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Dengue endemic is a serious healthcare concern in tropical and subtropical countries. Although well-established laboratory tests can provide early diagnosis of acute dengue infections, access to these tests is limited in developing countries, presenting an urgent need to develop simple, rapid, and robust diagnostic tools. Point-of-care (POC) devices, particularly paper-based POC devices, are typically rapid, cost-effective and user-friendly, and they can be used as diagnostic tools for the prompt diagnosis of dengue at POC settings. Here, we review the importance of rapid dengue diagnosis, current dengue diagnostic methods, and the development of paper-based POC devices for diagnosis of dengue infections at the POC.

Human mesenchymal stem cells (hMSCs) hold great promise in cardiac fibrosis therapy, due to their potential ability of inhibiting cardiac myofibroblast differentiation (a hallmark of cardiac fibrosis). However, the mechanism involved in their effects remains elusive. To explore this, it is necessary to develop an in vitro cardiac fibrosis model that incorporates pore size and native tissue-mimicking matrix stiffness, which may regulate cardiac myofibroblast differentiation. In the present study, collagen coated polyacrylamide hydrogel substrates were fabricated, in which the pore size was adjusted without altering the matrix stiffness. Stiffness is shown to regulate cardiac myofibroblast differentiation independently of pore size. Substrate at a stiffness of 30 kPa, which mimics the stiffness of native fibrotic cardiac tissue, was found to induce cardiac myofibroblast differentiation to create in vitro cardiac fibrosis model. Conditioned medium of hMSCs was applied to the model to determine its role and inhibitory mechanism on cardiac myofibroblast differentiation. It was found that hMSCs secrete hepatocyte growth factor (HGF) to inhibit cardiac myofibroblast differentiation via downregulation of angiotensin II type 1 receptor (AT 1 R) and upregulation of Smad7. These findings would aid in establishment of the therapeutic use of hMSCs in cardiac fibrosis therapy in future.

The need to have a better and safer culture condition for expansion of human mesenchymal stem cells (MSCs) is crucial particularly to prevent infection and immune rejection. This is normally associated with the use of animal-based serum in the culture media for cell expansion. The aim of this study is to investigate alternative culture conditions which may provide better and safer environment for cell growth. In the present study, human adipose-derived stem cells (ASCs) at passage 3 were subjected to treatment in 4 conditions: (1) 21 % O2 with fetal bovine serum (FBS), (2) 21 % O2 without FBS, (3) 2 % O2 with FBS and (4) 2 % O2 without FBS followed by subsequent analysis of their phenotype, viability and functionality. We observed that ASCs cultured in all conditions present no significant phenotypic changes. It was found that ASCs cultured in 2 % O2 without serum showed an increase in viability and growth to a certain extent when compared to those cultured in 21 % O2 without serum. However, ASCs cultured in 2 % O2 without serum displayed a relatively low adipogenic and osteogenic potential. On the other hand, interestingly, there was a positive enhancement in chondrogenic differentiation of ASCs cultured in 21 % O2 without serum. Our findings suggest that different culture conditions may be suitable for different indications. In summary, ASCs cultured in serum-free condition can still survive, proliferate and undergo subsequent adipogenic, osteogenic and chondrogenic differentiation. Therefore, FBS is feasible to be excluded for culture of ASCs, which avoids clinical complications., Competing Interests: All authors declare that there is no conflict of interest.

Lateral flow assays (LFAs) have currently attracted broad interest for point-of-care (POC) diagnostics, but their application has been restricted by poor quantification and limited sensitivity. While the former has been currently solved to some extent by the development of handheld or smartphone-based readers, the latter has not been addressed fully, particularly the potential influences of environmental conditions (e.g., temperature and relative humidity (RH)), which have not yet received serious attention. The present study reports the use of a portable temperature-humidity control device to provide an optimum environmental requirement for sensitivity improvement in LFAs, followed by quantification by using a smartphone. We found that a RH beyond 60% with temperatures of 55-60°C and 37-40°C produced optimum nucleic acid hybridization and antigen-antibody interaction in LFAs, respectively representing a 10-fold and 3-fold signal enhancement over ambient conditions (25°C, 60% RH). We envision that in the future the portable device could be coupled with a fully integrated paper-based sample-to-answer biosensor for sensitive detection of various target analytes in POC settings., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Lateral flow assays (LFAs) have been extensively explored in nucleic acid testing (NAT) for medical diagnostics, food safety analysis and environmental monitoring. However, the amount of target nucleic acid in a raw sample is usually too low to be directly detected by LFAs, necessitating the process of amplification. Even though cost-effective paper-based amplification techniques have been introduced, they have always been separately performed from LFAs, hence increasing the risk of reagent loss and cross-contaminations. To date, integrating paper-based nucleic acid amplification into colorimetric LFA in a simple, portable and cost-effective manner has not been introduced. Herein, we developed an integrated LFA with the aid of a specially designed handheld battery-powered system for effective amplification and detection of targets in resource-poor settings. Interestingly, using the integrated paper-based loop-mediated isothermal amplification (LAMP)-LFA, we successfully performed highly sensitive and specific target detection, achieving a detection limit of as low as 3 × 10(3) copies of target DNA, which is comparable to the conventional tube-based LAMP-LFA in an unintegrated format. The device may serve in conjunction with a simple paper-based sample preparation to create a fully integrated paper-based sample-to-answer diagnostic device for point-of-care testing (POCT) in the near future.

With advances in point-of-care testing (POCT), lateral flow assays (LFAs) have been explored for nucleic acid detection. However, biological samples generally contain complex compositions and low amounts of target nucleic acids, and currently require laborious off-chip nucleic acid extraction and amplification processes (e.g., tube-based extraction and polymerase chain reaction (PCR)) prior to detection. To the best of our knowledge, even though the integration of DNA extraction and amplification into a paper-based biosensor has been reported, a combination of LFA with the aforementioned steps for simple colorimetric readout has not yet been demonstrated. Here, we demonstrate for the first time an integrated paper-based biosensor incorporating nucleic acid extraction, amplification and visual detection or quantification using a smartphone. A handheld battery-powered heating device was specially developed for nucleic acid amplification in POC settings, which is coupled with this simple assay for rapid target detection. The biosensor can successfully detect Escherichia coli (as a model analyte) in spiked drinking water, milk, blood, and spinach with a detection limit of as low as 10-1000 CFU mL(-1), and Streptococcus pneumonia in clinical blood samples, highlighting its potential use in medical diagnostics, food safety analysis and environmental monitoring. As compared to the lengthy conventional assay, which requires more than 5 hours for the entire sample-to-answer process, it takes about 1 hour for our integrated biosensor. The integrated biosensor holds great potential for detection of various target analytes for wide applications in the near future.

Nucleic acid testing (NAT), as a molecular diagnostic technique, including nucleic acid extraction, amplification and detection, plays a fundamental role in medical diagnosis for timely medical treatment. However, current NAT technologies require relatively high-end instrumentation, skilled personnel, and are time-consuming. These drawbacks mean conventional NAT becomes impractical in many resource-limited disease-endemic settings, leading to an urgent need to develop a fast and portable NAT diagnostic tool. Paper-based devices are typically robust, cost-effective and user-friendly, holding a great potential for NAT at the point of care. In view of the escalating demand for the low cost diagnostic devices, we highlight the beneficial use of paper as a platform for NAT, the current state of its development, and the existing challenges preventing its widespread use. We suggest a strategy involving integrating all three steps of NAT into one single paper-based sample-to-answer diagnostic device for rapid medical diagnostics in the near future., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Mesenchymal stem cells (MSCs) hold many advantages over embryonic stem cells (ESCs) and other somatic cells in clinical applications. MSCs are multipotent cells with strong immunosuppressive properties. They can be harvested from various locations in the human body (e.g., bone marrow and adipose tissues). Cryopreservation represents an efficient method for the preservation and pooling of MSCs, to obtain the cell counts required for clinical applications, such as cell-based therapies and regenerative medicine. Upon cryopreservation, it is important to preserve MSCs functional properties including immunomodulatory properties and multilineage differentiation ability. Further, a biosafety evaluation of cryopreserved MSCs is essential prior to their clinical applications. However, the existing cryopreservation methods for MSCs are associated with notable limitations, leading to a need for new or improved methods to be established for a more efficient application of cryopreserved MSCs in stem cell-based therapies. We review the important parameters for cryopreservation of MSCs and the existing cryopreservation methods for MSCs. Further, we also discuss the challenges to be addressed in order to preserve MSCs effectively for clinical applications.

In recent years, computerized posturography has become an essential tool in quantitative assessment of postural steadiness in the clinical settings. The purpose of this study was to explore the ability of the Biodex(®) Stability System (BSS) to quantify postural steadiness in below-knee amputees. A convenience sample of 10 below-knee amputees participated in the study. The overall (OSI), anterior-posterior (APSI) and medial-lateral (MLSI) stability indexes as well as the percentage of time spent in left and right quadrants and four concentric zones were measured under altered sensory conditions while standing with solid ankle cushion heel (SACH), single-axis (SA) and energy storage and release (ESAR) feet. Significant difference was found between sensory conditions in SACH and ESAR feet for OSI (SACH, p = 0.002; ESAR, p = 0.005), APSI (SACH, p = 0.036; ESAR, p = 0.003) and MLSI (SACH, p = 0.008; ESAR, p = 0.05) stability indexes. The percentage of time spent in Zone A (0°-5°) was significantly greater than the other three concentric zones (p < 0.01). The loading time percentage on their intact limb (80%-94%) was significantly longer than the amputated limb (20%-6%) in all conditions for all three prosthetic feet. Below-knee amputees showed compromised postural steadiness when visual, proprioceptive or vestibular sensory input was altered. The findings highlight that the characteristics of postural stability in amputees can be clinically assessed by utilizing the outcomes produced by the BSS., (© IMechE 2015.)

Extracellular environments can regulate cell behavior because cells can actively sense their mechanical environments. This study evaluated the adhesion, proliferation and morphology of endothelial cells on polydimethylsiloxane (PDMS)/alumina (Al2 O3 ) composites and pure PDMS. The substrates were prepared from pure PDMS and its composites with 2.5, 5, 7.5, and 10 wt % Al2 O3 at a curing temperature of 50°C for 4 h. The substrates were then characterized by mechanical, structural, and morphological analyses. The cell adhesion, proliferation, and morphology of cultured bovine aortic endothelial (BAEC) cells on substrate materials were evaluated by using resazurin assay and 1,1'-dioctadecyl-1,3,3,3',3'-tetramethylindocarbocyanine perchlorate-acetylated LDL (Dil-Ac-LDL) cell staining, respectively. The composites (PDMS/2.5, 5, 7.5, and 10 wt % Al2 O3 ) exhibited higher stiffness than the pure PDMS substrate. The results also revealed that stiffer substrates promoted endothelial cell adhesion and proliferation and also induced spread morphology in the endothelial cells compared with lesser stiff substrates. Statistical analysis showed that the effect of time on cell proliferation depended on stiffness. Therefore, this study concludes that the addition of different Al2 O3 percentages to PDMS elevated substrate stiffness which in turn increased endothelial cell adhesion and proliferation significantly and induced spindle shape morphology in endothelial cells., (© 2014 Wiley Periodicals, Inc.)

Background: Lower limb amputee's are greatly affected in dealing with the environmental barriers such as ramps and stairs and reported high interface pressure between the residual limb and socket/liner. Interface pressure between the residual limb and socket/liner can affect the satisfaction and use of the prosthesis. Until now, little attention has been paid to interface pressure between socket and stump during ramp negotiation and its effect on amputee's satisfaction., Aim: The aim of this study was to evaluate the interface pressure produced by two different liners (Seal-In X5 and Dermo) between the residual limb and socket, and their effects on amputee's satisfaction during ramp negotiation., Design: Observational study., Setting: The study was performed in rehabilitation and biomedical departments of University Malaya Medical Centre., Population: Total ten (7 male, 3 female) transtibial amputees with unilateral amputation were included., Methods: Two prostheses were fabricated for each amputee. After four weeks of acclimation period, interface pressure between socket and residual limb was measured during walking on ramp and Prosthetic Evaluation Questionnaire (PEQ) was filled for each liner., Results: Mean peak pressure was significantly (P<0.05) lower with the Dermo liner compared with the Seal-In X5 liner in ramp walking. In addition, the participants were more satisfied with the Dermo liner (83.50 vs. 71.50) and mentioned fewer problems (87.00 vs. 69.00) compared with the Seal-In X5 liner during ramp negotiation., Conclusion: It might be concluded that Dermo liner could be a good choice for the transtibial level of amputation due to relative decrease in interface pressure, satisfaction and fewer problems., Clinical Rehabilitation Impact: The advantages of the Dermo liner may improve clinical rehabilitation of transtibial amputee's, as it provides more satisfaction and experienced fewer problems during ramp negotiation. This provides an improved walking and better quality of life in long term.

Adipose tissue-derived stromal cells (ASCs) natively reside in a relatively low-oxygen tension (i.e., hypoxic) microenvironment in human body. Low oxygen tension (i.e., in situ normoxia), has been known to enhance the growth and survival rate of ASCs, which, however, may lead to the risk of tumourigenesis. Here, we investigated the tumourigenic potential of ASCs under their physiological condition to ensure their safe use in regenerative therapy. Human ASCs isolated from subcutaneous fat were cultured in atmospheric O2 concentration (21% O2) or in situ normoxia (2% O2). We found that ASCs retained their surface markers, tri-lineage differentiation potential, and self-renewal properties under in situ normoxia without altering their morphology. In situ normoxia displayed a higher proliferation and viability of ASCs with less DNA damage as compared to atmospheric O2 concentration. Moreover, low oxygen tension significantly up-regulated VEGF and bFGF mRNA expression and protein secretion while reducing the expression level of tumour suppressor genes p16, p21, p53, and pRb. However, there were no significant differences in ASCs telomere length and their relative telomerase activity when cultured at different oxygen concentrations. Collectively, even with high proliferation and survival rate, ASCs have a low tendency of developing tumour under in situ normoxia. These results suggest 2% O2 as an ideal culture condition for expanding ASCs efficiently while maintaining their characteristics.

Circulating tumor cells (CTCs) are tumor cells that have detached from primary tumor site and are transported via the circulation system. The importance of CTCs as prognostic biomarker is leveraged when multiple studies found that patient with cutoff of 5 CTCs per 7.5 mL blood has poor survival rate. Despite its clinical relevance, the isolation and characterization of CTCs can be quite challenging due to their large morphological variability and the rare presence of CTCs within the blood. Numerous methods have been employed and discussed in the literature for CTCs separation. In this paper, we will focus on label free CTCs isolation methods, in which the biophysical and biomechanical properties of cells (e.g., size, deformability, and electricity) are exploited for CTCs detection. To assess the present state of various isolation methods, key performance metrics such as capture efficiency, cell viability, and throughput will be reported. Finally, we discuss the challenges and future perspectives of CTC isolation technologies.

Background Aims: Numerous protocols for the isolation of bovine aortic endothelial cells have been described in the previous literature. However, these protocols prevent researchers from obtaining the pure population of endothelial cells. Thus, this study aimed to develop a new and economical method for the isolation of pure endothelial cells by introducing a new strategy to the enzymatic digestion method proposed by previous researchers., Methods: With the use of this method, the lumen of a bovine aorta was filled with wash medium and the outer surface of the sample was washed with alcohol for 30 seconds. Under a laminar flow hood, the inner surface of the sample was covered with filter paper. Collagenase type II was dripped onto the filter paper as a digestion enzyme. The digestion fluid was seeded in T25 flasks and fed with complete medium every 3 days., Results: The isolated cells were characterized by markers such as CD31, von Willebrand factor, 1,1'-dioctadecyl-1,3,3,3',3'-tetramethylindocarbocyanine perchlorate acetylated low-density lipoprotein and angiogenesis behavior. The purity of endothelial cells was detected by flow cytometry to be of nearly 90% purity; these results were confirmed by immunostaining. Moreover, endothelial cells formed blood vessel-like tubes in a three-dimensional environment, which is specific dynamic behavior for endothelial cells., Conclusions: The new strategy presented in the current report enables isolation of a highly pure population of endothelial cells that can survive long-term culture without inducing an overgrowth of fibroblast cells., (Copyright © 2014 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Adipose-derived stem cells (ASCs) have been found adapted to a specific niche with low oxygen tension (hypoxia) in the body. As an important component of this niche, oxygen tension has been known to play a critical role in the maintenance of stem cell characteristics. However, the effect of O2 tension on their functional properties has not been well determined. In this study, we investigated the effects of O2 tension on ASCs stemness, differentiation and proliferation ability. Human ASCs were cultured under normoxia (21% O2) and hypoxia (2% O2). We found that hypoxia increased ASC stemness marker expression and proliferation rate without altering their morphology and surface markers. Low oxygen tension further enhances the chondrogenic differentiation ability, but reduces both adipogenic and osteogenic differentiation potential. These results might be correlated with the increased expression of HIF-1α under hypoxia. Taken together, we suggest that growing ASCs under 2% O2 tension may be important in expanding ASCs effectively while maintaining their functional properties for clinical therapy, particularly for the treatment of cartilage defects., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Prosthetic suspension system is an important component of lower limb prostheses. Suspension efficiency can be best evaluated during one of the vital activities of daily living, i.e. walking. A new magnetic prosthetic suspension system has been developed, but its effects on gait biomechanics have not been studied. This study aimed to explore the effect of suspension type on kinetic and kinematic gait parameters during level walking with the new suspension system as well as two other commonly used systems (the Seal-In and pin/lock). Thirteen persons with transtibial amputation participated in this study. A Vicon motion system (six cameras, two force platforms) was utilized to obtain gait kinetic and kinematic variables, as well as pistoning within the prosthetic socket. The gait deviation index was also calculated based on the kinematic data. The findings indicated significant difference in the pistoning values among the three suspension systems. The Seal-In system resulted in the least pistoning compared with the other two systems. Several kinetic and kinematic variables were also affected by the suspension type. The ground reaction force data showed that lower load was applied to the limb joints with the magnetic suspension system compared with the pin/lock suspension. The gait deviation index showed significant deviation from the normal with all the systems, but the systems did not differ significantly. Main significant effects of the suspension type were seen in the GRF (vertical and fore-aft), knee and ankle angles. The new magnetic suspension system showed comparable effects in the remaining kinetic and kinematic gait parameters to the other studied systems. This study may have implications on the selection of suspension systems for transtibial prostheses. Trial registration: Iranian Registry of Clinical Trials IRCT2013061813706N1.

This report compares wrist supination and pronation and flexion and extension movements with the common body-powered prosthesis and a new biomechatronics prosthesis with regard to patient satisfaction and problems experienced with the prosthesis. Fifteen subjects with traumatic transradial amputation who used both prosthetic systems participated in this study. Each subject completed two questionnaires to evaluate their satisfaction and problems experienced with the two prosthetic systems. Satisfaction and problems with the prosthetic's wrist movements were analyzed in terms of the following: supination and pronation; flexion and extension; appearance; sweating; wounds; pain; irritation; pistoning; smell; sound; durability; and the abilities to open a door, hold a cup, and pick up or place objects. This study revealed that the respondents were more satisfied with the biomechatronics wrist prosthesis with regard to supination and pronation, flexion and extension, pain, and the ability to open a door. However, satisfaction with the prosthesis showed no significant differences in terms of sweating, wounds, irritation, pistoning, smell, sound, and durability. The abilities to hold a cup and pick up or place an object were significantly better with the body-powered prosthesis. The results of the survey suggest that satisfaction and problems with wrist movements in persons with transradial amputation can be improved with a biomechatronics wrist prosthesis compared with the common body-powered prosthesis.

The measurements of postural balance often involve measurement error, which affects the analysis and interpretation of the outcomes. In most of the existing clinical rehabilitation research, the ability to produce reliable measures is a prerequisite for an accurate assessment of an intervention after a period of time. Although clinical balance assessment has been performed in previous study, none has determined the intrarater test-retest reliability of static and dynamic stability indexes during dominant single stance. In this study, one rater examined 20 healthy university students (female=12, male=8) in two sessions separated by 7 day intervals. Three stability indexes--the overall stability index (OSI), anterior/posterior stability index (APSI), and medial/ lateral stability index (MLSI) in static and dynamic conditions--were measured during single dominant stance. Intraclass correlation coefficient (ICC), standard error measurement (SEM) and 95% confidence interval (95% CI) were calculated. Test-retest ICCs for OSI, APSI, and MLSI were 0.85, 0.78, and 0.84 during static condition and were 0.77, 0.77, and 0.65 during dynamic condition, respectively. We concluded that the postural stability assessment using Biodex stability system demonstrates good-to-excellent test-retest reliability over a 1 week time interval.

Balance is essential for mobility and performing activities of daily living. People with knee osteoarthritis display impairment in knee joint proprioception. Thus, the aim of this study was to evaluate balance and risk of fall in individuals with bilateral mild and moderate knee osteoarthritis. Sixty subjects aged between 50 and 70 years volunteered in this study. They were categorized into three groups which were healthy (n = 20), mild (n = 20) and moderate (n = 20) bilateral knee osteoarthritis groups. Dynamic and static balance and risk of fall were assessed using Biodex Stability System. In addition, Timed Up and Go test was used as a clinical test for balance. Results of this study illustrated that there were significant differences in balance (dynamic and static) and risk of fall between three groups. In addition, the main (most significant) difference was found to be between healthy group and moderate group. Furthermore, on clinical scoring of balance, the "Timed Up and Go" test, all three groups showed significant difference. In conclusion, bilateral knee osteoarthritis impaired the balance and increased the risk of fall, particularly in people with moderate knee osteoarthritis.

Background: Achieving independent upright posture has known to be one of the main goals in rehabilitation following lower limb amputation. The purpose of this study was to compare postural steadiness of below knee amputees with visual alterations while wearing three different prosthetic feet., Methods: Ten male below-knee amputees were instructed to stand quietly on the Biodex® balance platform while wearing solid ankle cushion heel (SACH), single axis (SA) and energy storage and release (ESAR) prosthetic foot under different visual input conditions (eyes-opened and eyes-closed). The overall stability index (OSI), anterior- posterior stability index (APSI), and medial-lateral stability index (MLSI) were computed. Perceived balance assessment of each foot was evaluated using Activities-specific Balance Confidence (ABC) score., Results: The findings highlights that SACH showed lowest overall stability index (indicating less body sway) during eyes-opened (OSI: SACH = 1.09, SA = 1.58, ESAR = 1.59) and SA showed lowest overall stability index during eyes-closed (OSI: SACH = 2.52, SA = 2.30, ESAR = 2.76) condition. However, overall stability indexes between foot types did not differ significantly during eyes-opened or eyes-closed (p = 0.651). There was a trend of instability which occurred more in medial-lateral compared to anterior-posterior direction for all foot types, with significant result in ESAR foot(eyes-opened: MLSI = 1.59, APSI = 0.65, p = 0.034; eyes-closed: MLSI = 2.76, APSI = 1.80, p = 0.017, respectively). When comparing between visual conditions, stability score was significantly higher during eyes-closed compared to eyes-opened situations for SACH and ESAR foot (eyes-closed vs opened; SACH OSI: 3.43 vs 1.71, p = 0.018 and MLSI: 3.43 vs 1.71, p = 0.018; ESAR OSI: 3.58 vs 1.86, p = 0.043 and APSI: 1.80 vs 0.65, p = 0.027)., Conclusions: The results of this study suggested postural steadiness in below-knee amputees was not affected by the types of prosthetic foot during quiet upright standing, but was significantly affected when visual cues was absent.

Postural control has been widely evaluated for the normal population and different groups over the past 20 years. Numerous studies have investigated postural control in quiet standing posture among amputees. However, a comprehensive analysis is lacking on the possible contributing factors to balance. The present systematic review highlights the current findings on variables that contribute to balance instability for lower extremity amputees. The search strategy was performed on PubMed, Web of Science, Medline, Scopus, and CINAHL and then followed by additional manual searching via reference lists in the reviewed articles. The quality of the articles was evaluated using a methodological quality assessment tool. This review included and evaluated a total of 23 full-text articles. Despite the inconsistencies in the methodological design of the studies, all articles scored above the acceptable level in terms of quality. A majority of the studies revealed that lower extremity amputees have increased postural sway in the standing posture. Asymmetry in body weight, which is mainly distributed in the non-amputated leg, was described. Aside from the centre of pressure in postural control, sensory inputs may be a related topic for investigation in view of evidence on their contribution, particularly visual input. Other balance-related factors, such as stump length and patients' confidence level, were also neglected. Further research requires examination on the potential factors that affect postural control as the information of standing postural is still limited., (Copyright © 2013 The Authors. Published by Elsevier B.V. All rights reserved.)

The knee adduction moment represents the medial knee joint load, and greater value is associated with higher load. In people with knee osteoarthritis, it is important to apply proper treatment with the least side effects to reduce knee adduction moment and, consequently, reduce medial knee joint load. This reduction may slow the progression of knee osteoarthritis. The research team performed a literature search of electronic databases. The search keywords were as follows: knee osteoarthritis, knee adduction moment, exercise program, exercise therapy, gait retraining, gait modification and knee joint loading. In total, 12 studies were selected, according to the selection criteria. Findings from previous studies illustrated that exercise and gait retraining programs could alter knee adduction moment in people with knee osteoarthritis. These treatments are noninvasive and nonpharmacological which so far have no or few side effects, as well as being low cost. The results of this review revealed that gait retraining programs were helpful in reducing the knee adduction moment. In contrast, not all the exercise programs were beneficial in reducing knee adduction moment. Future studies are needed to indicate best clinical exercise and gait retraining programs, which are most effective in reducing knee adduction moment in people with knee osteoarthritis.

Background: Good prosthetic suspension system secures the residual limb inside the prosthetic socket and enables easy donning and doffing. This study aimed to introduce, evaluate and compare a newly designed prosthetic suspension system (HOLO) with the current suspension systems (suction, pin/lock and magnetic systems)., Methods: All the suspension systems were tested (tensile testing machine) in terms of the degree of the shear strength and the patient's comfort. Nine transtibial amputees participated in this study. The patients were asked to use four different suspension systems. Afterwards, each participant completed a questionnaire for each system to evaluate their comfort. Furthermore, the systems were compared in terms of the cost., Results: The maximum tensile load that the new system could bear was 490 N (SD, 5.5) before the system failed. Pin/lock, magnetic and suction suspension systems could tolerate loads of 580 N (SD, 8.5), 350.9 (SD, 7) and 310 N (SD, 8.4), respectively. Our subjects were satisfied with the new hook and loop system, particularly in terms of easy donning and doffing. Furthermore, the new system is considerably cheaper (35 times) than the current locking systems in the market., Conclusions: The new suspension system could successfully retain the prosthesis on the residual limb as a good alternative for lower limb amputees. In addition, the new system addresses some problems of the existing systems and is more cost effective than its counterparts.

Socket is an important part of every prosthetic limb as an interface between the residual limb and prosthetic components. Biomechanics of socket-residual limb interface, especially the pressure and force distribution, have effect on patient satisfaction and function. This paper aimed to review and evaluate studies conducted in the last decades on the design of socket, in-socket interface pressure measurement, and socket biomechanics. Literature was searched to find related keywords with transtibial amputation, socket-residual limb interface, socket measurement, socket design, modeling, computational modeling, and suspension system. In accordance with the selection criteria, 19 articles were selected for further analysis. It was revealed that pressure and stress have been studied in the last decaeds, but quantitative evaluations remain inapplicable in clinical settings. This study also illustrates prevailing systems, which may facilitate improvements in socket design for improved quality of life for individuals ambulating with transtibial prosthesis. It is hoped that the review will better facilitate the understanding and determine the clinical relevance of quantitative evaluations.

This study focused on developing a 3D finite element model of functionally graded femoral prostheses to decrease stress shielding and to improve total hip replacement performance. The mechanical properties of the modeled functionally graded femoral prostheses were adjusted in the sagittal and transverse planes by changing the volume fraction gradient exponent. Prostheses with material changes in the sagittal and transverse planes were considered longitudinal and radial prostheses, respectively. The effects of cemented and noncemented implantation methods were also considered in this study. Strain energy and von Mises stresses were determined at the femoral proximal metaphysis and interfaces of the implanted femur components, respectively. Results demonstrated that the strain energy increased proportionally with increasing volume fraction gradient exponent, whereas the interface stresses decreased on the prostheses surfaces. A limited increase was also observed at the surfaces of the bone and cement. The periprosthetic femur with a noncemented prosthesis exhibited higher strain energy than with a cemented prosthesis. Radial prostheses implantation displayed more strain energy than longitudinal prostheses implantation in the femoral proximal part. Functionally graded materials also increased strain energy and exhibited promising potentials as substitutes of conventional materials to decrease stress shielding and to enhance total hip replacement lifespan., (Copyright © 2013 John Wiley & Sons, Ltd.)

Background: A clinical parameter commonly used to assess the neurological status of an individual is the tendon reflex response. However, the clinical method of evaluation often leads to subjective conclusions that may differ between examiners. Moreover, attempts to quantify the reflex response, especially in older age groups, have produced inconsistent results. This study aims to examine the influence of age on the magnitude of the patellar tendon reflex response., Methodology/principal Findings: This study was conducted using the motion analysis technique with the reflex responses measured in terms of knee angles. Forty healthy subjects were selected and categorized into three different age groups. Patellar reflexes were elicited from both the left and right patellar tendons of each subject at three different tapping angles and using the Jendrassik maneuver. The findings suggested that age has a significant effect on the magnitude of the reflex response. An angle of 45° may be the ideal tapping angle at which the reflex can be elicited to detect age-related differences in reflex response. The reflex responses were also not influenced by gender and were observed to be fairly symmetrical., Conclusions/significance: Neurologically normal individuals will experience an age-dependent decline in patellar reflex response.

Background: Reflex assessment, an essential element in the investigation of the motor system, is currently assessed through qualitative description, which lacks of normal values in the healthy population. This study quantified the amplitude and latency of patellar tendon reflex in normal subjects using motion analysis to determine the factors affecting the reflex amplitude., Methods: 100 healthy volunteers were recruited for patellar tendon reflex assessments which were recorded using a motion analysis system. Different levels of input strength were exerted during the experiments., Results: A linear relationship was found between reflex input and reflex amplitude (r = 0.50, P <0.001). The left knee was found to exhibit 26.3% higher reflex amplitude than the right (P <0.001). The Jendrassik manoeuvre significantly increased reflex amplitude by 34.3% (P = 0.001); the effect was especially prominent in subjects with weak reflex response. Reflex latency normality data were established, which showed a gradual reduction with increasing input strength., Conclusion: The quantitative normality data and findings showed that the present method has great potential to objectively quantify deep tendon reflexes., Analyse du mouvement du réflexe rotulien normal.

Background: Transtibial amputees encounter stairs and steps during their daily activities. The excessive pressure between residual limb/socket may reduce the walking capability of transtibial prosthetic users during ascent and descent on stairs. The purposes of the research were to evaluate the interface pressure between Dermo (shuttle lock) and Seal-In X5 (prosthetic valve) interface systems during stair ascent and descent, and to determine their satisfaction effects on users., Methods: Ten amputees with unilateral transtibial amputation participated in the study. Interface pressure was recorded with F-socket transducer (9811E) during stair ascent and descent at self-selected speed. Each participant filled in a questionnaire about satisfaction and problems encountered with the use of the two interface systems., Findings: The resultant mean peak pressure (kPa) was significantly lower for the Dermo interface system compared to that of the Seal-In X5 interface system at the anterior, posterior and medial regions during stair ascent (63.14 vs. 80.14, 63.14 vs. 90.44, 49.21 vs. 66.04, respectively) and descent (67.11 vs. 80.41, 64.12 vs. 88.24, 47.33 vs. 65.11, respectively). Significant statistical difference existed between the two interface systems in terms of satisfaction and problems encountered (P<0.05)., Interpretation: The Dermo interface system caused less pressure within the prosthetic socket compared to the Seal-In X5 interface system during stair negotiation. The qualitative survey also showed that the prosthesis users experienced fewer problems and increased satisfaction with the Dermo interface system., (© 2013. Published by Elsevier Ltd. All rights reserved.)

Purpose: This study examined the kinematic differences between a body-powered prosthesis and a biomechatronics prosthesis as a transradial amputee performed activities that involve flexion/extension and supination/pronation of the wrist., Method: The subject's wrist movements were calculated and compared as he completed a wrist range of motion test involving simulated flexion/extension and supination/pronation., Results: The results revealed that, under the test conditions, the body-powered prosthesis limits an individual's ability to complete four different tasks of wrist movement especially when it comes to complete the supination/pronation movement. Conversely, while using biomechatronics wrist prosthesis, the user was able to compensate for limited wrist motion through an ability to achieve a greater range of wrist movement., Conclusions: The biomechatronics wrist prosthesis provides a greater degree of freedom of wrist flexion/extension and supination/pronation movements.

The present study aims to evaluate the serum level of copper (Cu) in lambs suffering from subclinical forms of white muscle disease (WMD) and its relationship with cardiac troponin I (cTn-I) as a novel biomarker of cardiovascular disorders. Ten milliliters of jugular blood were taken from 200 lambs less than one year old to measure serum concentrations of Cu, selenium (Se), and cTn-I. The subjects were divided into 2 groups, namely, the deficient group which included 36 lambs, and the control group which included 164 lambs according to the reference serum Se concentration (50 ng/mL). Serum Se levels in the deficient group were lower than 50 ng/mL. By contrast, the control group showed Se levels higher than 50 ng/mL. Differences among the serum Cu and cTn-I levels were determined in both groups. The mean ±SD and median of serum Cu and cTn-I levels in the deficient group were lower and higher than those in the control group, respectively. A significant positive correlation was observed between serum Cu and Se levels, and also serum Cu and Se levels showed a negative correlation with serum cTn-I concentrations. Stepwise linear regression analysis showed that serum Cu levels were correlated positively with serum Se levels (p<0.05). Receiver operating characteristic (ROC) curve analysis indicated that the area under curve (AUC) of Cu was significantly higher than that of cTn-I based on the reference diagonal line. It is important to keep in mind that the value of AUC for the ROC curve is between 0.5 and 1.00, in which the lowest accuracy is related to the reference diagonal line with AUC of 0.5. A cut-off was determined to indicate which Cu level can discriminate between affected and healthy lambs. The cut-off level, sensitivity, and specificity of Cu in this study were 144.5 ng/mL, 74%, and 61%, respectively.

Background: The deep tendon reflex assessments that are essential to the accurate diagnosis of neurological or neuromuscular disorders are conducted subjectively in clinical neurology. Our aim was to assess deep tendon reflexes objectively with a new reflex quantification method., Methodology/principal Findings: The present study used a motion analysis technique to collect quantitative measurements for both the input and output of normal patellar tendon reflex. Reflex responses were measured as knee angles. The patellar tendon reflexes of 100 healthy subjects were examined using 6 levels of tendon taps, where all the assessments were captured using motion capture system. A linear relationship was found between the experimental maximum tapping velocity and tapping angle (coefficient of determination = 0.989), which was consistent with the theoretical values. Tapping velocities were predictable according to tapping angles. The findings proved the reproducibility of tapping method in producing consistent input. The reflex amplitude was consistent between two randomly assigned groups, and linearly proportionate to the tapping velocity., Conclusions/significance: The findings on reflex amplitude indicate that motion analysis is a valid and reliable method of assessing and measuring deep tendon reflexes.

Background: Different suspension systems that are used within prosthetic devices may alter the distribution of pressure inside the prosthetic socket in lower limb amputees. This study aimed to compare the interface pressure of a new magnetic suspension system with the pin/lock and Seal-In suspension systems., Methods: Twelve unilateral transtibial amputees participated in the study. The subjects walked on a level walkway at a self-selected speed. The resultant peak pressure with the three different suspension systems was recorded using F-socket transducers., Findings: There were significant statistical differences between the three studied suspension systems. Pair-wise analyses revealed that the mean peak pressure (kPa) was lower with the magnetic system than it was with the pin/lock system over the anterior and posterior aspects during one gait cycle (89.89 vs. 79.26 and 47.22 vs. 26.01, respectively). Overall, the average peak pressure values were higher with the Seal-In system than they were with the new magnetic lock and pin/lock system., Interpretation: The new magnetic system might reduce the pressure within the prosthetic socket in comparison to the pin/lock and Seal-In system during one gait cycle. This is particularly important during the swing phase of gait and may reduce the pain and discomfort at the distal residual limb in comparison to the pin/lock system., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: The objectives of this study were to compare the effects of a newly designed magnetic suspension system with that of two existing suspension methods on pistoning inside the prosthetic socket and to compare satisfaction and perceived problems among transtibial amputees., Design: In this prospective study, three lower limb prostheses with three different suspension systems were fabricated for ten transtibial amputees. The participants used each of the three prostheses for 1 mo in random order. Pistoning inside the prosthetic socket was measured by motion analysis system. The Prosthesis Evaluation Questionnaire was used to evaluate satisfaction and perceived problems with each suspension system., Results: The lowest pistoning motion was found with the suction system compared with the other two suspension systems (P < 0.05). The new suspension system showed peak pistoning values similar to that of the pin lock system (P = 0.086). The results of the questionnaire survey revealed significantly higher satisfaction rates with the new system than with the other two systems in donning and doffing, walking, uneven walking, stair negotiation, and overall satisfaction (P < 0.05)., Conclusions: The new suspension system has the potential to be used as an alternative to the available suspension systems. The pistoning motion was comparable to that of the other two systems. The new system showed compatible prosthetic suspension with the other two systems (suction and pin lock). The satisfaction with donning and doffing was high with the magnetic system. Moreover, the subjects reported fewer problems with the new system.

Background: The interface pressure between the residual limb and prosthetic socket has a significant effect on an amputee's satisfaction and comfort. Liners provide a comfortable interface by adding a soft cushion between the residual limb and the socket. The Dermo and the Seal-In X5 liner are two new interface systems and, due to their relative infancy, very little are known about their effect on patient satisfaction. The aim of this study was to compare the interface pressure with these two liners and their effect on patient satisfaction., Methods: Nine unilateral transtibial amputees participated in the study. Two prostheses were fabricated for each amputee, one with the Seal-In liner and one with the Dermo liner. Interface pressure was measured at the anterior, posterior, medial and lateral regions during walking on the level ground. Each subject filled in a Prosthetic Evaluation Questionnaire (PEQ) regarding the satisfaction with the two liners. Findings The mean peak pressures with the Seal-In liner was 34.0% higher at the anterior, 24.0% higher at the posterior and 7.0% higher at the medial regions of the socket (P=0.008, P=0.046, P=0.025) than it was with the Dermo Liner. There were no significant differences in the mean peak pressures between the two liners at the lateral regions. In addition, significant difference was found between the two liners both for satisfaction and problems (P<0.05). Interpretation There was less interface pressure between the socket and the residual limb with the Dermo liner. The results indicated that the Dermo liner provides more comfort in the socket than the Seal-In liner., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The effects of Seal-In X5 and Dermo liner (Össur) on suspension and patient's comfort in lower limb amputees are unclear. In this report, we consider the case of a 51-yr-old woman with bilateral transtibial amputation whose lower limbs were amputated because of peripheral vascular disease. The subject had bony and painful residual limbs, especially at the distal ends. Two prostheses that used Seal-In X5 liners and a pair of prostheses with Dermo liners were fabricated, and the subject wore each for a period of 2 wks. Once the 2 wks had passed, the pistoning within the socket was assessed and the patient was questioned as to her satisfaction with both liners. This study revealed that Seal-In X5 liner decreased the residual limb pain experienced by the patient and that 1-2 mm less pistoning occurred within the socket compared with the Dermo liner. However, the patient needed to put in extra effort for donning and doffing the prosthesis. Despite this, it is clear that the Seal-In X5 liner offers a viable alternative for individuals with transtibial amputations who do not have enough soft tissue around the bone, especially at the end of the residual limb.

Postural stability is crucial in maintaining body balance during quiet standing, locomotion, and any activities that require a high degree of balance performance, such as participating in sports and dancing. Research has shown that there is a relationship between stability and body mass. The aims of this study were to examine the impact that two variables had on static postural control: body mass index (BMI) and gender. Eighty healthy young adults (age=21.7±1.8 yr; height=1.65±0.09 m; mass=67.5±19.0 kg) participated in the study and the static postural control was assessed using the Biodex Balance System, with a 20 Hz sampling rate in the bipedic stance (BLS) and unipedic stance (ULS) for 30s. Five test evaluations were performed for each balance test. Postural control was found to be negatively correlated with increased adiposity, as the obese BMI group performed significantly poorer than the underweight, normal weight and overweight groups during BLS and ULS tests. The underweight, normal weight and overweight groups exhibited greater anterior-posterior stability in postural control during quiet stance. In addition, female displayed a trend of having a greater postural sway than male young adults, although it was evidenced in only some BMI groups. This study revealed that BMI do have an impact on postural control during both BLS and ULS. As such, BMI and gender-specific effects should be taken into consideration when selecting individuals for different types of sporting activities, especially those that require quiet standing., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Background: Postural balance is vital for safely carrying out many daily activities, such as locomotion. The purpose of this study was to determine how changes in normal standing (NS) and standing with toe-extension (SWT) impact postural control during quiet standing. Furthermore, the research aimed to examine the extent to which the effect of these factors differed between genders., Methodology/principal Findings: Thirty healthy young adults (age = 21.2±1.3 y; height = 1.63±0.07 m; mass = 56.0±9.3 kg) with no prior lower limb injuries participated in the study. A postural stability test using the Biodex Balance System was used for both NS and SWT conditions. The three measurements from the BBS were Overall Stability Index (OSI), Medial-Lateral Stability Index (MLSI) and Anterior-Posterior Stability Index (APSI). No significant difference was found between NS and SWT in the OSI, MLSI or APSI (F(2, 28) = 3.357, p = 0.077). The main difference between the stability index scores was significant (F(2, 28) = 275.1, p<0.001). The Bonferroni post-hoc test showed significant differences between the OSI and MLSI (p<0.001); the OSI and APSI (p<0.001); and the MLSI and the APSI (p<0.001). Significant differences were found during NS (p<0.001), for the MLSI when compared with the APSI, but this was not found during the SWT condition. Additionally, no gender effects were proven to exist that altered postural sway during quiet standing., Conclusions/significance: This study reveals significant interaction between the stability indices measured; OSI, APSI and MLSI in both NS and SWT. Standing with toe extended does not have a significant impact on an individual's ability to control their balance during normal quiet standing. However, the findings revealed that the sway tendency in the medial-lateral direction might serve as a factor in an individual's ability to regain balance.

Poor suspension increases slippage of the residual limb inside the socket during ambulation. The main purpose of this article is to evaluate the pistoning at the prosthetic liner-socket interface during gait and assess patients' satisfaction with two different liners. Two prostheses with seal-in and locking liners were fabricated for each of the 10 subjects with transtibial amputation. The Vicon motion system was used to measure the pistoning during gait. The subjects were also asked to complete a Prosthesis Evaluation Questionnaire. The results revealed higher pistoning inside the socket during gait with the locking liner than with the seal-in liner (p < 0.05). The overall satisfaction with the locking liner was higher (p < 0.05) because of the relative ease with which the patients could don and doff the device. As such, pistoning may not be the main factor that determines patients' overall satisfaction with the prosthesis and other factors may also contribute to comfort and satisfaction with prostheses. The article also verifies the feasibility of the Vicon motion system for measuring pistoning during gait.

This paper describes the water compartments in healthy subjects and dengue patients on the day of defervescence of fever using bioelectrical impedance analysis. A total of 223 healthy subjects (65 males and 158 females) and 210 dengue patients (119 males and 91 females) in Hospital Universiti Kebangsaan Malaysia (HUKM), were studied. The ages for healthy subjects vary between 14 and 60 years old with mean age of 26.05 years while the ages for the dengue patients vary between 12 and 83 years old with mean age of 30.14 years. The parameters of water compartments investigated were total body water (TBW), extracellular water (ECW) and intracellular water (ICW). There were significant difference between healthy subjects and dengue patients for both male (p<0.05) and female (p<0.001) beginning on fever day 0 till fever day 4. The mean TBW and ECW values of dengue patients obtained were found to be higher than the normal healthy subjects while the mean ICW was lower. The mean TBW and ICW for male were higher than female while the mean ECW for male was lower than female for healthy subjects and dengue patients.

This paper describes a model for predicting hemoglobin (Hb) by using bioelectrical impedance analysis (BIA) in dengue patients in the Hospital Universiti Kebangsaan Malaysia (HUKM). Bioelectrical impedance measurements were conducted on 83 (47 males and 36 females) serologically confirmed dengue fever (DF) and dengue hemorrhagic fever (DHF) patients during their hospitalization. The predictive equation for Hb was derived using multivariate analysis. We investigated all the parameters in BIA, patients' symptom and demographic data. In this developed model, four predictors (reactance (XC), sex, weight and vomiting) were found to be the best predictive factors for modeling Hb in dengue patients. However, the model can only explain approximately 42% of the variation in Hb status, thus single frequency bio-impedance stand-alone technique is insufficient to monitor Hb for the DF and DHF patients. Further investigation using multi-frequency BIA is recommended in modeling Hb to achieve the most parsimonious model.

The response of human skin to "stress relaxation" tests at low loads in vitro was investigated. A number of behaviours, other than those already well established and documented, were observed. The significant behaviours are pure recovery and relaxation-recovery. Other behaviours observed are temporary stress recovery during the relaxation process, and momentary sudden non-linear drop in stress value followed by a second relaxation. The pure recovery and relaxation-recovery responses are repeatable. The latter represents the transitional response between the well-known behaviour of stress relaxation and the behaviour of stress recovery.

Local strains acting across an area of skin loaded uniaxially in vivo are converted to stresses using the standard elastic formulae. The stress values are compared to those obtained using the classical Bossinesq and Michell stress functions. The results indicate that these functions are capable of describing the response of the skin, both in the low load and the high load regions.

The response of human skin to biaxial stretch tests in vivo was investigated and compared to the response to uniaxial tension. The results obtained illustrate the nonlinear, anisotropic, and viscoelastic (time-dependent) properties of skin under biaxial stretch. Preconditioning in the load-extension response was found not to be prominent. The results also suggest that the response of skin to a biaxial stretch in vivo is qualitatively similar to that in vitro. Values of the terminal stiffness and limit strain of skin under a biaxial stretch are found.

The application of uniaxial tension in vivo is a common test method for investigating mechanical properties of the skin. This paper reports an investigation of the strain distributions on the skin surface produced by such a test method. The strains were shown to be non-homogeneous with major concentrations being present near the area of load application. At all sites within the test area, axial, lateral and shear strains were present but their magnitude depended both on their position within the test site and the overall extension. The axial and lateral strains were largest and most uniformly distributed within the area bounded by th loading tabs. The shear strains, however, were smallest in the are bounded by the tabs. The distribution of the three strains became similar if they were referred to the principal axes. The area of skin within the strained area became larger as the overall deformation increased because additional skin was recruited from the sites lateral to the strained area. The general form of the load/strain relations and lateral contractions were site- and extension-dependent, but were similar to those found in vitro.