Femoral Stem Displacement in a Patient Suffering Recurrent Dislocations After Hip Hemiarthroplasty: Case Report

Displacement of the femoral component during attempt to closed reduction of a dislocated hip arthroplasty is an exceptionally rare, catastrophic event, which renders operative management obligatory. We report the proximal migration of a femoral stem during attempt to closed reduction in a patient with recurrent postoperative dislocations after hip hemiarthroplasty, and describe successful management by conversion to a standard total hip arthroplasty, retaining the same stem in the existing cement mantle. This illustrative case is reported not only as an extremely rare event, but also to highlight and discuss pitfalls and efficient measures in the management of this complex issue

CLU blocks HDACI-mediated killing of neuroblastoma

Clusterin is a ubiquitously expressed glycoprotein with multiple binding partners including IL-6, Ku70, and Bax. Clusterin blocks apoptosis by binding to activated Bax and sequestering it in the cytoplasm, thereby preventing Bax from entering mitochondria, releasing cytochrome c, and triggering apoptosis. Because increased clusterin expression correlates with aggressive behavior in tumors, clusterin inhibition might be beneficial in cancer treatment. Our recent findings indicated that, in neuroblastoma cells, cytoplasmic Bax also binds to Ku70; when Ku70 is acetylated, Bax is released and can initiate cell death. Therefore, increasing Ku70 acetylation, such as by using histone deacetylase inhibitors, may be therapeutically useful in promoting cell death in neuroblastoma tumors. Since clusterin, Bax, and Ku70 form a complex, it seemed likely that clusterin would mediate its anti-apoptotic effects by inhibiting Ku70 acetylation and blocking Bax release. Our results, however, demonstrate that while clusterin level does indeed determine the sensitivity of neuroblastoma cells to histone deacetylase inhibitor-induced cell death, it does so without affecting histone deacetylase-inhibitor-induced Ku70 acetylation. Our results suggest that in neuroblastoma, clusterin exerts its anti-apoptotic effects downstream of Ku70 acetylation, likely by directly blocking Bax activation

Incorporation of albumin fusion proteins into fibrin clots in vitro and in vivo: comparison of different fusion motifs recognized by factor XIIIa

<p>Abstract</p> <p>Background</p> <p>The transglutaminase activated factor XIII (FXIIIa) acts to strengthen pathological fibrin clots and to slow their dissolution, in part by crosslinking active α₂-antiplasmin (α₂AP) to fibrin. We previously reported that a yeast-derived recombinant fusion protein comprising α₂AP residues 13-42 linked to human serum albumin (HSA) weakened <it>in vitro </it>clots but failed to become specifically incorporated into <it>in vivo </it>clots. In this study, our aims were to improve both the stability and clot localization of the HSA fusion protein by replacing α₂AP residues 13-42 with shorter sequences recognized more effectively by FXIIIa.</p> <p>Results</p> <p>Expression plasmids were prepared encoding recombinant HSA with the following N-terminal 23 residue extensions: H₆NQEQVSPLTLLAG₄Y (designated XL1); H₆DQMMLPWAVTLG₄Y (XL2); H₆WQHKIDLPYNGAG₄Y (XL3); and their 17 residue non-His-tagged equivalents (XL4, XL5, and XL6). The HSA moiety of XL4- to XL6-HSA proteins was C-terminally His-tagged. All chimerae were efficiently secreted from transformed <it>Pichia pastoris </it>yeast except XL3-HSA, and following nickel chelate affinity purification were found to be intact by amino acid sequencing, as was an N-terminally His-tagged version of α₂AP(13-42)-HSA. Of the proteins tested, XL5-HSA was cross-linked to biotin pentylamine (BPA) most rapidly by FXIIIa, and was the most effective competitor of α₂AP crosslinking not only to BPA but also to plasma fibrin clots. In the mouse ferric chloride <it>vena cava </it>thrombosis model, radiolabeled XL5-HSA was retained in the clot to a greater extent than recombinant HSA. In the rabbit jugular vein stasis thrombosis model, XL5-HSA was also retained in the clot, in a urea-insensitive manner indicative of crosslinking to fibrin, to a greater extent than recombinant HSA.</p> <p>Conclusions</p> <p>Fusion protein XL5-HSA (DQMMLPWAVTLG₄Y-HSAH₆) was found to be more active as a substrate for FXIIIa-mediated transamidation than seven other candidate fusion proteins <it>in vitro</it>. The improved stability and reactivity of this chimeric protein was further evidenced by its incorporation into <it>in vivo </it>clots formed in thrombosis models in both mice and rabbits.</p

Surviving streptococcal toxic shock syndrome: a case report

Streptococcal toxic shock syndrome and associated myositis caused by group A beta-hemolytic streptococcus pyogenes generally have a poor outcome despite aggressive operative treatment. Frequently the diagnosis is missed initially as the clinical features are non-specific. The progression to a toxic state is rapid and unless definitive treatment measures are initiated early, the end result can be catastrophic. We report a previously healthy patient who had features of toxic shock syndrome due to alpha haemolytic (viridans) streptococcus mitis which was treated successfully with antibiotics, aggressive intensive care support including the use of a 'sepsis care bundle', monitoring and continuous multidisciplinary review. Life and limb threatening emergencies due to streptococcus mitis in an immune-competent person are rare and to our knowledge, have not previously been described in the English scientific literature. Successful outcome is possible provided a high degree of suspicion is maintained and the patient is intensively monitored

Patterning in Birthweight in India: Analysis of Maternal Recall and Health Card Data

National data on birthweight from birth certificates or medical records are not available in India. The third Indian National Family Health Survey included data on birthweight of children obtained from health cards and maternal recall. This study aims to describe the population that these data represent and compares the birthweight obtained from health cards with maternal recall data in terms of its socioeconomic patterning and as a risk factor for childhood growth failure.The analytic sample consisted of children aged 0 to 59 months with birthweight data obtained from health cards (n = 3227) and maternal recall (n = 16,787). The difference between the card sample and the maternal recall sample in the distribution across household wealth, parental education, caste, religion, gender, and urban residence was compared using multilevel models. We also assessed the ability of birthweight to predict growth failure in infancy and childhood in the two groups. The survey contains birthweight data from a majority of household wealth categories (>5% in every category for recall), both genders, all age groups, all caste groups, all religion groups, and urban and rural dwellers. However, children from the lowest quintile of household wealth were under-represented (4.73% in card and 8.62% in recall samples). Comparison of data across health cards and maternal recall revealed similar social patterning of low birthweight and ability of birthweight to predict growth failure later in life. Children were less likely to be born with low birthweight if they had mothers with over 12 years of education compared to 1-5 years of education with relative risk (RR) of 0.79 (95% confidence interval [CI]: 0.52, 1.2) in the card sample and 0.70 (95% CI: 0.59, 0.84) in the recall sample. A 100 gram difference in a child's birthweight was associated with a decreased likelihood of underweight in both the card (RR: 0.95; 95% CI: 0.94, 0.96) and recall (RR: 0.96; 95% CI: 0.96, 0.97) samples.Our results suggest that in the absence of other sources, the data on birthweight in the third Indian National Family Health Survey is valuable for epidemiologic research

A meta-analysis of the effect of antibody therapy for the prevention of severe respiratory syncytial virus infection

Abstract Background The primary objective of this meta-analytic study was to determine the impact of RSV-IGIV and palivizumab on risk of respiratory syncytial virus (RSV)-related hospitalization. Secondary objectives were to determine if antibody therapy decreases the risk of RSV infection, intensive care admission, mechanical ventilation, and mortality in high risk infant populations. Methods We performed searches of electronic data bases from 1966 to April 2009. Inclusion and exclusion criteria were defined a priori. Inclusion criteria were as follows: 1) There was randomization between polyclonal or monoclonal antibodies and placebo or no therapy, and 2) Polyclonal or monoclonal antibodies were given as prophylaxis. Results Of the six included studies, three utilized RSV-IGIV (total of 533 randomized to treatment groups) and three utilized palivizumab (total of 1,663 randomized to treatment groups). The absolute risk of hospitalization in the control arms was 12% and overall RR for all 2,196 children who received one of the antibody products was 0.53 (95% CI 0.43, 0.66), P < 0.00001. When looking only at the children who received palivizumab, the RR for hospitalization was 0.50 (95% CI 0.38, 0.66), P < 0.00001. For the children receiving RSV-IGIV, the RR for hospitalization was 0.59 (95% CI 0.42, 0.83, P < 0.002). The use of palivizumab resulted in a significant decrease in admission to the ICU (RR 0.29 (95% CI 0.14, 0.59; P = 0.0007). There was no significant reduction in the risk of mechanical ventilation or mortality with the use of antibody prophylaxis. Infants born at less than 35 weeks gestational age, and those with chronic lung and congenital heart disease all had a significant reduction in the risk of RSV hospitalization with children born under 35 weeks gestational age showing a trend towards the greatest benefit. Conclusion Both palivizumab and RSV-IGIV decrease the incidence of RSV hospitalization and ICU admission and their effect appears to be qualitatively similarly. There was neither a statistically significant reduction in the incidence of mechanical ventilation nor in all cause mortality. This meta-analysis separately quantifies the impact of RSV-IGIV and palivizumab on various measures of severe RSV disease and builds upon a previous study that was only able to examine the pooled effect of all antibody products together

Biochemical Properties of a Novel Cysteine Protease of Plasmodium vivax, Vivapain-4

Plasmodium vivax affects hundreds of millions each year and results in severe morbidity and mortality. Plasmodial cysteine proteases (CPs) play crucial roles during the progression of malaria since inhibition of these molecules impairs parasite growth. These CPs might be targeted for new antimalarial drugs. We characterized a novel P. vivax CP, vivapain-4 (VX-4), which appeared to evolve differentially among primate Plasmodium species. VX-4 showed highly unique substrate preference depending on surrounding micro-environmental pH. It effectively hydrolyzed benzyloxycarbonyl-Leu-Arg-4-methyl-coumaryl-7-amide (Z-Leu-Arg-MCA) and Z-Phe-Arg-MCA at acidic pH and Z-Arg-Arg-MCA at neutral pH. Three amino acids (Ala90, Gly157 and Glu180) that delineate the S2 pocket were found to be substituted in VX-4. Alteration of Glu180 abolished hydrolytic activity against Z-Arg-Arg-MCA at neutral pH, indicating Glu180 is intimately involved in the pH-dependent substrate preference. VX-4 hydrolyzed actin at neutral pH and hemoglobin at acidic pH, and participated in plasmepsin 4 activation at neutral/acidic pH. VX-4 was localized in the food vacuoles and cytoplasm of the erythrocytic stage of P. vivax. The differential substrate preferences depending on pH suggested a highly efficient mechanism to enlarge biological implications of VX-4, including hemoglobin degradation, maturation of plasmepsin, and remodeling of the parasite architecture during growth and development of P. vivax

MAO-B Elevation in Mouse Brain Astrocytes Results in Parkinson's Pathology

Age-related increases in monoamine oxidase B (MAO-B) may contribute to neurodegeneration associated with Parkinson's disease (PD). The MAO-B inhibitor deprenyl, a long-standing antiparkinsonian therapy, is currently used clinically in concert with the dopamine precursor L-DOPA. Clinical studies suggesting that deprenyl treatment alone is not protective against PD associated mortality were targeted to symptomatic patients. However, dopamine loss is at least 60% by the time PD is symptomatically detectable, therefore lack of effect of MAO-B inhibition in these patients does not negate a role for MAO-B in pre-symptomatic dopaminergic loss. In order to directly evaluate the role of age-related elevations in astroglial MAO-B in the early initiation or progression of PD, we created genetically engineered transgenic mice in which MAO-B levels could be specifically induced within astroglia in adult animals. Elevated astrocytic MAO-B mimicking age related increase resulted in specific, selective and progressive loss of dopaminergic neurons in the substantia nigra (SN), the same subset of neurons primarily impacted in the human condition. This was accompanied by other PD-related alterations including selective decreases in mitochondrial complex I activity and increased mitochondrial oxidative stress. Along with a global astrogliosis, we observed local microglial activation within the SN. These pathologies correlated with decreased locomotor activity. Importantly, these events occurred even in the absence of the PD-inducing neurotoxin MPTP. Our data demonstrates that elevation of murine astrocytic MAO-B by itself can induce several phenotypes of PD, signifying that MAO-B could be directly involved in multiple aspects of disease neuropathology. Mechanistically this may involve increases in membrane permeant H2O2 which can oxidize dopamine within dopaminergic neurons to dopaminochrome which, via interaction with mitochondrial complex I, can result in increased mitochondrial superoxide. Our inducible astrocytic MAO-B transgenic provides a novel model for exploring pathways involved in initiation and progression of several key features associated with PD pathology and for therapeutic drug testing

Diversity among clients of female sex workers in India: comparing risk profiles and intervention impact by site of solicitation. implications for the vulnerability of less visible female sex workers.

BACKGROUND: It seems generally accepted that targeted interventions in India have been successful in raising condom use between female sex workers (FSWs) and their clients. Data from clients of FSWs have been under-utilised to analyse the risk environments and vulnerability of both partners. METHODS: The 2009 Integrated Biological and Behavioural Assessment survey sampled clients of FSWs at hotspots in Andhra Pradesh, Maharashtra and Tamil Nadu (n=5040). The risk profile of clients in terms of sexual networking and condom use are compared across usual pick-up place. We used propensity score matching (PSM) to estimate the average treatment effect on treated (ATT) of intervention messages on clients' consistent condom use with FSW. RESULTS: Clients of the more hidden sex workers who solicit from home or via phone or agents had more extensive sexual networks, reporting casual female partners as well as anal intercourse with male partners and FSW. Clients of brothel-based sex workers, who were the least educated, reported the fewest number/categories of partners, least anal sex, and lowest condom use (41%). Consistent condom use varied widely by state: 65% in Andhra Pradesh, 36% in Maharashtra and 29% in Tamil Nadu. Exposure to intervention messages on sexually transmitted infections was lowest among men frequenting brothels (58%), and highest among men soliciting less visible sex workers (70%). Exposure had significant impact on consistent condom use, including among clients of home-based sex workers (ATT 21%; p=0.001) and among men soliciting other more hidden FSW (ATT 17%; p=0.001). In Tamil Nadu no impact could be demonstrated. CONCLUSION: Commercial sex happens between two partners and both need to be, and can be, reached by intervention messages. Commercial sex is still largely unprotected and as the sex industry gets more diffuse a greater focus on reaching clients of sex workers seems important given their extensive sexual networks

Effect of a mixed reality-based intervention on arm, hand, and finger function on chronic stroke

[EN] Background: Virtual and mixed reality systems have been suggested to promote motor recovery after stroke. Basing on the existing evidence on motor learning, we have developed a portable and low-cost mixed reality tabletop system that transforms a conventional table in a virtual environment for upper limb rehabilitation. The system allows intensive and customized training of a wide range of arm, hand, and finger movements and enables interaction with tangible objects, while providing audiovisual feedback of the participants' performance in gamified tasks. This study evaluates the clinical effectiveness and the acceptance of an experimental intervention with the system in chronic stroke survivors. Methods: Thirty individuals with stroke were included in a reversal (A-B-A) study. Phase A consisted of 30 sessions of conventional physical therapy. Phase B consisted of 30 training sessions with the experimental system. Both interventions involved flexion and extension of the elbow, wrist, and fingers, and grasping of different objects. Sessions were 45-min long and were administered three to five days a week. The body structures (Modified Ashworth Scale), functions (Motricity Index, Fugl-Meyer Assessment Scale), activities (Manual Function Test, Wolf Motor Function Test, Box and Blocks Test, Nine Hole Peg Test), and participation (Motor Activity Log) were assessed before and after each phase. Acceptance of the system was also assessed after phase B (System Usability Scale, Intrinsic Motivation Inventory). Results: Significant improvement was detected after the intervention with the system in the activity, both in arm function measured by the Wolf Motor Function Test (p < 0.01) and finger dexterity measured by the Box and Blocks Test (p < 0.01) and the Nine Hole Peg Test (p < 0.01); and participation (p < 0.01), which was maintained to the end of the study. The experimental system was reported as highly usable, enjoyable, and motivating. Conclusions: Our results support the clinical effectiveness of mixed reality interventions that satisfy the motor learning principles for upper limb rehabilitation in chronic stroke survivors. This characteristic, together with the low cost of the system, its portability, and its acceptance could promote the integration of these systems in the clinical practice as an alternative to more expensive systems, such as robotic instruments.The authors wish to thank the staff and patients of the Servicio de Neurorrehabilitación y Daño Cerebral de los Hospitales NISA for their involvement in the study. The authors also wish to thank the staff of LabHuman for their support in this project, especially Francisco Toledo and José Roda for their assistance. This study was funded in part by the Project TEREHA (IDI-20110844) and Project NeuroVR (TIN2013-44741-R) of the Ministerio de Economia y Competitividad of Spain, the Project Consolider-C (SEJ2006-14301/PSIC) of the Ministerio de Educacion y Ciencia of Spain, the "CIBER of Physiopathology of Obesity and Nutrition, an initiative of ISCIII", and the Excellence Research Program PROMETEO of the Conselleria de Educacion of Generalitat Valenciana (2008-157).Colomer Font, C.; Llorens Rodríguez, R.; Noé Sebastián, E.; Alcañiz Raya, ML. (2016). Effect of a mixed reality-based intervention on arm, hand, and finger function on chronic stroke. Journal of NeuroEngineering and Rehabilitation. 13:1-10. https://doi.org/10.1186/s12984-016-0153-6S11013Fregni F, Pascual-Leone A. Hand motor recovery after stroke: tuning the orchestra to improve hand motor function. Cogn Behav Neurol. 2006;19(1):21–33.Patten C, Condliffe EG, Dairaghi CA, Lum PS. Concurrent neuromechanical and functional gains following upper-extremity power training post-stroke. J Neuroeng Rehabil. 2013;10:1.Turolla A, Dam M, Ventura L, Tonin P, Agostini M, Zucconi C, et al. Virtual reality for the rehabilitation of the upper limb motor function after stroke: a prospective controlled trial. J Neuroeng Rehabil. 2013;10:85.Dancause N, Nudo RJ. Shaping plasticity to enhance recovery after injury. Prog Brain Res. 2011;192:273–95.Kwakkel G, Kollen B, Lindeman E. Understanding the pattern of functional recovery after stroke: facts and theories. Restor Neurol Neurosci. 2004;22(3–5):281–99.Nielsen JB, Willerslev-Olsen M, Christiansen L, Lundbye-Jensen J, Lorentzen J. Science-based neurorehabilitation: recommendations for neurorehabilitation from basic science. J Mot Behav. 2015;47(1):7–17.Shaughnessy M, Resnick BM. Using theory to develop an exercise intervention for patients post stroke. Top Stroke Rehabil. 2009;16(2):140–6.Subramanian SK, Massie CL, Malcolm MP, Levin MF. Does provision of extrinsic feedback result in improved motor learning in the upper limb poststroke? A systematic review of the evidence. Neurorehabil Neural Repair. 2010;24(2):113–24.Arya KN, Verma R, Garg RK, Sharma VP, Agarwal M, Aggarwal GG. Meaningful task-specific training (MTST) for stroke rehabilitation: a randomized controlled trial. Top Stroke Rehabil. 2012;19(3):193–211.Levin MF, Weiss PL, Keshner EA. Emergence of Virtual Reality as a Tool for Upper Limb Rehabilitation: Incorporation of Motor Control and Motor Learning Principles. Phys Ther. 2015;95(3):415–25.Laver K, George S, Thomas S, Deutsch JE, Crotty M. Cochrane review: virtual reality for stroke rehabilitation. Eur J Phys Rehabil Med. 2012;48(3):523–30.Cameirao MS, Badia SB, Duarte E, Frisoli A, Verschure PF. The combined impact of virtual reality neurorehabilitation and its interfaces on upper extremity functional recovery in patients with chronic stroke. Stroke. 2012;43(10):2720–8.Saposnik G, Levin M, G. Outcome Research Canada Working. Virtual reality in stroke rehabilitation: a meta-analysis and implications for clinicians. Stroke. 2011;42(5):1380–6.Viau A, Feldman AG, McFadyen BJ, Levin MF. Reaching in reality and virtual reality: a comparison of movement kinematics in healthy subjects and in adults with hemiparesis. J Neuroeng Rehabil. 2004;1(1):11.Thornton M, Marshall S, McComas J, Finestone H, McCormick A, Sveistrup H. Benefits of activity and virtual reality based balance exercise programmes for adults with traumatic brain injury: perceptions of participants and their caregivers. Brain Inj. 2005;19(12):989–1000.Mazzoleni S, Puzzolante L, Zollo L, Dario P, Posteraro F. Mechanisms of motor recovery in chronic and subacute stroke patients following a robot-aided training. IEEE Trans Haptics. 2014;7(2):175–80.Duff M, Chen Y, Cheng L, Liu SM, Blake P, Wolf SL, et al. Adaptive mixed reality rehabilitation improves quality of reaching movements more than traditional reaching therapy following stroke. Neurorehabil Neural Repair. 2013;27(4):306–15.Mousavi Hondori, H., M. Khademi, L. Dodakian, A. McKenzie, C.V. Lopes, and S.C. Cramer, Choice of Human-Computer Interaction Mode in Stroke Rehabilitation. Neurorehabil Neural Repair, 2015.Bohannon RW, Smith MB. Interrater reliability of a modified Ashworth scale of muscle spasticity. Phys Ther. 1987;67(2):206–7.Paternostro-Sluga T, Grim-Stieger M, Posch M, Schuhfried O, Vacariu G, Mittermaier C, et al. Reliability and validity of the Medical Research Council (MRC) scale and a modified scale for testing muscle strength in patients with radial palsy. J Rehabil Med. 2008;40(8):665–71.Kopp B, Kunkel A, Flor H, Platz T, Rose U, Mauritz KH, et al. The Arm Motor Ability Test: reliability, validity, and sensitivity to change of an instrument for assessing disabilities in activities of daily living. Arch Phys Med Rehabil. 1997;78(6):615–20.Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12(3):189–98.Romero M, Sanchez A, Marin C, Navarro MD, Ferri J, Noe E. Clinical usefulness of the Spanish version of the Mississippi Aphasia Screening Test (MASTsp): validation in stroke patients. Neurologia. 2012;27(4):216–24.Llorens R, Marín C, Ortega M, Alcaniz M, Colomer C, Navarro MD, et al. Upper limb tracking using depth information for rehabilitative tangible tabletop systems, in 9th International Conference on Disability, Virtual Reality & Associated Technologies. Laval, France: The University of Reading; 2012. p. 463–466.Alt Murphy M, Resteghini C, Feys P, Lamers I. An overview of systematic reviews on upper extremity outcome measures after stroke. BMC Neurol. 2015;15:29.Sloan RL, Sinclair E, Thompson J, Taylor S, Pentland B. Inter-rater reliability of the modified Ashworth Scale for spasticity in hemiplegic patients. Int J Rehabil Res. 1992;15(2):158–61.van der Ploeg RJ, Fidler V, Oosterhuis HJ. Hand-held myometry: reference values. J Neurol Neurosurg Psychiatry. 1991;54(3):244–7.Duncan PW, Propst M, Nelson SG. Reliability of the Fugl-Meyer assessment of sensorimotor recovery following cerebrovascular accident. Phys Ther. 1983;63(10):1606–10.Miyamoto S, Kondo T, Suzukamo Y, Michimata A, Izumi S. Reliability and validity of the Manual Function Test in patients with stroke. Am J Phys Med Rehabil. 2009;88(3):247–55.Woodbury M, Velozo CA, Thompson PA, Light K, Uswatte G, Taub E, et al. Measurement structure of the Wolf Motor Function Test: implications for motor control theory. Neurorehabil Neural Repair. 2010;24(9):791–801.Mathiowetz V, Volland G, Kashman N, Weber K. Adult norms for the Box and Block Test of manual dexterity. Am J Occup Ther. 1985;39(6):386–91.Oxford Grice K, Vogel KA, Le V, Mitchell A, Muniz S, Vollmer MA. Adult norms for a commercially available Nine Hole Peg Test for finger dexterity. Am J Occup Ther. 2003;57(5):570–3.Hammer AM, Lindmark B. Responsiveness and validity of the Motor Activity Log in patients during the subacute phase after stroke. Disabil Rehabil. 2010;32(14):1184–93.Bullinger HJ, F.-I.f.A.u. Organisation, and U.S.I.f.A.u. Technologiemanagement. Human Aspects in Computing: Design and use of interactive systems and work with terminals. Elsevier; 1991.McAuley E, Duncan T, Tammen VV. Psychometric properties of the Intrinsic Motivation Inventory in a competitive sport setting: a confirmatory factor analysis. Res Q Exerc Sport. 1989;60(1):48–58.Mazzoleni S, Sale P, Tiboni M, Franceschini M, Carrozza MC, Posteraro F. Upper limb robot-assisted therapy in chronic and subacute stroke patients: a kinematic analysis. Am J Phys Med Rehabil. 2013;92(10 Suppl 2):e26–37.Lin KC, Hsieh YW, Wu CY, Chen CL, Jang Y, Liu JS. Minimal detectable change and clinically important difference of the Wolf Motor Function Test in stroke patients. Neurorehabil Neural Repair. 2009;23(5):429–34.Fu TS, Wu CY, Lin KC, Hsieh CJ, Liu JS, Wang TN, et al. Psychometric comparison of the shortened Fugl-Meyer Assessment and the streamlined Wolf Motor Function Test in stroke rehabilitation. Clin Rehabil. 2012;26(11):1043–7.Hsieh YW, Wu CY, Lin KC, Chang YF, Chen CL, Liu JS. Responsiveness and validity of three outcome measures of motor function after stroke rehabilitation. Stroke. 2009;40(4):1386–91.van der Lee JH, Beckerman H, Lankhorst GJ, Bouter LM. The responsiveness of the Action Research Arm test and the Fugl-Meyer Assessment scale in chronic stroke patients. J Rehabil Med. 2001;33(3):110–3.Wolf SL, Catlin PA, Ellis M, Archer AL, Morgan B, Piacentino A. Assessing Wolf Motor Function Test as Outcome Measure for Research in Patients After Stroke. Stroke. 2001;32(7):1635–9.Reinkensmeyer DJ, Wolbrecht ET, Chan V, Chou C, Cramer SC, Bobrow JE. Comparison of three-dimensional, assist-as-needed robotic arm/hand movement training provided with Pneu-WREX to conventional tabletop therapy after chronic stroke. Am J Phys Med Rehabil. 2012;91(11 Suppl 3):S232–41.Takahashi CD, Der-Yeghiaian L, Le V, Motiwala RR, Cramer SC. Robot-based hand motor therapy after stroke. Brain. 2008;131(Pt 2):425–37.Sale P, Mazzoleni S, Lombardi V, Galafate D, Massimiani MP, Posteraro F, et al. Recovery of hand function with robot-assisted therapy in acute stroke patients: a randomized-controlled trial. Int J Rehabil Res. 2014;37(3):236–42.Hwang CH, Seong JW, Son DS. Individual finger synchronized robot-assisted hand rehabilitation in subacute to chronic stroke: a prospective randomized clinical trial of efficacy. Clin Rehabil. 2012;26(8):696–704.Timmermans AA, Seelen HA, Willmann RD, Kingma H. Technology-assisted training of arm-hand skills in stroke: concepts on reacquisition of motor control and therapist guidelines for rehabilitation technology design. J Neuroeng Rehabil. 2009;6:1.Levin MF, Kleim JA, Wolf SL. What do motor “recovery” and “compensation” mean in patients following stroke? Neurorehabil Neural Repair. 2009;23(4):313–9.Rosati G, Oscari F, Spagnol S, Avanzini F, Masiero S. Effect of task-related continuous auditory feedback during learning of tracking motion exercises. J Neuroeng Rehabil. 2012;9:79.Imam B, Jarus T. Virtual reality rehabilitation from social cognitive and motor learning theoretical perspectives in stroke population. Rehabil Res Pract. 2014;2014:594540.Schuster-Amft C, Henneke A, Hartog-Keisker B, Holper L, Siekierka E, Chevrier E, et al. Intensive virtual reality-based training for upper limb motor function in chronic stroke: a feasibility study using a single case experimental design and fMRI. Disabil Rehabil Assist Technol. 2015;10(5):385–92.Llorens R, Noe E, Colomer C, Alcaniz M. Effectiveness, usability, and cost-benefit of a virtual reality-based telerehabilitation program for balance recovery after stroke: a randomized controlled trial. Arch Phys Med Rehabil. 2015;96(3):418–25. e2.Llorens R, Gil-Gomez JA, Alcaniz M, Colomer C, Noe E. Improvement in balance using a virtual reality-based stepping exercise: a randomized controlled trial involving individuals with chronic stroke. Clin Rehabil. 2015;29(3):7