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Title: The effect of sensomotoric stimulation on flat foot of children Introduction: Flat foot is a common health problem in childhood. Its development is related to congenital or acquired dysfunction of the plantar vault. There is no single opinion on the criteria for diagnosis and therapy forms. The aftereffects and health risks of flat foot are often neglected. The therapy form of sensomotoric stimulation, including balance exercises and walking barefoot over different surfaces, could be an appropriate part of the physical activities and games for children in kindergarten. Objectives: The main objective of this thesis was to compare foot prints of a group of children from one kindergarten class before and after six months of sensomotoric stimulation by three different methods (the Chippaux-Šmiřák method, the Godunov-Sztriter method and the Mayer method.). The second objective was to determine at what age category will be the highest prevalence of flat feet and also at what age group is the biggest improvement of the foot arch. The third objective was to compare each other method and determine whether the results will match. Hypothesis 1: After six months of sensomotoric stimulation of the feet of children occurs in the majority of feet of probands the improvement of the longitudinal foot arch...

Title: The effect of sensomotoric stimulation on flat foot of children Introduction: Flat foot is a common health problem in childhood. Its development is related to congenital or acquired dysfunction of the plantar vault. There is no single opinion on the criteria for diagnosis and therapy forms. The aftereffects and health risks of flat foot are often neglected. The therapy form of sensomotoric stimulation, including balance exercises and walking barefoot over different surfaces, could be an appropriate part of the physical activities and games for children in kindergarten. Objectives: The main objective of this work is to evaluate the effect of sensomotoric stimulation of flat foot at preschool age. Methods: The research contains 21 children. Forty-two foot prints were taken at the beginning of the therapy. Three methods were used to evaluate the foot prints: the Chippaux-Šmiřák method, the Godunov-Sztriter method and the Mayer method. The therapy form of sensomotoric stimulation included balance exercises and walking barefoot over different surfaces. The duration of therapy was 15 minutes each school day for six months. The control foot prints of 15 children were taken after the therapy and the results were compared with the foot prints before therapy. Results: The research contains twenty-one...

1 Abstract The aim is to investigate whether the distal femoral cartilage (DFC), Achilles tendon (AT) and plantar fascia (PF) were different between healthy young women wearing high-heel shoes (HHS) (> 5 cm) and flat shoes (< 1.4 cm). Measurements from aforementioned structures were obtained by using ultrasound. There were 910 measurement parameters analyzed in total. There were 34 women in the HHS group (mean age 31.1±6.4 years; BMI 21.6 ± 2.3 kg/m2 ) and 57 women in the control group (mean age; 29.5 ± 7.3 years; BMI 22.5 ± 3.4 kg/m2 ). Wearing HHS resulted in thickening of the right medial DFC (2.00 ± 0.41 mm) and left AT (4.07 ± 0.48 mm) in women wearing HHS compared to flat shoes (1.96 ± 0.35 mm, 3.76 ± 0.66 mm, respectively). This might be interpreted as secondary to chronic overload. PF thicknesses were similar both within and between group. Our findings have shown significant thickening of the right medial DFC and left AT in women wearing HHS and these changes might be interpreted as secondary to chronic overload. Further follow-up studies are definitely awaited to provide a better insight into understanding the musculoskeletal consequences of this "social" issue ever-existing in ladies lives. The secondary aim of the thesis comprises two case reports: 1. the first is describing the usefulness of MSK...

Background Anticipatory and compensatory balance responses are used by the central nervous system (CNS) to preserve balance, hence they significantly contribute to the understanding of physiological mechanisms of postural control. It is well established that various sensory systems contribute to the regulation of balance. However, it is still unclear which role each individual sensory system (e.g. plantar mechanoreceptors) plays in balance regulation. This becomes also evident in various patient populations, for instance in diabetics with reduced plantar sensitivity. To investigate these sensory mechanisms, approaches like hypothermia to deliberately reduce plantar afferent input have been applied. But there are some limitations regarding hypothermic procedures in previous studies: Not only plantar aspects of the feet might be affected and maintaining the hypothermic effect during data collection. Therefore, the aim of the present study was to induce a permanent and controlled plantar hypothermia and to examine its effects on anticipatory and compensatory balance responses. We hypothesized deteriorations in anticipatory and compensatory balance responses as increased center of pressure excursions (COP) and electromyographic activity (EMG) in response to the hypothermic plantar procedure. 52 healthy and young subjects (23.6 ± 3.0 years) performed balance tests (unexpected perturbations). Subjects’ foot soles were exposed to three temperatures while standing upright: 25, 12 and 0 °C. COP and EMG were analyzed during two intervals of anticipatory and one interval of compensatory balance responses (intervals 0, 1 and 2, respectively). Results Similar plantar temperatures confirmed the successful implementation of the thermal platform. No significant COP and EMG differences were found for the anticipatory responses (intervals 0 and 1) under the hyperthermia procedure. Parameters in interval 2 showed generally decreased values in response to cooling. Conclusion No changes in anticipatory responses were found possibly due to sensory compensation processes of other intact afferents. Decreased compensatory responses may be interpreted as the additional balance threat, creating a more cautious behavior causing the CNS to generate a kind of over-compensatory behavior. Contrary to the expectations, there were different anticipatory and compensatory responses after reduced plantar inputs, thereby, revealing alterations in the organization of CNS inputs and outputs according to different task difficulties.

Pharmacological treatment of neuropathic pain is still insufficient. Methylphenidate, a psychostimulant that increases the dopamine and noradrenaline levels, is commonly used for treating ADHD. There have been reports of changes in patients pain thresholds by ADHD patients treated with methylphenidate. The aim of the study is to examine if methylphenidate can affect peripheral neuropathic pain. Neuropathic pain has been modelled on laboratory rats by chronic constriction of the ischiatic nerve. The effect of methylphenidate on the evoked pain component was evaluated on control animals and on animals with neuropathic pain using reflex (plantar test, vonFrey test) and operanting test (thermal place preference). The effect of methylphenidate on the spontaneous components of pain was evaluated using the methods of conditioned place preference. This study has proven that methylphenidate in an applicable dose of 1 mg/kg has an antialodynic effect but does not act antinociceptively. This study further confirms that methylphenidate in low doses does not act as attractant and has no effect on spontaneous pain. The last part of the study compares the different methods for pain measurement and comes to the conclusion that the plantar test is not an adequate method for evaluating the effect of analgesics...

Background 3D manufacturing is a newer technology that shows potential and has gained interest in the world of medical devices. It has been used to produce custom made foot orthotics (CFO)s, but little evidence on the biomechanical effects is available. The literature suggests that the 3D manufactured CFOs (3DMCFO) have comparable outcomes as conventional manufactured CFOs (CMCFO). Purpose The purpose of this pilot study was to investigate biomechanics and comfort in the 3D manufacturing method, because of the lack of biomechanical evidence in literature, and because comfortable orthotics are a prerequisite for an optimal foot orthosis. Methods This pilot project uses a randomized crossover study design to test if there is a difference in plantar pressure distribution and comfort between 3DMCFOs and CMCFOs on two participants (n=2). To investigate the plantar pressure distribution the F-scan® in-shoe sensors was used to measure peak plantar pressures. To evaluate comfort the Orthosis Comfort Score (OCS) was used. Result For both participants similar results of mean peak pressures could be seen in some areas in the two CFOs, where in other areas contradictory results were seen. The comfort in the two CFOs was similar. Conclusion Similarities was seen in plantar pressure distribution and comfort in the two CFOs in both participants. However, the validity and reliability are low because of the low number of participants. / Baggrund 3D print er en nyere produktionsmetode som viser potentiale og har vækket interesse inden for medicinske hjælpemidler. 3D printning er blevet brugt til at producere specialfremstillede fod ortoser (SFO), men der er lav evidens for dens biomekaniske effekt. Litteraturen viser at 3D printede SFOer har sammenlignelige resultater som konventionel produceret SFOer. Formål Formålet med dette projekt var at undersøge biomekanik og komfort for 3D- produktionsmetoden. Dette blev undersøgt fordi der er lidt evidens inden for området, og fordi komfort er en forudsætning for en optimal fod ortose. Metode Dette pilotstudie bruger et randomiseret kontrolleret studie design for at teste om der er en forskel imellem 3D produktionsmetoden og den konventionelle produktionsmetode når der kigges på trykfordeling og komfort i to deltagere (n=2). For at undersøge trykfordeling under foden bruges F- scan® indlæg-sensor, for komfort bruges The Orthosis Comfort Score. Resultat For begge deltagere var der overensstemmelser i de gennemsnitlige høje tryk og i komfort for begge SFOer, hvor der i nogen områder var uoverensstemmelser. Konklusion For de to SFOer, overensstemmelser kunne ses i trykfordelingen under foden og i komfort. Validiteten og pålideligheden for dette projekt er dog ikke højt på grund af det lave deltagerantal.

Nos mamíferos, a determinação sexual é governada pelo equilíbrio entre duas vias de sinalização paralelas e antagônicas: a via masculina SOX9/FGF9 e a via feminina RSPO1/beta-catenina/WNT4. A R-spondina 1 é uma importante reguladora do processo de diferenciação ovariana e atua modulando a via de sinalização Wnt canônica (Wnt/beta-catenina). Em humanos, mutações em RSPO1 causam uma rara síndrome genética autossômica recessiva caracterizada por Distúrbios do Desenvolvimento Sexual (DDS) 46,XX Testicular ou Ovotesticular, hiperceratose palmoplantar (HPP) e predisposição para o desenvolvimento de carcinoma de células escamosas (MIM 610644). Identificamos um paciente brasileiro, proveniente de uma grande família consanguínea, que apresentava a associação de HPP e DDS 46,XX Testicular SRY negativo. A avaliação da região codificadora do gene RSPO1 identificou a nova variante alélica c.305G>A (p.Cys102Tyr). O estudo de segregação realizado em 67 familiares demonstrou que a variante c.305G>A segrega em perfeita concordância com o fenótipo de HPP, exibindo um padrão de herança autossômico recessivo. Na família foram identificados 10 indivíduos afetados pelo fenótipo de HPP. As avaliações clínica e hormonal e os estudos molecular e citogenético nesses indivíduos resultou na caracterização de: (a) quatro indivíduos do sexo masculino 46,XX e/ou SRY negativo, com ambiguidade genital e perfil hormonal alterado; (b) cinco indivíduos do sexo masculino 46,XY e/ou SRY positivo, sem ambiguidade genital, com perfil hormonal normal e (c) uma mulher 46,XX, fértil. Experimentos de transfecção transitória in vitro demostraram que a proteína mutante tem menor capacidade de transativação do plasmídio reporter da via Wnt. As simulações de dinâmica molecular constataram que a troca p.Cys102Tyr aumenta a flexibilidade do backbone da R-spondina-1, diminuindo a energia de ligação da proteína ao complexo de receptores, LGR5 e RNF43. Em conjunto, nossos achados demonstram que a variante c.305G > A é patogênica, sendo responsável pela síndrome genética diagnosticada na família brasileira. As análises de expressão gênica e os estudos de imuno-histoquímica, por sua vez, detectaram um aumento da expressão do gene SOX9 e maior imonorreatividade para a proteína Sox9 no tecido testicular do caso índice. Esses resultados sugerem que o processo de reversão sexual nos indivíduos XX ocorra por uma hiperexpressão de SOX9 secundária à menor ativação da via Wnt/beta-catenina na gônada durante a embriogênese. No presente estudo também relatamos o primeiro caso de indivíduo de cariótipo 46,XX portador de mutação em homozigose no gene RSPO1 que não desenvolveu DDS. A variabilidade do fenótipo sexual não está associada com alterações no número de cópias dos genes WNT4 ou do SOX9 e região cis-regulatória. No entanto, a avaliação do exoma da família encontrou uma associação entre o polimorfismo do receptor LGR5 rs17109924 e a atenuação do fenótipo de DDS. Todavia, serão necessários estudos funcionais para esclarecer o impacto biológico da interação das variantes RSPO1 p.Cys102Tyr e LGR5 rs171099 / In mammals, sex determination is governed by the balance between two parallel and antagonic signaling pathways: the male SOX9/FGF9 and the female, RSPO1/beta-catenin/WNT4 pathways. R-spondin 1 regulates the ovarian differentiation process by its modulating action through the canonic Wnt pathway (Wnt/beta-catenin). In humans, patogenic mutations in RSPO1 cause a rare, autosomic recessive syndrome characterized by 46,XX Testicular or Ovotesticular disorders of sexual development (DSD), palmoplantar keratosis (PPK) and predisposition to squamous cell carcinoma (MIM 610644). We identified and studied a SRY-negative 46,XX DSD patient with PPK from a large, consaguineous, brazillian family. Through a \"candidate gene\" approach we identified in the proband a new allelic variant in the coding region of RSPO1, c.305G > A. This variant presented full concordance with the PPK phenotype by segregation analyses in 10 of 67 members of this family. Clinical, hormonal, cytogenetic and molecular genetic studies characterized three patterns in individuals with this variant: (a) four 46,XX and/or SRY-negative males with ambiguous genitalia and altered hormonal profile; (b) five 46,XY and/or SRY-positive males without ambiguous genitalia with normal hormonal profile; (c) one 46,XX fertile woman. In vitro experiments demonstrated that transient transfection of the mutant protein resulted in lower transactivation of the Wnt pathway-reporter plasmid. Moreover, molecular dinamic studies showed that p.Cys102Tyr increased the R-spondin-1 backbone flexibility, thus decreasing the interaction between this protein and its receptors, LGR5 and RNF43. Thus, both in vitro and in silico analysis demonstrate the pathogenicity of the RSPO1 variant c.305G > A. In addition, in the index case, a higher expression of SOX9, corroborated by a reactive immunohistochemistry in testicular tissue, suggested that the process of sexual reversal in the XX individual is driven by a higher SOX9 expression possibly due to a lower Wnt/beta-catenin signaling pathway activation during embriogenesis. In this study, we also reported the first 46,XX individual with RSPO1 mutation without DSD, in which no copy number abnormality was detected in WNT4, SOX9 and its cisregulatory regions. Whole exome sequencing of the affected individuals revealed, in turn, that the LGR5 rs17109924 polymorphism associates with a protacted DSD phenotype in the fertile woman with normal hormonal profile. Despite this evidence, future studies are nedded to address causality and biological impact between RSPO1 p.Cys102Tyr and LGR5 rs17109924 variants

L'objectif de ce travail de thèse est d'étudier d'une part les spécificités de la commande nerveuse lors de la contraction excentrique en explorant les mécanismes impliqués au niveau spinal et d'autre part d'examiner les mécanismes nerveux responsables de la plasticité du système neuromusculaire après un entraînement de force excentrique sous-maximal. A travers ce travail de thèse, nous mettons en évidence la contribution de l'inhibition récurrente à la réduction de l'activation musculaire classiquement observée lors de la contraction excentrique. Par ailleurs, nous montrons que l'inhibition récurrente est majorée lors des contractions sous-maximales indépendamment du mode de contraction. Ces résultats soulignent le rôle important de l'inhibition récurrente dans la spécificité de la commande nerveuse lors de la contraction excentrique. Nous confirmons que le pilotage nerveux de la contraction excentrique peut être modulé par l'entraînement de force excentrique même si les modulations de l'excitabilité spinale semblent dépendre des caractéristiques de l'entraînement. / The purpose of this PhD research is, on the one hand, to study the neural drive specificities during eccentric contractions by exploring the neural mechanisms involved at spinal level and, on the other hand, to examine the neural mechanisms responsible for the modulations of neuromuscular system following a strength submaximal eccentric training. Through this PhD research we highlight the contribution of recurrent inhibition by the Renshaw cell to the decrease of muscular activation typically observed during eccentric contraction. Furthermore, we show that recurrent inhibition is enhanced during submaximal contractions regardless of the contraction type. These results emphasize the important role of recurrent inhibition in the specificity of neural control during eccentric contractions. We confirm that the neural drive of the eccentric contraction may be modulated by eccentric strength training although modulations of spinal excitability seem to depend on the characteristics of training.

Nos mamíferos, a determinação sexual é governada pelo equilíbrio entre duas vias de sinalização paralelas e antagônicas: a via masculina SOX9/FGF9 e a via feminina RSPO1/beta-catenina/WNT4. A R-spondina 1 é uma importante reguladora do processo de diferenciação ovariana e atua modulando a via de sinalização Wnt canônica (Wnt/beta-catenina). Em humanos, mutações em RSPO1 causam uma rara síndrome genética autossômica recessiva caracterizada por Distúrbios do Desenvolvimento Sexual (DDS) 46,XX Testicular ou Ovotesticular, hiperceratose palmoplantar (HPP) e predisposição para o desenvolvimento de carcinoma de células escamosas (MIM 610644). Identificamos um paciente brasileiro, proveniente de uma grande família consanguínea, que apresentava a associação de HPP e DDS 46,XX Testicular SRY negativo. A avaliação da região codificadora do gene RSPO1 identificou a nova variante alélica c.305G>A (p.Cys102Tyr). O estudo de segregação realizado em 67 familiares demonstrou que a variante c.305G>A segrega em perfeita concordância com o fenótipo de HPP, exibindo um padrão de herança autossômico recessivo. Na família foram identificados 10 indivíduos afetados pelo fenótipo de HPP. As avaliações clínica e hormonal e os estudos molecular e citogenético nesses indivíduos resultou na caracterização de: (a) quatro indivíduos do sexo masculino 46,XX e/ou SRY negativo, com ambiguidade genital e perfil hormonal alterado; (b) cinco indivíduos do sexo masculino 46,XY e/ou SRY positivo, sem ambiguidade genital, com perfil hormonal normal e (c) uma mulher 46,XX, fértil. Experimentos de transfecção transitória in vitro demostraram que a proteína mutante tem menor capacidade de transativação do plasmídio reporter da via Wnt. As simulações de dinâmica molecular constataram que a troca p.Cys102Tyr aumenta a flexibilidade do backbone da R-spondina-1, diminuindo a energia de ligação da proteína ao complexo de receptores, LGR5 e RNF43. Em conjunto, nossos achados demonstram que a variante c.305G > A é patogênica, sendo responsável pela síndrome genética diagnosticada na família brasileira. As análises de expressão gênica e os estudos de imuno-histoquímica, por sua vez, detectaram um aumento da expressão do gene SOX9 e maior imonorreatividade para a proteína Sox9 no tecido testicular do caso índice. Esses resultados sugerem que o processo de reversão sexual nos indivíduos XX ocorra por uma hiperexpressão de SOX9 secundária à menor ativação da via Wnt/beta-catenina na gônada durante a embriogênese. No presente estudo também relatamos o primeiro caso de indivíduo de cariótipo 46,XX portador de mutação em homozigose no gene RSPO1 que não desenvolveu DDS. A variabilidade do fenótipo sexual não está associada com alterações no número de cópias dos genes WNT4 ou do SOX9 e região cis-regulatória. No entanto, a avaliação do exoma da família encontrou uma associação entre o polimorfismo do receptor LGR5 rs17109924 e a atenuação do fenótipo de DDS. Todavia, serão necessários estudos funcionais para esclarecer o impacto biológico da interação das variantes RSPO1 p.Cys102Tyr e LGR5 rs171099 / In mammals, sex determination is governed by the balance between two parallel and antagonic signaling pathways: the male SOX9/FGF9 and the female, RSPO1/beta-catenin/WNT4 pathways. R-spondin 1 regulates the ovarian differentiation process by its modulating action through the canonic Wnt pathway (Wnt/beta-catenin). In humans, patogenic mutations in RSPO1 cause a rare, autosomic recessive syndrome characterized by 46,XX Testicular or Ovotesticular disorders of sexual development (DSD), palmoplantar keratosis (PPK) and predisposition to squamous cell carcinoma (MIM 610644). We identified and studied a SRY-negative 46,XX DSD patient with PPK from a large, consaguineous, brazillian family. Through a \"candidate gene\" approach we identified in the proband a new allelic variant in the coding region of RSPO1, c.305G > A. This variant presented full concordance with the PPK phenotype by segregation analyses in 10 of 67 members of this family. Clinical, hormonal, cytogenetic and molecular genetic studies characterized three patterns in individuals with this variant: (a) four 46,XX and/or SRY-negative males with ambiguous genitalia and altered hormonal profile; (b) five 46,XY and/or SRY-positive males without ambiguous genitalia with normal hormonal profile; (c) one 46,XX fertile woman. In vitro experiments demonstrated that transient transfection of the mutant protein resulted in lower transactivation of the Wnt pathway-reporter plasmid. Moreover, molecular dinamic studies showed that p.Cys102Tyr increased the R-spondin-1 backbone flexibility, thus decreasing the interaction between this protein and its receptors, LGR5 and RNF43. Thus, both in vitro and in silico analysis demonstrate the pathogenicity of the RSPO1 variant c.305G > A. In addition, in the index case, a higher expression of SOX9, corroborated by a reactive immunohistochemistry in testicular tissue, suggested that the process of sexual reversal in the XX individual is driven by a higher SOX9 expression possibly due to a lower Wnt/beta-catenin signaling pathway activation during embriogenesis. In this study, we also reported the first 46,XX individual with RSPO1 mutation without DSD, in which no copy number abnormality was detected in WNT4, SOX9 and its cisregulatory regions. Whole exome sequencing of the affected individuals revealed, in turn, that the LGR5 rs17109924 polymorphism associates with a protacted DSD phenotype in the fertile woman with normal hormonal profile. Despite this evidence, future studies are nedded to address causality and biological impact between RSPO1 p.Cys102Tyr and LGR5 rs17109924 variants