Development of mortality from malignant neoplasm of bronchus and lung in the Czech Republic Abstract Malignant neoplasm of bronchus and lung is one of the most common causes of death in the Czech Republic and this diploma thesis aims to evaluate and describe the development of mortality from this disease since the mid-nineties to the present time in the Czech Republic compared to other European countries and on district level. The main goal of this thesis is to analyze the indicators evaluating the structure and intensity of mortality on this common cause of death. The theoretical part describes the selected disease, all the important risk factors, possibilities of prevention, diagnosis, treatment and prognosis of the disease. There are some other theoretical concepts described especially the tobacco epidemic, as smoking is without a doubt the most important risk factor for this disease. Throughout the study period, mortality rates have been converging in the Czech Republic and other selected European countries for malignant neoplasm of bronchus and lung by sex when mortality has decreased significantly for men population, while for women it is slightly increasing. Keywords: mortality, cause of death, malignant neoplasm, bronchus, lung, Czech Republic

Magister Scientiae Dentium - MSc(Dent) / Oral epithelial dysplasia (OED) is a growth anomaly which occurs as a result of atypical, abnormal proliferation and a change in the architecture and cytological features of cells of epithelial origin, which ultimately results in the formation of a lesion with disturbed differentiation and maturation The purpose of this study was to describe the OED cases diagnosed at Tygerberg Oral health centre in a 7-year period between 2012 and 2019. The patients’ medical records from Tygerberg Oral Health Centre and National Health Laboratory Service (NHLS) were reviewed. All diagnosed cases of OED were identified and the data retrieved for further assessment and comparison. The individual medical records and follow up data were assessed. Seventy cases of OED were diagnosed in the period assessed. Of those 70 cases, the median age was 58 and the interquartile range was from 48 – 62. Thirty-six of the diagnosed patients were female and thirty-four were males. The majority of lesions diagnosed with OED were found on the tongue, floor of the mouth (FOM) and buccal mucosa. Majority of the lesions were found in non-smokers and non-alcohol consumers. These two categories both presented with mild cases of OED. From the results, it was derived that OED has no intra-oral location predilection. Moreover, OED is not directly associated with smoking.

Malignant transformation of cell is characterized by genomic instability that involves unbalanced changes besides other things. We analyzed genomic aberrations, promoter methylation and mutations of several clinically relevant genes using I-FISH, mFISH, mBAND, CGH array, SNP array, MLPA, MS-MLPA and MS-PCR methods. We focused on two groups of patients well known for frequent appearance of unbalanced changes - patients with malignant brain tumors (gliomas) and patients with myelodyspastic syndromes (MDS). In patients with low grade glioma (WHO grade I - II), the codeletion of 1p/19q (82,6% oligodendrogliomas and oligoastrocytomas), mutation of IDH1/IDH2 genes (87% WHO grade I-II gliomas), copy neutral loss of heterozygozyty of 17p (72,2% astrocytomas) and higher presence of unbalanced aberration in astrocytomas belongs to the most frequent findings. We described yet unpublished methylation of MLH3 gene promoter in 60,9% oligodendrogliomas and in 27,3% astrocytomas. We also observed clonal evolution in patients with recurrent tumors. We studied secondary rearrangements of deleted chromosome 5 in patients with MDS and complex karyotype and we described its most recurrent translocation partners and breakpoints. We observed chromothripsis in 49% of these patients and it was frequently associated with...

This clinical enquiry, based on clinical work undertaken during an internship, explores the role of music therapy in the nurturing of personhood of persons in a male psychogeriatric ward. The purpose of the enquiry is to draw insights into the role of music therapy in fostering personhood, not only in patients, but nursing staff members, who were included in the weekly music therapy group. The music therapy sessions included a variety of musical activities with many opportunities for performing. Over the course of thirteen sessions, clinical material was selected via purposive sampling, in the form of three video excerpts, and text lifted from observation notes. This material was analyzed using the research methods of coding, categorizing and identifying themes. The emerging themes are opportunities for growth of personal worth; experience of a changing group and self-identity; community: being in social relationship with others; and musical interplay: expression through music. It appears that music therapy indeed played a role in nurturing the personhood of group members, through the affordance of opportunities, and through enablement and empowerment of the individuals and the group. It would seem that including staff in the music therapy groups, developed not only their own personhood, but the personhood of the patient. This may have implications in music therapists’ view of the role of the nursing staff member within a music therapy group. Staff may be seen as, not only perfunctory helpers, but as a contributing, equal members of a music therapy group. / Dissertation (MMus)--University of Pretoria, 2008. / Music / UCTD / Unrestricted

OBJECTIVES: Models for the development of new treatment options in vestibular schwannoma (VS) treatment are lacking. The purpose of this study is to establish a quantifiable human VS xenograft model in mice. STUDY DESIGN AND METHODS: Both rat malignant schwannoma cells (KE-F11 and RT4) and human malignant schwannoma (HMS-97) cells were implanted near the sciatic nerve in the thigh of severe combined immunodeficiency (SCID) mice. Additionally, human benign VS specimens were implanted in another set of SCID mice. Three-dimensional tumor volumes were calculated from magnetic resonance images over the next 6 months. RESULTS: Mice implanted with malignant schwannoma cells developed visible tumors within 2 weeks. Imaging using a 4.7-tesla magnetic resonance imaging and immunohistopathologic examination identified solid tumors in all KE-F11 and HMS-97 xenografts, whereas RT4 xenografts consistently developed cystic schwannomas. VS xenografts demonstrated variability in their growth rates similar to human VS. The majority of VS xenografts did not grow but persisted throughout the study, whereas two of 15 xenografts grew significantly. Histopathologic examination and immunohistochemistry confirmed that VS xenografts retained their original microscopic and immunohistochemical characteristics after prolonged implantation. CONCLUSIONS: This study describes the first animal model for cystic schwannomas. Also, we demonstrate the use of high-field magnetic resonance imaging to quantify VS xenograft growth over time. The VS xenografts represent a model complimentary to Nf2 transgenic and knockout mice for translational VS research.

Magister Chirurgiae Dentium (MChD) / Oral submucous fibrosis (OSMF) is a chronic disorder characterized by the fibrosis of the mucosal lining of the upper digestive tract involving the oral cavity, oropharynx, hypopharynx and the upper third of the oesophagus. Areca nut chewing has been implicated in the aetiology of this condition. This condition is prevalent in Kwa-Zulu Natal (KZN), South Africa, with many patients suffering from varying degrees of severity of this disease. At Inkosi Albert Luthuli Central Hospital autogenous fat injections into the fibrous bands are being used as a means of treating OSMF. Anecdotal evidence suggested that this type of treatment modality helps to relieve the symptoms experienced by patients. There is no scientific data supporting this claim. The aim of the study was to establish the effectiveness of intralesional autogenous fat injections in patients with oral submucous fibrosis. The objectives of this study was to record the demographic details and medical information of the patients, evaluate the inter-incisal mouth opening, to assess the presence or absence of restricted tongue movements, record pain of the patients and record quality of life via a condition specific questionnaire prior to treatment and at six months post operatively

Melanocytic neoplasms have been genetically characterized in detail during the last decade. Recurrent CTNNB1 exon 3 mutations have been recognized in the distinct group of melanocytic tumors showing deep penetrating nevus-like morphology. In addition, they have been identified in 1–2% of advanced melanoma. Performing a detailed genetic analysis of difficult-to-classify nevi and melanomas with CTNNB1 mutations, we found that benign tumors (nevi) show characteristic morphological, genetic and epigenetic traits, which distinguish them from other nevi and melanoma. Malignant CTNNB1-mutant tumors (melanomas) demonstrated a different genetic profile, instead grouping clearly with other non-CTNNB1 melanomas in methylation assays. To further evaluate the role of CTNNB1 mutations in melanoma, we assessed a large cohort of clinically sequenced melanomas, identifying 38 tumors with CTNNB1 exon 3 mutations, including recurrent S45 (n = 13, 34%), G34 (n = 5, 13%), and S27 (n = 5, 13%) mutations. Locations and histological subtype of CTNNB1-mutated melanoma varied; none were reported as showing deep penetrating nevus-like morphology. The most frequent concurrent activating mutations were BRAF V600 (n = 21, 55%) and NRAS Q61 (n = 13, 34%). In our cohort, four of seven (58%) and one of nine (11%) patients treated with targeted therapy (BRAF and MEK Inhibitors) or immune-checkpoint therapy, respectively, showed disease control (partial response or stable disease). In summary, CTNNB1 mutations are associated with a unique melanocytic tumor type in benign tumors (nevi), which can be applied in a diagnostic setting. In advanced disease, no clear characteristics distinguishing CTNNB1-mutant from other melanomas were observed; however, studies of larger, optimally prospective, cohorts are warranted.

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Anthracene was attached to light activated, ruthenium-based DNA disruptors to probe their distribution in cancer cells. The objective of this research is to understand the photophysical properties (Chapter 2), photoreactivity toward DNA and proteins (Chapter 3), and localization within cancer cells (Chapter 4) of ruthenium complexes that demonstrate promise as photodynamic therapy (PDT) agents. [(AnthbpyMe)(bpy)Ru(dpp)]2+ (1) and [(AnthbpyMe)2Ru(dpp)]2+ (2) absorb visible light with metal-to-ligand charge transfer (MLCT) transitions at 459 nm (16,000 M-1 cm-1 ) and 461 nm (21,000 M-1 cm-1 ), respectively. These species exhibit 3 MLCT emissions at λem = 661 nm and λem = 663 nm for 1 and 2, respectively, while the anthracene show emissions at 450 – 560 nm. The anthracene unit(s) quench the 3 MLCT to give quantum yields (lifetime) of Φem = 0.0059 [398(1) ns] and Φem = 0.0011 [414(1) ns] for 1 and 2, respectively. Voltammetry shows an irreversible anthracene oxidation at 1.23 – 1.28 V, RuIII/II oxidation at 1.53 – 1.55 V, and quasi-reversible reduction couples attributed to dpp0/-1 at 0.98 V. DNA gel shift assays demonstrate that complexes 1 and 2 modify DNA in the presence and absence of 3 O2 upon light activation to convert supercoiled DNA to a mixture of open circular (OC) DNA and a species that exhibit sa distinctly different migration rate than either OC and linear DNA. Binding constants, Kb, for complexes 1 and 2, toward DNA are 3.50 × 105 (3.50 × 104 ) and 4.50 × 103 (4.50 × 102 ) respectively. SDS-PAGE assays show that the complexes 1 and 2 modify bovine serum albumin (BSA) through an 3 O2-dependent mechanism upon light iii activation. The localization and PDT potency of the anthracene-Ru-dpp complexes are tested against F98 cells, which are rat glioma cells that simulate the infiltrative patterns of growth in cancer. Confocal microscopy demonstrates that complexes 1 and 2 internalize and localize primarily along the cell membrane and associate with dot-like vesicles within the cytoplasm. Complexes 1 and 2 show IC50 values of 107 µM and 85 µM, respectively, after 15 min of drug exposure and 1 h of PDT-treatment (λPDT = 455 nm). / Ph. D.