• 【乳酸和丙酮酸测量值对评估大鼠心脏细胞质中游离烟酰胺-腺嘌呤二核苷酸氧化还原状态的价值。】 复制标题 收藏 收藏
    DOI:10.1111/eci.1971.1.4.295 复制DOI
    作者列表:Opie LH,Mansford KRL
    BACKGROUND & AIMS: :In the isolated rat heart perfused with glucose as substrate, measurements were made of perfusate and tissue lactate and pyruvate concentrations, and of tissue α-glycerophosphate and dihydroxyacetone phosphate concentrations. The conditions studied included increased heart work, anoxia, the addition of insulin, acute alloxan diabetes, chronic streptozotocin diabetes, and the addition of ketone bodies. True intracellular lactate values (estimated from the lactate and sorbitol spaces) and apparent tissue values exceeded perfusate values, showing the existence of a lactate concentration gradient. During anoxia, the lactate gradient diminished. Cytoplasmic free NAD+/NADH ratios calculated from the extracellular lactate/pyruvate ratio were similar to and changed in the same direction as the NAD+/NADH ratios calculated from the tissue α-glycerophosphate/dihydroxyacetone phosphate ratios in non-diabetic hearts. In diabetio hearts, extracellular and tissue lactate/pyruvate ratios gave different values for the cytoplasmic free NAD+/NADH ratios than did tissue α-glycero-phoaphate/dihydroxyacetone phosphate ratios. These discrepancies were associated with accumulation of pyruvate in the perfusate and the tissue. Changes in the extracellular lactate/pyruvate ratio gave a better differentiation between acute heart work and acute anoxia than did changes in the heart lactate/pyruvate ratio. The use of extracellular lactate/ pyruvate measurements in assessing the state of myocardial oxygenation is supported by these observations, provided that nutritional factors are taken into account and the diabetic state is excluded.
    背景与目标: :在以葡萄糖为底物灌注的离体大鼠心脏中,测量灌注液,组织乳酸和丙酮酸的浓度,以及组织α-甘油磷酸和二羟基丙酮磷酸的浓度。研究的疾病包括心脏工作增加,缺氧,胰岛素的添加,急性四氧嘧啶糖尿病,慢性链脲佐菌素糖尿病和酮体的添加。真实的细胞内乳酸值(从乳酸和山梨糖醇空间估算)和表观组织值超过灌注液值,表明存在乳酸浓度梯度。在缺氧期间,乳酸梯度降低。由细胞外乳酸盐/丙酮酸盐比率计算出的细胞质游离NAD / NADH比率与在非糖尿病性心脏中由组织α-甘油磷酸酯/二羟基丙酮磷酸盐比率计算出的NAD / NADH比率相似并且在相同的方向上改变。在糖尿病心脏中,细胞外和组织中乳酸/丙酮酸的比率与组织α-甘油-磷酸盐/二羟基丙酮磷酸盐的比率给出的细胞质游离NAD / NADH比率值不同。这些差异与丙酮酸在灌注液和组织中的积累有关。细胞外乳酸/丙酮酸比的变化比心脏乳酸/丙酮酸比的变化更好地区分了急性心脏功和急性缺氧。这些观察结果支持在评估心肌氧合状态时使用细胞外乳酸/丙酮酸的测量结果,但要考虑到营养因素并且排除糖尿病状态。
  • 【血清和转化生长因子β调节无血清来源的小鼠胚胎细胞中的神经胶质纤维酸性蛋白。】 复制标题 收藏 收藏
    DOI:10.1073/pnas.87.21.8378 复制DOI
    作者列表:Sakai Y,Rawson C,Lindburg K,Barnes D
    BACKGROUND & AIMS: :Serum-free mouse embryo (SFME) cells, derived in medium in which serum is replaced with growth factors and other supplements, display distinctive properties: (i) SFME cells do not lose proliferative potential or show gross chromosomal aberration upon extended culture, (ii) these cells depend on epidermal growth factor for survival; and (iii) SFME cell proliferation is reversibly inhibited by serum. Treatment of SFME cells with serum or transforming growth factor beta led to the appearance of glial fibrillary acidic protein, a specific marker for astrocytes. The appearance of glial fibrillary acidic protein in cultures was reversed upon removal of transforming growth factor beta or serum. Cells with properties similar to SFME cells were also isolated from adult mouse brain. These results suggest a role for transforming growth factor beta in astrocyte differentiation in developing organisms and in response to injury and identify the cell type that has the unusual properties of SFME cells.
    背景与目标: :无血清的小鼠胚胎(SFME)细胞衍生于用生长因子和其他补品替代血清的培养基中,显示出独特的特性:(i)SFME细胞在长期培养后不会丧失增殖潜能或显示总体染色体畸变,( ii)这些细胞的生存依赖于表皮生长因子; (iii)血清可逆地抑制SFME细胞的增殖。用血清或转化生长因子β处理SFME细胞导致出现神经胶质纤维酸性蛋白(星形胶质细胞的特异性标记物)的出现。去除转化生长因子β或血清后,培养物中胶质原纤维酸性蛋白的出现被逆转。还从成年小鼠脑中分离出具有与SFME细胞相似性质的细胞。这些结果表明,在发育中的生物体中星形胶质细胞分化中转化生长因子β的作用以及对损伤的反应,并鉴定出具有SFME细胞异常特性的细胞类型。
  • 【对于慢性髓样白血病,骨髓移植后的供体嵌合症是无病生存的重要指标。】 复制标题 收藏 收藏
    DOI: 复制DOI
    作者列表:Gardiner N,Lawler M,O'Riordan J,De'Arce M,McCann SR
    BACKGROUND & AIMS: Although Chronic Myeloid Leukaemia (CML) can be treated successfully with allogeneic bone marrow transplantation (BMT), leukaemia relapse remains a significant clinical problem. Molecular monitoring of the post transplant marrow can be useful in predicting relapse particularly in CML patients where the Philadelphia chromosome or its molecular counterpart, the BCR-ABL fusion messenger RNA can be used as a leukaemia specific marker of minimal residual disease (MRD). We have investigated chimaerism (using polymerase chain reaction of short tandem repeat sequences (STR-PCR)) and MRD status (using reverse transcriptase PCR of the BCR-ABL fusion mRNA) in a serial fashion in 18 patients who were in clinical and haematological remission post allogeneic BMT for chronic phase CML. Eleven patients exhibited complete donor chimaerism with no evidence of minimal residual disease. Five patients had transient or low level stable MC. Late MC and MRD was observed in two patients who relapsed > 6 years after T cell depleted BMT for CML. Thus STR-PCR is an appropriate screening test in the post transplant setting for CML patients, but those patients exhibiting mixed haemopoietic chimaerism should also be monitored using a leukaemia specific sensitive molecular assay.

    背景与目标: 尽管同种异体骨髓移植(BMT)可以成功治疗慢性粒细胞白血病(CML),但白血病复发仍然是一个重要的临床问题。移植后骨髓的分子监测可用于预测复发,特别是在CML患者中,其中费城染色体或其分子对应物,BCR-ABL融合信使RNA可用作最小残留疾病(MRD)的白血病特异性标志物。我们以临床和血液学缓解的18例患者为研究对象,连续研究了嵌合症(使用短串联重复序列的聚合酶链反应(STR-PCR))和MRD状态(使用BCR-ABL融合mRNA的逆转录酶PCR)。后异基因BMT治疗慢性期CML。 11名患者表现出完全的供体嵌合症,没有最小残留病的证据。 5例患者有短暂或低水平的稳定MC。在T细胞耗尽BMT的CML后复发> 6年的两名患者中观察到晚期MC和MRD。因此,STR-PCR是适合于CML患者移植后环境的筛查测试,但对于那些表现出混合造血干细胞病的患者,也应使用白血病特异性敏感分子测定法进行监测。

  • 【游离皮质醇测定在全身感染中的价值。】 复制标题 收藏 收藏
    DOI:10.1055/s-2007-980200 复制DOI
    作者列表:Torpy DJ,Ho JT
    BACKGROUND & AIMS: :Systemic infection induces an increase in plasma cortisol which accords approximately with illness severity. However, both basal and synthetic ACTH stimulated cortisol levels are not strong predictors of mortality. Moreover, plasma cortisol levels do not readily define those patients who have been clinically observed to respond, with respect to blood pressure elevation, to exogenous hydrocortisone. It is likely that free cortisol, accounting for 6-20% of circulating total (bound plus free) cortisol has most of the life-saving effects on circulation and metabolism in severe sepsis, as corticosteroid-binding globulin bound and albumin-bound cortisol have reduced access to tissues. In addition, sepsis reduces CBG and albumin levels, hence blunting the effect of increasing illness severity on total cortisol. Our recent studies suggest that free cortisol correlates more closely to sepsis severity than total cortisol and that free cortisol levels can be estimated using the plasma CBG and total cortisol, obviating the need for direct free cortisol measurement. Studies directed at determining if free cortisol is a better guide than total cortisol to the need for hydrocortisone supplementation may be of value.
    背景与目标: :全身性感染可引起血浆皮质醇增加,这与疾病的严重程度大致相符。但是,无论是基础还是人工合成的促肾上腺皮质激素刺激皮质醇水平都不是死亡率的强力预测指标。此外,血浆皮质醇水平不能轻易定义那些在临床上已观察到对血压升高对外源性氢化可的松有反应的患者。游离皮质醇可能占严重脓毒症中循环和代谢的大部分挽救生命的作用,而游离皮质醇占循环总量(结合的+游离的)皮质醇的6-20%,因为与皮质类固醇结合的球蛋白结合和与白蛋白结合的皮质醇具有减少进入组织的机会。此外,败血症可降低CBG和白蛋白水平,从而减弱疾病严重程度对总皮质醇的影响。我们最近的研究表明,游离皮质醇与败血症严重程度的关系比总皮质醇更密切,并且可以使用血浆CBG和总皮质醇来估算游离皮质醇的水平,从而无需直接测量游离皮质醇。旨在确定游离皮质醇是否比总皮质醇更好的指南的研究对于补充氢化可的松的需求可能是有价值的。
  • 【全乳切除与腋窝淋巴结清扫术。一种改良的根治性乳房切除术。】 复制标题 收藏 收藏
    DOI:10.1016/0002-9610(77)90459-7 复制DOI
    作者列表:Roses DF,Harris MN,Gumport SL
    BACKGROUND & AIMS: :A technic for total mastectomy with complete axillary dissection has been described. The procedure utilizes division of the pectoralis major muscle between its clavicular and sternal portions, perservation of its innervation, and reconstruction after completion of the dissection. The pectoralis minor muscle is resected. This modification facilitates a thorough axillary dissection, particularly at the apex, while preserving the cosmetic and functional benefits of the Patey operation.
    背景与目标: :已经描述了一种具有完全腋窝清扫术的全乳切除技术。该程序利用胸大肌在锁骨和胸骨部分之间的分割,保留神经支配以及在解剖完成后进行重建。切除胸小肌。这种修改有助于彻底进行腋窝解剖,尤其是在根尖处,同时保留Patey手术的美观和功能优势。
  • 【细胞外镁的升高迅速升高人主动脉内皮细胞中的细胞内游离Mg2:细胞外Mg2是调节性阳离子吗?】 复制标题 收藏 收藏
    DOI:10.2741/a157 复制DOI
    作者列表:Zhang A,Altura BT,Altura BM
    BACKGROUND & AIMS: :Extracellular magnesium ions [Mg2+]o are known to regulate functions of endothelial cells, but whether [Mg2+]o can alter intracellular free ionized magnesium [Mg2+]i in these cells remains unknown. The present studies, using digital imaging microscopy and the Mg2+ fluorescent probe, mag-fura-2, determined effects of elevation of [Mg2+]o on [Mg2+]i in cultured human aortic endothelial cells. With normal Mg2+(1.2 mM)-containing incubation media, [Mg2+]i was 0.51+/-0.04 mM with a heterogeneous distribution. The ratio of [Mg2+]i/[Mg2+]o was 0.52+/-0.07. Elevation of [Mg2+]o up to 4.8 mM increased [Mg2+]i to 0.80+/-0.07 mM in 2-10 min and lowered the ratio of [Mg2+]i/[Mg2+]o to 0.16+/-0.02. Irrespective of the observed increments of [Mg2+]i, a subcellular heterogeneous distribution of [Mg2+]i was always evident in all cells tested. Our results suggest that [Mg2+]o can regulate [Mg2+]i more rapidly than heretofore believed, supporting the hypothesis that extracellular Mg2+ can exert regulatory effects on endothelial cell functions and probably act as extracellular regulatory cations
    背景与目标: :已知细胞外镁离子[Mg2] o调节内皮细胞的功能,但是[Mg2] o是否可以改变这些细胞中的细胞内游离离子化镁[Mg2] i,仍然未知。本研究使用数字成像显微镜和Mg2荧光探针mag-fura-2,确定了培养的人主动脉内皮细胞中[Mg2] o升高对[Mg2] i的影响。在含有正常Mg2(1.2 mM)的培养培养基中,[Mg2] i为0.51 / 0.04 mM,分布不均。 [Mg 2] i / [Mg 2] o的比例为0.52 / -0.07。 [Mg2] o升高至4.8 mM会使[Mg2] i在2-10分钟内增加到0.80 /-0.07 mM,并使[Mg2] i / [Mg2] o的比率降低到0.16 /-0.02。不管观察到的[Mg2] i增量如何,在所有测试的细胞中[Mg2] i的亚细胞异质分布总是很明显的。我们的结果表明,[Mg2] o可以比以前认为的更快地调节[Mg2] i,支持以下假设:细胞外Mg2可以对内皮细胞功能发挥调节作用,并且可能充当细胞外调节阳离子
  • 【白内障晶状体中蛋白质结合的和游离的紫外线滤光片。紫外线滤光片的浓度比普通镜片低得多。】 复制标题 收藏 收藏
    DOI:10.1016/j.exer.2007.04.004 复制DOI
    作者列表:Korlimbinis A,Aquilina JA,Truscott RJ
    BACKGROUND & AIMS: :In human cataract lenses the UV filters, 3-hydroxykynurenine glucoside (3OHKG) and kynurenine (Kyn) were found to be covalently bound to proteins and the levels in the nucleus were much higher than in the cortex. The levels of the bound UV filters in cataract nuclei were much lower than those in age-matched normal lenses. 3-Hydroxykynurenine could not be detected in cataract lenses. As with normal lenses, protein-bound 3OHKG in cataract lenses was found at the highest levels followed by Kyn. Free UV filter concentrations were also markedly reduced in cataract lenses. This feature may well contribute to the lower protein-bound levels; however, there was no clear relationship between free and bound UV filter contents when individual lenses were examined. We propose that since cysteine is a major site for UV filter binding, the well-documented oxidation of protein sulfhydryl groups during the progression of nuclear cataract may account, in part, for the pronounced decrease in bound UV filters in cataract lenses.
    背景与目标: :在人类白内障镜片中,发现紫外线滤光片,3-羟基犬尿氨酸糖苷(3OHKG)和犬尿氨酸(Kyn)与蛋白质共价结合,并且细胞核中的含量远高于皮质。白内障细胞核中结合的紫外线过滤剂的水平远低于年龄匹配的正常晶状体中的水平。在白内障晶状体中未检出3-羟基犬尿氨酸。与正常晶状体一样,白内障晶状体中结合蛋白的3OHKG含量最高,其次是Kyn。白内障晶状体中游离UV过滤剂的浓度也显着降低。此功能很可能有助于降低蛋白结合水平。然而,当检查单个镜片时,游离和结合的紫外线过滤剂含量之间没有明确的关系。我们建议,由于半胱氨酸是紫外线滤光片结合的主要部位,在核性白内障发展过程中,蛋白质硫氢基团的有据可查的氧化可能部分解释了白内障晶状体中结合的紫外线滤光片的明显减少。
  • 【受唐氏综合症影响的怀孕中的早孕期无尿β-hCG,β核心和总雌三醇:含环半透明和无血清β-hCG的早孕筛查的意义。】 复制标题 收藏 收藏
    DOI:10.1002/(sici)1097-0223(199706)17:6<525::aid-pd105 复制DOI
    作者列表:Spencer K,Noble P,Snijders RJ,Nicolaides KH
    BACKGROUND & AIMS: :We have examined maternal urine concentrations of beta core, free beta human chorionic gonadotrophin (hCG), and total oestriol in 373 control pregnancies and 43 pregnancies affected by aneuploidy (including 22 cases of Down's syndrome) in an attempt to see if any of the analytes have a value in Down's syndrome screening between the tenth and 14th week of pregnancy. We have compared the performance of these analytes against nuchal translucency measurement combined with maternal serum free beta hCG at the same period of pregnancy. Our results show that levels of urine free beta hCG and beta core are increased in Down's syndrome with average multiple of the median levels of 1.81 and 2.91, respectively. Urine total oestriol was reduced (0.83) whilst maternal serum free beta hCG was increased (1.72). In trisomy 18 the levels of all analytes were reduced, although serum free beta hCG was the most discriminating. The spread of results in the control and the Down's group for urine beta core was more than three times than that for serum free beta hCG and with urine free beta hCG it was two times wider. In combination with maternal age, urine total oestriol had a 32 per cent detection rate at a fixed 5 per cent false-positive rate; urine beta core 34 per cent, urine free beta hCG 36 per cent, maternal serum free beta hCG 44 per cent, and nuchal translucency 82 per cent. In combination with nuchal translucency, urine total oestriol added an extra 1 per cent detection, urine beta core an extra 2 per cent, urine free beta hCG an extra 3 per cent, and serum free beta hCG an extra 5 per cent. It is unlikely that any of the urine markers will be of value in first-trimester screening. Optimal first-trimester screening programmes will rely for the foreseeable future on nuchal translucency, serum free beta hCG, and possibly pregnancy-associated plasma protein A.
    背景与目标: :我们检查了373例非整倍性(包括22例唐氏综合症患者)的孕妇和43例孕妇的β核心,游离β人绒毛膜促性腺激素(hCG)和总雌三醇的孕妇尿液浓度,以查看是否存在任何在妊娠的第十至十四周期间,分析物在唐氏综合症筛查中具有价值。我们已将这些分析物的性能与在怀孕同一时期与孕妇血清游离βhCG相结合的颈部半透明测量结果进行了比较。我们的结果表明,唐氏综合症中无尿的βhCG和β核心水平升高,分别为中位数水平的平均倍数1.81和2.91。尿中总雌三醇减少(0.83),而孕妇血清游离β-hCG增加(1.72)。在三体性18中,所有血清分析物的含量都降低了,尽管无血清的βhCG最为明显。对照组和唐氏组中尿β-核心的结果分布是无血清β-hCG的三倍以上,而无尿β-hCG的结果则宽了两倍。结合产妇年龄,尿中总雌三醇的检出率为32%,假阳性率为5%。尿β-核心34%,尿β-hCG36%,孕妇血清β-hCG44%,口腔半透明82%。结合颈部半透明性,尿液中总雌三醇的含量增加了1%,尿液β-核心的含量增加了2%,无尿β-hCG的增加了3%,​​无血清β-hCG的增加了5%。任何尿液标记物在孕早期筛查中都没有价值的可能性很小。最佳的早孕筛查程序将在可预见的将来依赖于颈部半透明性,无血清βhCG以及可能与妊娠相关的血浆蛋白A。
  • 【在自由呼吸的幼儿肺中通过0.3秒电影CT获得的吸气和呼气相位图像上的空气捕获检测。】 复制标题 收藏 收藏
    DOI:10.2214/AJR.05.0895 复制DOI
    作者列表:Goo HW,Kim HJ
    BACKGROUND & AIMS: OBJECTIVE:The objective of our study was to evaluate whether 0.3-second cine CT can be used to detect air trapping in the lungs of young children. SUBJECTS AND METHODS:In 30 children (mean age, 25 months), 0.3-second cine CT was performed at six levels during 3 seconds of quiet breathing. The study population was divided into an air trapping group (n = 24) and a no-air trapping group (n = 6). Lung density was measured at an abnormal area (with or without air trapping) and an adjacent normal area on inspiratory and expiratory phase images. Lung density differences between inspiration and expiration were calculated and compared in abnormal areas (with or without air trapping) and in normal areas. Their percentages were calculated and compared between the two groups. In addition, lung density differences between abnormal and adjacent normal areas were calculated and compared between the two groups. RESULTS:Lung density differences between inspiration and expiration were smaller in areas with air trapping (mean +/- SD, -19 +/- 34 H) than in abnormal areas without air trapping (138 +/- 36 H) (p < 0.001) or in normal areas (111 +/- 49 H) (p < 0.001). Their percentages were smaller in the group with air trapping (-27% +/- 54%) than in the group with no air trapping (120% +/- 87%) (p < 0.001). In the group with air trapping, lung density differences were larger at the expiratory phase (260 +/- 77 H) than at the inspiratory phase (129 +/- 69 H) (p < 0.001), but did not change through the respiratory cycle in the group with no air trapping (p > 0.05). CONCLUSION:Air trapping can be accurately detected in the lungs of free-breathing young children using 0.3-second cine CT.
    背景与目标: 目的:本研究的目的是评估0.3秒的电影CT是否可用于检测年幼儿童肺部的空气滞留情况。
    研究对象和方法:在30名儿童(平均年龄25个月)中,在安静呼吸的3秒内以六个级别进行了0.3秒的电影CT检查。研究人群分为空气诱捕组(n = 24)和无空气诱捕组(n = 6)。在吸气和呼气相位图像上的异常区域(有或没有空气滞留)和相邻的正常区域测量肺密度。计算了吸气和呼气之间的肺密度差异,并在异常区域(有或没有空气滞留)和正常区域中进行了比较。计算他们的百分比,并在两组之间进行比较。此外,计算并比较了正常和邻近正常区域之间的肺密度差异。
    结果:有空气滞留的区域(平均/-SD,-19 /-34 H)的吸气和呼气之间的肺密度差异要小于没有空气滞留的异常区域(138 /-36 H)(p <0.001)或在有空气滞留的区域。正常区域(111 /-49 H)(p <0.001)。有空气滞留组的百分比(-27%/-54%)比没有空气滞留组的百分比(120%/-87%)小(p <0.001)。在有空气滞留的组中,呼气阶段(260 /-77 H)的肺密度差异大于吸气阶段(129 /-69 H)的肺密度差异(p <0.001),但在整个呼吸周期中没有变化。没有空气滞留的组(p> 0.05)。
    结论:使用0.3秒的电影CT可以准确地检测自由呼吸的幼儿的肺部空气捕获。
  • 【来自烟草的反馈不敏感邻氨基苯甲酸合酶基因的表达增加了大豆植物中的游离色氨酸。】 复制标题 收藏 收藏
    DOI:10.1007/s00299-007-0381-0 复制DOI
    作者列表:Inaba Y,Brotherton JE,Ulanov A,Widholm JM
    BACKGROUND & AIMS: :Soybean [Glycine max (L.) Merr.] embryogenic cultures were transformed by particle bombardment with the feedback-insensitive tobacco anthranilate synthase (AS) gene ASA2 driven by the CaMV 35S promoter and selected using hph as the selectable marker gene. Only one of eight regenerated lines that set seed and contained ASA2 expressed the gene highly and contained increased free tryptophan (Trp) levels in leaves, seeds and embryogenic cultures. Leaf extracts of the ASA2 expressing line contained about twice as much AS enzyme activity as the untransformed control and this activity was only slightly more feedback-insensitive. Amino acid analysis showed that both leaves and embryogenic tissue cultures of the ASA2 expressing line had four to five-times the normal levels of free Trp and slightly higher free tyrosine and phenylalanine. The seed total Trp content was only slightly increased. Metabolic profiling-analysis by GC-MS detected no other consistent differences. These studies show that the ASA2 gene can be expressed in soybean and that modest changes in Trp synthesis occurs.
    背景与目标: :大豆[Glycine max(L.)Merr。]胚性培养物通过由CaMV 35S启动子驱动的反馈不敏感的烟草邻氨基苯甲酸合酶(AS)基因ASA2进行粒子轰击进行转化,并使用hph作为选择标记基因进行选择。八个定植种子并含有ASA2的再生系中只有一个表达该基因,并且在叶片,种子和胚发生培养物中的游离色氨酸(Trp)水平升高。表达ASA2的品系的叶提取物所含的AS酶活性约为未转化对照的两倍,该活性对反馈的敏感性稍高。氨基酸分析表明,ASA2表达株系的叶片和胚发生组织培养物的游离Trp含量是正常水平的4至5倍,游离酪氨酸和苯丙氨酸含量稍高。种子总色氨酸含量仅略有增加。 GC-MS进行的代谢谱分析没有发现其他一致的差异。这些研究表明,ASA2基因可以在大豆中表达,并且Trp合成发生适度的变化。
  • 【一种自由市场的比赛方法:尚未到来的提议。】 复制标题 收藏 收藏
    DOI:10.1097/ACM.0000000000001782 复制DOI
    作者列表:Arnold L,Sullivan C,Okah FA
    BACKGROUND & AIMS: :The authors respond to a proposal in this issue of Academic Medicine by Ray, Bishop, and Dow, who recommend adopting a free-market approach to the Match in which applicants and programs negotiate directly with each other to find and fill residency positions year-round. This Invited Commentary examines and responds to the reasons Ray and colleagues give for changing the Match and explores their proposal's implications and likelihood of success.The authors question Ray and colleagues' argument that assumptions underlying the National Resident Matching Program algorithm have been violated. The authors suggest there is insufficient evidence for the "July effect" and that the possibility for improvement in physician supply due to the year-round entry of graduates into the workforce ultimately faces the rate-limiting step of caps on residency positions allocated to programs. Most important, competency-based medical education, on which the free-market proposal depends, is not yet sufficiently developed.Nonetheless, the imbalanced ratio of applicants to positions in the Match is contributing to a rise in the numbers of student applications and program interviews. Although the proposed free-market approach might, as Ray and colleagues envision, curtail applications as well as reduce time and financial resources currently expended on the process, it would require significant changes on the part of applicants, residency programs, medical schools, and other stakeholders.Because the proposed free-market approach could reduce some negative effects of the imbalance of applicants and positions, it merits ongoing discussion along with other more immediate practical solutions to issues with the Match.
    背景与目标: :作者回应了Ray,Bishop和Dow在本期《学术医学》中提出的建议,他们建议对比赛采用自由市场的方法,在这种方法中,申请人和计划彼此直接协商以寻找并填补当年的居留职位-圆形的。本受邀评论对Ray和同事提出的更改比赛的原因进行了调查并做出回应,并探讨了其提议的含义和成功的可能性。作者质疑Ray和同事的论点,即违反了《美国国家居民匹配计划》算法的假设。作者认为,“七月效应”没有足够的证据,而且由于毕业生全年进入劳动力队伍而改善医生供应的可能性最终面临着分配给计划的居留职位上限的限速步骤。最重要的是,基于自由市场的建议所依赖的基于能力的医学教育尚未得到充分发展,尽管如此,申请人与比赛中职位的比例失衡导致学生申请和计划面试的人数增加。尽管如雷及其同事所设想的那样,提议的自由市场方法可能会减少申请,并减少目前在该过程中花费的时间和财务资源,但仍需要对申请人,居住计划,医学院和其他方面进行重大更改。由于拟议的自由市场方法可以减少申请人和职位失衡的某些负面影响,因此值得进行中的讨论以及针对Match问题的其他更直接的实际解决方案。
  • 【鸣禽的超长寿命与细胞色素b的高进化速率有关,这表明选择减少自由基的产生。】 复制标题 收藏 收藏
    DOI:10.1242/jeb.004861 复制DOI
    作者列表:Rottenberg H
    BACKGROUND & AIMS: :In animals, longevity (maximal lifespan) is inversely related to mass-specific basal metabolic rates. However, contrary to expectation, in several mammalian taxa, exceptional longevity is associated with high basal metabolic rate, and also fast evolution of mtDNA-coded proteins. The association of these traits was suggested to result from adaptive selection of mutations in mtDNA-coded proteins, which accelerates basal respiration, thus inhibiting the generation of reactive oxygen species that constrain longevity. In birds, all the genera with high rate of cytochrome b evolution are songbirds (oscines). Within the songbirds group, both longevity residuals and lifetime expenditure of energy are positively correlated with the rate of cytochrome b evolution. Moreover, within the large songbirds family Fringillidae (true finches) mass-specific basal metabolic rates, longevity, longevity residuals and lifetime expenditure of energy are all positively correlated with the rate of evolution of cytochrome b. In Serinus, a genus of finches (canaries) that exhibits the highest rate of cytochrome b evolution, and the highest values of exceptional longevity and lifetime expenditure of energy in all birds, many of the substitutions in cytochrome b are clustered around Qi, a ubiquinone binding site adjacent to the mitochondrial matrix, apparently selected to increase the rate of ubiquinone reduction. We therefore suggest that, in songbirds, the accelerated evolution of cytochrome b involved selection of mutations that reduce the generation of reactive oxygen species, thus contributing to the evolution of exceptional longevity, and possibly also exceptional long-term memory, which is necessary for learning songs.
    背景与目标: 在动物中,寿命(最大寿命)与特定于质量的基础代谢率成反比。然而,与预期相反,在几种哺乳动物类群中,超长寿命与高基础代谢率以及mtDNA编码蛋白的快速进化有关。这些特性的关联被认为是由mtDNA编码蛋白中突变的适应性选择导致的,该突变可加速基础呼吸,从而抑制了限制寿命的活性氧的产生。在鸟类中,所有具有高细胞色素b进化率的属都是鸣鸟(oscines)。在鸣鸟组中,长寿残差和终生能量消耗都与细胞色素b的进化速率正相关。此外,在大型鸣鸟科(Fringillidae(真雀科))中,特定质量的基础代谢率,寿命,寿命残差和终生能量消耗均与细胞色素b的进化速率呈正相关。在Serinus(一种雀科(金丝雀))中表现出最高的细胞色素b进化速率,并且在所有鸟类中具有最高的超常寿命和终生能量消耗值,在许多鸟类中,细胞色素b的许多替代物聚集在Qi周围,即泛醌与线粒体基质相邻的结合位点,显然是为了增加泛醌还原率而选择的。因此,我们建议,在鸣禽中,细胞色素b的加速进化涉及选择减少活性氧物种生成的突变,从而促进了超长寿命的发展,并且可能也促进了超长记忆的发展,这对于学习是必不可少的。歌曲。
  • 【自由意志信念可以预测人们对不道德行为和刑事处罚的态度。】 复制标题 收藏 收藏
    DOI:10.1073/pnas.1702119114 复制DOI
    作者列表:Martin ND,Rigoni D,Vohs KD
    BACKGROUND & AIMS: :Do free will beliefs influence moral judgments? Answers to this question from theoretical and empirical perspectives are controversial. This study attempted to replicate past research and offer theoretical insights by analyzing World Values Survey data from residents of 46 countries (n = 65,111 persons). Corroborating experimental findings, free will beliefs predicted intolerance of unethical behaviors and support for severe criminal punishment. Further, the link between free will beliefs and intolerance of unethical behavior was moderated by variations in countries' institutional integrity, defined as the degree to which countries had accountable, corruption-free public sectors. Free will beliefs predicted intolerance of unethical behaviors for residents of countries with high and moderate institutional integrity, but this correlation was not seen for countries with low institutional integrity. Free will beliefs predicted support for criminal punishment regardless of countries' institutional integrity. Results were robust across different operationalizations of institutional integrity and with or without statistical control variables.
    背景与目标: :信仰自由会影响道德判断吗?从理论和经验的角度对这个问题的回答是有争议的。这项研究试图通过分析来自46个国家(n = 65111人)的居民的世界价值调查数据来复制过去的研究并提供理论上的见解。证实实验结果,自由意志信念预测不道德行为的不容忍,并支持严厉的刑事处罚。此外,自由意志信仰与不道德行为的不容忍之间的联系因国家体制完整性的变化而缓和,后者的定义是国家对问责制,无腐败公共部门的重视程度。自由意志信念预示着制度健全程度中等的国家的居民对不道德行为的不容忍,但对于制度健全程度较低的国家则没有这种相关性。自由意志信念预示了对刑事惩罚的支持,而与国家的体制完整性无关。在有或没有统计控制变量的情况下,机构完整性的不同运作结果均十分可靠。
  • 【使用三氟乙酸进行的实用且无催化剂的胺三氟乙基化反应。】 复制标题 收藏 收藏
    DOI:10.1038/ncomms15913 复制DOI
    作者列表:Andrews KG,Faizova R,Denton RM
    BACKGROUND & AIMS: :Amines are a fundamentally important class of biologically active compounds and the ability to manipulate their physicochemical properties through the introduction of fluorine is of paramount importance in medicinal chemistry. Current synthesis methods for the construction of fluorinated amines rely on air and moisture sensitive reagents that require special handling or harsh reductants that limit functionality. Here we report practical, catalyst-free, reductive trifluoroethylation reactions of free amines exhibiting remarkable functional group tolerance. The reactions proceed in conventional glassware without rigorous exclusion of either moisture or oxygen, and use trifluoroacetic acid as a stable and inexpensive fluorine source. The new methods provide access to a wide range of medicinally relevant functionalized tertiary β-fluoroalkylamine cores, either through direct trifluoroethylation of secondary amines or via a three-component coupling of primary amines, aldehydes and trifluoroacetic acid. A reduction of in situ-generated silyl ester species is proposed to account for the reductive selectivity observed.
    背景与目标: 胺是生物活性化合物的根本上重要的一类,通过引入氟来控制其理化性质的能力在药物化学中至关重要。当前用于构造氟化胺的合成方法依赖于对空气和湿气敏感的试剂,这些试剂需要特殊的处理或苛刻的还原剂,从而限制了其功能性。在这里我们报告了表现出显着的官能团耐受性的游离胺的实用,无催化剂的还原性三氟乙基化反应。反应在不严格排除水分或氧气的情况下在常规玻璃器皿中进行,并使用三氟乙酸作为稳定且廉价的氟源。通过仲胺的直接三氟乙基化或伯胺,醛和三氟乙酸的三组分偶联,新方法提供了广泛的与医学相关的官能化叔丁基氟烷基胺核的使用途径。提出减少原位产生的甲硅烷基酯种类以解决所观察到的还原选择性。
  • 【丹参根中的新分子及其清除自由基的能力以及对H2O2诱导的H9c2细胞的保护作用。】 复制标题 收藏 收藏
    DOI:10.1016/j.fitote.2017.06.018 复制DOI
    作者列表:Zhang J,Jin Q,Deng Y,Hou J,Wu W,Guo D
    BACKGROUND & AIMS: :Phytochemical investigation of the roots of Salvia miltiorrhiza led to isolations of two new depsides (1-2), along with thirteen known compounds (3-15). Their structures and relative stereochemistry were elucidated by NMR spectral (1H and 13C NMR, HSQC, HMBC), CD and HR-ESIMS data analyses. The absolute configuration of 1 was determined by comparison of the experimental and calculated ECD spectra. All the depsides (1-10) were found to exhibit stronger free radical scavenging capacity (ranging from 2.62 to 22.05μM) than diterpenoids (11-15, IC50>100μM), among which Salvianolic acid A and Salvianolic acid B were the most potent compounds. Additionally, most of depsides (1, 3, 5, 7, 8, 9, 10) possessed significant protective effects against H2O2-induced H9c2 apoptosis in low concentrations. The negative mode collision-induced dissociations of compound 1 and 2 were featured by the α-cleavage and β-cleavage to lose danshensu (198Da) and caffeic acid (180Da), respectively, while α,β-dihydroxybenzenes depsides (8-hydroxy) showed characteristic neutral elimination of H2O.
    背景与目标: 丹参的根的植物化学研究导致分离出两个新的糊精(1-2)以及十三种已知化合物(3-15)。通过NMR光谱(1H和13C NMR,HSQC,HMBC),CD和HR-ESIMS数据分析阐明了它们的结构和相对立体化学。通过比较实验和计算出的ECD光谱,可以确定1的绝对构型。发现所有糊精(1-10)都比二萜类化合物(11-15,IC50>100μM)表现出更强的自由基清除能力(范围为2.62至22.05μM),其中丹酚酸A和丹酚酸B最有效。化合物。另外,大多数低浓度的分散剂(1、3、5、7、8、9、10)对H2O2诱导的H9c2细胞凋亡具有显着的保护作用。化合物1和2的负模式碰撞诱导解离的特征是α裂解和β裂解分别失去了丹参素(198Da)和咖啡酸(180Da),而α,β-二羟基苯多酚(8-羟基)表现出中性消除H2O的特性。

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