Correlation between CAT polymorphism and susceptibility to DMAc-induced abnormal liver function: a case-control study of Chinese population

Context: Acute or chronic exposure of N,N-dimethylacetamide (DMAc) is responsible for abnormal liver function. It appears that DMAc is mainly metabolized by cytochrome P450 in the liver and thereby produces reactive oxygen species (ROS). The elimination of ROS and the repairing of ROS-induced DNA damage are relevant to the ultimate toxicity of DMAc.

Objective: To investigate whether the polymorphisms in the CAT (rs564250, rs769214 and rs7943316), hOGG1 (rs2072668 and rs159153) and XRCC1 (rs25487 and rs1799782) genes are associated with susceptibility to DMAc-induced abnormal liver function in Chinese population.

Methods: Samples were obtained from 108 workers with DMAc-induced abnormal liver function and 108 workers with normal liver function.

Results: Subjects with the CAT rs769214 GA/GG genotypes had a reducing risk of abnormal liver function, which was more evident in the subgroups exposed to DMAc?<10?years, exposed to DMAc?<5?mg/m³, never smoked and never drank.

Conclusions: CAT rs769214 (-844?G?>?A) polymorphism may be associated with DMAc-induced abnormal liver function in Chinese population.     

A pharmacodynamic comparison of 5 anti-platelet protocols in patients with ST-elevation myocardial infarction undergoing primary PCI

Background

Ivabradine (IVBD), a novel I(f)-channel inhibitor and specific heart rate-lowering agent, is known to have anti-oxidative activity that promotes endothelial function. However, the molecular mechanism through which IVBD acts on cardiac function has yet to be elucidated, especially in experimental diabetic animals.

Methods

For this reason, twenty diabetic mice were randomly assigned to IVBD-treated (10 mg/kg/day) and control (saline) groups. After a 3-month treatment, microarray assay was performed to identify differentia expressed genes, and cardiac function was measured by echocardiography, with subsequent immunohistochemistry analysis and western blotting.

Results

Our results showed that ivabradine treatment attenuated the expression and staining score of matrix metalloproteinase (MMP)-2, induced the dephosphorylation of caspase 3, BAX and MMP-2, and enhanced the phosphorylation of NF-κB. Ivabradine treatment led to a significant improvement in cardiac function.

Conclusion

Ivabradine significantly improved cardiac function by attenuating apoptosis and inhibiting the expression and activity of MMP-2 in diabetic mice, which underscored the novel clinical implications of ivabradine for diabetic patients.

     

Changes in the Pulmonary Function Test after Radioactive Iodine Treatment in Patients with Pulmonary Metastases of Differentiated Thyroid Cancer

ObjectivePulmonary function test (PFT) is a useful tool for an objective assessment of respiratory function. Impaired pulmonary function is critical for the survival and quality of life in patients with pulmonary metastases of solid cancers including thyroid cancer. This study aimed to evaluate clinical factors associated with severely impaired pulmonary function by serial assessment with PFT in patients with pulmonary metastasis of differentiated thyroid cancer (DTC) who received radioactive iodine treatment (RAIT).PatientsThis retrospective study enrolled 31 patients who underwent serial PFTs before and after RAIT for pulmonary metastasis of DTC. We evaluated the risk factors for severe impairment of pulmonary function.ResultsThe median age of the patients was 44.1 years and 18 of them were female patients. Severe impairment of pulmonary function was observed in five patients (16%) after a median of three RAITs (cumulative I-131 activity = 20.4 GBq). These patients were older and more frequently had mild impairment of baseline pulmonary function, respiratory symptoms, or progressive disease compared with patients with stable pulmonary function. Neither cumulative dose nor number of RAIT was associated with decreased pulmonary function. Coexisting pulmonary diseases, presence of respiratory symptoms, and metastatic disease progression were significantly associated with severe decrease in forced vital capacity during follow-up (p =.047, p =.011, and p =.021, respectively).ConclusionsPulmonary function was severely impaired during follow-up in some patients with pulmonary metastasis of DTC after a high-dose RAITs. Neither the number of RAIT nor the cumulative I-131 activity was associated with decreased pulmonary function. Serial PFT might be considered for some high-risk patients during follow-up.     

L1.LtrB内含子编码蛋白反转录结构域关键催化位点分析及功能验证

【目的】筛选影响Ll.LtrB内含子编码蛋白(Intron encoded protein,IEP)反转录功能的关键催化位点,并获得无反转录活性的IEP突变体。【方法】首先,利用NCBI数据库,通过序列比对及同源建模方法筛选影响IEP反转录功能的关键氨基酸催化位点;然后,对筛选获得的关键催化位点进行定点突变,同时以Targetron载体为模板,构建无反转录功能的突变型Targetron打靶系统;最后,以大肠杆菌lacZ基因为例,体内验证IEP突变体的功能及其对Ⅱ型内含子"归巢"效率的影响。【结果】筛选到C164和G214两个位点是影响内含子编码蛋白反转录功能的关键氨基酸残基,并获得C164K和G214W两个突变体。体内功能分析表明,此两个位点突变完全失活了Ⅱ型内含子的"归巢"功能。【结论】筛选并获得了失活反转录功能的Ll.LtrB内含子编码蛋白突变体,为深入研究Ⅱ型内含子的结构和"归巢"机理奠定了基础。     

Nonlocal nature of the electron energy spectrum in a glow discharge in pure O2: I. Nonlocal character of the electron distribution function

Abstrac A study is made of the nonlocal nature of the electron energy distribution function in the positive column of a glow discharge in a tube filled with pure oxygen. The distribution function and the axial (E _z) and radial (E _r) electric fields as functions of radius are measured using an array of mobile probes. The experimentally obtained spatial profiles of the distribution function are used to test the applicability of the two-term approximation to the distribution function of the electrons with a nonlocal energy spectrum. The distribution function in a specified electric field E=E _z +E _r (where E _z ⊥ E _r) is calculated by solving the coordinate-dependent Boltzmann equation in the two-term approximation and by directly integrating the equations of electron motion using the Monte Carlo method. A comparison between the experimental data and the results of simulations carried out for a broad parameter range shows that, in the case of a highly nonlocal electron energy spectrum, the two-term approximation makes it possible to calculate the electron distribution function with a fairly good accuracy, in which case, however, in imposing the boundary conditions, the electron losses at the plasma surface should be treated in the kinetic approximation. It is shown that using the reflection coefficient of the plasma surface for electrons instead of the loss cone in space makes it possible to accurately calculate the electron energy distribution function over the entire parameter range under consideration, including the transient region in which the electron-energy relaxation length is comparable to the characteristic plasma dimension. __________ Translated from Fizika Plazmy, Vol. 26, No. 11, 2000, pp. 1038–1045. Original Russian Text Copyright ? 2000 by Ivanov, Klopovskii, Lopaev, Rakhimov, Rakhimova.     

物流云平台在大型综合性医院耗材管理中的应用研究

?????? 目的 确定大型综合性医院消耗品物流云平台的建设方案,提升医院耗材管理的质量和效率,降低医院管理成本。方法 采用定性研究中的深度个案访谈与小组焦点访谈相结合的研究方法。结果 明确物流云平台的定义,确定建设的必要性、功能定位和应用范围。结论 物流云平台的建设在大型综合性医院耗材管理中具有创新意义,根据功能定位的开发具有一定的复杂性,需进行4阶段15期的分期建设,同时需注重系统安全、数据同步联动以及培训推广等开发难点。     

Glycerol-Furcated Oligonucleotides: Synthesis and Aggregation

Abstract

The synthesis of the bi-furcated complementary oligonucleotides 2 and 3 is described and their complex formation is studied as a function of their molar ratio and ionic strength by means of temperature-dependent UV- and CD spectroscopy as well as by dynamic light scattering. Structural proposals for the different aggregates are given.     

Pre-culturing islets with mesenchymal stromal cells using a direct contact configuration is beneficial for transplantation outcome in diabetic mice

Background aimsWe recently showed that co-transplantation of mesenchymal stromal cells (MSCs) improves islet function and revascularization in vivo. Pre-transplant islet culture is associated with the loss of islet cells. MSCs may enhance islet cell survival or function by direct cell contact mechanisms and soluble mediators. We investigated the capacity of MSCs to improve islet cell survival or β-cell function in vitro using direct and indirect contact islet-MSC configurations. We also investigated whether pre-culturing islets with MSCs improves islet transplantation outcome.MethodsThe effect of pre-culturing islets with MSCs on islet function in vitro was investigated by measuring glucose-stimulated insulin secretion. The endothelial cell density of fresh islets and islets cultured with or without MSCs was determined by immunohistochemistry. The efficacy of transplanted islets was tested in vivo using a syngeneic streptozotocin-diabetic minimal islet mass model. Graft function was investigated by monitoring blood glucose concentrations.ResultsIndirect islet-MSC co-culture configurations did not improve islet function in vitro. Pre-culturing islets using a direct contact MSC monolayer configuration improved glucose-stimulated insulin secretion in vitro, which correlated with superior islet graft function in vivo. MSC pre-culture had no effect on islet endothelial cell number in vitro or in vivo.ConclusionsPre-culturing islets with MSCs using a direct contact configuration maintains functional β-cell mass in vitro and the capacity of cultured islets to reverse hyperglycemia in diabetic mice.     

Preservation of Beta-Cell Function in Type 2 Diabetes

ObjectiveTo review available data on preservation and potential improvement of beta-cell function in patients with type 2 diabetes mellitus (T2DM) with use of currently available strategies and agents.MethodsUsing key words, we performed a MEDLINE search of the relevant literature published through 2009 regarding the effects of available agents on beta-cell function in humans with T2DM.ResultsOn the basis of current clinical data, no uniformly effective treatment for beta-cell preservation has been found. Lifestyle intervention and early intensive insulin therapy appear to have some preservative properties on beta-cell function. Glucagonlike peptide-1 agonists, dipeptidyl-peptidase-4 inhibitors, and thiazolidinediones result in maintenance and often improvement of beta-cell function during their active use; however, data on their ability to preserve beta-cell function when patients are not receiving active treatment are limited.ConclusionThe continuous loss of beta-cell mass and beta-cell function is a critical mechanism underlying the progressive deterioration of glycemic control in T2DM. In light of the projected increase in individuals at risk for developing T2DM, strategies and agents aimed at delaying or preventing the progression and inducing a remission of the disease are needed. Future research on this topic should include comparative efficacy trials with washout periods incorporating currently available and novel medications and strategies for preservation of beta cells. (Endocr Pract. 2010;16:1038-1055)     

炭团木霉中非核糖体多肽基因NRPS1的功能研究

[目的] 木霉属真菌是应用最为广泛和潜力最大的生防真菌,其产生的典型化合物哌珀霉素（peptaibols）类抗生素在生物防治中发挥重要作用。本研究采用基因组挖掘技术（genome mining）发现炭团木霉（Trichoderma hypoxylon）的潜在哌珀霉素生物合成基因簇及对病原菌的防治作用。[方法] 生物信息学分析预测合成哌珀霉素的基因簇,利用Quick-change技术构建基因骨架敲除盒,通过PEG介导的原生质体转化方法获得敲除突变株,通过平板对峙法和菌丝生长毒力实验验证该基因簇对炭团木霉生物活性的影响。[结果] 基因挖掘鉴定一个非核糖体多肽合成酶（nonribosomal peptide synthetases,NRPS）可能合成哌珀霉素类抗生素,命名为NRPS1,对该基因进行部分敲除,成功获得3株NRPS1缺失突变株。对峙实验表明,突变株对寄生曲霉（Aspergillus parasiticus）、尖孢镰刀菌（Fusarium oxysporum）、黑白轮枝菌（Verticillium alboatrum）等9株植物病原真菌的抑制作用与野生株相比显著下降,且突变株的粗提物的抑菌活性明显弱于野生型。[结论] NRPS1是一个潜在的哌珀霉素合成基因,该基因在宿主与病原真菌对抗过程中起关键作用,该研究为炭团木霉哌珀霉素结构解析及生物防治机理研究奠定了基础。     

Sensory retraining improves light touch threshold of the paretic hand in chronic stroke survivors: a single-subject A-B design

Abstract

Background: Light touch, one of the primary and basic sensations, is often neglected in sensory retraining programmes for stroke survivors.

Objective: This study aimed to investigate the effects of sensory retraining on the light touch threshold of the hand, dexterity and upper limb motor function of chronic stroke survivors.

Methods: Five chronic stroke survivors with sensory impairment participated in this single-subject A-B design study. In baseline (A) phase, they only received standard rehabilitation. In the treatment (B) phase, they received a 6-week sensory retraining intervention in addition to standard rehabilitation. In both phases, they were evaluated every 3 days. Light touch threshold, manual dexterity and upper limb motor function were assessed using Semmes-Weinstein Monofilaments, Box-Block Test and Fugl-Meyer Assessment, respectively. Visual analysis, nonparametric Mann-Whitney U test and, c-statistic were used for assessing the changes between phases.

Results: All participants indicated changes in trend or slope of the total score of light touch or both between the two phases. The results of the c-statistic also showed the statistical difference in the total score of light touch between baseline and treatment in all participants (p?<?0.001). Also, the results of the c-statistic and Mann-Whitney U test supported the difference of manual dexterity and motor function of the upper limb between baseline and treatment in all participants (p?<?0.001).

Conclusion: Current findings showed that sensory retraining may be an effective adjunctive intervention for improving the light touch threshold of the hand, dexterity and upper limb motor function in chronic stroke survivors.     

等速肌力康复训练对阿尔茨海默病患者认知功能及运动功能的影响

目的:探讨等速肌力康复训练对阿尔茨海默病患者认知功能及运动功能的影响。方法:符合入组条件的40例阿尔茨海默病患者随机分为试验组和对照组,两组常规治疗相同,试验组在常规治疗的同时予等速肌力康复训练,两组治疗时间均为2个月。在纳入研究1周内和研究结束1周内进行认知功能和运动功能评价,对前后两次评分进行对比分析。结果:试验组患者与对照组比较,剑桥老年认知量表、Berg平衡、功能伸展测试、起立-行走计时测试改善差异有统计学意义,试验组明显优于对照组(P0.05)。结论:等速肌力康复训练能明显促进阿尔茨海默病患者的认知功能和运动功能的改善。     

Hypothermic reconditioning by gaseous oxygen persufflation after cold storage of porcine kidneys

BackgroundDelayed graft function still represents a major complication in clinical kidney transplantation. Here we tested the possibility to improve functional outcome of cold stored kidneys a posteriori by hypothermic reconditioning using retrograde oxygen persufflation (ROP) immediately prior to reperfusion.MethodsKidneys from female German Landrace pigs were flushed with Histidine–Tryptophan–Ketoglutarate (HTK) solution and cold-stored for 18 h (control).Some grafts were subsequently subjected to 90 min of retrograde oxygen persufflation (ROP) via the renal vein during cold preservation. Early graft function of all kidneys was assessed thereafter by warm reperfusion in vitro (n = 6, resp.).ResultsRenal function upon reperfusion was significantly enhanced by ROP with an approximately twofold increase in renal clearances of creatinine and urea. ROP also led to higher renal vascular flow rates, enhanced urine output and mitigated histological alterations.ConclusionIt is concluded that initial graft function can be improved by 90 min of hypothermic gaseous oxygenation after arrival of the preserved organ in the transplantation clinic.     

Morphometric sex determination of young Ospreys Pandion haliaetus using discriminant analysis

Capsule Discriminant functions based on morphometric variables provide a reliable method for sex identification of free‐living and hacked young Ospreys.

Aims To describe an easy, accurate and low‐cost method for sex determination of fully grown nestling and fledgling Ospreys Pandion haliaetus based on morphometric measurements.

Methods Four different measurements were taken in 114 birds (40–73 days old) and a DNA analysis, using PCR amplification, was carried out for sex identification. A forward stepwise discriminant analysis was performed to build the best explanatory discriminant models, which were subsequently validated using statistics and external samples.

Results Our best discriminant function retained forearm and tarsus as the best predictor variables and classified 95.1% of the sample correctly, supported also by external cross‐validations with both hacked and free‐living birds. Moreover, a discriminant function with only forearm as predictor showed a similar high correct classification power (93.4%).

Conclusions These discriminant functions can be used as a reliable and immediate method for sex determination of young Ospreys since they showed high discriminant accuracy, close to that of molecular procedures, and were supported by external cross‐validations, both for free‐living and hacked birds. Thus, these morphometric measurements should be considered as standard tools for future scientific studies and management of Osprey populations     

On the Green’s function for a one-dimensional random walk

The Green’s function of a random walk on a lattice is defined as the inverse of the operatorK-z1, whereK is the matrix of transition rates and z is an arbitrary complex parameter. The Green’s function for a symmetrical random walk in one dimension is here explicitly given in closed form for reflecting, periodic, and absorbing boundaries, and also for an infinite lattice.     

N-acetylcysteine decreases urinary level of neutrophil gelatinase-associated lipocalin in deceased-donor renal transplant recipients: a randomized clinical trial

Context: Acute kidney injury (AKI) is a common complication after kidney transplantation (KT), especially in recipients from deceased donors. Urinary neutrophil gelatinase-associated lipocalin (u-NGAL) is an early and sensitive marker of AKI after transplantation.

Objectives: We assessed the renoprotective effect of N-acetylcysteine (NAC) on u-NGAL levels as an early prognostic marker of graft function immediately after transplantation.

Materials and methods: A double-blind, randomized, placebo-controlled trial was conducted on 70 deceased-donor KT recipients (www.irct.ir, trial registration number: IRCT2014090214693N4). Patients received 600?mg oral NAC or placebo twice daily from day 0 to 5 and urine samples were taken before, and on the first and fifth days after transplantation. U-NGAL and early graft function were compared between the two groups.

Results: NAC significantly reduced u-NGAL levels compared to placebo (p value?=?0.02), while improvement in early graft function with NAC did not reach statistical significance.

Conclusions: This study showed that NAC administration in deceased-donor KT recipients can reduce tubular kidney injury, evidenced by u-NGAL measurements. Improvement in early graft function needs a larger sample size to reach a statistical conclusion.     

The genotype x environment-to-phenotype relationship

Summary Proceeding from the formal genotype x environment-to-phenotype functional relationship, a few common concepts essentially based upon this relationship have been reviewed and redefined. Particular attention was given to forming unambiguous representations. In summary, these concepts were: the reaction norm and phenotypic range of a genotype, the genetic control of traits, the general representation of genotypic and environmental contributions to a phenotype and the related problem of genotype x environment interaction, the fitness function, selective neutrality and superiority. The role of joint frequency distributions of genotypes and environmental situations for detecting and describing certain properties of the underlying genotype x environment-to-phenotype functional relationship has been demonstrated by means of models for genotype x environment interaction and the fitness function.     

Recovery function of somatosensory evoked potentials in juvenile myoclonic epilepsy*

Abstract

Objective: We analysed the recovery function of somatosensory evoked potentials (SEPs) in juvenile myoclonic epilepsy (JME) patients. We hypothesized that there may be disinhibition in the recovery of SEPs at 20–100?ms intervals in JME patients.

Methods: We recorded SEPs and SEP recovery in 19 consecutive patients with JME admitted for a routine follow-up examination, and in a control group composed of 13 healthy subjects who were similar to the patient group regarding age and sex. The recovery function of SEPs was examined using paired stimuli at 30, 40, 60, and 100?ms intervals.

Results: The amplitudes of N20-P25 and P25-N33 components were higher in patients with JME. Ten patients had high-amplitude SEPs. By paired stimulation, there was inhibition of SEPs in both groups. The mean recovery percentages of N20-P25 and P25-N33 components at 30, 40, 60, and 100?ms were not different between healthy subjects and patients with JME.

Conclusions: The recovery function of SEP is normal in JME even in the presence of high-amplitude SEPs.     

A Lichenological Excursion to the West of Scotland

ABSTRACT

Background: Hybridisation can be a threat for the survival of a rare species because, in the case of insufficient numbers of appropriate mates, a rare form is much more likely to cross with a widespread taxon.

Aims: In the present study, we tested hypotheses concerning the level of hybridisation between endangered Betula humilis and its widespread congeners: B. pendula and B. pubescens as a function of habitat conditions.

Methods: We genotyped 312 individuals of three species using AFLP markers. B. humilis specimens were sampled in populations with low and high groundwater levels. Morphological identification of B. pubescens and B. pendula was verified using the Atkinson discriminant function.

Results: Altogether, 15 individuals (4.8%) were indicated as putative hybrids. The B. humilis hybrids were found in dry habitats and they could be classified as F1 or F2 generation. Tree hybrids could represent backcrosses to either B. pendula or B. pubescens.

Conclusions: Genetic analyses contradicted the idea that hybridisation between B. humilis and its close relatives was extensive. On the other hand, the presence of introgressed individuals in the populations in areas with low groundwater levels implied that pollen swamping might be a threat for declining B. humilis stands.