Name: multi-modal home sleep monitoring in older adults
Uploaded: 2019-01-26T14:00:00
Description: Watch this Scientific Journal Video about Multi-Modal Home Sleep Monitoring in Older Adults at JoVE.com

We thank the participants for their time.
Funding: This study was supported by the following grants from the National Institutes of Health: P01 AG03991; P01 AG026276; P50 AG05681; K76 AG054863; UL1 TR000448; KL2 TR000450. The Ellison Medical Foundation and a Physician Scientist Training Award from the American Sleep Medicine Foundation also supported this study. The funding sources had no role in the study design, data collection, management, analysis, interpretation of the data, or manuscript preparation.

This protocol was approved by the Washington University Human Research Protection Office.
Instructions were written specific to commercially available devices and their related software for data collection (see Table of Materials).
1. Set up of the sleep monitoring devices prior to the participant visit
<ol>
	<li>Connect a fully charged actigraphy device to the docking station and open the actigraphy software. Initialize actigraphy device to record for the desired...

<ol>
	<li>Ju, Y. -. E., Lucey, B. P., Holtzman, D. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sleep+and+Alzheimer+disease+pathology-a+bidirectional+relationship.">Sleep and Alzheimer disease pathology-a bidirectional relationship.</a> Nature Reviews Neurology. 10 (2), 115-119 (2014).</li><li>Musiek, E. S., Holtzman, D. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Mechanisms+linking+circadian+clocks,+sleep,+and+neurodegeneration.">Mechanisms linking circadian clocks, sleep, and neurodegeneration.</a> Science. 354 (6315), 1004-1008 (2016).</li><li>Kushida, C. A., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Practice+parameters+for+the+indications+for+polysomnography+and+related+procedures:+an+update+for+2005.">Practice parameters for the indications for polysomnography and related procedures: an update for 2005.</a> Sleep. 28 (4), 499-521 (2005).</li><li>Drogos, L. L., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evidence+of+association+between+sleep+quality+and+APOE.&#949;4+in+healthy+older+adults:+a+pilot+study.">Evidence of association between sleep quality and APOE.&#949;4 in healthy older adults: a pilot study.</a> Neurology. 87 (17), 1836-1842 (2016).</li><li>Lucey, B. 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A., Peral-Peral, B., Arenas-Gaitan, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Elderly+Persons+and+Internet+Use.">Elderly Persons and Internet Use.</a> Social Science Computer Review. 31 (4), 389-403 (2013).</li><li>Cohen-Mansfield, J., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Electronic+memory+aids+for+community-dwelling+elderly+persons:+attitudes,+preferences,+and+potential+utilization.">Electronic memory aids for community-dwelling elderly persons: attitudes, preferences, and potential utilization.</a> Journal of Applied Gerontology. 24 (1), 3-20 (2005).</li><li>Lin, C. I. C., Tang, W. -. h., Kuo, F. -. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term="Mommy+wants+to+learn+the+computer":+how+middle-aged+and+elderly+women+in+Taiwan+learn+ICT+through+social+support.">"Mommy wants to learn the computer": how middle-aged and elderly women in Taiwan learn ICT through social support.</a> Adult Education Quarterly. 62 (1), 73-90 (2012).</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=.">.</a> Alice PDX Provider Manual. , (2013).</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=.">.</a> Sleep Profiler Patient Instructions. , (2012).</li><li>Altaf, Q. -. a. A., Ali, A., Piya, M. K., Raymond, N. T., Tahrani, A. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+relationship+between+obstructive+sleep+apnea+and+intra-epidermal+nerve+fiber+density,+PARP+activation+and+foot+ulceration+in+patients+with+type+2+diabetes.">The relationship between obstructive sleep apnea and intra-epidermal nerve fiber density, PARP activation and foot ulceration in patients with type 2 diabetes.</a> Journal of Diabetes Complications. 30 (7), 1315-1320 (2016).</li><li>Nilius, G., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+randomized+controlled+trial+to+validate+the+Alice+PDX+ambulatory+device.">A randomized controlled trial to validate the Alice PDX ambulatory device.</a> Nature and Science of Sleep. 9, 171-180 (2017).</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=.">.</a> Actiwatch technicial guide. , (2015).</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=.">.</a> Sleep profiler portal technical manual. , (2013).</li><li>Ju, Y. -. E., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sleep+quality+and+preclinical+Alzheimer's+disease.">Sleep quality and preclinical Alzheimer's disease.</a> JAMA Neurolgy. 70 (5), 587-593 (2013).</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=.">.</a> Acitwatch clinician guide. , (2015).</li><li>Berry, R. B., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+AASM+manual+for+the+scoring+of+sleep+and+associated+events:+rules,+terminology+and+technical+specifications.+Version+2.4.">The AASM manual for the scoring of sleep and associated events: rules, terminology and technical specifications. Version 2.4.</a> American Academy of Sleep Medicine. , (2017).</li><li>Agnew, H., Webb, W. B., Williams, R. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+first+night+effect:+an+EEG+study+of+sleep.">The first night effect: an EEG study of sleep.</a> Psychophysiology. 2 (3), 263-266 (1966).</li><li>Barnes, C. M., Drake, C. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prioritizing+sleep+health:+public+health+policy+recommendations.">Prioritizing sleep health: public health policy recommendations.</a> Perspectives on Psychological Science. 10 (6), 733-737 (2015).</li></ol>

This protocol is the novel application of instructional manuals in conjunction with participant education for in-home ambulatory sleep monitoring. Based on the results, the implementation of the protocol with instruction manuals improves the feasibility of in-home sleep testing in older adults. In-lab polysomnography remains the gold standard for sleep monitoring but may be limited by cost as well as disrupted sleep due to the new environment (i.e., the &#34;first night&#34; effect19). This protoc...

The relationship between sleep and Alzheimer&#39;s disease (AD) is a growing area of research with sleep disturbances hypothesized to have a role in both AD pathogenesis and as a biomarker for AD pathology1,2. In order to study the relationship between sleep and AD biomarkers, cognitively normal or very mildly impaired participants aged &#8805;65 years old are recruited from a longitudinal study of aging at the Knight Alzheimer&#39;s Disease Research Center (ADRC) at Washington University School of Medicine. Although this study was focused on AD research, the methods presented here have broad applicability to home sleep testing in older adults. Attended in-lab polysomnography is the gold standard for sleep monitoring3, but such monitoring can be cost-prohibitive and inconvenient for participants. An alternative is home sleep testing. The accuracy of home sleep studies may be improved by having trained sleep technicians assist participants inside their homes with device placement, but this can also be intrusive and time-consuming4. Therefore, this protocol was developed to instruct the participants how to set up sleep monitoring devices at home and still collect reliable data.
Participants were asked to wear a home sleep test (HST) for measuring sleep-disordered breathing (e.g., obstructive sleep apnea) and periodic leg movements. Following HST recording, participants wore a single-channel EEG device for 6 nights to monitor brain waves for EEG-based sleep staging. Previous findings indicate that the single-channel EEG device has a high level of agreement with polysomnography for multiple sleep parameters5. Throughout the single-channel EEG and HST monitoring period, participants completed a sleep log and were asked to wear actigraphy on their nondominant wrist for the entire duration of the sleep study to track activity. Studies were defined as acceptable if there were at least 2 nights recorded by the single-channel EEG device with &#60;10% artifact and at least 1 night recorded on the HST with &#8805;4 hours of scorable data. Initially, the failure rate due to poor data quality was ~40&#8722;50%. Repeat monitoring for participants with poor data quality was deemed too burdensome, therefore, this protocol was developed.
Previous work found that many elderly persons have difficulty adjusting to technological interventions6,7,8,9. This impacts numerous fields from geriatrics to education and is particularly relevant to medical studies in which older adults must use or interact with unfamiliar technologies. In order to reduce in-home study failure rates, education manuals were created that provided pictures and step-by-step directions to set up the HST and single-channel EEG devices. The education manuals were derived from the device user manuals10,11. Additionally, a 24-hour helpline was provided to participants, so they could reach a member of the study team at any time with any questions or concerns.
To analyze the impact of this protocol, a retrospective review was conducted on the success and failure rates for acceptable data quality from the at-home sleep monitoring before and after implementation of the education manuals. The data sources were successful recordings and participant calls to research study staff with questions. Participants were asked to come into the sleep center to learn about the sleep monitoring equipment. During the 2-hour visit, a study team member educated each participant about the equipment using the manuals, which provided step-by-step instructions for device usage. After reviewing the manuals in the office and being guided through the application and use of the devices, participants were given the opportunity to independently practice applying the home sleep monitoring devices using the manuals as a guide. Feedback was provided to participants during the visit and they were given the opportunity to ask questions in addition to reapplying the equipment as needed. Participants then took the equipment home, put the ambulatory equipment on themselves at night, and were encouraged to call a study team member at any time, day or night, for assistance troubleshooting any questions or problems.
All single-channel EEG studies were scored manually by registered sleep technologists who were validated, gold-standard scorers using modified American Academy of Sleep Medicine (AASM) scoring criteria5. HST recordings included airflow measured by nasal pressure transducer and thermistor, respiratory effort measured by thoracic and abdominal respiratory inductance plethysmograph belts, body position, pulse oximetry, and leg electromyogram (EMG) using the optional ExG yoke. Lights off and lights on were determined by the time that each participant pressed the event button on the HST device and/or entry in a sleep log. A registered sleep technologist manually scored the HST studies and then a board-certified sleep physician performed an epoch-by-epoch review of each study.
Following the introduction of this protocol, the failure rate was reduced to 19% and reliable data was obtained. The protocol represents a novel, low-cost, and effective way to increase the success rate of at-home sleep studies. While the HST device has been used in some studies, it is primarily used as a diagnostic tool and not for scientific studies12,13. This protocol also provides a method that allows participants to easily use a Positive Airway Pressure (PAP) machine while they are wearing either the HST or single-channel EEG device. The use of the HST and single-channel EEG devices with education manuals is a particularly useful research tool that could be more widely utilized using the method shown in this protocol.

<table border="0" cellpadding="0" cellspacing="0" style="width:1063px;" width="1062">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="40">
			<td height="40" style="height:40px;width:353px;">Actigraph</td>
			<td style="width:188px;">Phillips Respironics</td>
			<td style="width:293px;">1048090</td>
			<td style="width:228px;">Actiwatch 2</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Actiware site license</td>
			<td>Phillips Respironics</td>
			<td>1114828</td>
			<td>Actigraphy software</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Actigraphy docking station</td>
			<td>Phillips Respironics</td>
			<td>1048092</td>
			<td>Actiwatch charger</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Home Sleep Test (HST)</td>
			<td>Phillips Respironics</td>
			<td>1043941</td>
			<td>Alice PDX device</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Sleepware G3 software</td>
			<td>Phillips Respironics</td>
			<td>1082462</td>
			<td>Alice PDX software</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">CPAP titration kit</td>
			<td>Pro-tech</td>
			<td>P1391</td>
			<td>Connects PAP to HST</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">&#160;3-foot SpO2 Extension Cable (Nonin)&#160;</td>
			<td>Phillips Respironics</td>
			<td>927-3</td>
			<td>Oximeter cable for HST</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">SpO2 Sensor (Nonin)</td>
			<td>Phillips Respironics</td>
			<td>936</td>
			<td>Oximeter finger clip for HST</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">SD Card Reader</td>
			<td>Phillips Respironics</td>
			<td>1047300</td>
			<td>card reader for HST</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">EXG yoke</td>
			<td>Phillips Respironics</td>
			<td>1040808</td>
			<td>HST cable for leg leads</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Dual Snap Leg Lead Wires</td>
			<td>MVAP</td>
			<td>TLC0048</td>
			<td>leg leads for HST</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Small Foam Electrodes</td>
			<td>MVAP</td>
			<td>5000ZT</td>
			<td>electrodes for leg leads</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Thermistor Airflow Sensor</td>
			<td>Pro-tech</td>
			<td>P1388</td>
			<td>HST thermoistor</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Oral/Nasal Air flow Pressure Cannula</td>
			<td>Saltar Labs</td>
			<td>5760-7</td>
			<td>Pressure Transducer</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Zrip DuraBelt kit</td>
			<td>Phillips Respironics</td>
			<td>P1837</td>
			<td>HST Thoracic and Abdominal belt kit</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">Single-channel EEG</td>
			<td>Advanced Brain Monitoring</td>
			<td>SP40-1001</td>
			<td>Sleep Profiler device</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">SP Sensor EEG kit</td>
			<td>Advanced Brain Monitoring</td>
			<td>SP40-4225.1</td>
			<td>Sleep Profiler electrodes</td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;">CPAP masks</td>
			<td>Resmed</td>
			<td>62925, 63504, 63506, 63507, 63445, 63446, 63447</td>
			<td></td>
		</tr>
	</tbody>
</table>

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.

Single-channel EEG 
At the start of the study, an acceptable overnight recording with the single-channel EEG device was defined as 1) aligning with the sleep period defined by sleep log and/or actigraphy device, and 2) &#60;10% of the recording unscorable due to movement, myogenic, electrode, or other artifacts. Each participant needed at least 2 nights meeting these criteria. Prior to the implementation of the single-channel EEG manual, 14 participants wore the sing...

Watch this Scientific Journal Video about Multi-Modal Home Sleep Monitoring in Older Adults at JoVE.com

Multi-Modal Home Sleep Monitoring in Older Adults

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 ...

Our protocol has increased both the reliability of acquiring high quality sleep monitoring data in the home as well as the ease of use for older adults. The implementation of an educational flip manual has created consistency during in-person training. In addition to providing step-by-step instructions for participants to reference at home.This protocol improved the reliability of home sleep testing which can be used to diagnose some sleep disorders such as sleep apnea and periodic limb movement disorder. Monitoring sleep-wake activity in older adults may be important for studies and many areas of research including cardiovascular disease and dementia. Home sleep monitoring is more naturalistic and has a lower cost than sleep testing in a laboratory.Begin by escorting the participant into the set up room. Instruct the participant about the home sleep test device or HST. Place the black lanyard strap around the neck and tighten until it is comfortably snug.Next, have the participant stand up and position the blue belt with the holster around the chest directly under the armpits with the buckle almost centered. Then, place the other blue belt around the waist and tighten the belt until it is snug enough so it does not slide when moving during the night. Point the arrow on the belt buckle facing down.Next, snap the white box into the holster on the chest belt. And open the device by sliding the button at the top of the device to the right. Plug the chest wires into the ports on the bottom of the chest belt buckle.And plug the abdominal wires into the ports on the bottom of the abdominal belt buckle. Place the prongs of the white wire in the nose and wrap the wire around their ears. Pull the plastic piece up toward the neck to secure.Position the second set of prongs in their nostrils and wrap tubing around the participants ears. Ensure that the two prongs from the canula fit just inside the nose and position the longer prong in front of the mouth. Slide the plastic piece up toward the neck to secure and use a small piece of tape to affix both sets of tubing to each cheek.Then, run the long red and white leg wires through each pant leg along the side to avoid them getting tangled during the night and affix with sticky patches. Next, locate the anterior tibialis muscle on the outside of the participant's leg and place the sticky patches directly on the muscle at least two finger widths apart from one another. Lastly, apply tape over each sticky patch to cover it.Bend the knee and tape the wire above each knee to prevent them from getting tangled. Begin by pinching the top of the oximeter to open the clip. Match up the picture of a fingernail on the outside of the clip to the fingernail of the middle or index finger and place the oximeter on the index or middle finger.Wrap tape around the outside of the oximeter clip to secure and tuck the extra oximeter cable in the chest belt to avoid getting tangled in the wire. Then unless using PAP look at the man on the display screen and confirm that no signals are flashing. Once all sensors are on properly, and lines are solid, close the device.Tell the participant that if the yellow light on the outside of the device starts flashing during the night the device has lost a signal. If this happens, open up the device to check the display window to determine which signal has been lost. Once identified, reattach the sensor that has come off.Then, press the circular event button on the outside of the device at lights out and again at lights on. Open the device and check the good study indicator circle. If the participant wears PAP attach a PAP titration kit to the device to measure PAP flow by twisting it into the connector designated for the nasal canula.Ask the participant to attach the PAP mask to one side of the titration kit adaptor and the hose to the other side of the adaptor. Inform the participant that the line connected to the mouth and the yellow light on the device will flash the entire time if used with positive airway pressure or PAP. A piece of tape is placed over both flashing lights as a reminder to the participant.Then, place the single channel EEG device over the participant's head to demonstrate proper placement. Instruct the participant on how to adjust the head gear for proper fit and where to affix the electrodes on the forehead for accurate placement. Finally, instruct the participant to apply the device before the mask at night in order to allow removal of the mask without dislodging the device.These results indicate a single channel EEG hypnogram showing artifact free data collection during different sleep stages. On the other hand these results show a hypnogram in which there was artifact. And thus the sensors on the single channel EEG were unable to record brain wave activity during different sleep stages.Further, it is feasible to obtain high quality sleep monitoring at home in an elderly population with a single channel EEG device for sleep staging and an HST to screen for sleep disorders such as obstructive sleep apnea as shown here. The most important thing to remember in this protocol is to break the instructions down into small steps to simplify the procedure as much as possible for the participant. Following this procedure a clinical participant or research patient should be able to independently apply the home sleep testing equipment.This procedure has allowed researchers to perform detailed sleep-wake assessments at home in older adults. Additionally we have used this procedure to study how sleep changes at different stages of Alzheimer's disease.

multi-modal-home-sleep-monitoring-in-older-adults

Research

JoVE Journal

Medicine

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 ...

Collecting Saliva and Measuring Salivary Cortisol and Alpha-amylase in Frail Community Residing Older Adults via Family Caregivers

Salivary measures have emerged in bio-behavioral research that are easy-to-collect, minimally invasive, and relatively inexpensive biologic markers of stress. This article we present the steps for collection and analysis of two salivary assays in research with frail, community residing older adults-salivary cortisol and salivary alpha amylase. The field of salivary bioscience is rapidly advancing and the purpose of this presentation is to provide an update on the developments for investigators interested in integrating these measures into research on aging. Strategies are presented for instructing family caregivers in collecting saliva in the home, and for conducting laboratory analyses of salivary analytes that have demonstrated feasibility, high compliance, and yield quality specimens. The protocol for sample collection includes: (1) consistent use of collection materials; (2) standardized methods that promote adherence and minimize subject burden; and (3) procedures for controlling certain confounding agents. We also provide strategies for laboratory analyses include: (1) saliva handling and processing; (2) salivary cortisol and salivary alpha amylase assay procedures; and (3) analytic considerations.

We demonstrate: (1) procedures for collection of salivary samples in cognitive impaired older adults by family caregivers in the home setting, (2) procedures for measuring stress activity via salivary cortisol and alpha amylase, and (3) representative profiles. Protocols that allow researchers to study stress-linked processes advance our understanding of biological sensitivity and susceptibility.

Salivary measures have emerged in bio-behavioral research  that are easy-to-collect, minimally invasive, and relatively inexpensive  biologic markers of ...

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.

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

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.

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 ...

Home-Based Transcranial Direct Current Stimulation Device Development: An Updated Protocol Used at Home in Healthy Subjects and Fibromyalgia Patients

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation (NIBS) method, which modulates the membrane potential of neurons in the cerebral cortex by a low-intensity direct current. tDCS is a low-cost technique with minimal adverse effects and easy application. This neurostimulation method has a promising future to improve pain therapy, treatment of neuropsychiatric disorders, and physical rehabilitation.
Current studies demonstrate the benefits of using tDCS over consecutive multiple sessions. However, the daily displacement to the specialized centers, travel costs, and disruptions to daily activities are some of the difficulties faced by patients. Thus, to be more comfortable, easy-to-use, and not disrupt daily commitments, a home-based tDCS was designed. Therefore, the objective of this study was to evaluate the feasibility of a portable tDCS device for home use in healthy subjects and fibromyalgia patients.
Despite increased tDCS use and a reasonably large body of research on the effects across a range of clinical conditions, there is a limited amount of research on developing secure devices that guarantee the dose and contain a block system to avoid excessive use. Therefore, we used a tDCS device with a security system to permit daily use for 20 minutes with a minimal interval of 12 hours between sessions. A programmer preconfigures the equipment, which has a neoprene cap that allows the electrode positions in any assembly, according to individualized protocols for treatments or research. After, researchers can assess the effectiveness of treatment, and its adherence using information kept in the device software.
Results suggest that the device is feasible for home use, with proper monitoring of adherence and contact impedance. There were reports of a few adverse effects, which do not differ from those reported in the literature in studies with the treatment under direct supervision.

This study provides an updated home-based tDCS protocol that enables subjects to receive the beneficial effects of tDCS at home with an easy to use device with settings to control the use and dosage, enhancing the feasibility for long-term use at home.

Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation (NIBS) method, which modulates the membrane potential of neurons in the ...

CO2-Lasertonsillotomy Under Local Anesthesia in Adults

Tonsil-related complaints are very common among the adult population. Tonsillectomy under general anesthesia is currently the most performed surgical treatment in adults for such complaints. Unfortunately, tonsillectomy is an invasive treatment associated with a high complication rate and a long recovery time. Complications and a long recovery time are mostly related to removing the vascular and densely innervated capsule of the tonsils. Recently, CO2-lasertonsillotomy under local anesthesia has been demonstrated to be a viable alternative treatment for tonsil-related disease with a significantly shorter and less painful recovery period. The milder side-effect profile of CO2-lasertonsillotomy is likely related to leaving the tonsil capsule intact. The aim of the current report is to present a concise protocol detailing the execution of CO2-lasertonsillotomy under local anesthesia. This intervention has been performed successfully in our hospital in more than 1,000 patients and has been found to be safe and to be associated with a steep learning curve.

CO2-Lasertonsillotomy Under Local Anesthesia in Adults

CO2-lasertonsillotomy under local anesthesia is an interesting alternative treatment method for tonsillectomy under general anesthesia for tonsil-related complaints in adults. This report presents a step-by-step protocol detailing the execution of CO2-lasertonsillotomy under local anesthesia.

Tonsil-related complaints are very common among the adult population. Tonsillectomy under general anesthesia is currently the most performed surgical ...

A Training Program Using an Agility Ladder for Community-Dwelling Older Adults

Aging impairs physical and cognitive functions and limits daily activities. Agility training can improve or maintain physical functioning in older people. The purpose of this study is to report the physical fitness benefits of a training program for independent community-dwelling older adults using an agility ladder. Each training session lasted approximately 30 minutes, and the benefits were achieved with two sessions per week for 14 weeks. Training was timed and involved four different drills and varying levels of difficulty through time. The exercises were performed at the School of Physical Education of the University of Campinas, S&#227;o Paulo state, Brazil. The study participants (n = 16; mean age of 66.9 &#177; 5.0 years) were instructed to perform the exercises as quickly as possible without making mistakes and were assisted by a physical trainer when they made mistakes. Assessments were performed both before and after training using five functional tests (i.e., Illinois agility, five times sit-to-stand, timed up-and-go, walking usual speed, and one-leg stand). Although the study sample was not compared with a control group, the results indicate that training protocols using an agility ladder are easy and practical and improve physical function performance in older adults.

The aim of this study is to present an agility training program for older people. The feasibility of this program is described, and the training protocol demonstrated by video imaging.

Aging impairs physical and cognitive functions and limits daily activities. Agility training can improve or maintain physical functioning in older people. ...

Oral Health Assessment by Lay Personnel for Older Adults

Oral health is an often-undervalued contributor to overall health. The literature, however, underscores the myriad of systemic diseases influenced by oral health, including type II diabetes, heart disease, and atherosclerosis. Thus, assessments of oral health, called oral screenings, have a significant role in assessing risk of disease, managing disease, and even improving disease by oral care. Here we present a method to assess oral health quickly and consistently across time. The protocol is simple enough for non-oral health professionals such as students, family, and caregivers. Useful for any age of patient, the method is particularly key for older individuals who are often at risk of inflammation and chronic disease. Components of the method include existing oral health assessment scales and inventories, which are combined to produce a comprehensive assessment of oral health. Thus, oral characteristics assessed include intraoral and extraoral structures, soft and hard tissues, natural and artificial teeth, plaque, oral functions such as swallowing, and the impact this oral health status has on the patient&#39;s quality of life. Advantages of this method include its inclusion of measures and perceptions of both the observer and patient, and its ability to track changes in oral health over time. Results acquired are quantitative totals of questionnaire and oral screening items, which can be summed for an oral health status score. The scores of successive oral screenings can be used to track the progression of oral health across time and guide recommendations for both oral and overall health care.

The goal of this protocol is to enable non-dental professionals to assess oral health status for research or health-screening purposes. Aspects assessed include lips, tongue, soft and hard tissues, natural and artificial teeth, oral cleanliness, plaque, swallowing, and impact of oral health on quality of life.

Oral health is an often-undervalued contributor to overall health. The literature, however, underscores the myriad of systemic diseases influenced by oral ...

Digital Home-Monitoring of Patients after Kidney Transplantation: The MACCS Platform

The MACCS (Medical Assistant for Chronic Care Service) platform enables secure sharing of key medical information between patients after kidney transplantation and physicians. Patients provide information such as vital signs, well-being, and medication intake via smartphone apps. The information is transferred directly into a database and electronic health record at the kidney transplant center, which is used for routine patient care and research. Physicians can send an updated medication plan and laboratory data directly to the patient app via this secure platform. Other features of the app are medical messages and video consultations. Consequently, the patient is better-informed, and self-management is facilitated. In addition, the transplant center and the patient's local nephrologist automatically exchange notes, medical reports, laboratory values, and medication data via the platform. A telemedicine team reviews all incoming data on a dashboard and takes action, if necessary. Tools to identify patients at risk for complications are under development. The platform exchanges data via a standardized secure interface (Health Level 7 (HL7), Fast Healthcare Interoperability Resources (FHIR)). The standardized data exchange based on HL7 FHIR guarantees interoperability with other eHealth solutions and allows rapid scalability to other chronic diseases. The underlying data protection concept is in concordance with the latest European General Data Protection Regulation. Enrollment started in February 2020, and 131 kidney transplant recipients are actively participating as of July 2020. Two large German health insurance companies are currently funding the telemedicine services of the project. The deployment for other chronic kidney diseases and solid organ transplant recipients is planned. In conclusion, the platform is designed to enable home monitoring and automatic data exchange, empower patients, reduce hospitalizations, and improve adherence, and outcomes after kidney transplantation.

The MACCS platform&#160;is a comprehensive telemedicine concept aiming at better outcomes after kidney transplantation by sharing key medical information between patients and physicians. A telemedicine team reviews incoming data to detect potential complications and to improve adherence in kidney transplant recipients to achieve better long-term outcomes.

The MACCS (Medical Assistant for Chronic Care Service) platform enables secure sharing of key medical information between patients after kidney ...

Synthesis and Characterization of Multi-Modal Phase-Change Porphyrin Droplets

Phase-change droplets are a class of ultrasound contrast agents that can convert into echogenic microbubbles in situ with the application of sufficient acoustic energy. Droplets are smaller and more stable than their microbubble counterparts. However, traditional ultrasound contrast agents are not trackable beyond acoustic feedback measurements, which makes quantifying contrast agent bio-distribution or accumulation ex vivo difficult. Researchers may have to rely on fluorescent or optically absorbent companion diagnostic particles to infer bio-distribution. The purpose of this protocol is to detail steps for creating multi-modal phase-change porphyrin droplets using a condensation method. Porphyrins are fluorescent molecules with distinct absorbance bands that can be conjugated onto lipids and incorporated into droplets to extend droplet versatility, enabling more robust bio-distribution while retaining acoustic properties. Seven formulations with varying porphyrin-lipid and base lipid contents were made to investigate microbubble and droplet size distributions. Characterizations suited to porphyrin-containing structures are also described in the protocol to demonstrate their analytic versatility in-solution. Sizing showed that the post-condensed mean diameters were 1.72 to 2.38 times smaller than precursor populations. Absorbance characterization showed intact assemblies had a Q-band peak of 700 nm while disrupted samples had an absorbance peak at 671 nm. Fluorescence characterization showed intact 30% porphyrin-lipid assemblies were fluorescently quenched (&gt;97%), with fluorescence recovery achieved upon disruption. Acoustic vaporization showed that porphyrin droplets were non-echogenic at lower pressures and could be converted into echogenic microbubbles with sufficient pressures. These characterizations show the potential for porphyrin droplets to eliminate the need for absorbance or fluorescence-based companion diagnostic strategies to quantify ultrasound contrast agent bio-distribution for delivery or therapeutic applications in vivo or ex vivo.

In this protocol, methods for synthesizing and characterizing multi-modal phase-change porphyrin droplets are outlined.

Phase-change droplets are a class of ultrasound contrast agents that can convert into echogenic microbubbles in situ with the application of sufficient ...