Thesis (Ph. D.)--University of Washington, 1999. / Vita. Includes bibliographical references (leaves 84-94).

Thesis (M.S.) -- University of Texas Southwestern Medical Center at Dallas, 2005. / Embargoed. Vita. Bibliography: 83-96.

Orientador: Patrícia Petromilli Nordi Sasso Garcia / Resumo: Os objetivos deste estudo foram adaptar um instrumento sobre fatores do trabalho que podem contribuir para sintomas osteomusculares para estudantes de Odontologia e avaliar suas propriedades psicométricas; estimar a validade e confiabilidade do University Student Engagement Inventory - USEI e do Dental Environment Stress Questionnaire - DES e verificar a contribuição do gênero, das variáveis acadêmicas e do estresse no ambiente odontológico na percepção dos estudantes quanto aos fatores de risco para sintomas osteomusculares. Foram convidados para participar do estudo 314 estudantes da Faculdade de Odontologia de Araraquara (UNESP) e 170 da Universidade de Araraquara (UNIARA). Foram coletadas informações referentes à idade, gênero e seriação do curso. Avaliou-se a percepção dos estudantes por meio do instrumento adaptado. O envolvimento escolar foi avaliado pelo USEI e o estresse foi medido pelo DES. Para a adaptação do instrumento utilizou-se o Job Factors Questionnaire, a revisão da literatura e a análise do Grupo Focal. A partir disso, novos itens foram criados e distribuídos dentro dos fatores Repetitividade, Postura de Trabalho e Fatores Externos. A sensibilidade dos itens foi avaliada por meio da assimetria e curtose. Foi conduzida a Análise Fatorial Confirmatória utilizando-se os índices de qualidade do ajustamento razão de qui-quadrado por graus de liberdade (2/gl), comparative fit index (CFI), goodness of fit index (GFI) e root mean square error of aproximation (RM... (Resumo completo, clicar acesso eletrônico abaixo) / Doutor

Fatores como aumento na expectativa de vida da população brasileira e o aumento de número de pessoas com estilo de vida predominantemente sedentário vem gerando o crescimento da incidência de uma série de doenças crônicas e degenerativas. A prática de exercícios físicos para esta considerável parcela da sociedade é importante, entretanto, a prescrição e execução da prática de exercícios físicos requerem cuidados especiais, como o reconhecimento de sinais que permitam a suspeita de doenças e lesões, principalmente as doenças musculosesqueléticas que podem ser agravados devido a atividades físicas, sem tratamento médico adequado. Através de um levantamento realizado no início deste trabalho, constatou-se a deficiência ou até ausência de matérias ou disciplinas que abordassem temas relacionados a doenças do sistema osteoarticular nas grades curriculares de cursos de graduação em educação física. Atualmente as academias de ginástica são em grande parte freqüentadas por pessoas que tem como objetivo a manutenção ou aquisição de uma melhor condição de saúde, não se restringindo apenas a objetivos relacionados com a estética corporal. As modalidades de exercícios mais praticados são: ginástica e musculação, segundo pesquisa realizada pelo Conselho Regional de Educação Física do Estado de São Paulo. Em outro levantamento realizado, neste presente trabalho, nas academias de ginástica, revelou que: a incidência de queixas de dores por parte dos freqüentadores destas academias se concentravam nas regiões lombar da coluna e joelho e; os professores destas academias careciam de conhecimentos para reconhecimento dos sinais destas doenças. O objetivo deste trabalho foi, estruturar um modelo de teleducação interativa para o treinamento de educadores físicos na identificação de sinais precoces de doenças osteoarticulares, apoioado na estruturação de um curso com inserção em um tutor eletrônico baseado na internet (cybertutor), transmissão de vídeos dos autores dos módulos em forma de video streaming e; utilização de iconografias de computação gráfica 3D (projeto homem virtual). Foi elaborada uma prova para avaliação de conhecimento dos estudantes de graduação dos cursos de educação física e ciências da atividade física da Universidade de São Paulo. Os estudantes foram avaliados quanto ao conhecimento temático do curso concomitante com avaliação do grau de inclusão digital e avaliação subjetiva dos estudantes em relação à aplicabilidade do curso. Como resultado, foi desenvolvido um curso interativo, com video streaming e 3 seqüências do homem virtual como recurso de apoio didático. O trabalho demonstrou que os estudantes tiveram incremento de conhecimento, inclusive os estudantes reprovados; a facilidade de acesso a recursos tecnológicos e de telecomunicação não constituíram fatores determinantes em relação ao grau de desempenho dos estudantes e; a sensação subjetiva dos estudantes em relação à aplicabilidade e relevância do curso foi maior entre os estudantes aprovados / Factors as increase in the expectative of life of Brazilian population and the growth of people with predominantly sedentary style of life are generating the growth of the incidence of many chronic and degenerative illnesses. The practice of physical exercises for this considerable portion of the society is important, however, to prescribe and execute the practice of physical exercises requires special cares, such as the recognition of these signals that can allow to suspect of illnesses and injuries, mainly the musculoskeletal diseases that can be aggravated due to practice of physical exercises, without adjusted medical treatment. Through a collection of data in the initial phases of this work was evidenced that theres a lack or none of disciplines that speech about themes related with diseases of the musculoskeletal system in the curriculum of the graduations courses in physical education. Nowadays, the gymnastics academies are frequented by people with the objective of improving health condition, not only improving the corporal esthetic condition. The modalities of the most practiced exercises in these environments are: gymnastics and muscular exercises, accordingly to a research done by CREF (Regional Counsel of Physical Education of the State of São Paulo). Another collection of data in this work was in the gymnastics academies that revealed that the incidence of pains complaints of the people who goes to academy was concentrated in the lumbar regions of the column and knee; the professors of these academies need of knowledge for recognition of the signal of these illnesses. The objective of this work was to structure a model interactive teleducation for the training of physical educators in the identification precocious signals of osteoarticular illnesses, which was supported of a structured course inserted in an electronic tutor based in the internet (cybertutor), transmission of videos of the modules authors presented as streaming videos and use of 3D iconography of graphical computation (virtual man project). It was applied an evaluation test of knowledge for students from graduations courses in physical education and physical activity sciences of the University of São Paulo. They were submitted to an evaluation about their knowledge of the courses theme, an evaluation of the degree of digital inclusion and a subjective evaluation in relation to the applicability of the course. As result, an interactive course was developed, with video streaming and 3 sequences of the virtual man as resource of didactic support. This work demonstrated that the students had had knowledge increment, including the disapproved ones, the facility of access to technological and telecommunication resources had not constituted determinative factors in relation to the performance degree of students and the subjective sensation of the students in relation to the applicability and relevance of the course was bigger between the approved students

Abstract Magnetic resonance imaging (MRI) has excellent soft tissue contrast, which can be enhanced by different contrast agents, multiplanar imaging capability and high temporal and spatial resolution. Even blood vessels can be easily visualised, and MRI parameters are sensitive to temperature. Therefore, MRI has the greatest potential for guiding and monitoring interventional and surgical procedures. The aim of this study was to design and evaluate new solutions for MR-guided procedures and surgery, to develop the technique and to assess the feasibility of MR-guided nerve root infiltration, bone biopsy and sacroiliac (SI) joint arthrography. The possibilities for versatile use of MR scanners were studied with a setup where an MR scanner with a 0,23 T open magnet was installed in a full-scale operating room (OR) to allow diagnostic MRI examinations, research, radiological interventions and neurosurgical operations to be performed in the same facility. All of the 144 MR-guided radiological interventions and neurosurgical operations performed in Oulu University Hospital between February 1999 and September 2000 were included in the study. The studied setup was a functionally feasible solution for combined neurosurgical and radiological use. To further improve MR-guided interventions, a new user interface was developed and preliminary tested with simulated clinical experiments. The new user interface seemed to be easily adobted by radiologists for interventional procedures. MR-guided nerve root infiltrations were studied by using MRI guidance on 34 consequent patients referred for first sacral root infiltration. Needle placement into the first sacral nerve root sheath was successful in 34 of the 35 (97%) cases, and the average duration of the procedure was 32 minutes. Bone biopsies were performed using a bone biopsy set designed in our institution to be connected to an optical tracking system. The feasibility of this new guiding system was evaluated with biopsies from five different anatomical areas. The bone biopsy system was successfully applied to all patients and provided a safe and accurate guidance method for all phases of the procedure. Twenty patients with low back pain suspected to arise from the SI joint underwent MR-guided SI joint arthrography. The procedure was successfully performed in all cases. The needle guiding with optical tracking inside the soft tissues proved to be accurate enough for successful procedures. In conclusion, versatile use of MR scanners for diagnostic imaging, radiological procedures and neurosurgery is feasible if planned properly. The prototype of a new user interface for MR-guided procedures allows radiologist to fully control the MR-scanner during the procedure. MRI is a suitable and accurate guidance method for musculoskeletal interventions.

Abstract The objectives of the study were to evaluate factors associated with work ability and musculoskeletal symptoms among food industry workers, to evaluate thermal and neuromuscular responses during repetitive work in the cold and to find out whether cold-induced deterioration in neuromuscular function can be prevented by using additional torso heating or altering work intensity during repetitive work at 4 °C. A questionnaire study (1,117 respondents) and measurements of physical work strain (18 subjects) were performed among workers in food-processing industry. The impact of changes of ambient temperature (16 subjects) and work intensity (8 subjects) on thermal responses and neuromuscular function was evaluated during repetitive work in laboratory conditions. The results from the questionnaire study indicated that self-assessed poor work ability and musculoskeletal symptoms were associated with impaired individual health resources and work-related factors, including higher number of years working in the cold, experience of draught and body cooling at work. Measurements during repetitive work in cold food-processing facilities showed that muscular strain was localized in forearm muscles. Laboratory studies showed that compared with 19 °C, repetitive work at 4 °C increased muscular strain in forearm and upper arm extensors significantly only in men, although the level of muscular strain remained lower and mean skin temperature higher compared with women. Working at 4 °C indicated more continuous activation of the working muscles compared with work at 19 °C. By intermittently increasing the workload at 4 °C the more continuous activation could be counteracted, thus leading to lower strain and fatigue of the working muscles. Additional torso heating did not affect muscular strain of the working muscles at 4 °C. In conclusion, the results indicate a multifactorial feature of work ability and musculoskeletal symptoms among workers in food-processing industry. Gender affects both thermal and neuromuscular responses, which should be considered in the area of work demands and work organization in cold conditions. Altering work intensity could be considered beneficial for reducing muscular strain during repetitive work in cold conditions.

Background: Knee osteoarthritis (OA) is the most common type of OA and is a major cause of pain and thus results in disability for daily activities among persons living in the community. OA currently has no cure. In addition to the conflicting recommendations from clinical guidelines, evidence about the extent to which long-term use of intra-articular injections improves patient outcomes is also lacking. Methods: Using data from the Osteoarthritis Initiative (OAI), marginal structural models (MSMs) applying inverse probability treatment weights (IPTW) were used to examine the effectiveness of intra-articular injections and changes in symptoms over time. The specific aims of this dissertation were to: 1) evaluate longitudinal use of intra-articular injections after treatment initiation among persons with radiographic knee OA; 2) quantify the extent to which intra-articular injection relieves symptoms among persons with radiographic knee OA; and 3) evaluate the performance of missing data techniques under the setting of MSMs. Results: Of those initiating injections, ~19% switched, ~21% continued injection type, and ~60% did not report any additional injections. For participants initiating corticosteroid (CO) injections, greater symptoms post-initial injection rather than changes in symptoms over time were associated with continued use compared to one-time use. Among participants with radiographic evidence of knee OA, initiating treatments with either CO or hyaluronic acid (HA) injections was not associated with reduced symptoms compared to non-users over two years. Compared to inverse probability weighting (IPW), missing data techniques such as multiple imputation (MI) produced less biased marginal causal effects (IPW: -2.33% to 15.74%; -1.88% to 4.24%). For most scenarios, estimates using MI had smaller mean square error (range: 0.013 to 0.024) than IPW (range: 0.027 to 0.22). Conclusions: Among participants with radiographic evidence of knee OA living in the community, the proportion of those switching injection use and one-time users was substantial after treatment initiation. In addition, initiating injection use was not associated with reduced symptoms over time. With respect to issues of missing data, using MI may confer an advantage over IPW in MSMs applications. The results of this work highlight the importance of using comparative effectiveness research with non-experimental data to study these commonly used injections and may help to understand the usefulness of these treatments for patients with knee OA.

Background: Neuromuscular Scoliosis is a frequent complication of Cerebral Palsy that requires surgical management including spinal fusion. The objective of this observational study was to describe differences in the frequency of postoperative complications in children with Cerebral Palsy following spinal fusion surgery compared to children with Idiopathic Scoliosis. Methods: The 2016 Kids’ Inpatient Database was queried to identify pediatric patients (old) with concurrent diagnoses of Cerebral Palsy and Neuromuscular Scoliosis undergoing spinal fusion surgery. Cases were compared to children without Cerebral Palsy and with a diagnosis of Idiopathic Scoliosis undergoing the same procedure. Fitted Poisson regression analysis with robust variance was performed to estimate relative risks in the frequency of various clinical complications while adjusting for several potentially confounding variables of importance. Results: A total of 660 cases and 5,244 comparators were identified. Compared to children with Idiopathic Scoliosis, children with Cerebral Palsy were younger (13.6 vs. 14.3 years), more likely to be male (54% vs. 23%), and more likely to have had governmental insurance (52% vs. 32%). They also had longer hospital lengths of stay (8 days vs. 4 days). After adjusting for a number of potentially confounding sociodemographic and clinical variables, children with Cerebral Palsy were more likely to have postoperative pulmonary, gastrointestinal, and surgical complications, receive blood transfusions, and be admitted to the ICU. Conclusions: Children with Cerebral Palsy have an increased risk of complications following spinal fusion surgery leading to longer hospital stays. These results further inform surgical decision-making and anticipatory guidance for these children and their caregivers.

The effects of pain suffered from musculoskeletal disorders by dental professionals may lead to reduced work hours, loss of production, and early retirement. Although third- and fourth-year dental students are provided lectures about musculoskeletal disorders, proper positioning and ergonomics, they are at an increased risk of developing MSD. This study was conducted to evaluate the prevalence on musculoskeletal disorders in third- and fourth-year dental students and to determine if third-year dental students experience more MSD pain than fourth-year dental students at the University of Tennessee Health Science Center College of Dentistry. A total of 50 third- and fourth- year dental students responded to the online questionnaire, 21 third-year dental students and 29 fourth-year dental students. Both third- and fourth-year dental students report experiencing MSD pain over the last twelve months. There was no statistically significant difference between MSD pain felt between third- or fourth-year dental students.

Autoimmune diseases such as rheumatoid arthritis (RA) are associated with debilitating chronic inflammation, autoantibody production, articular bone erosions and systemic bone loss. The underlying mechanisms and cell types that initiate these diseases are not fully understood, and current therapies mainly address downstream mechanisms and do not fully halt disease progression in all patients. Moreover, previous studies have largely focused on the role of adaptive immunity in driving these diseases, and less attention has been given to the contribution of innate immune pathways such as DNA sensor signaling pathways in initiating and/or perpetuating autoimmunity and erosive inflammatory arthritis. Detection of microbial nucleic acids by DNA sensors such as endosomal toll-like receptors (TLRs) and cytosolic sensors is an early form of antiviral defense. Upon detection of nucleic acid, TLRs dependent on Unc93B and cytosolic sensors dependent on the adaptor stimulator of interferon genes (STING) orchestrate production of type 1 interferons and pro-inflammatory cytokines to resolve infection. Additionally, the cytosolic DNA sensor absent in melanoma 2 (AIM2), which is not dependent on STING, also recognizes microbial DNA and coordinates the cleavage of pro-IL-1β. Previous studies have largely focused on the role of these DNA sensors in macrophages and dendritic cells in the context of antiviral immunity. In recent years, however, the inappropriate recognition of host nucleic acids by these sensors has been associated with several autoimmune diseases including RA. This dissertation aims to delineate the mechanisms by which DNA sensors contribute to inflammatory arthritis and bone remodeling in the context of a murine model of autoimmunity. In DNase II deficient mice, excessive accrual of undegraded, endogenous DNA leads to robust production of type 1 interferons (IFNs) and proinflammatory cytokines. The high levels of type 1 IFNs result in anemia and embryonic lethality; therefore, the gene for the type 1 IFN receptor (IFNaR) has also been deleted so that the mice survive. DNase II-/- IFNaR-/- double knockout (DKO) mice develop erosive inflammatory arthritis, anti-nuclear antibodies, and splenomegaly not seen in the DNase II+/- IFNaR-/- (Het) control group. To evaluate whether cytosolic or endosomal DNA sensors contribute to the clinical manifestations of DKO mice, genes involved in TLR or cytosolic sensor signaling were deleted on the DKO background. Genetically altered mice include STING/DNaseII/IFNaR TKO (STING TKO), AIM2/DNase II/IFNaR TKO (AIM2 TKO), and Unc93b/DNase II/IFNaR TKO (Unc93 TKO) mice. Our hypothesis was that the STING, AIM2, and/or Unc93 pathways would contribute to the autoimmune manifestations in DNase II deficient mice. Rigorous examination of inflammation in these lines revealed important roles for both the STING and AIM2 pathways in arthritis. Despite the substantial effects of the STING and AIM2 pathways on arthritis, STING TKO and AIM2 TKO mice still exhibited prominent autoantibody production. Interestingly, inflammation persisted in Unc93 TKO mice while autoantibody production to nucleic acids was abrogated. Collectively, these data indicate that innate immune pathways contribute to the initiation/perpetuation of inflammatory arthritis and demonstrate that cytosolic and endosomal pathways play distinct roles in the manifestations of autoimmunity. Moreover, they reveal a previously undescribed role for AIM2 as a sensor of endogenous nucleic acids in inflammatory arthritis. Thus, therapeutics that target the STING and AIM2 pathways may be beneficial for the treatment of inflammatory joint diseases. While the role of hematopoietic cells in driving autoimmunity has been well established, the contribution of stromal elements to disease pathogenesis is less well understood. Therefore, we generated bone marrow chimeras to delineate the contribution of hematopoietic and non-hematopoietic cells to the various autoimmune manifestations in DKO mice. These studies revealed that both donor hematopoietic and host radioresistant cells are required for inflammation in the joint as well as for other features of autoimmunity in DKO mice, including splenomegaly, extramedullary hematopoiesis, and autoantibody production. This data demonstrates that stromal host cells play a major role in DNA-driven autoimmunity. Moreover, these results suggest that targeting not only hematopoietic but also stromal elements may be advantageous in the setting of inflammatory arthritis. In the final chapter of this thesis, a role for innate immune sensor pathways in bone is described. The majority of inflammatory arthritides have been shown to lead to systemic loss of bone. Surprisingly, however, we found that DKO mice accumulate trabecular bone in the long bones over time as well as ectopic bone in the spleens, both sites of robust DNA accrual. Moreover, deficiency of the STING pathway abrogated this bone accumulation. Collectively, these data demonstrate that DNA accrual promotes dysregulated bone remodeling through innate immune sensing pathways. These findings are the first to reveal a role for the STING pathway in bone and may unveil novel targets for the treatment of diseases associated with bone disorders.