BACKGROUND & AIMS: The health care industry is in the throes of remarkably penetrating and destabilizing change, the effects of which have been felt earliest by perinatal service directors. In anticipation of future trends marked by rampant change, a survey of perinatal service directors and vice presidents was conducted to elicit their opinions about the current and future states of perinatal health care. Findings supported the notions that change is a constant, that clinical and service excellence is a mandate, and that collaboration is key. Future success will require many old behaviors and systems to be replaced. Leadership to guide us to the future has never been more important.

背景与目标： 卫生保健行业正处在深刻渗透和破坏稳定的变革的阵痛之中，围产期服务主管最早感受到了这种变革的影响。为了预见未来变化趋势明显的趋势，对围产期服务主管和副总裁进行了一项调查，以征询他们对围产期保健的当前和未来状态的意见。研究结果支持以下观念：变革是永恒的，临床和服务卓越是使命，协作是关键。未来的成功将需要替换许多旧的行为和系统。引领我们走向未来的领导力从未如此重要。

BACKGROUND & AIMS: :Biopsies of human subcutaneous adipose tissue were taken from healthy donors. Samples were high-pressure frozen, freeze-fractured, and freeze dried. Imaging mass spectrometry of samples was performed in a TOF-SIMS mass spectrometer equipped with a bismuth cluster ion source. Blood vessels, the connective tissue, and adipocytes can be seen in TOF-SIMS images. Blood vessels were found labeled by a high content of sodium ions and potassium ions in their lumen and phosphocholine signal in smooth muscle cells of the vessel wall. The connective tissue showed high signal levels of CN(-) fragments, derived from proteins and nucleic acids. Adipocytes showed high signal levels of phosphocholine and cholesterol ubiquitously in their membranes and diacylglycerols in some membrane sites. The central part of adipocytes showed high levels of triacylglycerols and fatty acids. These results are in accordance to those of biochemical studies; however, a precise spatial localization of lipids in adipocytes is demonstrated with MS imaging.

背景与目标： ：人皮下脂肪组织的活检取自健康供体。将样品高压冷冻，冷冻断裂并冷冻干燥。在配备有铋簇离子源的TOF-SIMS质谱仪中进行样品的成像质谱。在TOF-SIMS图像中可以看到血管，结缔组织和脂肪细胞。发现在血管壁的平滑肌细胞中，内腔中的钠离子和钾离子含量较高，并且磷酸胆碱信号标记了高含量的血管。结缔组织显示高信号水平的CN（-）片段，来源于蛋白质和核酸。脂肪细胞的膜中普遍存在高水平的磷酸胆碱和胆固醇信号，某些膜部位普遍存在二酰基甘油。脂肪细胞的中央部分显示出高水平的三酰基甘油和脂肪酸。这些结果与生化研究结果一致；然而，通过MS成像证实了脂肪细胞中脂质的精确空间定位。

BACKGROUND & AIMS: In cultured rat pituitary gonadotrophs, GnRH-induced oscillations in cytosolic calcium concentration ([Ca2+]i) are associated with periodic membrane hyperpolarization. The hyperpolarizing waves are secondary to the activation of apamin-sensitive Ca2+-activated K+ channels that account for a single class of 125I-apamin binding sites present in these cells. In a substantial fraction of gonadotrophs, however, we observed a Ca2+-controlled oscillatory current that was resistant to apamin, even at concentrations five orders of magnitude higher than the dissociation constant (Kd) observed in the binding experiments. With the K+ in the pipette, the apamin-resistant current showed a reversal potential of -42 mV, nearly 40 mV more positive than that of the apamin-sensitive current. With Cs+ in place of K+ in the pipette solution, both the size of the apamin-insensitive current and its reversal potential remained unchanged. Ion substitution studies further revealed that the reversal potential was independent of Cl-. In contrast, an 11 mV hyperpolarizing shift in the reversal potential occurred when extracellular Na+ was reduced to 80 mM. In cells expressing apamin-resistant conductances, addition of apamin evoked a marked increase in the duration of the action potentials and reduction in the frequency of spontaneous spiking. In the presence of GnRH, gonadotrophs exhibit the typical burst pattern of electrical activity. Further exposure of the cells to apamin depolarized the membrane from a silent phase bursting level of about -80 mV to a new level of about -40 mV. These observations indicate that, in addition to apamin-sensitive current, a subpopulation of pituitary gonadotrophs also expresses a cationic component of the Ca2+-activated membrane conductance that has the potential to remodulate spontaneous and agonist-induced electrical activity.

背景与目标： 在培养的大鼠垂体促性腺激素中，GnRH诱导的胞浆钙浓度（[Ca2] i）振荡与周期性膜超极化有关。超极化波是对罂粟碱敏感的Ca2激活的K通道的激活的继发子，这些通道解释了这些细胞中存在的一类125I-apapamin结合位点。然而，在相当一部分的促性腺激素中，即使在比结合实验中观察到的解离常数（Kd）高5个数量级的浓度下，我们也观察到了对apamin有抗性的Ca2控制的振荡电流。当移液器中的K值时，抗木瓜蛋白酶的电流显示出-42 mV的反向电势，比对木瓜蛋白酶敏感的电流的正电势高近40 mV。在移液器中用Cs代替K时，对罂粟碱不敏感电流的大小及其逆转电位均保持不变。离子取代研究进一步表明，逆转电位独立于Cl-。相反，当细胞外Na降至80 mM时，逆转电位发生11 mV超极化变化。在表达抗谷氨酰胺的电导的细胞中，添加谷氨酰胺可引起动作电位持续时间的显着增加和自发加标频率的降低。在存在GnRH的情况下，促性腺激素表现出典型的电活动猝发模式。将细胞进一步暴露于罂粟碱可使膜从约-80 mV的无声相爆发水平去极化至约-40 mV的新水平。这些观察结果表明，除了对罂粟碱敏感的电流外，垂体促性腺激素亚群还表达了Ca2激活的膜电导的阳离子成分，该成分可能会重新调节自发和激动剂诱导的电活动。

BACKGROUND & AIMS: The kinetics of flash-induced H+ ion binding by isolated reaction centers (RCs) of Rhodobacter sphaeroides, strain R-26, were measured, using pH indicators and conductimetry, in the presence of terbutryn to block electron transfer between the primary and secondary quinones (QA and QB), and in the absence of exogenous electron donors to the oxidized primary donor, P+, i.e., the P+QA-state. Under these conditions, proton binding by RCs is to the protein rather than to any of the cofactors. After light activation to form P+QA-, the kinetics of proton binding were monoexponential at all pH values studied. At neutral pH, the apparent bimolecular rate constant was close to the diffusional limit for proton transfer in aqueous solution (approximately 10(11) M-1 s-1), but increased significantly in the alkaline pH range (e.g., 2 x 10(13) M-1 s-1 at pH 10). The average slope of the pH dependence was -0.4 instead of -1.0, as might be expected for a H+ diffusion-controlled process. High activation energy (0.54 eV at pH 8.0) and weak viscosity dependence showed that H+ ion uptake by RCs is not limited by diffusion. The salt dependence of the H+ ion binding rate and the pK values of the protonatable amino acid residues of the reaction center implicated surface charge influences, and Gouy-Chapman theory provided a workable description of the ionic effects as arising from modulation of the pH at the surface of the RC. Incubation in D2O caused small increases in the pKs of the protonatable groups and a small, pH (pD)-dependent slowing of the binding rate. The salt, pH, temperature, viscosity, and D2O dependences of the proton uptake by RCs in the P+QA- state were accounted for by three considerations1) parallel pathways of H+ delivery to the RC, contributing to the observed (net) H+ disappearance; 2) rate limitation of the protonation of target groups within the protein by conformational dynamics; and 3) electrostatic influences of charged groups in the protein, via the surface pH.

背景与目标： 在特布瑞林存在下，通过阻断pH值和电导测定了球形球形红球菌R-26的分离反应中心（RC）的闪光诱导的H离子结合的动力学，并测定了叔丁烯的存在以阻止电子在伯醌和仲醌之间的转移（ QA和QB），并且在没有外源电子给体到氧化的初级给体P的情况下，即P QA状态。在这些条件下，RC的质子结合是蛋白质而不是任何辅因子。光活化形成P QA-后，质子结合的动力学在所有研究的pH值下都是单指数的。在中性pH下，表观双分子速率常数接近质子在水溶液中的扩散极限（约10（11）M-1 s-1），但在碱性pH范围内显着增加（例如2 x 10（ 13）pH值为10的M-1 s-1。 pH依赖性的平均斜率是-0.4而不是-1.0，这可能是H扩散控制过程所期望的。高活化能（pH 8.0时为0.54 eV）和较弱的粘度依赖性表明RC吸收H离子不受扩散的限制。 H离子结合率与盐的依赖性以及反应中心质子化氨基酸残基的pK值都牵涉表面电荷影响，Gouy-Chapman理论提供了对由于在pH值下pH值的调节而产生的离子效应的可行描述。 RC的表面。在D2O中孵育会导致可质子化基团的pK小幅增加，并导致pH（pD）依赖性的结合速率减慢。 P QA状态下RC吸收质子的盐，pH，温度，粘度和D2O依赖性是由以下三个因素造成的：1）H传递至RC的平行途径，导致观测到的（净）H消失； 2）通过构象动力学限制蛋白质内目标基的质子化速率；和3）通过表面pH值对蛋白质中带电基团的静电影响。

BACKGROUND & AIMS: :Results are presented comparing Monte Carlo (MC) calculations for dynamic IMRT treatments of tumors in the sinus region with Eclipse treatment planning system dose calculations, and ion chamber measurements. The EGS4nrc MC code, BEAMnrc, was commissioned to simulate a Varian 21Ex Linac for both open and IMRT fields. The accuracy of the simulation for IMRT plans was evaluated using a head phantom by comparing MC, Eclipse, TLD results, and ion chamber in solid water phantom measurements. The MC code was then used to simulate dose distributions for five patients who were treated using dynamic IMRT for tumors in the sinus region. The results were compared with absolute and relative dose distributions calculated using Eclipse (pencil beam, modified-Batho inhomogeneity correction). Absolute dose differences were also compared with ion chamber results. Comparison of the doses calculated on the head phantom using MC, compared with Eclipse, ion chamber, and TLD measurements showed differences of -3.9%, -1.4%, and -2.0%, respectively (MC is colder). Relative dose distributions for the patient plans calculated using MC agreed well with those calculated using Eclipse with respect to targets and critical organs, indicating the modified-Batho correction is adequate. Average agreement for mean absolute target doses between MC and Eclipse was -3.0 +/-; 2.3% (1 s.d.). Agreement between ion chamber and Eclipse for these patients was -2.2 +/- 1.9%, compared with 0.2 +/- 2.0% for all head and neck IMRT patients. When Eclipse doses were corrected based on ion chamber results, agreement between MC and Eclipse was -0.7 +/- 2.0%, indicating a small systematic uncertainty in the doses calculated using the treatment planning system for this subset of patients.

背景与目标： ：结果比较了用蒙特卡洛（MC）计算窦道区域肿瘤的动态IMRT治疗与Eclipse治疗计划系统剂量计算和离子室测量值的比较结果。调试了EGS4nrc MC代码BEAMnrc，以针对开放领域和IMRT领域模拟Varian 21Ex Linac。通过比较MC，Eclipse，TLD结果和固体水体模测量中的离子室，使用头部体模评估了IMRT计划仿真的准确性。然后，将MC代码用于模拟五名使用动态IMRT进行鼻窦区域肿瘤治疗的患者的剂量分布。将结果与使用Eclipse计算出的绝对和相对剂量分布（铅笔束，改良的Batho不均匀性校正）进行比较。还将绝对剂量差异与离子室结果进行了比较。与使用Eclipse，离子室和TLD进行的测量相比，使用MC在头部模型上计算的剂量进行了比较，分别显示出-3.9％，-1.4％和-2.0％的差异（MC更冷）。对于目标和关键器官，使用MC计算的患者计划的相对剂量分布与使用Eclipse计算的相对剂量分布非常吻合，表明改良的Batho校正是足够的。 MC和Eclipse之间的平均绝对目标剂量的平均一致性为-3.0 /-； 2.3％（1 s.d.）。对于这些患者，离子室和Eclipse之间的一致性为-2.2 /-1.9％，而所有头颈部IMRT患者的一致性为0.2 /-2.0％。根据离子室结果校正Eclipse剂量后，MC和Eclipse之间的一致性为-0.7 /-2.0％，这表明使用治疗计划系统为该患者子集计算的剂量存在很小的系统不确定性。

BACKGROUND & AIMS: :The effects of neurokinin A (NKA) on freshly isolated smooth muscle cells from the rat vas deferens were investigated electrophysiologically. NKA (10(-7) M) prolonged the duration of action potentials without affecting resting potentials. Under voltage-clamp conditions, NKA (10(-7) M) suppressed an outward K+ current activated by depolarizing voltage steps. Substance P (SP, 10(-7) M) did not affect the K+ current, suggesting that NKA is more potent in suppressing the K+ current than SP is, as is also true for the contractions of smooth muscles of the rat vas deferens. The suppression of the K+ conductance now reported may contribute to NKA-induced smooth muscle contraction.

背景与目标： ：电生理学研究了神经激肽A（NKA）对新鲜分离自大鼠输精管的平滑肌细胞的作用。 NKA（10（-7）M）延长了动作电位的持续时间，而不会影响静息电位。在电压钳位条件下，NKA（10（-7）M）抑制了因去极化电压阶跃而激活的向外的K电流。 P物质（SP，10（-7）M）不影响K电流，这表明NKA比SP抑制K电流更有效，大鼠输精管平滑肌的收缩也是如此。现在报道的钾电导的抑制可能有助于NKA诱导的平滑肌收缩。

BACKGROUND & AIMS: BACKGROUND:We compared transcranial direct-current stimulation (tDCS) with a selective serotonin-reuptake inhibitor for the treatment of depression. METHODS:In a single-center, double-blind, noninferiority trial involving adults with unipolar depression, we randomly assigned patients to receive tDCS plus oral placebo, sham tDCS plus escitalopram, or sham tDCS plus oral placebo. The tDCS was administered in 30-minute, 2-mA prefrontal stimulation sessions for 15 consecutive weekdays, followed by 7 weekly treatments. Escitalopram was given at a dose of 10 mg per day for 3 weeks and 20 mg per day thereafter. The primary outcome measure was the change in the 17-item Hamilton Depression Rating Scale (HDRS-17) score (range, 0 to 52, with higher scores indicating more depression). Noninferiority of tDCS versus escitalopram was defined by a lower boundary of the confidence interval for the difference in the decreased score that was at least 50% of the difference in the scores with placebo versus escitalopram. RESULTS:A total of 245 patients underwent randomization, with 91 being assigned to escitalopram, 94 to tDCS, and 60 to placebo. In the intention-to-treat analysis, the mean (±SD) decrease in the score from baseline was 11.3±6.5 points in the escitalopram group, 9.0±7.1 points in the tDCS group, and 5.8±7.9 points in the placebo group. The lower boundary of the confidence interval for the difference in the decrease for tDCS versus escitalopram (difference, -2.3 points; 95% confidence interval [CI], -4.3 to -0.4; P=0.69) was lower than the noninferiority margin of -2.75 (50% of placebo minus escitalopram), so noninferiority could not be claimed. Escitalopram and tDCS were both superior to placebo (difference vs. placebo, 5.5 points [95% CI, 3.1 to 7.8; P<0.001] and 3.2 points [95% CI, 0.7 to 5.5; P=0.01], respectively). Patients receiving tDCS had higher rates of skin redness, tinnitus, and nervousness than did those in the other two groups, and new-onset mania developed in 2 patients in the tDCS group. Patients receiving escitalopram had more frequent sleepiness and obstipation than did those in the other two groups. CONCLUSIONS:In a single-center trial, tDCS for the treatment of depression did not show noninferiority to escitalopram over a 10-week period and was associated with more adverse events. (Funded by Fundação de Amparo à Pesquisa do Estado de São Paulo and others; ELECT-TDCS ClinicalTrials.gov number, NCT01894815 .).

背景与目标： 背景：我们比较了经颅直流电刺激（tDCS）和选择性5-羟色胺再摄取抑制剂治疗抑郁症的效果。
方法：在一项涉及成人单相抑郁症的单中心，双盲，非自卑性试验中，我们随机分配患者接受tDCS联合口服安慰剂，假tDCS联合依西酞普兰或假tDCS联合口服安慰剂。 tDCS在30分钟，2 mA的额前刺激中连续15个工作日进行给药，然后每周进行7次治疗。依西酞普兰的剂量为每天10 mg，持续3周，之后每天20 mg。主要结局指标是17个项目的汉密尔顿抑郁量表（HDRS-17）得分的变化（范围从0到52，得分越高表示抑郁越多）。 tDCS与依西酞普兰的非劣效性是由置信区间的下限定义的，即降低分数的差异至少是安慰剂与依西酞普兰分数差异的50％。
结果：共有245例患者接受了随机分组，其中91例患者被分配为依他普仑，94例被分配给tDCS，60例被分配给安慰剂。在意向性治疗分析中，依他普仑组的基线平均得分下降（±SD）为11.3±6.5分，tDCS组为9.0±7.1分，而安慰剂组为5.8±7.9分。 tDCS与依西酞普兰的降幅差异的置信区间的下限（差异-2.3点； 95％的置信区间[CI]，-4.3至-0.4； P = 0.69）低于- 2.75（安慰剂减去艾司西酞普兰的50％），因此不能主张非自卑。 Escitalopram和tDCS均优于安慰剂（差异与安慰剂相比，分别为5.5分[95％CI，3.1至7.8； P <0.001]和3.2分[95％CI，0.7至5.5； P = 0.01]。接受tDCS的患者的皮肤发红，耳鸣和神经质发生率高于其他两组，并且tDCS组中的2例患者出现了新发躁狂症。接受艾司西酞普兰治疗的患者比其他两组患者更容易出现困倦和便秘。
结论：在一项单中心试验中，tDCS治疗抑郁症在10周内并未显示出依他普仑的非劣效性，并伴有更多不良事件。 （由圣保罗埃斯帕多萨基金会和圣保罗基金会资助； ELECT-TDCS ClinicalTrials.gov编号，NCT01894815。）。

BACKGROUND & AIMS: :In recent years, there have been major advances in the treatment of multiple myeloma. Among previously untreated patients, different combinations of dexamethasone, lenalidomide, thalidomide, and bortezomib have produced overall response rates of 80%-90% with complete response rates of 10%-32%, and remissions are often achieved after only 2 cycles of initiating systemic therapy. Subsequent intensification with high-dose chemotherapy supported by autologous stem cell transplantation has enabled younger patients to achieve partial and complete responses with evidence of prolonged survival. Tandem autologous stem cell transplantation and reduced-intensity allogeneic stem cell transplantation are under investigation in attempts to improve outcomes. For patients unable to pursue consolidation therapy with stem cell transplantation, remissions obtained with induction therapy can often be extended with the use of maintenance systemic therapy. Despite available therapies, relapse of disease is inevitable for nearly all patients, and treatment strategies with novel agents and novel combinations of established agents are under study.

背景与目标： ：近年来，多发性骨髓瘤的治疗取得了重大进展。在先前未接受治疗的患者中，地塞米松，来那度胺，沙利度胺和硼替佐米的不同组合产生的总缓解率为80％-90％，完全缓解率为10％-32％，并且通常仅在2个周期的全身性启动后即可缓解治疗。自体干细胞移植支持的大剂量化疗随后的强化治疗使年轻患者能够获得部分和完全缓解，并具有延长生存期的证据。串联自体干细胞移植和强度降低的异体干细胞移植正在研究中，以期改善治疗效果。对于无法通过干细胞移植进行巩固治疗的患者，诱导治疗获得的缓解通常可通过维持全身治疗来扩大。尽管有可用的疗法，对于几乎所有患者来说疾病的复发都是不可避免的，并且正在研究用新型药物和已建立药物的新型组合的治疗策略。

BACKGROUND & AIMS: :Lethal ventricular tachyarrhythmia (LVTA) is the most prevalent electrophysiological underpinning of sudden cardiac death (SCD), a condition that occurs in response to multiple pathophysiological abnormalities. The aim of this study was to identify common lipid features of LVTA that were induced by distinct pathophysiological conditions, thereby facilitating the discovery of novel SCD therapeutic targets. Two rat LVTA-SCD models were established to mimic myocardial infarction (MI) and myocardial ion channel diseases. Myocardial and serum specimens were analyzed using ultra-performance liquid chromatography-mass spectrometry (UPLC-MS)-based lipidomics. The lipid profiles of the myocardial and serum specimens were similar between the models. Eleven myocardial lipid classes were altered, including downregulations of: cardiolipin, ceramide, phosphatidylinositol, phosphatidylethanolamine, triacylglycerol, diacylglycerol, phosphatidylglycerol, lysophosphatidylethanolamine and phosphatidylserine, and upregulations of: lysophosphatidylcholine and phosphatidic acid. Serum concentrations of triacylglycerol, lysophosphatidylcholine, phosphatidylethanolamine and phosphatidylinositol were also altered. Alterations of lipids in paired myocardia and sera were closely correlated. Cardiolipin 70:5, cardiolipin 74:9 and ceramide d34:2 were tested as potential biomarkers of LVTA. The results indicate that there are common LVTA lipid profiles induced by MI and myocardial ion channel diseases, potentially offering novel LVTA-SCD therapeutic targets.

背景与目标： ：致命性室性心律失常（LVTA）是心脏猝死（SCD）的最普遍的电生理基础，这种情况是由于多种病理生理异常而引起的。这项研究的目的是确定由不同的病理生理条件诱导的LVTA的常见脂质特征，从而促进新的SCD治疗靶标的发现。建立了两种大鼠LVTA-SCD模型来模拟心肌梗塞（MI）和心肌离子通道疾病。使用基于超高效液相色谱-质谱（UPLC-MS）的脂质组学分析心肌和血清标本。在两个模型之间，心肌和血清标本的脂质谱相似。改变了11种心肌脂质的类别，包括下调：心磷脂，神经酰胺，磷脂酰肌醇，磷脂酰乙醇胺，三酰基甘油，二酰基甘油，磷脂酰甘油，溶血磷脂酰乙醇胺和磷脂酰丝氨酸，以及溶血磷脂酰磷酸的上调。血清三酰甘油，溶血磷脂酰胆碱，磷脂酰乙醇胺和磷脂酰肌醇的浓度也发生了改变。配对的心肌和血清中脂质的变化密切相关。心磷脂70：5，心磷脂74：9和神经酰胺d34：2被测试为LVTA的潜在生物标志物。结果表明存在由MI和心肌离子通道疾病引起的常见LVTA脂质谱，可能提供新的LVTA-SCD治疗靶标。

BACKGROUND & AIMS: :Na-rich birnessite (NRB) was synthesized by a simple synthesis method and used as a high-efficiency adsorbent for the removal of ammonium ion (NH4+) from aqueous solution. In order to demonstrate the adsorption performance of the synthesized material, the effects of contact time, pH, initial ammonium ion concentration, and temperature were investigated. Adsorption kinetics showed that the adsorption behavior followed the pseudo second-order kinetic model. The equilibrium adsorption data were fitted to Langmuir and Freundlich adsorption models and the model parameters were evaluated. The monolayer adsorption capacity of the adsorbent, as obtained from the Langmuir isotherm, was 22.61mg NH4+-N/g at 283K. Thermodynamic analyses showed that the adsorption was spontaneous and that it was also a physisorption process. Our data revealed that the higher NH4+ adsorption capacity could be primarily attributed to the water absorption process and electrostatic interaction. Particularly, the high surface hydroxyl-content of NRB enables strong interactions with ammonium ion. The results obtained in this study illustrate that the NRB is expected to be an effective and economically viable adsorbent for ammonium ion removal from aqueous system.

背景与目标： ：富钠水钠锰矿（NRB）通过简单的合成方法合成，并用作高效吸附剂，用于从水溶液中去除铵离子（NH4）。为了证明合成材料的吸附性能，研究了接触时间，pH，初始铵离子浓度和温度的影响。吸附动力学表明，吸附行为遵循伪二级动力学模型。将平衡吸附数据拟合到Langmuir和Freundlich吸附模型，并评估模型参数。从Langmuir等温线获得的吸附剂的单层吸附容量在283K为22.61mg NH 4 -N / g。热力学分析表明吸附是自发的，也是物理吸附过程。我们的数据表明，较高的NH4吸附能力可能主要归因于吸水过程和静电相互作用。特别是，NRB的高表面羟基含量使它能够与铵离子发生强烈的相互作用。这项研究中获得的结果表明，NRB有望成为一种有效且经济可行的吸附剂，用于从水性系统中去除铵离子。

BACKGROUND & AIMS: :The World Health Organization European Region has one of the highest rates of multidrug-resistant tuberculosis (MDR-TB) in the world, resulting in many vulnerable children being exposed each year. Evidence for preventive therapy following MDR-TB exposure is limited and current guidance is conflicting. An internet-based survey was performed to determine clinical practice in this region. Seventy-two clinicians from 25 countries participated. Practices related to screening and decision-making were highly variable. Just over half provided preventive therapy for children exposed to MDR-TB; the only characteristic associated with provision was practice within the European Union (adjusted OR 4.07, 95%CI 1.33-12.5).

背景与目标： ：世界卫生组织欧洲区域是世界上耐多药结核病（MDR-TB）发病率最高的国家之一，每年导致许多弱势儿童被暴露。耐多药结核病暴露后进行预防性治疗的证据有限，目前的指导意见相互矛盾。进行了基于互联网的调查，以确定该地区的临床实践。来自25个国家的72名临床医生参加了会议。与筛查和决策有关的实践是高度可变的。刚刚超过一半的人为患有耐多药结核病的儿童提供了预防性治疗；与规定相关的唯一特征是欧盟内部的惯例（调整后的OR 4.07，95％CI 1.33-12.5）。

BACKGROUND & AIMS: OBJECTIVE:To compare the effectiveness of transcutaneous electrical nerve stimulation and interferential current in primary dysmenorrhea. DESIGN:A prospective, randomized, and controlled study. SETTING:Hacettepe University School of Physical Therapy and Rehabilitation. PATIENTS:Thirty-four volunteer subjects with primary dysmenorrhea (mean age: 21.35 +/- 1.70 years) were included. Statistical analyses were performed in 32 subjects who completed all measures. INTERVENTIONS:Fifteen subjects received interferential current application for 20 minutes and 17 subjects received transcutaneous electrical nerve stimulation for 20 minutes when they were experiencing dysmenorrhea. OUTCOME MEASURES:Physical characteristics, years since menarche, length of menstrual cycle (days), and duration of menstruation (days) were recorded. Visual analog scale ( VAS) intensities of menstrual pain, referred lower limb pain, and low back pain were recorded before treatment, and immediately, 8 hours, and 24 hours after treatment. RESULTS:Intensities of the evaluated parameters decreased beginning from just after the applications in both groups (P<0.05). Intensity of referring low back pain in first three measurement times was different between the groups (P<0.05), but this difference is thought to be due to the baseline values of the groups. So, it can be said that no superiority existed between the methods (P>0.05). CONCLUSION:Both transcutaneous electrical nerve stimulation and interferential current appear to be effective in primary dysmenorrhea. As they are free from the potentially adverse effects of analgesics, and no adverse effects are reported in the literature nor observed in this study, a clinical trial of their effectiveness in comparison with untreated and placebo-treated control groups is warranted.

背景与目标： 目的：比较经皮电神经刺激和干扰电流治疗原发性痛经的有效性。
设计：一项前瞻性，随机对照研究。
地点：哈特佩特大学物理治疗与康复学院。
患者：包括34名原发性痛经的志愿者受试者（平均年龄：21.35 /-1.70岁）。对完成所有测量的32位受试者进行了统计分析。
干预：15名受试者在遭受痛经时接受了20分钟的干扰电流施加，而17名受试者在经历了痛经时接受了20分钟的经皮电神经刺激。
观察指标：记录生理特征，初潮以来的时间，月经周期的天数（天）和月经的持续时间（天数）。在治疗前以及治疗后立即，分别在治疗后8小时和24小时记录月经痛，下肢偏头痛和下背痛的视觉模拟量表（VAS）强度。
结果：两组的应用后刚开始，评估参数的强度均降低（P <0.05）。各组之间在前三个测量时间内下腰痛的转诊强度有所不同（P <0.05），但这种差异被认为是由于各组的基线值所致。因此，可以说这两种方法之间没有优势（P> 0.05）。
结论：经皮电神经刺激和干扰电流治疗均对原发性痛经有效。由于它们没有止痛药的潜在不利作用，并且在文献中也没有观察到不良影响，也没有在这项研究中观察到，因此与未治疗和安慰剂治疗的对照组相比，它们的有效性值得进行临床试验。

BACKGROUND & AIMS: :Most of type II restriction endonucleases show an absolute requirement for divalent metal ions as cofactors for DNA cleavage. While Mg(2+) is the natural cofactor other metal ions can substitute it and mediate the catalysis, however Ca(2+) (alone) only supports DNA binding. To investigate the role of Mg(2+) in DNA cleavage by restriction endonucleases, we have studied the Mg(2+) and Mn(2+) concentration dependence of DNA cleavage by SepMI and EhoI. Digestion reactions were carried out at different Mg(2+) and Mn(2+) concentrations at constant ionic strength. These enzymes showed different behavior regarding the ions requirement, SepMI reached near maximal level of activity between 10 and 20mM while no activity was detected in the presence of Mn(2+) and in the presence of Ca(2+) cleavage activity was significantly decreased. However, EhoI was more highly active in the presence of Mn(2+) than in the presence of Mg(2+) and can be activated by Ca(2+). Our results propose the two-metal ion mechanism for EhoI and the one-metal ion mechanism for SepMI restriction endonuclease. The analysis of the kinetic parameters under steady state conditions showed that SepMI had a K(m) value for pTrcHisB DNA of 6.15 nM and a V(max) of 1.79×10(-2)nM min(-1), while EhoI had a K(m) for pUC19 plasmid of 8.66 nM and a V(max) of 2×10(-2)nM min(-1).

背景与目标： ：大多数II型限制性核酸内切酶显示了对二价金属离子作为DNA切割辅助因子的绝对要求。 Mg（2）是天然的辅助因子，其他金属离子可以替代它并介导催化作用，但是Ca（2）（单独）仅支持DNA结合。要研究Mg（2）在限制性内切核酸酶切割DNA中的作用，我们研究了SepMI和EhoI对Mg（2）和Mn（2）浓度依赖性的DNA切割的依赖性。在恒定的离子强度下，以不同的Mg（2）和Mn（2）浓度进行消化反应。这些酶在离子需求方面表现出不同的行为，SepMI在10至20mM之间达到最大活性水平，而在Mn（2）存在下未检测到活性，而在Ca（2）存在下裂解活性显着降低。但是，EhoI在存在Mn（2）时比在存在Mg（2）时具有更高的活性，并且可以被Ca（2）激活。我们的研究结果提出了EhoI的两种金属离子机制和SepMI限制性核酸内切酶的一种金属离子机制。稳态条件下的动力学参数分析表明，SepMI的pTrcHisB DNA的K（m）值为6.15 nM，V（max）为1.79×10（-2）nM min（-1），而EhoI为pUC19质粒的K（m）为8.66 nM，V（max）为2×10（-2）nM min（-1）。

BACKGROUND & AIMS: :The accumulation of non-enzymatic modifications on both DNA and protein molecules under the attack of reactive oxygen species (ROS), is one of the most possible factors responsible for the functional deterioration in aged cells. Direct protein modifications as well as DNA damages may be detectable, in part, by proteome analysis if the gene expression is affected by the damages on DNA. The novel term "proteome", which is a compound of "protein" and "genome", means a whole set of proteins expressed in a tissue or a cell strain to be investigated. Proteomics is a methodology for analyzing proteomes. In proteomics, two-dimensional gel electrophoresis is performed primarily to separate constitutive proteins, followed by mass spectrometry to identify each protein of interest and to determine a possible post-translational modification. Proteomics has offered us an innovative tool for investigating the molecular mechanisms of cellular aging.

背景与目标： ：在活性氧（ROS）的攻击下，DNA和蛋白质分子上非酶修饰的积累是导致衰老细胞功能恶化的最可能因素之一。如果基因表达受DNA损伤的影响，则可以通过蛋白质组分析来部分检测直接的蛋白质修饰以及DNA损伤。新的术语“蛋白质组”是“蛋白质”和“基因组”的化合物，是指在要研究的组织或细胞株中表达的整套蛋白质。蛋白质组学是一种分析蛋白质组学的方法。在蛋白质组学中，主要执行二维凝胶电泳以分离组成性蛋白，然后进行质谱分析以鉴定每种目的蛋白并确定可能的翻译后修饰。蛋白质组学为我们提供了研究细胞衰老的分子机制的创新工具。

BACKGROUND & AIMS: :Citrate uptake in Bacillus subtilis is stimulated by a wide range of divalent metal ions. The metal ions were separated into two groups based on the expression pattern of the uptake system. The two groups correlated with the metal ion specificity of two homologous B. subtilis secondary citrate transporters, CitM and CitH, upon expression in Escherichia coli. CitM transported citrate in complex with Mg(2+), Ni(2+), Mn(2+), Co(2+), and Zn(2+) but not in complex with Ca(2+), Ba(2+), and Sr(2+). CitH transported citrate in complex with Ca(2+), Ba(2+), and Sr(2+) but not in complex with Mg(2+), Ni(2+), Mn(2+), Co(2+), and Zn(2+). Both transporters did not transport free citrate. Nevertheless, free citrate uptake could be demonstrated in B. subtilis, indicating the expression of at least a third citrate transporter, whose identity is not known. For both the CitM and CitH transporters it was demonstrated that the metal ion promoted citrate uptake and, vice versa, that citrate promoted uptake of the metal ion, indicating that the complex is the transported species. The results indicate that CitM and CitH are secondary transporters that transport complexes of divalent metal ions and citrate but with a complementary metal ion specificity. The potential physiological function of the two transporters is discussed.

背景与目标： ：广泛的二价金属离子刺激枯草芽孢杆菌中的柠檬酸盐吸收。根据吸收系统的表达方式，将金属离子分为两组。当在大肠杆菌中表达时，这两组与两个同源枯草芽孢杆菌二级柠檬酸盐转运蛋白CitM和CitH的金属离子特异性相关。 CitM运送柠檬酸盐与Mg（2），Ni（2），Mn（2），Co（2）和Zn（2）形成复合物，但不与Ca（2），Ba（2）和Sr（2）形成复合物。 ）。 CitH运送柠檬酸盐与Ca（2），Ba（2）和Sr（2）形成复合物，但不与Mg（2），Ni（2），Mn（2），Co（2）和Zn（2）形成复合物。 ）。两种运输者均未运输游离柠檬酸盐。然而，枯草芽孢杆菌中可以证明有游离柠檬酸盐的摄取，这表明至少有第三种柠檬酸盐转运蛋白的表达，其身份尚不清楚。对于CitM和CitH转运蛋白，都证明了金属离子促进了柠檬酸根的吸收，反之亦然，柠檬酸根促进了金属离子的吸收，表明该络合物是被转运的物质。结果表明，CitM和CitH是二级转运蛋白，可转运二价金属离子和柠檬酸盐的配合物，但具有互补的金属离子特异性。讨论了两种转运蛋白的潜在生理功能。