BACKGROUND & AIMS: :Apically secreted 80-kDa glycoprotein (gp 80) from Madin-Darby canine kidney cells was found to be immunoprecipitated by the polyclonal antiserum against fibronectin or a monoclonal antibody specific for the fibronectin C-terminal fibrin binding domain. Upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), gp 80 migrated as a doublet band under nonreducing conditions. Under reducing conditions, gp 80 was resolved into three distinct bands, respectively of 45-, 40-, and 35-kDa molecular mass. Analysis by two-dimensional SDS-PAGE revealed that gp 80 exists in two molecular forms: one consisting of a 45-kDa subunit and a 40-kDa subunit, and one consisting of a 45-kDa subunit and a 35-kDa subunit. V-8 protease mapping indicated the 40 and 35-kDa subunits as being of the same homologous group and also as bearing partial homology to the 45-kDa subunit. Radioactive labeling revealed that labeled gp 80 was subjected to covalent modifications by sulfation and phosphorylation. Sulfate analysis showed that [35S]sulfate-labeled gp 80 contained ca. 2.45 +/- 0.07% tyrosine-bound [35S]sulfate with the rest being presumably carbohydrate-bound. [32P]-Phosphate-labeled gp 80, on the other hand, was found to contain serine-O-phosphate as the predominant phosphorylated amino acid residue. Employing the affinity gel fractionation technique, it was shown that gp 80 exhibited binding affinities toward heparin and fibrin. Binding of gp 80 to heparin-agarose or fibrin-Sepharose, however, was inhibited in the presence of added fibronectin or the monoclonal antibody. Tryptic peptide mapping revealed common peptide spots between fibronectin and the three subunits of gp 80. Furthermore, Western blot analysis showed that fibronectin could be recognized and bound by anti-gp 80 antibodies. These results indicate that gp 80 bears both structural and functional similarities to the C-terminal portion of the fibronectin molecule.

背景与目标： : 发现从Madin-Darby犬肾细胞中分泌的80 kDa糖蛋白 (gp 80) 被针对纤连蛋白的多克隆抗血清或对纤连蛋白C末端纤维蛋白结合域具有特异性的单克隆抗体免疫沉淀。在十二烷基硫酸钠-聚丙烯酰胺凝胶电泳 (sds-page) 下，gp 80在非还原条件下以双峰带的形式迁移。在还原条件下，gp 80分解为三个不同的带，分别为45，40和35 kDa分子量。通过二维sds-page进行的分析表明，gp 80以两种分子形式存在: 一种由45 kDa亚基和40 kDa亚基组成，另一种由45 kDa亚基和35 kDa亚基组成。V-8蛋白酶作图表明40和35 kDa亚基属于同一同源组，并且与45 kDa亚基具有部分同源性。放射性标记显示，标记的gp 80通过硫酸化和磷酸化进行共价修饰。硫酸盐分析表明，[35S] 硫酸盐标记的gp 80含有约2.45 +/- 0.07% 酪氨酸结合的 [35S] 硫酸盐，其余的大概是碳水化合物结合的。[32P]-磷酸盐标记的gp 80，另一方面，发现含有丝氨酸-O-磷酸作为主要的磷酸化氨基酸残基。使用亲和凝胶分级技术，表明gp 80表现出与肝素和纤维蛋白的结合亲和力。gp 80与肝素-琼脂糖或纤维蛋白-琼脂糖的结合，在添加纤连蛋白或单克隆抗体的情况下被抑制。胰蛋白酶肽作图显示纤连蛋白与gp 80的三个亚基之间的共同肽点。此外，蛋白质印迹分析表明，纤连蛋白可以被抗gp 80抗体识别和结合。这些结果表明，gp 80与纤连蛋白分子的C端部分具有结构和功能相似性。

BACKGROUND & AIMS: :The repair of ionising-radiation-induced DNA double-strand break type damage was measured by Kohn neutral elution in an X-ray-sensitive mutant of V79-4, irs1. This was done in order to investigate further the likelihood that irs1 carries a defect which leads to error-prone repair of DNA damage, and not simply a reduced ability to rejoin DNA double-strand breaks. The mutant displayed an equal increase in sensitivity to the lethal effects of neutrons, as compared to X-rays. Both irs1 and V79-4 showed an increased sensitivity to the killing effects of neutrons of around 2 at 10% survival. irs1 also showed an exponential survival after either X-rays or neutrons. The induction of DNA double-strand breaks was measured in both cell lines over a dose range of 10-40 Gy using Kohn neutral filter elution. Induction of breaks by X-rays in irs1 seemed to increase slightly with dose, relative to induction in V79-4, so that at 40 Gy 1.5 times more DNA double-strand breaks were measured in irs1 cells than in V79-4. Neutron irradiation resulted in a more similar level of induction in either strain after 10-40 Gy. This difference in induction of damage may be due to a different cell-cycle composition in either cell line. The rejoining of X-ray induced double-strand breaks showed a very similar pattern (on a percentage rejoined basis) in both cell lines, although from the induction data at 40 Gy, the dose at which rejoining was measured, fewer breaks were rejoined in V79-4 but also fewer breaks remained unsealed. Neutron-induced breaks, however, were rejoined more efficiently in irs1 again on a percentage basis, but also in absolute terms since similar induction was seen after 40 Gy. This data, together with the differences seen in the rejoining of X-ray compared to neutron induced breaks, may indirectly support the proposal that irs1 is a misrepair mutant.

背景与目标： : 电离辐射诱导的DNA双链断裂型损伤的修复是通过Kohn中性洗脱在V79-4的x射线敏感突变体irs1中进行的。这样做是为了进一步研究irs1携带缺陷的可能性，该缺陷导致容易出错的DNA损伤修复，而不仅仅是降低重新连接DNA双链断裂的能力。与x射线相比，该突变体对中子致死效应的敏感性相同。irs1和V79-4在10% 存活时对中子的杀伤作用均显示出增加的敏感性，约为2。irs1在x射线或中子后也显示出指数生存。使用Kohn中性滤镜洗脱在10-40 Gy的剂量范围内测量了两种细胞系中DNA双链断裂的诱导。相对于V79-4中的诱导，irs1中x射线对断裂的诱导似乎随剂量略有增加，因此在40 Gy时，irs1细胞中测得的DNA双链断裂比V79-4中多1.5倍。10-40 Gy后，中子辐照在任一菌株中的诱导水平均更为相似。损伤诱导的这种差异可能是由于两种细胞系中的细胞周期组成不同所致。X射线诱导的双链断裂的重新结合在两种细胞系中显示出非常相似的模式 (以百分比重新结合为基础)，尽管从40 gy的诱导数据 (测量重新结合的剂量) 来看，在V79-4中重新结合的断裂更少，但仍保持未密封的断裂更少。然而，中子诱导的断裂在irs1中再次以百分比为基础更有效地重新结合，但也以绝对值重新结合，因为在40 Gy之后看到了类似的诱导。该数据以及与中子诱导的断裂相比，x射线重新结合所看到的差异，可能间接支持irs1是误修突变体的提议。

BACKGROUND & AIMS: :Formation of protein aggregates in the aging eye lens has been shown to correlate with progressive accumulation of specific low-molecular weight (LMW) peptides derived from crystallins. Prominent among the LMW fragments is αA66-80, a peptide derived from αA-crystallin and present at higher concentrations in the water-insoluble nuclear fractions of the aging lens. The αA66-80 peptide has amyloid-like properties and preferentially insolubilizes α-crystallin from soluble lens fractions. However, the specific interactions and mechanisms by which the peptide induces α-crystallin aggregation have not been delineated. To gain insight into the mechanisms of peptide-induced aggregation, we investigated the interactions of the peptide with α-crystallin by various biochemical approaches. The peptide weakens α-crystallin chaperone ability and drastically promotes α-crystallin aggregation via the formation of insoluble peptide-protein complexes through transient intermediates. 4,4'-Dianilino-1,1'-binaphthyl-5,5'-disulfonic acid studies suggest that the peptide induces changes in the hydrophobicity of α-crystallin that could trigger the formation and growth of aggregates. The peptide-α-crystallin aggregates were found to be resistant to dissociation by high ionic strengths, whereas guanidinium hydrochloride and urea were effective dissociating agents. We conclude that the αA66-80 peptide forms a hydrophobically driven, stable complex with α-crystallin and reduces its solubility. Using isotope-labeled chemical cross-linking and mass spectrometry, we show that the peptide binds to multiple sites, including the chaperone site, the C-terminal extension, and subunit interaction sites in αB-crystallin, which may explain the antichaperone property of the peptide and the consequential age-related accumulation of aggregated proteins. Thus, the α-crystallin-derived peptide could play a role in the pathogenesis of cataract formation in the aging lens.

背景与目标： : 已显示老化眼晶状体中蛋白质聚集体的形成与衍生自晶体蛋白的特定低分子量 (LMW) 肽的逐渐积累相关。LMW片段中最突出的是 αA66-80，这是一种衍生自 α a-晶体蛋白的肽，以较高浓度存在于老化晶状体的水不溶性核部分中。Αa66-80肽具有类似淀粉样蛋白的特性，并且优先使可溶性晶状体部分中的 α-晶体蛋白不溶解。然而，尚未描述肽诱导 α-晶体蛋白聚集的特定相互作用和机制。为了深入了解肽诱导聚集的机制，我们通过各种生化方法研究了肽与 α-晶体蛋白的相互作用。该肽通过瞬时中间体形成不溶性肽-蛋白质复合物，削弱 α-晶体蛋白伴侣的能力，并极大地促进 α-晶体蛋白聚集。4,4 '-Dianilino-1，1'-binaphthyl-5，5 '-二磺酸研究表明，该肽诱导 α-晶体蛋白疏水性的变化，这可能触发聚集体的形成和生长。发现肽-α-晶体蛋白聚集体可耐因高离子强度而解离，而盐酸胍和尿素是有效的解离剂。我们得出的结论是，αA66-80肽与 α-晶体蛋白形成疏水驱动的稳定复合物，并降低其溶解度。使用同位素标记的化学交联和质谱，我们显示该肽与多个位点结合，包括伴侣位点，C末端延伸和 α b-晶体蛋白中的亚基相互作用位点，这可以解释肽的抗伴侣特性以及随之而来的与年龄相关的聚集蛋白的积累。因此，α-晶状体蛋白衍生肽可能在衰老晶状体中白内障形成的发病机理中起作用。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :Physical performance declines with age, even in exercising, healthy individuals without major illnesses or orthopedic issues. The rate of performance decline is often reported to accelerate after the age of 70 years, but almost no data are available on performance in the fittest oldest-old. To assess their rate of decline in performance, the biggest data set of track and field athletes aged ≥80 years (1567 results) ever published was generated for different disciplines from German Athletics Federations including 1997-2019. Performance at age 80 years of athletes still participating at age 85 years was compared with those who discontinued. Only 1 of every 22 athletes competing at age 80 years still competed at age 90 years. The performance decline was more than three times as steep in athletes aged ≥80 years (on average 1.62%/year, men: 100 m, R = 0.31, p < 0.001; 200 m, R = 0.17, p = 0.037; long jump, R = -0.37, p < 0.001; shot put, R = -0.32, p < 0.001; discus, R = -0.34, p < 0.001; javelin, R = -0.43, p < 0.001; women: shot put, R = -0.24, p = 0.017; discus, R = -0.33, p = 0.010) compared with athletes aged 30-69 years (0.46%/year) and accelerated at an average of 67 years. This accelerated decline was most pronounced in the sprint disciplines and lowest in the throws. Performance at age 80 years was similar in athletes still participating at age 85 years to those who discontinued, and the variability in results was decreased after age 90 years. In conclusion, physical performance declines more than three times as fast after around the age of 67 years compared with before. This was particularly the case for sprinting but was not a result of dropout of poorer performing athletes.

背景与目标： : 身体表现随着年龄的增长而下降，即使在运动中，健康的人没有重大疾病或骨科问题。据报道，性能下降的速度通常会在70岁以后加速，但是几乎没有关于适龄最老的性能的数据。为了评估他们的表现下降速度，德国田径联合会 (包括1997-2019) 针对不同学科生成了有史以来最大的年龄 ≥ 80岁的田径运动员数据集 (1567结果)。将仍在85岁时参加比赛的80岁运动员的表现与停赛者进行了比较。在80岁时参加比赛的22名运动员中，只有1名仍在90岁时参加比赛。年龄 ≥ 80岁的运动员成绩下降幅度超过3倍 (平均1.62%/年，男性: 100  m，r   =   0.31，p  <  0.001; 200  m，r   =   0.17，p   =   0.037; 跳远，r   =  -0.37，P  <  0.001; 铅球，r   =  -0.32，p  <  0.001; 铁饼，r   =  -0.34，p  <  0.001; 标枪，r   =  -0.43，p  <  0.001; 女子: 铅球，r   =  -0.24，P   =   0.017; discus，r   =  -0.33，p   =   0.010) 与30-69岁 (0.46%/年) 的运动员相比，平均加速67岁。这种加速下降在冲刺学科中最为明显，在投掷中最低。仍在85岁时参加比赛的运动员在80岁时的表现与停课运动员相似，并且在90岁时成绩的变异性降低了。总之，在67岁左右的年龄之后，身体机能下降的速度是以前的三倍以上。短跑尤其如此，但这并不是表现较差的运动员辍学的结果。

BACKGROUND & AIMS: :The objective of this work was to study the differences in terms of early biological effects that might exist between different X-rays energies by using a mechanistic approach. To this end, radiobiological experiments exposing cell monolayers to three X-ray energies were performed in order to assess the yields of early DNA damage, in particular of double-strand breaks (DSBs). The simulation of these irradiations was set in order to understand the differences in the obtained experimental results. Hence, simulated results in terms of microdosimetric spectra and early DSB induction were analyzed and compared to the experimental data. Human umbilical vein endothelial cells (HUVECs) were irradiated with 40, 220 kVp, and 4 MV X-rays. The Geant4 Monte Carlo simulation toolkit and its extension Geant4-DNA were used for the simulations. Microdosimetric calculations aiming to determine possible differences in the variability of the energy absorbed by the irradiated cell population for those photon spectra were performed on 10,000 endothelial cell nuclei representing a cell monolayer. Nanodosimetric simulations were also carried out using a computation chain that allowed the simulation of physical, physico-chemical, and chemical stages on a single realistic endothelial cell nucleus model including both heterochromatin and euchromatin. DNA damage was scored in terms of yields of prompt DSBs per Gray (Gy) and per giga (109) base pair (Gbp) and DSB complexity was derived in order to be compared to experimental data expressed as numbers of histone variant H2AX (γ-H2AX) foci per cell. The calculated microdosimetric spread in the irradiated cell population was similar when comparing between 40 and 220 kVp X-rays and higher when comparing with 4 MV X-rays. Simulated yields of induced DSB/Gy/Gbp were found to be equivalent to those for 40 and 220 kVp but larger than those for 4 MV, resulting in a relative biological effectiveness (RBE) of 1.3. Additionally, DSB complexity was similar between the considered photon spectra. Simulated results were in good agreement with experimental data obtained by IRSN (Institut de radioprotection et de sûreté nucléaire) radiobiologists. Despite differences in photon energy, few differences were observed when comparing between 40 and 220 kVp X-rays in microdosimetric and nanodosimetric calculations. Nevertheless, variations were observed when comparing between 40/220 kVp and 4 MV X-rays. Thanks to the simulation results, these variations were able to be explained by the differences in the production of secondary electrons with energies below 10 keV.

背景与目标： : 这项工作的目的是通过使用机械方法研究不同x射线能量之间可能存在的早期生物学效应的差异。为此，进行了放射生物学实验，将细胞单层暴露于三个x射线能量，以评估早期DNA损伤的产量，特别是双链断裂 (dsb) 的产量。设置这些照射的模拟是为了了解获得的实验结果的差异。因此，分析了根据微剂量学光谱和早期DSB诱导的模拟结果，并将其与实验数据进行了比较。用40、220 kVp和4 MV x射线照射人脐静脉内皮细胞 (huvec)。使用Geant4蒙特卡洛模拟工具包及其扩展Geant4-DNA进行模拟。针对那些光子光谱，在代表细胞单层的10,000内皮细胞核上进行了旨在确定辐照细胞群吸收的能量变异性的微剂量计算。还使用计算链进行了纳米剂量模拟，该计算链允许在包括异染色质和常染色质的单个现实内皮细胞核模型上模拟物理，物理化学和化学阶段。根据每灰色 (Gy) 和每giga (109) 碱基对 (Gbp) 的快速DSB的产量对DNA损伤进行评分，并得出DSB的复杂性，以便与表示为每个细胞的组蛋白变体H2AX (γ-H2AX) 灶数的实验数据进行比较。当在40和220 kVp x射线之间进行比较时，所计算的在被照射的细胞群中的微剂量分布是相似的，而当与4 MV x射线相比时，所计算的微剂量分布是更高的。发现诱导的DSB/Gy/Gbp的模拟产量等于40和220 kVp的模拟产量，但大于4 MV的模拟产量，导致相对生物有效性 (RBE) 为1.3。此外，所考虑的光子光谱之间的DSB复杂度相似。模拟结果与IRSN (放射防护和放射生物研究所) 获得的实验数据非常吻合。尽管光子能量存在差异，但在微剂量和纳米剂量计算中比较40和220 kVp x射线时观察到的差异很少。然而，当比较40/220 kVp和4 mv x射线时观察到变化。由于模拟结果，这些变化可以通过能量低于10 keV的二次电子产生的差异来解释。

BACKGROUND & AIMS: :To evaluate the effects of two fall-prevention and anti-osteoporotic protocols in elderly patients with osteopenia (OPA). METHODS:The present randomized controlled study included patients with OPA (n =123). The age of these patients was ≥80 years old, with the mean age of 83.54 ± 2.99 years, and the male-to-female ratio was 2.97:1.00. Fall-prevention guidance was given to all patients. Patients in the experiment group (n = 62) orally received 600 mg/d of calcium carbonate, 0.5 μg/d of alfacalcidol, and 70 mg/week of alendronate, while patients in the control group (n = 61) orally received 600 mg/d of calcium carbonate and 0.5 μg/d of alfacalcidol for 18 months. The grip strength, gait speed, bone turnover markers, serum calcium, serum phosphorus, parathyroid hormone (PTH), and bone mineral density were measured, and the Timed Up and Go (TUG) test and the chair rising test (CRT) were performed. Falls, fragility fractures, medication compliance, and side effects of the drugs were recorded. RESULTS:The serum levels of bone turnover markers (type I procollagen amino-terminal peptide [P1NP], type I collagen carboxyl terminal peptide [β-CTx], and osteocalcin [OC]) decreased, while the bone mineral density of the lumbar spine and bilateral femoral neck increased after treatment in the experiment group (P < 0.05, P < 0.01). The rate of change in bone mineral density of the bilateral femoral neck was higher in the experiment group than the control group (3.43% vs 0.03%, P < 0.05; 2.86% vs -0.02%, P < 0.01). After treatment, the proportion of patients with increased hip T scores in the experiment group (66.1%, 41/62) was significantly higher than the proportion (35.0%, 21/60) in the control group (P = 0.001). The incidence of fall decreased in both groups after treatment compared to that before treatment (54.8% vs 33.9% and 54.1% vs 36.7%, respectively; P < 0.05). The incidence of fragility fractures was lower in the experiment group than the control group (8.1% vs 20.0%, P = 0.057). During the intervention period, the incidence of fragility fractures in patients who did not fall (3.8%, 3/79) was significantly lower than that in patients who fell (32.6%, 14/43) (P = 0.000). The risk of fragility fractures was significantly lower in patients who did not fall compared to patients who fell (relative risk: 0.117, 95% confidence interval: 0.035-0.384). CONCLUSION:The combination of alendronate sodium with alfacalcidol and calcium can significantly improve the bone mineral density of the lumbar spine and femoral neck. For older patients with OPA, subjectively paying attention to avoiding falls can significantly reduce the risk of fragility fractures.

背景与目标：

BACKGROUND & AIMS: :Treatment guidelines recommend that curative radiation treatment of prostate cancer be offered only to men whose life expectancy is greater than 10 years. The average life expectancy of North American males is less than 10 years after age 75, yet many men older than 75 years receive curative radiation treatment for prostate cancer. This study used the provincial cancer registry in British Columbia, Canada, to determine median non-prostate cancer survival for men who were aged 75 to 82 years at start of radiation treatment. Median survival was found to be greater than 10 years in men aged up to 80 years at the start of their radiation treatment. This finding suggests that radiation oncologists are able to appropriately select elderly men with greater than average life expectancy to receive curative radiation treatment.

背景与目标： : 治疗指南建议仅对预期寿命超过10年的男性提供前列腺癌的根治性放射治疗。北美男性的平均预期寿命在75岁后不到10岁，但许多75岁以上的男性接受了前列腺癌的根治性放射治疗。这项研究使用了加拿大不列颠哥伦比亚省的省级癌症登记处，以确定放射治疗开始时年龄在75至82岁之间的男性的非前列腺癌中位生存期。在放射治疗开始时，年龄在80岁以下的男性的中位生存期已超过10年。这一发现表明，放射肿瘤学家能够适当选择寿命超过平均预期寿命的老年男性接受治愈性放射治疗。

BACKGROUND & AIMS: :The estrogenic effect of the ethylenebisdithiocarbamate fungicide Novozír MN 80 (Duslo, Sal') was studied by means of the screening method determining the reproductive risk of chemical substances, recommended by the Environmental Protection Agency. Compared to intact controls, a significant increase in relative uterine weight was recorded in the group of animals which received 1/25 of the maximal tolerable concentration of Novozír MN 80. Compared to negative controls (Tween 80), the relative uterine weight was increased significantly after administration of 1/25 and 1/50 of the maximal tolerable concentration of Novozír MN 80. On histologic examination the cuboidal epithelium of the mucous membrane was found to be changed into columnar epithelium, with uneven distribution of enlarged nuclei in the vacuolized cytoplasm. At 1/25 maximal tolerable concentration thickening of the uterine wall was observed.

背景与目标： : 通过环境保护局推荐的确定化学物质生殖风险的筛选方法，研究了亚乙基双硫代氨基甲酸杀菌剂novox í rmn80 (Duslo，Sal') 的雌激素作用。与完整对照组相比，在接受最大耐受浓度novox í rmn80的1/25的动物组中记录到相对子宫重量的显着增加。与阴性对照 (Tween 80) 相比，给予1/25后相对子宫重量显着增加，并1/50了诺维兹mn80的最大耐受浓度。在组织学检查中，发现粘膜的立方上皮变成柱状上皮，在空泡化的细胞质中扩大的核分布不均匀。在1/25最大耐受浓度下观察到子宫壁增厚。

BACKGROUND & AIMS: BACKGROUND:Based on biological and behavioural diversity sex and gender may affect comorbidities associated with prediabetes and diabetes. Besides evaluating the prevalence of prediabetes and diabetes (using fasting plasma glucose and HbA1c levels), the primary aim of the study is to investigate sex and gender differences in the prevalence of comorbidities in subjects with prediabetes and diabetes and to identify possible risk factors associated with prediabetes and diabetes. DESIGN:This observational, population-based cohort study included 11.014 subjects aged 6-80 years. Examinations included blood samples, ankle-brachial index, ECG, dual-energy X-ray absorptiometry scan and an interviewer-administered questionnaire. RESULTS:Across all ages, prevalence of prediabetes was 20.2% (male 23.6%; female 17.1%), and 5.4% for diabetes (male 7.3%; female 3.7%). The prevalence of prediabetes ranged from 4.4% (6-<10 years) up to 40.4% (70+ years) in men and from 4.8% up to 42.3% in women. Comorbidity profile was markedly different between male and female, particularly in those with prediabetes: women more often suffered from arrhythmia, noncoronary artery disease, osteoporosis, increased systemic inflammatory biomarkers and depression, while men with prediabetes more often showed angina pectoris, myocardial infarction and media sclerosis. CONCLUSIONS:The unexpected 4.6% prevalence of prediabetes in children aged 6-10 underscores the need for population-based studies across all ages and the onset of prevention of diabetes at a young age. Marked differences have been found in comorbidities as men with prediabetes and diabetes more often suffer from cardiovascular disease, while women more often show arrhythmia, noncoronary artery disease, increased systemic inflammatory biomarkers and depression.

背景与目标：

BACKGROUND & AIMS: :Mast cells mediate allergies, hypersensitivities, host defense, and venom neutralization. An area of recent interest is the contribution of mast cells to inflammatory pain. Here we found that specific, local activation of mast cells produced plantar hyperalgesia in mice. Basic secretagogue compound 48/80 induced plantar mast cell degranulation accompanied by thermal hyperalgesia, tissue edema, and neutrophil influx in the hindpaws of ND4 Swiss mice. Blocking mast cell degranulation, neutrophil extravasation, and histamine signaling abrogated these responses. Compound 48/80 also produced edema, pain, and neutrophil influx in WT C57BL/6 but not in genetically mast cell-deficient C57BL/6-Kit(W-sh)(/)(W-sh) mice. These responses were restored following plantar reconstitution with bone marrow-derived cultured mast cells.

背景与目标： : 肥大细胞介导过敏，超敏反应，宿主防御和毒液中和。最近引起关注的领域是肥大细胞对炎性疼痛的贡献。在这里，我们发现肥大细胞的特异性局部激活会在小鼠中产生足底痛觉过敏。碱性促分泌剂化合物48/80诱导的足底肥大细胞脱颗粒，伴有热痛觉过敏，组织水肿和中性粒细胞流入ND4瑞士小鼠的后爪。阻断肥大细胞脱颗粒，中性粒细胞外渗和组胺信号消除了这些反应。化合物48/80还在WT C57BL/6中产生水肿、疼痛和中性粒细胞流入，但在遗传肥大细胞缺陷型C57BL/6-Kit (w-sh)(/)(w-sh) 小鼠中不产生。用骨髓来源的培养的肥大细胞重建足底后，这些反应得以恢复。

BACKGROUND & AIMS: :Predictors of survival and length of stay (LOS) in the advanced elderly with burn injuries is not well studied. Because of progress in burn wound and critical care, we hypothesized that a contemporary analysis would show improved outcomes. Clinical data were collected on 45 consecutive patients older than 80 years of age that were treated for burn injury at our institution during the past 10 years. Regression analysis was used to identify predictors of LOS and survival. Overall rate of mortality was 29%, and no patient survived a burn more than 60% TBSA. The strongest predictor of survival was percent TBSA burn. LOS of survivors was dependent on presence of inhalation injury and total number of operations. The survival of patients older than 80 years of age with burn injury is better than reported. Modern burn care allows survival in many patients over 80 with less than 60% TBSA burns without significant other co-morbidities.

背景与目标： : 没有很好地研究患有烧伤的晚期老年人的生存和住院时间 (LOS) 的预测指标。由于烧伤伤口和重症监护方面的进展，我们假设当代分析将显示出改善的结果。收集了过去10年中在我们机构接受烧伤治疗的45例80岁以上连续患者的临床数据。回归分析用于确定LOS和生存的预测因子。总死亡率为29%，没有患者在烧伤后存活超过60% TBSA。生存的最强预测指标是TBSA烧伤百分比。幸存者的LOS取决于吸入性损伤的存在和手术总数。80岁以上烧伤患者的生存率优于报道。现代烧伤护理允许许多80岁以上的患者存活，烧伤少于60% TBSA，而没有其他重大合并症。

BACKGROUND & AIMS: :Polysorbate 80 (Tween 80) has been widely used as an emulsifier with excellent effects in nanoparticles technology for biomedical applications. This work was thus triggered to synthesize poly(lactide)/Tween 80 copolymers with various copolymer blend ratio, which were synthesized by ring-opening polymerization and characterized by 1H NMR and TGA. Nanoparticles of poly(lactide)/Tween 80 copolymers were prepared by the dialysis method without surfactants/emulsifiers involved. Paclitaxel was chosen as a prototype anticancer drug due to its excellent therapeutic effects against a wide spectrum of cancers. The drug-loaded nanoparticles of poly(lactide)/Tween 80 copolymers were then characterized by various state-of-the-art techniques, including laser light scattering for particles size and size distribution, field emission scanning electron microscopy (FESEM) and atomic force microscopy (AFM) for surface morphology; laser Doppler anemometry for zeta potential; differential scanning calorimetry (DSC) for the physical status of the drug encapsulated in the polymeric matrix; X-ray photoelectron spectrometer (XPS) for surface chemistry; high performance liquid chromatography (HPLC) for drug encapsulation efficiency; and in vitro drug release kinetics. HT-29 cells and Glioma C6 cells were used as an in vitro model of the GI barrier for oral chemotherapy and a brain cancer model to evaluate in vitro cytotoxicity of the paclitaxel-loaded nanoparticles. The viability of C6 cells was decreased from 37.4 +/- 4.0% for poly(D,L-lactide-co-glycolic acid) (PLGA) nanoparticles to 17.8 +/- 4.2% for PLA-Tween 80-10 and 12.0 +/- 5.4% for PLA-Tween 80-20 copolymer nanoparticles, which was comparable with that for Taxol at the same 50 microg/mL drug concentration.

背景与目标： 聚山梨醇酯80 (吐温80) 作为一种乳化剂已被广泛应用于生物医学应用的纳米颗粒技术中。因此，这项工作被触发合成了具有各种共聚物共混比的聚 (丙交酯)/吐温80共聚物，这些共聚物是通过开环聚合合成的，并通过1H NMR和TGA进行了表征。通过透析方法制备了聚 (丙交酯)/吐温80共聚物的纳米颗粒，而不涉及表面活性剂/乳化剂。紫杉醇因其对多种癌症的出色治疗作用而被选为原型抗癌药物。然后通过各种最新技术对聚丙交酯/吐温80共聚物的载药纳米颗粒进行表征，包括激光散射颗粒尺寸和尺寸分布，场发射扫描电子显微镜 (FESEM) 和原子力显微镜 (AFM) 表面形貌; zeta电位的激光多普勒风速仪; 聚合物基质中封装的药物的物理状态的差示扫描量热法 (DSC); 表面化学的x射线光电子能谱仪 (XPS); 药物封装效率的高效液相色谱 (HPLC); 和体外药物释放动力学。将HT-29细胞和神经胶质瘤C6细胞用作口服化疗的GI屏障的体外模型和脑癌模型，以评估负载紫杉醇的纳米颗粒的体外细胞毒性。C6细胞的活力从聚 (D，L-丙交酯-共-乙醇酸) (PLGA) 纳米粒子的37.4 +/- 4.0% 降低到PLA-Tween 80-10的17.8 +/- 4.2% 和PLA-Tween 80-20共聚物纳米粒子的12.0 +/- 5.4%，在相同的50微克/毫升药物浓度下，这与紫杉醇相当。

BACKGROUND & AIMS: :Absorbed dose rate measurements of a 50 kV(p) handheld X-ray probe source in a water phantom are described. The X-ray generator is capable of currents of up to 40 microA, and is designed for cranial brachytherapy and intraoperative applications with applicators. The measurements were performed in a computer-controlled water phantom in which both the source and the detectors are mounted. Two different LiF thermoluminescence dosemeter (TLD) phosphors were employed for the measurements, MTS-N (LiF:Mg,Ti) and MCP-N (LiF:Mg,Cu,P). Two small ionisation chambers (0.02 and 0.0053 cm(3)) were also employed. The TLDs and chambers were positioned in watertight mounts made of water-equivalent plastic. The chambers were calibrated in terms of air-kerma rate, and conventional protocols were used to convert the measurements to absorbed dose rate. The TLDs were calibrated at National Institute of Standards and Technology (NIST) in terms of absorbed dose rate using a (60)Co teletherapy beam and narrow-spectrum X-ray beams. For the latter, absorbed dose was inferred from air-kerma rate using calculated air-kerma-to-dose conversion factors. The reference points of the various detectors were taken as the center of the TLD volumes and the entrance windows of the ionisation chambers. Measurements were made at distances of 3-45 mm from the detector reference point to the source center. In addition, energy dependence of response measurements of the TLDs used was made using NIST reference narrow spectrum X-ray beams. Measurement results showed reasonable agreement in absorbed dose rate determined from the energy dependence corrected TLD readings and from the ionisation chambers. Volume averaging effects of the TLDs at very close distances to the source were also evident.

背景与目标： : 描述了水模中50 kV(p) 手持式x射线探针源的吸收剂量率测量。X射线发生器能够高达40 microA的电流，并设计用于颅骨近距离放射治疗和术中应用与应用程序。测量是在计算机控制的水模中进行的，其中安装了源和检测器。使用两种不同的LiF热发光剂量计 (TLD) 荧光粉进行测量，mts-n (LiF:Mg，Ti) 和mcp-n (LiF:Mg，Cu，P)。还使用了两个小的电离室 (0.02和0.0053厘米 (3))。Tld和腔室放置在由水当量塑料制成的水密支架中。根据空气-比速率对腔室进行了校准，并使用常规协议将测量值转换为吸收剂量率。使用 (60)Co远程治疗束和窄光谱x射线束，根据吸收剂量率在美国国家标准技术研究院 (NIST) 对tld进行了校准。对于后者，使用计算出的空气-比剂量转换因子从空气-比速率推断吸收剂量。各种检测器的参考点被视为TLD体积的中心和电离室的入口窗口。在从检测器参考点到源中心的3-45毫米的距离处进行测量。此外，使用NIST参考窄光谱x射线束对所使用的tld响应测量的能量依赖性进行了测量。测量结果显示，根据能量依赖性校正的TLD读数和电离室确定的吸收剂量率合理一致。距源非常近的tld的体积平均效果也很明显。

BACKGROUND & AIMS: :Although many investigations examined the relationship between body mass index (BMI) and mortality, little is known about the possible associations between BMI and disease-specific mortality in very elderly people. Here we evaluated this association in an 80-year-old population. In 1998, 675 residents in Japan's Fukuoka Prefecture participated. They were followed up for 12 years after the baseline examination; 37 subjects (5.5%) were lost to follow-up. The subjects were divided into six groups by their BMI values: <19.5 (most-thin), 19.5 to <21.1 (relatively thin), 21.1 to <22.5 (thin/normal), 22.5 to <23.8 (normal/overweight), 23.8 to <26.0 (relatively obese), ≥26.0 (most-obese). The most-thin group had the highest mortality from all-causes, and from respiratory disease. The normal/overweight group had the lowest overall mortality among the six BMI groups. These associations were found in the men, but not in the women. The most-obese group did not have higher mortality from all-causes or cardiovascular disease compared to the normal/overweight group. Respiratory disease-related mortality was lowest in the most-obese group. No association was found between BMI group and mortality from cancer. In conclusion, in an 80-year-old Japanese population, mortality from all-causes or respiratory disease was highest in the most-lean group (BMI <19.5), and mortality from all-causes or cardiovascular disease was lowest in the group with BMI 22.5 to <23.8.

背景与目标： : 尽管许多调查研究了体重指数 (BMI) 与死亡率之间的关系，但对于非常老年人的BMI与疾病特异性死亡率之间的可能关联知之甚少。在这里，我们在80岁的人群中评估了这种关联。1998年，日本福冈县有675名居民参加。基线检查后随访12年; 37名受试者 (5.5% 名) 失访。根据BMI值将受试者分为六组: <19.5 (最瘦)，19.5 <21.1 (相对瘦)，21.1 <22.5 (瘦/正常)，22.5 <23.8 (正常/超重)，23.8 <26.0 (相对肥胖)，≥ 26.0 (最肥胖)。最瘦的组的所有原因和呼吸系统疾病的死亡率最高。在六个BMI组中，正常/超重组的总死亡率最低。这些关联在男性中发现，但在女性中没有。与正常/超重组相比，最肥胖组的全因或心血管疾病死亡率不高。在最肥胖的人群中，与呼吸系统疾病相关的死亡率最低。BMI组与癌症死亡率之间没有关联。总之，在80岁的日本人群中，最瘦组 (BMI <19.5) 的全因或呼吸系统疾病死亡率最高，而BMI 22.5 <23.8的全因或心血管疾病死亡率最低。