BACKGROUND & AIMS: BACKGROUND:The optimal approach to initiate positive-pressure therapy in patients with obstructive sleep apnea is still debated. Current options are autotitrating positive airway pressure (APAP) or manual titration with continuous positive airway pressure (CPAP). Procedures differ by parameters and by algorithms used for adapting pressure. OBJECTIVES:To evaluate the efficacy of attended automatic titration in a randomized crossover study compared with manual titration over 2 nights where the sequence of the titration mode was changed. Therapy outcome was controlled after 6 weeks. METHODS:21 sleep apnea patients were treated using manual CPAP versus automatic APAP titration. The mode used during the 2nd night was continued for 6 weeks. Cardiorespiratory polysomnography, Epworth Sleepiness Scale (ESS), SF-36 score and compliance were assessed. RESULTS:Apnea-hypopnea index reduction was equally effective at similar effective pressure independent of the titration mode. If APAP was applied during the 1st night, total sleep time was longer (384 vs. 331 min, p < 0.01) and sleep efficacy was higher (91 vs. 81%, p < 0.01) than after starting with manual titration with CPAP. Compliance was comparable in both groups (4.6 +/- 1.9 h). The ESS improved in both groups (from 12.9 to 6.5). SF-36 scores and therapeutic pressure did not much change. CONCLUSIONS:Taking the sequence of titration into account, we found equal effectiveness of CPAP and APAP. Sleep quality was better with initial application of APAP - which favors attended automatic titration if only 1 titration night is possible. Both modes are comparable after 6 weeks regarding therapeutic pressure, efficacy, compliance and quality of life.

背景与目标：

BACKGROUND & AIMS: :Adherence is still an important issue considering new advances in Obstructive Sleep Apnea (OSA) treatment, as automatic positive airway pressure (APAP). The aim of the present study was to identify and explore relationships between identified predictors of adherence, over time. After overnight sleep study and OSA diagnosis and during a six-month APAP treatment period, a total of 153 patients underwent a three time psychological protocol evaluation. Generalized estimating equations were applied to analyzed repeated measurements in the same individuals. Results show that 40% of patients were poorly adherent and 60% were adherent after six months of treatment. The results confirmed a predictive value of age, self-efficacy, decisional balance index and health-related quality of life (HRQoL) in APAP adherence. Furthermore, the results revealed an interaction between time and illness cognitive representations, and self-efficacy and family coping, in explaining adherence patterns over time. Therefore, understanding the causality of theoretically derived constructs is crucial to predict the continuity of APAP adherence.

背景与目标： : 考虑到阻塞性睡眠呼吸暂停 (OSA) 治疗的新进展，如自动气道正压通气 (APAP)，依从性仍然是一个重要问题。本研究的目的是随着时间的推移，确定并探索已确定的依从性预测因子之间的关系。经过过夜睡眠研究和OSA诊断后，在六个月的APAP治疗期间，共有153名患者接受了三次心理方案评估。将广义估计方程应用于同一个体的重复测量分析。结果显示，治疗六个月后，40% 的患者粘附不良，60% 的患者粘附不良。结果证实了年龄，自我效能，决策平衡指数和健康相关生活质量 (HRQoL) 对APAP依从性的预测价值。此外，结果揭示了时间与疾病认知表征，自我效能感与家庭应对之间的相互作用，以解释随时间推移的依从性模式。因此，了解理论上得出的结构的因果关系对于预测APAP遵守的连续性至关重要。

BACKGROUND & AIMS: PURPOSE:In heart failure with reduced ejection fraction (HFrEF), the effects of automatic positive airway pressure therapy (APAP) for obstructive sleep apnea (OSA) on sleep quality and sympatho-vagal balance (SVB) are unknown. METHODS:In this randomized controlled trial (6 months of APAP vs. nasal strips as control), sleep quality and SVB in patients with HFrEF and OSA were monitored. The distinction was made between different breathing conditions (5-min segments of OSA or normal breathing [NB] during stable N2 sleep) at baseline (T0), APAP initiation (T1), and 6 months of successful APAP treatment (T2). RESULTS:Of 75 patients enrolled, 61 were men with average age of 65 ± 12 years and LVEF of 31 ± 9%; 37 patients were randomized into the APAP and 38 into the control (nasal strips only) group. At T0, OSA was associated with a 17% increase in the low-frequency/high-frequency component ratio of heart rate variability (LF/HF) versus baseline, suggesting an increase in sympathetic drive (SVB) with OSA compared with normal breathing. Respiratory indices and oxygen saturation all significantly improved at both T1 and T2, but at 6 months, APAP had no clinically relevant effect on objective sleep quality versus control. In fact, in patients with HFrEF (n = 23 with data suitable for HRV analysis), there was even a trend (p = 0.097) towards an additional 17% increase in LF/HF at T2 in the therapy group, suggesting (undesired) increased SVB in the APAP group. CONCLUSION:Treatment of OSA in patients with systolic HF improves respiratory indices but does not have a favorable effect on sleep quality. While OSA per se was associated with an increase in sympathetic drive, APAP treatment was not associated with a reduction in sympathetic drive. After 6 months of treatment, there was even a trend towards additional increases in sympathetic drive in the APAP group.

背景与目标：

BACKGROUND & AIMS: The time development of the biodistribution and the hepatotoxicity following peroral administration of 14C-acetaminophen (APAP 400 or 800 mg.kg-1; 1 microCi) was characterized in a trial procedure using male BomNMRI mice. APAP (400 mg.kg-1) caused a transitory hepatic glutathione (GSH) depletion while APAP 800 mg.kg-1 maximally depleted hepatic GSH throughout the 12 h trial period. A lag time between the initial GSH depletion and the ensuing hepatic necrosis was seen. From 8 h post dosing a decrease of 14C-APAP or its metabolites coincided with recovery of the hepatic GHS level and the regeneration of the hepatic cells caused by APAP 400 mg.kg-1. Hepatic glycogen depletion preceded centrilobular necrosis, and irrespective of APAP dose definite kidney damage was absent. Irrespective of APAP dose the biodistribution of 14C-APAP or its metabolites was predominantly in organs associated with metabolism and excretion. After APAP (800 mg.kg-1) significant amounts of 14C-APAP or its metabolites were present up to 24 h post dosing. The operative status of the hepatic GSH conjugative system has an important influence on the rate of elimination of toxic APAP doses. Hepatic cell necrosis with a possible effect on the circulation may play an important secondary role in the elimination of toxic APAP doses. Factors which may influence the status of the hepatic GSH conjugative system and toxicokinetics of perorally administered APAP doses are discussed.

背景与目标： 在使用雄性BomNMRI小鼠的试验过程中，对经口施用14c-对乙酰氨基酚 (APAP 400或800 mg.kg-1; 1 microCi) 后的生物分布和肝毒性的时间发展进行了表征。APAP (400 mg.kg-1) 引起短暂的肝谷胱甘肽 (GSH) 耗竭，而APAP 800 mg.kg-1在整个12小时的试验期间最大程度地耗竭了肝GSH。观察到最初的GSH耗竭与随后的肝坏死之间的滞后时间。从给药后8小时起，14C-APAP或其代谢物的减少与肝GHS水平的恢复以及由APAP 400 mg.kg-1引起的肝细胞的再生相吻合。肝糖原耗竭先于小叶中心坏死，无论APAP剂量如何，均不存在明确的肾脏损害。与APAP剂量无关，14C-APAP或其代谢产物的生物分布主要在与代谢和排泄相关的器官中。在APAP (800 mg.kg-1) 后，在给药后24小时内存在大量的14C-APAP或其代谢物。肝GSH结合系统的手术状态对毒性APAP剂量的消除速率有重要影响。可能对循环产生影响的肝细胞坏死可能在消除有毒的APAP剂量中起重要的次要作用。讨论了可能影响肝GSH结合系统状态和口服APAP剂量的毒代动力学的因素。

BACKGROUND & AIMS: PURPOSE:Auto-titrating continuous positive airway pressure (APAP) devices were developed to improve treatment efficacy and compliance in patients with obstructive sleep apnoea syndrome (OSAS). Since there are insufficient data on the optimal pressure range setting, we aimed to compare the adherence, efficacy and tolerability of treatment with high-span versus low-span APAP. METHODS:Seventy-six newly diagnosed OSAS patients fulfilling the treatment criteria were randomised to receive high-span (HS, range 4-15cmH2O, n = 38) or low-span (LS, range 8-12cmH2O, n = 38) APAP. Patients were assessed at 1 and 3 months. RESULTS:Median Epworth sleepiness scale (ESS) was 13 (IQR, 6-16) and median apnoea-hypopnoea index (AHI) was 35.9 (IQR, 27.6-56.3). There were no significant differences in baseline demographic and clinical characteristics between groups. Overall, no significant differences were found at the first month assessment. After 3 months of therapy, we found again no differences in residual AHI or ESS. However, the group HS proved less adherent than group LS, respectively, with median 87 % (IQR, 60.5-97.5) versus 94 % (IQR, 80.0-98.3) of the nights using ≥4 h (P = 0.014) and mean (±SD) usage 5.7 ± 1.6 versus 6.4 ± 1.2 h/night (P = 0.049). The group HS reported more frequently nasal congestion, excessive oronasal dryness and nocturnal awakenings of at least moderate intensity, the latter with statistical significance (P = 0.005). CONCLUSIONS:Both pressure ranges appear to be equally effective to correct AHI and to improve symptoms. Though, patients with high-span APAP were less compliant to treatment, raising issues about the tolerability of wide pressure range settings of these devices.

背景与目标：

BACKGROUND & AIMS: :Due to its widespread availability, acetaminophen (APAP) is the leading cause for drug-induced liver injury in many countries including United States and United Kingdom. When used as recommended, APAP is relatively safe. However, in overdose cases, increased metabolism of APAP to N-acetyl-para-benzoquinoneimine (NAPQI), a reactive metabolite, leads to glutathione (GSH) depletion, oxidative stress, and cellular injury. Throughout this process, a variety of factors play important roles in propagating toxicity, including c-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase (MAPK) family. Because of its involvement in multiple cellular processes, biomarkers associated with MAPK signaling have generated interest as a mechanistic target for protecting against APAP-induced liver injury and hepatocellular injury, in general. This review summarizes mechanistic details by which natural products, specifically those containing polyphenolic moieties, are capable of attenuating APAP-induced toxicity, at least in part through an ability to modulate MAPKs. These compounds include carnosic acid, chlorogenic acid, davallialactone, extracts from Hibiscus sabdariffa, quercetin-based compounds, and resveratrol. Despite variations in the experimental designs across these studies, common pathways and biomarkers were implicated in cytoprotection when polyphenolic compounds were given with APAP, such as enhanced antioxidant gene expression and reversal of APAP-induced changes in oxidative stress markers and MAPK signaling. Overall, an emphasis should be placed on method standardization for future studies if we are to gain a more in-depth understanding of how polyphenolic moieties contribute to cytoprotection during an APAP overdose event.

背景与目标： : 由于对乙酰氨基酚 (APAP) 的广泛使用，在包括美国和英国在内的许多国家/地区，对乙酰氨基酚 (APAP) 是药物性肝损伤的主要原因。按推荐使用时，APAP相对安全。然而，在过量的情况下，APAP向活性代谢物N-乙酰基对苯醌亚胺 (NAPQI) 的代谢增加会导致谷胱甘肽 (GSH) 消耗，氧化应激和细胞损伤。在整个过程中，多种因素在繁殖毒性中起着重要作用，包括有丝分裂原活化蛋白激酶 (MAPK) 家族成员c 6月N端激酶 (JNK)。由于其参与多个细胞过程，与MAPK信号相关的生物标志物已引起人们的兴趣，通常作为预防APAP诱导的肝损伤和肝细胞损伤的机制靶标。这篇综述总结了机理细节，通过这些机理，天然产物，特别是含有多酚部分的天然产物，至少部分通过调节MAPKs的能力，能够减弱APAP诱导的毒性。这些化合物包括肌糖酸，绿原酸，davalalactone，木槿提取物，槲皮素基化合物和白藜芦醇。尽管这些研究的实验设计存在差异，但当使用APAP给予多酚化合物时，常见的途径和生物标志物与细胞保护有关，例如增强的抗氧化剂基因表达和逆转APAP诱导的氧化应激标记物和MAPK信号传导的变化。总体而言，如果我们要更深入地了解多酚部分如何在APAP过量事件中促进细胞保护作用，则应将重点放在方法标准化上，以用于未来的研究。

BACKGROUND & AIMS: :Constant positive airway pressure (cPAP) is the predominant noninvasive therapy for the obstructive sleep apnea syndrome (OSAS). The average pressure thereby applied can be reduced by online-identification of respiratory events. Oscillatory impedance measurement as an indicator for airway patency can identify central and obstructive apneas and hypopneas. Our goal was to reduce the sensors needed, to auto-calibrate the signals to each individual patient and to rule out patient induced artifacts.

背景与目标： : 持续气道正压通气 (cPAP) 是阻塞性睡眠呼吸暂停综合征 (OSAS) 的主要无创疗法。通过在线识别呼吸事件，可以降低由此施加的平均压力。振荡阻抗测量作为气道通畅的指标可以识别中枢和阻塞性呼吸暂停和呼吸不足。我们的目标是减少所需的传感器，自动校准每个患者的信号，并排除患者诱发的伪影。

BACKGROUND & AIMS: PURPOSE:Surgeons are increasingly confronted by patients on long-term low-dose acetylsalicylic acid (ASA). However, owing to a lack of evidence-based data, a widely accepted consensus on the perioperative management of these patients in the setting of non-cardiac surgery has not yet been reached. Primary objective was to evaluate the safety of continuous versus discontinuous use of ASA in the perioperative period in elective general or abdominal surgery. METHODS:Fifty-two patients undergoing elective cholecystectomy, inguinal hernia repair or colonic/colorectal surgery were recruited to this pilot study. According to cardiological evaluation, non-high-risk patients who were on long-term treatment with low-dose ASA were eligible for inclusion. Patients were allocated randomly to continuous use of ASA or discontinuation of ASA intake for 5 days before until 5 days after surgery. The primary outcome was the incidence of major haemorrhagic and thromboembolic complications within 30 days after surgery. RESULTS:A total of 26 patients were allocated to each study group. One patient (3.8%) in the ASA continuation group required re-operation due to post-operative haemorrhage. In neither study group, further bleeding complications occurred. No clinically apparent thromboembolic events were reported in the ASA continuation and the ASA discontinuation group. Furthermore, there were no significant differences between both study groups in the secondary endpoints. CONCLUSIONS:Perioperative intake of ASA does not seem to influence the incidence of severe bleeding in non-high-risk patients undergoing elective general or abdominal surgery. Further, adequately powered trials are required to confirm the findings of this study.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Due to the increase of cardiovascular diseases acetylsalicylic acid (ASA) has become one of the most frequently prescribed drugs these days. Despite the rising number of patients with ASA medication presenting for elective general and abdominal surgery and the potentially increased risk of hemorrhage in these patients, there are no clear, evidence-based guidelines for the perioperative use of antiplatelet agents. The present randomised controlled trial was designed to evaluate the safety and optimize the use of ASA in the perioperative management of patients undergoing general and abdominal surgery. METHODS/DESIGN:This is a two-arm, monocenter randomised controlled trial. Patients scheduled for elective surgical treatment (i.e. inguinal hernia repair, cholecystectomy and colorectal resections) with ASA as a permanent medication are randomised equally to perioperative continuation or discontinuation of ASA. Patients who are randomised in the discontinuation group stop the administration of ASA five days prior to surgical treatment and start intake of ASA on postoperative day 5. Fifty-two patients will be enrolled in this trial. The primary outcome is the incidence of postoperative bleeding and cardiovascular events at 30 days after surgery. In addition a set of general as well as surgical variables are analysed. DISCUSSION:This is a randomised controlled two-group parallel trial designed to assess the safety and optimize the use of ASA in the perioperative management of patients undergoing general and abdominal surgery. The results of this pilot study build the basis for a confirmative randomised controlled trial that may help to clarify the use and potential risk/benefits of perioperative ASA medication in patients undergoing elective surgery. TRIAL REGISTRATION:The trial is registered with Current Controlled Trials ISRCTN45810007.

背景与目标：

BACKGROUND & AIMS: :We have previously described a novel cancer chemotherapeutic approach based on the induction of apoptosis in targeted cells by homing pro-apoptotic peptides. In order to improve this approach we developed a computational method (approach for detecting potential apoptotic peptides, APAP) to detect short PAPs, based on the prediction of the helical content of peptides, the hydrophobic moment, and the isoelectric point. PAPs are toxic against bacteria and mitochondria, but not against mammalian cells when applied extracellularly. Among other peptides, substance P was identified as a PAP and subsequently demonstrated to be a pro-apoptotic peptide experimentally. APAP thus provides a method to detect and ultimately improve pro-apoptotic peptides for chemotherapy.

背景与目标： : 我们先前已经描述了一种新的癌症化学治疗方法，该方法基于通过归巢促凋亡肽诱导靶向细胞凋亡。为了改进这种方法，我们基于对肽的螺旋含量，疏水矩和等电点的预测，开发了一种计算方法 (用于检测潜在凋亡肽的方法，APAP) 来检测短PAPs。PAPs对细菌和线粒体具有毒性，但在细胞外使用时对哺乳动物细胞没有毒性。在其他肽中，p物质被鉴定为PAP，随后通过实验证明是促凋亡肽。因此，APAP提供了一种检测并最终改善用于化学疗法的促凋亡肽的方法。

BACKGROUND & AIMS: :As a well-known analgesic drug, acetaminophen (APAP) is commonly used to relieve pain for patients with chronic painful diseases. Our previous study has shown that long-term ingestion of APAP caused liver fibrosis in mice. This study further investigated the critical role of nuclear factor erythroid 2-related factor 2 (Nrf2) in regulating APAP-induced liver fibrosis in mice and the anti-fibrotic effect of natural compound andrographolide (Andro). Our results showed that hepatic collagen deposition and hepatic stellate cells (HSCs) activation induced by APAP were more serious in Nrf2 knock-out mice than in normal wild-type mice. Andro reduced HSCs activation in vitro, and also decreased hepatic collagen deposition and HSCs activation induced by APAP in mice. Andro alleviated liver oxidative stress injury induced by APAP in mice and reduced cellular formation of reactive oxygen species (ROS) in HSCs. Andro enhanced Nrf2 nuclear translocation and increased the expression of Nrf2 downstream antioxidant genes both in vitro and in vivo. Furthermore, the Andro-provided protection against APAP-induced liver fibrosis was diminished in Nrf2 knock-out mice. In summary, Nrf2 is critically involved in preventing liver fibrosis induced by long-term administration of APAP in mice, and Andro alleviates APAP-induced liver fibrosis by attenuating liver oxidative stress injury via inducing Nrf2 activation. This study points out the potential application of Andro in the treatment of liver fibrosis in clinic.

背景与目标： : 作为一种众所周知的镇痛药物，对乙酰氨基酚 (APAP) 通常用于缓解慢性疼痛性疾病患者的疼痛。我们先前的研究表明，长期摄入APAP会导致小鼠肝纤维化。本研究进一步探讨了核因子红细胞2相关因子2 (Nrf2) 在调节APAP诱导的小鼠肝纤维化中的关键作用以及天然化合物穿心莲内酯 (Andro) 的抗纤维化作用。我们的结果表明，在Nrf2敲除小鼠中，APAP诱导的肝胶原沉积和肝星状细胞 (HSCs) 激活比正常野生型小鼠更严重。Andro在体外减少了HSCs的激活，也减少了APAP诱导的小鼠肝胶原沉积和HSCs的激活。Andro减轻了APAP引起的小鼠肝脏氧化应激损伤，并减少了hsc中活性氧 (ROS) 的细胞形成。在体外和体内，Andro增强了Nrf2核易位，并增加了Nrf2下游抗氧化基因的表达。此外，在Nrf2敲除小鼠中，对APAP诱导的肝纤维化的保护作用减弱。总之，Nrf2在小鼠中通过长期施用APAP诱导的肝纤维化的预防中至关重要，并且Andro通过诱导Nrf2激活减轻肝脏氧化应激损伤来减轻APAP诱导的肝纤维化。本研究指出了Andro在临床治疗肝纤维化中的潜在应用。

BACKGROUND & AIMS: BACKGROUND:Although continuous positive airway pressure (CPAP) is effective in treating obstructive sleep apnoea (OSA), inadequate adherence remains a major cause of treatment failure. This study aimed to determine long term adherence to auto adjusting-CPAP (APAP) and its influencing factors including the role of initial compliance. METHODS:Eighty-eight male patients with newly diagnosed moderate/severe OSA were included. After initiation of APAP treatment, patients had periodic follow-up appointments at 2 weeks, 6 months and then annually for at least 5 years. Patient's compliance to therapy was assessed in each appointment and predictors to treatment abandonment and poor compliance were evaluated. RESULTS:The studied population had a mean age of 53.8 years and mean apnoea-hypopnoea index of 52.71/h. The mean time of follow-up was 5.2 (± 1.6) years, during that time 22 (25%) patients abandoned APAP, those who maintained treatment had good compliance to it since 94% of them used it more than 4 h/day for at least 70% of days. A significant negative association was found between age, % of days and mean time of APAP use on 12th day and 6th month and the risk of abandoning. APAP use lower than 33% and 57% of days at 12th day and 6th month, respectively had high specificity (≈ 100%) to detect treatment abandonment. CONCLUSIONS:the majority of patients adheres to long term APAP treatment and has good compliance after 5-years of follow-up. Age and initial compliance (% days of use and mean hour/day) have the ability to predict future adherence, as soon as 12 days and 6 months after initiation.

背景与目标：

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: PURPOSE:Auto-titrating continuous positive airway pressure (APAP) is an effective treatment for obstructive sleep apnea/hypopnea syndrome (OSAHS). We investigated whether a single group education session on APAP therapy is effective in promoting adherence among patients with OSAHS. METHODS:This prospective, randomized, controlled, parallel group study included patients newly diagnosed with OSAHS who met criteria for APAP therapy. Patients were randomized into a study group and a control group. All patients in the study group were assigned to a single group education session, 1 month after beginning APAP therapy. RESULTS:We evaluated 146 patients. The median percentage of APAP usage days was 88.3 %, with a median duration per day of use of 6.02 h; 59 % were classified as adherent. Overall, no significant difference in adherence was seen between the study and the control groups. Analyzing patient subgroups, the group session significantly improved APAP adherence among males and patients who were younger (<65 years old), obese (BMI ≥ 35 kg/m(2)), non-sleepy (Epworth sleepiness scale ≤ 11), smokers or past smokers, had hypertension or nocturia and those with non-severe OSAHS. CONCLUSION:To maximize the impact of group education sessions and, by that, saving resources, it may be important to select patients likely to benefit from these sessions.

背景与目标：

BACKGROUND & AIMS: :Epicatechin (EC) is the most effective compound in Euonymus alatus (Thunb.)Sieb, and possesses a series of benefits, including anti-inflammatory, antioxidant, antiobesity and anticancer effects. In this study, we investigated the protective effects of EC in Acetaminophen(N-acetyl-p-aminophenol, APAP)-induced acute liver injury in C57BL/6J mice and explored the possible mechanisms involved in these effects.[Formula: see text].

背景与目标： : 表儿茶素 (EC) 是卫矛 (Thunb.)Sieb中最有效的化合物，具有一系列益处，包括抗炎，抗氧化，抗肥胖和抗癌作用。在这项研究中，我们研究了EC在对乙酰氨基酚 (N-乙酰对氨基苯酚，APAP) 诱导的C57BL/6J小鼠急性肝损伤中的保护作用，并探索了参与这些作用的可能机制。[公式: 见正文]。