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<p>In this thesis, we discuss the study and realization of surface plasmon polaritons (SPPs) and their devices. Plasmonics is the emerging field that will help technologies advance further into the nano-scale without the concern for delays or size limitations. SPPs are a more advanced field of photonics as they use metals instead of the semiconductors or insulators used in optics. They operate at frequencies in the light and near infrared spectrum, as this range produces their unique characteristics. Plasmonics possess the miniaturization of electronics and the speed of photonics. They do not suffer from both the delays in nano-electronics, and the size limitations faced in optics. In this thesis, we present the optimization of plasmonic slit arrays by designing the parabolic phase profile of the array. Moreover, we present a novel multilevel plasmonic coupler that will aid in the realization of 3-D plasmonic chips, as well as quadrature modulation. The theory, procedures, and results are all presented and discussed.</p> / Master of Applied Science (MASc)

Neuronen sind erregbare Systeme. Ihre Antwort auf Anregungen oberhalb eines bestimmten Schwellwertes sind Pulse. Häufig wird die Pulserzeugung von verschiedenen Rückkopplungsmechanismen beeinflusst, die auf langsamen Zeitskalen agieren. Das kann zu Phänomenen wie Feuerraten-Adaptation, umgekehrter Feuerraten-Adaptation oder zum Feuern von Pulsen in Salven führen. Weiterhin sind Neuronen verschiedenen Rauschquellen ausgesetzt und wechselwirken mit anderen Neuronen, in neuronalen Netzen. Doch wie beeinflusst das Zusammenspiel von Rückkopplungsmechanismen, Rauschen und der Wechselwirkung mit anderen Neuronen die Pulserzeugung? Diese Arbeit untersucht, wie die Pulserzeugung in rauschgetriebenen erregbaren Systemen von langsamen Rückkopplungsmechanismen und der Wechselwirkung mit anderen erregbaren Systemen beeinflusst wird. Dabei wird die Pulserzeugung in drei Szenarien betrachtet: (i) in einem einzelnen erregbaren System, das um einen langsamen Rückkopplungsmechanismus erweitert wurde, (ii) in gekoppelten erregbaren Systemen und (iii) in stark gekoppelten salvenfeuernden Neuronen. In jedem dieser Szenarien wird die Pulsstatistik mit Hilfe von analytischen Methoden und Computersimulationen untersucht. Das wichtigste Resultat im ersten Szenario ist, dass das Zusammenspiel von einer stark anregenden Rückkopplung und Rauschen zu rauschkontrollierter Bistabilität führt. Das erlaubt es dem System zwischen verschiedenen Modi der Pulserzeugung zu wechseln. In (ii) wird die Pulserzeugung stark von der Wahl der Kopplungsstärken und der Anzahl der Verbindungen beeinflusst. Analytische Näherungen werden abgeleitet, die einen Zusammenhang zwischen der Anzahl der Verbindungen und der Pulsrate, sowie der Pulszugvariabilität herstellen. In (iii) wird festgestellt, dass eine hemmende Rückkopplung zu sehr unregelmäßigem Verhalten der isolierten Neuronen führt, wohingegen eine starke Kopplung mit dem Netzwerk ein regelmäßigeres Feuern von Salven hervorruft. / Neurons are excitable systems. Their responses to excitations above a certain threshold are spikes. Usually, spike generation is shaped by several feedback mechanisms that can act on slow time scales. These can lead to phenomena such as spike-frequency adaptation, reverse spike-frequency adaptation, or bursting. In addition to these, neurons are subject to several sources of noise and interact with other neurons, in the connected complexity of a neural network. Yet how does the interplay of feedback mechanisms, noise as well as interaction with other neurons affect spike generation? This thesis examines how spike generation in noise-driven excitable systems is influenced by slow feedback processes and coupling to other excitable systems. To this end, spike generation in three setups is considered: (i) in a single excitable system, which is complemented by a slow feedback mechanism, (ii) in a set of coupled excitable systems, and (iii) in a set of strongly-coupled bursting neurons. In each of these setups, the statistics of spiking is investigated by a combination of analytical methods and computer simulations. The main result of the first setup is that the interplay of strong positive (excitatory) feedback and noise leads to noise-controlled bistability. It enables excitable systems to switch between different modes of spike generation. In (ii), spike generation is strongly affected by the choice of the coupling strengths and the number of connections. Analytical approximations are derived that relate the number of connections to the firing rate and the spike train variability. In (iii), it is found that negative (inhibitory) feedback causes very irregular behavior of the isolated bursters, while strong coupling to the network regularizes the bursting.

Surgical repair of torn rotator cuff tendons have a high rate of failure and does not address the underlying pathophysiology. Tissue engineering strategies, employing the use of multipotent progenitor cells or growth factors, represent potential therapies to improve the outcome of rotator cuff surgery. The use of glycosaminoglycan-based biomaterials in these therapies may enhance the effectiveness of cell and growth factor delivery techniques. Furthermore, understanding the cellular and molecular mediators in tendon overuse can help elucidate the causes of tendon degeneration. Thus the overall goals of this dissertation were to 1) develop heparin-based biomaterials to enhance cell pre-culture and maintain growth factor bioactivity and 2) characterize the histological and enzymatic changes in a supraspinatus tendon overuse model. To investigate the use of heparin in enhancing dynamic signaling, mesenchymal stem cells (MSCs) were encapsulated in heparin-containing hydrogels and evaluated for differentiation markers when cocultured with a small population of differentiated cells. To probe the effect of sulfation of heparin on the interactions with protein, selectively desulfated heparin species were synthesized and evaluated for their ability to bind and protect proteins. Finally, to develop a tendon overuse model that can become a test bed for testing future targeted therapeutics, an animal model was evaluated for tissue damage and protease activity. Together these studies represent a multi-pronged approach to understanding how tendon tissues become degenerative and for developing technologies to improve the biological fixation of tendon to bone in order to reduce the need for revision surgeries.

Rotator cuff disease is multi-factored and has been attributed to both intrinsic and extrinsic factors. Extrinsic factors contribute to compression of the rotator cuff tendons. Intrinsic factors that contribute to rotator cuff tendon degradation with tensile/shear overload include alterations in biology, mechanical properties, morphology, and vascularity. Subacromial impingement is related to factors that encroach upon the subacromial space, while internal impingement affects the articular side of the tendons adjacent to glenoid. While the mechanisms of impingement are varied, further research is necessary to improve treatment and patient outcomes. Chapter 2 is a thorough review of literature on the mechanisms of rotator cuff disease. Alterations in scapular kinematics may influence subacromial space and either contribute to the etiology of subacromial impingement with rotator cuff tendon compression or serve as a compensation to alleviate compression. Furthermore alterations in scapular position may directly influence rotator cuff muscle strength. Chapter 3 compares the influence of the scapular assistance test on scapular upward rotation, posterior tilt, subacromial space, and shoulder strength between healthy individuals and subjects with subacromial impingement syndrome. Scapular upward rotation and posterior tilt induced with scapular assistance test appears to influence subacromial space, but not shoulder muscle strength; however, the influence of these scapular rotations do not differ between asymptomatic individuals and those with subacromial impingement. Furthermore scapular posterior tilt appears to have a greater influence on increasing subacromial space and should be emphasized in the treatment of individuals with subacromial impingement. In chapter 4, we examine the influence that obvious scapular dyskinesis and passive scapular correction with the scapular assistance test have on 3D scapular kinematics and subacromial space. Scapular dyskinesis did not alter scapular kinematics or acromiohumeral distance during active elevation in static positions, in the scapular plane, and without a load when compared to those without scapular dyskinesis. This suggests other contributing factors, such as pain, increased load, or fatigue is requisite to alterations in scapular kinematics or AHD. Passive correction with the scapular assistance test increased scapular upward rotation, posterior tilt, and subacromial space in individuals with and without dyskinesis. In patients with obvious dyskinesis, there was a greater increase in scapular upward rotation with passive scapular assistance. This increased scapular upward rotation had a negative relationship with change in the acromiohumeral distance. The scapular dyskinesis test increased acromiohumeral distance and therefore may be helpful identifying individuals where subacromial compression is producing symptoms, regardless of dyskinesis. The results of this research suggest scapular kinematics and subacromial space are altered with the passive maneuver of the scapular assistance test in all individuals, regardless of subacromial impingement syndrome or scapular dyskinesis. Scapular dyskinesis alone may not be detrimental to scapular position and subacromial space when evaluated in static positions of active arm elevation. Other potential factors may be required to alter scapular kinematics to reduce subacromial space including pain, dynamic movement, load or fatigue. Further study is necessary to determine the influence of the combination of these factors in individuals with scapular dyskinesis.

To explore the potential mechanisms of tendon degeneration, we investigated the role of c-Jun N-terminal Kinase (JNK) activation and the regulation of matrix metalloproteinase 1 (MMP1) in tendon matrix degradation under oxidative stress. JNK and MMP1 activity in samples from normal and ruptured human supraspinatus tendons were evaluated by immunohistochemistry. Real-time quantitative PCR was utilized to evaluate MMP1 mRNA expression and western blotting for MMP1 and JNK protein detection. JNK activation and increased MMP1 activity were found in the torn human supraspinatus tendon tissue, as well as in human tendon cells under in vitro oxidative stress. Inhibition of JNK prevented MMP1 over-expression in oxidative stressed human tendon cells. Results from the current study indicated that stress activated JNK plays an important role in tendon matrix degradation, possibly through upregulating of MMP1.

Tendonopathy, resulting in the loss of mechanical strength of a tendon, is a serious health problem affecting many people. The common symptom of tendonopathy is pain – patients' daily activities, their participation in sport and exercise, and their ability to work are greatly compromised. Tendonopathy is considered to be a degenerative disorder caused by repetitive injury of the tendon. The most common tendon lesions are Achilles tendon rupture, lateral epicondylitis (tennis elbow) and rotator cuff tear. However, in spite of its clinical significance, our knowledge about tendonopathy is still very poor. This research was undertaken to investigate the pathology of tendonopathy. It is proposed that apoptosis, autophagic cell death and myofibroblasts play a role in the progression of tendonopathy in the rotator cuff; the aim of this study was therefore to determine if this was indeed the case. Tendon tissues were collected from 30 patients suffering from rotator cuff tears. A terminal deoxynucleotidyl transferase biotin-dUTP nick end labelling (TUNEL assay) was performed to detect apoptosis. Autophagic cell death of the tenocytes in the ruptured rotator cuff tendon was detected by immunohistochemical staining for ubiquitin. Myofibroblasts were identified immunohistochemically with anti-alpha-smooth muscle actin (anti--SMA) antibody. The distribution of apoptosis, autophagic cell death and myofibroblasts, as well as the total cell density, were assessed respectively and were correlated using a four-category (i.e. graded from 0-3) degeneration of collagen matrix. – 6 – The results showed that apoptosis, autophagic cell death and myofibroblasts were observed in all of the samples. The highest percentage of autophagic cell death was evidenced in the Grade 2 matrix, while the percentage of apoptosis increased significantly with the increase of matrix degeneration from Grade 0-3; a similar pattern was found for myofibroblasts. The total cell numbers varied among the matrix grades, with the maximum and minimum percentages occurring in Grades 1 and 3, respectively. It can be concluded that apoptosis, autophagic cell death and myofibroblasts might be closely related to the damage of the extracellular matrix (ECM) structure.

Orientador: Jose Inacio de Oliveira / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-06T19:26:31Z (GMT). No. of bitstreams: 1 Shiraishi_WilmaHideko_M.pdf: 1998354 bytes, checksum: 503ec8f6636f894c6c459636f7045b26 (MD5) Previous issue date: 2006 / Resumo: Neste estudo analisa-se o perfil epidemiológico dos pacientes com diagnóstico clinico de tendinite do supra-espinhal relacionada ao trabalho, atendidos no Ambulatório de Medicina do Trabalho do Hospital das Clínicas da UNICAMP, no período de janeiro de 2002 a dezembro de 2004 e verifica-se, dentre as lesões do manguito rotador, quais as tendinites mais freqüentes. Trata-se de um estudo descritivo, com dados coletados dos prontuários do Serviço de Arquivo Medico (SAME), utilizando-se o Software Epi-info 6 para o registro de dados. Foram analisados 246 prontuários de pacientes atendidos no Ambulatório com diagnóstico clínico de Distúrbios Osteomusculares Relacionados ao Trabalho (DORT). Desses, identificaram-se 112 pacientes com lesão do manguito rotador e, dentre estes, 106 eram especificamente tendinites do tendão do músculo supra-espinhal. Foram investigadas as variáveis relacionadas a sexo, idade, procedência, ocupação, lado do ombro comprometido, tipo de lesão, ramo de atividade econômica, situação de trabalho no primeiro atendimento, benefícios previdenciários, nexo com o trabalho e distribuição do diagnóstico clinico geral dos DORT neste período. Os resultados mostraram que, dentre as lesões do manguito rotador, a tendinite do tendão do músculo supra-espinhal obteve a maior freqüência, com 106 casos (94,6%); seguida do músculo subescapular com 4 (3,6%); músculo ínfra-espinhal com 2 (1,7%) e nenhuma referência do redondo menor. O grupo concentra-se na faixa etária de 22 a 71 anos de idade, com média de idade de 40 anos (dp= 8,75) sendo que, destes, 74 (69,8%) eram do sexo feminino. O lado do ombro mais comprometido foi o direito em 52 casos (49,1%), o esquerdo em 28 (26,4%) e bilateral em 26 (24,5%). Dentre as principais ocupações, os operadores de máquina e os auxiliares de produção tiveram a maior prevalência (25,4%). Em seguida, auxiliar de cozinha (11,3%) e auxiliar de serviços gerais (6,6%). Do total, 44 (41,5%) pacientes pertenciam à indústria alimentícia e 25 (23,6%) à indústria metalúrgica. Dos pacientes com diagnóstico clínico de tendinite de supra-espinhal o nexo causal com o trabalho foi estabelecido em 100 pacientes (94,3%) / Abstract: Epidemiological profile of pacients with supraspinatus tendinitis related to work in an outpatient Clinic of A Medical School Hospital. This study analyzes the epidemiological profile of patients that consulted at the Occupational Health Outpatient Clinic of the UNICAMP General Hospital, in the period between January 2002 and December 2004, and had clinical diagnosis of work-related Supraspinatus Tendinitis. It also verifies the most frequent tendinitis among rotator cuff injuries. It is a descriptive study using data collected from patients' records in the Medical Record File Service (SAME) and Epi-info6 software was used for recording the data. A total of 246 records of outpatients seen at the Hospital Clinic with clinical diagnoses of Work Related Musculoskeletal Disorder (WRMD) were analyzed. In this group, 112 patients with Rotator Cuff Tendinitis were selected and among these there were 106, specifically, with Supraspinatus Tendinitis. Variables such as gender, age, origin, occupation, side of injured shoulder, type of injury, area of economic activity, work status at first appointment, workers compensation benefits, relation of injury to work, and the distribution of clinical diagnoses of WRMD during the period mentioned, were examined. The results showed that among rotator cuff injuries, supraspinatus tendinitis was the most frequent with 106 cases (94.6%); next came subscapular]s injuries with 4 cases (3.6%), infraspinatus with 2 (1.7%), and there was no reference to teres minor. The age of this group varies from 22 to 71 years old, mean age being 40 (sd=8,75). Among them, 74 (69.8%) patients were female. The side most frequently injured was the right shoulder in 52 cases (49.1%), the left in 28 (26.4%) and both in 26 (24.5%). Among the main occupations, machine operators and production helpers were the most prevalent, both with 25.4%. Next came cooks (11.3%) and all-task helpers (6.6%). A total of 44 (41.5%) patients pertained to the food industry and 25 (23.6%) to metallurgical industry. In the group of patients with clinical diagnosis of supraspinatus tendinitis the relation of injury to work was established in 100 patients (94.3%) / Mestrado / Saude Coletiva / Mestre em Saude Coletiva

Rotator cuff injuries cause pain, disability, and loss of shoulder function in over 17 million individuals in the United States that result in over 500,000 surgeries performed annually, though with alarming failure rates of 20-94% (Colvin et al., 2012; Galatz et al., 2004; Harryman et al., 1991; Jain et al., 2014; Mather et al., 2013; Oh et al., 2007; Vitale et al., 2007; Yamaguchi et al., 2006). These surgeries involve repair or reconstruction of the damaged rotator cuff tendon(s) along with enlargement of the subacromial space by debriding the overlying bone (acromion) and removing the subacromial bursa (Beard et al., 2018; Burkhart et al., 2016; Dines et al., 2006; Lo & Burkhart, 2003; Rossi & Ranalletta, 2020). The subacromial bursa is a synovial-like tissue that is situated between the acromion and the tendons of the rotator cuff. This tissue has been long understood to serve a primarily mechanical role by providing cushioning and protecting from friction-wear from the acromion on the underlying tendons. More recently, the identification of a robust vascular network within the bursa, a resident population of mesenchymal stem cells, and inflammatory responsiveness to rotator cuff pathology have supported the existence of a biological role of this tissue in addition to its mechanical one (Blevins et al., 1997; Gotoh et al., 1998, 2001; Põldoja et al., 2017; Rathbun & Macnab, 1970; Steinert et al., 2015; Yepes et al., 2007). These observations make surgical excision of the bursa problematic, given our current lack of understanding of the implications of removing the bursa on the biological response to tendon injury. Therefore, the goals of this dissertation were three-fold: (1) to determine the role of the subacromial bursa in the rotator cuff tendon response to injury and healing, (2) to interrogate patterns of cellular crosstalk between the subacromial bursa and the rotator cuff following injury, and (3) to demonstrate therapeutic potential of targeting the subacromial bursa for modulating inflammation and improving tendon healing.Motivated by clinically observed phenotypic changes in the subacromial bursa with rotator cuff pathology, the profiles of human bursa and rotator cuff tendon tissues were assessed using histology, proteomics, and transcriptomics. This data set, analyzed in the context of patient demographics and diagnoses, revealed distinct bursa proteomes according to tissue phenotype (i.e., fibrous, vascular, or fatty), patient age, and presence of a tear in the underlying rotator cuff. These results suggested the presence of crosstalk between the rotator cuff and the bursa that had not been previously appreciated. Employing multiple methods of validation, including histology, microcomputed tomography, gene expression, and flow cytometry, the rat bursa was established as an appropriate animal model of the human bursa. Therefore, we used the rat model to investigate the role of the bursa in tendon injury response and healing; tendon injuries were created surgically with or without a subsequent repair to study healing and responses to injury, respectively. The role of the bursa in the response to injury was assessed using gene expression, transcriptomics, and histology. The bursa promoted inflammatory gene expression in the injured supraspinatus but resolved inflammatory gene expression in the intact infraspinatus. The role of the bursa in tendon healing was assessed using gene expression, histology, microcomputed tomography, and tensile mechanical testing of the cuff tendons. Consistent with responses during the inflammatory phase of healing, the bursa promoted expression of genes related to aberrant, scar-mediated healing in the supraspinatus, whereas it promoted tenogenic and tendon extracellular matrix gene expression in the intact infraspinatus. Mechanical testing demonstrated that the bursa protected the infraspinatus from the inflammatory environment caused by the supraspinatus injury but had a limited functional effect on the healing supraspinatus. Microcomputed tomography also indicated bursa-dependence in cortical and trabecular bone remodeling following tendon injury. Cross-talk between the bursa and the tendon was then studied in a novel tissue explant co-culture platform using gene expression and nitric oxide release as outcome measures. These experiments revealed that the activated bursa engaged in immunomodulation of tendon fibroblast responses to inflammatory stimulus. The in vitro platform also established the glucocorticoid dexamethasone as a viable therapeutic candidate for bursa-targeted treatment based on its capacity to regulate the bursa’s response to an inflammatory stimulus and enhance the bursa’s immunomodulatory potential. Therefore, in the final component of this thesis, dexamethasone was delivered via PLGA microspheres in vivo to the bursa to modulate the post-injury inflammatory response in the supraspinatus and the infraspinatus tendons. Results supported the therapeutic potential of this treatment approach to improve rotator cuff healing outcomes. This body of work demonstrated a robust involvement of the bursa in rotator cuff responses to injury, with distinct roles in the underlying injured and intact tendons. This work also established, for the first time, the immunomodulatory capacity of the activated bursa and provided strong evidence against the clinical practice of bursectomy. Finally, use of sustained-release dexamethasone to dampen the inflammatory responses to rotator cuff injury offers a new direction for harnessing the inherent properties of the subacromial bursa therapeutically for improved rotator cuff tendon healing.

Author: Anna Reiterová Title: Early rehabilitation in comparison with the traditional approach after arthroscopic surgery of the rotator cuff - literature research Aim: To process a literature search concerning the reconstruction of the rotator cuff with regard to early physiotherapy, its safety and effectiveness.To map the approach to the issue from the point of view of surgeons in the form of a non-standardized questionnaire survey. To compile a systematic review of studies comparing early and delayed physiotherapy in the form of passive movements. Backgroung: The primary goals in the postoperative period after rotator cuff repair are to minimize pain, protect the repaired muscle and tendon, and finally restore shoulder function. At a time when the gold standard was open access, surgeons recommended an early passive range of motion after repairing the rotator cuff in an effort to reduce the likelihood of the formation of adhesions leading to stiffness of the operated arm. Although early passive movement may minimize the chance of a stiff arm, it may not be optimal for the early stages of rotator cuff healing. Metoda: thesis is processed in the form of literary research. Literary sources of the work were searched in the databases PubMed, MEDLINE, PEDro, Web of Science, EBSCOhost and Scopus. The...