We greatly appreciate the contributions of our expert anthropometry trainers Irwin Shorr and Jorge Chavarro; the many volunteers who have allowed themselves to be pinched and measured in our anthropometry workshops, and the Project Viva mothers and children for their invaluable contributions. We'd like to extend a special thanks to members of the Project Viva research staff, past and present, especially to Nicole Witham and Marleny Ortega, for their contribution to the video accompanying this manuscript. Funding from the National Institutes of Health supported this work (R01 HD 034568, K24 HD069408).

所有的程序是由哈佛朝圣者医疗保健机构审查委员会批准。 1.培训过程<ol><li>有学员（研究助理）完成多日，多小时的培训学习正确定位，观看培训视频，并从经验丰富的auxologist接受现场培训。 <ol><li>指导学员练习对方进行测量，而一个auxologist或居民人体测量学专家评估每个学员的技术，使适当的调整。 </li><li>举办一次研讨会与外部志愿者的最佳各种年龄和体型，理想情况下，研究人群的代表性样本。有学员测量每个志愿者至少每次测量两次。 </li></ol></li><li>完成培训计划后，有学员花大约一个额外的40 - 50 H练人体测量手册彼此和志愿者技巧。在此期间，观察学员，监督遵守协议和适当的技术。给每个学员的基础上先天的技术水平和以往的经验培训所需的量。 </li></ol> 2.主题的制备<ol><li>指导参与者穿着轻便的衣服，这样可以方便的四肢和躯干，同时保持谦虚，最好是通过科研人员提供的标准装备。 </li></ol> 3.高度<ol><li>通过构建良好的测距仪，可以是壁挂式或便携式测量高度。无论哪种方式，进行测量，同时确保测距仪设置靠墙放置在坚硬，平坦的表面上。 注：在2岁以下的儿童，测量身长，而不是站在高处。身长测量需要不同的程序8，在这个协议不细致。 </li><li>一个SK参与者，踩着测距仪之前，以消除可能妨碍测量的任何项目。例如，鞋，厚袜子，帽子和发饰（ 如帽子，头巾，在头顶的发箍）。 </li><li>引导与会者返回到电路板上，直到参与者的臀部，肩胛骨，或者后脑勺与板接触。 </li><li>而面对参与者，指导参与者站在板分开约2英尺的脚。请参与者他/她的双腿慢慢英寸背在一起，直到双腿，中大腿，膝盖，或脚进行接触。 </li><li>指示参与者尽可能直站立，不懒散或倾斜。确保双脚平放在高度板或地板的底部，两臂下垂的参与者的两侧。确认重量身体的左侧和右侧之间是均匀分布的。 </li><li>直观地验证了腋中线是垂直于地面。指示参与者从测距仪背面移开他/她的脚，如果要达到这个位置。 注：腋中线是在腋前线和腋后线之间的冠状面中间的假想线，向下穿过髂嵴（ 图1）的最优越的部分，从腋下的中心延伸。 </li></ol><img alt="图1" src="/files/ftp_upload/54895/54895fig1.jpg" /> 图1： 在腋中线的位置。冠向中间线的前部和腋后纹15之间。 <a href="http://ecsource.jove.com/files/ftp_upload/54895/54895fig1large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <ol start="7"><li>请参与者站直。确保一种或多种的<html>以下的身体部位，使与测距仪的背面接触：脚，头，肩或臀部。 </li><li>放置参与者的头进法兰克福平面（ 图2）。 <ol><li>通过执行以下操作确定法兰克福平面：纵观参与者的头部的一侧，在耳道开幕借鉴了眼眶的最低保证金的假想线最高的利润率。使假想线是平行于地面并垂直于测距仪的头位置。 </li></ol></li></ol><img alt="图2" src="/files/ftp_upload/54895/54895fig2.jpg" /> 图 2： 法兰克福平面。穿过轨道的下缘和所述tragion（缺口耳朵的耳屏上）经过一个水平平面 16。4895fig2large.jpg“目标=”_空白“&gt;点击此处查看该图的放大版本。 <ol start="9"><li>提醒参与者站在高大挺拔，以及头盔上他/她的头以足够的压力之上坚定立场压缩头发和化妆与颅骨接触。随着在视线水平的头盔，进行测量一厘米的最近的十分之一。 </li></ol> 4.坐高<ol><li>放置在一个坚固的凳子足够高以允许参加者的腿，以形成一个90°的角度与地面的顶部的测距仪。或者，如果测距仪是壁挂式，放置已知高度的粪便中的测距仪的前面。 </li><li>请参与者坐在测距仪或凳子上的顶部，这样的臀部接触电路板的背面。 </li><li>有与会者坐在尽可能直立，臀部有，肩膀和/或头部接触电路板的背面。确保中期axill进制线（如在3.6中描述）是垂直于粪便并平行于测距仪。 </li><li>直接引导参与者的膝盖在他/她的身体面前，把他/她的手放在大腿上。 </li><li>参与者的头部放置到法兰克福平面。参照3.8。 </li><li>在头盔上的参与者的头部具有足够的压力之上坚定立场压缩头发和化妆与颅骨接触。 </li><li>虽然直接面对与眼睛水平的头盔测量指标，采取测量一厘米的最近的十分之一。 </li></ol> 5.重量<ol><li>指示参与者要么穿轻便服装，或在人体测量的发作提供的制式服装，空他/她的膀胱，并试图体重测量之前删除他/她的鞋。 </li><li>请参与者，站在规模。记录测量到一公斤的最近的十分之一。 </li></ol> 6.腰围<ol><li>指导参与者挺身直立，仍然和横向在椅子上，最好在镜子前面。坐在对着镜子，与眼睛水平参与者的右侧或左侧髋骨。指导参与者过他/她的手臂在眼前，而他举起了他/她的衬衫。 </li><li>坐在到与会者的一侧，定位髋骨，这通常是最容易通过致密脂肪组织所确定的髋骨的部分的前部。向上触诊沿胯骨定位髂嵴，髋骨的优越脊。继续触诊髂嵴直到到达髂嵴的最上点和腋中线的交点（参照第3.6节来定位腋中线）。识别网站与自粘贴纸。 </li><li>对参加者的身体的另一侧重复6.2。 </li><li>虽然参与者站在垂直于镜，轻轻地放在围绕腰部的卷尺上的两个贴纸与下面的卷尺的零侧（或碱）的顶部。使用反射镜作为引导，调节带，使得它在一个水平，在整个前水平面，背面和两侧上。 </li><li>拧紧带，不提拉肌肤。由于这是一个微妙的平衡，开始与卷尺稍微捏肌肤。然后缓慢地松开卷尺，以形成沿皮肤光滑线，从而使皮肤不再收缩。放置卷尺牢牢皮肤无收紧参与者的腰部，从而有在卷尺也不夹住皮肤既不间隙。 </li><li>在参加者的自然呼气结束，读出的磁带一厘米的最接近的十分之一。 注：这一测量反射镜或两个研究助理的情况下最有效地进行。一位研究人员，独自一人，无法观察各方的卷尺妥善安置体。镜子和/或其它工作人员补偿受阻的地方，适当的通知卷尺位置。 </li></ol> 7.臀围<ol><li>指导参与者旁边屹立在椅子上，垂直镜像。请参与者折叠他/她的手臂在身体的前面与压在一起的脚。 </li><li>坐到与会者的一侧和面对反射镜，从而使眼睛是与会者的臀部水平。 </li><li>将周围的臀部过轻便，紧战斗服装卷尺。锚卷尺在臀部的最大突起。调整带，使得它在身体周围的水平面。握住卷尺牢固。同样的腰围，收紧卷尺，使皮肤夹住。松开卷尺慢慢地，直到有卷尺周围流畅的线条。 </li><li>拿着卷尺坚决和断然，阅读措施<html>换货到厘米的最近的十分之一。 </li></ol> 8.上臂围（MUAC） <ol><li>指导参与者解除他/她的袖子到肩的高度，以确保测量直接在皮肤上进行的。而参与者站立，因此这是在用手掌朝上和指尖指向正前方的弯头以90°角弯曲位置他/她的右臂。 </li><li>站在后面的参与者。找到后外侧肩胛骨连接参与者的肩胛骨和锁骨（ 图3）。这种骨骼结构，被称为肩峰过程中，将作为在卷尺初始点零。 </li></ol><img alt="图3" src="/files/ftp_upload/54895/54895fig3.jpg" /> 图3： 肩部的解剖。肩部解剖包括肩峰过程中，红色标识屁股=“外部参照”&gt; 17。 <a href="http://ecsource.jove.com/files/ftp_upload/54895/54895fig3large.jpg" target="_blank">请点击此处查看该图的放大版本。</a> <ol start="3"><li>延长磁带走在臂的后面的中线，过去的弯头，称为鹰嘴的骨小费。使用磁带测量一厘米的最近的十分之一肩峰过程和鹰嘴之间的距离和鹰嘴和在幽默的后部中心肩峰过程之间自粘贴纸中途放置。 </li><li>按住参与者的手臂从身体稍远一点，以确保肌肉是放松的。 </li><li>站在右边，稍微落后的参与者，包裹MUAC磁带（小，翻转磁带）在上臂，以便它涵盖了自不干胶。确保该卷尺垂直于臂的长度。 </li><li>所以，有在磁带没有间隙或皮肤收缩的区域拉带。与臀部和臂周长，这是一个良好的平衡。使用更大的张力，直到有捏皮肤没有进一步的领域慢慢松开磁带。 </li><li>读取测量和记录一厘米的最近的十分之一。 </li></ol> 9.三头肌皮褶厚度<ol><li>使用标签放置在参与者的手臂的后中点（如步骤8.1确定 - 8.3）。指示参与者挺立，双肩放松，双臂垂松散。 </li><li>站在参与者背后，确定在上臂中点贴纸上方约2cm的位置。掌握约1拇指和食指之间的皮肤的一个相当大的折叠 - 2厘米的皮肤上。滚手指之间的皮肤。 注意：如果皮褶之间的手指易万卷，它可能只包含的皮肤和皮下脂肪。如果皮褶不容易滚动或把握为参与者特别痛苦，它可能包含亩SCLE。 </li><li>摇动皮肤和/或使之只包含的皮肤和皮下脂肪，而不是肌肉卷手指慢慢调整折。测量所有皮下脂肪肌肉上面。 </li><li>保持平行于臂的皮褶。放置皮褶厚度颚垂直于褶皱的长度和在标记中点的两侧。 </li><li>按住皮褶，完全靠制动钳杆释放的抓地力。卡尺表盘将继续减少，因为皮肤是由卡钳爪压缩。持卡钳钳口之间的皮肤为4个全S，在此之后向皮肤应充分压缩。 4秒钟后，记录测量一厘米的最近的十分之二。 注意：如果是皮肤和皮下组织的正确数量，测量（如阅读上的卡尺转盘）将降低较慢或不会减少在所有4秒钟后。如果卡尺表盘测量值继续快速下降，皮褶不包含足够的皮下脂肪。如果是这种情况，等待两分钟，压缩皮肤恢复正常。通过抓住厚倍重试测量。 </li></ol> 10.肩胛下皮褶厚度<ol><li>指示参与者挺立，双肩放松，双臂垂松散。 </li><li>站在后面的参与者，触诊肩胛骨的最尖端。找到测量点，肩胛骨下尖下方2厘米，然后将卡钳那里。 </li><li>握住一对角约2厘米以上，并测量部位的左拇指和食指之间的皮肤的一个相当大的褶皱。外观应它只包含的皮肤和皮下脂肪手指之间容易滚动。调整皮褶，从而使测量只包含皮肤和皮下脂肪。 </li><li>放置卡钳钳口垂直于测量部位，使得测量时平行于内侧，下侧肩胛骨骨。按住皮褶，完全靠制动钳杆释放的抓地力。记录测量后4个厘米的最近的十分之二。 </li><li>保证表盘卡尺保持一致或4秒钟后只是最低限度地减少。在卡尺表盘迅速下降的措施表明已经获得没有足够的皮下脂肪。如果是这样的情况下，等待2分钟的压缩皮肤返回到正常。通过抓住厚倍重试测量。 </li></ol> 11.质量控制（QC）程序<ol><li>要求所有工作人员，包括经验和新的研究人员，在QC会议来衡量的志愿者。获得志愿者和工作人员的数量相等，以最大限度地提高效率。如果研究人员组成的1-3人，要求至少有四名志愿者，以确保可靠性适当评估。 </li><li>指定一个人成为了QC届的金标准评估者，无论是从研究人员质量评估者或外部专家。保证（相比，无论一个熟练的auxologist或金标准，如DXA当内部信度和可靠性两者），他/她的可靠性记录证明。 </li><li>让所有研究人员两次或多次进行每本手册的人体测量每个志愿者。 </li><li>计算内部评估者和评估者间可靠性QC会议结束后，使用测量（TEM）技术错误。 注：TEM用于评估两个测量之间的差是由于测量误差12。 TEM是测量误差方差的平方根：TEM = <img alt="式（1）" src="/files/ftp_upload/54895/54895eq1.jpg" /> ，其中d 2是要么由每个研究助理（帧内评价者可靠性）或人体测量专家的重复的总和减去一个研究的辅助的总和之间的差重复测量值之间的差蚂蚁的重复（评判间可靠性）12。 </li><li>确定工作人员，其间或内部评估者TEM值落在可接受14的预定TEM范围之外。为工作人员，其人体测量落在可接受的范围，允许从研究参与者野外数据采集之前，更多的培训。 </li></ol>

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W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cohort+profile:+Project+Viva.">Cohort profile: Project Viva.</a> Int J Epidemiol. 44 (1), 37-48 (2015).</li><li>Ulijaszek, S. J., Lourie, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Intra-+and+inter-observer+error+in+anthropometric+measurement.">Intra- and inter-observer error in anthropometric measurement.</a> Anthropometry: the Individual and the Population. , 30-55 (1994).</li><li>H&#228;ggstr&#246;m, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Medical+gallery+of+Mikael+H&#228;ggstr&#246;m+2014.">Medical gallery of Mikael H&#228;ggstr&#246;m 2014.</a> Wikiversity Journal of. Medicine. 1 (2), (2014).</li><li>. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Acromion+of+Scapula05.">Acromion of Scapula05.</a> DBCLS. , (2013).</li></ol>

The authors have nothing to disclose.

准确的身体组成的措施是正确的评估研究报告童年成长的关键。研究人员广泛接受DXA为金标准方法，而且很多批评手工人体测量指标作为是不准确和不准确的。然而，这种分析的人体测量技术来估算体内脂肪表明，训练有素的研究助理谁遵循的标准化协议可进行具有优异的精度手动人体测量，产生一个高度与DXA 1肥胖相关的估计。除了个别的措施，手动人体测量，如皮褶厚度和?...

超重和肥胖保持在流行水平，与美国儿童和有超重或肥胖的成年人的三分之二的大约三分之一，根据2011至2012年的估计2。超重，肥胖和体内多余的脂肪赋予心脏代谢不良的结果，其中包括2型糖尿病和心血管疾病的风险更大，以及其他不利身体和心理健康状况，包括哮喘和抑郁症3，4，5，6。 该研究肥胖和晚年的健康结果之间的关联大多数研究认为体重和身长/身高的精确测量。在成人和儿童的体重状况类别包括体重（身体质量指数（BMI）&lt;18.0公斤/米2名成人和&lt;5 个年龄性别特异性百分儿童），无RMAL体重（BMI 18.0到&lt;25.0公斤/米2名成人和5 日为儿童&lt;85 百分位数），超重（BMI 25.0〜&lt;30.0千克/米2名成人和85 日至&lt;95 百分位数为儿童）和肥胖（BMI≥为30kg / m 2的成人和≥95儿童百分位数）。即使是轻微的测量误差可以影响这些分类已，尤其是儿童对他们来说，出现小的绝对规模错误可以代表相对较大的孩子的大小7错误。例如，在儿童的2岁以下的现有研究中，长度的比较通过与横卧长度板上方法中的常规临床纸和铅笔法测定表明平均系统高估长度纸和铅笔方法为1.3（1.5）厘米-其导致相当大的误分类7错误。 1。因此，直接测量肥胖的方法也可用于理解与健康结果的关系很重要。 肥胖和身体成分测量的金标准方法一般依靠技术方法，包括排气量体积描记法（ADP），静水称重，磁共振成像（MRI）和计算机断层扫描（CT），以及双能X线骨密度仪（DXA ）8，9，10。虽然这些方法提供一些身体组成的最准确的措施，其中许多人是不是在儿科的调查研究实践，尤其是那些基于现场的。例如，静流称重要求个人在水中完全淹没。 ADP设备有，直到最近，一直只适用于6岁以上的达8公斤的儿童和成年人测量婴儿，但不能幼儿或学龄前儿童。 CT扫描发射与其它技术相比，大量的辐射，并且长采集时间用于MRI使它不切实际的许多研究8。 DXA发射大约1/500 CT扫描的辐射剂量，自然背景辐射11的一天大约相当于，使之成为涉及儿童调查研究有吸引力的选择。所有这些方法，但是，是购买昂贵的并且没有一个是便携式的，使得它们不可能具有有限基金场为基础的研究ING。生物电阻抗分析（BIA），其测量通过人体发送来估计身体组成一分钟电信号的阻抗，可更便宜和更便于携带，但假设身体脂肪计算基础并不适用于小的孩子10。 相对于这些技术为基础的措施，可以通过在多数场设置一个受过训练的观察者，并在一个基本上较低的设备成本来进行手动人体测量。手册人体测量包括高度的测量，重量，圆周，和皮褶厚度8。手工人体测量的其他优点是，它不涉及不必要的辐射照射，和熟练的员工能够有效地得到它们。然而，有关手动人体测量一个共同的问题是，它们可以是两个不准确和不精确12。 获取准确和公关ecise测量是可能的标准化程序，充分的培训和足够的重视，质量控制（QC）程序。项目万岁团队开发了一个手动测量学培训协议，可以产生高品质的，身材，周长的重现性措施，并皮褶厚度。在十多年中，我们应用这个培训和质量控制规程，在项目万岁，纵向，产前队列研究13母亲和儿童。项目万岁人员在出生的访问过程中收集关于儿童的人体测量（0 - 3天），并与母亲都和儿童在以下时间点：婴儿期（4.9 - 10.6个月），幼儿期（2.8 - 10年），中-childhood（6.6 - 10.9岁），青少年早期（11.5 - 16.5年） 13。 本文介绍了我们开发的协议和精致的身高，体重，皮褶厚度（三头肌和subscapul测量AR皮褶厚度），和身体的周长（腰部，臀部，并在项目万岁上臂周长[MUAC]）。我们还描述了我们是如何在比较黄金标准DXA测量评价的测量（TEM）计算和精度的技术错误的方式手动人体测量精度。

<table border="0" cellpadding="0" cellspacing="0" width="596">
	<tbody>
		<tr height="210">
			<td height="210" style="height:210px;width:216px;">Stadiometer</td>
			<td style="width:95px;">Weigh and Measure, LLC&#160;</td>
			<td style="width:119px;">SSWM-1</td>
			<td style="width:167px;">Basic Shorr board (without smooth slide features) can also be used. In order to accommodate the width of children&#39;s hips during sitting height, the base of a stadiometer should be approximately 60 cm wide or larger.</td>
		</tr>
		<tr height="105">
			<td height="105" style="height:105px;width:216px;">Bioimpedance scale&#160;</td>
			<td style="width:95px;">Tanita Coporation of America</td>
			<td style="width:119px;">TBF 300A (model is discontinued), DC-430U is&#160; comparable&#160;&#160;&#160;</td>
			<td style="width:167px;">Scale is used for weight and bioimpedance. Any digital, standardized scale can be used for weight only.</td>
		</tr>
		<tr height="105">
			<td height="105" style="height:105px;width:216px;">Skinfold Caliper</td>
			<td style="width:95px;">Holtain Limited</td>
			<td style="width:119px;">n/a</td>
			<td style="width:167px;">This model uses a dial gauge in graduations of 0.2 mm. Models with a linear gauge are also acceptable.&#160;&#160;</td>
		</tr>
		<tr height="189">
			<td height="189" style="height:189px;width:216px;">Hip/waist tape measure</td>
			<td style="width:95px;">Gulick II Plus Measuring Tape</td>
			<td style="width:119px;">67019</td>
			<td style="width:167px;">This model uses compression bands, which makes it easier to identify how firmly the tape measure is being pulled. The compression band is not necessary, but highly recommended.</td>
		</tr>
		<tr height="105">
			<td height="105" style="height:105px;width:216px;">MUAC measuring tape (ShorrTape&#169; Measuring Tape)&#160;</td>
			<td style="width:95px;">Weigh and Measure, LLC</td>
			<td style="width:119px;">STape</td>
			<td style="width:167px;">The tape measure should be flexible with a single or double slotted insertion window.</td>
		</tr>
	</tbody>
</table>

assessment of child anthropometry in a large epidemiologic study

儿童比例高有超重和肥胖在美国和其他国家。人体测量的准确评估是必须了解孩子的生长和肥胖对健康的影响。测量肥胖的金标准方法，如双能X线骨密度仪（DXA），可能无法在大视场的研究是可行的。科研人员可以，但是，完整的人体测量，如身体周长和皮褶测量，使用廉价的便携式设备。在这个协议中，我们详细介绍了如何获得儿童，包括站立和坐高，体重，腰围，臀围，上臂围，三头肌皮褶厚度，肩胛下皮褶厚度手工人体测量和程序来评估的质量这些测量。为了证明这些测量精度，其中1,110名学龄儿童在我们计算斯皮尔曼科尔出生前队列项目万岁得意洋洋系数比较手工人体测量与人体脂肪，DXA脂肪量1黄金标准的措施。为了解决可靠性，我们在成年女性志愿者进行了质量控制会话评估测量的内部评估者的技术错误。

该分析涉及利用质量控制（QC）程序生成的数据手册人体测量精度，以及测量的技术错误评估内部评估者的测量误差（TEM） 12。可接受的透射电镜范围基于重复帧内评价者人体测量，其中测量误差的95％是由于比评价者不精确12,14的其他因素计算。较高的TEM表明测量之间的更大变化。可接受的测量，分?...

Watch this Scientific Journal Video about Assessment of Child Anthropometry in a Large Epidemiologic Study at JoVE.com

Assessment of Child Anthropometry in a Large Epidemiologic Study

In epidemiologic studies of children, well-trained research staff can accurately and precisely assess weight, height, sitting height, skinfold thicknesses, and body circumferences.

大型流行病学研究儿童人体测量评估

A high proportion of children have overweight and obesity in the United States and other countries. Accurate assessment of anthropometry is essential to ...

assessment-of-child-anthropometry-in-a-large-epidemiologic-study

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Biostatistics

SCIENTISTS IN ACTION

26.9K 次观看.  Harvard Medical School and Harvard Pilgrim Health Care Institute. In epidemiologic studies of children, well-trained research staff can accurately and precisely assess weight, height, sitting height, skinfold thicknesses, and body circumferences. 

视频: Assessment of Child Anthropometry in a Large Epidemiologic Study

Biomarkers in an Animal Model for Revealing Neural, Hematologic, and Behavioral Correlates of PTSD

Identification of biomarkers representing the evolution of the pathophysiology of Post Traumatic Stress Disorder (PTSD) is vitally important, not only for objective diagnosis but also for the evaluation of therapeutic efficacy and resilience to trauma. Ongoing research is directed at identifying molecular biomarkers for PTSD, including traumatic stress induced proteins, transcriptomes, genomic variances and genetic modulators, using biologic samples from subjects' blood, saliva, urine, and postmortem brain tissues. However, the correlation of these biomarker molecules in peripheral or postmortem samples to altered brain functions associated with psychiatric symptoms in PTSD remains unresolved. Here, we present an animal model of PTSD in which both peripheral blood and central brain biomarkers, as well as behavioral phenotype, can be collected and measured, thus providing the needed correlation of the central biomarkers of PTSD, which are mechanistic and pathognomonic but cannot be collected from people, with the peripheral biomarkers and behavioral phenotypes, which can.
Our animal model of PTSD employs restraint and tail shocks repeated for three continuous days - the inescapable tail-shock model (ITS) in rats. This ITS model mimics the pathophysiology of PTSD 17, 7, 4, 10. We and others have verified that the ITS model induces behavioral and neurobiological alterations similar to those found in PTSD subjects 17, 7, 10, 9. Specifically, these stressed rats exhibit (1) a delayed and exaggerated startle response appearing several days after stressor cessation, which given the compressed time scale of the rat's life compared to a humans, corresponds to the one to three months delay of symptoms in PTSD patients (DSM-IV-TR PTSD Criterian D/E 13), (2) enhanced plasma corticosterone (CORT) for several days, indicating compromise of the hypothalamopituitary axis (HPA), and (3) retarded body weight gain after stressor cessation, indicating dysfunction of metabolic regulation.
The experimental paradigms employed for this model are: (1) a learned helplessness paradigm in the rat assayed by measurement of acoustic startle response (ASR) and a charting of body mass; (2) microdissection of the rat brain into regions and nuclei; (3) enzyme-linked immunosorbent assay (ELISA) for blood levels of CORT; (4) a gene expression microarray plus related bioinformatics tools 18. This microarray, dubbed rMNChip, focuses on mitochondrial and mitochondria-related nuclear genes in the rat so as to specifically address the neuronal bioenergetics hypothesized to be involved in PTSD.

We describe a rat model of post traumatic stress disorder (PTSD) that reveals the persistent alterations in neuroendocrine function and the delayed long-term, exaggerated fear response, characteristic of PTSD patients. The animal model and methods described here are useful for correlating biomarkers in brain nuclei, which are mechanistic but cannot be measured in patients, with biomarkers in peripheral white blood cells, which can.

在动物模型揭示神经，血液，创伤后应激障碍和行为相关因素的生物标志物

Identification of biomarkers representing the evolution of the pathophysiology of Post Traumatic Stress Disorder (PTSD) is vitally important, not only for ...

科研

医学

Real-time fMRI Biofeedback Targeting the Orbitofrontal Cortex for Contamination Anxiety

We present a method for training subjects to control activity in a region of their orbitofrontal cortex associated with contamination anxiety using biofeedback of real-time functional magnetic resonance imaging (rt-fMRI) data. Increased activity of this region is seen in relationship with contamination anxiety both in control subjects1 and in individuals with obsessive-compulsive disorder (OCD),2 a relatively common and often debilitating psychiatric disorder involving contamination anxiety. Although many brain regions have been implicated in OCD, abnormality in the orbitofrontal cortex (OFC) is one of the most consistent findings.3, 4 Furthermore, hyperactivity in the OFC has been found to correlate with OCD symptom severity5 and decreases in hyperactivity in this region have been reported to correlate with decreased symptom severity.6 Therefore, the ability to control this brain area may translate into clinical improvements in obsessive-compulsive symptoms including contamination anxiety. Biofeedback of rt-fMRI data is a new technique in which the temporal pattern of activity in a specific region (or associated with a specific distributed pattern of brain activity) in a subject's brain is provided as a feedback signal to the subject. Recent reports indicate that people are able to develop control over the activity of specific brain areas when provided with rt-fMRI biofeedback.7-12 In particular, several studies using this technique to target brain areas involved in emotion processing have reported success in training subjects to control these regions.13-18 In several cases, rt-fMRI biofeedback training has been reported to induce cognitive, emotional, or clinical changes in subjects.8, 9, 13, 19 Here we illustrate this technique as applied to the treatment of contamination anxiety in healthy subjects. This biofeedback intervention will be a valuable basic research tool: it allows researchers to perturb brain function, measure the resulting changes in brain dynamics and relate those to changes in contamination anxiety or other behavioral measures. In addition, the establishment of this method serves as a first step towards the investigation of fMRI-based biofeedback as a therapeutic intervention for OCD. Given that approximately a quarter of patients with OCD receive little benefit from the currently available forms of treatment,20-22 and that those who do benefit rarely recover completely, new approaches for treating this population are urgently needed.

Here we present a method for training people to control a brain area involved in contamination anxiety and for probing the relationship between contamination anxiety and brain connectivity patterns.

实时功能磁共振成像生物反馈，针对污染焦虑的眶额皮层

We present a method for training subjects to control activity in a region of their orbitofrontal cortex associated with contamination anxiety using ...

A Novel Application of Musculoskeletal Ultrasound Imaging

Ultrasound is an attractive modality for imaging muscle and tendon motion during dynamic tasks and can provide a complementary methodological approach for biomechanical studies in a clinical or laboratory setting. Towards this goal, methods for quantification of muscle kinematics from ultrasound imagery are being developed based on image processing. The temporal resolution of these methods is typically not sufficient for highly dynamic tasks, such as drop-landing. We propose a new approach that utilizes a Doppler method for quantifying muscle kinematics. We have developed a novel vector tissue Doppler imaging (vTDI) technique that can be used to measure musculoskeletal contraction velocity, strain and strain rate with sub-millisecond temporal resolution during dynamic activities using ultrasound. The goal of this preliminary study was to investigate the repeatability and potential applicability of the vTDI technique in measuring musculoskeletal velocities during a drop-landing task, in healthy subjects. The vTDI measurements can be performed concurrently with other biomechanical techniques, such as 3D motion capture for joint kinematics and kinetics, electromyography for timing of muscle activation and force plates for ground reaction force. Integration of these complementary techniques could lead to a better understanding of dynamic muscle function and dysfunction underlying the pathogenesis and pathophysiology of musculoskeletal disorders.

We describe a new ultrasound-based vector tissue Doppler imaging technique to measure muscle contraction velocity, strain and strain rate with sub-millisecond temporal resolution during dynamic activities. This approach provides complementary measurements of dynamic muscle function and could lead to a better understanding of mechanisms underlying musculoskeletal disorders.

肌肉骨骼超声成像的一种新应用

Ultrasound is an attractive modality for imaging muscle and tendon  motion during dynamic tasks and can provide a complementary methodological  approach ...

An Isolated Working Heart System for Large Animal Models

Since its introduction in the late 19th century, the Langendorff isolated heart perfusion apparatus, and the subsequent development of the working heart model, have been invaluable tools for studying cardiovascular function and disease1-15. Although the Langendorff heart preparation can be used for any mammalian heart, most studies involving this apparatus use small animal models (e.g., mouse, rat, and rabbit) due to the increased complexity of systems for larger mammals1,3,11. One major difficulty is ensuring a constant coronary perfusion pressure over a range of different heart sizes &#8211; a key component of any experiment utilizing this device1,11. By replacing the classic hydrostatic afterload column with a centrifugal pump, the Langendorff working heart apparatus described below allows for easy adjustment and tight regulation of perfusion pressures, meaning the same set-up can be used for various species or heart sizes. Furthermore, this configuration can also seamlessly switch between constant pressure or constant flow during reperfusion, depending on the user&#8217;s preferences. The open nature of this setup, despite making temperature regulation more difficult than other designs, allows for easy collection of effluent and ventricular pressure-volume data.

Most studies involving the Langendorff apparatus use small animal models due to the increased complexity of systems for larger mammals. We describe a Langendorff system for large animal models that allows for use across a range of species, including humans, and relatively easy data acquisition.

一个孤立的工作心脏系统的大型动物模型

Since its introduction in the late 19th century, the Langendorff isolated heart perfusion apparatus, and the subsequent development of the working heart ...

Clinical Assessment of Spatiotemporal Gait Parameters in Patients and Older Adults

Spatial and temporal characteristics of human walking are frequently evaluated to identify possible gait impairments, mainly in orthopedic and neurological patients1-4, but also in healthy older adults5,6. The quantitative gait analysis described in this protocol is performed with a recently-introduced photoelectric system (see&#160;Materials table) which has the potential to be used in the clinic because it is portable, easy to set up (no subject preparation is required before a test), and does not require maintenance and sensor calibration. The photoelectric system consists of series of high-density floor-based photoelectric cells with light-emitting and light-receiving diodes that are placed parallel to each other to create a corridor, and are oriented perpendicular to the line of progression7. The system simply detects interruptions in light signal, for instance due to the presence of feet within the recording area. Temporal gait parameters and 1D spatial coordinates of consecutive steps are subsequently calculated to provide common gait parameters such as step length, single limb support and walking velocity8, whose validity against a criterion instrument has recently been demonstrated7,9. The measurement procedures are very straightforward; a single patient can be tested in less than 5 min&#160;and a comprehensive report can be generated in less than 1&#160;min.

This protocol is used to evaluate spatial and temporal gait variables of neurological/orthopedic patients and older persons by means of a recently-introduced floor-based photocell system.

时空步态参数的患者和老年人的临床评估

Spatial and temporal characteristics of human walking are frequently evaluated to identify possible gait impairments, mainly in orthopedic and ...

Surgical Angiogenesis in Porcine Tibial Allotransplantation: A New Large Animal Bone Vascularized Composite Allotransplantation Model

Segmental bone loss resulting from trauma, infection malignancy and congenital anomaly remains a major reconstructive challenge. Current therapeutic options have significant risk of failure and substantial morbidity.
Use of bone vascularized composite allotransplantation (VCA) would offer both a close match of resected bone size and shape and the healing and remodeling potential of living bone. At present, life-long drug immunosuppression (IS) is required. Organ toxicity, opportunistic infection and neoplasm risks are of concern to treat such non-lethal indications.
We have previously demonstrated that bone and joint VCA viability may be maintained in rats and rabbits without the need of long-term-immunosuppression by implantation of recipient derived vessels within the VCA. It generates an autogenous, neoangiogenic circulation with measurable flow and active bone remodeling, requiring only 2 weeks of IS. As small animals differ from man substantially in anatomy, bone physiology and immunology, we have developed a porcine bone VCA model to evaluate this technique before clinical application is undertaken. Miniature swine are currently widely used for allotransplantation research, given their immunologic, anatomic, physiologic and size similarities to man. Here, we describe a new porcine orthotopic tibial bone VCA model to test the role of autogenous surgical angiogenesis to maintain VCA viability.
The model reconstructs segmental tibial bone defects using size- and shape-matched allogeneic tibial bone segments, transplanted across a major swine leukocyte antigen (SLA) mismatch in Yucatan miniature swine. Nutrient vessel repair and implantation of recipient derived autogenous vessels into the medullary canal of allogeneic tibial bone segments is performed in combination with simultaneous short-term IS. This permits a neoangiogenic autogenous circulation to develop from the implanted tissue, maintaining flow through the allogeneic nutrient vessels for a short time. Once established, the new autogenous circulation maintains bone viability following cessation of drug therapy and subsequent nutrient vessel thrombosis.

Currently any kind of vascularized composite allotransplantation depends on long-term-immunosuppression, difficult to support for non-life-critical indications. We present a new porcine tibial VCA model that can be used to study bone VCA and demonstrate the use of surgical angiogenesis to maintain bone viability without the need of long-term immune-modulation.

猪胫骨移植术后血管生成的动物模型

Segmental bone loss resulting from trauma, infection malignancy and congenital anomaly remains a major reconstructive challenge. Current therapeutic ...

Assessment of Plasma Coagulation on Liver Tissue in a Large Animal Model In Vivo

Plasma coagulation as a form of electrocautery is used in liver surgery for decades to seal the large liver cut surface after major hepatectomy to prevent hemorrhages at a later stage. The exact effects of plasma coagulation on liver tissue are only poorly examined. In our porcine model, the coagulation effects can be examined close to the clinical application. A combined laser Doppler flowmeter and spectrophotometer documents microcirculation changes during coagulation at 8 mm tissue depth noninvasively, providing quantifiable information about hemostasis beyond the subjective clinical impression. The temperature at coagulation site is assessed with an infrared thermometer prior and post coagulation and with a thermographic camera during coagulation, a measurement of the gas beam temperature is not possible due to the upper threshold of the devices. The depth of coagulation is measured microscopically on hematoxylin/eosin stained sections after calibration with an object micrometer and gives an exact information about the power setting-coagulation depth-relation. The sealing effect is examined on the bile ducts as it is not possible for a plasma coagulator to seal larger blood vessels. Burst pressure experiments are carried out on explanted organs to rule out blood pressure related effects.

Assessment of Plasma Coagulation on Liver Tissue in a Large Animal Model In Vivo

Here we present a protocol to experimentally assess plasma coagulation in liver tissue in vivo. In a porcine model, microcirculation is examined by laser Doppler, coagulation depth is measured histologically, temperature at coagulation site by infrared thermometer and thermographic camera, and duct sealing effect is documented by burst pressure experiments.

大动物模型肝组织血浆凝固的评价

Plasma coagulation as a form of electrocautery is used in liver surgery for decades to seal the large liver cut surface after major hepatectomy to prevent ...

Objective Nociceptive Assessment in Ventilated ICU Patients: A Feasibility Study Using Pupillometry and the Nociceptive Flexion Reflex

The concept of objective nociceptive assessment and optimal pain management have gained increasing attention. Despite the known negative short- and long-term consequences of unresolved pain or excessive analgosedation, adequate nociceptive monitoring remains challenging in non-communicative, critically ill adults. In the intensive care unit (ICU), routine nociceptive evaluation is carried out by the attending nurse using the Behavior Pain Scale (BPS) in mechanically ventilated patients. This assessment is limited by medication use (e.g., neuromuscular blocking agents) and the inherent subjective character of nociceptive evaluation by third parties.
Here, we describe the use of two nociceptive reflex testing devices as tools for objective pain evaluation: the pupillary dilation reflex (PDR) and nociception flexion reflex (NFR). These measurement tools are non-invasive and well tolerated, providing clinicians and researchers with objective information regarding two different nociceptive processing pathways: (1)&#160;the pain-related autonomic reactivity&#160;and (2) the ascending component of the somatosensory system. The use of PDR and NFR measurements are currently limited to specialized pain clinics and research institutions because of impressions that these are technically demanding or time-consuming procedures, or even because of a lack of knowledge regarding their existence.
By focusing on the two abovementioned nociceptive reflex assessments, this study evaluated their feasibility as a physiological pain measurement method in daily practice. Pursuing novel technologies for evaluating the analgesia level in unconscious patients may further improve individual pharmacological treatment and patient related outcome measures. Therefore, future research must include large well-designed clinical trials in a real-life environment.

Pain assessment in anesthetized patients who cannot communicate with the outside world in any way remains challenging despite the development of innovative objective pain evaluation tools. In this project, the pupillary dilation reflex and the nociception flexion reflex are assessed in critically ill, mechanically ventilated adult patients.

应用 Pupillometry 和伤害性屈曲反射的可行性研究--通气 ICU 患者的客观伤害评估

The concept of objective nociceptive assessment and optimal pain management have gained increasing attention. Despite the known negative short- and ...

In Vitro Model of Coronary Angiogenesis

Here, we describe an in vitro culture assay to study coronary angiogenesis. Coronary vessels feed the heart muscle and are of clinical importance. Defects in these vessels represent severe health risks such as in atherosclerosis, which can lead to myocardial infarctions and heart failures in patients. Consequently, coronary artery disease is one of the leading causes of death worldwide. Despite its clinical importance, relatively little progress has been made on how to regenerate damaged coronary arteries. Nevertheless, recent progress has been made in understanding the cellular origin and differentiation pathways of coronary vessel development. The advent of tools and technologies that allow researchers to fluorescently label progenitor cells, follow their fate, and visualize progenies in vivo have been instrumental in understanding coronary vessel development. In vivo studies are valuable, but have limitations in terms of speed, accessibility, and flexibility in experimental design. Alternatively, accurate in vitro models of coronary angiogenesis can circumvent these limitations and allow researchers to interrogate important biological questions with speed and flexibility. The lack of appropriate in vitro model systems may have hindered the progress in understanding the cellular and molecular mechanisms of coronary vessel growth. Here, we describe an in vitro culture system to grow coronary vessels from the sinus venosus (SV) and endocardium (Endo), the two progenitor tissues from which many of the coronary vessels arise. We also confirmed that the cultures accurately recapitulate some of the known in vivo mechanisms. For instance, we show that the angiogenic sprouts in culture from SV downregulate COUP-TFII expression similar to what is observed in vivo. In addition, we show that VEGF-A, a well-known angiogenic factor in vivo, robustly stimulates angiogenesis from both the SV and Endo cultures. Collectively, we have devised an accurate in vitro culture model to study coronary angiogenesis.

In vitro models of coronary angiogenesis can be utilized for the discovery of the cellular and molecular mechanisms of coronary angiogenesis. In vitro explant cultures of sinus venosus and endocardium tissues show robust growth in response to VEGF-A and display a similar pattern of COUP-TFII expression as in vivo.

冠状血管生成体模型

Here, we describe an in vitro culture assay to study coronary angiogenesis. Coronary vessels feed the heart muscle and are of clinical importance. Defects ...

Using a Chemical Biopsy for Graft Quality Assessment

Kidney transplantation is a life-saving treatment for a large number of people with end-stage renal dysfunction worldwide. The procedure is associated with an increased survival rate and greater quality of patient&#8217;s life when compared to conventional dialysis. Regrettably, transplantology suffers from a lack of reliable methods for organ quality assessment. Standard diagnostic techniques are limited to macroscopic appearance inspection or invasive tissue biopsy, which do not provide comprehensive information about the graft. The proposed protocol aims to introduce solid phase microextraction (SPME) as an ideal analytical method for comprehensive metabolomics and lipidomic analysis of all low molecular compounds present in kidneys allocated for transplantation. The small size of the SPME probe enables performance of a chemical biopsy, which enables extraction of metabolites directly from the organ without any tissue collection. The minimum invasiveness of the method permits execution of multiple analyses over time: directly after organ harvesting, during its preservation, and immediately after revascularization at the recipient&#8217;s body. It is hypothesized that the combination of this novel sampling method with a high-resolution mass spectrometer will allow for discrimination of a set of characteristic compounds that could serve as biological markers of graft quality and indicators of possible development of organ dysfunction.

The protocol presents utilization of the chemical biopsy approach followed by comprehensive metabolomic and lipidomic analysis for quality assessment of kidney grafts allocated for transplantation.

使用化学活检进行移植质量评估

Kidney transplantation is a life-saving treatment for a large number of people with end-stage renal dysfunction worldwide. The procedure is associated ...