We would like to thank the Canadian Institutes of Health Research (CIHR) who have provided funding for this research. Further, we would like to acknowledge Dr. Tim Taha and Dr. Scott Thomas from the University of Toronto for their assistance with the development of our protocol for the collection of resting state heart rate variability data.

The described protocol includes pre-injury/baseline testing and post-injury follow-up assessment and is completed using three stations. This testing can be completed individually or in groups of four subjects at each station at a time. Subjects proceed through each station in the order listed below. Table 1 illustrates the protocol&#8217;s testing administration schedule. Ethics approval for this research was obtained from the Holland Bloorview Research Ethics Board at the Holland Bloorview Kids Rehabilitation Hospital. All participants and their legal guardians provide signed informed consent prior to completing the protocol and related data collection.
Pre-injury/Baseline Testing
1. Station 1: Obtaining Pre-injury Demographic Information, Post-concussion Symptom Report and Resting State Heart Rate Variability (HRV) Data
<ol>
	<li>Prior to subject(s) arriving for testing, ensure all equipment is functioning properly and ready for testing and that the assessment rooms are free from unnecessary distractions.</li>
	<li>After reviewing parental and subject consent, measure and record the subject&#8217;s height and weight. Set up heart rate monitor straps and watches on each subject properly.</li>
	<li>Administer the demographic information form and collect post-concussion symptom report using the Child version of the Post-Concussion Symptom Inventory(PCSI-C) while each subject is seated for 5 min.</li>
	<li>Have each subject lay supine on the ground on a clean sanitized mat. Turn on the heart rate monitors to record resting state heart rate variability (HRV) data (with R-R interval function set to [On]). Have each subject remain lying in supine quietly without talking for 10 min while recording HR.</li>
	<li>After 10 min, click the lap button on the watch to indicate the end of supine lying resting state HRV data collection. Ask the subject to return to a seated position, click the lap button on the watch again to indicate beginning of resting state seated HRV data collection.</li>
	<li>Have each subject remain in the seated position for 5 min without talking. After 5 min, stop the watch recording function to end the session and resting state HRV data collection. Ask the subject to take off the heart rate strap and watches.</li>
</ol>
2. Station 2: Obtaining Cognitive Performance Data
<ol>
	<li>Have each subject sit at an individual cubicle with a personal laptop set up with a mouse. Ensure testing environment is free from distraction.</li>
	<li>Administer the Immediate Post-concussion Assessment and Cognitive Testing (ImPACT), a rapid and computerized neuropsychological assessment tool (approximately 25 min to complete).</li>
</ol>
3. Station 3: Obtaining Static Balance, Grip Strength and Agility/Motor Skills Data
<ol>
	<li>Administer the static balance assessment using the modified Clinical Test of Sensory Integration of Balance (m-CTSIB) on the portable balance system. While standing on the balance system forceplate, the subject completes four ordered conditions that include standing with eyes open for 20 sec; standing with eyes closed for 20 sec; standing with eyes open on indexed foam pad for 20 sec; and standing with eyes closed on indexed foam pad for 20 sec.</li>
	<li>Using a Dynamometer, measure and record hand grip strength in kg for both right and left hands. Record the dominant hand for each subject while still completing 3 consecutive trials for each hand starting with the dominant hand. Out of the 3 trials taken, the maximum hand grip on each hand will also be recorded. For each trial the subject is told to squeeze the grip as hard as they can for 3 sec keeping a neutral upper extremity position (standing upright, straight arm parallel beside the body, palm facing the body and wrist neutral).</li>
	<li>In a hallway or gym at least 2.5 m wide and 15 m long administer the agility/motor skills assessment using the ABI-Challenge Assessment (ABI-CA) - Concussion Module. Lay tape on the ground in a straight line marking points for every 1 m. In the following order administer these 6 tests following the guidelines and scoring criteria provided in the concussion module.
	<ol>
		<li>Jumping-jacks (Timed):
		<ol>
			<li>Stand with your arms at your sides and jump into an &#8220;X&#8221; position with arms and legs, and then instantly jump back into starting position. Count how many can be done in 15 sec.</li>
		</ol>
		</li>
		<li>Pylon/cone obstacle course run (Timed):
		<ol>
			<li>Run in and out of the pylons to the end (10 m) and back as fast as you can but at a speed that you feel safe. Do not touch the pylons. Run straight through the finish line. (Pylons located at 3, 5, 7, 10 m)</li>
		</ol>
		</li>
		<li>Backwards tandem walking (Timed):
		<ol>
			<li>On the lined track, walk backwards in a tandem pattern for 5 m. Tandem pattern is touching their heel to their opposite toe on each step.</li>
		</ol>
		</li>
		<li>Modified shuttle run (Timed):
		<ol>
			<li>Run along the 10 m track, pick up a beanbag at the end of the course, and run back to place the beanbag in a basket at the starting point. They must touch the starting line with their foot each time they return to the basket. Repeat this three times until all the beanbags are in the basket at the starting point.</li>
		</ol>
		</li>
		<li>Ins and outs (Timed):
		<ol>
			<li>Stand with both feet inside of two parallel lines (in the path) that are 40 cm apart. Move one foot outside of the corresponding line followed by the opposite leg moving outside of the other line. The first foot is then returned to the inside, followed by the second foot. Cycles must be consecutive and should be performed in a rhythmical fashion (equal time between each step), and will be repeated 10x not moving forward or backward.</li>
		</ol>
		</li>
		<li>Standing long jump: Jump forward from standing with both feet as far as you can and hold the landing for 3 sec. Measure and record the distance from the front of the furthest back foot. Three trials are given to achieve the farthest distance</li>
	</ol>
	</li>
</ol>
4. Post-injury/Follow-up Testing
<ol>
	<li>Obtaining post-concussion data while subject is experiencing post-concussion symptoms
	<ol>
		<li>On the same day a subject suffers an injury, research staff is contacted by subject using either phone or email. Research staff records clinical and functional details regarding the injury.</li>
		<li>Immediately following concussion (24-48 hr post injury), collect: resting state HRV data (repeat steps 1.3, 1.5-1.10); post-concussion symptom data (repeat step 1.4); and balance data (repeat step 3.1). If symptoms are exacerbated during testing, stop data collection and allow subject to rest.</li>
		<li>Continue to collect resting state HRV data (repeat steps 1.3, 1.5-1.10), post-concussion symptom data (repeat step 1.4), and balance data (repeat step 3.1) weekly until post-concussion symptoms have resolved. If symptoms are exacerbated during testing, stop data collection and allow subject to rest.</li>
		<li>Research staff follows up with subject weekly by phone to determine when post-concussion symptoms resolve (using PCSI-C).</li>
	</ol>
	</li>
</ol>
5. Obtaining Post-concussion Data While Subject is no Longer Experiencing Post-concussion Symptoms
<ol>
	<li>At 1 week after post-concussion symptoms have resolved, collect: resting state HRV data (repeat steps 1.3, 1.5-1.10); post-concussion symptom data (repeat step 1.4); cognitive performance data (repeat steps 2.1-2.2); balance data (repeat step 3.1); hand grip data (repeat step 3.2); and, agility/motor skills data (repeat step 3.3). If symptoms are exacerbated during testing, stop data collection and allow subject to rest.</li>
	<li>At 1 month after post-concussion symptoms have resolved, repeat step 5.1. At 3 months after post-concussion symptoms have resolved, repeat step 5.1. At 6 months after post-concussions symptoms have resolved, repeat step 5.1.</li>
</ol>

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H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Injury+rates,+risk+factors,+and+mechanisms+of+injury+in+minor+hockey.">Injury rates, risk factors, and mechanisms of injury in minor hockey.</a> The American journal of sports medicine. 34 (12), 1960-1969 (2006).</li><li>Keightley, M., Reed, N., Green, S., Taha, T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Age+and+competition+level+on+injuries+in+female+ice+hockey.">Age and competition level on injuries in female ice hockey.</a> International journal of sports medicine. 34 (8), 756-759 (2013).</li><li>McCrory, P., Meeuwisse, W. 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(43 Suppl), 28-60 (2004).</li><li>Collins, M. W., Lovell, M. R., Iverson, G. L., Cantu, R. C., Maroon, J. C., Field, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cumulative+effects+of+concussion+in+high+school+athletes.">Cumulative effects of concussion in high school athletes.</a> Neurosurgery. 51 (5), 1175-1179 (2002).</li><li>Lovell, M. R., Collins, M. W., Iverson, G. L., Johnston, K. M., Bradley, J. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Grade+1+or+&#8220;ding&#8221;+concussions+in+high+school+athletes.">Grade 1 or &#8220;ding&#8221; concussions in high school athletes.</a> The American Journal of Sports Medicine. 32 (1), 47-54 (2004).</li><li>Guskiewicz, K. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Postural+stability+assessment+following+concussion:+one+piece+of+the+puzzle.">Postural stability assessment following concussion: one piece of the puzzle.</a> Clinical journal of sport medicine: official journal of the Canadian Academy of Sport Medicine. 11 (3), 182-189 (2001).</li><li>Guskiewicz, K. 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G., Poirier, J., Laurent-Vannier, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+comprehensive+model+of+care+for+rehabilitation+of+children+with+acquired+brain+injuries.">A comprehensive model of care for rehabilitation of children with acquired brain injuries.</a> Child: care, health and development. 36 (1), 31-43 (2010).</li><li>Goldstein, B., Toweill, D., Lai, S., Sonnenthal, K., Kimberly, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Uncoupling+of+the+autonomic+and+cardiovascular+systems+in+acute+brain+injury.">Uncoupling of the autonomic and cardiovascular systems in acute brain injury.</a> The American journal of physiology. 275 (4 Pt 2), R1287-R1292 (1998).</li><li>Korpelainen, J. T., Huikuri, H. V., Sotaniemi, K. A., Myllyl&#228;, V. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Abnormal+heart+rate+variability+reflecting+autonomic+dysfunction+in+brainstem+infarction.">Abnormal heart rate variability reflecting autonomic dysfunction in brainstem infarction.</a> Acta neurologica Scandinavica. 94 (5), 337-342 (1996).</li><li>Leddy, J. J., Kozlowski, K., Fung, M., Pendergast, D. R., Willer, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Regulatory+and+autoregulatory+physiological+dysfunction+as+a+primary+characteristic+of+post+concussion+syndrome:+implications+for+treatment.">Regulatory and autoregulatory physiological dysfunction as a primary characteristic of post concussion syndrome: implications for treatment.</a> NeuroRehabilitation. 22 (3), 199-205 (2007).</li><li>Covassin, T., Weiss, L., Powell, J., Womack, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+a+maximal+exercise+test+on+neurocognitive+function.">Effects of a maximal exercise test on neurocognitive function.</a> British journal of sports medicine. 41 (6), 370-374 (2007).</li><li>McCrory, P., Collie, A., Anderson, V., Davis, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Can+we+manage+sport+related+concussion+in+children+the+same+as+in+adults?.">Can we manage sport related concussion in children the same as in adults?.</a> British Journal of Sports Medicine. 38 (5), 516-519 (2004).</li></ol>

The authors have nothing to disclose.

This protocol presents a multi-modal approach to measuring recovery in youth athletes following a concussion. A critical feature of this protocol is the comparison of post-concussion data across a wide range of performance domains (cognition, balance, strength, agility, resting state heart rate variability, etc.) to pre-injury/baseline. These data serve as a means to indicate recovery amongst individual youth athletes following a concussion. By using common and readily available clinical measures of cognition, b...

Concussion can be defined as &#34;a complex pathophysiologic process affecting the brain induced by traumatic biomechanical forces&#34;1, and can result in short and long-term somatic, cognitive and/or emotional/behavioral symptoms2. Functionally, concussion and related symptoms can have a significant impact on one&#39;s participation in daily activities and pursuits3. It has been estimated that within the United States, between 1.6 and 3.8 million concussion occur each year as a result of sport participation4. Specific to children and youth involved in sports, concussion is one of the most commonly reported injuries5-7. Despite the impact concussion can have on daily activities and the prevalence of concussion amongst children and youth, there remains a lack of scientific data reporting how the youth brain responds to concussion across a variety of performance domains.
Baseline testing, or the use of pre-injury testing scores as a benchmark for comparison against post-injury testing scores to inform recovery, is a practice of growing popularity within the youth sport community and has been suggested internationally8 to be &#34;helpful to add useful information&#34; (p.3) during the management of concussion. In order to best represent the varied nature of post-concussion symptoms (somatic, cognitive and emotional/behavioral), it is important that the assessment of post-concussion recovery include a variety of outcome measures. Further, current concussion management relies heavily on subjective report of post-concussion symptoms. The validity of this subjective report can be influenced by a variety of factors9 and may lead to both under-reporting of symptoms10,11 and a less accurate and reliable index of recovery. As a result, there is a significant need to explore approaches to measuring post-concussion recovery across performance domains that are both objective and sensitive.
It has been demonstrated that cognition, balance, strength and agility can be impaired in youth following concussion and brain injury12-17. The measures included within this testing protocol were chosen to provide insight into recovery across these domains following concussion and to incorporate the use of validated clinical testing tools that are commonly used across clinical settings focused on concussion management. Further, from a more exploratory perspective, resting state HRV can be seen as an accurate measure of sympathovagal balance18,19 . In a healthy population, sympathovagal balance is defined as the parasympathetic system being dominant at rest, while the sympathetic system is under tonic inhibitory control. It is hypothesized that post-concussion, due to physiological stress, an imbalance between the two systems will exist and resting state may shift to hyperactivity of the sympathetic system and hypoactivity of the parasympathetic system20.
The goal of this study&#39;s protocol is to conduct a multi-modal assessment of pre- and post-concussion performance amongst youth athletes (ages 10-18 years) in order to gain a more holistic, objective and accurate understanding of recovery following concussion. This study aims to provide insight into the development and delivery of concussion management and rehabilitation protocols specific to children and youth.

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	<tbody>
		<tr>
			<td>Name of Reagent/ Equipment</td>
			<td>Company</td>
			<td>Catalog Number</td>
			<td>Comments/Description</td>
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			<td>Scale</td>
			<td>Weight Watchers: Conair&#160;</td>
			<td>WW30WB</td>
			<td></td>
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		<tr>
			<td>Measuring Tape</td>
			<td>Hi-Viz Lufkin</td>
			<td>HVC716CME</td>
			<td></td>
		</tr>
		<tr>
			<td>Heart Rate Monitor (Chest Strap and Watch)</td>
			<td>Polar</td>
			<td>RS800CX GPS</td>
			<td></td>
		</tr>
		<tr>
			<td>Exercise/Yoga Mat</td>
			<td>Pur Athletics</td>
			<td>WTE10126</td>
			<td></td>
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		<tr>
			<td>Sportline Stopwatch (Model 228)</td>
			<td>EB Sport Group</td>
			<td>#2787</td>
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			<td>Laptop - MacBook Pro</td>
			<td>Apple</td>
			<td>A1278</td>
			<td></td>
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		<tr>
			<td>Computerized Cognitive Assessment- Immediate Post-Concussion Assessment and Cognitive Task</td>
			<td>ImPACT Application&#39;s Inc.&#160;</td>
			<td></td>
			<td></td>
		</tr>
		<tr>
			<td>Hand Grip Dynamometer</td>
			<td>Sammons Preston- Smedley-Type</td>
			<td>5032P</td>
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			<td>BioSway</td>
			<td>Biodex Medical Supplies Inc.&#160;</td>
			<td>950-510</td>
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			<td>Painter&#39;s Mate Green Tape</td>
			<td>ShurTech Brands LLC</td>
			<td>#49462</td>
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			<td>Pylons/Cones (12&#34;)</td>
			<td>Canadian Tire</td>
			<td>84-295-4</td>
			<td></td>
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			<td>Basket</td>
			<td>Canadian Tire</td>
			<td>42-9919-2</td>
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			<td>Bean Bags</td>
			<td>Eastpoint/Go Gater</td>
			<td>1-1-16392</td>
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</table>

a multi-modal approach to assessing recovery in youth athletes following concussion

Concussion is one of the most commonly reported injuries amongst children and youth involved in sport participation. Following a concussion, youth can experience a range of short and long term neurobehavioral symptoms (somatic, cognitive and emotional/behavioral) that can have a significant impact on one&#8217;s participation in daily activities and pursuits of interest (e.g., school, sports, work, family/social life, etc.). Despite this, there remains a paucity in clinically driven research aimed specifically at exploring concussion within the youth sport population, and more specifically, multi-modal approaches to measuring recovery. This article provides an overview of a novel and multi-modal approach to measuring recovery amongst youth athletes following concussion. The presented approach involves the use of both pre-injury/baseline testing and post-injury/follow-up testing to assess performance across a wide variety of domains (post-concussion symptoms, cognition, balance, strength, agility/motor skills and resting state heart rate variability). The goal of this research is to gain a more objective and accurate understanding of recovery following concussion in youth athletes (ages 10-18 years). Findings from this research can help to inform the development and use of improved approaches to concussion management and rehabilitation specific to the youth sport community.

The presented protocol is an ongoing investigation. Table 1 depicts the protocol&#8217;s testing administration schedule. Representative results are presented to demonstrate the feasibility of collecting baseline/pre-injury and post-concussion data across a variety of performance domains known to be impacted by concussion in youth. A single case of a concussed youth who has completed all stages of the protocol is presented to demonstrate recovery trajectories across selected outcome measures. Fig...

Watch this Scientific Journal Video about A Multi-Modal Approach to Assessing Recovery in Youth Athletes Following Concussion at JoVE.com

A Multi-Modal Approach to Assessing Recovery in Youth Athletes Following Concussion

This article provides an overview of a multi-modal approach to assessing recovery following concussion in youth athletes. The described protocol uses pre- and post-concussion assessment of performance across a wide variety of domains and can inform the development of improved concussion rehabilitation protocols specific to the youth sport community.

Concussion is one of the most commonly reported injuries amongst children and youth involved in sport participation. Following a concussion, youth can ...

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13.3K 조회수.  Holland Bloorview Kids Rehabilitation Hospital. This article provides an overview of a multi-modal approach to assessing recovery following concussion in youth athletes. The described protocol uses pre- and post-concussion assessment of performance across a wide variety of domains and can inform the development of improved concussion rehabilitation protocols specific to the youth sport community.

비디오: A Multi-Modal Approach to Assessing Recovery in Youth Athletes Following Concussion

An Investigation of the Effects of Sports-related Concussion in Youth Using Functional Magnetic Resonance Imaging and the Head Impact Telemetry System

One of the most commonly reported injuries in children who participate in sports is concussion or mild traumatic brain injury (mTBI)1. Children and youth involved in organized sports such as competitive hockey are nearly six times more likely to suffer a severe concussion compared to children involved in other leisure physical activities2. While the most common cognitive sequelae of mTBI appear similar for children and adults, the recovery profile and breadth of consequences in children remains largely unknown2, as does the influence of pre-injury characteristics (e.g. gender) and injury details (e.g. magnitude and direction of impact) on long-term outcomes. Competitive sports, such as hockey, allow the rare opportunity to utilize a pre-post design to obtain pre-injury data before concussion occurs on youth characteristics and functioning and to relate this to outcome following injury. Our primary goals are to refine pediatric concussion diagnosis and management based on research evidence that is specific to children and youth. To do this we use new, multi-modal and integrative approaches that will:
 1.Evaluate the immediate effects of head trauma in youth 
2.Monitor the resolution of post-concussion symptoms (PCS) and cognitive performance during recovery 
3.Utilize new methods to verify brain injury and recovery
To achieve our goals, we have implemented the Head Impact Telemetry (HIT) System. (Simbex; Lebanon, NH, USA). This system equips commercially available Easton S9 hockey helmets (Easton-Bell Sports; Van Nuys, CA, USA) with single-axis accelerometers designed to measure real-time head accelerations during contact sport participation 3 - 5. By using telemetric technology, the magnitude of acceleration and location of all head impacts during sport participation can be objectively detected and recorded. We also use functional magnetic resonance imaging (fMRI) to localize and assess changes in neural activity specifically in the medial temporal and frontal lobes during the performance of cognitive tasks, since those are the cerebral regions most sensitive to concussive head injury 6. Finally, we are acquiring structural imaging data sensitive to damage in brain white matter.

This article provides an overview of a multi-modal approach to mild traumatic brain injury diagnosis and recovery in youth. This approach combines neuropsychological testing with functional magnetic resonance imaging and the Head Impact Telemetry System to monitor the relationship between head impacts and brain activity during cognitive testing.

One of the most commonly reported injuries in children who participate in sports is concussion or mild traumatic brain injury (mTBI)1. Children and youth ...

Assessing Teratogenic Changes in a Zebrafish Model of Fetal Alcohol Exposure

Fetal alcohol syndrome (FAS) is a severe manifestation of embryonic exposure to ethanol. It presents with characteristic defects to the face and organs, including mental retardation due to disordered and damaged brain development. Fetal alcohol spectrum disorder (FASD) is a term used to cover a continuum of birth defects that occur due to maternal alcohol consumption, and occurs in approximately 4% of children born in the United States. With 50% of child-bearing age women reporting consumption of alcohol, and half of all pregnancies being unplanned, unintentional exposure is a continuing issue2. In order to best understand the damage produced by ethanol, plus produce a model with which to test potential interventions, we developed a model of developmental ethanol exposure using the zebrafish embryo. Zebrafish are ideal for this kind of teratogen study3-8. Each pair lays hundreds of eggs, which can then be collected without harming the adult fish. The zebrafish embryo is transparent and can be readily imaged with any number of stains. Analysis of these embryos after exposure to ethanol at different doses and times of duration and application shows that the gross developmental defects produced by ethanol are consistent with the human birth defect. Described here are the basic techniques used to study and manipulate the zebrafish FAS model.

In order to understand the molecular mechanisms of the ethanol-induced developmental damage, we have developed a zebrafish model of ethanol exposure and are exploring the physical, cellular, and genetic alterations that occur after ethanol exposure1. We then seek to find potential interventions and rapidly test them in this animal model.

Fetal alcohol syndrome (FAS) is a severe manifestation of embryonic exposure to ethanol. It presents with characteristic defects to the face and organs, ...

Multi-modal Imaging of Angiogenesis in a Nude Rat Model of Breast Cancer Bone Metastasis Using Magnetic Resonance Imaging, Volumetric Computed Tomography and Ultrasound

Angiogenesis is an essential feature of cancer growth and metastasis formation. In bone metastasis, angiogenic factors are pivotal for tumor cell proliferation in the bone marrow cavity as well as for interaction of tumor and bone cells resulting in local bone destruction. Our aim was to develop a model of experimental bone metastasis that allows in vivo assessment of angiogenesis in skeletal lesions using non-invasive imaging techniques.
For this purpose, we injected 105 MDA-MB-231 human breast cancer cells into the superficial epigastric artery, which precludes the growth of metastases in body areas other than the respective hind leg1. Following 25-30 days after tumor cell inoculation, site-specific bone metastases develop, restricted to the distal femur, proximal tibia and proximal fibula1. Morphological and functional aspects of angiogenesis can be investigated longitudinally in bone metastases using magnetic resonance imaging (MRI), volumetric computed tomography (VCT) and ultrasound (US).
MRI displays morphologic information on the soft tissue part of bone metastases that is initially confined to the bone marrow cavity and subsequently exceeds cortical bone while progressing. Using dynamic contrast-enhanced MRI (DCE-MRI) functional data including regional blood volume, perfusion and vessel permeability can be obtained and quantified2-4. Bone destruction is captured in high resolution using morphological VCT imaging. Complementary to MRI findings, osteolytic lesions can be located adjacent to sites of intramedullary tumor growth. After contrast agent application, VCT angiography reveals the macrovessel architecture in bone metastases in high resolution, and DCE-VCT enables insight in the microcirculation of these lesions5,6. US is applicable to assess morphological and functional features from skeletal lesions due to local osteolysis of cortical bone. Using B-mode and Doppler techniques, structure and perfusion of the soft tissue metastases can be evaluated, respectively. DCE-US allows for real-time imaging of vascularization in bone metastases after injection of microbubbles7.
In conclusion, in a model of site-specific breast cancer bone metastases multi-modal imaging techniques including MRI, VCT and US offer complementary information on morphology and functional parameters of angiogenesis in these skeletal lesions.

In the pathogenesis of bone metastasis, angiogenesis is a crucial process and therefore represents a target for imaging and therapy. Here, we present a rat model of site-specific breast cancer bone metastasis and describe strategies to non-invasively image angiogenesis in vivo using magnetic resonance imaging, volumetric computed tomography and ultrasound.

Angiogenesis is an essential feature of cancer growth and metastasis formation. In bone metastasis, angiogenic factors are pivotal for tumor cell ...

A Neuroscientific Approach to the Examination of Concussions in Student-Athletes

Concussions are occurring at alarming rates in the United States and have become a serious public health concern. The CDC estimates that 1.6 to 3.8 million concussions occur in sports and recreational activities annually. Concussion as defined by the 2013 Concussion Consensus Statement &#8220;may be caused either by a direct blow to the head, face, neck or elsewhere on the body with an &#8216;impulsive&#8217; force transmitted to the head.&#8221; Concussions leave the individual with both short- and long-term effects. The short-term effects of sport related concussions may include changes in playing ability, confusion, memory disturbance, the loss of consciousness, slowing of reaction time, loss of coordination, headaches, dizziness, vomiting, changes in sleep patterns and mood changes. These symptoms typically resolve in a matter of days. However, while some individuals recover from a single concussion rather quickly, many experience lingering effects that can last for weeks or months. The factors related to concussion susceptibility and the subsequent recovery times are not well known or understood at this time. Several factors have been suggested and they include the individual&#8217;s concussion history, the severity of the initial injury, history of migraines, history of learning disabilities, history of psychiatric comorbidities, and possibly, genetic factors. Many studies have individually investigated certain factors both the short-term and long-term effects of concussions, recovery time course, susceptibility and recovery. What has not been clearly established is an effective multifaceted approach to concussion evaluation that would yield valuable information related to the etiology, functional changes, and recovery. The purpose of this manuscript is to show one such multifaceted approached which examines concussions using computerized neurocognitive testing, event related potentials, somatosensory perceptual responses, balance assessment, gait assessment and genetic testing.

There is great variability in an individual&#8217;s risk for concussion and their corresponding recovery. A multifaceted approach to concussion evaluation is warranted; including baseline testing of athletes before participation in sport and timely evaluation post injury. The goal of this protocol is to provide an appropriate multifaceted approach to examine concussions.

Concussions are occurring at alarming rates in the United States and have become a serious public health concern. The CDC estimates that 1.6 to 3.8 ...

Non-invasive Assessments of Subjective and Objective Recovery Characteristics Following an Exhaustive Jump Protocol

Fast recovery after strenuous exercise is important in sports and is often studied via cryotherapy applications. Cryotherapy has a significant vasoconstrictive effect, which seems to be the leading factor in its effectiveness. The resulting enhanced recovery can be measured by using both objective and subjective parameters. Two commonly measured subjective characteristics of recovery are delayed-onset muscle soreness (DOMS) and ratings of perceived exertion (RPE). Two important objective recovery characteristics are countermovement jump (CMJ) performance and peak power output (PPO). Here, we provide a detailed protocol to induce muscular exhaustion of the frontal thighs with a self-paced, 3 x 30 countermovement jump protocol (30-s rest between each set). This randomized controlled trial protocol explains how to perform local cryotherapy cuff application (+ 8 &#176;C for 20 min) and thermoneutral cuff application (+ 32 &#176;C for 20 min) on both thighs as two possible post-exercise recovery modalities. Finally, we provide a non-invasive protocol to measure the effects of these two recovery modalities on subjective (i.e., DOMS of both frontal thighs and RPE) and objective recovery (i.e., CMJ and PPO) characteristics 24, 48, and 72 h post-application. The advantage of this method is that it provides a tool for researchers or coaches to induce muscular exhaustion, without using any expensive devices; to implement local cooling strategies; and to measure both subjective and objective recovery, without using invasive methods. Limitations of this protocol are that the 30 s rest period between sets is very short, and the cardiovascular demand is very high. Future studies may find the assessment of maximum voluntary contractions to be a more sensitive assessment of muscular exhaustion compared to CMJs.

This protocol describes the procedure for non-invasive recovery assessments during a 72 h recovery period. This protocol induces muscular exhaustion of the frontal thighs using countermovement jumps and uses either local cold-cuff or thermoneutral-cuff application as a recovery modality.

Fast recovery after strenuous exercise is important in sports and is often studied via cryotherapy applications. Cryotherapy has a significant ...

A Clinical Trial Assessing the Safety, Efficacy, and Delivery of Olive-Oil-Based Three-Chamber Bags for Parenteral Nutrition

Limited evidence exists to precisely estimate efficacy and safety differences between parenteral nutrition (PN) prepared using olive-oil-based three-chamber bags (3CBs) and soybean-oil-based compounded bags (CoBs) in hospitalized adult patients. We designed a multicenter, randomized, prospective, open-label, noninferiority protocol to compare the efficacy, safety, and distribution of olive-oil-based 3CBs and soybean-oil-based CoB formulations in adult Chinese patients requiring PN during surgical intervention. Subjects were randomized to receive either one of the study treatments using an interactive voice or web-based recognition system in accordance with the randomization code. Randomization was further stratified based on the study site and surgical category. Both treatment groups received similar amounts of calories and protein. In addition, the two study treatments contained a similar composition of the amino-acid component. The only difference between the two PN formulations was the lipid constitution. The duration of administration of study treatments was a minimum of 5 days up to a maximum of 14 days after the surgical procedure. The primary efficacy endpoint was serum prealbumin levels on day 5 of the study. Noninferiority was proved if the anti-log of the lower bound of the 95% confidence interval (CI) of the treatment difference was at least 0.80. Other efficacy measures included treatment preparation time; duration to achieve tolerability of oral nutrition; associated infectious complications; length of hospitalization; and laboratory assessment of markers of nutrition, inflammation, metabolism, and oxidative stress. A total of 458 patients were enrolled in the study. The results showed that olive-oil-based 3CBs were non-inferior to soybean-based CoBs, besides being well tolerated. The infection rate was found to be significantly lower in the olive-oil-based 3CB group. Thus, this study may be used as a reference for future research on lipid emulsion and 3CBs.

Here, we present a protocol for a study comparing the efficacy, safety, and delivery of olive-oil-based 3CB and soybean-oil-based CoB formulations in adults requiring parenteral nutrition. The results revealed that olive-oil-based 3CBs is non-inferior and well tolerated compared to soybean formulations.

Limited evidence exists to precisely estimate efficacy and safety differences between parenteral nutrition (PN) prepared using olive-oil-based ...

An In Vitro Approach to Photodynamic Therapy

Photodynamic therapy (PDT) is a medical procedure that involves incubation of an exogenously applied photosensitizer (PS) followed by visible light photoactivation to induce cell apoptosis. The Federal Drug Administration has approved PDT for the treatment of actinic keratosis, and clinical guidelines recommend PDT as a treatment for certain non-melanoma skin cancers and acne vulgaris. PDT is an advantageous therapeutic modality as it is low cost, non-invasive, and associated with minimal adverse events and scaring. In the first step of PDT, a PS is applied and allowed to accumulate intracellularly. Subsequent light irradiation induces reactive oxygen species formation, which may ultimately lead to cell apoptosis, membrane disruption, mitochondrial damage, immune modulation, keratinocyte proliferation, and collagen turnover. Herein, we present an in vitro method to study PDT in an adherent cell line. This treatment protocol is designed to simulate PDT and may be adjusted to studying the use of PDT with various cell lines, photosensitizers, incubation temperatures, or photoactivation wavelengths. Squamous cell carcinoma cells were incubated with 0, 0.5, 1.0, and 2 mM 5-aminolevulinic acid (5-ALA) for 30 min and photoactivated with 417 nm blue light for 1,000 s. The primary outcome measure was apoptosis and necrosis, as measured by annexin-V and 7-aminoactinomycin D flow cytometry. There was a dose-dependent increase in cell apoptosis following thirty-minute incubation of 5-ALA. To achieve high inter-test validity, it is important to maintain consistent incubation and light parameters when performing in vitro PDT experiments. PDT is a useful clinical procedure and in vitro research may allow for the development of novel PSs, optimization of protocols, and new indications for PDT.

An In Vitro Approach to Photodynamic Therapy

Photodynamic therapy (PDT) is a medical procedure that involves incubation of an exogenously applied photosensitizer (PS) followed by visible light photoactivation to induce apoptosis. We present an in vitro PDT protocol designed to simulate PDT that may be used to study differences in PS incubation and light treatment parameters.

Photodynamic therapy (PDT) is a medical procedure that involves incubation of an exogenously applied photosensitizer (PS) followed by visible light ...

Autonomic Function Following Concussion in Youth Athletes: An Exploration of Heart Rate Variability Using 24-hour Recording Methodology

Participation in organized sports makes a significant contribution to youth development, but places youth at a higher risk for sustaining a concussion. To date, return-to-activity decision-making has been anchored in the monitoring of self-reported concussion symptoms and neurocognitive testing. However, multi-modal assessments that corroborate objective physiological measures with traditional subjective symptom reporting are needed and can be valuable. Heart rate variability (HRV) is a non-invasive physiological indicator of the autonomic nervous system, capturing the reciprocal interplay between the sympathetic and parasympathetic nervous systems. There is a dearth of literature exploring the effect of concussion on HRV in youth athletes, and developmental differences preclude the application of adult findings to a pediatric population. Further, the current state of HRV methodology has primarily included short-term (5-15 min) recordings, by using resting state or short-term physical exertion testing to elucidate changes following concussion. The novelty in utilizing a 24 h&#160;recording methodology is that it has the potential to capture natural variation in autonomic function, directly related to the activities a youth athlete performs on a regular basis. Within a prospective, longitudinal research setting, this novel approach to quantifying autonomic function can provide important information regarding the recovery trajectory, alongside traditional self-report symptom measures. Our objectives regarding a 24 h recording methodology were to (1) evaluate the physiological effects of a concussion in youth athletes, and (2) describe the trajectory of physiological change, while considering the resolution of self-reported post-concussion symptoms. To achieve these objectives, non-invasive sensor technology was implemented. The raw beat-to-beat time intervals captured can be transformed to derive time domain and frequency domain measures, which reflect an individual&#39;s ability to adapt and be flexible to their ever-changing environment. By using non-invasive heart rate technology, autonomic function can be quantified outside of a traditional controlled research setting.

We demonstrate a 24 h heart rate recording methodology to evaluate the influence of concussion across the recovery trajectory in youth athletes, within an ecologically valid context.

Participation in organized sports makes a significant contribution to youth development, but places youth at a higher risk for sustaining a concussion. To ...

A Novel Approach to Monitoring Graft Neovascularization in the Human Gingiva

Laser speckle contrast imaging (LSCI) is a novel method for measuring superficial blood perfusion over large areas. Since it is non-invasive and avoids direct contact with the measured area, it is suitable for monitoring blood flow changes during wound healing in human patients. Vestibuloplasty is periodontal surgery to the oral vestibule, aiming to restore vestibular depth with simultaneous enlargement of the keratinized gingiva. In this special clinical case, a split thickness flap was elevated at the first upper premolar and a xenogenic collagen matrix was adapted to the resulting recipient bed. LSCI was used to monitor the re- and neovascularization of the graft and the surrounding mucosa for one year. A protocol is introduced for the correct adjustment of microcirculation measurement in the oral mucosa, highlighting difficulties and possible failures.
The clinical case study presented demonstrated that &#8212; following the appropriate protocol &#8212; LSCI is a suitable and reliable method for following up microcirculation in a healing wound in the human oral mucosa and gives useful information on graft integration.

This study introduces a protocol for measuring microcirculation in human oral mucosa by laser speckle contrast imaging. The monitoring of wound healing after vestibuloplasty combined with a xenogenic collagen graft is presented on a clinical case.

Laser speckle contrast imaging (LSCI) is a novel method for measuring superficial blood perfusion over large areas. Since it is non-invasive and avoids ...

Multi-Modal Home Sleep Monitoring in Older Adults

The gold standard for sleep monitoring is attended in-lab polysomnography; however, this method may be cost-prohibitive and inconvenient for patients and research participants. Home sleep testing has gained momentum in the field of sleep medicine due to its convenience and lower cost, as well as being more naturalistic. The accuracy and quality of home sleep testing, however, may be variable because studies are not monitored by sleep technologists. There has been some success in improving the accuracy of home sleep studies by having trained sleep technicians assist participants inside their homes with putting on the devices, but this can be intrusive and time-consuming for those involved. In this protocol, participants undergo at-home sleep monitoring with multiple devices: 1) a single-channel EEG device; 2) a home sleep test for sleep-disordered breathing and periodic limb movements; 3) actigraphy; and 4) sleep logs. A major challenge of this study is obtaining high-quality sleep monitoring data on the first attempt in order to minimize participant burden. This protocol describes the implementation of educational manuals with step-by-step instructions and photos. The goal is to improve the quality of home sleep testing.

Here, we present a protocol to improve the quality of data from home sleep testing by providing a method to enhance instructions through a structured participant visit. This protocol includes the implementation of a step-by-step educational manual with photos to ensure proper placement of equipment.

The gold standard for sleep monitoring is attended in-lab polysomnography; however, this method may be cost-prohibitive and inconvenient for patients and ...