On the pulmonary toxicity of oxygen: III. The induction of oxygen dependency by oxygen use

Oxygen is central to the development of neonatal lung injury. The increase in oxygen exposure of the neonatal lung during the onset of extrauterine air breathing is an order of magnitude, from a range of 10-12 to 110-120 Torr. The contributions of oxygen and the volume and pressure relationships of ventilatory support to lung injury are not easily distinguished in the clinical setting. Sequential changes in inspired air or 100% oxygen were studied in 536 newborn rabbits without ventilatory support. Bilateral cervical vagotomies (BCV) were performed at 24 h post natal to induce ventilatory distress which eventuates in hyaline membrane disease. The sequences applied yielded evidence for an induced state of oxygen dependency from oxygen use which was reflected in differences in survival and the extent of pulmonary injury. The median survival for animals kept in air throughout was 3 h. Oxygen before vagotomy or during the first 3 h afterwards extended the survival significantly but produced more extensive, more severe, and more rapid lung lesions. Returning animals to air after prior oxygen exposure reduced the number of survivors past 10 h and shortened the maximum survival in those groups. These features indicate the development of a dependency of the defense mechanisms on the availability of oxygen at the higher level for metabolic and possibly other aspects of the pulmonary and systemic response to injury, beyond the usual physiological need. Subset analysis revealed additive and latent effects of oxygen and demonstrated a remarkable rapidity in onset of severe lesions under some circumstances, illustrating the toxicity of oxygen per se.     

Using the Jigsaw Cooperative Learning Method to Teach Medical Students About Long-Term and Postacute Care

Since many of the frailest and most vulnerable Americans reside in nursing homes, medical students need focused education and training pertaining to this setting. A unique cooperative learning experience utilizing the jigsaw method was developed to engage and expose students to the institutional long-term and postacute care (LTPAC) setting and the roles of personnel there. To accomplish these goals, small groups of medical students interviewed LTPAC personnel about their role, generally, and in relation to a specific patient case. These groups were then rearranged into new groups containing 1 student from each of the original groups plus a faculty facilitator. Each student in the new groups taught about the role of the LTPAC professional they interviewed. To assess the effectiveness of this learning experience, students and LTPAC personnel provided written feedback and rated the activity using a 5-point Likert scale (1 = worst; 5 = best). Students also took a knowledge test. The activity received ratings from students of 3.65 to 4.12 (mean = 3.91). The knowledge test results indicated that students understood the roles of the LTPAC personnel. In general, the jigsaw exercise was well-received by participants and provided an effective means of introducing medical students to the nursing home environment.     

Roles of glutamates and metal ions in a rationally designed nitric oxide reductase based on myoglobin

A structural and functional model of bacterial nitric oxide reductase (NOR) has been designed by introducing two glutamates (Glu) and three histidines (His) in sperm whale myoglobin. X-ray structural data indicate that the three His and one Glu (V68E) residues bind iron, mimicking the putative Fe_B site in NOR, while the second Glu (I107E) interacts with a water molecule and forms a hydrogen bonding network in the designed protein. Unlike the first Glu (V68E), which lowered the heme reduction potential by ∼110 mV, the second Glu has little effect on the heme potential, suggesting that the negatively charged Glu has a different role in redox tuning. More importantly, introducing the second Glu resulted in a ∼100% increase in NOR activity, suggesting the importance of a hydrogen bonding network in facilitating proton delivery during NOR reactivity. In addition, EPR and X-ray structural studies indicate that the designed protein binds iron, copper, or zinc in the Fe_B site, each with different effects on the structures and NOR activities, suggesting that both redox activity and an intermediate five-coordinate heme-NO species are important for high NOR activity. The designed protein offers an excellent model for NOR and demonstrates the power of using designed proteins as a simpler and more well-defined system to address important chemical and biological issues.     

Visualizing Scientific Inference

The sciences use a wide range of visual devices, practices, and imaging technologies. This diversity points to an important repertoire of visual methods that scientists use to adapt representations to meet the varied demands that their work places on cognitive processes. This paper identifies key features of the use of visualization in a range of scientific domains and considers the implications of this repertoire for understanding scientists as cognitive agents.     

Half of the Variation in Susceptibility to Mortality Is Genetic: Findings from Swedish Twin Survival Data

Molecular epidemiological studies confirm tremendous variability in genetic and environmental susceptibility to disease and death for humans. This variability as well as the roles of genetic and environmental factors in susceptibility to death can be estimated in the analysis of survival data on related individuals (e.g., twins). In this paper, correlated gamma-frailty models are applied to survival data on Swedish twins to estimate genetic parameters in six models of susceptibility. It is shown that the frailty model with additive genetic and nonshared environmental components fits the data best. The estimate of narrow-sense heritability in gamma frailty is about 50%. The results of genetic analysis confirm our earlier findings from the studies of Danish twins that about 50% of individual susceptibility approximated by gamma-distributed frailty is heritable.     

咖啡酸对阿糖胞苷致小鼠白细胞、血小板减少及血小板体积变化的预防和治疗作用

目的：观察咖啡酸对阿糖胞苷（Ara-C）诱发小鼠白细胞、血小板减少及血小板体积（MPV）变化的影响。方法：参照徐国良等方法诱发Ara-C致小鼠白细胞、血小板减少及MPV变化模型,分为咖啡酸600、300、150mg·kg^-1·d^-1剂量组、复方阿胶浆组（阳性对照组）、模型对照组、正常对照组。小鼠给Ara-C造模同时连续灌胃用药12d,分别于给药6、8、10、12d自小鼠尾部取血检测白细胞计数（WBC）、血小板计数（PLT）及MPV,观察咖啡酸对小鼠白细胞及血小板的预防和治疗作用。结果：咖啡酸300mg·kg^-1·d^-1组给药6dWBC为4.8±1.2,600、300mg·kg^-1·d^-1剂量组给药10dWBC为（909±179）、（1056±135）×10^9/L;咖啡酸各剂量组给药12dMPV分别为（6.00±0.23）、（5.90±0.20）和（6.03±0.21）fL,与模型对照组比较差异有统计学意义（P〈0.05）。结论：咖啡酸可用于治疗临床化疗后引起的白细胞及血小板减少,保护血小板的损伤。     

多因子降维法和Logistic回归交互效应分析对比研究

目的比较多因子降维法(MDR)和Logistic回归在分析交互作用时的优劣,探讨MDR和Logistic回归在不同条件下的适用情况。方法用MDR和Logistic回归实现不同条件下的交互作用分析。结果MDR可用以发现高阶交互作用,但不能发现主效应;Logistic回归能很好地分析主效应,且在发现低阶交互作用(二阶交互作用)方面的能力比MDR更强大,但在分析高阶交互作用方面有着很大的局限性。结论MDR和Logistic回归在分析交互作用时有各自的适用条件和优点,遇有交互作用分析要求时,二者的联合应用效果更佳。     

基于最大方差的免疫细胞图像双阈值分割

细胞图像分割是医学图像处理的热点研究内容，论文针对传统的阚值分割方法，将最大方差阈值选择函数进行推广，获得双阈值选择函数，实现了免疫细胞图像的自动双阈值分割，并采用数学形态学方法中的开运算进行后处理，有效消除了阈值分割所带来的毛刺及噪声。实验结果表明，该方法简单、快速，分割结果令人满意。     

胰岛素抵抗与冠心病危险因素的相关性分析

目的:探讨胰岛素抵抗(IR)与冠心病常见危险因素之间的关系。方法:采用回顾性研究,整理自2005年4月—2006年8月住院并行冠状动脉造影确诊冠心病的患者资料,分析胰岛素抵抗与冠心病常见危险因素之间的关系。结果:IR组患者高血压发生率、收缩压、体质量指数(BMI)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、空腹血糖(FPG)、空腹胰岛素(FINS)、尿酸(UA)高于胰岛素敏感(IS)组,高密度脂蛋白胆固醇(HDL-C)低于IS组(P<0.05或P<0.01);经Spearman相关分析表明HOMA-IR与患者的高血压、收缩压、TG、FINS、FPG、BMI和UA水平呈正相关(r在0.283～0.937,P<0.05或P<0.01),与HDL-C呈负相关(r=-0.455,P<0.01);经多元逐步Logistic回归分析表明HOMA-IR与高血压、收缩压、TG、FINS、FPG、BMI、UA和HDL-C相关。结论:IR患者存在冠心病危险因素的聚集趋势,常合并高血压、肥胖、血脂代谢紊乱、血糖和胰岛素代谢紊乱,IR可能是冠心病的危险因素。