Human activity data discovery based on accelerometry

Dissertation to Obtain Master Degree in Biomedical Engineering

Adaptação cultural e contributo para a validação da escala petterns of activity measura - pain (POAM-P)

RESUMO: A dor lombar crónica (DLC) é uma das condições clínicas mais comuns e com elevados custos socioeconómicos no mundo ocidental. Estudos recentes indicam que os utentes com DLC apresentam diferentes padrões de atividade que influenciam os níveis de incapacidade funcional. Contudo, a evidência acerca destas associações é, ainda, limitada e inconclusiva. Em Portugal, não existe, do nosso conhecimento, nenhuma escala validada para a população portuguesa que meça estes padrões de atividade em utentes com DLC. Objetivos: Adaptar culturalmente a escala Patterns of Activity Measure – Pain (POAM-P) para a população portuguesa com dor lombar crónica inespecífica (DLCI) e contribuir para a sua validação. Metodologia: A versão original (inglesa) do POAM-P foi traduzida e adaptada para a língua portuguesa (POAM-P-VP) através de uma equipa multidisciplinar que incluiu tradutores, retrotradutores (cegos e independentes), peritos de diferentes áreas e utentes com DLCI, de acordo com as recomendações de linhas orientadoras atuais para este processo. A análise factorial e das propriedades psicométricas da POAM-P-VP contou com uma amostra de 132 utentes. A consistência interna foi analisada através do coeficiente alpha de Cronbach (α) e para a análise da fiabilidade teste-reteste recorreu-se ao coeficiente de correlação intraclasse (ICC:2,1). A análise da validade de construto convergente e discriminativa das componentes da POAM-P-VP foi conseguida através da aplicação da versão portuguesa da escala Tampa Scale of Kinesiophobia (TSK-13-VP), e recorrendo ao cálculo do coeficiente de Spearman. Todos os cálculos estatísticos foram realizados no software IBM SPSS Statistics (versão 20). Resultados: A análise factorial permitiu identificar três componentes da POAM-P-VP (evitamento, persistência excessiva e persistência consistente com a dor), sendo estruturalmente diferentes das subescalas do POAM-P original. Estas componentes apresentaram uma consistência interna boa a elevada. As componentes 1 e 2 apresentaram uma fiabilidade teste-reteste moderada a excelente, e a componente 3 uma fiabilidade teste-reteste pobre, limitando o seu poder de uso na prática clínica e em investigação. Relativamente à validade de construto, nenhuma das hipóteses estabelecidas no estudo apriori foram verificadas, não podendo aferir acerca da relação dos padrões de atividade com a cinesiofobia, medida pelo TSK-13-VP. Porém, a componente de evitamento da POAM-P-VP parece medir conteúdos partilhados com a TSK-13-VP (rs = 0.15, p<0.048). Conclusão: A adaptação e contributo para a validação da versão portuguesa da escala POAM-P constituiu um ponto de partida para a existência de um instrumento de medição de padrões de atividade de utentes portugueses com DLC, requerendo mais estudos para a sua validação. Apesar de algumas limitações, considera-se que este estudo é de grande importância para os fisioterapeutas e investigadores que buscam um maior conhecimento e efetividade das abordagens de intervenção em utentes com dor lombar crónica.-------------- ABSTRACT: Chronic low back pain (CLBP) is one of the most common clinical conditions as well as one with high economical costs within western countries. Recent studies have shown that patients with LBP present different patterns of activity which influence their levels of functional capacity. However, evidence on these associations is still limited and inconclusive. To our knowledge, there is in Portugal no valid scale for measuring these patterns of activity in CLBP patients. Purpose: Culturally adapt the Patterns of Activity Measure – Pain (POAM-P) scale to the Portuguese population with non-specific chronic low back pain (NSLBP) and contribute to its validation. Method: The original English version of POAM-P was blindly and independently translated, back translated and adapted to the Portuguese language (POAM-P-VP) by a multidisciplinary team of translators, experts from different fields, and patients with NSLBP, according to established guidelines for this process. Factorial and psychometric properties’ analysis of POAM-P-VP comprised a sample of 132 patients. The internal consistency was analyzed based on Cronbach's alpha-coefficient (α) and for test-retest reliability analysis the Intraclass Correlation Coefficient (ICC) was used. The analysis of convergent and discriminant construct validity of POAM-P-VP components was achieved through the use of the Portuguese version of the Tampa Scale of Kinesiophobia (TSK-13-VP), using the Spearman coefficient calculation. All statistical calculations were performed using IBM SPSS Statistics software (v.20). Results: The factor analysis allowed for the identification of three components of POAM-P-VP (avoidance, excessive persistence and pain-contingent persistence), structurally different from the original POAM-P subscales. These components demonstrated a good to high level of internal consistency. Components 1 and 2 demonstrated moderate to excellent test-retest reliability, whereas component 3 presented low test-retest reliability thus limiting its clinical and investigative use. With regard to construct validity, none of the previously established hypothesis was verified, therefore not making it possible to assess the relation between activity patterns and kinesiophobia, measured by TSK-13-VP. However, the avoidance component of POAM-P-VP seems to share measurable contents with TSK-13-VP (rs = 0.15, p<0.048). Conclusion: The adaptation and contribution to the validation of the Portuguese version of POAM-P scale, sets a starting point to the existence of a useful instrument for measuring activity patterns in Portuguese CLBP patients, requiring further studies towards its validation. Despite some limitations, this study is considered of high importance to physiotherapists as well as investigators in search of deeper knowledge and effective practical approaches on chronic low back pain patients.

Atividade física e Saúde Pública : políticas e estratégias de ação intersectorial na promoção de health-enhancing physical activity (HEPA) em Portugal

RESUMO - INTRODUÇÃO: A promoção de health-enhancing physical activity (HEPA), entendida como atividade física para a saúde, revela-se um dos aspectos fulcrais do trabalho de ação intersectorial da saúde pública e um dos principais desafios atuais no combate a esta pandemia da inatividade física de consequências na saúde, económicas, ambientais e sociais. A inatividade física está identificada como sendo um dos fatores de risco que contribui largamente para a mortalidade global. Análises às abordagens políticas de promoção da atividade física para a saúde são importantes instrumentos de sistematização da informação relacionada com o estudo deste problema. OBJETIVOS: É objetivo deste estudo analisar políticas e estratégias de ação intersectorial na promoção da atividade física para a saúde em Portugal. Em específico, elencar e analisar: 1) principais políticas e estratégias atuais dos diferentes sectores; 2) consideração de qual é o papel do sector da saúde no assunto; 3) fatores-chave e critérios de sucesso para a implementação de políticas de promoção de HEPA. METODOLOGIA: Estudo qualitativo, descritivo e transversal, por meio de entrevistas semiestruturadas e abertas pelos sectores da saúde, educação, desporto, transportes/planeamento urbano e ação social; análise documental, relativamente aos últimos 3 anos, com análise de conteúdo quanto aos critérios de sucesso presentes. RESULTADOS: Foram encontradas várias categorias nas dimensões macroambiente, microambiente e individual dos determinantes da atividade física no trabalho dos diferentes sectores; o sector da saúde não foi habitualmente considerado como devendo proporcionar administração para a ação intersectorial neste domínio; foram identificados os critérios: com menor expressão no material analisado, aos quais é atribuída maior importância e aqueles com menor aplicabilidade nos documentos analisados. CONCLUSÕES: Não podemos afirmar que exista uma abordagem política/estratégica integrada de abrangência nacional, operacional, no que respeita à promoção da atividade física para a saúde. São limitadas as conclusões pelas características inerentes ao tipo de estudo desenhado, no entanto, pensamos ter contribuído para descrever as principais políticas e estratégias de ação intersectorial na promoção de HEPA em Portugal. Estudos mais abrangentes em termos de níveis de governação, sectores envolvidos e período temporal deverão ser desenvolvidos de forma a potenciar o desenvolvimento da atividade física e saúde pública.

Development of a "green process" for the isolation of natural functional extracts with anti-cancer activity - Application of high-pressure technology

Dissertação para obtenção do Grau de Mestre em Engenharia Química e Bioquímica

Green synthesis of 2-Oxazoline-based polymers with antimicrobial activity using scCO2

Using a green methodology, 17 different poly(2-oxazolines) were synthesized starting from four different oxazoline monomers. The polymerization reactions were conducted in supercritical carbon dioxide under a cationic ring-opening polymerization (CROP) mechanism using boron trifluoride diethyl etherate as the catalyst. The obtained living polymers were then end-capped with different types of amines, in order to confer them antimicrobial activity. For comparison, four polyoxazolines were end-capped with water, and by their hydrolysis the linear poly(ethyleneimine) (LPEI) was also produced. After functionalization the obtained polymers were isolated, purified and characterized by standard techniques (FT-IR, NMR, MALDI-TOF and GPC). The synthesized poly(2-oxazolines) revealed an unusual intrinsic blue photoluminescence. High concentration of carbonyl groups in the polymer backbone is appointed as a key structural factor for the presence of fluorescence and enlarges polyoxazolines’ potential applications. Microbiological assays were also performed in order to evaluate their antimicrobial profile against gram-positive Staphylococcus aureus NCTC8325-4 and gram-negative Escherichia coli AB1157 strains, two well known and difficult to control pathogens. The minimum inhibitory concentrations (MIC)s and killing rates of three synthesized polymers against both strains were determined. The end-capping with N,N-dimethyldodecylamine of living poly(2- methyl-2-oxazoline) and poly(bisoxazoline) led to materials with higher MIC values but fast killing rates (less than 5 minutes to achieve 100% killing for both bacterial species) than LPEI, a polymer which had a lower MIC value, but took a longer time to kill both E.coli and S.aureus cells. LPEI achieved 100% killing after 45 minutes in contact with E. coli and after 4 hours in contact with S.aureus. Such huge differences in the biocidal behavior of the different polymers can possibly underlie different mechanisms of action. In the future, studies to elucidate the obtained data will be performed to better understand the killing mechanisms of the polymers through the use of microbial cell biology techniques.

Osteoclast activity in ankylosing spondylitis patients before and after TNF-blocking therapy

Ankylosing spondylitis (AS) is a chronic inflammatory rheumatic disease of the axial skeleton. The major outcome of this disease is defined by new bone formation, commonly observed in the ligaments of the intervertebral joints, that can lead to the formation of bony spurs, known as syndesmophytes. Previous studies have shown that serum levels of TNF, IL-6 and IL-17 are increased in AS patients and may be implicated in the development of secondary osteoporosis, since these cytokines are able to induce osteoclast (OC) differentiation and, therefore, bone resorption. In this work we aimed to assess the effects of TNF-blocking therapy in the systemic inflammatory environment of AS patients with active disease as well as in OC differentiation and activity. To accomplish this objective, we cultured circulating monocytes from AS patients, before and after therapy, under osteoclastogenic conditions and we performed two functional assays (TRAP staining and resorption pit assay) and analyzed the expression of osteoclast specific genes. We have shown that AS patients with active disease have increased levels of pro-inflammatory cytokines when compared with healthy subjects. We also found that IL-17, TGF-β and osteoprotegerin are decreased after TNF-blocking therapy. Interestingly, we also observed that after TNF-blocking therapy the expression of some genes is favoring osteoclastogenesis and that differentiated OCs have increased resorption activity. These results suggest that in active AS there may be an uncoupling between inflammation and OC activity that is reset by TNF-blocking therapy.

Human activity recognition with accelerometry: novel time and frequency features

Human Activity Recognition systems require objective and reliable methods that can be used in the daily routine and must offer consistent results according with the performed activities. These systems are under development and offer objective and personalized support for several applications such as the healthcare area. This thesis aims to create a framework for human activities recognition based on accelerometry signals. Some new features and techniques inspired in the audio recognition methodology are introduced in this work, namely Log Scale Power Bandwidth and the Markov Models application. The Forward Feature Selection was adopted as the feature selection algorithm in order to improve the clustering performances and limit the computational demands. This method selects the most suitable set of features for activities recognition in accelerometry from a 423th dimensional feature vector. Several Machine Learning algorithms were applied to the used accelerometry databases – FCHA and PAMAP databases - and these showed promising results in activities recognition. The developed algorithm set constitutes a mighty contribution for the development of reliable evaluation methods of movement disorders for diagnosis and treatment applications.

Trans-Synaptic Signaling by Activity-Dependent Cleavage of Neuroligin-1

Throughout the brain, patterns of activity in postsynaptic neurons influence the properties of synaptic inputs. Such feedback regulation is central to neural network stability that underlies proper information processing and feature representation in the central nervous system. At the cellular level, tight coupling of presynaptic and postsynaptic function is fundamental to neural computation and synaptic plasticity. The cohort of protein complexes at the pre and postsynaptic membrane allows for tight synapse-specific segregation and integration of diverse molecular and electrical signals.(...)

Structural and functional studies of a high activity NiFeSe Hydrogenase

Theawareness that fossil fuels exist in limited quantities has stimulated research into energy production from renewable sources. Future energy sources! should! be! plentiful! with! negligible! impact! on! the! environment.! Hydrogen!has!the!potential!to!satisfy!these!requirements.!Nevertheless,!current! methods! of! H2! production! rely! on! nonOrenewable! resources.! Biological! H2! production! from! sunlight! or! biomass! is! an! appealing! alternative! to! current! production!methods.!!(...)

Efficiency optimization of the transportation supply chain activity: the maritime option for Volkswagen Autoeuropa

Field Lab of Entrepreneurial Innovative Ventures

Autonomia funcional em idosos : caracterização multidimensional em idosos utentes de um centro de saúde urbano

RESUMO: Tivemos como objectivo do presente trabalho avaliar a capacidade funcional, e factores eventualmente a ela associados, numa amostra de 152 idosos ambulatórios, sem doenças agudas ou graves, utentes de um centro de saúde urbano. Cada avaliação consistiu numa entrevista, mediante um inquérito sobre capacidade funcional, morbilidade, estado mental e aspectos sociais, e no estudo da composição corporal. As perguntas referentes às variáveis estudadas foram por nós desenvolvidas e estruturadas com base em escalas internacionais validadas e de utilização comum na avaliação de idosos, excepto para as variáveis em que não encontrámos escalas com essas características. Os seus quesitos foram incluídos como perguntas e respostas estruturadas e pré-codificadas, permitindo a atribuição de uma pontuação a cada variável e a sua posterior divisão dicotómica. Aplicámos as escalas de Katz e de Lawton para a avaliação das actividades de autonomia física e instrumental da vida diária, a escala de Grimby para a avaliação da actividade física, a escala de Hamilton e o teste de Folstein para a avaliação do estado mental nas vertentes afectiva e cognitiva e a escala de Graffar para caracterizar a classe social, e perguntas sobre locomoção, autoavaliação da saúde, queixas de saúde presentes e rede social. Fizemos o registo da morbilidade segundo a International Classification of Primary Care - ICPC. A avaliação antropométrica constou da medição do peso, da altura, dos perímetros do braço, da cintura, da anca e proximal da coxa, e das pregas bicipital, tricipital, sub-escapular e supra-ilíaca. Foi também feita a estimativa da composição corporal por cálculos derivados de índices antropométricos e de bioimpedância eléctrica corporal total, o doseamento de algumas proteínas plasmáticas e a quantificação da força de preensão. Analisámos os resultados obtidos por grupos quanto ao sexo e à idade, dividida nos escalões etários 65 a 74 anos e mais do que 74 anos. Por regressão linear múltipla, foi testado o efeito do sexo e da idade sobre os valores medidos, para cada uma das variáveis e cada uma das suas pontuações parciais, sendo considerado como evidência de um efeito estaticamente significativo um valor “p” inferior a 0,05.Resumimos do seguinte modo os dados obtidos e a sua comparação com os dos estudos que seleccionámos como referência: A média de idades da amostra foi de 74 anos, sendo um terço destes do sexo masculino. Na sua maioria eram independentes em locomoção e funcionalidade, praticavam alguma actividade física, classificavam a sua saúde como razoável ou boa, apresentavam sintomatologia activa, não tinham depressão ou demência, tinham quem os acompanhasse embora cerca de metade apresentasse algum grau de isolamento, eram de baixa classe social, tinham excesso de peso, valores elevados de massa gorda, parâmetros plasmáticos proteicos compatíveis com ausência de doenças agudas ou graves e considerável força muscular de preensão. Na análise descritiva por grupos quanto ao sexo e/ou à idade, verificou-se que as mulheres e os mais idosos apresentavam maior isolamento social e os valores mais baixos de massa magra, hemoglobina e força de preensão. As mulheres tinham maior prevalência de dependência em autonomia física, depressão e valores mais baixos de transferrina. Os mais idosos apresentavam maior dependência em funcionalidade, menor actividade física, maior prevalência de demência, índice de massa corporal menos elevado, e valores mais baixos de albumina. Não se verificou prevalência de piores resultados dicotómicos nos homens nem no escalão etário menos idoso. Não teve relação com o sexo ou a idade o compromisso em autonomia instrumental, a presença de morbilidade ou a baixa classe social, assim como a não perturbação da locomoção e dos níveis de somatomedina-C. A análise comparativa com estudos multidimensionais em idosos portugueses e europeus ambulatórios revelou que a nossa amostra apresentava muitas características semelhantes às desses idosos. Assim, tinham elevada independência em locomoção, considerável independência em autonomia física e menor independência em autonomia instrumental; prática de actividade física ligeira, as mulheres dentro e os homens fora de casa; maior prevalência de morbilidade a nível dos aparelhos locomotor e cardiocirculatório, nos nossos idosos com pouca flutuação na autoavaliação de saúde; pequena prevalência de depressão e de demência; maior isolamento social nas mulheres e nas mais idosas; factores de classe social de baixo nível, diferindo apenas em relação aos idosos do norte da Europa que apresentavam elevada escolaridade e profissões mais diferenciadas; características biométricas sobreponíveis às dos idosos portugueses e às dos do sul da Europa, com tendência para o excesso de peso e proporção elevada de massa gorda; e doseamentos plasmáticos proteicos e força muscular de preensão compatíveis com ausência de doenças agudas ou crónicas graves. A comparação com os referidos estudos em relação ao risco de dependência, revelou semelhanças na associação entre dependência funcional e idade avançada, morbilidade, alteração do estado mental e isolamento social. Na amostra que estudámos não obtivemos associação entre dependência e o sexo feminino, facto que se verificou no estudo nacional de Almeida et al. e nos estudos multicêntricos europeus, ou o grau de escolaridade, como no estudo francês. Podemos concluir que, com o instrumento de avaliação que utilizámos, foi possível detectar e caracterizar perturbações numa amostra de idosos ambulatórios, a maioria funcionalmente independentes, sem alterações do estado mental, mas apresentando morbilidade activa, tendência para a obesidade, e actividade física ligeira. Nos que apresentaram alterações, estas foram mais frequentes no sexo feminino e nos indivíduos com mais de 74 anos. A escala de funcionalidade desenvolvida foi sensível aos efeitos da idade e permitiu o cálculo do risco de dependência em relação às outras variáveis estudadas, sendo mais marcante a associação com baixa actividade física, presença de queixas de saúde, demência e índice de massa corporal elevado. Consideramos que a metodologia que empregámos poderá contribuir para a avaliação de capacidades, cujo conhecimento sistemático nos idosos se impõe. ------------- ABSTRACT: The main objective of the present work was to evaluate functional capacity and related factors, in a sample of 152 ambulatory elderly, free from acute or serious disease, attending an urban health centre. Each evaluation included an interview, with a questionnaire about functional capacity, morbidity, mental health and social aspects, and the study of body composition. The questions were developed and structured in accordance with international validated scales usually applied in the evaluation of the elderly, whenever there were scales for that purpose. Their items were included as structured pre-coded questions and answers, so that each variable could have its own quotation and be dichotomised. We employed Katz and Lawton scales for basic and instrumental activities of daily living, Grimby scale for physical activity, Hamilton scale for depression, Folstein’s Mini Mental State Examination for cognitive ability and Graffar scale for social class, and questions about walking, health perception, active complaints and social network. The symptoms register was done according to the International Classification of Primary Care - ICPC. The anthropometric exam involved the determination of height and weight, arm, waist, hip and proximal thigh circumferences, and biceps, triceps, subscapular and suprailiac skinfolds. For the body composition calculation we employed equations derived from anthropometric indices, and from measurement of total body bioelectric impedance. We also measured some plasma proteins and handgrip strength. The analysis of results was done by sex and age groups, separating those with 65 to 74 years from those older than 74 years. The effects of sex and age were tested by linear multiple regression, for each variable and its components. Presented "p" values being considered statistically significative if less than 0,05. The results we obtained and their comparison with the studies we choose as reference can be summarised as follows: Mean age of the sample was 74 years and about one third were men. Most of them were independent in gait and functionality, practised some physical activity, rate their health as fair or good, had physical complaints, had not depression or dementia, had some companionship although almost half of them with stigmas of isolation, belonged to low social class, were in the range of overweight, had raised values of fat mass, plasma proteins in accordance with no acute or serious disease, and considerable handgrip strength. The analysis of groups by sex and age revealed that women and the eldest had the greater social isolation and the lowest values of free fat mass, haemoglobin and handgrip strength. Women had the higher dependence in basic activities of daily living, more depression and lower levels of transferrin. The eldest were more dependent in functionality, had greater prevalence of dementia, less physical activity, less raised body mass index and lower levels of albumin. Men alone and the age range of 65 to 74 did not show any prevalence of the worse dichotomised results. There was no relationship between sex or age and instrumental activities of daily living, morbidity or low social class, and unaffected gait or somatomedin-C levels. The comparison of results with multidimensional studies in portuguese and european ambulatory elderly showed that our sample had many similarities with theirs. They were independent in gait and activities of daily living; practiced light physical activity, women indoors and men outdoors; had greater morbidity at locomotor and cardiovascular systems, with small latitude in health evaluation; low prevalence of depression and dementia; social isolation predominantly in older women; and low social class factors, witch is only different from those of north Europe who had higher education levels and professional carriers; biometric characteristics similar to other portuguese and south Europe elders, with tendency for overweight and high proportion of fat mass; and plasma protein levels and handgrip strength in accordance with no acute or chronic serious disease. The comparison to the referred studies in relation to dependency risk, showed similarities in the association of dependency and age, morbidity,altered mental state and social isolation. We did not find association between dependency and sex, as it was found in the portuguese study of Almeida et al. and the european multicentric studies, or the education level, as in the french study. We conclude that, with the evaluation battery we employed, it was possible to detect and characterise alterations in a sample of ambulatory elderly, most of whom were functionally independent and had no alterations in mental state, but had active morbidity, tendency to obesity, and only light physical activity. Those that had some alteration, were more frequently women and the eldest. The functionality scale we developed showed to be sensitive to age effects and suitable for the calculation of risk of dependency, being more important the association with low physical activity, active complaints, dementia and high body mass index. We consider that the methodology we applied can contribute to the evaluation of capabilities that should be systematically sought for in the elderly.

Assessment by doppler ultrasound of entheseal lesions in spondyloarthritis : a longitudial study to determine structural damage and disease activity lesions

RESUMO: Enthesitis is the hallmark of spondyloarthritis (SpA), and is observed in all subtypes. Wide information on SpA abnormalities, including synovitis, tendinitis and enthesitis, can be efficiently perceived by Doppler ultrasound. Furthermore, several studies on imaging of enthesis showed that imaging techniques are better than clinical examination to detect enthesis alterations; and vascularized enthesitis detected by Doppler ultrasound appears to be a valuable diagnostic tool to confirm SpA diagnosis. However, data published until now concerning entheseal elementary alterations that characterize SpA enthesitis (enthesis inflammatory activity) or enthesopathy (permanent structural changes) reflect rather the authors’ empiric opinion than a methodological validation process. In this sense it seems crucial to identify elementary entheseal lesions associated with activity or damage, in order to improve monitoring and treatment response in SpA patients. The development of better assessment tools is today a challenge and a need in SpA. The first study of this thesis focused on the analysis of the reliability of inter-lector and inter-ultrasonography equipment of Madrid sonography enthesitis index (MASEI). Fundamental data for the remaining unrolling project validity. In the second and third studies we concerned about two entheseal elemental lesions: erosions and bursa. In literature erosions represent a permanent structural damage, being useful for monitoring joint injury, disease activity and therapeutic response in many rheumatic diseases; and to date, this concept has been mostly applied in rheumatoid arthritis (RA). Unquestionably, erosion is a tissue-related damage and a structural change. However, the hypothesis that we decided to test was if erosions represent a permanent structural change that can only grow and worsen over time, as occurs in RA, or a transitory alteration. A longitudinal study of early SpA patients was undertaken, and the Achilles enthesis was used as a model. Our results strongly suggested that previously detected erosions could disappear during the course of the disease, being consistent with the dynamic behavior of erosion over time. Based on these striking results it seems reasonable to suggest that the new-bone formation process in SpA could be associated with the resolution of cortical entheseal erosion over time. These results could also be in agreement with the apparent failure of anti-tumor necrosis factor (TNF) therapies to control bone proliferation in SpA; and with the relation of TNF-α, Dickkopf-related protein 1 (Dkk-1) and the regulatory molecule of the Wnt signaling pathway in the bone proliferation in SpA. In the same model, we then proceeded to study the enthesis bursa. Interestingly, the Outcome Measures in Rheumatology Clinical Trials (OMERACT) enthesopathy definition does not include bursa as an elementary entheseal lesion. Nonetheless, bursa was included in 46% of the enthesis studies in a recently systematic literature review, being in agreement with the concept of “synovio-entheseal complex” that includes the link between enthesitis and osteitis in SpA. It has been clarified in recent data that there is not only a close functional integration of the enthesis with the neighboring bone, but also a connection between enthesitis and synovitis. Therefore, we tried to assess the prevalence and relevance of the bursa-synovial lesion in SpA. Our findings showed a significant increase of Achilles bursa presence and thickness in SpA patients compared to controls (healthy/mechanical controls and RA controls). These results raise awareness to the need to improve the enthesopathy ultrasonographic definition. In the final work of this thesis, we have explored new perspectives, not previously reported, about construct validity of enthesis ultrasound as a possible activity outcome in SpA. We performed a longitudinal Achilles enthesis ultrasound study in patients with early SpA. Achilles ultrasound examinations were performed at baseline, six- and twelve-month time periods and compared with clinical outcome measures collected at basal visit. Our results showed that basal erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are higher in patients with Doppler signal in enthesis, and even that higher basal ESR, CRP and Ankylosing Spondylitis Disease Activity Score (ASDAS) predicted a higher Doppler signal (an ultrasound alteration accepted as representative of inflammation) six months later. Patients with very high disease activity assessed by ASDAS (>3.5) at baseline had significantly higher Achilles total ultrasound score verified at the same time; and ASDAS <1.3 predicted no Doppler signal at six and twelve months. This seems to represent a connection between classical biomarkers and clinical outcomes associated with SpA activity and Doppler signal, not only at the same time, but also for the following months. Remarkably, patients with inactive disease (ASDAS < 1.3) at baseline had no Doppler signal at six and twelve months. These findings reinforce the potential use of ultrasound related techniques for disease progression assessment and prognosis purposes. Intriguingly, Ankylosing Spondylitis Disease Activity Index (BASDAI) didn’t show significant differences between different cut-offs concerning ultrasound lesions or Doppler signal, while verified with ASDAS. These results seem to indicate that ASDAS reflects better than BASDAI what happens in the enthesis. The work herein discussed clearly shows the potential utility of ultrasound in enthesis assessment in SpA patients, and can be important for the development of ultrasound activity and structural damage scores for diagnosis and monitoring purposes. Therefore, local promotion of this technique constitutes a medical intervention that is worth being tested in SpA patients for diagnosis, monitoring and prognosis purposes.