BACKGROUND & AIMS: Visual optics is taking on new clinical significance. Given that current refractive procedures can and do induce large amounts of higher order ocular aberration that often affects the patient's daily visual function and quality of life, we can no longer relegate the considerations of ocular aberrations to academic discussions. Instead, we need to move toward minimizing (not increasing) the eye's aberrations at the same time we are correcting the eye's spherical and cylindrical refractive error. These are exciting times in refractive surgery, which need to be tempered by the fact that after all the research, clinical, and marketing dust settles, the level to which we improve the quality of the retinal image will be guided by the trade-off between cost and the improvement in the quality of life that refractive surgery offers.

背景与目标： 视觉光学具有新的临床意义。鉴于当前的屈光手术可以并且确实会引起大量的高阶眼像差，这些像差通常会影响患者的日常视觉功能和生活质量，因此我们不能再将眼像差的考虑因素置于学术讨论中。相反，我们需要在校正眼睛的球形和圆柱形屈光不正的同时，朝着最小化 (不增加) 眼睛的像差的方向发展。在屈光手术中，这是激动人心的时刻，需要通过以下事实来缓解: 在所有研究，临床和营销尘埃落定之后，我们提高视网膜图像质量的水平将取决于成本与屈光手术提供的生活质量之间的权衡。

BACKGROUND & AIMS: An important step in the processing of visual patterns is the segmentation of the retinal image. Neuronal responses evoked by the contours of individual objects need to be identified and associated for further joint processing. These grouping operations are based on a number of Gestalt criteria. Here we report that connections in the visual cortex of the cat exhibit a highly significant anisotropy, preferentially linking neurons activated by contours that have similar orientation and are aligned colinearly. These anatomical data suggest a close relation between the perceptual grouping criterion of colinearity and the topology of tangential intracortical connections. We propose that tangential intracortical connections support perceptual grouping by modulating the saliency of distributed cortical responses in a context-dependent way. The present data are compatible with the hypothesis that the criteria for this grouping operation are determined by the architecture of the tangential connections.

背景与目标： 视觉图案处理中的一个重要步骤是视网膜图像的分割。需要识别并关联单个物体轮廓引起的神经元反应，以进行进一步的关节处理。这些分组操作基于许多格式塔标准。在这里，我们报告说，猫的视觉皮层中的连接表现出高度显着的各向异性，优先连接由具有相似方向且对齐的轮廓激活的神经元。这些解剖学数据表明共线性的感知分组标准与切向皮质内连接的拓扑之间存在密切关系。我们建议，切向皮质内连接通过以上下文相关的方式调节分布式皮质反应的显着性来支持感知分组。当前数据与以下假设兼容: 该分组操作的标准由切向连接的体系结构确定。

BACKGROUND & AIMS: :Our objective was to follow the course of a dysmyelinating disease followed by partial recovery in transgenic mice using non-invasive high-resolution (117 x 117 x 70 microm) magnetic resonance (microMRI) and evoked potential of the visual system (VEP) techniques. We used JOE (for J37 golli overexpressing) transgenic mice engineered to overexpress golli J37, a product of the Golli-mbp gene complex, specifically in oligodendrocytes. Individual JOE transgenics and their unaffected siblings were followed from 21 until 75-days-old using non-invasive in vivo VEPs and 3D T2-weighted microMRI on an 11.7 T scanner, performing what we believe is the first longitudinal study of its kind. The microMRI data indicated clear, global hypomyelination during the period of peak myelination (21-42 days), which was partially corrected at later ages (>60 days) in the JOE mice compared to controls. These microMRI data correlated well with [Campagnoni AT (1995) "Molecular biology of myelination". In: Ransom B, Kettenmann H (eds) Neuroglia--a Treatise. Oxford University Press, London, pp 555-570] myelin staining, [Campagnoni AT, Macklin WB (1988) Cellular and molecular aspects of myelin protein gene-expression. Mol Neurobiol 2:41-89] a transient intention tremor during the peak period of myelination, which abated at later ages, and [Lees MB, Brostoff SW (1984) Proteins in myelin. In: Morell (ed) Myelin. Plenum Press, New York and London, pp 197-224] VEPs which all indicated a significant delay of CNS myelin development and persistent hypomyelination in JOE mice. Overall these non-invasive techniques are capable of spatially resolving the increase in myelination in the normally developing and developmentally delayed mouse brain.

背景与目标： : 我们的目标是使用非侵入性高分辨率 (117x70 microm) 磁共振 (microMRI) 和视觉系统诱发电位 (VEP) 技术，跟踪畸形疾病的过程，然后在转基因小鼠中进行部分恢复。我们使用了JOE (用于J37 golli过表达) 转基因小鼠，该小鼠经过工程改造以过表达golli J37，Golli-mbp基因复合物的产物，特别是在少突胶质细胞中。从21天到75天大，在11.7 T扫描仪上使用非侵入性体内vep和3D T2-weighted显微mri跟踪了JOE transgenics及其未受影响的兄弟姐妹，我们认为这是同类研究中的首次纵向研究。microMRI数据表明，在髓鞘形成峰值期间 (21-42天)，明显的整体髓鞘减少，与对照组相比，JOE小鼠在以后的年龄 (>60天) 得到了部分纠正。这些显微mri数据与 [Campagnoni在 (1995) “髓鞘形成的分子生物学” 处具有很好的相关性。In: Ransom B，Kettenmann H (eds) 神经胶质-一篇论文。牛津大学出版社，伦敦，pp 555-570] 髓磷脂染色，[Campagnoni AT，macklin WB (1988) 髓鞘蛋白基因表达的细胞和分子方面。Mol Neurobiol 2:41-89] 在髓鞘形成的高峰期短暂的意图震颤，在以后的年龄减弱，并且 [Lees MB，Brostoff SW (1984) 蛋白在髓鞘中: morell (ed) 髓鞘。纽约和伦敦的Plenum出版社，pp 197-224] VEPs，所有这些都表明乔小鼠中枢神经系统髓鞘发育和持续的低髓鞘作用显着延迟。总体而言，这些非侵入性技术能够在空间上解决正常发育和发育延迟的小鼠大脑中髓鞘形成的增加。

BACKGROUND & AIMS: OBJECTIVE:The authors' goal was to test the hypothesis that the antidepressant effect of total sleep deprivation can be maintained by initially avoiding sleep during a supposedly "critical" time period in the early morning.

METHOD:They studied 33 inpatients with major depression, melancholic type, all of whom responded positively to total sleep deprivation. Twelve of the patients were men and 21 were women; their mean age was 46.7 years (SD = 13.7). After total sleep deprivation, the patients started a sleep schedule from 5:00 p.m. to 12:00 midnight, which then was shifted back by 1 hour each day until a sleep time of 11:00 p.m. to 6:00 a.m. was reached.

RESULTS:Twenty (61%) of the 33 patients who responded to total sleep deprivation with an improved state of mood maintained this improvement during sleep phase advance therapy. Drug-free and medicated patients did not differ from each other.

CONCLUSIONS:The rapid amelioration of mood observed with total sleep deprivation can be preserved with a succeeding phase shift of the sleep period.

背景与目标： 目的 : 作者的目标是检验以下假设: 完全睡眠剥夺的抗抑郁作用可以通过最初在清晨的一个所谓的 “关键” 时期避免睡眠来维持。
方法 : 他们研究了33名患有抑郁症，忧郁型的住院患者，他们都对完全睡眠不足有积极的反应。12名患者为男性，21名患者为女性; 他们的平均年龄为46.7岁 (SD = 13.7)。完全睡眠剥夺后，患者开始从下午5:00到午夜12:00的睡眠计划，然后每天向后转移1小时，直到达到下午11:00上午6:00的睡眠时间。
结果 : 33名对完全睡眠剥夺有改善的情绪状态有反应的患者中有20名 (61% 名) 在睡眠阶段提前治疗期间保持了这种改善。无药物和药物治疗的患者彼此之间没有差异。
结论 : 完全睡眠剥夺所观察到的情绪迅速改善可以通过睡眠期的后续相移来保持。

BACKGROUND & AIMS: :Retrospective analysis of a selected sample of children who presented with convergent squint has shown that abnormal meridional hypermetropia (3.5 D or more) at age 1 was the principal factor associated with severe amblyopia (6/24 or less) remaining after conventional treatment. Neither the reported age of onset nor delay in presentation influenced the final visual outcome.

背景与目标： 对选定的患有会聚斜视的儿童样本的回顾性分析表明，在1岁时出现的异常经络远视 (3.5 D或以上) 是与常规治疗后仍然存在的严重弱视 (6/24或以下) 相关的主要因素。报告的发病年龄和出现延迟都不会影响最终的视觉结果。

BACKGROUND & AIMS: :Diagnostic accuracy for radiologists is above that expected by chance when they are exposed to a chest radiograph for only one-fifth of a second, a period too brief for more than a single voluntary eye movement. How do radiologists glean information from a first glance at an image? It is thought that this expert impression of the gestalt of an image is related to the everyday, immediate visual understanding of the gist of a scene. Several high-speed mechanisms guide our search of complex images. Guidance by basic features (such as color) requires no learning, whereas guidance by complex scene properties is learned. It is probable that both hardwired guidance by basic features and learned guidance by scene structure become part of radiologists' expertise. Search in scenes may be best explained by a two-pathway model: Object recognition is performed via a selective pathway in which candidate targets must be individually selected for recognition. A second, nonselective pathway extracts information from global or statistical information without selecting specific objects. An appreciation of the role of nonselective processing may be particularly useful for understanding what separates novice from expert radiologists and could help establish new methods of physician training based on medical image perception.

背景与目标： : 放射科医生的诊断准确性高于偶然的预期，当他们仅暴露于胸片5分之1秒时，这一时期太短暂，无法进行一次自愿的眼球运动。放射科医生如何从图像的第一眼就收集信息？人们认为，对图像完形的这种专家印象与对场景要点的日常，即时视觉理解有关。几种高速机制指导我们搜索复杂的图像。基本特征 (例如颜色) 的指导不需要学习，而复杂场景属性的指导是学习的。基本特征的硬连线指导和场景结构的学习指导都可能成为放射科医生专业知识的一部分。场景中的搜索可以通过两途径模型来最好地解释: 对象识别是通过选择性途径执行的，在该途径中，必须单独选择候选目标进行识别。第二种非选择性途径从全局或统计信息中提取信息，而无需选择特定对象。了解非选择性处理的作用对于了解新手与专业放射科医生之间的区别可能特别有用，并且可以帮助建立基于医学图像感知的医师培训新方法。

BACKGROUND & AIMS: This paper reports on the application of an artificial neural network to the clinical analysis of ophthalmological data. In particular a 2-dimensional Kohonen self-organising feature map (SOM) is used to analyse visual field data from glaucoma patients. Importantly, the paper addresses the problem of how the SOM can be utilised to accommodate the noise within the data. This is a particularly important problem within longitudinal assessment, where detecting significant change is the crux of the problem in clinical diagnosis. Data from 737 glaucomatous visual field records (Humphrey Visual Field Analyzer, program 24-2) are used to train a SOM with 25 nodes organised on a square grid. The SOM clusters the data organising the output map such that fields with early and advanced loss are at extreme positions, with a continuum of change in place and extent of loss represented by the intervening nodes. For each SOM node 100 variants, generated by a computer simulation modelling the variability that might be expected in a glaucomatous eye, are also classified by the network to establish the extent of noise upon classification. Field change is then measured with respect to classification of a subsequent field, outside the area defined by the original field and its variants. The significant contribution of this paper is that the spatial analysis of the field data, which is provided by the SOM, has been augmented with noise analysis enhancing the visual representation of longitudinal data and enabling quantification of significant class change.

背景与目标： 本文报告了人工神经网络在眼科数据临床分析中的应用。特别是二维Kohonen自组织特征图 (SOM) 用于分析青光眼患者的视野数据。重要的是，本文解决了如何利用SOM来容纳数据中的噪声的问题。在纵向评估中，这是一个特别重要的问题，在纵向评估中，检测出明显的变化是临床诊断问题的关键。来自737青光眼视野记录 (Humphrey视野分析仪，程序24-2) 的数据用于训练具有25个节点的SOM在方形网格上。SOM对组织输出图的数据进行聚类，以使具有早期和高级损失的字段处于极端位置，并且由中间节点表示连续的变化和损失程度。对于每个SOM节点100变体，由对青光眼眼中可能预期的可变性建模的计算机模拟生成，也由网络分类以建立分类时的噪声程度。然后，针对原始字段及其变体定义的区域之外的后续字段的分类来测量字段变化。本文的重要贡献在于，由SOM提供的现场数据的空间分析已通过噪声分析得到了增强，从而增强了纵向数据的视觉表示并能够量化重大的类别变化。

BACKGROUND & AIMS: OBJECTIVES:To examine associations between sleep duration and health outcomes among distinct groups of sexual minority adults. METHODS:Using data from the 2014 Behavioral Risk Factor Surveillance System, we compared sleep duration (very short: ≤ 5 hr; short: 6 hr; normal: 7-8 hr; and long: ≥ 9 hr per day) between cisgender straight adults and distinct groups of sexual minorities. We further examined associations between sleep duration and 10 chronic health conditions among sexual minorities. RESULTS:Of 146,893 respondents, 142,507 (96.2%) were cisgender straight, and 4,386 (3.8%) were lesbian, gay, bisexual, transgender (LGBT). Overall, 17.3% of LGBT respondents reported very short sleep per day, compared with 12.2% for cisgender straight respondents (p < 0.0001). Among LGBT populations, the prevalence of very short sleep varied significantly among distinct groups, ranging from 13.2% among transgender female to male adults to 35.5% among transgender gender nonconforming adults. Very short sleep was further associated with increased odds of having stroke (aOR = 4.1, 95% CI [2.2-7.6]), heart attack (aOR = 3.0, CI [1.6-5.8]), coronary heart disease (aOR = 3.1, 95% CI [1.5-6.2]), asthma (aOR = 1.7, 95% CI [1.1-2.4]), chronic obstructive pulmonary disease (aOR = 2.5, CI [1.5-4.0]), arthritis (aOR = 2.1, CI [1.4-3.0]), and cancer (aOR = 1.8, 95% CI [1.0-3.2]) among sexual minorities. Disparities in the prevalence of stroke, heart attack, coronary health disease, COPD, diabetes, obesity, arthritis, and cancer were found among LGBT populations. CONCLUSIONS:Sexual minorities have a higher prevalence of sleep deprivation as compared with their straight counterparts. Sleep deprivation varies by sexual identity and gender. Very short sleep duration is associated with some chronic health conditions among LGBT populations. Promotion of sleep health education and routine medical assessment of sleep disorders are critically needed for sexual minority adults.

背景与目标：

BACKGROUND & AIMS: :Atomoxetine improves inhibitory control and visual processing in healthy volunteers and adults with attention-deficit/hyperactivity disorder (ADHD). However, little is known about the neural correlates of these two functions after chronic treatment with atomoxetine. This study aimed to use the counting Stroop task with functional magnetic resonance imaging (fMRI) and the Cambridge Neuropsychological Test Automated Battery (CANTAB) to investigate the changes related to inhibitory control and visual processing in adults with ADHD. This study is an 8-week, placebo-controlled, double-blind, randomized clinical trial of atomoxetine in 24 drug-naïve adults with ADHD. We investigated the changes of treatment with atomoxetine compared to placebo-treated counterparts using the counting Stroop fMRI and two CANTAB tests: rapid visual information processing (RVP) for inhibitory control and delayed matching to sample (DMS) for visual processing. Atomoxetine decreased activations in the right inferior frontal gyrus and anterior cingulate cortex, which were correlated with the improvement in inhibitory control assessed by the RVP. Also, atomoxetine increased activation in the left precuneus, which was correlated with the improvement in the mean latency of correct responses assessed by the DMS. Moreover, anterior cingulate activation in the pre-treatment was able to predict the improvements of clinical symptoms. Treatment with atomoxetine may improve inhibitory control to suppress interference and may enhance the visual processing to process numbers. In addition, the anterior cingulate cortex might play an important role as a biological marker for the treatment effectiveness of atomoxetine. Hum Brain Mapp 38:4850-4864, 2017. © 2017 Wiley Periodicals, Inc.

背景与目标： : 阿托莫西汀改善健康志愿者和患有注意力缺陷/多动障碍 (ADHD) 的成年人的抑制控制和视觉处理。然而，对于长期使用阿托莫西汀治疗后这两种功能的神经相关性知之甚少。这项研究旨在使用功能磁共振成像 (fMRI) 和剑桥神经心理测试自动电池 (CANTAB) 的计数Stroop任务来研究ADHD成人与抑制性控制和视觉处理相关的变化。这项研究是一项为期8周，安慰剂对照，双盲，随机临床试验的阿托莫西汀在24名未用药的ADHD成人中进行的试验。我们使用Stroop fMRI计数和两种CANTAB测试研究了与安慰剂治疗的对应物相比，托莫西汀治疗的变化: 用于抑制控制的快速视觉信息处理 (RVP) 和用于视觉处理的延迟匹配 (DMS)。阿托莫西汀降低了右下额回和前扣带回皮层的激活，这与RVP评估的抑制性控制的改善有关。此外，阿托莫西汀增加了左前肌的激活，这与DMS评估的正确反应的平均潜伏期的改善有关。此外，治疗前的扣带回激活能够预测临床症状的改善。用阿托莫西汀治疗可以改善抑制控制以抑制干扰，并可以增强视觉处理以处理数字。此外，前扣带回皮层可能是阿托莫西汀治疗效果的生物学标记。Hum Brain Mapp 38:4850-4864，2017。©2017威利期刊公司

BACKGROUND & AIMS: :The hierarchical development of the primate visual cortex and associated streams remains somewhat of a mystery. While anatomical, physiological, and psychological studies have demonstrated the early maturation of the dorsal "where"/"how" or motion cortical stream, little is known about the circuitry responsible. The influence of the retinogeniculostriate pathway has been investigated, but little attention has been paid to the role of two more recently described disynaptic retinothalamic projections to the middle temporal (MT) area, an early maturing dorsal stream cortical field, and which bypass the primary visual cortex (V1). These pathways are via the koniocellular layers of the lateral geniculate nucleus (LGN) and the medial portion of the inferior pulvinar (PIm). Both have been demonstrated in the adult nonhuman primate, but their influence during the maturation of the visual cortex is unknown. We used a combination of neural tracing and immunohistochemistry to follow the development of LGN and PIm inputs to area MT in the marmoset monkey. Our results revealed that the early maturation of area MT is likely due to the disynaptic retinopulvinar input and not the retinogeniculate input or the direct projection from V1. Furthermore, from soon after birth to adulthood, there was a dynamic shift in the ratio of input from these three structures to area MT, with an increasing dominance of the direct V1 afference.

背景与目标： : 灵长类视觉皮层和相关流的分层发展仍然是一个谜。尽管解剖学，生理学和心理学研究表明背侧 “where”/“how” 或运动皮质流的早期成熟，但对负责的电路知之甚少。已经研究了视网膜原肌纹状体途径的影响，但很少关注两个最近描述的双突触视网膜丘脑投射对中颞 (MT) 区域的作用，即早熟的背流皮层场，并且绕过了初级视觉皮层 (V1)。这些途径是通过外侧膝状核 (LGN) 和下牙髓 (PIm) 的内侧部分的细胞层。两者都已在成年非人类灵长类动物中得到证实，但它们在视觉皮层成熟过程中的影响尚不清楚。我们使用神经追踪和免疫组织化学的组合来跟踪LGN和PIm输入到mar猴中MT区域的发育。我们的结果表明，区域MT的早期成熟可能是由于非突触视网膜的输入，而不是视网膜的输入或来自v1的直接投影。此外，从出生后不久到成年，这三个结构的输入与区域MT的比率发生了动态变化，直接V1传入的优势越来越大。

BACKGROUND & AIMS: BACKGROUND:Extension of cavernous sinus meningiomas can compromise vision by compressing the optic nerves and chiasm. Surgical tumour removal aims to protect vision in the long-term. However, the risks of surgery include transient or permanent damage to the anterior visual pathways. This study aims to 1) analyse the visual status in unilateral cavernous sinus meningioma with extra-cavernous extension, before and after removal of the extra-cavernous portion, without any adjuvant treatment with radiotherapy, 2) identify pre-surgical and early post-surgical prognostic factors for long-term visual outcome and 3) compare these results to previous studies. METHODS:This is a retrospective study of 30 consecutive patients who underwent surgery between 1989 and 2004. Visual acuity, visual fields, and fundi were evaluated before surgery and during the mean follow-up period of 2 years. FINDINGS:Total visual loss occurred in the ipsilateral eye following surgery in 10% of patients. There was improvement in vision in 23%, no significant change in 27% and worsening in 50% of patients. Pre-surgical visual acuity was not predictive of final visual outcome, but initial optic disc pallor was a poor prognostic factor. In pre-operatively normal contralateral eyes, 10% developed a mild visual deficit (visual acuity = 20/32 or better, and visual field defect

BACKGROUND & AIMS: :Continuous observations of larvae of the silkworm, Bombyx mori, revealed that feeding occurred at regular intervals throughout larval development. To investigate possible factors influencing meal-timing, the behaviours of diet-deprived Bombyx larvae were also analysed. Diet-deprivation resulted in longer durations of the first meals after diet replacement, but did not affect feeding patterns. Furthermore, long-term diet-deprivation promoted wandering behaviour and a consequent delay in feeding after diet replacement. Under diet-deprivation conditions, meal-starts appeared to be inducible by defecation and physical stimulation. However, stimulation-induced meal-starts were dependent on the time elapsed since the larvae's previous meals. Provided that more than 1h had elapsed since their previous meals, larvae could be induced to feed by defecation and tapping. At less than 1h post-meal, larvae were less likely to begin feeding after defecation or physical stimulation. Activated locomotions such as wandering and feeding were observed in the long-term diet-deprived larvae only after diet blocks were replaced, while long-term diet-deprived larvae did not show activated locomotion during the absence of diet blocks. Collectively, these data suggest that a combination of elevated locomotion activity and the presence of diet may be necessary for the initiation of feeding in diet-deprived larvae.

背景与目标： : 对家蚕幼虫的连续观察表明，在整个幼虫发育过程中，有规律地进食。为了研究影响进餐时间的可能因素，还分析了饮食剥夺的家蚕幼虫的行为。饮食剥夺导致饮食替代后第一餐的持续时间更长，但不影响喂养方式。此外，长期的饮食剥夺会促进流浪行为，并在饮食替代后导致进食延迟。在饮食剥夺条件下，排便和身体刺激似乎可以诱导进餐。但是，刺激引起的进餐取决于幼虫以前进餐以来的时间。只要自以前进餐以来已经过了1小时以上，就可以通过排便和拍打来诱导幼虫进食。饭后不到1小时，排便或身体刺激后，幼虫开始进食的可能性较小。仅在更换饮食块后，在长期饮食剥夺的幼虫中观察到活跃的运动，例如游荡和进食，而长期饮食剥夺的幼虫在没有饮食块的情况下没有表现出活跃的运动。总的来说，这些数据表明，增加的运动活动和饮食的存在可能是在缺乏饮食的幼虫中开始进食所必需的。

BACKGROUND & AIMS: :We present a method for assessing visual neglect using oculography, the "midpoint-fixation" task. In the test, patients showed rightward deviation of the fixation point. Pure bias in visual neglect was considered to be assessed well by this method. Newly designed stimuli that lead to stable fixation and an effective calibration procedure are proposed. The method is suggested as useful in the assessment of visual neglect.

背景与目标： : 我们提出了一种使用眼术评估视觉疏忽的方法，即 “中点固定” 任务。在测试中，患者显示固定点向右偏离。这种方法认为可以很好地评估视觉忽视中的纯偏见。提出了新设计的刺激，可导致稳定的固定和有效的校准程序。建议该方法可用于评估视觉疏忽。

BACKGROUND & AIMS: :Interferons are used in the therapy of multiple sclerosis, Kaposi's sarcoma, hepatitis and melanoma. Their short half-life that requires frequent injections can be increased by polyethylene glycol (PEG) modification. A 50-year-old patient was diagnosed as having an acrolentiginous melanoma (Breslow >5 mm, Clark level IV) and inguinal lymph node metastases. After surgical excision and lymphadenectomy, immune therapy with 6.0 microg pegylated interferon alpha(2b)/kg body weight, s.c., was started. Cutaneous ulcerations at the injection sites developed 9 months after treatment initiation. The patient also developed blurred vision and presented with binasal scotomas and pathological visually evoked potentials and electroretinogram. The cutaneous ulcerations slowly healed under local therapy and reduction of the concentration of the PEG-modified interferon from 0.86 to 0.43 mg/ml. The dosage was maintained. Two months later, the therapy was stopped due to disease progression. Vision subsequently recovered. Cutaneous reactions evolved at the sites of subcutaneous injections of PEG-modified interferon alpha(2b). Changes in vision can probably be attributed to immunotherapy.

背景与目标： : 干扰素用于治疗多发性硬化症，卡波西氏肉瘤，肝炎和黑色素瘤。需要频繁注射的短半衰期可以通过聚乙二醇 (PEG) 改性来增加。一名50岁的患者被诊断为患有A性黑色素瘤 (Breslow> 5毫米，Clark IV级) 和腹股沟淋巴结转移。在手术切除和淋巴结切除术后，开始使用6.0 microg聚乙二醇化干扰素 α (2b)/kg体重，s.C.进行免疫治疗。治疗开始后9个月，注射部位出现皮肤溃疡。患者还出现了视力模糊，并出现了双耳暗点和病理性视觉诱发电位和视网膜电图。在局部治疗和PEG修饰的干扰素浓度从0.86降低到0.43 mg/ml的情况下，皮肤溃疡缓慢愈合。维持剂量。两个月后，由于疾病进展，治疗停止。视力随后恢复。皮肤反应在皮下注射PEG修饰的干扰素 α (2b) 的部位发生。视力的变化可能归因于免疫疗法。

BACKGROUND & AIMS: :Biotin deficiency (Bt-D) is usually studied at the point at which the animal model exhibits the signs of full-blown deficiency symptoms; in rats, this typically occurs at 6-8 weeks of feeding a deficient diet. To differentiate specific deficiency effects from those of undernutrition, biotin sufficient and deficient rats were studied at 2, 3, 4, and 5 weeks on the deficiency diet, before the onset of weight loss and deficiency signs. The deficiency state was confirmed by biochemical and molecular analyses. Blood and liver metabolites were determined and western blots of signaling proteins, and qRT-PCR gene expression studies. The main effects of Bt-D were already well established by the fourth week on the diet; thus, we consider the fourth week as the optimum time to study the consequences of biotin depletion. Early effects, which were already apparent at week 2, included cellular energy deficit (as assessed by increased AMP/ATP ratio), activation of the AMPK energy sensor, and changes of carbon metabolism gene transcripts (e.g., phosphoenolpyruvate carboxykinase, carnitine palmitoyl transferase 1, liver glucokinase and fatty acid synthetase). Reduced post-prandial blood concentrations of glucose were also observed early; we speculate that these are attributable to augmented sensitivity to insulin and increased glucose utilization, a likely effect of AMPK induction of translocation of glucose transporter GLUT4 to the cell membranes and increased hexokinase expression. Other late-onset changes (week 4) included increased serum concentrations of lactate and free fatty acids and decreased liver glycogen and serum concentrations of triglycerides and total cholesterol. The identification of the early specific molecular and metabolic disturbances of biotin deficiency might be useful in identifying individuals with marginal deficiency of this vitamin, which appears to be common in normal human pregnancy. The study of time-course of other vitamin deficiencies, such as this one, might help to better understand and cope with their effects.

背景与目标： : 生物素缺乏症 (bt-d) 通常在动物模型表现出完全缺乏症状的迹象时进行研究; 在大鼠中，这通常发生在喂养缺乏饮食的6-8周时。为了区分特定的缺乏症影响与营养不良的影响，在体重减轻和缺乏症状开始之前，在缺乏饮食的第2、3、4和5周研究了生物素充足和缺乏的大鼠。通过生化和分子分析证实了缺陷状态。测定了血液和肝脏代谢产物，并对信号蛋白进行了western印迹，并进行了qRT-PCR基因表达研究。到第四周，bt-d的主要作用已经在饮食上得到很好的确立; 因此，我们认为第四周是研究生物素耗竭后果的最佳时间。早期影响 (在第2周已经很明显) 包括细胞能量不足 (通过增加AMP/ATP比率评估)，AMPK能量传感器的激活以及碳代谢基因转录本的变化 (例如，磷酸烯醇丙酮酸羧激酶，肉碱棕榈酰转移酶1，肝葡萄糖激酶和脂肪酸合成酶)。早期还观察到餐后血糖浓度降低; 我们推测这些归因于对胰岛素的敏感性增强和葡萄糖利用率增加，AMPK诱导葡萄糖转运蛋白GLUT4转运至细胞膜的可能作用以及己糖激酶表达增加。其他迟发性变化 (第4周) 包括乳酸和游离脂肪酸的血清浓度增加，肝糖原和甘油三酸酯和总胆固醇的血清浓度降低。鉴定生物素缺乏的早期特定分子和代谢紊乱可能有助于鉴定这种维生素的边缘缺乏的个体，这在正常人的怀孕中很常见。对其他维生素缺乏症 (例如这一种) 的时间过程的研究可能有助于更好地理解和应对其影响。