BACKGROUND & AIMS: INTRODUCTION:Vismodegib was assessed as being of low risk for QT interval prolongation based on prior nonclinical and clinical experience. A dedicated study was conducted to further assess the potential for vismodegib to prolong the QTc interval. METHODS AND RESULTS:Given the nonlinear pharmacokinetics of vismodegib, a thorough QTc study as is typically designed was not possible, and an innovative design was employed. This dedicated QTc study was powered to exclude a 20-millisecond change from the baseline QTc interval. The subjects were administered daily oral 150 mg of vismodegib for 7 days, or a single dose of 400 mg of moxifloxacin, with corresponding matching placebos. The upper limits of the 90% confidence intervals for the difference in ΔQTcF between vismodegib and placebo at steady state were <20 milliseconds at all timepoints with a maximum of 10 milliseconds at 12 hours postdose. Exposure-response analysis yielded an estimated slope equal to 0.11 ms/μM, which was not statistically significant. After a single dose of moxifloxacin was administered, the lower limits of the 90% confidence interval of the difference in ΔQTcF between moxifloxacin and placebo were >5 milliseconds from 1-12 hours postdose, thereby establishing assay sensitivity. CONCLUSIONS:There was no effect of vismodegib on the QTc interval when dosed daily at 150 mg to steady state.

背景与目标： 简介：根据先前的非临床和临床经验，Vismodegib被评估为QT间期延长的低风险。进行了一项专门研究，以进一步评估vismodegib延长QTc间隔的可能性。
方法和结果：鉴于vismodegib的非线性药代动力学，不可能像通常设计的那样进行全面的QTc研究，并且采用了创新的设计。这项专门的QTc研究旨在从基线QTc间隔中排除20毫秒的变化。每天给受试者口服150 mg vismodegib，持续7天，或单剂量400 mg莫西沙星和相应的匹配安慰剂。稳态时，vismodegib与安慰剂之间的ΔQTcF差异的90％置信区间的上限在所有时间点均小于20毫秒，给药后12小时最大为10毫秒。暴露-响应分析得出的估计斜率等于0.11 ms /μM，在统计学上不显着。服用单剂莫西沙星后，从给药后1至12小时，莫西沙星与安慰剂之间的ΔQTcF差异的90％置信区间的下限为> 5毫秒，从而建立了测定灵敏度。
结论：每天以150 mg稳定剂量服用vismodegib对QTc间隔无影响。

BACKGROUND & AIMS: :This study aimed to investigate the prevalence of oral health impact on daily performance in Brazilian adults. 276 civil servants 35 to 44 years of age from the Public Works and Waste Disposal Department of Porto Alegre, in southern Brazil, were interviewed and clinically examined. Oral Impacts on Daily Performance (OIDP) was used to evaluate the impact of oral health status on daily performance. 73.6% of all subjects had at least one daily performance affected by an oral impact in the previous six months. The most commonly affected performance was eating (48.6%), while the most common symptoms were discomfort (40.6%) and dissatisfaction with one's appearance (31.5%). Missing teeth (21.7%) and toothache (20.7%) were recognized as the main causes of oral impacts on daily performance. OIDP was useful for measuring (physically, psychologically, and socially) the oral impacts on daily performance.

背景与目标： ：这项研究旨在调查巴西成年人口腔健康对日常工作表现的影响。来自巴西南部阿雷格里港公共工程和废物处理部门的276名35至44岁的公务员接受了采访并进行了临床检查。口腔对日常工作的影响（OIDP）用于评估口腔健康状况对日常工作的影响。在过去的六个月中，有73.6％的受试者每天至少有一次受口头影响的表现。影响最普遍的表现是进食（48.6％），而最常见的症状是不适（40.6％）和对外表的不满意（31.5％）。牙齿缺失（21.7％）和牙痛（20.7％）被认为是口腔影响日常工作的主要原因。 OIDP可用于（从身体，心理和社交方面）评估口腔对日常工作的影响。

BACKGROUND & AIMS: BACKGROUND:Adenosine induced hyperaemic fractional flow reserve (aFFR) is a validated predictor of clinical outcome and part of routine interventional practice. Protocol issues associated with the adenosine infusion limit the use of aFFR in clinical practice. Contrast medium induced hyperaemic FFR (cFFR) is a simpler procedure from a practical standpoint. We compared the two in a real world setting. METHODS:We analysed 76 patients that had both cFFR and aFFR assessment of 100 angiographically indeterminate coronary stenosis. cFFR was performed with intracoronary contrast medium injections (10ml for left coronary lesions and 8ml for right coronary lesions). The diagnostic performance of cFFR was analysed and compared to the gold standard aFFR. RESULTS:Mean cFFR was 0.87 (±0.07) and mean aFFR was 0.84 (±0.08). Bland-Altman analysis revealed a close agreement between cFFR and aFFR (0.035±0.032; 95% CI: -0.028 to 0.098) and good linear correlation (r=0.92, r2=0.86; p<0.0001). Using cFFR cut-off values of ≤0.83 in predicting an aFFR value of ≤0.80 or a cFFR value ≥0.88, predicting an aFFR value of >0.80 yielded a sensitivity of 100%, specificity of 96.1%, positive predictive value of 92.3%, negative predictive value of 100% and diagnostic accuracy of 96%. Only 24% of cFFR values were in the 0.84 to 0.87 range. CONCLUSION:Contrast medium induced hyperaemic FFR as an initial assessment may limit the need for adenosine to when cFFR falls in the 0.84 to 0.87 range. The use of adenosine infusion potentially could have been avoided in the majority of patients in this study.

背景与目标： 背景：腺苷诱导的高血流分数储备（aFFR）是临床结果的有效预测指标，是常规干预措施的一部分。与腺苷输注相关的协议问题限制了aFFR在临床实践中的使用。从实际的角度来看，造影剂诱导的高血FFR（cFFR）是一种更简单的方法。我们在现实世界中比较了两者。
方法：我们分析了76例同时进行了cFFR和aFFR评估的100例血管造影不确定的冠状动脉狭窄患者。 cFFR通过冠状动脉内造影剂注射（左冠状动脉病变为10ml，右冠状动脉病变为8ml）进行。分析了cFFR的诊断性能，并将其与金标准aFFR进行了比较。
结果：平均cFFR为0.87（±0.07），平均aFFR为0.84（±0.08）。 Bland-Altman分析显示cFFR和aFFR之间有密切的一致性（0.035±0.032; 95％CI：-0.028至0.098）和良好的线性相关性（r = 0.92，r2 = 0.86; p <0.0001）。在预测aFFR值≤0.80或cFFR值≥0.88时，使用cFFR截止值≤0.83，预测aFFR值> 0.80时，灵敏度为100％，特异性为96.1％，阳性预测值为92.3％，阴性预测值为100％，诊断准确性为96％。 cFFR值中只有24％在0.84至0.87范围内。
结论：造影剂诱导的高血流FFR作为初始评估可能将对腺苷的需求限制在cFFR降至0.84至0.87范围内时。在这项研究中，大多数患者都可能避免使用腺苷输注。

BACKGROUND & AIMS: :The objective indicators which reflect the past results of end-stage knee osteoarthritis (OA) patients who have already received total knee arthroplasty (TKA) could be helpful for physicians to discuss with patients who are considering TKA. The aim of this prospective cohort study was to examine whether we could predict the knee OA patients who would receive TKA in advance based on baseline data, and to set cut-off points for receiving TKA. The two-hundred and forty end-stage medial-type knee OA patients were enrolled and followed up for 6 months while performing therapeutic exercises. Radiographic findings, visual analog scale for pain and a patient-oriented outcome measure, the Japanese Knee Osteoarthritis Measure (JKOM), were recorded at baseline. Relative risks (RRs) using the area under the curve (AUC) for a receiver operating characteristic (ROC) curve were calculated to evaluate several scores for receiving TKA. While 119 patients (55.3 %) did not undergo TKA, the remaining 96 patients (44.7 %) underwent TKA during this period. The AUCs of the ROC curve for the JKOM total score [0.71 (95 % CI 0.64-0.79)] were higher than those for radiographic parameters. Among the JKOM subcategories, JKOM category III, which indicates the condition in daily life, showed the highest AUC of 0.72 (0.65-0.80). The JKOM total score (65/100) and JKOM category III score (17/40) showed RRs of 2.20 (1.33-3.63) and 1.95 (1.18-3.22) for receiving TKA, respectively. The presence of disability in daily living was found to be an important factor determining whether the patient should undergo TKA.

背景与目标： ：客观的指标反映了已经接受全膝关节置换术（TKA）的晚期膝关节骨关节炎（OA）患者的过去结果，可能有助于医生与正在考虑进行TKA的患者进行讨论。这项前瞻性队列研究的目的是检查我们是否可以根据基线数据预测可以提前接受TKA的膝骨OA患者，并设定接受TKA的临界点。入选了240例中晚期膝关节OA患者，并进行了6个月的随访，同时进行了治疗性锻炼。在基线记录影像学发现，疼痛的视觉模拟量表和以患者为导向的结果指标，即日本膝骨关节炎指标（JKOM）。使用接收者操作特征（ROC）曲线的曲线下面积（AUC）计算相对风险（RRs），以评估接收TKA的几个分数。虽然有119名患者（55.3％）没有接受过TKA，但其余96名患者（44.7％）在此期间接受了TKA。 JKOM总分[0.71（95％CI 0.64-0.79）]的ROC曲线的AUC高于射线照相参数的AUC。在JKOM子类别中，指示日常生活状况的JKOM第三类显示最高的AUC为0.72（0.65-0.80）。 JKOM总评分（65/100）和JKOM III类评分（17/40）分别显示接受TKA的RR为2.20（1.33-3.63）和1.95（1.18-3.22）。发现日常生活中是否存在残疾是决定患者是否应该接受TKA的重要因素。

BACKGROUND & AIMS: :This study was designed to measure symptoms, IL-4, IL-5, IFN-gamma, and eosinophilic cationic protein (ECP) in nasal secretions from subjects experiencing an artificial allergy season and to look for evidence of priming. Clinically relevant allergen was administered intranasally out of season to 12 asymptomatic individuals with seasonal allergic rhinitis. These individuals were then randomized to receive allergen or saline daily for the next 7 days. Nasal secretions and scrapings of nasal epithelium were obtained at baseline (day 1), 24 hours after the initial allergen administration (day 2), and 24 hours after the last instillation of allergen or saline (day 9). Nasal symptom scores (p < 0.0002), IL-5 mRNA (p = 0.03), and ECP (p < 0.02) increased after receiving the first challenge (day 2 compared with day 1). In the six subjects randomized to receive seven sequential daily challenges with allergen, symptom scores remained elevated (p < 0.02), IL-5 protein increased (p = 0.02), and IFN-gamma (p = 0.02) levels decreased (day 9 compared with day 1). In the six subjects randomized to receive seven sequential daily challenges with placebo, symptom scores, IL-5, and IFN-gamma levels were not significantly different (day 9 compared with day 1). Compared with the findings at day 2 (n = 12), the treated subjects (n = 6) had no further increase in symptoms but did show a further increase in IL-5 (p = 0.01) and a decrease in IFN-gamma (p = 0.02) at day 9. Daily instillation of moderate doses of allergen intranasally is characterized by persistent symptoms, elevation of IL-5, and reduced levels of IFN-gamma.

背景与目标： ：本研究旨在测量经历了人工过敏季节的受试者的鼻分泌物中的症状，IL-4，IL-5，IFN-γ和嗜酸性阳离子蛋白（ECP），并寻找引发的证据。临床相关的变应原是在季节外鼻内给予12例季节性变应性鼻炎的无症状个体。然后将这些个体随机分组，在接下来的7天中每天接受过敏原或生理盐水。在基线（第1天），首次施用过敏原后24小时（第2天）和最后滴入过敏原或生理盐水后第24天（第9天）获得鼻腔分泌物和鼻上皮的刮痕。接受首次攻击后（第2天与第1天相比），鼻症状评分（p <0.0002），IL-5 mRNA（p = 0.03）和ECP（p <0.02）升高。在随机接受每日两次连续性过敏原挑战的六名受试者中，症状评分保持升高（p <0.02），IL-5蛋白升高（p = 0.02），IFN-γ（p = 0.02）水平降低（与第9天相比与第1天）。在随机接受安慰剂的七个连续每日挑战的六名受试者中，症状评分，IL-5和IFN-γ水平无显着差异（第9天与第1天相比）。与第2天的发现相比（n = 12），接受治疗的受试者（n = 6）的症状没有进一步增加，但确实显示IL-5进一步增加（p = 0.01）和IFN-γ降低（ p = 0.02），在第9天。鼻内每日滴入中等剂量的过敏原的特征是持续的症状，IL-5升高和IFN-γ水平降低。

BACKGROUND & AIMS: :The purpose of this study was to clarify the effects of nutrients on the gonadal development of male rats kept under constant darkness as a model of disturbed daily rhythm. The present study examined protein and vitamins, and their interactions. This study was based on three-way ANOVA; the three factors were lighting conditions, dietary protein and dietary vitamins, respectively. The levels of dietary protein were low or normal: 9% casein or 20% casein. The levels of dietary vitamins were low, normal or high: 1/3.3 of normal (AIN-93G diet) content, normal content, or three times the normal content, respectively. Other compositions were the same as those of the AIN-93G diet, and six kinds of experimental diet were prepared. Four-week-old rats (Fischer 344 strain) were kept under constant darkness or normal lighting (12-h light/dark cycle) for 4 wk. After 4 wk, the gonadal weights and serum testosterone content were evaluated. In the constant darkness groups (D-groups), the low-protein diet induced reduction of gonadal organ weights and serum testosterone concentrations. This reduction of gonadal organ weights was exacerbated by progressively higher levels of dietary vitamins. In the case of a normal-protein diet, the depression of gonadal development was not accelerated by high-vitamin intake. In the normal lighting groups (N-groups), the low-protein and high-vitamin diet slightly depressed gonadal development. These results suggest that the metabolism of protein and vitamins is different in rats being kept under constant darkness, and that excess dietary vitamins have an adverse effect on gonadal development in rats fed a low-protein diet.

背景与目标： ：本研究的目的是阐明养分对处于持续黑暗中的雄性大鼠性腺发育的影响，这是日常节律紊乱的模型。本研究检查了蛋白质和维生素及其相互作用。本研究基于三向方差分析；这三个因素分别是光照条件，饮食蛋白和饮食维生素。膳食蛋白水平低或正常：酪蛋白9％或酪蛋白20％。饮食中维生素的水平低，中或高：分别为正常（AIN-93G饮食）含量的1 / 3.3，正常含量或正常含量的三倍。其他组成与AIN-93G饮食相同，准备了6种实验饮食。将四周大的大鼠（Fischer 344株）保持在恒定的黑暗或正常光照下（12小时光照/黑暗周期）4周。 4周后，评估了性腺的重量和血清睾丸激素的含量。在恒定的黑暗组（D组）中，低蛋白饮食导致性腺器官重量和血清睾丸激素浓度降低。逐渐增加饮食中的维生素水平会加剧性腺器官重量的减少。在正常蛋白质饮食的情况下，高维生素摄入不会促进性腺发育的抑制。在正常照明组（N组）中，低蛋白和高维生素饮食会稍微抑制性腺发育。这些结果表明，在恒定黑暗条件下的大鼠中蛋白质和维生素的代谢不同，并且饮食中过量的维生素对低蛋白质饮食的大鼠的性腺发育有不利影响。

BACKGROUND & AIMS: :This study sought to investigate the relationship between going outdoor daily and prefrontal cortex activation during execution of the VFT using near-infrared spectroscopy (NIRS) in community-dwelling older adults. Blood oxygenation changes in left and right prefrontal cortices were measured in twenty older adults (mean age 76.1 ± 6.7 years) by NIRS during VFT performance. In this task, participants were required to pronounce as many nouns as possible beginning with the letters "Shi," "I," and "Re." Changes in oxygenated hemoglobin (oxy-Hb) levels during the VFT were compared between two groups defined by the frequency of going outdoors: daily or non-daily within a week. Participants in both groups exhibited significantly increased oxy-Hb levels in the left and right prefrontal cortices during the VFT compared to a resting baseline condition. After controlling for age and gender, there were significant group-by-condition interactions on oxy-Hb levels with less activation during the execution of the VFT over both cortices in the non-daily group (left: F=4.76, p=0.04; right: F=6.32, p=0.02). These findings indicate that going outdoors daily is associated with increased activation in the prefrontal cortices during VFT performance in community-dwelling older adults.

背景与目标： ：这项研究旨在调查居住在社区的老年人中，每天进行户外运动与使用近红外光谱（NIRS）进行VFT期间前额叶皮层激活之间的关系。在VFT表现期间，通过NIRS对20名老年人（平均年龄76.1±6.7岁）测量了左前额叶皮层和右前额叶皮层中的血液氧合变化。在此任务中，要求参与者以字母“ Shi”，“ I”和“ Re”开头的尽可能多的名词发音。在VFT期间，比较了两组由户外活动频率定义的两组之间的氧化血红蛋白（oxy-Hb）水平的变化：每天或一周内的非每天一次。与静止的基线状态相比，两组的参与者在VFT期间左，右前额叶皮层的氧合血红蛋白水平均显着升高。在控制了年龄和性别之后，非每日组的两个皮层在执行VFT时，氧合血红蛋白水平存在显着的组间条件交互作用，而激活较少（左：F = 4.76，p = 0.04；右：F = 6.32，p = 0.02）。这些发现表明，在社区居住的老年人中，每天进行户外运动与在VFT表现中前额叶皮层的激活增加有关。

BACKGROUND & AIMS: :Impaired everyday function is a diagnostic criterion for dementia, and a determinant of healthcare utilization and caregiver burden. Although many previous studies have demonstrated a cross-sectional relationship between cognition (particularly executive functions and memory) and everyday function in older adults, very little is known about longitudinal relationships between these domains. This study examined the association between longitudinal change in episodic memory (MEM) and executive functioning (EXEC) and change in everyday function. Participants were a cognitively heterogeneous group of 100 elderly persons including those with normal cognition, as well as those with mild cognitive impairment and dementia. They were followed for an average of 5 years. Random effects modeling showed that change in both MEM and EXEC were independently associated with rate of change in informant-rated instrumental activities of daily living (IADLs), even after controlling for age, education, and gender. Findings indicate that declines in MEM and EXEC over time make unique and independent contributions to declines in older adults' ability to function in daily life.

背景与目标： ：日常功能受损是痴呆症的诊断标准，并且是医疗保健利用率和护理人员负担的决定因素。尽管许多先前的研究已经证明了老年人的认知（特别是执行功能和记忆）与日常功能之间的横断面关系，但对这些领域之间的纵向关系知之甚少。这项研究检查了情节性记忆（MEM）和执行功能（EXEC）的纵向变化与日常功能变化之间的关联。参与者是一个认知异质性的群体，由100名老年人组成，包括那些具有正常认知能力的人，以及那些患有轻度认知障碍和痴呆症的人。他们平均随访了5年。随机效应模型表明，即使在控制了年龄，教育程度和性别之后，MEM和EXEC的变化也与知情者评定的日常工具活动（IADLs）的变化率独立相关。研究结果表明，MEM和EXEC随时间的下降对老年人日常生活功能的下降做出了独特而独立的贡献。

BACKGROUND & AIMS: BACKGROUND:The Daily Mile is designed to increase physical activity levels with children running or walking around school grounds for 15-min daily. It has been adopted by schools worldwide and endorsed as a solution to tackle obesity, despite no robust evidence of its benefits. We conducted a cluster randomised controlled trial to determine its clinical and cost-effectiveness. METHODS:Forty schools were randomly assigned (1:1) to either the Daily Mile intervention or control group in which only the usual school health and wellbeing activities were implemented. The primary outcome was BMI z-score (BMIz) at 12 months follow-up from baseline, with planned subgroup analysis to examine differential effects. Primary economic analysis outcome was incremental cost per Quality-Adjusted-Life-Year (QALY) gained. RESULTS:Using a constrained randomisation approach, balanced on school size, baseline BMIz and proportion of pupils eligible for free school meals, 20 schools were allocated to intervention (n = 1,153 participants) and 20 to control (n = 1,127); 3 schools withdrew (2 intervention, 1 control). At 12 months, BMIz data were available for 18 intervention schools (n = 850) and 19 control schools (n = 820 participants). Using intention-to-treat analysis the adjusted mean difference (MD) in BMIz (intervention - control) was -0.036 (95% CI: -0.085 to 0.013, p = 0.146). Pre-specified subgroup analysis showed a significant interaction with sex (p = 0.001) suggesting a moderate size benefit of The Daily Mile in girls (MD -0.097, 95% CI -0.156 to -0.037). This was consistent with the exploratory economic results that showed The Daily Mile to be highly cost-effective in girls (£2,492 per QALY), but not in boys, and overall to have a 76% chance of cost-effectiveness for the whole sample, at the commonly applied UK threshold of £20,000 per QALY. CONCLUSIONS:Overall the Daily Mile had a small but non-significant effect on BMIz, however, it had a greater effect in girls suggesting that it might be considered as a cost-effective component of a system-wide approach to childhood obesity prevention.

背景与目标： 背景：“每日里程”旨在提高孩子们每天在校园内奔跑或行走15分钟的体育活动水平。尽管没有确凿的证据证明它是肥胖的益处，但它已被全世界的学校所采用，并被认为是解决肥胖的一种解决方案。我们进行了一项集群随机对照试验，以确定其临床和成本效益。
方法：将40所学校随机（1：1）分配给Daily Mile干预组或对照组，其中仅实施常规的学校健康和福祉活动。主要结果是从基线开始的12个月随访中的BMI z评分（BMIz），并计划进行亚组分析以检查差异影响。主要的经济分析结果是每获得的质量调整生命年（QALY）产生的增量成本。
结果：采用约束随机化方法，在学校规模，基线BMIz和有资格获得免费校餐的学生比例之间取得平衡，分配了20所学校进行干预（n intervention = 1,153参与者）和20所学校进行控制（n = 1,127）； 3所学校退出了（2干预，1对照）。在12个月时，可获得18所干预学校（n = 850）和19所对照学校（n = 820参与者）的BMIz数据。使用意向治疗分析，BMIz（干预-对照）的调整后平均差（MD）为-0.036（95％CI：-0.085至0.013，p = 0.146）。预先指定的亚组分析显示与性别之间存在显着相互作用（p = 0.001），表明女孩的“每日里程”有中等大小的益处（MD -0.097，95％CI -0.156至-0.037）。这与探索性的经济结果相吻合，该研究结果显示“每日里程”在女孩中具有很高的成本效益（每QALY为2,492英镑），而在男孩中则不然，总体而言，整个样本具有76％的成本效益机会，在英国，通常每QALY需支付20,000英镑。
结论：总体而言，“每日英里”对BMIz的影响很小，但没有显着影响，但对女孩的BMIz影响更大，表明它可能被认为是全系统预防儿童肥胖症的一种经济有效的方法。

BACKGROUND & AIMS: :We studied daily rhythmicity of body temperature (T(b)) before and during hibernation in Anatolian ground squirrels (Spermophilus xanthoprymnus) under natural and laboratory conditions using surgically implanted temperature loggers. Under both conditions, robust daily T(b) rhythmicity with parameters comparable to those of other ground squirrel species was observed before but not during hibernation. Euthermic animals had robust daily T(b) rhythms with a mean of 37.0 degrees C and a range of excursion of approximately 4 degrees C. No T(b) rhythm was detected during torpor bouts, either because T(b) rhythmicity was absent or because the daily range of excursion was smaller than 0.2 degrees C. The general patterns of hibernation that we observed in Anatolian ground squirrels were similar to those previously observed by other investigators in other species of ground squirrels.

背景与目标： ：我们在自然和实验室条件下，使用外科植入式温度记录仪研究了安纳托利亚松鼠（Spermophilus xanthoprymnus）冬眠前和休眠期间的每日体温节律（T（b））。在这两种情况下，冬眠前（而非冬眠期间）均观察到了具有与其他地松鼠种类相当的参数的稳定的每日T（b）节律。体温正常的动物每天平均有37.0摄氏度的T（b）节律，且偏移范围约为4摄氏度。在打架期间没有检测到T（b）节律，这是因为没有T（b）节律或因为每天的偏移范围小于0.2摄氏度。我们在安纳托利亚地松鼠中观察到的一般冬眠模式与之前在其他种类的地松鼠中的其他研究人员所观察到的冬眠模式相似。

BACKGROUND & AIMS: :Musculoskeletal disorders such as knee osteoarthritis (OA) are the primary cause of chronic pain in older adults. Recommended self-management strategies for knee OA include staying physically active in the face of pain, but many patients avoid activities they are capable of doing. The overall purpose of this study was to examine the extent to which daily pain catastrophizing, a maladaptive coping strategy, could influence OA patients' physical activity and sedentary behavior. The current study used data from 143 older knee OA patients who completed electronic daily diaries for 22 days and wore an accelerometer to capture physical activity and sedentary behavior. At the beginning of each day, patients reported their pain catastrophizing regarding the day ahead. Results from multilevel models demonstrated that on mornings when patients catastrophized more than usual about their pain in the day ahead, they spent more time in sedentary behavior and engaged in fewer minutes of moderate to vigorous physical activity that day. Cross-day lagged analyses further showed that the effect of morning pain catastrophizing on subsequent sedentary behavior extended to the next day. More time spent in sedentary behavior, in turn, contributed to greater pain catastrophizing the next morning. These findings support the mechanistic role of daily pain catastrophizing in the avoidance of physical activity for older OA patients, and suggest that effective interventions for pain catastrophizing may also reduce sedentary behavior and enhance physical activity, with longer-term benefits for pain management, physical function, and overall health.

背景与目标： ：肌肉骨骼疾病，例如膝骨关节炎（OA）是老年人慢性疼痛的主要原因。推荐的膝盖OA自我管理策略包括在面对疼痛时保持身体活动，但许多患者会避免进行自己能做的活动。这项研究的总体目的是研究灾难性的每日疼痛（一种适应不良的应对策略）在多大程度上影响OA患者的身体活动和久坐行为。当前的研究使用了143名年龄较大的膝盖OA患者的数据，这些患者完成了22天的每日电子日记，并佩戴了加速度计来捕捉身体活动和久坐的行为。在每天的开始，患者报告前一天的疼痛是灾难性的。多级模型的结果表明，早晨患者在前一天遭受的痛苦比平常多得多，他们在久坐行为上花费的时间更多，并且当天参加中度到剧烈运动的时间更少。跨日滞后分析进一步表明，早晨疼痛的灾难性后果对随后的久坐行为的影响延续到第二天。反过来，花在久坐行为上的时间更多，则导致第二天早上更大的痛苦成为灾难。这些发现支持了每日疼痛剧烈化在避免老年OA患者身体活动中的机械作用，并表明有效的疼痛剧烈化干预措施还可以减少久坐的行为并增强身体活动，对疼痛管理，身体机能具有长期益处，以及整体健康状况。

BACKGROUND & AIMS: PURPOSE:The aim of this study was to evaluate the extent of the variation in the position of the prostate bed with respect to the bony anatomy. METHODS AND MATERIALS:Four patients were treated to 70 Gy in 35 fractions. Before each fraction, a megavoltage computed tomography (CT) of the prostate bed was obtained, resulting in a total of 140 CT studies. Retrospectively, each CT scan was aligned to the simulation kilovoltage scan based on bony anatomy and the prostate bed. The difference between the 2 alignments was calculated for each scan. RESULTS:The average differences (+/-1 SD) between the two alignments were 0.06+/-0.37, 0.10+/-0.86, and 0.39+/-1.27 mm in the lateral, longitudinal (SI), and vertical (AP) directions, respectively. Laterally, there was no difference>or=3 mm. The cumulative frequency of SI differences were as follows; >or=3 mm: 3%, >or=4 mm: 1%, and >or=5 mm: 1% (maximum: 5 mm). The cumulative frequency of AP differences were as follows; >or=3 mm: 7%, and >or=4 mm: 3% (maximum: 4 mm). CONCLUSION:In patients with prostate cancer receiving postoperative radiotherapy, the prostate bed motion relative to the pelvic bony anatomy is of a relatively small magnitude. Significant motion (>or=3 mm) is infrequent. However, small differences between the prostate bed and the bony anatomy still exist. This might have implications on treatment margins when daily alignment on bony anatomy is performed.

背景与目标： 目的：本研究的目的是评估相对于骨解剖结构的前列腺床位置变化的程度。
方法和材料：四例患者按35份分次接受70 Gy的治疗。在每个部分之前，先获得了前列腺床的兆伏计算机断层扫描（CT），总共进行了140次CT研究。回顾性地，将每个CT扫描与基于骨骼解剖结构和前列腺床的模拟千伏扫描对齐。每次扫描计算两次比对之间的差异。
结果：两次排列之间的横向，纵向（SI）和垂直（AP）方向的平均差异（/ -1 SD）分别为0.06 /-0.37、0.10 /-0.86和0.39 /-1.27 mm。横向上，没有差异>或= 3 mm。 SI差异的累积频率如下： ≥3mm：3％，≥4mm：1％，≥5mm：1％（最大：5mm）。 AP差异的累积频率如下： ≥3mm：7％，≥4mm：3％（最大：4mm）。
结论：在接受术后放疗的前列腺癌患者中，相对于骨盆骨解剖结构而言，前列腺床运动相对较小。很少有明显的运动（>或= 3 mm）。但是，前列腺床和骨解剖结构之间仍然存在微小差异。每天进行骨骼解剖对准时，这可能对治疗余量有影响。

BACKGROUND & AIMS: AIMS:To investigate the effect of adding the short-acting glucagon-like peptide 1 receptor agonist (GLP-1RA) exenatide to insulin treatment on markers of cardiovascular risk in type 1 diabetes. MATERIALS AND METHODS:In a randomized, double-blind, parallel-group trial, 108 individuals with type 1 diabetes aged ≥18 years on multiple daily injection therapy with a body mass index >22.0 kg/m2 and glycated haemoglobin concentration of 59 to 88 mmol/mol (7.5%-10.0%) were randomized (1:1) to preprandial subcutaneous injection of 10 μg exenatide (Byetta®) or placebo three times daily over 26 weeks as add-on treatment to existing insulin therapy. Reported markers of cardiovascular risk were secondary endpoints and were analyzed in a baseline-adjusted linear mixed model in the intention-to-treat population. The primary results of this study, the MAG1C (Meal-time Administration of exenatide for Glycaemic control in type 1 diabetes Cases) trial, were previously reported. RESULTS:Exenatide changed total fat mass by -2.6 kg (95% confidence interval [CI] -3.6; -1.6; P < 0.0001) and lean body mass by -1.1 kg (95% CI -1.9; -0.4; P = 0.01) compared with placebo, as assessed by dual-energy X-ray absorptiometry. Fat mass reductions were similar for central and peripheral fat mass. Exenatide did not change levels of interleukin-2 or -6; tumour necrosis factor-α; C-reactive protein; N-terminal prohormone of brain natriuretic peptide; or 8-oxo-7,8-dihydroguanosine (RNA oxidation marker) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (DNA oxidation marker). CONCLUSIONS:Exenatide added to insulin therapy in type 1 diabetes for 26 weeks resulted in body weight loss primarily from fat mass reduction, but had no effect on biomarkers of cardiovascular disease risk.

背景与目标： 目的：研究在胰岛素治疗中添加短效胰高血糖素样肽1受体激动剂（GLP-1RA）艾塞那肽对1型糖尿病心血管风险标志物的影响。
材料与方法：在一项随机，双盲，平行组试验中，对108名≥18岁的1型糖尿病患者进行了多次每日注射治疗，体重指数> 22.0 kg / m2，糖化血红蛋白浓度为59至88在26周内，每天3次在餐前皮下注射10μg艾塞那肽（Byetta®）或安慰剂，随机（1：1）将mmol / mol（7.5％-10.0％）作为现有胰岛素治疗的补充治疗。报告的心血管风险标志物是次要终点，并在经过意向治疗的人群中进行了基线调整的线性混合模型中进行了分析。该研究的主要结果是MAG1C（艾塞那肽的全日制口服以控制1型糖尿病患者的血糖）试验，此前已有报道。
结果：艾塞那肽使总脂肪量减少-2.6千克（95％置信区间[CI] -3.6; -1.6; P <0.0001），瘦体重减少-1.1千克（95％CI -1.9; -0.4; P = 0.01） ）与安慰剂比较（通过双能X射线吸收法评估）。中央和周围脂肪量的脂肪减少量相似。艾塞那肽未改变白介素2或-6的水平；肿瘤坏死因子-α； C反应蛋白脑利钠肽的N端激素原；或8-oxo-7,8-dihydroguanosine（RNA氧化标记）和8-oxo-7,8-dihydro-2'-deoxyguanosine（DNA氧化标记）。
结论：艾塞那肽在1型糖尿病的胰岛素治疗中使用了26周，导致体重减轻，主要原因是脂肪减少，但对心血管疾病风险的生物标志物没有影响。

BACKGROUND & AIMS: :Objectives: The work interval duration between the end of one workday and the start of the following workday is referred to as the daily rest period (DRP). The present study examined whether DRP - a proxy for sleep opportunity between work shifts - is associated with indicators of sleep debt and social jetlag among daytime workers. Methods: We used a web-based survey to gather data on demographics, average DRP in the previous month, time in bed (TIB), bedtime, wake-up time, and sleep timing on workdays and non-workdays. The Japanese daytime workers (n = 3,914) were divided into seven DRP groups (hours) as follows: <11, 11, 12, 13, 14, 15, and ≥16. Results: The two-way analyses of covariance (DRP group x day) for TIB, mid-sleep as sleep timing, bedtime, and wake-up time showed significant interactions (all p < .001). Specifically, TIB was significantly shorter, and mid-sleep and wake-up time were significantly earlier on workdays than on non-workdays, across all DRP groups (all p < .001). Additionally, the different values for TIB (sleep debt), sleep timing (social jetlag), bedtime, and wake-up time were calculated by subtracting workdays from non-workdays. The trend analysis showed that workers with longer DRP (sleep opportunity) had smaller differences in TIB, sleep timing, and wake-up time between workdays and non-workdays (all p < .001). Conclusions: Overall, daytime workers reported significant sleep debt and misalignment between work and free sleep-wake periods. However, workers with shorter DRPs (less sleep opportunity between shifts) reported significantly greater amounts of sleep debt and social jetlag than did workers with longer DRPs.

背景与目标： 目标：一个工作日结束至下一个工作日开始之间的工作间隔持续时间被称为每日休息时间（DRP）。本研究调查了DRP（工作轮班之间的睡眠机会的代表）是否与白天工作人员的睡眠债务和社会时差指标相关。方法：我们使用基于网络的调查来收集有关人口统计数据，上个月的平均DRP，上床时间（TIB），就寝时间，起床时间以及工作日和非工作日的睡眠时间的数据。日本的日间工作人员（n = 3,914）被分为七个DRP组（小时），分别为：<11、11、12、13、14、15和≥16。结果：对TIB，半睡，睡眠时间，就寝时间和苏醒时间进行协方差（DRP组x天）的双向分析显示出显着的交互作用（所有p <0.001）。具体而言，在所有DRP组中，TIB显着缩短，并且在工作日的半睡眠和唤醒时间比在非工作日显着更早（所有p <0.001）。此外，通过从非工作日中减去工作日来计算TIB（睡眠债务），睡眠时间（社会时差），就寝时间和起床时间的不同值。趋势分析表明，工作日与非工作日之间具有较长DRP（睡眠机会）的工人在TIB，睡眠时间和唤醒时间方面的差异较小（所有p <0.001）。结论：总体而言，日间工作人员报告了严重的睡眠负担，以及工作与自由睡眠-觉醒时间之间的错位。但是，与具有较长DRP的工人相比，具有较短DRP的工人（轮班之间较少的睡眠机会）报告了更多的睡眠债务和社会时差。

BACKGROUND & AIMS: :Many disorders can injure the spinal cord resulting in long-term chronic myelopathy. Spinal cord dysfunction influences the homeostasis of multiple organ systems ranging from the heart or lung to the integument, thus presenting a wide variety of challenges for medical management. Although most of our knowledge about the consequences of myelopathies derives from the study of traumatic spinal cord injuries, similar complications occur in myelopathies of all etiologies. The authors survey some of the important clinical issues that the general neurologist needs to consider in caring for patients with chronic spinal cord disease.

背景与目标： ：许多疾病可能会损伤脊髓，导致长期的慢性脊髓病。脊髓功能障碍会影响从心脏或肺部到皮被的多个器官系统的体内平衡，从而给医疗管理带来了各种各样的挑战。尽管我们对脊髓病的后果的大多数了解来自对脊髓损伤的研究，但在所有病因的脊髓病中都发生了类似的并发症。作者调查了一般神经科医生在照顾慢性脊髓疾病患者时需要考虑的一些重要临床问题。