Name: adapted resistance training improves strength in eight weeks in individuals with multiple sclerosis
Uploaded: 2016-01-29T15:00:00
Description: Watch this Scientific Journal Video about Adapted Resistance Training Improves Strength in Eight Weeks in Individuals with Multiple Sclerosis at JoVE.com

The authors would like to thankfully acknowledge Rhul Marasigan and all of the participants in the study. The exercise illustrations were provided by Tziporah Thompson.

NOTE: The institutional review boards at Johns Hopkins University School of Medicine and Kennedy Krieger Institute approved this work. All participants provided written consent before participating.
1. Training
<ol>
	<li>Ensure that the instructor is adequately trained in the use of hand held dynamometry and specifics of exercise details prior to initiating this protocol. 
	NOTE: Test a mix of individuals with varying strength levels to assure competence and consistency following the sp...

<ol>
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G., Ringgaard, S., Stenager, E., Petersen, T., Dalgas, U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuromuscular+adaptations+to+long-term+progressive+resistance+training+translates+to+improved+functional+capacity+for+people+with+multiple+sclerosis+and+is+maintained+at+follow-up.">Neuromuscular adaptations to long-term progressive resistance training translates to improved functional capacity for people with multiple sclerosis and is maintained at follow-up.</a> Mult Scler. 21 (5), 599-611 (2015).</li><li>Kj&#248;lhede, T., Vissing, K., Dalgas, U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multiple+sclerosis+and+progressive+resistance+training:+a+systematic+review.">Multiple sclerosis and progressive resistance training: a systematic review.</a> Mult Scler. 18 (9), 1215-1228 (2012).</li><li>Dalgas, U., Stenager, E., Lund, C., 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=Neural+drive+increases+following+resistance+training+in+patients+with+multiple+sclerosis.">Neural drive increases following resistance training in patients with multiple sclerosis.</a> J Neurol. 260 (7), 1822-1832 (2013).</li><li>Dalgas, U., Stenager, E., Jakobsen, J., Petersen, T., Hansen, H. 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F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rating+neurologic+impairments+in+multiple+sclerosis:+an+expanded+disability+status+scale+(EDSS).">Rating neurologic impairments in multiple sclerosis: an expanded disability status scale (EDSS).</a> Neurology. 33 (11), 1444-1452 (1983).</li><li>Sahrmann, S. 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> Diagnosis and Treatment of Movement Impairment Syndromes. , (2002).</li><li>Bohannon, R. 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The protocol describes a progressive resistance training program using isolated muscle strengthening with resistance bands for people with MS. This protocol has unique features for individuals with degenerative conditions whose strength limitations may be compromising their ability to ambulate and maintain their quality of life. The focus is on improving proximal muscle strength in the lower extremities that is important for walking speed in MS21;4. One advantage of this protocol is that it emphasizes isolated...

In MS, compromised neural function typically leads to motor dysfunction, resulting in weakness. It is known that muscle weakness contributes to reduced daily activity in people with MS and inactivity further compromises functional ability1;2. Our lab has shown that weak hip flexor muscles in individuals with MS affect walking speed3, particularly in the weakest individuals4. The significance of weak proximal hip muscles to walking has been shown in MS as well as in other neurodegenerative conditions4;5. This vicious cycle contributes to increased disability and reduced quality of life6;7. Regular exercise can improve daily activity8, cardiovascular fitness8;9, muscle strength10, and fatigue8;11 in people with MS12. Strength training is known to promote neural adaptations that can lead to favorable functional outcomes in MS participants13-16.&#160;Since physical rehabilitation is often the only treatment offered to individuals with MS for recovery of function, it is critical to determine what is the most efficient way to improve strength.
Resistance strength training has been evaluated with no clear consensus on the minimal amount of time needed to see significant changes in muscle strength or the best method for optimizing strengthening. A current review reports that resistance training studies have varied in length from 3 to 26 weeks, mainly targeting the lower extremities in persons with MS suffering from low to moderate impairments (with an Expanded Disability Status Scale of 0-6.5)14;17;18. These studies primarily use isokinetic devices for training with direct supervision in a gym location. The use of isokinetic equipment is one way to isolate and strengthen single muscles, but it limits a person&#8217;s ability to complete the exercises without use of expensive equipment that is not always accessible. Resistance bands offer the advantage of controlling the direction of resistance as well as the placement of the resistance on the limb, thereby avoiding stresses to distal joints. Resistance bands also offer the opportunity to grade the resistance in finer increments then with other equipment such as with cuff weights.
Alignment and movement patterns are carefully addressed in the training of athletes, yet little attention is given to these factors in individuals with chronic degenerating conditions, in part because their limitations are so complex (e.g., sensory, motor control, cognition). The need to address alignment in exercises, as well as in everyday activities is critical19. Simple, but well-selected exercises that are precisely performed aid in the resolution of musculoskeletal syndromes in individuals with intact nervous systems19. Although many generic exercise programs are available, they do not address the specific impairments in MS that affect mobility and modifications necessary, given the progressive nature of the disease. For this program, we emphasize postural alignment, as well as specific exercises that are done in a position that is most optimal for how the muscle is used functionally.
The goal in this study was to create an accessible, inexpensive, resistance training program for the hip muscles that is generalizable to individuals with variable degrees of disability. Simple but precisely described hip strengthening exercises are adapted here emphasizing the strengthening of isolated muscles and guidelines are provided for individuals to further adapt the exercises depending on their current muscle strength. Recommendations are made so individuals can exercise with resistance bands in a systematic way that is easily adaptable to the home and details needed to replicate the program are specified.

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	<tbody>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">microFET2</td>
			<td style="width:169px;">Hoggan Scientific, LLC</td>
			<td style="width:147px;"></td>
			<td style="width:248px;">Digital hand held muscle tester</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:213px;">REP Bands (all colors)</td>
			<td style="width:169px;">Power Systems</td>
			<td style="width:147px;">5600-011</td>
			<td style="width:248px;">Resistance bands for the exercise program</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:213px;">TheraBand Latex-Free Exercise Bands (all colors)</td>
			<td style="width:169px;">TheraBand</td>
			<td style="width:147px;">11726-11730</td>
			<td style="width:248px;">Resistance bands for the exercise program</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:213px;">8&#39;&#39; Cable Ties</td>
			<td style="width:169px;">Lowes Home Improvement</td>
			<td style="width:147px;">76329</td>
			<td style="width:248px;">Tied into the resistance bands to provide places for the carabiner to clip onto</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">Door Anchor</td>
			<td style="width:169px;">GoFit</td>
			<td style="width:147px;"></td>
			<td style="width:248px;">Anchors the REP bands to doors</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:213px;">Hollow-Braid Poly Rope</td>
			<td style="width:169px;">Home Depot</td>
			<td style="width:147px;">140538</td>
			<td style="width:248px;">Anchors REP bands to table legs/other fixtures</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">Zinc-Plated Steel Hang All</td>
			<td style="width:169px;">Home Depot</td>
			<td style="width:147px;">550768</td>
			<td style="width:248px;">Thigh straps for the hip exercises</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">Neoprene Ankle Strap</td>
			<td style="width:169px;">TKO</td>
			<td style="width:147px;">106 BK</td>
			<td style="width:248px;">Ankle strap for leg exercises</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:213px;">Positron Carabiner</td>
			<td style="width:169px;">Black Diamond</td>
			<td style="width:147px;">BD2102610000ALL1</td>
			<td style="width:248px;">Carabiners to link ankle/thigh strap to REP bands</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:213px;">Fitness Gear 3mm Mat</td>
			<td style="width:169px;">Dick&#39;s Sporting Goods</td>
			<td style="width:147px;">41857546</td>
			<td style="width:248px;">Yoga mat for exercises on the ground</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:213px;">1/2 inch, 2 by 2 Exercise Tiles</td>
			<td style="width:169px;">FoamTiles</td>
			<td style="width:147px;"></td>
			<td style="width:248px;">Gym matting for exercies on the ground</td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:213px;">Spirit LT Portable Massage Table</td>
			<td style="width:169px;">EarthLite</td>
			<td style="width:147px;"></td>
			<td style="width:248px;">Table for hip extension and other exercises that required a raised platform</td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:213px;">Performa Treatment Table</td>
			<td style="width:169px;">Sammons Preston</td>
			<td style="width:147px;">553736</td>
			<td style="width:248px;">Heavy treatment table for testing/anchoring REP bands</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">STATA SE 11</td>
			<td style="width:169px;">STATA</td>
			<td></td>
			<td style="width:248px;">Software for statistical analysis</td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:213px;">STATISTICA</td>
			<td style="width:169px;">Dell Software</td>
			<td></td>
			<td style="width:248px;">Software for statistical analysis</td>
		</tr>
	</tbody>
</table>

adapted resistance training improves strength in eight weeks in individuals with multiple sclerosis

Hip weakness is a common symptom affecting walking ability in people with multiple sclerosis (MS). It is known that resistance strength training (RST) can improve strength in individuals with MS, however; it remains unclear the duration of RST that is needed to make strength gains and how to adapt hip strengthening exercises for individuals of varying strength using only resistance bands. This paper describes the methodology to set up and implement an adapted resistance strength training program, using resistance bands, for individuals with MS. Directions for pre- and post-strength tests to evaluate efficacy of the strength-training program are included. Safety features and detailed instructions outline the weekly program content and progression. Current evidence is presented showing that significant strength gains can be made within 8 weeks of starting a RST program. Evidence is also presented showing that resistance strength training can be successfully adapted for individuals with MS of varying strength with little equipment.

We show results from 26 individuals with MS who participated in a 12-week lower extremity progressive, resistance training (PRT) at our facility. Our participants have varying levels of disability with a median EDSS of 4.0 (range: 1-6.5), are on average 50.0 (11.3) years of age (youngest is 23 years, oldest is 64 years), 17 are female, and have an average symptom duration of 12.5 (8.7) years.
Figure 1 shows that hip strength improved following 12-weeks of training (p&#60;0.005...

Watch this Scientific Journal Video about Adapted Resistance Training Improves Strength in Eight Weeks in Individuals with Multiple Sclerosis at JoVE.com

Adapted Resistance Training Improves Strength in Eight Weeks in Individuals with Multiple Sclerosis

Hip weakness is a common symptom affecting walking ability in people with multiple sclerosis. Isolated muscle strengthening is a useful method to target specific weaknesses. This protocol describes a progressive resistance-training program using exercise bands to increase hip muscle strength.

Hip weakness is a common symptom affecting walking ability in people with multiple sclerosis (MS). It is known that resistance strength training (RST) can ...

The goal of this study was to create a progressive resistance training program to strengthen hip muscles in order to improve walking. This protocol provides a solution to address hip weakness which is a primary impairment that affects the quality of life of people with neurodegenerative diseases. The main advantage of this technique is that the program uses resistance bands in a systematic way that is accessible, inexpensive, and can be used in a group setting for people with variable levels of disability.We emphasize isolated muscle strengthening and proper alignment for how the muscle is used in walking. This progressive resistance training program can be individualized to accommodate asymmetric weakness, profound weakness or mild weakness. Demonstrating the procedure with me will Zipporah Thompson, a research coordinator from our laboratory.Begin by explaining the procedure to the participant. Assess baseline strength status for the hip flexor, hip extensor, and hip abductor muscles by using a handheld dynamometer during a break test. During the break test, obtain measures from each side of the body and repeat to obtain two consistent measures for each side within 45 newtons of eachother.Ask the participant to hold each position for four to five seconds at maximal effort and encourage the participant as they complete the test. Record each measure and average the two measures for each side. Begin the break test by measuring hip flexion.Instruct the participant to lie supine on a mat, legs extended, body relaxed, and head resting on a pillow. Have them bend one knee and hip and hold the hip at 90 degrees. Next, place the dynamometer on the distal femur.Instruct the participant to pull their knee toward their nose and to hold as strongly as possible. Then slowly and evenly pull the dynamometer in the direction of the particpant's toes. For the hip extension, instruct the participant to lie prone on a plinth with their legs extended and body relaxed.Ask them to bend one knee to 90 degrees flexion and hold. Then place the dynamometer on the distal femur. Instruct the participant to use their buttocks to lift their knee off the mat.Then hold and do not twist. Push the dynamometer down in the direction of the mat. Finally, for hip abduction, instruct the participant to lie on their side with their shoulders back and hips resting against a wall.Provide the participant with the option to rest their head on the bottom arm or hand. Ask the participant to bend their bottom leg knee and extend the top leg with the heel touching the wall and toes pointing slightly upward. Then instruct them to keep the top leg straight with their heel against the wall, lift the leg up to 45 degrees and hold.Place the dynamometer on the participant's distal femur and push down in the direction of the mat. Prior to each exercise, instruct the participant to look at their exercise log to determine which resistance level to use and to fill in the log after each exercise is complete. Begin with the hip flexion exercise by instructing the participant to lie supine with both hips straight.Ask them to slowly lift one knee towards the chest to end range of hip flexion, all the while keeping the knee close to the midline. Then instruct them to lower the leg with control to the starting position. For weaker participants, provide the option of performing this exercise side-lying with the top leg supported on a low bench placed in front of the participant.Next for hip abduction, instruct the participant to lie side-lying with their bottom leg slightly bent and the top leg straight. Instruct them to lift their top leg toward the ceiling, keeping the leg inline with the trunk and the knee facing straight ahead or slightly turned up toward the ceiling. Then ask them to lower their leg to the starting position.To perform hip extension instruct the participant to lie face-lying with one leg straight and one leg bent. Instruct them to raise the bent thigh off the support surface while keeping the knee bent. For knee flexion, instruct the participant to lie face-lying with both legs straight.Ask the participant to bend their knee as far as possible, keeping the pelvis and thigh still and keeping the hips on the support surface. Next, for hip external rotation, instruct the participant to start in a seated position. Then have them rotate the knee or thigh outward.Instruct stronger participants to perform hip external rotation while standing with their knee resting on a chair and hip maintained in extension. To perform knee extension, instruct the participant to lie supine with their exercise leg straight and resting leg bent. Then instruct them to raise the leg from the hip, keeping the knee straight and stopping at the height of the resting leg knee.Finally, provide each participant an individualized home exercise program for each weekend. Remind each participant to fill out the exercise log immediately following each exercise. In this study, individuals with varying levels of disability for multiple sclerosis participated in lower extremity resistance training in which statistically significant improvements were made in hip strength over the course of 12 weeks.Here, data from an individual with asymmetrical hip strength at baseline is shown. Following strength training, this individual gained hip flexion strength on their weaker left side. Additionally, hip abductor and extensor muscles were more symmetric and stronger post-intervention.These results demonstrate that significant strength improvements occur within eight weeks of training. In designing clinical trials that test pharmacologic or rehabilitative interventions, seeing change in eight weeks allows for expedient results. As with other intervention studies, participant compliance both with frequency and quality of performance is a potential issue.Providing specific feedback to the individual as well as maintaining a motivating group setting is essential for the success of the program. After watching this video, you should have a good understanding at how to quantitatively evaluate progress from a resistance training program. Don't forget that the reliability of the tester in the use of the dynamometer as well as properly instructing and encouraging the participant on giving their best performance is necessary.Resistance exercise is a common intervention used by therapists and has tremendous potential. However, it is necessary to provide appropriate supervision to ensure that proper alignment and safety is maintained throughout the program. Future application of this protocol in the home will provide greater opportunity for more individuals to benefit from this program.

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Research

JoVE Journal

Medicine

The Multiple Sclerosis Performance Test (MSPT): An iPad-Based Disability Assessment Tool

Precise measurement of neurological and neuropsychological impairment and disability in multiple sclerosis is challenging. We report a new test, the Multiple Sclerosis Performance Test (MSPT), which represents a new approach to quantifying MS related disability. The MSPT takes advantage of advances in computer technology, information technology, biomechanics, and clinical measurement science. The resulting MSPT represents a computer-based platform for precise, valid measurement of MS severity. Based on, but extending the Multiple Sclerosis Functional Composite (MSFC), the MSPT provides precise, quantitative data on walking speed, balance, manual dexterity, visual function, and cognitive processing speed. The MSPT was tested by 51 MS patients and 49 healthy controls (HC). MSPT scores were highly reproducible, correlated strongly with technician-administered test scores, discriminated MS from HC and severe from mild MS, and correlated with patient reported outcomes. Measures of reliability, sensitivity, and clinical meaning for MSPT scores were favorable compared with technician-based testing. The MSPT is a potentially transformative approach for collecting MS disability outcome data for patient care and research. Because the testing is computer-based, test performance can be analyzed in traditional or novel ways and data can be directly entered into research or clinical databases. The MSPT could be widely disseminated to clinicians in practice settings who are not connected to clinical trial performance sites or who are practicing in rural settings, drastically improving access to clinical trials for clinicians and patients. The MSPT could be adapted to out of clinic settings, like the patient&#8217;s home, thereby providing more meaningful real world data. The MSPT represents a new paradigm for neuroperformance testing. This method could have the same transformative effect on clinical care and research in MS as standardized computer-adapted testing has had in the education field, with clear potential to accelerate progress in clinical care and research.

The Multiple Sclerosis Performance Test MSPT: An iPad-Based Disability Assessment Tool

Precise measurement of neurological and neuropsychological impairment and disability in multiple sclerosis is challenging. We report methodologic details on a new test, the Multiple Sclerosis Performance Test (MSPT). This new approach to the objective of quantification of MS related disability provides a computer-based platform for precise, valid measurement of MS severity.

Precise measurement of neurological and neuropsychological impairment and disability in multiple sclerosis is challenging. We report a new test, the ...

Increasing Pulmonary Artery Pulsatile Flow Improves Hypoxic Pulmonary Hypertension in Piglets

Pulmonary arterial hypertension (PAH) is a disease affecting distal pulmonary arteries (PA). These arteries are deformed, leading to right ventricular failure. Current treatments are limited. Physiologically, pulsatile blood flow is detrimental to the vasculature. In response to sustained pulsatile stress, vessels release nitric oxide (NO) to induce vasodilation for self-protection. Based on this observation, this study developed a protocol to assess whether an artificial pulmonary pulsatile blood flow could induce an NO-dependent decrease in pulmonary artery pressure. One group of piglets was exposed to chronic hypoxia for 3 weeks and compared to a control group of piglets. Once a week, the piglets underwent echocardiography to assess PAH severity. At the end of hypoxia exposure, the piglets were subjected to a pulsatile protocol using a pulsatile catheter. After being anesthetized and prepared for surgery, the jugular vein of the piglet was isolated and the catheter was introduced through the right atrium, the right ventricle and the pulmonary artery, under radioscopic control. Pulmonary artery pressure (PAP) was measured before (T0), immediately after (T1) and 30 min after (T2) the pulsatile protocol. It was demonstrated that this pulsatile protocol is a safe and efficient method of inducing a significant reduction in mean PAP via an NO-dependent mechanism. These data open up new avenues for the clinical management of PAH.

Pulmonary hypertension is associated with a significant reduction in pulmonary artery pulsatility, contractility and elasticity, contributing to an increase in pulmonary artery pressure and pulmonary resistance. Using a hypoxic piglet model, this study demonstrated that improving pulmonary artery plasticity using a newly developed pulsatile catheter improves hypoxic pulmonary hypertension.

Pulmonary arterial hypertension (PAH) is a disease affecting distal pulmonary arteries (PA). These arteries are deformed, leading to right ventricular ...

A Method of Trigonometric Modelling of Seasonal Variation Demonstrated with Multiple Sclerosis Relapse Data

This report describes a novel Stata-based application of trigonometric regression modelling to 55 years of multiple sclerosis relapse data from 46 clinical centers across 20 countries located in both hemispheres. Central to the success of this method was the strategic use of plot analysis to guide and corroborate the statistical regression modelling. Initial plot analysis was necessary for establishing realistic hypotheses regarding the presence and structural form of seasonal and latitudinal influences on relapse probability and then testing the performance of the resultant models. Trigonometric regression was then necessary to quantify these relationships, adjust for important confounders and provide a measure of certainty as to how plausible these associations were. Synchronization of graphing techniques with regression modelling permitted a systematic refinement of models until best-fit convergence was achieved, enabling novel inferences to be made regarding the independent influence of both season and latitude in predicting relapse onset timing in MS. These methods have the potential for application across other complex disease and epidemiological phenomena suspected or known to vary systematically with season and/or geographic location.

Combining plot analysis with trigonometric regression is a robust method for exploring complex, cyclical phenomena such as relapse onset timing in multiple sclerosis (MS). This method enabled unbiased characterisation of seasonal trends in relapse onset permitting novel inferences around the influence of seasonal variation, ultraviolet radiation (UVR) and latitude.

This report describes a novel Stata-based application of trigonometric regression modelling to  55 years of multiple sclerosis relapse data from 46 ...

A Protocol for the Use of Remotely-Supervised Transcranial Direct Current Stimulation (tDCS) in Multiple Sclerosis (MS)

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses low amplitude direct currents to alter cortical excitability. With well-established safety and tolerability, tDCS has been found to have the potential to ameliorate symptoms such as depression and pain in a range of conditions as well as to enhance outcomes of cognitive and physical training. However, effects are cumulative, requiring treatments that can span weeks or months and frequent, repeated visits to the clinic. The cost in terms of time and travel is often prohibitive for many participants, and ultimately limits real-world access. 
Following guidelines for remote tDCS application, we propose a protocol that would allow remote (in-home) participation that uses specially-designed devices for supervised use with materials modified for patient use, and real-time monitoring through a telemedicine video conferencing platform. We have developed structured training procedures and clear, detailed instructional materials to allow for self- or proxy-administration while supervised remotely in real-time. The protocol is designed to have a series of checkpoints, addressing attendance and tolerability of the session, to be met in order to continue to the next step. The feasibility of this protocol was then piloted for clinical use in an open label study of remotely-supervised tDCS in multiple sclerosis (MS). This protocol can be widely used for clinical study of tDCS.

A Protocol for the Use of Remotely-Supervised Transcranial Direct Current Stimulation tDCS in Multiple Sclerosis MS

The goal of this pilot study is to describe a protocol for the remotely-supervised delivery of transcranial direct current stimulation (tDCS) so that the procedure maintains standards of in-clinic practice, including safety, reproducibility, and tolerability. The feasibility of this protocol was tested in participants with multiple sclerosis (MS).

Transcranial direct current stimulation (tDCS) is a noninvasive brain stimulation technique that uses low amplitude direct currents to alter cortical ...

Depletion of Mouse Cells from Human Tumor Xenografts Significantly Improves Downstream Analysis of Target Cells

The use of in vitro cell line models for cancer research has been a useful tool. However, it has been shown that these models fail to reliably mimic patient tumors in different assays1. Human tumor xenografts represent the gold standard with respect to tumor biology, drug discovery, and metastasis research 2-4. Tumor xenografts can be derived from different types of material like tumor cell lines, tumor tissue from primary patient tumors4 or serially transplanted tumors. When propagated in vivo, xenografted tissue is infiltrated and vascularized by cells of mouse origin. Multiple factors such as the tumor entity, the origin of xenografted material, growth rate and region of transplantation influence the composition and the amount of mouse cells present in tumor xenografts. However, even when these factors are kept constant, the degree of mouse cell contamination is highly variable.
Contaminating mouse cells significantly impair downstream analyses of human tumor xenografts. As mouse fibroblasts show high plating efficacies and proliferation rates, they tend to overgrow cultures of human tumor cells, especially slowly proliferating subpopulations. Mouse cell derived DNA, mRNA, and protein components can bias downstream gene expression analysis, next-generation sequencing, as well as proteome analysis 5. To overcome these limitations, we have developed a fast and easy method to isolate untouched human tumor cells from xenografted tumor tissue. This procedure is based on the comprehensive depletion of cells of mouse origin by combining automated tissue dissociation with the benchtop tissue dissociator and magnetic cell sorting. Here, we demonstrate that human target cells can be can be obtained with purities higher than 96% within less than 20 min independent of the tumor type.

Human tumor xenografts are vascularized and infiltrated by cells of mouse origin during the growth phase in vivo. To circumvent the bias caused by these contaminating cells during downstream analysis, we developed a method allowing for comprehensive depletion of all mouse cells by magnetic cell sorting.

The use of in vitro cell line models for cancer research has been a useful tool. However, it has been shown that these models fail to reliably mimic ...

Exergaming in Older People Living with HIV Improves Balance, Mobility and Ameliorates Some Aspects of Frailty

Approximately 1.2 million people in the United States live with HIV infection. Medical advancements have increased the life expectancy and this cohort is aging. HIV-positive individuals have a high incidence of frailty (~20%) characterized by depression and sedentary behavior. Exercise would be healthy, but due to the frail status of many HIV-positive individuals, conventional exercise is too taxing. The aim of this study was to evaluate the effectiveness and acceptability of a novel game-based training program (exergame) in ameliorating some aspects of frailty in HIV-infected individuals. Ten older people living with HIV were enrolled in an exergame intervention. Patients performed balance exercises such as weight shifting, ankle reaching, and obstacle crossing. Real-time visual/audio lower-extremity joint motion feedback was provided using wearable sensors to assist feedback and encourage subjects to accurately execute each exercise task. Patients trained twice a week for 45 min for 6 weeks. Changes in balance, gait, psychosocial parameters and quality of life parameters were assessed at the beginning, midterm and at conclusion of the training program. Ten patients completed the study and their results analyzed. The mean age was 57.2 &#177; 9.2 years. The participants showed a significant reduction in center of mass sway (78.2%, p = .045) during the semi-tandem balance stance with eyes closed and showed a significant increase in gait speed during a dual task motor-cognitive assessment (9.3%, p = .048) with an increase in stride velocity of over 0.1 m/sec. A significant reduction in reported pain occurred (43.5%, p = .041). Preliminary results of this exergame intervention show promise in improving balance and mobility while requiring older people living with HIV to be more active. The exergame can be continued at home and may have long term as well as short-term benefits for ameliorating frailty associated with HIV infection.

Persons infected with HIV are often frail, depressed and live a sedentary lifestyle for which conventional exercise is too taxing. Here, we present an exercise protocol that ameliorates aspects of frailty in HIV-infected persons. An exergame integrating cognitive control was developed using biosensors that measured balance, weight-shifting and obstacle crossing.

Approximately 1.2 million people in the United States live with HIV infection. Medical advancements have increased the life expectancy and this cohort is ...

Bioluminescence and Near-infrared Imaging of Optic Neuritis and Brain Inflammation in the EAE Model of Multiple Sclerosis in Mice

Experimental autoimmune encephalomyelitis (EAE) in SJL/J mice is a model for relapsing-remitting multiple sclerosis (RRMS). Clinical EAE scores describing motor function deficits are basic readouts of the immune-mediated inflammation of the spinal cord. However, scores and body weight do not allow for an in vivo assessment of brain inflammation and optic neuritis. The latter is an early and frequent manifestation in about 2/3 of MS patients. Here, we show methods for bioluminescence and near-infrared live imaging to assess EAE evoked optic neuritis, brain inflammation, and blood-brain barrier (BBB) disruption in living mice using an in vivo imaging system. A bioluminescent substrate activated by oxidases primarily showed optic neuritis. The signal was specific and allowed the visualization of medication effects and disease time courses, which paralleled the clinical scores. Pegylated fluorescent nanoparticles that remained within the vasculature for extended periods of time were used to assess the BBB integrity. Near-infrared imaging revealed a BBB leak at the peak of the disease. The signal was the strongest around the eyes. A near-infrared substrate for matrix metalloproteinases was used to assess EAE-evoked inflammation. Auto-fluorescence interfered with the signal, requiring spectral unmixing for quantification. Overall, bioluminescence imaging was a reliable method to assess EAE-associated optic neuritis and medication effects and was superior to the near-infrared techniques in terms of signal specificity, robustness, ease of quantification, and cost.

We show a technique for in vivo live bioluminescence and near-infrared imaging of optic neuritis and encephalitis in the experimental autoimmune encephalomyelitis (EAE) model for multiple sclerosis in SJL/J mice.

Experimental autoimmune encephalomyelitis (EAE) in SJL/J mice is a model for relapsing-remitting multiple sclerosis (RRMS). Clinical EAE scores describing ...

Improving Strength, Power, Muscle Aerobic Capacity, and Glucose Tolerance through Short-term Progressive Strength Training Among Elderly People

This protocol describes the simultaneous use of a broad span of methods to examine muscle aerobic capacity, glucose tolerance, strength, and power in elderly people performing short-term resistance training (RET). Supervised progressive resistance training for 1 h three times a week over 8 weeks was performed by RET participants (71&#177;1 years, range 65-80). Compared to a control group without training, the RET showed improvements on the measures used to indicate strength, power, glucose tolerance, and several parameters of muscle aerobic capacity. Strength training was performed in a gym with only robust fitness equipment. An isokinetic dynamometer for knee extensor strength permitted the measurement of concentric, eccentric, and static strength, which increased for the RET group (8-12% post- versus pre-test). The power (rate of force development, RFD) at the initial 0-30 ms also showed an increase for the RET group (52%). A glucose tolerance test with frequent blood glucose measurements showed improvements only for the RET group in terms of blood glucose values after 2 h (14%) and the area under the curve (21%). The blood lipid profile also improved (8%). From muscle biopsy samples prepared using histochemistry, the amount of fiber type IIa increased, and a trend towards a decrease in IIx in the RET group reflected a change to a more oxidative profile in terms of fiber composition. Western blot (to determine the protein content related to the signaling for muscle protein synthesis) showed a rise of 69% in both Akt and mTOR in the RET group; this also showed an increase in mitochondrial proteins for OXPHOS complex II and citrate synthase (both ~30%) and for complex IV (90%), in only the RET group. We demonstrate that this type of progressive resistance training offers various improvements (e.g., strength, power, aerobic capacity, glucose tolerance, and plasma lipid profile).

The effect of short-term resistance training on elderly people was investigated through the simultaneous use of several methods. Compared to a control group, many improvements were seen, including on muscle aerobic capacity, glucose tolerance, strength, power, and muscle quality (i.e., protein involved in cell signaling and muscle fiber type composition).

This protocol describes the simultaneous use of a broad span of methods to examine muscle aerobic capacity, glucose tolerance, strength, and power in ...

Muscle Imbalances: Testing and Training Functional Eccentric Hamstring Strength in Athletic Populations

Many hamstring injuries that occur during physical activity occur while the muscles are lengthening, during eccentric hamstring muscle actions. Opposite of these eccentric hamstring actions are concentric quadriceps actions, where the larger and likely stronger quadriceps straighten the knee. Therefore, to stabilize the lower limbs during movement, the hamstrings must eccentrically combat against the strong knee-straightening torque of the quadriceps. As such, eccentric hamstring strength expressed relative to concentric quadricep strength is commonly referred to as the &#34;functional ratio&#34; as most movements in sports require simultaneous concentric knee extension and eccentric knee flexion. To increase the strength, resiliency, and functional performance of the hamstrings, it is necessary to test and train the hamstrings at different eccentric speeds. The main purpose of this work is to provide instructions for measuring and interpreting eccentric hamstring strength. Techniques for measuring the functional ratio using isokinetic dynamometry are provided and sample data will be compared. Additionally, we briefly describe how to address hamstring strength deficiencies or unilateral strength differences using exercises that specifically focus on increasing eccentric hamstring strength.

The hamstrings are a group of muscles that are sometimes problematic for athletes, resulting in soft tissue injury in the lower limbs. To prevent such injuries, functional training of the hamstrings requires intensive eccentric contractions. Additionally, hamstring function should be tested in relation to quadricep function at different contraction speeds.

Many hamstring injuries that occur during physical activity occur while the muscles are lengthening, during eccentric hamstring muscle actions. Opposite ...

Involving Individuals with Developmental Language Disorder and Their Parents/Carers in Research Priority Setting

A protocol for involving individuals presenting with developmental language disorder (DLD) (iDLD) and their parents/carers (iDLDPC) in a research priority setting exercise is presented.
iDLD have difficulties with communication skills, such as understanding language, word-finding and discourse. Such difficulties mean existing research priority setting protocols are difficult for iDLD to access, since they require sophisticated communication skills. Thus, a novel protocol for involving iDLD in these exercises is warranted. The same protocol is recommended for use with iDLDPC, to ensure accessibility.
The protocol is presented in 4 steps. Step 1 describes a program of activities delivered by trained, specialist DLD speech and language therapists (SLTs) that prepares iDLD/iDLDPC for involvement. Step 2 outlines an approach to elicit iDLD/iDLDPC&#8217;s opinions on research priorities. Steps 3 and 4 describe methods to analyze and integrate this data at multiple stages of the research priority setting process.
9 trained specialist DLD SLTs delivered steps 1 and 2. 17 iDLDs and 25 iDLDPCs consented to involvement. Opinions from all participants were elicited, and this data was used to influence the process and output of the exercise.
An advantage of this protocol is its accommodation of the heterogeneity in support needs of iDLD/iDLDPC, through a menu of options, whilst also providing a structured framework. Due to the novelty of the protocol, the methods for data integration were developed by the research group. These are potential limitations of the protocol, and may bring the reliability and validity under scrutiny, which are yet to be tested.
This protocol enables meaningful involvement of iDLD/iDLDPC in&#160;research priority setting and could be utilized for people with other kinds of speech, language or communication needs. Further research should evaluate the effectiveness of the protocol and whether it can be adapted for involvement of such populations in other research studies.

A protocol to enable individuals with developmental language disorder (DLD) and their parents/carers to meaningfully participate in a research priority setting exercise is established. The protocol includes a defined program of activities for data collection, and methods to incorporate this data into the broader research priority setting process.

A protocol for involving individuals presenting with developmental language disorder (DLD) (iDLD) and their parents/carers (iDLDPC) in a research priority ...