Malignant melanoma is one of the most rapidly increasing cancers and accounts for about three-quarter of all skin cancer deaths worldwide. Despite compelling evidence that ultraviolet (UV) irradiation causes melanoma the knowledge how various wavelength spectra affect the balance between proliferation and apoptosis controlling the homeostasis of the melanocyte population is still limited. The aim of this thesis was to elucidate the regulation of UVA/B induced apoptotic signaling in human epidermal melanocytes in vitro in relation to redox alterations and antioxidant photoprotection. UVA irradiation induced changes in plasma membrane stability, decreased cell proliferation and increased apoptosis. In comparison, melanocyte plasma membrane was markedly resistant to UVB irradiation although apoptosis was triggered. Thus, UVA irradiation should not be overlooked as an etiologic factor in melanoma development. Further, after irradiation with UVA/B we found alterations in redox state manifested by a reduction of intracellular GSH levels, translocation of nuclear factor-κB from the cytosol to the nucleus, an increase of γ-glutamylcysteine synthetase, the rate-limiting enzyme in GSH synthesis, and an increased apoptosis frequency. α-Tocopherol provided photoprotection through several modes of action affecting redox alterations and signaling, stabilizing the plasma membrane, and decreased proliferation and apoptosis rate, while β-carotene did not show the same protective capacity. Altogether, α-tocopherol might be a useful substance in protecting melanocytes from UV induced damage. We demonstrate UVA/B irradiation to activate the intrinsic pathway of apoptosis in melanocytes where translocation of Bcl-2 family proteins to the mitochondria modulates the apoptosis signal. Interestingly, the anti-apoptotic Bcl-2 family proteins generally thought to be attached to membranes, were localized in the cytosol before UV irradiation and translocated to the mitochondria in the surviving population, which might be a critical event in preventing apoptotic cell death. Lysosomal cathepsins were released to the cytosol acting as pro-apoptotic mediators upstream of activation and translocation of Bax to the mitochondria. When melanocytes were exposed to UVA, p53 participated in apoptosis regulation through interaction with Bcl-2 family proteins, while UVB induced p53-transcriptional activity and apoptosis involving lysosomal membrane permeabilization. Thus, depending on the UV wavelength p53 mediated apoptosis in melanocytes by transcriptional dependent or independent activity. These results emphasize p53 as an important pro-apoptotic component in the regulation of apoptosis. This thesis gives new insight in the harmful and various effects of different wavelengths within the UV spectrum on human melanocytes in vitro. Improved knowledge of the apoptosis regulatory systems in melanocytes might lead to a better understanding of the formation of pigment nevi and malignant melanoma and, in the future, provide better strategies to prevent and eliminate tumor development and progression.

People with psoriasis are known to engage in high levels of unhealthy lifestyle behaviours which may lead to poorer psoriasis outcomes and increase the risk of cardiovascular disease (CVD). Thus, helping individuals with psoriasis understand the link between behaviours and health risks, that is health risk communication, and direct support for lifestyle behaviour change (LBC) are important aspects in optimal management of psoriasis, a long-term inflammatory skin condition. There are two aspects of the literature that remain unclear. First, whether adequate support is given to patients to enable them to understand the links between lifestyle behaviours and health outcomes is part of psoriasis patient management strategies. Second, whether there is agreement around effective health risk communication techniques. This programme of research aimed to examine these gaps in the literature using four related studies. The first study used content analysis to examine general and dermatology-specific healthcare professionals’ core training competencies for evidence of skills relating to LBC. An important finding was the lack of explicit skills relating to LBC and changing understanding of health risks. There was little or no reference to recognised LBC techniques that could be used to support and facilitate LBC with patients. The second study used observational techniques to examine messages about the links between behaviour and health outcomes and LBC signposting (such as leaflets or posters about healthy living) for patients with psoriasis in primary and secondary care patient waiting areas. There was little evidence of psoriasis-specific information about healthy living. Generic information (not specifically about psoriasis) was often of poor quality and was poorly displayed, and did not conform to evidence-based recommendations for effective LBC signposting. The third study combined observational and qualitative techniques to examine how healthcare professionals communicate information about CVD risk to patients and the role of LBC in reducing risk in the context of primary care risk assessments with people with psoriasis. A key finding was that interpretation of risk information was not always linked to specific advice about how to modify each risk factor. Discussion was mostly instructional rather than a shared collaborative discussion about behaviour change and risk reductionThe fourth study used experimental methods to examine the effects of message framing theory as a health risk communication strategy on reported behavioural intentions (BIs) in people with psoriasis. An important finding was that for messages about psoriasis symptom reduction, gain-framed (positively-framed) messages were more effective in increasing BIs for alcohol reduction. Conversely, for messages about CVD risk reduction, loss-framed (negatively-framed) messages were more effective for increasing BIs to reduce alcohol consumption. The body of work presented in this thesis demonstrated that much needs to be done to increase the skill sets of healthcare professionals in order to help people with psoriasis recognise the specific links between their own health behaviours and health outcomes. In addition specific recommendations have been suggested as a way of improving risk communication strategies, such as using theory-based personally-relevant health information for people with psoriasis.

A distribuição da energia espacial do feixe de laser é de grande importância para a eficiência em tratamentos dermatológicos. Os métodos existentes para a calibração do feixe podem ser realizados por meio de equipamentos óticos ou por materiais fotossensíveis. Este trabalho apresenta uma metodologia que pode ser descrita por quatro fases. Na primeira, foi obtido o polímero poliacetal, material que foi responsável por registrar o perfil transversal do feixe de laser (Nd:YAG 1064 nm). Na segunda fase os valores referenciais dos parâmetros do feixe foram extraídos por meio do método knife edge. Posteriormente, as técnicas de processamento de imagem foram aplicadas sendo responsáveis pela extração de características do feixe registradas no polímero. Como resultados, determinaram-se os seguintes parâmetros: área do feixe, circularidade, perfil da borda, assinatura, diâmetros, divergência e cintura do feixe. Na última fase o feixe foi classificado em calibrado e descalibrado por meio da Rede Neural Artificial (RNA) Multilayer Perceptron (MLP), que apresentou 88,5% de taxa de acertos. Outro parâmetro utilizado para a calibração foi a circularidade, onde adotou-se o valor limiar de 0,85 para decisão entre feixes calibrados e feixes descalibrados. Frente aos resultados obtidos, considera-se bem sucedida a proposta para a inspeção de qualidade de feixe laser para aplicação dermatológica, apresentando-se como um método de calibração alternativo com maior precisão quando comparado a análises por meio da visualização humana. / The spatial distribution of laser beam energy is of great importance to the efficiency of dermatologic treatments. The existing methods beam calibration can be performed with optical equipment or photosensitive materials. This paper presents a methodology which can be described by four phases. At first it was obtained polyacetal polymer, a material that was responsible for registering the transverse profile of the laser beam (Nd:YAG 1064 nm). In the second phase, the reference values of the beam parameters were extracted using the knife edge method. Subsequently, the image processing techniques were applied being responsible for extracting features of the beam recorded in the polymer. As a result, we determined the following parameters: beam area, circularity, the edge profile, signature, diameter, divergence and beam waist. In the last phase the beam was classified calibrated and uncalibrated with Artificial Neural Network (ANN) Multilayer Perceptron (MLP), which showed 88.5% hit ratio. Another parameter used for calibration was the circularity, where we adopted the threshold value of 0.85 for decision between calibrated and uncalibrated beams. Given our results, it is considered a successful proposal for the quality inspection of laser beam for dermatological application, presenting itself as an alternative method of calibration with greater precision when compared to analyzes by human viewing.

Orientador: Luciana Patrícia Fernandes Abbade / Resumo: Introdução: Estudos pilotos e de viabilidade são realizados em diversas áreas clínicas e têm importante papel no planejamento e desenvolvimento de ensaios clínicos aleatorizados (ECAs). Entretanto, na literatura existe grande número de ECAs declarados como pilotos e de viabilidade, mas não relatam claramente em seus objetivos e métodos quais itens são testados quanto aos processos e viabilidade e se são uma preparação para estudos maiores. Objetivos: avaliar a adequação dos relatos de ECAs denominados como pilotos ou de viabilidade publicados na área de dermatologia, em relação aos cincos pontos-chaves necessários para relato destes estudos e determinar quais são os fatores associados com adequação completa aos cincos pontoschaves. Métodos: pesquisa sistemática metodológica de ECAs pilotos e de viabilidade em dermatologia publicados no PubMed, no período de janeiro de 2012 a julho de 2018. Critérios de exclusão: protocolos, carta aos editores e estudos pilotos não aleatorizados. A extração de dados de cada artigo selecionado foi realizada por meio de uma planilha padronizada. Dois revisores extraíram os dados e qualquer desacordo foi resolvido através de consenso. Os estudos incluídos foram avaliados quanto sua adequação aos cincos pontos-chaves, os quais foram escolhidos pelos autores a partir do CONSORT Statement para estudos pilotos e de viabilidade, por considerarem que são itens fundamentais para um bom relato de ECA piloto e de viabilidade. Os cincos pontos-chaves são: ... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Background: Pilot and feasibility studies are carried out in several clinical areas and have an important role in the planning and development of randomized clinical trials (RCTs). However, in the literature there are a large number of RCTs declared as pilots and viability, but not clearly related in their objectives and methods. What are the items tested with regard to processes and feasibility and if it is a preparation for larger studies. Objectives: to assess RCT’s suitability reports referred to as tests or feasibility of publication in the field of dermatology, in relation to the values of key keys used for study reports and wich are the factors associated with complete adequacy to the key points. Methods: systematic survey of dermatology pilot’s RCT published in PubMed from January 2012 to July 2018. Exclusion criteria: protocols, letter to editorials and non-randomized pilot studies. Data extraction from each selected article was performed using a standardized spreadsheet. Two reviewers extracted the data and any disagreements were resolved by consensus. The included studies were assessed as to their suitability for the five key points, which were chosen by the authors from the CONSORT Statement for pilot and feasibility studies, as they consider that they are fundamental items for a good report of pilot and feasibility RCTs. The five key points are: i) title or abstract indicating that it is a pilot study; ii) objectives attesting to viability; iii) outcomes that ass... (Complete abstract click electronic access below) / Mestre

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Background: Groote Schuur Hospital (GSH) Division of Dermatology receives many referrals from local clinics and hospitals. Some of these patients are admitted to the dermatology wards for diagnosis and/or management. It is important to look at the spectrum and outcome of these patients who are admitted to dermatology wards at the hospital, to inform policy. Objectives: To characterise the spectrum of dermatological conditions requiring admission, to determine the outcome and to describe the factors that may influence the outcome of dermatological conditions in patients admitted to the dermatology wards at Groote Schuur Hospital in South Africa. Methods: This research employed descriptive retrospective analysis to describe the dermatology inpatients who were admitted to dermatology wards at Groote Schuur Hospital over the period January 2017 to December 2017. Results: There were a total of 120 admissions to Groote Schuur Hospital Dermatology wards in 2017. Of these, 89 (74.1%) were new admissions and 31 (25.8%) re-admissions. The most frequent diagnosis was drug reaction (27.5%), followed by psoriasis (23.3%), eczema (17.5%), and bullous disease (10%). Less common indications for admission were infections, lupus erythematosus, scabies, ulcers, pyoderma gangrenosum and cutaneous small-vessel vasculitis. The outcome of the admission was usually favorable. Conclusions: The most common diagnoses on admission were drug reactions, psoriasis, eczema, and bullous diseases. The generally favorable outcomes would support the future use of inpatient care for people with severe skin disorders.

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