In legged terrestrial locomotion, the duration of stance phase, i.e., when limbs are in contact with the substrate, is positively correlated with limb length, and negatively correlated with the metabolic cost of transport. These relationships are well documented at the interspecific level, across a broad range of body sizes and travel speeds. However, such relationships are harder to evaluate within species (i.e., where natural selection operates), largely for practical reasons, including low population variance in limb length, and the presence of confounding factors such as body mass, or training. Here, we compared spatiotemporal kinematics of gait in Longshanks, a long-legged mouse line created through artificial selection, and in random-bred, mass-matched Control mice raised under identical conditions. We used a gait treadmill to test the hypothesis that Longshanks have longer stance phases and stride lengths, and decreased stride frequencies in both fore- and hind limbs, compared with Controls. Our results indicate that gait differs significantly between the two groups. Specifically, and as hypothesized, stance duration and stride length are 8–10% greater in Longshanks, while stride frequency is 8% lower than in Controls. However, there was no difference in the touch-down timing and sequence of the paws between the two lines. Taken together, these data suggest that, for a given speed, Longshanks mice take significantly fewer, longer steps to cover the same distance or running time compared to Controls, with important implications for other measures of variation among individuals in whole-organism performance, such as the metabolic cost of transport.

Magister Scientiae (Physiotherapy) - MSc(Physio) / Background: Globally, the leading cause of lower limb amputation is diabetes mellitus. In South Africa, there is a rise in diabetes-related lower limb amputation with a marked increase in the number of persons with diabetes mellitus in rural areas. However, there is no information on the number of people who are living with a lower limb amputation. An amputation does not only have an impact on a person’s physical functioning but can result in poor quality of life, dependence and exclusion from societal participation. Rehabilitation and prosthetic interventions are known to facilitate those with a lower limb amputation to return to independence in activities of daily living, improved quality of life and inclusion in society. Access to health care is very challenging for persons living in rural areas. Challenges to accessing health care include limited rehabilitation staff, harsh terrain and far distances from services, a lack of access to transport, or the lack of confidence in the service provided by the healthcare institutions. For optimal and patient-centred outcomes, rehabilitation services are of paramount importance. Due to the challenges with providing services in rural areas, community-based rehabilitation is the ideal model for providing rehabilitation to persons with lower limb amputation in rural settings. In order to plan an appropriate community-based approach to rehabilitation, establishing the prevalence of disability and patient-specific needs are imperative. Aims of the study: The aims of this study were firstly, to determine the period prevalence of people living with a lower limb amputation within the rural OR Tambo District of the Eastern Cape in order to determine the need for services and secondly, to gain a deeper understanding of the rehabilitation needs of persons living with a lower limb amputation within the rural OR Tambo District of the Eastern Cape.

Thesis (M.Sc.(Physiotherapy)), Faculty of Health Sciences, University of the Witwatersrand, 2009 / Background: The impact of non-traumatic lower limb amputation on participant’s quality of life (QOL) is unknown. In an effort to provide better care for people with lower limb amputation, there is a need to first know the impact of this body changing operation on people’s quality of life. Aim of the study: To determine the impact of lower limb amputation on QOL in people in the Johannesburg metropolitan area during their reintegration to their society/community of origin. Objectives: 1. To establish the pre-operative and post-operative:  QOL of participants (including the feelings, experiences and impact of lower limb amputation during the time when they have returned home and to the community).  The functional status of participants.  Household economic and social status of these participants. 2. To establish factors influencing QOL. Methods: A longitudinal pre (amputation) test –post (amputation) test study utilized a combination of interviews to collect quantitative data and in-depth semistructured interviews to gather qualitative data. Consecutive sampling was used to draw participants (n=73) for the interviews at the study sites pre-operatively. The three study sites were Chris Hani Baragwanath Hospital, Charlotte Maxeke Johannesburg General Hospital and Helen Joseph Hospital. Participants were then followed up three months later for post-operative interviews and key informants were selected for in-depth interviews (n=12). Inclusion criteria: Participants were included if they were scheduled for first time unilateral (or bilateral amputation done at the same time) lower limb amputation. The participants were between the ages of 36-71 years. Exclusion criteria: Participants who had an amputation as a result of traumatic or congenital birth defects were excluded from the study. Participants with comorbidities that interfered with function pre-operatively were not included. Procedures: Ethics: Ethical clearance was obtained from the Committee for Research on Human Subjects at the University of the Witwatersrand and permission was obtained from the above hospitals. Participants gave consent before taking part in the study. Instrumentation: A demographic questionnaire, the EQ-5D, the Modified Household Economic and Social Status Index (HESSI), the Barthel Index (BI) and semi-structured in-depth interviews were used. Data collection: Participants were approached before the operation for their preoperative interviews using the above questionnaires and then followed up postoperatively using the same questionnaires and some were selected to participate in semi-structured in-depth interviews three months later. Pilot study: The demographics questionnaire and the modified HESSI were piloted to ensure validity and reliability. iii Data analysis: Data were analyzed using the SPSS Version 17.0 and STATA 10.0. The significance of the study was set at p=0.05. All continuous data are presented as means, medians, standard deviations and confidence intervals (CI 95%). Categorical data are presented as frequencies. Pre and post operative differences were analyzed using Wilcoxon Signed-rank test. A median regression analysis (both the univariate and multivariate regression) was done to establish factors influencing QOL. Pre and post operative differences in the EQ-5D items and the BI items were analyzed using Chi square/Fischer’s exact depending on the data. Data were pooled for presentation as statistical figures in tables. Both an intension to treat analysis and per protocol analysis were used. A grounded theory approach was used to analyze the concepts, categories and themes that emerged in the qualitative data. Results: Twenty-four participants (33%) had died by the time of follow up. At three months, n=9 (12%) had been lost to follow up and 40(55%) was successfully followed up. The preoperative median VAS was 60 (n=40). The postoperative median VAS was 70. The EQ-5D items on mobility and usual activities were reported as having deteriorated significantly postoperatively (p=0.04, p=0.001respectively) while pain/discomfort had improved (p=0.003). There was no improvement in QOL median VAS from the preoperative status to three months postoperatively The preoperative median total BI score was (n=40). The postoperative median total BI score was 19. There was a reduction in function (median BI) from the preoperative status to three months postoperatively (p<0.001). The ability to transfer was improved three months postoperatively (p=0.04). Participants were also found to have a decreased ability to negotiate stairs (p<0.001). Mobility was significantly reduced three months postoperatively (p=0.04). During the postoperative stage (n=40), 38% of the participants were married. Most (53%) of the participants had no form of income. The highest percentage of participants in all instances (35%) had secondary education (grade10-11), while 25% had less than grade 5. Only one participant was homeless, 18% lived in shacks, 55% lived in homes that were not shared with other families. People with LLA in the Johannesburg metropolitan area who had no problem with mobility preoperatively (EQ-5D mobility item), who were independent with mobility (BI mobility item) preoperatively, who were independent with transfer preoperatively (BI transfer item) had a higher postoperative quality of life (postoperative median EQ-5D- VAS) compared to people who were dependent or had problems with these functions preoperatively. Being females was a predictor of higher reported quality of life compared to being male. Emerging themes from the qualitative data were psychological, social and religious themes. Suicidal thoughts, dependence, poor acceptance, public perception about body image, phantom limb related falls and hoping to get a prosthesis were reported. Some reported poor social involvement due to mobility problems, employment concerns, while families and friends were found to be supportive. Participants had faith in God. Conclusion: Participants’ QOL and function were generally scored high both preoperatively and postoperatively but there was a significant improvement in QOL and a significant reduction in function after three months although participants were generally still functionally independent. Good mobility preoperatively is a predictor of good QOL postoperatively compared to people with a poor preoperative mobility status Generally, most participants had come to terms with the amputation and were managing well while some expressed that they were struggling with reintegration to their community of origin three months postoperatively with both functional and psychosocial challenges.

The extent to which sensory impairments in the foot, ankle and lower limb persist into the chronic phase of stroke is unclear. Furthermore, the extent to which these impairments influence walking, balance and falls is not well understood. This thesis investigated the prevalence, functional importance and measurement of lower limb somatosensory impairments in ambulatory people with chronic stroke. Methods This thesis comprised three studies: the first, a qualitative investigation, explored the views and experiences of people with chronic stroke (n=13). This led to the second study: a cross sectional observational study in which the prevalence, distribution and functional relevance of lower limb sensory impairments were investigated in chronic stroke participants (n=180) and healthy controls (n=46). The final study, informed by the findings from the first two studies, a “synthesis” review of current sensory measures and patient and carer involvement, developed and evaluated three novel, functionally oriented measures of lower limb somatosensory discrimination in chronic stroke (n=32) and healthy controls (n=32). Results People with stroke felt problems with foot, ankle and lower limb sensation affected their walking, balance and contributed to falls. Furthermore, sensory impairments in the lower limb are prevalent with up to 59% of chronic stroke survivors having a deficit of one or more somatosensory modality. Despite this, weak associations between traditional measures of tactile and proprioceptive sensation and walking, balance and falls were demonstrated. Novel, functionally oriented measures of tactile and proprioceptive discrimination were developed and evaluated. These measures were reliable and valid, showing greater sensitivity to predicting the presence of sensory impairments and had stronger associations with functional measures than traditional sensory tests. Conclusions This thesis has provided a comprehensive picture of lower limb somatosensory dysfunction in chronic stroke survivors. Sensory impairments persist into the chronic phase of stroke in the majority of stroke survivors. The extent to which such impairments influence functional ability warrants further investigation. The use of functionally oriented measures that assess higher-level somatosensation is encouraged.

This project aimed to provide a greater understanding of limb development through the characterisation of Mendelian disorders. The more specific aim was to identify the developmental basis of the Post Axial Longitudinal Limb Reduction Deformity (PALLRD) seen in the autosomal recessive Miller syndrome caused by mutations in Dihydroorotate Dehydrogenase (DHODH)[1]. In addition whole exome sequence analysis was used to identify further causative variants in a group of individuals with Non Classical Miller syndrome. These individuals were negative for mutations in DHODH although they had a clinically overlapping PALLRD. A single novel variant was discovered in Fibroblast Growth Factor Receptor 1 gene (FGF1) in one individual in this cohort. Due to the known vital role of FGF signaling in limb bud development the functional significance of this variant was investigated further[2]. In vitro data suggested that this variant has a dominant negative effect. Finally I compared the differential gene expression profile of embryonic mouse forelimb and hindlimb at a later stage of development. Digital Gene Expression Serial Analysis of Gene Expression (DGE-SAGE) produced gene-expression profiles of the forelimbs and hind limbs from 14.5 days post conception (d.p.c) murine embryos. This data included known differentially expressed genes as well as novel candidate genes that are putative regulators of limb growth. Whole mount In Situ Hybrisation (WISH) and Quantitative Real Time Polymerase Chain Reaction (qRTPCR) provided corroborating evidence for the differential expression of a subset of these genes between the forelimbs and hind limbs. This project suggests a role for DHODH in limb bud cell proliferation. It also demonstrates a novel potentially dominant negative mutation within FGFR1 in an individual with a limb deformity. Finally a subset of genes involved in regulating the differential growth between the forelimb and hindlimb were presented.

The gene PRICKLE1 is important for human brain function, as mutations in PRCKLE1 are associated with progressive myoclonus epilepsy (PME). Mutations in prickle orthologs could cause seizures in flies, zebrafish and mice, suggesting a conserved role of Prickle protein in seizure from fruit flies to humans. The underlying molecular mechanism how PRICKLE1 mutation causes PME is still unknown. Prickle1 is part of the planar cell polarity (PCP) pathway, which regulates cell polarity within plane of cell sheets. In Drosophila, prickle is recruited to one side of the cell by another PCP protein, Van Gogh. This asymmetric protein localization of Van Gogh/prickle establishes cell polarity. In zebrafish and Xenopus, loss of Prickle or Van Gogh like (Vangl) genes causes PCP phenotypes, which seemingly supports the Prickle/Vangl protein interaction and the role of Prickle in PCP pathway. The function of Prickle in mammals has not been analyzed. It is possible that mammalian Prickle also interacts with Vangl to mediate PCP signaling based on the conserved role of prickle from Drosophila to Xenopus. If Prickle1 interacts with Vangl and regulate PCP pathway, the PME we observed in humans might be associated with loss of neuronal polarity and impaired neuron activity. Therefore, to understand whether Prickle1 mediates Vangl signaling in mammals could be a step toward revealing the etiology of PME in human patients. Therefore, I analyzed the function of Prickle1 in three developmental processes, the limb development, the palate development, and the caudal migration of facial branchimotor neurons (FBMs), in which the function of PCP pathway, especially Vangl2, has been described. Supporting the interaction between Prickle1 and Vangl, mutations in either Prickle1 or Vangl2 leads to shorter limbs. However, Prickle1 and Vangl2 only have limited overlap in mRNA expression in the digit tips. This raises the question as to how impaired Prickle1/Vangl2 protein interaction in these cells in the digit tips cause defective growth of the whole limb. It also suggests alternate function of Prickle1 other than mediating Vangl2 function. This interaction between Prickle1 and Vangl2 is further challenged by the limited function of Vangl but the essential role of Prickle1 in palate development, which suggests that the function of Prickle1 is independent of Vangl2. In the caudal migration of FBMs, Prickle1 mutation impairs this migration process dose-dependently. This is different from Vangl2 mutation, which completely blocks the caudal migration and partially impairs the lateral migration of FBMs. More importantly, Prickle1 is expressed by the neurons, while Vangl2 functions in the surrounding cells, which again raises the question as to whether and how the two proteins could interact if they are not expressed in the same cell. These results together question the model that Prickle1 is the intracellular partner of Vangl2, but support Prickle1 function might be independent of Vangl. Actually, it is possible that Prickle1 is part of gene expression regulation machinery: Prickle1 mutation affects Wnt5a expression in the limb and Shh expression in the palate. Although this regulation mechanism is still unknown, it suggests that defective gene expression might be related to PME caused by PRICKLE1 mutation.

<p>Subsequent to a difficult surgery or a sever injury to the lower part of the body, often partial </p><p>load bearing is needed to stimulate an optimal rehabilitation. Today, this is achieved by teaching </p><p>the patient the optimal load by iteration. This has been shown insufficient for many patients, due </p><p>to their difficulties of remembering the correct amount of load. Furthermore, patients who lack </p><p>proprioception are unable to feel the load. </p><p> </p><p>A portable measuring system would enhance the patient possibility of optimal loadings. This </p><p>thesis has two main objects. 1. A study of the state of the art on existing commercial system, </p><p>related patents and measuring techniques. 2. A new measuring technique, which is the part that </p><p>most of all determine the system performance, was developed. A new design, using off the shelf, </p><p>products is proposed. </p><p> </p><p>The design uses a finite number of thin sensors placed onto an insole. By placing the sensors at </p><p>the plantar pressure points most of the total load is captured by the insole setups. To compensate </p><p>for the measuring error fitting methods were evaluated. The result depends on the insole </p><p>calibration methods. The best result without individual calibration is: mean error for the group of </p><p>0.5% of the total patient load and a deviation of 24%. With individual calibration reduces the </p><p>deviation to about 12%.</p>

Despite being a common childhood complaint there is little research on growing pains. Existing research is inconsistent with regard to sample selection and prevalence rates. There are only two English language intervention studies, and with the exception of associations noted in prevalence research, there has been no systematic research on the potential impact of growing pains on daily activities. Lack of a universal definition of growing pains poses difficulty for both diagnosis and research. The purposes of the current investigation were to propose a definition of growing pains grounded in literature and clinical practice, to develop a conceptual model of growing pains, and to understand childrens experiences with growing pains. A mixed-method research program involved four phases. In phase I, a survey of physicians indicated the following definition of growing pains: Intermittent pain of unknown etiology, occurring nocturnally in the lower limbs. Features that may occur in some cases, but not part of the definition, include arm pain and daytime pain. In phase II, non-parametric statistical analyses of child, familial, and environmental variables in a rheumatology clinic database were conducted to determine potential risk factors for growing pains. Logistic regression modeling indicated an association between growing pains and maternal illness or rash during the pregnancy, maternal smoking during the pregnancy, delayed pull to standing (i.e., greater than age 10 months), and family histories of back pain and arthritis. Potential mechanisms for these empirical associations are explored. In phase III, qualitative interviews with children were conducted to develop a grounded theory of how children process their experiences. Children engaged in a process of evaluating their current and past experiences of growing pains to determine how to manage specific pain episodes. Their evaluation was influenced by how they understood their pain which in turn was influenced by their intrapersonal and interpersonal experiences. Phase IV integrated results and existing literature to develop a conceptual model of growing pains which outlines characteristic features, predisposing factors, triggers, alleviating actions, and associated psychosocial features. Implications of the process theory and the conceptual model of growing pains with regard to clinical practice and future research are discussed.

Abstract: Previous lower limb weighting studies have placed a load on the legs bilaterally and tested different placement locations. It was previously determined that kinematic changes occur with greater masses and at joints proximal to weight placement [1]. Other studies have determined that these changes exist for a short adaptation period before parameters revert to a steady state [2]. Tasks that require voluntary gait modifications such as obstacle clearance have also been performed with lower leg bilateral weight addition [4]. In cases of normal obstacle clearance increased flexion at all three joints in the lower limb is needed to safely traverse the obstacle [3]. The goal of this study was to investigate joint kinematics and kinetics of unilaterally weighted participants using level ground force platform collection techniques, rather than a treadmill. It was hoped that this would allow for new insight into the adaptation periods and strategic motor pattern changes seen at the ankle, knee and hip. Kinematic and force platform data were collected on two groups of 10 healthy male subjects. Group 1 (mean age = 23years, mean weight = 82.181kg, mean height = 1.798m) was a normal walking group and group 2 (mean age = 24.8years, mean weight = 79.901kg, mean height = 1.773m) was an obstacle clearance group. Both groups participated in 20 trials each of three different conditions; normal, weighted and weight off using a 2.27kg limb mass attached just proximal to the right maleoli markers. A repeated-measures two-way ANOVA was carried out on relevant variables in order to determine statistical significance. Weight addition and removal affected the kinematics and kinetics of the normal walking and obstacle clearance groups. This effect was more prominent in the normal walking group. If changes were seen, trials 1 through 3 were the locations showing a quick adaptation followed by a leveling off back to a new steady state in later trials. Participants in the normal walking group chose to utilize the hip joint in order to control for weight addition and removal. Kinematically, changes in the hip joint angle occurred at all instances analyzed throughout the gait cycle with this effect being more prominent in the weight off condition. In conjunction with this, the hip joint energy generation increased during all phases of the gait cycle while the ankle and knee joints either decreased energy generation or increased energy absorption. In the obstacle group, participants also chose to increase flexion at the hip joint. However, the ankle joint also had either decreased plantarflexion or increased dorsiflexion at all the instances analyzed during the gait cycle. However, joint energy generation increases at these joints were only found during stance and at heel contact. The toe obstacle clearance values also showed a marked increase in trial 1 for the weighted condition which demonstrates a voluntary gait modification made by participants to safely traverse the obstacle that was quickly adapted for. Overall, the results found by previous studies using treadmill collection techniques were still seen in overground force platform data but they were not as robust. References: 1.Martin PE et al. J Biomech. 1990; 23(6):529-536. 2.Noble et al. Exp Brain Res. 2006; 169: 482-495. 3.Patla AE et al. Exp Brain Res. 1995; 196: 499-504. 4.Reid MJ et al. Neurosci Res Comm. 2001; 29(2): 79-87.

Subsequent to a difficult surgery or a sever injury to the lower part of the body, often partial load bearing is needed to stimulate an optimal rehabilitation. Today, this is achieved by teaching the patient the optimal load by iteration. This has been shown insufficient for many patients, due to their difficulties of remembering the correct amount of load. Furthermore, patients who lack proprioception are unable to feel the load. A portable measuring system would enhance the patient possibility of optimal loadings. This thesis has two main objects. 1. A study of the state of the art on existing commercial system, related patents and measuring techniques. 2. A new measuring technique, which is the part that most of all determine the system performance, was developed. A new design, using off the shelf, products is proposed. The design uses a finite number of thin sensors placed onto an insole. By placing the sensors at the plantar pressure points most of the total load is captured by the insole setups. To compensate for the measuring error fitting methods were evaluated. The result depends on the insole calibration methods. The best result without individual calibration is: mean error for the group of 0.5% of the total patient load and a deviation of 24%. With individual calibration reduces the deviation to about 12%.