Head and neck cancer is one of the most common cancers worldwide. The current standard of care for head and neck cancer includes surgical resection of the tumor followed by chemoradiation. This targeted head and neck radiation causes dysfunction of the salivary glands, which leads to xerostomia, mucositis, dysphagia, dental caries, and malnutrition. These side effects greatly decrease patient quality of life and increase their financial responsibility. Current therapies available to ameliorate these negative side effects are expensive, only provide short-term relief, and many of them have negative side effects of their own. Therefore, another therapy is needed to prevent salivary gland dysfunction or restore its function following targeted head and neck radiation. Autophagy is a homeostatic cellular mechanism that could be targeted as a therapeutic mechanism in the salivary glands following targeted head and neck radiation. Autophagy is a catabolic process necessary to maintain cellular homeostasis. It has been shown to play a beneficial role in a variety of disease states including diabetes mellitus, obesity, and cancer. The role of autophagy in the response of cancerous tissue to radiation has been vastly studied. However, the role autophagy plays in normal tissue response to radiation remains poorly understood and much more research in this area is needed.Atg5^(f/f);Aqp5-Cre mice have a conditional knockout of Atg5, a gene necessary for autophagy, in the salivary glands. These mice have unchanged baseline levels of apoptosis, proliferation, and stimulated salivary flow rates when compared to wild-type mice. Therefore, they are a useful model to investigate the role of autophagy in the response of the salivary glands to targeted head and neck radiation. These Atg5^(f/f);Aqp5-Cre autophagy-deficient mice display increased radiosensitivity following targeted head and neck radiation. Furthermore, post-therapy use of CCI-779, a rapalogue and inducer of autophagy, allowed for restoration of salivary gland function following targeted head and neck radiation. Taken together, these results implicate autophagy as playing a beneficial role in normal salivary function following radiation. Therefore, autophagy could be utilized by normal salivary gland tissue following targeted head and neck radiation to maintain salivary gland function.

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A dissertation presented to the Faculty of Health Sciences at the Durban University of Technology in partial compliance with the requirements for the Master’s Degree in Technology: Chiropractic, 2009 / Introduction: The aetiology of Temporomandibular Joint Dysfunction (TMJD) is not fully understood and the treatment of TMJD is controversial. Most treatment plans are based on postulated aetiology. Treatment plans currently range from pharmacological to surgical and occasionally physical therapy is also used for any myofascial component. Myofacial Trigger Points (MFTP’s) in the head and neck region have similar pain referral patterns as TMJD and there is overlap in aetiology and epidemiology. If correlation can be proved to exist between the severities of TMJD and MFTP’s then the treatment of MFTP’s can potentially decrease the severity of TMJD and then the more radical treatments can be avoided. Objectives: To determine whether TMJD was present and establish severity. To locate any MFTP’s in the Sternocleidomastiod (SCM), Temporalis, Masseter, Posterior Cervical (PC), Lateral and Medial Pterygoid muscles and determine their severity. Methods: A random sample of 25 participants were evaluated. A p value <0.05 was considered as statistically significant. Quantitative variables were summarized using median, inter-quartile range and range due to skewness of distribution, while categorical variables were described using frequency distributions and bar charts. Spearman’s nonparametric correlation analysis, and curve estimation were used to determine the existence of a relationship between TMJ severity and MFTP severity. A scatterplot was used to graphically assess the relationship. Conclusion: The results suggested that the participants were actually chronic neck pain suffers that developed TMJD over the long term as a result of chronic neck pain changing the kinematic biomechanics or as a result of a completely different and independent event as suggested by Foreman and Croft (1995).

Dissertation submitted in partial compliance with the requirements for a Masters Degree in Technology: Chiropractic, Durban University of Technology, 2010. / The aim of this study was to determine the prevalence of and risk factors for neck pain in the white population in the greater Durban area. The rational for this study was that there have been few epidemiological studies done on neck pain and even less when concerning different population groups. Discrepancies between population groups have been found in various pain related studies. The present epidemiological study eliminated any possible variables between population groups by studying only the white population in a specific geographical area (Durban). Therefore, physicians treating people with neck pain should use the risk factors that were established in this and other studies and integrate them in their treatment protocol. The study was conducted at three shopping centres around Durban that were randomly selected. Each shopping centre was grouped by the socio-economic status of the surrounding suburbs. There were 900 participants surveyed at three shopping centres by means of a questionnaire. The data were then statistically analysed using SPSS version 15. It was found that the overall prevalence of neck pain was 45%. The participants in this study that had neck pain were more likely to be females that were married or previously married, had a job that caused their heads to turn or to work with their arms above their heads. Lifestyle factors included one or a combination of the following: lead a stressful lifestyle, were emotional, had perceived bad posture, had previously experienced neck or head trauma, slept in awkward positions, watched television, required glasses and did not play squash.

Anatomical changes can have significant clinical impact during head and neck radiotherapy. Adaptive radiotherapy (ART) may be applied to account for such changes. Implementation of ART to alter dose delivery requires deformable image registration (DIR) to assess 3D deformations. This study evaluates the performance and accuracy of a commercial DIR system for clinical applications. The investigations in this project were carried out using images of induced changes in two standard radiotherapy phantoms (RANDO® and CIRS®) and one in-house built phantom. CT image data before and after deformation of the phantoms were processed using Eclipse / SmartAdapt® v.10 system employing a Demons-based algorithm. A DIR protocol was designed, and algorithm performance was assessed quantitatively, using volume analysis and the Dice Similarity Index (DSI), and also evaluated qualitatively. In addition, algorithm performance was assessed for 5 head and neck cancer patients using clinical CT images. Each original planning CT image containing contours of 10 volumes of interest including treatment target volumes and organs at risk was deformed to match a second CT image acquired during the course of the treatment. The original structures were deformed, copied onto the target image and compared to reference contours drawn by 3 radiation oncologists. Phantom investigations gave varied results with average DSI scores ranging from 0.69 to 0.93, with an overall average of 0.86 ± 0.08. These quantitative results were reflected qualitatively, with generally accurate matching between reference and DIR-generated structures. Although air gaps in the phantoms compromised algorithm performance and gave rise to physically aberrant results. Clinical results were generally better with a DSI range of 0.75-0.99 and an overall average of 0.89 ± 0.05, suggesting high DIR accuracy. Qualitatively, some minor contour deformations were noted, as well as artefacts in the axial direction that were due to the CT slice resolution (3 mm) that was used to scan the patients. In addition, contour propagation between images using DIR reduced the time required by physicians to contour the images of head and neck cancer patients by ~47%. This study demonstrated that deformable image registration using a Modified Demons algorithm yields clinically acceptable results and time-saving benefits in contouring that improve clinical workflow. The study also showed that it is feasible to incorporate deformable image registration as part of an adaptive radiotherapy strategy for head and neck cancer, provided further studies are designed to carry out accurate and verifiable dose deformation.

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Nackbesvär är vanligt förekommande vid datorarbete. Stående datorarbete har i visats ha en gynnsam effekt på nackbesvär. Nackflexion kan ge en ökad belastning på nacken. Syftet med studien var att jämföra flexion i nacken vid sittande och stående datorarbete för personer som utför datorarbete under en stor del av dagen i sitt ordinarie arbete. Sammanlagt tio personer, åtta kvinnor och två män, som arbetar på en företagshälsovård deltog i studien. De arbetade med datorarbete i växel, kundservice, sjukvårdsrådgivning eller sjuk och frisktjänst (en tjänst där arbetsgivare får hjälp att hantera sjuk och friskanmälningar, sammanställning av sjukskrivningsstatistik samt med rådgivning till sjukskrivna). Nackflexion mättes vid två tillfällen, två timmar per person, sittande och stående under en timme var. Mätningarna gjordes med triaxiala accelerometrar med placering i pannan, över Thorakalkota I samt på utsidan av låret för att säkerställa positionen.  Den relativa vinkeln mellan Thorakalkota I och pannan utgjorde flexionsvinkeln. Ingen 0-position användes vid beräkningen. Resultat: Jämförelsen av nackflexion mellan sittande och stående datorarbete kunde i den här studien inte påvisa någon skillnad mellan de två positionerna (medelvärde för nackflexion i sittande 29,2°, stående 28,1°, p:0,35) . Resultaten i den här undersökningen stödjer behovet av att undersöka fler variablar än nackflexion för belastning av nacken vid stående och sittande datorarbete till exempel om den spänning i nackmuskulaturen som arbete med armarna kan ge skiljer sig mellan de olika positionerna. / Neck pain is frequent during computer work. Standing during computer work has been shown to have a beneficial effect on neck pain. Flexion of the neck may cause an increased load on the neck. The aim of this study was to compare flexion of the neck while sitting and standing during computer work for people who perform computer work during most of the day in their regular work. Ten individuals, eight women and two men, working in an occupational health service participated in the study. They worked with computer work in customer service, healthcare advice or sickness and recovery service (a service where employers get service to carry out sickness and recovery notifications, statistics of sick leaves, and counseling services to persons on sick leave). Neck flexion was measured on two occasions, during two hours per person each time, sitting and standing for one hour each. The measurement was made with triaxial accelerometers placed on the forehead, on Thoracic segment I, and on the outside of the thigh to verify the positions. The relative angle between Thoracic segment I and the forehead formed the flexion angle. No 0-position was used in the calculations. Results: The comparison of neck flexion between sitting and standing computer work, in this study, did not show any difference between the two positions (averaged neck flexion, sitting 29.2°,  standing 28.1°, p:0.35). The result supports the need for more research to examine the load of the neck during standing and sitting computer work examining more variables than neck flexion, for example, if muscular activity in the neck differs between the two positions during arm work.

Submitted in partial compliance with the requirements for the Master’s Degree in Technology: Chiropractic Durban University of Technology, 2013. / Background : Chronic non-specific neck pain is a common condition that negatively affects cervical muscle functioning and activities of daily living. Combined exercise and mobilisation are currently recommended as the most effective treatment for this condition. Mobilisation, such as mobilisation of the cervical spine, provides short-term pain relief and affects neural activity, while the craniocervical flexion exercise provides immediate pain relief and activates the deep cervical flexors. The short-term effect of mobilisation and the craniocervical flexion exercise have not been compared. Objectives : This study aimed to compare mobilisation and craniocervical flexion exercise in terms of subjective and objective outcome measures at a short-term follow-up consultation for the treatment of chronic non-specific neck pain. The null-hypothesis was that the mobilisation group would not respond differently to the craniocervical flexion exercise group. Method : A group of thirty females between the ages of 20 and 35 complaining of non-specific neck pain for more than three months were randomly allocated into either the mobilisation or craniocervical flexion exercise groups. During the first two consultations, a mobilisation was administered to the mobilisation group. Whereas the craniocervical flexion exercise and a posture correcting exercise were taught to the participants of the craniocervical flexion exercise group. The Numerical Pain Rating Scale, Neck Disability Index, Neck Bournemouth Questionnaire, cervical range of motion and algometer readings were taken at each of the three consultations. The Patient Global Impression of Change Scale was administered at the last consultation one week after the first consultation. Results : Both the mobilisation and craniocervical flexion exercise groups showed significant improvements in all of the subjective outcomes. The Neck Disability Index score of the craniocervical flexion exercise group was the only subjective outcome that did not decrease enough to be considered clinically significant. The PGIC score of the mobilisation group was slightly higher than that of the craniocervical flexion exercise group. There was no statistically significant improvement in the objective outcomes of either group. All ranges of motion decreased in both groups, while pain pressure threshold improved in both groups. There was no significant difference between the results of the subjective and objective outcomes of the mobilisation and craniocervical flexion exercise groups. Conclusions and recommendations : The two interventions were found to have a similar effect in the treatment of chronic non-specific neck pain in terms of subjective and objective outcome measures. Participants of both groups indicated on the subjective scales that their conditions improved, even though objective outcomes showed no significant change. In future studies, a larger sample size should be used and the sample should be stratified for ethnicity to increase validity of the results.

Receptor Tyrosine Kinase (RTK) inhibitors, such as erlotinib/tarceva, have been introduced in the past decade as a promising therapeutic option in Head and Neck Squamous Cell Carcinoma (HNSCC), however, they lack significant efficacy as single agents. As a result, RTK inhibitors require a combination based therapeutic approach with other treatment modalities. To uncover such a combination of agents, we performed a high throughput Prestwick library screen that included 1200 compounds approved by the FDA on HNSCC cell lines and found that monensin, a coccidial antibiotic, synergistically enhanced the cytotoxicity of erlotinib. RT-PCR revealed that monensin induced the expression of Activation of Transcription Factor (ATF) 3 and its downstream target C/EBP homologous protein (CHOP) which are key regulators of apoptosis. Furthermore, RNA-Seq analysis suggests that monensin augments erlotinib cytotoxicity by disturbing lipid and sterol biosynthesis. Therefore, identifying the mechanism of action exerted by monensin may open alternative avenues of cancer treatment.