Le travail présenté dans le manuscrit concerne la conception d'un dispositif médical de classe III pour des applications en ingénierie tissulaire du derme et du disque intervertébral.Il s'agit d'une solution aqueuse de chitosane, stérilisée par autoclave, et dont le pH et l'osmolarité ont été ajustés selon un procédé de dialyse classique. Cette solution possède des propriétés de gélification in situ innovantes, ce qui lui confère de très bonnes propriétés mécaniques quelques minutes après l'injection, sans l'utilisation d'agents de réticulation mais de façon modulable en fonction de la concentration en polymère. De plus, cette solution possède une bonne injectabilité favorisant le développement d'une technique d'implantation mini-invasive pour la régénération du derme et du disque intervertébral. Un critère de performance rhéologique a notamment été mis au point afin de relier l'injectabilité aux propriétés mécaniques de l'injectât (dermal filler).Les propriétés mécaniques de l'injectât gélifié doivent être comparables au tissu natif en particulier pour le dermal filler mais aussi pour le disque intervertébral. Le comportement mécanique viscoélastique du disque intervertébral a été évalué par des essais de relaxation de contraintes et modélisé avec un modèle de Maxwell solide à trois branches. Ces essais ont été conduits sur des disques sains, ayant subi une altération de structure (fenestration) et après l'injection de biopolymères.La solution de chitosane a été injectée (i) dans le tissu cutané de deux modèles animaux : le porc et le rat et (ii) dans le disque intervertébral de deux modèles animaux : le porc et le lapin. La biocompatibilité ainsi que la réponse biologique de solutions/gels physique de chitosane in vivo ont été validées pour tous ces modèles animaux / This work deals with the conception of a class III medical device for applications in tissue engineering of dermis and intervertebral disc.This device consists in an aqueous chitosan solution, sterilized by autoclaving, with pH and osmolality adjusted by a dialysis process. This chitosan solution shows in situ gelation ability with a post-injection increase of mechanical properties. This feature is related to polymer concentration, gelation time, and is performed without external cross-linking agent. In addition, the solution exhibits a good injectability allowing the development of minimally invasive techniques to treat dermis and intervertebral disc diseases. A rheological performance criterion was defined linking injectability to mechanical properties of the implant (dermal filler).Mechanical properties of gel implant formed in contact with body fluids, in situ, have to be similar to that of native tissues. The viscoelastic behavior characterization of intervertebral disc was performed using stress relaxation and was modeled using a generalized solid Maxwell model (composed of three Maxwell elements). The tests were performed on healthy disc, fenestrated discs and after biopolymers injection.Chitosan solutions were injected into (i) porcine and rat cutaneous tissue and (ii) porcine and rabbit intervertebral discs. The biocompatibility and biofunctionality of chitosan solutions and physical hydrogels was evidenced in vivo for all animals

A tese propõem uma metodologia, em nível de pesquisa, por intermédio do desenvolvimento e da adaptação de ferramentas de apoio computadorizado, capaz de realizar a segmentação da imagem dos discos intervertebrais da região lombar da coluna vertebral humana, de maneira semiautomática reduzindo drasticamente o tempo gasto manualmente neste procedimento, sem perder sua acurácia e, ainda, garantindo maior reprodutibilidade em seus resultados. Foram utilizadas imagens sagitais de ressonância magnética ponderadas em T2 de 285 discos intervertebrais de 70 pacientes, classificados segundo o grau de severidade da degeneração discal definido pelo critério proposto por Pfirrmann. A classificação computacional dos discos foi realizada com base em atributos quantitativos extraídos dos histogramas de níveis de cinza e de informações de textura das imagens. O desempenho dos métodos computacionais de segmentação foi avaliado com base no Coeficiente de Jaccard, na distância de Hausdorff e no Erro Médio Quadrático. O desempenho dos métodos computacionais de classificação foi também avaliado com base em medidas similares à aplicação da sensibilidade, da especificidade e da área sob a curva ROC. A segmentação manual e a classificação por inspeção visual dos discos realizadas por três profissionais experientes foram utilizadas como padrão ouro para a comparação. Os principais resultados indicaram a médio de 63,22% para o Coeficiente de Jaccard, as médias de 0,044 das distâncias de Hausdoff e de 0,014 para o EMQ na comparação entre as imagens. Além disso, a segmentação semiautomatizada diferiu em uma taxa média de 30% em relação à segmentação manual e a classificação da degeneração discal, por redes neurais artificiais difere em menos de 2%, ao ser comparada ao procedimento de classificação manual realizado pelos especialistas. / The thesis proposes a methodology at the level of research through the development and adaptation of computerized support tools, able to perform the image segmentation of the intervertebral discs of the lumbar region of the human spine, semiautomatic way dramatically reducing time spent manually in this procedure, without losing its accuracy and also ensuring more reproducible in their results. Were used sagittal MRI T2- weighted of 285 intervertebral discs from 70 patients, classified according to the severity of disc degeneration defined by the criteria proposed by Pfirrmann. The computational classification of disks was based on quantitative attributes extracted from histograms of gray level images and the texture information. The performance of computational segmentation methods was evaluated based on Jaccard coefficient, Hausdorff distance and Mean Square Error. The performance of the computational classification methods was evaluated based on measures of sensitivity, specificity and the area under the ROC curve. The manual segmentation and visual inspection classification of the discs made by three experienced professionals were used as the gold standard for comparison. The main results showed an average Jaccard coefficient of 63.22%, the average Hausdoff of distances was 0.044 and 0.014 Mean Square Error average when comparing the images from both segmentation targets. Additionally, the targeting semiautomatic differed by an average of 30% compared with manual segmentation and classification of disc degeneration provided from an artificial neural networks differs by less than 2% when compared to manual sorting procedure performed by experts.

Ce travail de thèse a porté sur de nouveaux implants intervertébraux en céramique. Au cours du projet dans son ensemble (projet européen Longlife), un nouveau matériau et de nouveaux designs d’implants ont été développés, ainsi qu’un nouveau test destiné à simuler les sollicitations subies in vivo par les implants afin d’estimer leur durée de vie. Le nouveau matériau développé est un composite triphasé composé d’une matrice de zircone dopée à l’oxyde de cérium (pour sa résistance au vieillissement), d’une phase globulaire d’alumine α (pour affiner la microstructure) et d’une phase allongée composée d’aluminates de strontium (pour augmenter la ténacité). La première partie du travail a consisté à caractériser ce matériau afin de connaître son comportement en termes de résistance mécanique, stabilité thermique, et de résistance à la stérilisation. Une deuxième partie a été consacrée au développement d’un test multiphysique regroupant les différentes sollicitations attendues par une prothèse in vivo (fatigue axiale, micro-séparation, vieillissement et usure). Il a fallu pour cela s’appuyer sur des simulations numériques qui ont permis de développer le système. Les données de la littérature ont été utilisées afin de choisir les paramètres du test (durée, fréquence, milieu d’essai). Enfin, la dernière partie de ce travail a été la mise à l’épreuve de différents prototypes à travers le test multiphysique et leur caractérisation en cours d’essai. Les principaux résultats de ce travail de thèse sont les suivants : le composite montre un comportement pseudo-plastique sous charge, avec une nette transformation de phase avant rupture, ce qui est positif dans le cadre de son utilisation. De plus, il ne semble pas affecté par la stérilisation. Du point de vue des implants développés, peu passent le test multiphysique. Le design, ainsi que la géométrie (notamment la clearance des échantillons) sont des leviers d’amélioration qui permettront d’augmenter la fiabilité des implants. / This work deals with the development of new intervertebral prostheses, made with ceramics. A whole European project, Longlife, was dedicated to the development of such implants. To achieve this goal, several axes have been followed: the synthesis of a new material, the development of new designs of intervertebral bodies, and the set-up of a new test aimed at reproducing in vitro the different solicitations undergone by an intervertebral implant in vivo. The new material developed is a triphasic composite composed of a matrix of ceria-doped zirconia (insensitive to ageing), a secondary globular phase of α-alumina (to reduce the grain size), and a third, elongated phase composed of strontium aluminates platelets (in order to improve fracture toughness). The first part of this work was to characterize this new material in order to forecast its behaviour under mechanical solicitation, thermal stability and resistance to sterilization. Secondly, the set-up of the new test is exposed. Different steps were chosen (axial fatigue, micro-separation, ageing and wear) in order to reproduce the “real-life” solicitations. To achieve this goal, Finite Elements simulations were performed, allowing the development of specific specimen holders that mimic the fixation of the implants in the vertebrae. The parameters of the test (duration, frequency, medium) were chosen after a details survey of the literature and of standards. At the end, we tested different prototypes trough this new multiphysic assessment set up. As a main result of this thesis, the chosen ceramic composite exhibits a pseudo-plastic behaviour, with a large deformation due to phase transformation before fracture, which is a positive result in the framework of the forecast applications. Moreover, the material doesn’t seem degraded by the sterilization processes. Concerning the multiphysic test, only a few implants resisted it. The design of the implants is a key-point, as well as the geometry (in particular, clearance seems to be critical).

Disc degenerative changes are directly or indirectly associated with spinal pain and disability. Literature revealed a high prevalence of disc degeneration in the thoracic region, however thoracic MRI degeneration trends and information on disc biochemical matrix constituents are limited for thoracic discs compared to lumbar and cervical discs. The objective of this thesis was to use MRI to investigate the prevalence of disc degenerative changes affecting the human thoracic spine, and to determine the factors affecting spinal disc biochemical matrix. A 3-point subjective MRI grading scale was used to grade the films. The feasibility of using archived formalin-fixed cadaver material was investigated to analyse collagen and elastin crosslinks. The prevalence of degenerative changes in human thoracic discs and vertebrae (T1 to T12) was determined retrospectively from an audit of 216 MRI cases, using sagittal T1- and T2-weighted MR images. In a subsequent series of ex-vivo studies, human thoracic discs and LF from 26 formalin-fixed and two fresh spines, involving all thoracic levels, were examined macroscopically to determine the degeneration status. Subsequently, disc and ligament tissues were analysed biochemically for collagen (pyridinoline and deoxypyridinoline) and elastin (desmosine and isodesmosine) crosslinks. These crosslinks were extracted from hydrolysed samples by cellulose partition chromatography, and analysed by reverse-phase HPLC. Collagen content was determined using its hydroxyproline content, and proteoglycan content was assayed using a modified DMB assay for chondroitin sulphate. Finally the MRI and macroscopic assessments of thoracic discs, were compared with the biochemical data from two fresh cadaver thoracic spines. The 3-point MRI grading scale had a high inter- (k = 0.57 to 0.78) and intra-rater (k = 0.71 to 0.87) reliability. There were no significant differences in the collagen and elastin content and extent of collagen crosslinks between formalin fixed and unfixed ligament and disc tissues, after 25 weeks of formalin fixation. From the in-vivo MRI series of investigations (n = 216 MRI films), the prevalence of thoracic disc degenerative and vertebral morphological changes revealed significant age, gender and spinal level trends (p < 0.05).Generally, males had a higher propensity for disc degeneration in contrast to females, especially older females, where the trend showed a higher prevalence of osteophytes and vertebral body changes. In particular, the mid and lower thoracic levels have a higher prevalence of degenerative changes, except for osteophytes and anterior vertebral wedging. With increased age, there was a concomitant increase in anterior wedging and bi-concavity and disc degenerative changes except for end-plates. The biochemical investigations on the ex-vivo series of formalin-fixed thoracic discs (n = 303) also revealed significant changes in the disc matrix due to degeneration status, age, gender and spinal regional factors. With increased age, normal disc matrices have significantly lower collagen content and extent of pyridinoline (p < 0.001). In contrast, the degenerated disc matrix revealed significantly higher collagen content and extent of deoxypyridinoline (p < 0.05). These findings suggest that an altered matrix existed in normal ageing discs, which render the disc prone to injury and degeneration over the life span. The higher collagen and deoxypyridinoline in degenerated disc matrices reflects an increase in chondrocyte synthesis, and is also a novel finding, suggesting that they may be used as markers of ageing and degeneration processes. The biochemical investigations on another series of ex-vivo spinal LF tissues (n = 364), revealed that this had a lower collagen and pyridinoline, but significantly higher elastin and deoxypyridinoline compared to spinal discs (p < 0.05). Elastin crosslinks however were difficult to detect in spinal discs, being present in negligible amounts in a few lumbar discs. The elastin crosslinks in the LF were not significantly affected by age, but were significantly higher in calcified, and female ligamentum tissues, and also in the lumbar region (p < 0.05). These MRI prevalence findings enhanced our knowledge of vertebral body and disc degeneration trends in the thoracic region and contributed to the interpretation of MR images for pathology in the human thoracic spine. Information on the associated collagenous and elastic changes in the disc and ligamentum matrices provide original data and insight on the pathogenesis of degeneration in the disc matrix from a biochemical perspective, highlighting gender, age and spinal level influences on the matrix tensile strength and cellular synthetic activities.

A tese propõem uma metodologia, em nível de pesquisa, por intermédio do desenvolvimento e da adaptação de ferramentas de apoio computadorizado, capaz de realizar a segmentação da imagem dos discos intervertebrais da região lombar da coluna vertebral humana, de maneira semiautomática reduzindo drasticamente o tempo gasto manualmente neste procedimento, sem perder sua acurácia e, ainda, garantindo maior reprodutibilidade em seus resultados. Foram utilizadas imagens sagitais de ressonância magnética ponderadas em T2 de 285 discos intervertebrais de 70 pacientes, classificados segundo o grau de severidade da degeneração discal definido pelo critério proposto por Pfirrmann. A classificação computacional dos discos foi realizada com base em atributos quantitativos extraídos dos histogramas de níveis de cinza e de informações de textura das imagens. O desempenho dos métodos computacionais de segmentação foi avaliado com base no Coeficiente de Jaccard, na distância de Hausdorff e no Erro Médio Quadrático. O desempenho dos métodos computacionais de classificação foi também avaliado com base em medidas similares à aplicação da sensibilidade, da especificidade e da área sob a curva ROC. A segmentação manual e a classificação por inspeção visual dos discos realizadas por três profissionais experientes foram utilizadas como padrão ouro para a comparação. Os principais resultados indicaram a médio de 63,22% para o Coeficiente de Jaccard, as médias de 0,044 das distâncias de Hausdoff e de 0,014 para o EMQ na comparação entre as imagens. Além disso, a segmentação semiautomatizada diferiu em uma taxa média de 30% em relação à segmentação manual e a classificação da degeneração discal, por redes neurais artificiais difere em menos de 2%, ao ser comparada ao procedimento de classificação manual realizado pelos especialistas. / The thesis proposes a methodology at the level of research through the development and adaptation of computerized support tools, able to perform the image segmentation of the intervertebral discs of the lumbar region of the human spine, semiautomatic way dramatically reducing time spent manually in this procedure, without losing its accuracy and also ensuring more reproducible in their results. Were used sagittal MRI T2- weighted of 285 intervertebral discs from 70 patients, classified according to the severity of disc degeneration defined by the criteria proposed by Pfirrmann. The computational classification of disks was based on quantitative attributes extracted from histograms of gray level images and the texture information. The performance of computational segmentation methods was evaluated based on Jaccard coefficient, Hausdorff distance and Mean Square Error. The performance of the computational classification methods was evaluated based on measures of sensitivity, specificity and the area under the ROC curve. The manual segmentation and visual inspection classification of the discs made by three experienced professionals were used as the gold standard for comparison. The main results showed an average Jaccard coefficient of 63.22%, the average Hausdoff of distances was 0.044 and 0.014 Mean Square Error average when comparing the images from both segmentation targets. Additionally, the targeting semiautomatic differed by an average of 30% compared with manual segmentation and classification of disc degeneration provided from an artificial neural networks differs by less than 2% when compared to manual sorting procedure performed by experts.

Made available in DSpace on 2015-03-26T13:46:43Z (GMT). No. of bitstreams: 1 texto completo.pdf: 1498735 bytes, checksum: e65541cd95115cdcb1835feee29a3615 (MD5) Previous issue date: 2004-08-13 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The present study has as objectives to evaluate the clinical-surgical, radiological and histological aspects of canine cervical intervertebral disks after chemonucleolysis with chymopapain associated to the ventral slot. For that, it was used 24 dogs randomly divided into six equal groups. The ventral slot was accomplished in the area of the intervertebral disk C2-C3 and chemonucleolysis in the other cervical disks. Each group of four animals was submitted to euthanasia with an anesthetic overdose 24 hours, eight, 30, 60, 90 and 120 days after the enzyme injection and sagittal sections of the treated disks, associated to adjacent cartilaginous endplates and bony structures were obtained for histological analysis. The dogs were also monitored clinically and radiographically for up to 120 days, according to the groups. In this study, all dogs tolerated the surgical procedure, without detectable postoperative pain, neurological deficit or alteration of the conscience state. In the radiographic evaluation, it was observed consistent disk space narrowing 24 hours after the procedure and total absence of space from the eighth to the 90th day after chemonucleolysis in the area of all treated disks. However, at 120 days of postoperative there was an increase in disk height, corresponding, on average, to 59.13% of the preinjection value. Also, on the 30th day of postoperative, it was noted absorption of the vertebral bodies adjacent to the treated disks that progressed to healing, with evidences of vertebral fusion 120 days after the treatment. In the histological evaluation, it was observed 24 hours after disk injection nuclear digestion, characterized by cavitations and decrease of safranin-O staining intensity, indicating loss of proteoglycans. At eight days, the nuclear content was still vacuolated but more fibrillar. At 30 days, it was noted lesions and hemorrhage in the cartilaginous endplates. An irregularly defined mass in the nuclear space was observed on days 60th and 90th, but it seemed fibrocartilaginous tissue on day 120th. It was also observed microfractures and bone necrosis on day 90th, which were healed by day 120th. Chemonucleolysis with chymopapain associated to the ventral slot in the cervical column of dogs determines lysis of intervertebral disks, cervical instability and lesions of cartilaginous and bone adjacent structures that tend to repair with fibrocartilaginous tissue along the time. / Foram avaliados os aspectos clínico-cirúrgicos, radiográficos e histológicos de discos intervertebrais cervicais após quimionucleólise com quimiopapaína associada à fenda ventral. Foram utilizados 24 cães separados, aleatoriamente, em seis grupos iguais e de acordo com o tempo de observação pós-operatório. A fenda ventral foi realizada na região do disco intervertebral C2-C3 e as quimionucleólises nos demais discos cervicais. Cada grupo de quatro animais foi eutanasiado por sobredose anestésica 24 horas, oito, 30, 60, 90 e 120 dias após aplicação da enzima e foram obtidos cortes sagitais dos discos intervertebrais tratados, associados a estruturas cartilaginosas e ósseas adjacentes, para análise histológica. Os cães foram também avaliados, de acordo com o grupo, clinica e radiograficamente por até 120 dias. Todos os cães toleraram bem o procedimento cirúrgico, não apresentando déficit neurológico, alteração do estado de consciência e dor aparente na região cervical. Na avaliação radiográfica, com 24 horas, observou-se marcada redução da espessura dos espaços intervertebrais. Do oitavo ao 90º dia, foi verificada ausência total de espaço intervertebral na região de todos os discos tratados. Aos 120 dias, entretanto, as espessuras dos espaços intervertebrais correspondiam, em média, a 59,13% da espessura anterior ao procedimento. Ainda, radiograficamente, verificou-se aos 30 dias, absorção das porções dos corpos vertebrais adjacentes aos discos tratados, que progrediu para reparação, inclusive com evidências de fusão vertebral aos 120 dias. Na avaliação histológica, 24 horas após a quimionucleólise, foi observada digestão nuclear caracterizada por cavitações e redução da intensidade de coloração pela safranina-O, indicando perda de proteoglicanos. Aos oito dias, o conteúdo nuclear apresentou-se ainda vacuolizado, contudo mais fibrilar. Aos 30 dias, foram observadas lesões e áreas de hemorragia nas placas terminais cartilaginosas. A partir do 60º dia, notou-se a presença de material amorfo no espaço nuclear, que, aos 120 dias, tinha aparência de tecido fibrocartilaginoso. Aos 90 dias, verificou-se presença de microfraturas e osteonecrose, que estavam reparadas aos 120 dias. A quimionucleólise com quimiopapaína concomitante à fenda ventral na coluna cervical de cães determinou a lise dos discos intervertebrais, instabilidade cervical e lesões nas estruturas cartilaginosas e ósseas adjacentes, que tendem à reparação por tecido fibrocartilaginoso ao longo do tempo. Os trabalhos apresentados como parte integrante desta tese estão seguindo as normas de publicação do Arquivo Brasileiro de Medicina Veterinária e Zootecnia da Universidade Federal de Minas Gerais, indexada ao ISI, AGRIS, BIOSIS, CAB, CAS, MEDLARS e LILACS. ISSN 01020935.

Zielsetzung Die Konsensempfehlungen zur Begutachtung der Berufskrankheiten Nr. 2108 und Nr. 2110 (bandscheibenbedingte Erkrankungen der Lendenwirbelsäule) setzen bei der häufigsten Fallkonstellation, der sog. B2-Konstellation, voraus, dass mindestens eines von 3 Zusatzkriterien erfüllt ist. Zwei dieser Zusatzkriterien werden in der vorliegenden Sonderauswertung der Deutschen Wirbelsäulenstudie (DWS) empirisch überprüft. Methoden Untersucht wurden die einwirkungsabhängigen Zusatzkriterien „besonders intensive Belastung“ (2. Zusatzkriterium) und „Belastungsspitzen“ (3. Zusatzkriterium). Mittels logistischer Regressionsanalyse wurden für Alter und Studienzentrum adjustierte Odds-Ratios (als Schätzer des relativen Bandscheiben-Erkrankungsrisikos) mit 95 %-Konfidenzintervallen (95 % KI) berechnet. Es wurden jeweils im gleichen Regressionsmodell Odds-Ratios für die Erfüllung und für die fehlende Erfüllung eines Zusatzkriteriums ermittelt. Grundsätzlich ist ein Kriterium dann zur Unterscheidung zwischen beruflich verursachten und nicht beruflich verursachten bandscheibenbedingten Erkrankungen geeignet, wenn die Risikoschätzer bei Erfüllung des jeweiligen Kriteriums deutlich höher liegen als bei fehlender Erfüllung des Kriteriums. Bei den Belastungsspitzen wurde die Höhe der mit Hebe- oder Tragevorgängen verbundenen Druckkräfte in der Lendenwirbelsäule (LWS) variiert, ab der das Kriterium der Belastungsspitzen als erfüllt angesehen wurde; ferner wurde die Zahl der Schichten variiert, in denen das Kriterium der Belastungsspitzen erfüllt sein musste. Alle Berechnungen wurden getrennt für Männer und Frauen für die Dosismodelle „Original-MDD“ und „BSG-Modell“ durchgeführt. Ergebnisse Bei Vorliegen einer „besonders intensiven Belastung“ finden sich keine höheren bandscheibenbezogenen Erkrankungsrisiken als bei fehlendem Vorliegen dieses Zusatzkriteriums. Als „best estimate“ kann von der Erfüllung des Zusatzkriteriums „Belastungsspitzen“ dann ausgegangen werden, wenn beim BSG-Modell in mindestens 600 Schichten des gesamten Berufslebens Tagesdosen von mindestens 2,0 kNh (Kilonewton-Stunden = 1000 Newton-Stunden) pro Schicht bei Männern bzw. mindestens 0,5 kNh bei Frauen durch Belastungsspitzen (Druckkraft ≥ 6,0 kN bei Männern, ≥ 4,5 kN bei Frauen) erreicht werden. Schlussfolgerung Die Sonderauswertung der Deutschen Wirbelsäulenstudie kann keine Bestätigung des 2. Zusatzkriteriums der B2-Konstellation „besonders intensive Belastung“ erbringen. Das 3. Zusatzkriterium „Belastungsspitzen“ wird hingegen grundsätzlich bestätigt – es sollte über mindestens 600 Arbeitsschichten erfüllt sein, um als Positivkriterium für die Anerkennung einer bandscheibenbedingten Berufskrankheit fungieren zu können.

<p dir="ltr">People suffering from COPD are also known to suffer from other musculoskeletal issues like fracture risk, back pain, etc. Intervertebral disc degeneration (IVD) is a prominent cause of back pain and inflammation, influenced by factors such as aging, sudden loading, and genetics. <i>SERPINA1</i>, a common genetic variant in individuals with chronic obstructive pulmonary disease (COPD), encodes the alpha-antitrypsin protein (AAT). AAT deficiency is also associated with IVD degeneration, bone loss, and gait impairment. Currently, AAT-deficient individuals receive costly and short-lived weekly AAT injections, with no established guidelines for managing IVD degeneration and osteoporosis. Our primary research objective was to examine the effects of <i>serpinA1a/c</i> using a mouse model with global knockout (KO) of <i>serpinA1a/c</i>, generated through CRISPR technology, on intervertebral discs (IVD) and bone. We found that global deletion of <i>serpinA1a/c</i> was found to cause IVD elastin degradation, leading to a loss of mechanical properties. Moreover, <i>serpinA1</i> was associated with increased bone-resorbing cells (osteoclasts) and a reduction in bone-forming cells (osteoblasts). Notably, sexual dimorphism was observed, with female IVDs exhibiting less degeneration than male counterparts, and <i>serpinA1a/c</i> KO mice were protected from mechanically-induced tail compression. Even in human IVDs, males expressed more AAT-1 compared to female IVDs. There are no FDA-approved drugs currently existing for IVD degeneration. Since IVD degeneration frequently occurs in individuals with osteoporosis, it shows a probable cross-talk happening between IVD and bone. In our study, we found the association of <i>serpinA1 </i>with estrogen receptor alpha and osteoclasts. Hence, we investigated the potential of raloxifene, an FDA-approved selective estrogen receptor modulator (SERM) typically prescribed to post-menopausal women for osteoporosis treatment, in averting IVD degeneration and improving mechanical characteristics in IVD. Our findings suggest that raloxifene injection may retard IVD degeneration induced by AAT deficiency, particularly in male mice. Furthermore, the latter study touched upon a conditional <i>serpinA1a</i> mouse model crossed with aggrecan-cre, specifically targeting <i>serpinA1a</i>-expressing cells in the IVD while sparing bone. Conditional <i>serpinA1a</i> deletion induced mild IVD degeneration without affecting bone loss. In summary, this study serves as a foundation for testing potential treatments for AAT patients with IVD degeneration and osteoporosis. It also provides compelling evidence for considering raloxifene as a treatment option for IVD degeneration in AAT-deficient patients experiencing IVD-related pain.</p>

<p>Povratak na posao nakon operacije lumbalne diskus hernije determinisan je funkcionalnim stanjem, prisustvom i stepenom tegoba od strane lumbosakralne kičme, zahtevima na radnom mestu bolesnika ali i psihosocijalnim faktorima, koji pri oceni radne sposobnosti zaposlnih zahtevaju individualni pristup. Grupa pacijenata koja se neće vratiti na posao može biti identifikovana putem prognostičkog modela. Cilj ove studije je definisanje prognostičkog modela za povratak na posao bolesnika operisanih zbog lumbalne diskus hernije kao i identifikacija najznačajnijih faktora rizika odgovornih za lo&scaron; ishod operativnog lečenja, posmatrano kroz prizmu povratka na posao. Istraživanje je prospektivna studija koja je obuhvatila ukupno 200 ispitanika, koji su operisani zbog lumbalne diskus hernije na jednom nivou i praćeni su u vremenskom period do 12 meseci nakon operativnog lečenja. U statističku ananlizu je u&scaron;lo 153 bolesnika, koji su ispunili kriterijume selekcije ispitanika studije. Nakon određivanja značaja posmatranih biolo&scaron;kih, profesionalnih i psihosocijalnih faktora rizika za povratak na posao, kreirani su i evaluirani prognostički modeli bazirani na svim i na odabranim atributima desetostrukom kros-validacijom: stablo odlučivanja (DT), model vi&scaron;eslojnih perceptrona (MLP) i model potpornih vektora (SVM). Za predviđanje povratka na posao najveću tačnost, specifičnost i senzitivnost za odabrane atribute postiže model potpornih - podržavajućih vektora (SVM). Najbolju intuitivnu i praktičnu vrednost za predviđanje povratka na posao pruža model stabla odluka (DT). Identifikacijom najznačajnijih faktora rizika za nepovoljan ishod povratka na posao omogućeno je preventivno delovanje na iste, u cilju smanjenja broja pacijenata sa umanjenjem radne sposobnosti i invaliditeta.</p> / <p>Return to work after lumbar discectomy is determinated by functional status, presence and degree of discomfort in the lumbosacral spine, the requirements in the workplace of patients and psychosocial factors that in the assessment of working capabilities require an individual approach. Groups of patients which don&rsquo;t return to work after surgery could be identified by predictive model. The aim of this study is to define prognostic model to return to work patients after lumbar discectomy, as well as the identification major risk factors responsible for the poor outcome of operative treatment viewed through the prism of returning to work. This prospective study included a total of 200 patients, who underwent surgery for lumbar disc herniation on one level and were followed up in period of 12 months following surgery. The statistical analysis included 153 patients who fulfilled all selection criteria of the study subjects. After determining significance of the observed biological, professional and psychosocial risk factors for return to work, prognostic models were designed and evaluated based on all and selected attributes by tenfold cross-validation: decision tree (DT) model of multilayer perception (MLP) model and support vector (SVM). For the prediction of return to work best accuracy, specificity and sensitivity for selected attributes, is achieved by supporting vector model (SVM). The decision tree model (DT) provides the best intuitive and practical value for predicting return to work. By identifying the most important risk factors for adverse outcome for return to work it is made possible for preventive actions, to reduce the number of patients with reduced work ability and disability.</p>

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