Background: Patients with nonallergic irritant rhinitis (NAIR) have symptoms of nasal congestion, nasal irritation, rhinorrhea, and sneezing in response to nasal irritants. We currently have no reliable objective means to quantify these patients' subjective symptoms. In this study, we used the transient receptor potential vanilloid receptor (TRPV1) receptor agonist, capsaicin, as an intranasal challenge while comparing the changes in blood flow with optical rhinometry between subjects with NAIR and healthy controls (HCs). Methods: Six HCs and 6 NAIR subjects were challenged intranasally with saline solution followed by increasing concentrations of capsaicin (0.005 mM, 0.05 mM, and 0.5 mM) at 15-minute intervals. We recorded maximum optical density (OD) and numeric analog scores (NAS) for nasal congestion, nasal irritation, rhinorrhea, and sneezing for each subject after each challenge. Correlations between NAS and maximum OD were calculated. Results: Maximum OD increased with increasing concentrations of intranasal capsaicin in NAIR subjects. There were significant differences in maximum OD obtained for 0.05 mM and 0.5 mM capsaicin between NAIR subjects and HCs. Significant differences were found in the NAS for nasal irritation at 0.005 mM, 0.05 mM, and 0.5 mM, and nasal congestion at 0.5 mM. Correlation between maximum OD and mean NAS was most significant for 0.05 mM capsaicin. Conclusion: Optical rhinometry with intranasal capsaicin challenge could prove a viable option in the diagnosis of NAIR. Further studies will investigate its use to monitor a patient's response to pharmacologic therapy and provide further information about the underlying mechanisms of NAIR.

No description available.

Thymic stromal lymphopoietin (TSLP), an epithelial-derived cytokine, has a critical role in the development of allergic inflammatory responses and have been implicated in type 2 allergic disease, including asthma, allergic rhinitis, and atopic dermatitis. Genetic polymorphisms in the TSLP gene are among the most commonly cited variants associated with asthma and allergic disease, however, the functional effects of these polymorphism are not fully understood. The objective of this study was to investigate the role of a TSLP polymorphism in the Th2 inflammatory responses of the nasal epithelium, as well as in responding to nasal allergen provocation and intranasal corticosteroid treatment. We cultured nasal epithelial cells from allergic asthmatic subjects and examined cytokine and chemokine secretions and gene expression profiles in response to polyinosinic:polycytidylic acid treatment. To explore the functional consequences of the rs1837253 polymorphism we analyzed the two TSLP gene isoforms, as they have shown dichotomous effects, however, no associations were found between rs1837253 genotype and the expression of TSLP and gene isoforms. We did not find any associations of TSLP or cytokine production between genotypes, or in relation to response to nasal allergen challenge or corticosteroid treatment. Exploration of local and systemic effects of the rs1837253 SNP did not show any differences in response to INCS treatment in vitro or ex vivo. We did demonstrate that nasal epithelial cell-derived factors are capable of stimulating eosinophil/basophil colony forming units in the absence and presence of exogenous IL-3. Overall, the results indicate a role of the nasal epithelium in driving eosinophil/basophil differentiation and highlight the complexity of gene-environment interactions and the mechanisms of asthma and allergic inflammation. / Thesis / Master of Science (MSc)

Purpose: Cancers of the sinonasal tract are rare, comprise a diverse group of histologies and are known for their poor prognostic outcomes. The primary aim of this study was to evaluate the 2- and 5-year overall survival (OS) rates in patients treated with radical and palliative intent for sinonasal squamous cell carcinoma (SNSCC). Methods: A retrospective review of medical records of all patients presenting to Cape Town's Groote Schuur Hospital between January 2003 and December 2013 was carried out. All patients with histologically proven squamous cell carcinoma (SCC) of the maxillary sinus and nasoethmoidal complex who underwent treatment at Groote Schuur Hospital and/or iThemba LABS (Laboratory for Accelerator Based Sciences) were included. Fifty-five patients with cancers of the sinonasal tract were identified from the electronic patient system; 23 were excluded either because of different histologies, lack of histology or having initiated treatment outside of Groote Schuur Hospital. The medical records of 32 patients were utilised for final analysis. 2- and 5-year OS was calculated using Kaplan-Meier analysis. Results: The majority (75%) of patients had an ECOG performance status of 1 with facial asymmetry secondary to tumour mass or swelling being the most common presenting symptom (present in 68,75% of cases). 62,50% of cases originated within the maxillary antrum and 56,25% of cases were classified as keratinizing SCC. Twenty-six (81,25%) patients presented with stage IV disease; nodal disease was seen in 13 (40,63%) patients and distant metastasis in 4 (12,50%) patients. Most patients underwent palliative intent treatment with only 11 (34,38%) having radical treatment. The cumulative 2- and 5-year OS from the date of treatment initiation was 26% and 19% respectively. Median OS for the entire cohort was 7,7 months and was statistically significant between intent groups at 5,19 months (95% CI:3.43– 6.95) for palliative compared to 35,45 months (95% CI: 0.00–138.52) for radical patients (c2 = 7.80, p = 0.005). Conclusion: Despite a decline in incidence of disease over the last 30 years and the improved diagnostic and therapeutic modalities available today, the prognosis and survival outcomes for SNSCC remains poor.

Staphylococcus is a significant cause of human infection and mortality, worldwide. Currently, there are greater than 60 taxa within Staphylococcus, and nearly all are pathogenic. The collective potential for virulence among species of Staphylococcus heightens the overall clinical significance of this genus and argues for a thorough understanding of the evolutionary relationships among species. Within Staphylococcus, aureus is the most common cause of human infection, where nasal carriage of this bacterium is a known risk factor for autoinfection. The predisposition to infection by nasal carriers of S. aureus, and the ease with which strains are transferred between individuals, suggests that nasal carriage is a major vector for the transmission of virulent strains throughout the community. This hypothesis, however, has not been assessed in any great detail to identify the genetic relationships between clinical isolates of S. aureus and those strains being carried asymptomatically throughout the community. Also lacking within this field is a unified and robust estimate of phylogeny among species of Staphylococcus. Here, we report on a highly unified species phylogeny for Staphylococcus that has been derived using multilocus nucleotide data under multiple Bayesian and maximum likelihood approaches. Our findings are in general agreement with previous reports of the staphylococcal phylogeny, although we identify multiple previously unreported relationships. Regardless of methodology, strong nodal support and high topological agreement was observed with only minor variations in results between methods. Based on our phylogenetic estimates, we propose that Staphylococcus species can be evolutionarily clustered into 15 groups, and six species groups. In addition, our more defined phylogenetic analyses of S. aureus revealed strong genetic associations between both nasal carriage strains and clinical isolates. Genetic analyses of hypervariable regions from virulence genes revealed that not only do clinically relevant strains belong to identical genetic lineages as the nasal carriage isolates, but they also exhibited 100% sequence similarity within these regions. Our findings indicate that strains of S. aureus being carried asymptomatically throughout the community via nasal colonization are genetically related to those responsible for high levels of infection and mortality. Due to nasal carriage of S. aureus being a risk factor for autoinfection, standardized preoperative decolonization has become a major consideration for the prevention of nosocomial infection. Toward this end, we have identified the macrocyclic ?-defensin analogue RC-101 as a promising anti-S. aureus agent for nasal decolonization. RC-101 exhibited bactericidal effects against S. aureus in both epithelium-free systems, and ex vivo models containing human airway epithelia. Importantly, RC-101 exhibited potent anti-S. aureus activities against all strains tested, including USA300. Moreover, RC-101 significantly reduced the adherence, survival, and proliferation of S. aureus on human airway epithelia without any noted cellular toxicity or the induction of a proinflammatory response. Collectively, our findings identify RC-101 as a potential preventative of S. aureus nasal colonization.

No description available.

The purpose of this dissertation is to examine the occurrence of facial fractures in automotive collisions and to determine the tolerance of the facial bones to blunt impact. The effects of restraint use, impact severity and impact direction on facial fractures were evaluated using the NASS-CDS database. The association between brain injury and facial fractures was also examined. The tolerance of the frontal bone, nasal bone, maxilla and mandible was determined using the flat surface of a cylindrical impactor. The influence of anthropometric measures and geometrical descriptors on the tolerance of the facial bones is also presented. The force-displacement response of each impacted region was also determined and response corridors were created. These corridors were used to evaluate the biofidelity of the FOCUS headform under the same impact conditions. Mathematical models were also created to predict the force and displacement resulting from facial impact. The data contained in this dissertation can be used to determine the risk of facial fracture as a function of impact force and evaluate the biofidelity of models simulating facial impact. / Ph. D.

Les adultes peuvent éprouver des difficultés à discriminer des phonèmes d’une langue seconde (L2) qui ne servent pas à distinguer des items lexicaux dans leur langue maternelle (L1). Le Feature Model (FM) de Brown (1998) propose que les adultes peuvent réussir à créer des nouvelles catégories de sons seulement si celles-ci peuvent être construites à partir de traits distinctifs existant dans la L1 des auditeurs. Cette hypothèse a été testée sur plusieurs contrastes consonantiques dans différentes langues; cependant, il semble que les traits qui s’appliquent sur les voyelles n’aient jamais été examinés dans cette perspective et encore moins les traits qui opèrent à la fois dans les systèmes vocalique et consonantique et qui peuvent avoir un statut distinctif ou non-distinctif. Le principal objectif de la présente étude était de tester la validité du FM concernant le contraste vocalique oral-nasal du portugais brésilien (PB). La perception naïve du contraste /i/-/ĩ/ par des locuteurs du français, de l’anglais, de l’espagnol caribéen et de l’espagnol conservateur a été examinée, étant donné que ces quatre langues diffèrent en ce qui a trait au statut de la nasalité. De plus, la perception du contraste non-naïf /e/-/ẽ/ a été inclus afin de comparer les performances dans la perception naïve et non-naïve. Les résultats obtenus pour la discrimination naïve de /i/-/ĩ/ a permis de tirer les conclusions suivantes pour la première exposition à un contraste non natif : (1) le trait [nasal] qui opère de façon distinctive dans la grammaire d’une certaine L1 peut être redéployé au sein du système vocalique, (2) le trait [nasal] qui opère de façon distinctive dans la grammaire d’une certaine L1 ne peut pas être redéployé à travers les systèmes (consonne à voyelle) et (3) le trait [nasal] qui opère de façon non-distinctive dans la grammaire d’une certaine L1 peut être ou ne pas être redéployé au statut distinctif. En dernier lieu, la discrimination non-naïve de /e/-/ẽ/ a été réussie par tous les groupes, suggérant que les trois types de redéploiement s’avèrent possibles avec plus d’expérience dans la L2. / Adults may experience difficulties discriminating phonemes of a second language (L2) that do not serve to distinguish lexical items in their native language (L1). Brown’s (1998) Feature Model (FM) advances that adults may be able to create new sound categories only if these can be built from contrastive features existing in their L1. This hypothesis has been tested on various consonant contrasts in a number of languages; however, it appears that features applying on vowels have never been examined from this perspective and neither have features that operate both in the vowel and the consonant systems and that may have a contrastive or a non-contrastive status. The main purpose of the present study was to test the validity of the FM with respect to the oral-nasal vowel contrast of Brazilian Portuguese. The naïve perception of the contrast /i/-/ĩ/ by French, English, Caribbean Spanish, and conservative Spanish speakers was examined, given that these four languages differ with respect to the status of nasality. Moreover, the perception of the non-naïve contrast /e/-/ẽ/ was included to compare naïve and non-naïve perception performances. The obtained data for the naïve discrimination of /i/-/ĩ/ allowed to draw the following conclusions for the first exposure to a non-native contrast: (1) the feature [nasal] operating contrastively in the grammar of a given L1 can be redeployed within the vowel system, (2) the feature [nasal] operating contrastively in the grammar of a given L1 may not be redeployed across systems (consonant to vowel), and (3) the feature [nasal] operating non-contrastively in the grammar of a given L1 might or might not be redeployed to contrastive status. Lastly, the non-naïve perception of /e/-/ẽ/ was successful for all groups, suggesting that the three types of redeployment are possible with more experience in the L2.

A fita nasal é amplamente utilizada em equinos durante o exercício, porém seus resultados são controversos e pouco conhecidos em animais que disputam provas de resistência. Os objetivos desse trabalho foram verificar se o uso da fita nasal influencia parâmetros durante o exercício predominantemente aeróbico, como frequência respiratória, volume tidal, volume minuto, tempos de inspiração e expiração, população de células por meio de lavado broncoalveolar, frequência cardíaca e lactato sanguíneo. Foram utilizados seis equinos da raça Árabe que realizaram dois testes de longa duração em esteira, sendo um teste com fita e outro sem a fita nasal. Durante os testes eram realizadas coletas de sangue, espirometria com obtenção de curvas de fluxo e volume respiratório, e registro da frequência cardíaca por meio de frequencímetro. Duas horas após o término do exercício foi realizado lavado broncoalveolar para realização de citologia da secreção pulmonar. Não houveram diferenças entre os parâmetros ventilatórios analisados entre os animais quando correram com ou sem a fita nasal. Entretanto, a frequência cardíaca foi em média menor durante o exercício nos animais que se exercitaram com a fita nasal (p<0,05), podendo indicar uma melhor oferta de oxigênio durante o exercício de longa duração com o uso da fita nasal, apesar de não encontrarmos alterações nos parâmetros de fluxo e volume respiratório. Na avaliação citológica do conteúdo do lavado broncoalveolar, foi verificada maior porcentagem de neutrófilos após o exercício nos animais que se exercitaram com a fita nasal (p<0,05), indicando que o turbilhonamento na passagem do ar através da cavidade nasal pode ter diminuído permitindo que partículas maiores se depositassem em porções mais distais do sistema respiratório, induzindo uma resposta neutrofílica mais intensa. O uso da fita nasal parece influenciar alguns parâmetros durante e após o exercício em animais que realizam provas de longa duração. Outros estudos devem ser realizados para verificar se essa influência pode melhorar o desempenho desses animais em exercícios predominantemente aeróbicos / The nasal strip is widely used in horses during exercise, but the results are controversial and little known in animals that compete for endurance events. The aim of this study was to determine whether the use of nasal strips influence parameters during predominantly aerobic exercise, such as respiratory frequency, tidal volume, minute ventilation, inspiratory and expiratory times, population of cells by bronchoalveolar lavage, heart rate and blood lactate. Six Arabian horses were submitted to two low intensity tests on a treadmill, one of them with nasal strip and one without nasal strip. During the tests were carried out blood samples, airflow and volume curves with spirometry mask, and heart rate was recorded through heart rate monitor. Two hours after the exercise was performed bronchoalveolar lavage to perform cytology of pulmonary secretions. There were no differences among ventilatory parameters analyzed when the horses performed the exercise with or without the nasal strip. However, heart rate was lower on average during the exercise when the horses were exercised with nasal strip (p <0.05), which may indicate a better supply of oxygen during the low intensity exercise with the use of nasal strip, despite we did not find changes in the airflow and respiratory volume parameters. In cytological evaluation of the content of bronchoalveolar lavage, increased percentage of neutrophils was observed after exercise in animals with nasal strip (p <0.05), indicating that turbulence in the airflow through the nasal cavity may have diminished allowing larger particles to be deposited in distal portions of the respiratory system, inducing a more intense neutrophilic response. The use of nasal strips appears to influence some parameters during and after exercise in horses that perform low intensity and endurance tests. Further studies should be conducted to verify that this influence can improve the performance of these horses in predominantly aerobic exercises

Neste trabalho avaliou-se o comportamento coloidal de suspensões nasais contendo micropartículas de celulose (MCC-NaCMC) com o objetivo de desenvolver um produto genérico compatível com o produto referência de mercado. As propriedades reológicas destas formulações possuem alta influência nos atributos críticos de qualidade do produto, como uniformidade de dose, devido sedimentação durante estocagem em prateleira, e também na performance in-vitro/ in-vivo. Realizaram-se testes com diferentes concentrações de MCC-NaCMC e diferentes parâmetros de processo (tempo e taxa de cisalhamento) utilizando um planejamento de experimentos (DoE) de superfície de respostas através de um modelo composto central. As respostas avaliadas foram tamanho de partículas (quantidade em porcentagem de partículas menores que 1µm e D90) através da técnica por difração a laser e viscosidade/tixotropia através de um reômetro rotacional. Influências significativas dos três fatores e efeitos sinérgicos entre eles nas respostas analisadas foram observadas. Desta maneira foi possível obter respostas próximas ao do produto referência de mercado através deste mapeamento. Observou-se também uma alta correlação entre as respostas, pois este estudo mostrou que o tamanho das partículas coloidais controla a viscosidade e tixotropia das dispersões coloidais. Este trabalho mostrou a significativa influência das etapas de processo no comportamento coloidal das formulações. Idealmente o processo deveria ser monitorado por medidas reológicas, porém este controle é inviável devido ao tempo para a reestruturação do sistema (24 horas). Portanto, a melhor alternativa seria o monitoramento do processo por análise de tamanho de partículas online. / In this work, the colloidal behavior of nasal suspensions containing cellulose microparticles (MCC-NaCMC) was evaluated, in order to develop a generic product compatible with the brand-name product. The rheological properties of these formulations have high influence on the critical quality attributes of the product, such as dose uniformity, due to sedimentation during shelf life, and also on in-vitro/in-vivo performance. Tests were performed with different concentrations of MCC-NaCMC and different process parameters (time and shear rate) using a Design of Experiments (DoE) with response surface by central composite design. The responses evaluated were particle size (amount in percentage of particles smaller than 1m and D90) by means of laser diffraction, and viscosity / thixotropy using a rotational rheometer. Significant influences of the three factors and synergic effects among responses were observed. Through this mapping it was possible to obtain nearby responses to the brand-name product. There was also a strong correlation between the responses, because the size of colloidal particles controlled the dispersion viscosity and thixotropy. This study showed the significant influence of the process steps on the colloidal behavior of the formulations. Ideally the process should be monitored by rheological measurements, but this control is not feasible due to the time required for the system rebuilding (24 hours). Therefore, the best alternative would be monitoring the process by the online particle size analysis.