Development of novel active pharmaceutical ionic liquids and salts based on antibiotics and anti-fungal drugs

Ionic Liquids (ILs) are class of compounds, which have become popular since the mid-1990s. Despite the fact that ILs are defined by one physical property (melting point), many of the potential applications are now related to their biological properties. The use of a drug as a liquid can avoid some problems related to polymorphism which can influence a drug´s solubility and thus its dosages. Also, the arrangement of the anion or cation with a specific drug might be relevant in order to: a) change the correspondent biopharmaceutical drug classification system; b) for the drug formulation process and c) the change the Active Pharmaceutical Ingredients’ (APIs). The main goal of this Thesis is the synthesis and study of physicochemical and biological properties of ILs as APIs from beta-lactam antibiotics (ampicillin, penicillin G and amoxicillin) and from the anti-fungal Amphotericin B. All the APIs used here were neutralized in a buffer appropriate hydroxide cations. The cation hydroxide was obtained on Amberlite resin (in the OH form) in order to exchange halides. The biological studies of these new compounds were made using techniques like the micro dilution and colorimetric methods. Overall a total of 19 new ILs were synthesised (6 ILs based on ampicillin, 4 ILs, based on amoxicillin, 6 ILs based on penicillin G and 4 ILs based on amphotericin B) and characterized by spectroscopic and analytical methods in order to confirm their structure and purity. The study of the biological properties of the synthesised ILs showed that some have antimicrobial activity against bacteria and yeast cells, even in resistant bacteria. Also this work allowed to show that ILs based on ampicillin could be used as anti-tumour agents. This proves that with a careful selection of the organic cation, it is possible to provoke important physico-chemical and biological alteration in the properties of ILs-APIs with great impact, having in mind their applications.

State detection in a financial portfolio: a self-organizing maps approach for financial time series

This study analyses financial data using the result characterization of a self-organized neural network model. The goal was prototyping a tool that may help an economist or a market analyst to analyse stock market series. To reach this goal, the tool shows economic dependencies and statistics measures over stock market series. The neural network SOM (self-organizing maps) model was used to ex-tract behavioural patterns of the data analysed. Based on this model, it was de-veloped an application to analyse financial data. This application uses a portfo-lio of correlated markets or inverse-correlated markets as input. After the anal-ysis with SOM, the result is represented by micro clusters that are organized by its behaviour tendency. During the study appeared the need of a better analysis for SOM algo-rithm results. This problem was solved with a cluster solution technique, which groups the micro clusters from SOM U-Matrix analyses. The study showed that the correlation and inverse-correlation markets projects multiple clusters of data. These clusters represent multiple trend states that may be useful for technical professionals.

A built-in self-test technique for high speed analog-to-digital converters

Fundação para a Ciência e a Tecnologia (FCT) - PhD grant (SFRH/BD/62568/2009)

Indexing and active fund management: International evidence

Author's pre-print

A qualidade de vida e a satisfação dos utentes em unidades de internamento da Rede Nacional de Cuidados Continuados Integrados (RNCCI)

RESUMO - Enquadramento: Com o aumento da Esperança Média de Vida, e o consequente envelhecimento generalizado da população portuguesa, envelhecer com boa saúde e com elevada qualidade de vida, onde as pessoas com mais de 65 anos tenham a possibilidade de expressar todas as suas potencialidades e manterem um papel ativo na sua vida e na sociedade, é vincadamente um dos maiores desafios da sociedade contemporânea. Desta forma, foi imposto à sociedade e aos sistemas de saúde, a criação de novas estratégias, que promovessem a reabilitação, a autonomia e a qualidade de vida dos idosos. Nesta linha, surgiu em Portugal a criação da Rede Nacional de Cuidados Continuados Integrados, combinando os cuidados de saúde com o apoio social adequado a esta população. Objetivos: Num primeiro objetivo, pretende-se avaliar os diferentes domínios da autoperceção de qualidade de vida de indivíduos com idade igual ou superior a 65 anos, que se encontrem em período de internamento nas diferentes tipologias de Unidades de internamento da RNCCI (Unidade de Convalescença, Unidade de Média Duração e Reabilitação e Unidade de Longa Duração e Manutenção), bem como o seu grau de (in) dependência, de risco de falha de auto-cuidado, e de risco de quedas. Como segundo objetivo propomo-nos a avaliar o grau de satisfação desses mesmos utentes, relativamente à equipa de profissionais de saúde e aos aspetos organizacionais e serviços prestados pela Unidade da RNCCI, onde se encontram internados. Por último, pretendemos averiguar a existência ou inexistência de relação entre as demais variáveis em estudo com a tipologia de Unidade de internamento onde o utente se encontra a receber cuidados. Métodos: O presente estudo é caraterizado como um estudo quantitativo, de caráter exploratório, e de índole descritivo-correlacional, que visa descrever fenómenos e, posteriormente, identificar e explorar possíveis relações entre variáveis. O estudo centrou-se em indivíduos, com idade igual ou superior a 65 anos, internados em Unidades de Cuidados Continuados da Rede Nacional de Cuidados Continuados Integrados, tendo sido efetuados dois questionários distintos: um de satisfação, e um segundo instrumento de perceção da qualidade de vida, denominado de EasyCare, estando este já cientificamente validado a nível internacional e nacional. Foi obtida uma amostra de 35 utentes.

Nutritional assessment and lipid profile in HIV-infected children and adolescents treated with highly active antiretroviral therapy

INTRODUCTION: HIV-infected children and adolescents treated with highly active antiretroviral therapy (HAART) regimens that include a protease inhibitor (PI) can show significant improvements in clinical outcomes, nutritional status and quality of life. The study aimed to report nutritional and metabolic alterations for pediatric patients continuously exposed to HAART and for healthy controls for up to 1 year. METHODS: Clinical, anthropometric, lipid profile and food intake data were collected prospectively over approximately 12-months for each patient. RESULTS: Fifty-one individuals were studied, of these, 16 were healthy. After 12 months follow-up, HIV-positive individuals remained below the healthy control group parameters. No change was observed concerning food intake. Triglyceride serum levels were higher in patients using protease inhibitor at the onset of the study [PI groups: 114 (43 - 336), and 136 (63 - 271) versus control group: 54.5 (20 - 162); p = 0.003], but after twelve months follow-up, only the group using protease inhibitor for up to two months presented higher values [140 (73 - 273) versus 67.5 (33 - 117); p = 0.004]. HDL-cholesterol was lower in HIV-positive individuals [HIV-positive groups: 36 (27 - 58) and 36 (23 - 43); control 49.5 (34 - 69); p = 0.004]. CONCLUSIONS: HIV-infected children and adolescents treated with highly active antiretroviral therapy showed compromised nutritional parameters compared to a paired healthy control group. Individuals using protease inhibitor presented worse triglyceride serum levels compared to their healthy counterparts.

Lipodystrophy in HIV/AIDS patients with different levels of physical activity while on antiretroviral therapy

INTRODUCTION: Lipodystrophy is related to the use of highly active antiretroviral therapy (HAART) and can cause aesthetic stigma and increase the risk of developing cardiovascular diseases. Physical activity may be a valid alternative for the treatment and prevention of lipodystrophy. However, few studies address this issue. The objective of this study was to assess lipodystrophy related to highly active antiretroviral therapy in HIV/AIDS patients with different physical activity habits. METHODS: The sample was composed of 42 HIV/AIDS patients taking HAART medication who were visiting the Counseling and Testing Center (CTC) in Presidente Prudente. The level of physical activity was obtained using the International Physical Activity Questionnaire (IPAQ); lipodystrophy was diagnosed using a self-report questionnaire that was administered to the patient and then followed up by medical confirmation. The percentage of trunk fat was estimated by dual X-Ray absorptiometry (DEXA). Information about sex, age, length of HAART treatment, CD4+ T lymphocyte count (CD4) and viral load was also collected. RESULTS: A higher prevalence of lipodystrophy was observed in the sedentary group when compared to the physically active group, which indicates that physical activity may be a protective factor in relation to the occurrence of lipodystrophy. The group that had a higher CD4 had a higher proportion of lipodystrophy and a higher proportion of younger and physically active individuals. The patients with lipodystrophy had a higher percentage of trunk fat and were more sedentary than active individuals. CONCLUSIONS: A physically active lifestyle has a protective effect against the occurrence of lipodystrophy related to HAART.

Enteric parasites in HIV-1/AIDS-infected patients from a Northwestern São Paulo reference unit in the highly active antiretroviral therapy era

INTRODUCTION: We describe the epidemiology of intestinal parasites in patients from an AIDS reference service in Northeastern São Paulo, Brazil. METHODS: Retrospective evaluation was done for all HIV-1/AIDS-positive patients whose Hospital de Base/São José do Rio Preto laboratorial analysis was positive for enteroparasites after diagnosis of HIV-1 infection, from January 1998 to December 2008. Statistical analysis was performed using the R statistical software version 2.4.1. The level of significance adopted was 5%. RESULTS: The most frequent protozoan was Isospora belli (4.2%), followed by Giardia lamblia (3.5%), Entamoeba coli (2.8%), and Cryptosporidium parvum (0.3%). Ancylostoma duodenale (1.4%) was the most frequently detected helminth, while Taenia saginata and Strongiloides stercoralis were found in 0.7% of the samples. The results showed that diarrhea was significantly associated with giardiasis and isosporiasis. However, no association was observed between CD4+ cell counts, viral load, and the characteristics of any particular parasite. CONCLUSIONS: Our data may be useful for further comparisons with other Brazilian regions and other developing countries. The data may also provide important clues toward improving the understanding, prevention, and control of enteric parasites around the world.

Self-initiation expatriation: A focus on Italian and Portuguese students

The purpose of this work project is to analyze the phenomenon of self-initiated expatriation (SIE) through its link to the Protean Career and Career Capital theories, focusing in particular on Italian and Portuguese students attending a Master in the business area. The main research questions are to understand the reasons driving the intention to expatriate, after the conclusion of the academic path, using three main categories (Adventure Motivation, Work Characteristic Motivation and instrumental Motivation) and the intention to repatriate. A sample of Italian and Portuguese students was obtained. Italians show a higher intention to expatriate relative to Portuguese; nevertheless, no other significant differences were found among the two populations, because of the similar cultural background and economic situation. Additionally, several heterogeneities were observed considering other clusters defined by Gender, Teaching Language of the Master and Past International Experiences, across the two nationalities. Furthermore, possible future researches and practical implications were discussed.

Active surveillance of American tegumentary leishmaniasis in endemic areas in rural Bolivia

INTRODUCTION: American tegumentary leishmaniasis (ATL), including mucocutaneous leishmaniasis (MCL) and localized cutaneous leishmaniasis (LCL), is endemic in Bolivia. We describe the results of active surveillance of ATL from 2001 to 2006 and assess demographic data related to ATL epidemiology in the Yungas valleys. METHODS: Community-based active ATL surveillance was performed by the institutions SERVIR, CÁRITAS, and the Health Services Department of La Paz, whose files were reviewed retrospectively. A cross-sectional survey was carried out to assess demographic data in two communities. RESULTS: Two thousand nine hundred nine cases of ATL were detected from 2001 to 2006: 2,488 (85.5%) corresponded to LCL and 421 (14.5%) to MCL. A reduction in the proportion of mucosal cases was observed between 2001 and 2006. The proportion of MCL cases increased with age and was higher among males (15.5% versus 12.1%, p=0.018). The rate of positivity via direct observation of the parasite in dermal scrapings and in parasite cultivation was significantly higher for LCL than for MCL (p<0.001 and p=0.009, respectively). The rate of reactivity in the leishmanin skin test was higher in the group with mucosal lesions (p=0.012). The cross-sectional survey showed that 40% of the families had emigrated from the Altiplano. CONCLUSIONS: It is necessary to undertake continuous case detection of ATL in the area, where the disease presents a high rate of mucosal cases. Increasing incidence seems to be associated with immigration and continuous deforestation to expand the crop-growing areas.

Leprosy in Buriticupu, state of Maranhão: active search in the general population

INTRODUCTION: This study was developed to evaluate the situation of leprosy in the general population of the municipality of Buriticupu, State of Maranhão, Brazil. METHODS: We used the method of active search to identify new cases from 2008 to 2010. Bacilloscopy of intradermal scrapings was performed in all patients with skin lesions compatible with leprosy, and histopathological examination in those who had doubts on the definition of the clinical form. RESULTS: The study included 19,104 individuals, with 42 patients diagnosed with leprosy after clinical examination, representing a detection rate of 219.84 per 100,000 inhabitants. The predominant clinical presentation was tuberculoid with 24 (57.1%) cases, followed by borderline with 11, indeterminate with four, and lepromatous with three cases. The study also allowed the identification of 81 patients with a history of leprosy and other skin diseases, such as pityriasis versicolor, dermatophytosis, scabies, vitiligo, and skin carcinoma. The binomial test showed that the proportion of cases in the headquarters was significantly higher than that in the villages (p = 0.04), and the generalized exact test showed that there was no association between age and clinical form (p = 0.438) and between age and gender (p = 0.083). CONCLUSIONS: The elevated detection rate defines the city as hyperendemic for leprosy; the active search for cases, as well as the organization of health services, is an important method for disease control.

Momentum risk: An approach following the correlations between active stocks

The momentum anomaly has been widely documented in the literature. However, there are still many issues where there is no consensus and puzzles left unexplained. One is that strategies based on momentum present a level of risk that is inconsistent with the diversification that it offers. Moreover, recent studies indicate that this risk is variable over time and mostly strategy-specific. This work project hypothesises and proves that this evidence is explained by the portfolio constitution of the momentum strategy over time, namely the covariance and correlation between companies in the top and down deciles and across them.

New focus of active transmission of Chagas disease in indigenous populations in the Peruvian Amazon basin

Introduction Several cases of acute Chagas disease (ACD) have been reported in the Peruvian Amazon basin. Methods The objective was to describe and investigate 6 ACD cases in children from indigenous Amazon communities in the province of Datem del Marañón in Loreto department (2006-2010). Results The mean age was 3.6 years. All patients had fever, 4/6 hepatomegaly, 2/6 splenomegaly, and 5/6 had trypomastigotes of Trypanosoma cruzi on thick smears. The fatality rate was 33.3%. Rhodnius pictipes and Rhodnius robustus adults were found inside the homes and in the peri-domiciles. Conclusions All cases reported were isolated cases. We report a new focus of ACD in indigenous populations.

Positive serology for viral hepatitis and donor self-exclusion in Southern Brazil

Introduction Despite the great advances in serological testing for transfusion-transmitted infections, the selection of blood donors by blood bank operators remains the only way to avoid transmission within the testing window period. Part of this selection is the self-exclusion form, on which the donors can exclude their blood from donation without any explanation. This study assessed the clinical and epidemiological characteristics related to positivity for viral hepatitis and to the use of the confidential self-exclusion (CSE) form. Methods This transversal study analyzed the data collected from blood donors' files in a hospital in Southern Brazil. Univariate and multivariate analyses identified the clinical and epidemiological variables related to positive serologies of viral hepatitis and to whether the donor was self-excluded. Results Of the 3,180 donors included in this study, 0.1% tested positive for HBsAg, 2.1% for anti-HBc, and 0.9% for anti-HCV. When the 93 donors with positive serologies for viral hepatitis were compared with those who were negative, a greater proportion of the positive serology group was found to have had a history of blood transfusions (OR=4.908; 95%CI=1.628 - 14.799; p<0.01), had repeatedly donated (OR=2.147; 95%CI=1.236 - 3.729; p<0.01), and used the CSE form for self-exclusion (OR=7.139; 95%CI=2.045 - 24.923; p<0.01). No variables were independently associated with self-exclusion. Conclusions A history of blood transfusion, repeated donations, and self-exclusion are factors that should be considered during viral hepatitis screenings in blood banks.

Active and latent tuberculosis in prisoners in the Central-West Region of Brazil

Introduction Jailed populations exhibit high rates of tuberculosis (TB) infection and active disease. Methods A cross-sectional study was performed to estimate the prevalence of latent and active TB and to identify factors associated with latent infection in inmates. Results The prevalence of latent TB was 49%, and the prevalence of active TB was 0.4%. The presence of a Bacille Calmette-Guérin (BCG) scar (prevalence ratio (PR)=1.65; 95% confidence interval (CI): 1.09-2.50; p=0.0162) and the World Health Organization (WHO) score for active TB in prisons (PR=1.07; 95% CI: 1.01-1.14; p=0.0181) were correlated with infection. Conclusions The identification of associated factors and the prevalence of latent and active TB allows the development of plans to control this disease in jails.