9月入住我院的经皮肾镜取石术或输尿管镜取石术治疗的特发性钙结石患者100例,前瞻性将其随机分为治疗组和观察组,两组各50例。治疗组予三金排石汤每日一剂分两次煎服,观察组予正常饮食,测定和比较两组患者治疗前和治疗1个月后的24小时尿成石危险因素水平。结果:治疗1个月后,观察组24小时尿成石危险因素水平与治疗前比较差异均无统计学意义(P0.05);治疗组24小时尿量较治疗前显著增加,尿pH值、尿枸橼酸含量明显升高,尿钙显著降低,差异均有统计学意义(P0.05),但尿钠、尿镁、尿磷、尿尿酸及尿草酸水平与治疗前比较差异均无统计学意义(P0.05);与观察组比较,治疗组24小时尿量明显增加,尿pH值、尿枸橼酸含量显著升高,尿钙水平明显降低,差异均有统计学意义(P0.05),但两组尿钠、尿镁、尿磷、尿尿酸及尿草酸水平比较差异均无统计学意义(P0.05)。结论:三金排石汤治疗手术取石后特发性钙结石患者能够显著增加其24小时尿量及尿枸橼酸含量,并减少尿钙含量,抑制结石形成,这可能有助于降低特发性钙结石患者手术取石后的复发风险,值得临床研究和推广。     

医学专业学生确立自主学习观的必要性和重要性

目前,高等医学教育的主要任务是培养学生的综合能力,对于医学院校的学生来说,掌握扎实的医学基础知识至关重要。然而,大多医学专业的学生习惯于被动接受老师传授的知识,而严重缺乏主观能动性。医学知识涉及的内容广、难度大,初学者很难迅速掌握其精髓之处,因此确立一种高效的学习模式帮助医学生更好的理解并掌握专业理论是医学院校教育改革的重点。自主学习能力是现代教育学所提倡的相对于传统学习模式的一种现代化学习理念。自主学习的主体是学生,自主学习的过程要求主体发挥其主观能动性,自我督促、自我激励,以独立自主的方式完成高效的学习,帮助学生牢固地掌握专业理论,同时又可以灵活的运用在临床实践中。本文通过对自主学习的含义进行阐述,分析医学生确立自主学习观的必要性和重要性,并对如何确立自主学习观提出相应的建议,以推进我校教育体制改革的进度,进一步完善医学教育教学的质量。     

西北某医院老年性白内障不同付费方式患者费用构成分析

目的:通过对比分析,总结西北某医院老年性白内障自费、医保、新农合三类付费方式患者医疗费用差异及其原因。方法:提取西北地区某医院2010-2012年老年性白内障患者的基本病例信息及住院费用清单,利用EXCEL2007软件和SPSS18.0软件对数据进行统计分析。结果:本院老年性白内障患者人均住院总费用最高为自费患者,其次是医保患者,最低为新农合患者。其中,药品费用差异悬殊是导致三类患者住院总费用差异的最主要原因。结论:不同付费方式对医疗收费行为产生不同影响,医保和新农合政策的制定应兼顾效率与公平。     

Ethical consideration in invasion ecology: A marine perspective

Biological introductions of species to regions outside their known natural distribution are considered a major threat to native marine biodiversity and a key consideration for ecological management. For most invasive species in marine systems, however, little is known about potential impacts. If we are to increase our knowledge of the processes and mechanisms behind the spread of nonindigenous species or determine economic or ecological impacts, manipulative ecological field experiments are the best way to unambiguously ascribe causal relationships. For studies of invasions, such research may result in species spread and the establishment of new viable populations. Is it ethical then, to take the risk of potentially modifying or endangering other species, populations or ecosystems? Is it possible to mitigate the risks? Or should invasion ecologists work under restrictions that limit their ability to fully assess the impact of invaders? Consideration of the ethics of experimentation is rarely carried out. As a consequence, we propose a decision model that includes possible risk of escape/establishment versus the value of the research to allow researchers and/or managers to critically evaluate what type of experimental approach is appropriate.     

Sublethal neonicotinoid insecticide exposure reduces solitary bee reproductive success

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