Long-Term Evaluation of Recurrence after Photodynamic Therapy with Topical Methyl Aminolevulinate for Non-Melanoma Skin Cancer: a Hospital-Based Study

Introduction & Objectives: Several factors may influence the decision to pursue nonsurgical modalities for the treatment of non-melanoma skin cancer. Topical photodynamic therapy (PDT) is a non-invasive alternative treatment reported to have a high efficacy when using standardized protocols in Bowen’s disease (BD), superficial basal cell carcinoma (BCC) and in thin nodular BCC. However, long-term recurrence studies are lacking. The aim of this study was to evaluate the long-term efficacy of PDT with topical methylaminolevulinate (MAL) for the treatment of BD and BCC in a dermato-oncology department. Materials & Methods: All patients with the diagnosis of BD or BCC, treated with MAL-PDT from the years 2004 to 2008, were enrolled. Treatment protocol included two MAL-PDT sessions one week apart repeated at three months when incomplete response, using a red light dose of 37-40 J/cm2 and an exposure time of 8’20’’. Clinical records were retrospectively reviewed, and data regarding age, sex, tumour location, size, treatment outcomes and recurrence were registered. Descriptive analysis was performed using chi square tests, followed by survival analysis with the Kaplan-Meier and Cox regression models. Results: Sixty-eight patients (median age 71.0 years, P25;P75=30;92) with a total of 78 tumours (31 BD, 45 superficial BCC, 2 nodular BCC) and a median tumour size of 5 cm2 were treated. Overall, the median follow-up period was 43.5 months (P25;P75=0;100), and a total recurrence rate of 33.8% was observed (24.4 % for BCC vs. 45.2% for BD). Estimated recurrence rates for BCC and BD were 5.0% vs. 7.4% at 6 months, 23.4% vs. 27.9% at 12 months, and 30.0% vs. 72.4% at 60 months. Both age and diagnosis were independent prognostic factors for recurrence, with significantly higher estimated recurrence rates in patients with BD (p=0.0036) or younger than 58 years old (p=0.039). The risk of recurrence (hazard ratio) was 2.4 times higher in patients with BD compared to superficial BCC (95% CI:1.1-5.3; p=0.033), and 2.8 times higher in patients younger than 58 years old (95% CI:1.2-6.5; p=0.02). Conclusions: In the studied population, estimated recurrence rates are higher than those expected from available literature, possibly due to a longer follow-up period. To the authors’ knowledge there is only one other study with a similar follow-up period, regarding BCC solely. BD, as an in situ squamous cell carcinoma, has a higher tendency to recur than superficial BCC. Despite greater cosmesis, PDT might no be the best treatment option for young patients considering their higher risk of recurrence.

PREVALENCE OF ANTIBODIES AGAINST INFLUENZA VIRUS IN NON-VACCINATED EQUINES FROM THE BRAZILIAN PANTANAL

The prevalence of antibodies against Equine Influenza Virus (EIV) was determined in 529 equines living on ranches in the municipality of Poconé, Pantanal area of Brazil, by means of the hemagglutination inhibition test, using subtype H3N8 as antigen. The distribution and possible association among positive animal and ranches were evaluated by the chi-square test, spatial autoregressive and multiple linear regression models. The prevalence of antibodies against EIV was estimated at 45.2% (95% CI 30.2 - 61.1%) with titers ranging from 20 to 1,280 HAU. Seropositive equines were found on 92.0% of the surveyed ranches. Equine from non-flooded ranches (66.5%) and negativity in equine infectious anemia virus (EIAV) (61.7%) were associated with antibodies against EIV. No spatial correlation was found among the ranches, but the ones located in non-flooded areas were associated with antibodies against EIV. A negative correlation was found between the prevalence of antibodies against EIV and the presence of EIAV positive animals on the ranches. The high prevalence of antibodies against EIV detected in this study suggests that the virus is circulating among the animals, and this statistical analysis indicates that the movement and aggregation of animals are factors associated to the transmission of the virus in the region.

Esclonamento de máquinas de cogeração utilzando programação inteira mista

As centrais termoelétricas convencionais convertem apenas parte do combustível consumido na produção de energia elétrica, sendo que outra parte resulta em perdas sob a forma de calor. Neste sentido, surgiram as unidades de cogeração, ou Combined Heat and Power (CHP), que permitem reaproveitar a energia dissipada sob a forma de energia térmica e disponibilizá-la, em conjunto com a energia elétrica gerada, para consumo doméstico ou industrial, tornando-as mais eficientes que as unidades convencionais Os custos de produção de energia elétrica e de calor das unidades CHP são representados por uma função não-linear e apresentam uma região de operação admissível que pode ser convexa ou não-convexa, dependendo das caraterísticas de cada unidade. Por estas razões, a modelação de unidades CHP no âmbito do escalonamento de geradores elétricos (na literatura inglesa Unit Commitment Problem (UCP)) tem especial relevância para as empresas que possuem, também, este tipo de unidades. Estas empresas têm como objetivo definir, entre as unidades CHP e as unidades que apenas geram energia elétrica ou calor, quais devem ser ligadas e os respetivos níveis de produção para satisfazer a procura de energia elétrica e de calor a um custo mínimo. Neste documento são propostos dois modelos de programação inteira mista para o UCP com inclusão de unidades de cogeração: um modelo não-linear que inclui a função real de custo de produção das unidades CHP e um modelo que propõe uma linearização da referida função baseada na combinação convexa de um número pré-definido de pontos extremos. Em ambos os modelos a região de operação admissível não-convexa é modelada através da divisão desta àrea em duas àreas convexas distintas. Testes computacionais efetuados com ambos os modelos para várias instâncias permitiram verificar a eficiência do modelo linear proposto. Este modelo permitiu obter as soluções ótimas do modelo não-linear com tempos computationais significativamente menores. Para além disso, ambos os modelos foram testados com e sem a inclusão de restrições de tomada e deslastre de carga, permitindo concluir que este tipo de restrições aumenta a complexidade do problema sendo que o tempo computacional exigido para a resolução do mesmo cresce significativamente.

SURVIVAL, INDUCTION AND RESUSCITATION OF Vibrio cholerae FROM THE VIABLE BUT NON-CULTURABLE STATE IN THE SOUTHERN CARIBBEAN SEA

The causative agent of cholera, Vibrio cholerae, can enter into a viable but non-culturable (VBNC) state in response to unfavorable conditions. The aim of this study was to evaluate the in situ survival of V. cholerae in an aquatic environment of the Southern Caribbean Sea, and its induction and resuscitation from the VBNC state. V. cholerae non-O1, non-O139 was inoculated into diffusion chambers placed at the Cuare Wildlife Refuge, Venezuela, and monitored for plate, total and viable cells counts. At 119 days of exposure to the environment, the colony count was < 10 CFU/mL and a portion of the bacterial population entered the VBNC state. Additionally, the viability decreased two orders of magnitude and morphological changes occurred from rod to coccoid cells. Among the aquatic environmental variables, the salinity had negative correlation with the colony counts in the dry season. Resuscitation studies showed significant recovery of cell cultivability with spent media addition (p < 0.05). These results suggest that V. cholerae can persist in the VBNC state in this Caribbean environment and revert to a cultivable form under favorable conditions. The VBNC state might represent a critical step in cholera transmission in susceptible areas.

Contribuição ao estudo da mistura néon-azoto a baixas temperaturas

Dissertação para obtenção do Grau de Mestre em Engenharia Física

Adaptive Game Design Study of a fully adaptive framework

Adventure! The Paladin Order foi um projecto ambicioso que começou por ser desenvolvido como um video jogo completo. Tinha como objéctivo implementar uma ferramenta diferente que permitisse tornar o jogo completamente adaptativo às decisões do jogador tanto nas interacções e no diálogo com outras personagens, assim como no combate contra os variados inímigos do jogo. Devido à inexperiência do autor uma grande parte do tempo foi passado a estudar e a pesquisar várias possíveis soluções que permitissem criar um ambiente que fosse adaptativo de uma forma simples e interessante, não só para os programadores mas também para qualquer pessoa que fosse responsável por editar o diálogo e a história do jogo. Os resultados foram bastante interessantes, revelando um sistema que depende simultaneamente dos ficheiros de onde é retirado o diálogo, e de um sistema de personalidades que permite definir qual será o comportamento de qualquer objecto do jogo ou, pelo menos, como as outras personagens irão reagir. O produto final é uma ferramenta de bases sólidas que permite uma implementação relativamente simples de um sistema abrangente e adaptativo, com poucas falhas e apenas algumas questões de simplicidade de código.

On the track of β-lactam resistance: Studies on the regulation of methicillinresistance in Staphylococcus aureus

Dissertação para obtenção do Grau de Doutor em Biologia

CHEMOPROPHYLAXIS TO CONTROL LEPROSY AND THE PERSPECTIVE OF ITS IMPLEMENTATION IN BRAZIL: A PRIMER FOR NON-EPIDEMIOLOGISTS

The occurrence of leprosy has decreased in the world but the perspective of its elimination has been questioned. A proposed control measure is the use of post-exposure chemoprophylaxis (PEP) among contacts, but there are still questions about its operational aspects. In this text we discuss the evidence available in literature, explain some concepts in epidemiology commonly used in the research on this topic, analyze the appropriateness of implementing PEP in the context of Brazil, and answer a set of key questions. We argue some points: (1) the number of contacts that need to receive PEP in order to prevent one additional case of disease is not easy to be generalized from the studies; (2) areas covered by the family health program are the priority settings where PEP could be implemented; (3) there is no need for a second dose; (4) risk for drug resistance seems to be very small; (5) the usefulness of a serological test to identify a higher risk group of individuals among contacts is questionable. Given that, we recommend that, if it is decided to start PEP in Brazil, it should start on a small scale and, as new evidence can be generated in terms of feasibility, sustainability and impact, it could move up a scale, or not, for a wider intervention.

HEPATOCELLULAR CARCINOMA IN A NON-CIRRHOTIC PATIENT WITH SUSTAINED VIROLOGICAL RESPONSE AFTER HEPATITIS C TREATMENT

Chronic infection by hepatitis C virus (HCV) is one of the main risk factors for the development of liver cirrhosis and hepatocellular carcinoma. However, the emergence of hepatocellular carcinoma (HCC) in non-cirrhotic HCV patients, especially after sustained virological response (SVR) is an unusual event. Recently, it has been suggested that HCV genotype 3 may have a particular oncogenic mechanism, but the factors involved in these cases as well as the profile of these patients are still not fully understood. Thus, we present the case of a non-cirrhotic fifty-year-old male with HCV infection, genotype 3a, who developed HCC two years after treatment with pegylated-interferon and ribavirin, with SVR, in Brazil.

Non-clinical isolates bring new findings on enterococcal virulence

Dissertation presented to obtain the PhD degree in Biology

FACTORS RELATED TO ORAL CANDIDIASIS IN ELDERLY USERS AND NON-USERS OF REMOVABLE DENTAL PROSTHESES

This study examined the association between oral candidiasis in elderly users and nonusers of prosthesis and its predisposing factors. To this end, we performed a cross-sectional study where saliva samples from 48 patients were collected they used prosthesis and 43 patients (control group) who did not use. Among the 91 patients, Candida spp were isolated in 40 (83.3%) who used prosthesis and in 23 (53.5%) in the control group. A statistically significant association was determined between the two groups, the isolation of yeasts and dental prosthesis (p < 0.05, OR = 4.3). The most common etiological agent was Candida albicans (37 isolates), with 23 (62.2%) in the denture group and 14 (37.8%) (control group). Among patients who presented clinical manifestations of oral candidiasis (n = 24), 83.3% (n = 20) belonged to the group that wore dentures, while only 16.7% (n = 4) belonged to the control group. Elderly patients with diabetes had 4.4 times higher estimated risk of developing oral candidiasis when compared with individuals without this condition. There was no statistically significant association between being user prostheses and have diabetes with the onset of candidiasis. No statistically significant association was determined between xerostomia, use of prosthesis and oral candidiasis. The use of prosthetics and poor oral hygiene in elderly patients predisposes to the development of oral candidiasis.

Optimal Cut-Off Value for Homeostasis Model Assessment (HOMA) Index of Insulin-Resistance in a Population of Patients Admitted Electively in a Portuguese Cardiology Ward

INTRODUCTION: Insulin resistance is the pathophysiological key to explain metabolic syndrome. Although clearly useful, the Homeostasis Model Assessment index (an insulin resistance measurement) hasn't been systematically applied in clinical practice. One of the main reasons is the discrepancy in cut-off values reported in different populations. We sought to evaluate in a Portuguese population the ideal cut-off for Homeostasis Model Assessment index and assess its relationship with metabolic syndrome. MATERIAL AND METHODS: We selected a cohort of individuals admitted electively in a Cardiology ward with a BMI < 25 Kg/m2 and no abnormalities in glucose metabolism (fasting plasma glucose < 100 mg/dL and no diabetes). The 90th percentile of the Homeostasis Model Assessment index distribution was used to obtain the ideal cut-off for insulin resistance. We also selected a validation cohort of 300 individuals (no exclusion criteria applied). RESULTS: From 7 000 individuals, and after the exclusion criteria, there were left 1 784 individuals. The 90th percentile for Homeostasis Model Assessment index was 2.33. In the validation cohort, applying that cut-off, we have 49.3% of individuals with insulin resistance. However, only 69.9% of the metabolic syndrome patients had insulin resistance according to that cut-off. By ROC curve analysis, the ideal cut-off for metabolic syndrome is 2.41. Homeostasis Model Assessment index correlated with BMI (r = 0.371, p < 0.001) and is an independent predictor of the presence of metabolic syndrome (OR 19.4, 95% CI 6.6 - 57.2, p < 0.001). DISCUSSION: Our study showed that in a Portuguese population of patients admitted electively in a Cardiology ward, 2.33 is the Homeostasis Model Assessment index cut-off for insulin resistance and 2.41 for metabolic syndrome. CONCLUSION: Homeostasis Model Assessment index is directly correlated with BMI and is an independent predictor of metabolic syndrome.

Atheroembolic Renal Disease As a Cause of Allograft Primary Non-Function

Atheroembolic renal disease, also referred to as cholesterol crystal embolization, is a rare cause of renal failure, secondary to occlusion of renal arteries, renal arterioles and glomerular capillaries with cholesterol crystals, originating from atheromatous plaques of the aorta and other major arteries. This disease can occur very rarely in kidney allografts in an early or a late clinical form. Renal biopsy seems to be a reliable diagnostic test and cholesterol clefts are the pathognomonic finding. However, the renal biopsy has some limitations as the typical lesion is focal and can be easily missed in a biopsy fragment. The clinical course of these patients varies from complete recovery of the renal function to permanent graft loss. Statins, acetylsalicyclic acid, and corticosteroids have been used to improve the prognosis. We report a case of primary allograft dysfunction caused by an early and massive atheroembolic renal disease. Distinctive histology is presented in several consecutive biopsies. We evaluated all the cases of our Unit and briefly reviewed the literature. Atheroembolic renal disease is a rare cause of allograft primary non -function but may become more prevalent as acceptance of aged donors and recipients for transplantation has become more frequent.

Evolutive pattern of schistosomiasis and life-span of S. mansoni in patients living in non-endemic area in Brazil

Out of 2484 patients harboring S. mansoni seen in Rio de Janeiro, 1197 had been living permanently out of endemic area frorn one to 30 years, without any possibility of reinfection; 90.1% of these 1197 patients were first seen with, hepato-intestinal schistosomiasis and only 9.9% with hepatosplenic form. 55% of thern still had S. mansoni active infection 6 years or more after they had left the endemic area and 26.5% remained infected for more than 10 years. The patients with intestinal or hepato-intestinal schistosomiasis did not develop the most severe form whether they had been treated or not, and the hepatosplenic patients had a long time to deteriorate.

Non-Progressive Leukoencephalopathy with Bilateral Temporal Cysts

We report two cases of a peculiar leukoencephalopathy with temporal cysts. Both patients have a non-progressive neurological disorder with mental retardation, microcephaly and sensorineural deafness although clinical differences between them may reflect a different aetiology. The metabolic disorders with white matter involvement and the recently described leukoencephalopathies (Van Der Knaap disease, 'vanishing white matter disease') were excluded based on clinical, biologic and imaging findings. Cytomegalovirus infection is a likely possibility in the first case although the magnetic resonance imaging picture is only partially similar to previously reported cases. Our patients are strikingly similar to the patients reported by Deonna et al. and Olivier et al. We discuss the clinical and imaging findings in our patients and the differential diagnosis considering the known disorders of the white matter in childhood.