FUNCIÓ DE LA CALCINEURINA AL SISTEMA IMMUNITAR

Patients suffering from diseases such as diabetes mellitus (DM), spina bifida and rheumatoid arthritis are particularly susceptible to ulceration to the plantar surface of the foot resulting from excessive interface pressure between the foot and the inlay inserted in a shoe during walking. The use of rocker soles when added to footwear has historically been mainly targeted on the reduction of plantar foot pressures associated with these conditions during ambulation. Other applications for rocker soles have included the treatment of hallux rigidus by supplying a surrogate motion where lack of dorsiflexion of the first metatarsal head is experienced (Trepman and Yeo, 1995). They are also used to protect parts of the foot which have been surgically fused or become stiff and painful due to osteoarthritis (OA) in order to reduce the pain associated with walking. Such areas include the ankle, the rearfoot, the midfoot and the forefoot (Cracchiolo, 1979).

Forefoot plantar pressure in subjects with DM may be reduced using both traditional (angled) and curved rocker soles. The amount of forefoot pressure reduction achieved when analysing curved rocker soles in people with diabetes mellitus has been shown to be different for individual subjects. This is because it depends on the shape of the individual’s foot, and the subsequent position of the rocker sole apex relative to the metatarsal heads, and also its orientation angle transversely across the shoe; as well as its apex angle (Chapman et al., 2013). This means that each subject should ideally have a bespoke prescription. However, it has been shown that to achieve maximal plantar pressure reduction for the great toe using angled rocker soles, the rocker angle needs to be 30o _and positioned behind the metatarsal heads at a position of 55% of shoe length (Geary and Klenerman, 1987). This prevents the distal end of the foot experiencing plantar loading until as late as possible during propulsion.

This degree of rocker angle also makes the rocker sole very deep at its apex, but crucially theoretically makes the sole unit stiffest at that point so that it can rock without the shoe flexing. Rocker sole profiles which are comparatively less deep at their apex point tend to have lower apex angles, and this theoretically makes the shoe more flexible during stance phase than those with deeper profiles and larger rocker apex angles. However, the effect on

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specific gait parameters of varying the thickness of the sole using rocker sole profiles in footwear and therefore also varying their stiffness is not well known and is analysed in this study.

Rocker sole designs may also affect the kinetics and kinematics of gait and also muscle function and activity in the lower limbs. However, little evidence exists with regards to these points. Although alterations to rocker sole apex angles and orientations have been extensively studied with regards to plantar pressure reductions (Hutchins et al., 2009), their effect on muscle function and activity is not well understood. Compared to barefoot walking, ambulation in a shoe incorporating a heel unit significantly alters gait parameters, but currently little is known how this affects parameters associated with muscle tendon units (MTUs) in the lower limbs. The alterations to gait kinetics and kinematics when walking with shoes adapted with the more commonly-prescribed rocker sole units such as the toe- only, the negative heel and the double rocker sole have been studied in the literature (Long et al., 2004, Van Bogart et al., 2005, Myers et al., 2006). However, these alterations have been shown to be clinically insignificant.

Currently it is unknown whether specific alterations to bespoke rocker sole design parameters can significantly affect the kinetics and kinematics of gait, and how they alter the operation of specific lower limb MTUs and the magnitude alteration which may be expected. Many studies have shown that the length and velocity of contraction of muscle fibres can have a significant effect on muscle force generation (Arnold et al., 2013). However, there is limited evidence in the literature and little understanding with regards to how much the force-length and force-velocity properties of the main muscles acting on the ankle affect force generation during walking in different footwear conditions.

Previous studies have provided limited contribution to the literature in this area, which would be potentially useful to enable footwear conditions for specific pathologies to be designed. Therefore, there is a need to expand the current knowledge in this area by analysing what effects rocker soles have on lower limb MTUs. Diseases such as intermittent claudication (IC) which adversely affect muscles acting on the ankle such as the triceps surae, may be responsive to orthotic intervention in the form of rocker soles, and evidence is needed as to which designs can, for instance, induce an offloading of this muscle group, or indeed increase loading in it for building up muscle strength. This may be achieved by

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analysing a series of rocker sole profiles, which have targeted amendments to their profiles in order to identify these alterations. Therefore, muscle biomechanics and muscle parameters should be examined in relation to different footwear adaptations to understand how different designs can help in achieving the individual aims for different complications. In addition to the conditions previously mentioned, there are numerous other conditions which affect the lower limb and foot which have been shown to be amenable to treatment using rocker soles. For instance, subjects with plantar fasciitis have been successfully treated with the toe-only rocker sole in conjunction with functional foot orthoses (FFOs) by reducing the intensity of the pain associated with the condition (Fong et al., 2012). It has been hypothesised that this improvement in symptoms may be associated with a reduction in the windlass mechanism affecting the plantar fascia due to restriction in 1st metatarsophalangeal joint (MTP) dorsiflexion during the propulsive phase of gait (Lin et al., 2013). However, analysis of the effect on the ankle plantarflexor MTUs with simultaneous analysis of kinetic and kinematics would have been useful in these studies, as it is known that subjects with plantar fasciitis may also have an ankle plantarflexor MTU contracture. Subjects with Achilles tendonitis may benefit from a reduction in the activity of the ankle plantarflexors during gait by using a rocker sole specifically designed to place the ankle in a relatively plantarflexed position during stance phase in order to reduce the work done by these muscles. This may be achieved by analysing the associated reduction in Achilles tendon lengthening and shortening during gait.

One pathology which has received a great deal of attention in the literature in recent years, and one which is known to adversely affect the ankle plantarflexor musculature is intermittent claudication (IC). This is a condition where vascular supply to the lower limbs is compromised due to peripheral vascular disease (PVD); otherwise known as peripheral occlusive arterial disease (POAD) or peripheral arterial disease (PAD). IC limits a patient’s ability to walk because of pain being experienced in the calf muscles due to the muscle tissues becoming ischemic. This causes limping and eventually forces people with IC (known as claudicants) to stop walking in order to rest for a period of time after which they can continue to ambulate. This cycle of walking and resting typifies the gait of claudicants (Allaqaband et al., 2009, Wessler, 1955).

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It is also important to look at muscle-tendon length changes during gait, because they actuate movement by developing force and generating internal moments (Delp, 1990). This may be an important factor when developing orthotic intervention for claudicants. Whilst the most commonly prescribed design of rocker sole profiles (such as the toe-only, double and negative heel rockers) have been shown to initiate small alterations to knee and ankle sagittal plane angles and ROMs during stance phase, little evidence exists regarding the ability of specific muscle groups to generate force when walking with rocker soles, because their effect on muscle-tendon lengths, muscle moment arms, and also their velocity of contraction is largely unknown. This is because when a muscle-tendon unit is lengthened or shortened to a certain point, the muscle fibres may be too long or too short to generate the required amount of active force in the lower limb. Skeletal muscle develops only 50% of the maximum force when its length is shortened to 85% of its resting length (Panjabi and White, 2001).

In addition, the type of muscle contraction demonstrated by specific muscles in the lower limb (i.e. concentric eccentric or isometric) may also be altered by rocker sole profiles, along with the EMG activity levels detected and the subsequent forces generated about the joint the muscle is attached to. Specific rocker sole designs may therefore affect muscle activity, and also alter gait patterns.

In order to evaluate the effects of muscle-tendon properties and skeletal geometry in determining moment-generating characteristics of selected muscles, a technique was developed by using Visual3D and OpenSim software. EMG data can indicate when a muscle is active or inactive and if larger groups of motor units are recruited to perform the task, but interpretation of EMG data does not determine what causes an increase muscle activity or which joint motion produced it.

OpenSim allows researchers to analyse exported dynamic motion data from Visual3d and examine musculoskeletal dynamic motions using a specially-developed model of the adult lower limb. This model was initially developed from data that quantified muscle architecture in cadavers (Arnold et al., 2010). It allows the user to export data, which is scaled by segments, length, mass, the average geometrical shape of bones and the height of the subject. This computer model can feasibly assist in understanding the biomechanical consequences of musculoskeletal dynamic changes when walking with different footwear

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rocker sole profiles and influence the design of future footwear with the specific aim of treating patients with IC and the other conditions previously mentioned.

The focal aim of this research is to inform the development of rocker shoes for patients with IC. A significant percentage of claudicants are also diabetic. The starting age for vascular complications in the diabetic population is approximately 45 years of age. IC adversely changes claudicants’ quality of life and makes them more sedentary which can cause medical complications. Such complications include muscle atrophy, stiff joints and stiff MTUs, decreased storage of muscle fuel, de-capilliarisation in muscles, cardiovascular weakness, reduction in stroke volume performed by the heart to deliver oxygen, reduced oxygen extraction from the blood, reduced blood flow and distribution and increased blood pressure. Claudicants’ main musculoskeletal symptom is the development of calf pain during ambulation due to vascular problems which makes them walk with a limp after walking a certain distance.

Exercise training has provided improvement for claudicants in these factors (Abernethy et al., 2013, Katch et al., 2011). Rocker soled shoes, which, if specifically-designed, may prove to reduce the work done by the ankle plantarflexors during ambulation, could be beneficial for claudicants by increasing their pain-free walking distance, reducing the intensity of their pain whilst claudicating, and by fighting against a sedentary lifestyle and naturally improving their cardiovascular system and therefore increasing oxygen delivery to the muscles without the need to attend supervised exercise programs. Moreover, alternative designs of footwear which increase work done by the muscles acting on the ankle joint could be used for short distances to build up calf musculature, increase capillary density and develop muscle fibres, which would result in improvement in oxygen delivery and muscle fuel storage.

Both these footwear features could replace supervised walking exercise programs, which are not always available or possible to attend for all patients. However, to achieve the optimal design to achieve this target would require extensive research. Before this could be achieved however, it would be necessary to more fully understand the muscular and biomechanical effects of different footwear features on muscle properties and walking patterns to inform the final designs. Therefore, in this thesis, one footwear feature was altered at a time in a series of tests to inform changes in parameters from identifiable shoe design alterations.

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Walking speed was controlled within set limits during gait laboratory testing, and healthy young male subjects were recruited for the research to minimise any external influences and effects on the primary outcome measures. This approach is different from most previous studies because factors such as the control of walking speed, alteration of one distinct footwear feature at a time, and the ability to produce an analysis of muscle-tendon properties and force generation by novel use of OpenSim software during walking trials, would enable a direct comparison of shoe design alterations to be made.

In summation, the research contained in this thesis is therefore aimed at systematically understanding the precise effects of altering parameters associated with different footwear rocker sole profiles on lower limb kinematics and kinetics, linked to muscle biomechanics and alterations to muscle activity in the lower limbs (especially for the calf group of muscles and anterior leg muscles). It was thought important for the purposes of this thesis to primarily examine the effect of such interventions on healthy subjects’ gait. This is because it would afford the opportunity to judge the results more precisely without other factors which may have an effect on the gait and muscle changes at the ankle and knee if subjects were to have varying amounts of disability. In addition, it would be necessary to perform gait laboratory testing on subjects who would be able to walk at similar speeds to negate the effects of walking speed on the comparative effects of altering the soles and heels of shoes. The intention was therefore to understand the precise effect of five different footwear design features (rocker sole apex position, rocker sole relative stiffness level, the type of heel shape, the rocker apex angle and alteration to heel height) on gastrocnemius medial head, soleus, tibialis anterior, rectus femoris and biceps femoris muscle activity and specific MTU parameters, plus temporal-spatial parameters during walking in adult healthy subjects. The results were intended to inform and make recommendations as to which footwear sole and heel unit design features would be suitable to alleviate symptoms associated with IC during rehabilitation protocols and also give indications for suitable intervention for various other pathologies.

By reducing the work done by the calf muscles, patients with IC may improve their free-pain walking distance and at the same time exercise their cardiovascular system by walking greater distances. Footwear which increases the work done by the calf muscles could conversely be used for exercising and strengthening their calf muscles as a parallel

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treatment to also improve their fitness as well as improving their pain-free walking distances.

Therefore the overall hypothesis was, that by altering shoe features such as heel height, rocker apex position, addition of a curved heel, alteration to apex angle and relative rocker sole stiffness, this would produce significant alterations to lower limb muscle EMG activity, kinetics and kinematics, the type and velocity of muscle contractions in specific lower limb muscles and their MTUs, alteration to fibre and tendon length, joint rotations and temporal and spatial gait parameters.

A design of shoe which incorporates sole and heel unit features which maintains the calf muscle-tendon length close to its optimal length whilst simultaneously reducing the velocity of concentric contraction in the calf muscles may significantly offload the calf muscle (i.e. affect ankle power generation and absorption) more than by simply reducing the sagittal plane moments about ankle during stance phase of gait. It is as yet unknown how variation in externally-applied sagittal plane moments via the ground reaction force (GRF) affect lower limb MTUs when walking with adapted shoes. This may prove in the future to be of benefit to subjects with plantar fasciitis, Achilles tendonitis as well as IC – indeed any pathology which adversely affects the muscles acting on the foot and ankle. However, it is the intention of this thesis to base its analysis on the specific needs of patients with IC. This study therefore presents data that permits the main muscles acting on the ankle to be studied by relating muscle fibre/tendon dynamics and force generation to the mechanical demands of walking in different footwear conditions.