Mansonella ozzardi (Nematoda: Onchocercidae) in the riverine population of the Tefé River, State of Amazonia, Brazil

Introduction: This study assessed the prevalence of Mansonella ozzardi in riverine communities of the Tefé River, Amazonas, Brazil. Methods: The prevalence of M. ozzardi was estimated by microscopic examination of thick blood smears. Results: The M. ozzardi prevalence rate was 6.3% (19/300). Filarial infection was found in 8 of the 11 communities surveyed, with prevalence rates varying from 2.5% to 22.2%. Conclusions: Tefé is a region of oil and natural gas exploration, in which there is a high turnover of workers. Migration patterns may facilitate the dissemination of mansonelliasis to other regions.

Technical optimization of the synthesis of flavours

The goal of this thesis is the investigation and optimization of the synthesis of potential fragrances. This work is projected as collaboration between the University of Applied Sciences in Merseburg and the company Miltitz Aromatics GmbH in Bitterfeld‐Wolfen (Germany). Flavoured compounds can be synthesized in different ways and by various methods. In this work, methods like the phase transfer catalysis and the Cope‐rearrangement were investigated and applied, for getting a high yield and quantity of the desired substances and without any by‐products or side reactions. This involved the study of syntheses with different process parameters such as temperature, solvent, pressure and reaction time. The main focus was on Cope‐rearrangement, which is a common method in the synthesis of new potential fragrance compounds. The substances synthesized in this work have a hepta‐1,5‐diene‐structure and that is why they can easily undergo this [3,3]‐sigma tropic rearrangement. The lead compound of all research was 2,5‐dimethyl‐2‐vinyl‐4‐hexenenitrile (Neronil). Neronil is synthesized by an alkylation of 2‐methyl‐3‐butenenitrile with prenylchloride under basic conditions in a phase‐transfer system. In this work the yield of isolated Neronil is improved from about 35% to 46% by according to the execution conditions of the reaction. Additionally the amount of side product was decreased. This synthesized hexenenitrile involved not only the aforementioned 1,5‐diene‐structure, but also a cyano group, that makes this structure a suitable base for the synthesis of new potential fragrance compounds. It was observed that Neronil can be transferred into 2,5‐dimethyl‐2‐vinyl‐4‐hexenoic acid by a hydrolysis under basic conditions. After five hours the acid can be obtained with a yield of 96%. The following esterification is realized with isobutanol to produce 2,5‐dimethyl‐2‐vinyl‐4‐hexenoic acid isobutyl ester with quantitative conversion. It was observed that the Neronil and the corresponding ester can be converted into the corresponding Cope‐product, with a conversion of 30 % and 80%. Implementing the Cope‐rearrangement, the acid was heated and an unexpected decarboxylated product is formed. To achieve the best verification of reaction development and structure, scrupulous analyses were done using GC‐MS, 1H‐NMR and 13C‐ NMR.

Prevalence of neurocognitive disorders and depression in a Brazilian HIV population

AbstractINTRODUCTION:Combined antiretroviral therapy has enabled human immunodeficiency virus (HIV) carriers to live longer. This increased life expectancy is associated with the occurrence of degenerative diseases, including HIV-associated neurocognitive disorders (HAND), which are diagnosed via a complex neuropsychological assessment. The International HIV Dementia Scale (IHDS) is a screening instrument validated in Brazil for use in the absence of neuropsychological evaluation. HIV patients are frequently diagnosed with depression. We aimed to determine the prevalence of neurocognitive impairment using the IHDS and depressive disorders using the Hamilton Rating Scale for Depression (HAM-D17), compare the IHDS performance with the performances on the Timed Gait Test (TGT), the Digit Symbol Coding Test (DS) and the Brazilian version of the Scale of Instrumental Activities of Daily Living (IADL), and evaluate the association between the IHDS performance and clinical-demographic variables.METHODS:One hundred fourteen patients were evaluated in a cross-sectional study conducted in a public outpatient clinic for infectious diseases in Marília City, State of São Paulo, Brazil. Data were collected following consultation. Statistical analysis was performed in accordance with the nature and distribution of the data and hypotheses.RESULTS:According to the IHDS, 53.2% of the sampled patients were neuropsychologically impaired. According to the HAM-D17, 26.3% had depressive disorders. There were significant associations between the IHDS and the TGT and DS. Multiple regression analysis indicated that female gender, educational level, and cluster of differentiation 4 (CD4) levels were significantly and independently associated with neurocognitive impairment.CONCLUSIONS:The prevalence of neurocognitive impairment according to the IHDS is high and associated with female gender, education level, and low CD4 levels.

Synthesis of precursors of the rare 3-O-methylmannose polysaccharides present in Nontuberculous Mycobacteria

3-O-methylmannose polysaccharides (MMPs) are cytoplasmic carbohydrates synthesized by mycobacteria, which play important intracellular roles, such as for example in metabolism regulation. An important way to confirm if the inhibition of the synthesis of these polysaccharides will critically affect the survival of mycobacteria is the study of the biosynthetic pathways from these molecules on these microorganisms. The purpose of this work is the efficient synthesis of three saccharides, which are rare cellular precursors from the biosynthesis of the mycobacterial polysaccharides, allowing its study. In order to obtain these molecules, a chemical strategy to connect two precursors was used. This process is called chemical glycosylation and its importance will be highlighted as an important alternative to enzymatic glycosylation. The first objective was the synthesis of the disaccharides Methyl (3-O-methyl-α-D-mannopyranosyl)-(1→4)-3-O-methyl-α-D-mannopyranoside and (3-O-Methyl-α-D-mannopyra- nosyl)-(1→4)-3-O-methyl-(α/β)-D-mannopyranose. The mannose precursors were prepared before the glycosylation reaction. The same mannosyl donor was used in the preparation of both molecules and its efficient synthesis was achieved using a 8 step synthetic route from D-mannose. A different mannosyl acceptor was used in the synthesis of each disaccharide and their syntheses were also efficient, the first one a 4 step synthetic route from α-methyl-D-mannose and the second one as an intermediate from the synthesis of the mannosyl donor. The stereoselective preparation of these disaccharides was performed successfully. The second and last objective of the proposed work was the synthesis of the tetrasaccharide methyl (3-O-methyl-α-D-mannopyranosyl-(1→4)-3-O-methyl-α-D-mannopyra- nosyl-(1→4)-3-O-methyl-α-D-mannopyranosyl-(1→4)-3-O-methyl-α-D-mannopyranoside. The disaccharide acceptor and donor to be linked through a stereoselective glycosidic reaction had to be first synthesized. Several synthetic strategies were studied. Neither the precursors nor the tetrasaccharide were synthesized, but a final promising synthetic route for its preparation has been proposed.

Rifapentine for latent tuberculosis infection treatment in the general population and human immunodeficiency virus-positive patients: summary of evidence

AbstractLatent tuberculosis infection (LTBI) and human immunodeficiency virus (HIV)-coinfection are challenges in the control of tuberculosis transmission. We aimed to assess and summarize evidence available in the literature regarding the treatment of LTBI in both the general and HIV-positive population, in order to support decision making by the Brazilian Tuberculosis Control Program for LTBI chemoprophylaxis. We searched MEDLINE, Cochrane Library, Centre for Reviews and Dissemination, Embase, LILACS, SciELO, Trip database, National Guideline Clearinghouse, and the Brazilian Theses Repository to identify systematic reviews, randomized clinical trials, clinical guidelines, evidence-based synopses, reports of health technology assessment agencies, and theses that investigated rifapentine and isoniazid combination compared to isoniazid monotherapy. We assessed the quality of evidence from randomized clinical trials using the Jadad Scale and recommendations from other evidence sources using the Grading of Recommendations, Assessment, Development, and Evaluations approach. The available evidence suggests that there are no differences between rifapentine + isoniazid short-course treatment and the standard 6-month isoniazid therapy in reducing active tuberculosis incidence or death. Adherence was better with directly observed rifapentine therapy compared to self-administered isoniazid. The quality of evidence obtained was moderate, and on the basis of this evidence, rifapentine is recommended by one guideline. Available evidence assessment considering the perspective of higher adherence rates, lower costs, and local peculiarity context might support rifapentine use for LTBI in the general or HIV-positive populations. Since novel trials are ongoing, further studies should include patients on antiretroviral therapy.

Occurrence of Mansonella ozzardi diagnosed using a polycarbonate membrane in a riverside population of Lábrea in the Western Brazilian Amazon

Abstract: INTRODUCTION Mansonella ozzardi is a widely distributed filaria worm in the Amazon region. This study aimed to determine the prevalence of M. ozzardi infection in riverine communities of Lábrea municipality, Amazonas State, Brazil. METHODS A diagnostic blood filtration method in a polycarbonate membrane was used. RESULTS M. ozzardi was found in 50.3% of the sample, with the highest prevalence in farmers/fishermen (69.4%; χ 2 = -19.14, p<0.001). The prevalence was higher in longer-term residents (≥11 years; 60.2%). CONCLUSIONS M. ozzardi infection rates are high near the Purus River, much greater than those previously reported based on diagnosis using thick blood smears.

Study of the role of wall teichoic acids in the localization Staphylococcus aureus cell wall synthesis protein PBP4

The cell wall of Staphylococcus aureus is a highly complex network mainly composed of highly cross-linked peptidoglycan (PG) and teichoic acids (TAs), both important for the maintenance of the integrity and viability of bacteria. The penicillin binding proteins (PBPs), which catalyse the final stage of PG biosynthesis, are targets of β-lactam antibiotics and have been a key focus of antibacterial research. S. aureus has four native PBPs, PBP1-4 carried by both methicillin-sensitive (MSSA) and –resistant (MRSA) strains. PBP4 is required for the synthesis of the highly cross-linked PG and, as shown in recent studies, is essential for the expression of β-lactam resistance in community-acquired strains (CA-MRSA). This protein has a septal localization that seems to be spatially and temporally regulated by an unknown intermediate of the wall teichoic acids (WTA) biosynthesis pathway. Therefore, if WTA synthesis is compromised, PBP4 becomes dispersed throughout the entire cell membrane. The aim of this project was to identify the WTA precursor responsible for the septal recruitment of PBP4. In order to do so, inducible mutants of tarB and tarL genes in the background of NCTCPBP4-YFP were constructed allowing for the study of PBP4 localization in the presence and absence of these specific tar genes.With this work we were able to show that the absence of TarB or TarL leads to the delocalization of PBP4, indicating that TarL or a protein/WTA precursor whose localization/synthesis is dependent on TarL is responsible for the recruitment of PBP4.

Liver synthesis function in chronic asymptomatic or oligosymptomatic alcoholics: correlation with other liver tests

Liver function and its correlation with bilirubin and hepatic enzymes were evaluated in 30 male chronic asymptomatic or oligosymptomatic alcoholics admitted into the psychiatric hospital for detoxification and treatment of alcoholism. Hypoalbuminemia, lowered prothrombin activity, hypotransferrinemia and hypofibrinogenemia were detected in 32 %, 32 %, 28 %, and 24 % of patients, respectively. Transferrin was elevated in 8 %. Greater prevalence of hyperbilirubinemia was found in patients with lowered prothrombin activity, hypofibrinogenemia, or hypotransferrinemia. No correlation was found between serum bilirubin or aminotransferase levels and normal or elevated albumin levels, time or activity of prothrombin, and fibrinogen levels. Serum alkaline phosphatase was elevated in normoalbuminemics and gamma-glutamyltransferase in patients with lowered prothrombin activity. Hypoalbuminemia was associated with hypofibrinogenemia, hypotransferrinemia with elevated aspartate aminotransferase or gamma-glutamyltransferase, and hypertransferrinemia with elevation of alanine aminotransferase. These data indicated the occurrence of hepatic dysfunction due to liver damage caused directly by alcohol or by alcoholism-associated nutritional deficiencies.

Al-doped ZnO ceramic sputtering targets based on nanocrystalline powders produced by emulsion detonation synthesis – deposition and application as a transparent conductive oxide material

Transparent conducting oxides (TCOs) have been largely used in the optoelectronic industry due to their singular combination of low electrical resistivity and high optical transmittance. They are usually deposited by magnetron sputtering systems being applied in several devices, specifically thin film solar cells (TFSCs). Sputtering targets are crucial components of the sputtering process, with many of the sputtered films properties dependent on the targets characteristics. The present thesis focuses on the development of high quality conductive Al-doped ZnO (AZO) ceramic sputtering targets based on nanostructured powders produced by emulsion detonation synthesis method (EDSM), and their application as a TCO. In this sense, the influence of several processing parameters was investigated from the targets raw-materials synthesis to the application of sputtered films in optoelectronic devices. The optimized manufactured AZO targets present a final density above 99 % with controlled grain size, an homogeneous microstructure with a well dispersed ZnAl2O4 spinel phase, and electrical resistivities of ~4 × 10-4 Ωcm independently on the Al-doping level among 0.5 and 2.0 wt. % Al2O3. Sintering conditions proved to have a great influence on the properties of the targets and their performance as a sputtering target. It was demonstrated that both deposition process and final properties of the films are related with the targets characteristics, which in turn depends on the initial powder properties. In parallel, the influence of several deposition parameters in the film´s properties sputtered from these targets was investigated. The sputtered AZO TCOs showed electrical properties at room temperature that are superior to simple oxides and comparable to a reference TCO – indium tin oxide (ITO), namely low electrical resistivity of 5.45 × 10-4 Ωcm, high carrier mobility (29.4 cm2V-1s-1), and high charge carrier concentration (3.97 × 1020 cm-3), and also average transmittance in the visible region > 80 %. These superior properties allowed their successful application in different optoelectronic devices.

Salivary gland tumors in a Brazilian population: a retrospective study of 124 cases

Salivary gland tumors constitute a highly heterogeneous histopathologic group. There are few epidemiological studies of large series of benign and malignant salivary gland tumors in Brazil. MATERIAL AND METHODS: Hospital records of 124 patients with salivary gland tumors diagnosed from January 1993 to December 1999 were reviewed. The patients were analyzed according to gender, age, size, location, and histopathology of the tumor. RESULTS AND CONCLUSIONS: Patients with benign and malignant tumors presented with a mean age of 47.7 and 48.8 years, respectively. The frequency of benign tumors was 80% (n = 99) and malignant tumors 20% (n = 25). Tumors were localized in the parotid gland 71% (n = 88), in the submandibular gland 24% (n = 30), and in the minor salivary glands 5% (n = 6). The most common benign tumors were pleomorphic adenoma in 84% (n = 84) and Warthin's tumor in 13% (n = 13). Among malignant tumors, mucoepidermoid carcinoma was the most common in 52% (n = 13), adenoid cystic carcinoma occurred in 20% (n = 5), and carcinoma ex pleomorphic adenoma was detected in 12% (n = 3).

Systemic hypertension, diabetes mellitus, and dyslipidemia in relation to body mass index: evaluation of a Brazilian population

OBJECTIVE: To determine the prevalence of systemic hypertension, diabetes mellitus, hypercholesterolemia, and hypertriglyceridemia in a Brazilian population in relation to body mass index. METHOD: Retrospective evaluation of 1213 adults (mean age: 45.2 ± 12.8; 80.6% females) divided into groups according to body mass index [normal (18.5 - 24.4 kg/m²); overweight (25 - 29.9 kg/m²); grade 1 obesity (30 - 34.9 kg/m²); grade 2 obesity (35 - 39.9 kg/m²), and grade 3 obesity (> 40 kg/m²)]. The prevalence of hypertension, diabetes mellitus, hypercholesterolemia, and hypertriglyceridemia were analyzed in each group. The severity of cardiovascular risk was determined. High-risk patients were considered those reporting 2 or more of the following factors: systemic hypertension, HDL < 35 mg/dL, total cholesterol > 240 mg/dL, triglycerides > 200 mg/dL when HDL < 35 mg/dL, and glycemia > 126 mg/dL. Moderate-risk patients were those reporting 2 or more of the following factors: systemic hypertension, HDL < 45, triglycerides > 200 mg/dL, and total cholesterol > 200 mg/dL. RESULTS: The prevalence of systemic hypertension, diabetes mellitus, hypertriglyceridemia, and low HDL-cholesterol levels increased along with weight, but the prevalence of hypercholesterolemia did not. The odds ratio adjusted for gender and age, according to grade of obesity compared with patients with normal weight were respectively 5.9, 8.6, and 14.8 for systemic hypertension, 3.8, 5.8, and 9.2 for diabetes mellitus and 1.2, 1.3, and 2.6 for hypertriglyceridemia. We also verified that body mass index was positively related to cardiovascular high risk (P < .001) CONCLUSION: In our population, cardiovascular risk increased along with body mass index.

The burden of chronic low back pain in the adult Portuguese population : an epidemiological population-based study under the scope of Epireumapt

RESUMO: Nos países desenvolvidos a lombalgia é a condição músculo-­‐esquelética mais prevalente. Quando evolui para um quadro crónico é responsável por um encargo económico bastante considerável, não só em relação aos indivíduos, mas também para a sociedade. A lombalgia crónica é por isso uma das principais causas de perda de produtividade e de perda de independência económica, nomeadamente através do absenteísmo (ausência do trabalho), do presenteísmo (perda de produtividade no trabalho, devido à capacidade diminuída provocada pela lombalgia) e da incapacidade para trabalhar (invalidez permanente, total ou parcial). Até à data, em Portugal, a prevalência e carga social da lombalgia crónica eram desconhecidas. Até agora não existiam estudos populacionais de grande dimensão sobre este tema. O objetivo principal desta tese foi determinar a prevalência de lombalgia crónica, e também avaliar a carga social que esta tem na população adulta Portuguesa. O trabalho de investigação foi desenvolvido no âmbito do Estudo Epidemiológico de Doenças Reumáticas em Portugal (EpiReumaPt). Este foi o primeiro estudo de larga escala e de base populacional, que determinou a prevalência de doenças reumáticas e músculo-­‐ esqueléticas na população adulta portuguesa. Foi realizado numa amostra aleatória e representativa, de 10.661 indivíduos do Continente, da Região Autónoma dos Açores e da Região Autónoma da Madeira, entre Setembro de 2011 e Dezembro de 2013. Esta tese foi dividida em duas secções. A primeira secção incluiu o detalhe das questões relativas ao desenvolvimento e gestão do EpiReumaPt, constituindo-­‐se como um guia prático sobre como realizar um estudo de base populacional de larga escala, em Portugal. A metodologia detalhada do EpiReumaPt foi também descrita nesta secção e incluiu os objectivos, o desenho do estudo, as características de recrutamento e a preparação de dados para análise. Nesta secção foram ainda descritos os principais resultados do EpiReumaPt. Estes evidenciaram que a lombalgia foi a condição músculo-­‐esquelética com maior prevalência na população adulta portuguesa.A segunda secção desta tese estimou a prevalência da lombalgia crónica ativa na população adulta Portuguesa, e avaliou a carga social esta condição. A lombalgia ativa foi definida com base na dor auto-­‐relatada no dia da entrevista e que persistia há pelo menos 90 dias (independentemente da causa). A lombalgia foi definida como dor na área definida entre a margem inferior das décimas segundas costelas até às pregas glúteas inferiores, com ou sem dor nos membros inferiores. A carga social foi medida tendo em conta os seguintes parâmetros: qualidade de vida, função, consumo de recursos de saúde, consumo de analgésicos e outros fármacos usados no alívio da dor, sintomas de ansiedade e sintomas de depressão. Os resultados mostraram que o consumo de recursos em saúde e a carga social da lombalgia crónica na população adulta Português é significativa. Também a incapacidade causada pela lombalgia crónica,nos indivíduos com idade ativa, é responsável por elevadas taxas de absenteísmo e má qualidade de vida, aos quais acresce o consequente ónus socioeconómico. Esta tese também concluiu que o consumo de analgésicos e outros medicamentos para alívio da dor, na população adulta portuguesa com lombalgia crónica ativa, é relativamente baixa. A maioria destes indivíduos não tomava nenhum medicamento analgésico, independentemente da intensidade da dor. Mesmo os indivíduos que reportaram dor intensa, apenas 4.0% estavam no primeiro degrau da escada analgésica da Organização Mundial de Saúde; 2.3% usavam opióides fracos e 0.03% usavam opióides fortes para controlar a dor (segundo e terceiro degrau da escada analgésica da Organização Mundial da Saúde). O trabalho de investigação também confirmou que a prevalência de sintomas de ansiedade e depressão entre os indivíduos adultos portugueses com lombalgia crónica ativa é elevada. Nestes indivíduos, registou-­‐se um consumo mais elevado de analgésicos e outros medicamentos para alívio da dor, quando comparados com os indivíduos com lombalgia crónica activa sem esses sintomas psicológicos. Os grupos terapêuticos mais utilizados foram os ansiolíticos, sedativos e hipnóticos, os antidepressivos e os anti-­‐inflamatórios não esteróides. A intensidade média da dor reportada foi também maior entre os indivíduos com lombalgia ativa e sintomas de ansiedade e/ou depressão. Também nestes, foi reportada pior função e pior estado de saúde. Em relação ao consumo de recursos de saúde foram encontradas diferenças significativas entre as duas populações: os indivíduos com lombalgia ativa e sintomas psicológicos concomitantes registaram maior número de consultas de psiquiatria de outras especialidades médicas, assim como precisaram de mais apoio domiciliário nos 12 meses prévios à entrevista do EpiReumaPt. Foram também identificados os fatores associados a sintomas isolados de ansiedade, a sintomas isolados de depressão e a sintomas de ansiedade e depressão. Resumindo,esta tese permitiu concluir que a lombalgia crónica é um problema de saúde comum na população adulta portuguesa, contribuindo para um elevado grau de incapacidade e que consequentemente afeta o desempenho laboral e o bem-­‐estar dos indivíduos. A lombalgia crónica é também responsável por um consumo considerável de recursos de saúde. Acresce ainda que os sintomas de ansiedade e depressão são comuns, entre os indivíduos com lombalgia crónica, contribuindo com uma carga social adicional.---------------------------------- ABSTRACT:Low Back Pain(LBP) is the most prevalent of musculoskeletal condition in developed countries.When it becomes chronic, LBP causesan enormous economic burden on individuals and society -­‐ it is one of the leading causes of loss of productivity and economic independence through absenteeism (time off work), presenteeism (lost productivity because of diminished capacity while at work) and work disability (permanent, partial or complete disablement for work purposes). In Portugal the prevalence and burden of LBP and chronic LBP (CLBP) were poorly defined. Until now no large population-­‐based studies have focused on this. The main aim of this thesis was to determine the prevalence of LBP and CLBP, and also to assess the burden of CLBP in the adult rtuguese population. The research work was developed under the scope of EpiReumaPt (the Portuguese Epidemiologic Study of Rheumatic Diseases). EpiReumaPt was the first national large population-­‐based and prevalence study of rheumatic and musculoskeletal diseases (RMD). It was performed among a randomized and representative sample of 10,661 adult Portuguese subjects recruited in Mainland, Azores and Madeira Islands, from September 2011 to December 2013. The first section of this thesis included detailed issues regarding the development and management of EpiReumaPt, and provided a practical guide on how to set-­‐up a large population-­‐based study in Portugal. The detailed methodology of EpiReumaPt, including its objectives,study design,recruitment features,and data preparation for analyses were also described. The main results from EpiReumaPt study were provided in this section and showed that LBP was the musculoskeletal condition with highest prevalence among Portuguese population. The second section of this thesis estimated the prevalence of active CLBP among adult Portuguese population, and assessed the social burden of this condition. Active CLBP was defined based on self-­‐reported pain on the day of the interview, and for most of the time for at least 90 days (independently from cause). LBP was defined as pain in the back area from the lower margin of the twelfth ribs to he lower gluteal folds, with or without pain referred to the lower limbs. Social burden was measured taking into account the following outcomes: quality of life, function, healthcare resources consumption, analgesic and other pain relief drugs intake, anxiety and depression symptoms. Results showed that the healthcare consumption and social burden of CLBP among adult Portuguese population were enormous, and the disability caused by CLBP among subjects in a working age provides high rates of absenteeism (work loss) and poor quality of life, with a consequent socioeconomic burden. This thesis also concluded that analgesic and other pain relief drugs untake among adult Portuguese population with active CLBP was very low. Most of the subjects with active CLBP did not take any analgesic drug regardless pain severity. Even when subjects self-­‐reported severe pain, only 24.0% were in the 1st step of the analgesic ladder,2.3% used weak analgesic opioids and 0.03% used strong opioids (2nd and 3rd step of WHO analgesic ladder, respectively) to control pain . The research work also confirmed that the prevalence of anxiety and depression symptoms among adult Portuguese subjects with active CLBP was high. Regarding pharmacological therapy, the intake of analgesic and other pain relief drugs was higher among subjects with anxiety and/or depression symptoms, when compared with subjects without these psychological symptoms. Anxiolytics, sedatives and hypnotics, antidepressants and NSAIDs intake had higher usage rates among these subjects. The pain severity mean was also higher among this subjects and function and health status was worse. Regarding healthcare resources consumption,significant differences between the two populations were found. Subjects with ctive CLBP and concomitant psychological symptoms had a higher number of psychiatrist and other physician visits. They also needed more home care in the previous 12 months. Factors associated with isolated symptoms of anxiety, depression,and concomitant anxiety and depression symptoms were also identified. Summarizing, we concluded that CLBP is a common health problem among adult Portuguese population contributing to disability and affecting labor performance, and the well being of subjects. it is also responsible for considerable healthcare resource consumption. Anxiety and depression symptoms are common among subjects with CLBP and provided an additional burden among them.

Photochemical synthesis and functional transformations of bicyclic vinyl aziridines

Aziridines, a class of organic compounds containing a three membered heterocycle with a nitrogen atom, are extremely valuable molecules in organic and medicinal chemistry. They are frequently used as versatile precursors in the synthesis of natural products, and many biologically active molecules possess the aziridine moiety. The reactivity of aziridines has been studied, for example, in ring-opening reactions with thiols. However, not much interest seems to be given to reactions of aziridines in aqueous media, despite the numberless advantages of using water as solvent in organic chemistry. The nucleophilic ring-opening reaction of aziridines in aqueous media was here explored. Following the Kaplan aziridine synthetic methodology, in which pyridinium salts undergo a photochemical transformation to give bicyclic vinyl aziridines, new aziridines were synthetized. Their nucleophilic ring-opening reaction in water under physiological conditions was investigated and a range of sulphur, nitrogen, carbon and oxygen nucleophiles tested. Thiols, anilines and azide proved to be good nucleophiles to react with the aziridines, giving the ring-opening product in moderate to good yields. The best results were obtained with thiols, more specifically with cysteine-derived nucleophiles. Preliminary results show that these bicyclic vinyl aziridines can modify calcitonin, a peptide containing two cysteine amino acids residues, grating them the potential to be used in bioconjugation as ligands to cysteine-containing proteins, or even as enzyme inhibitors of, for example, cysteine proteases. Additionally, exploratory investigations suggest that the separation of both enantiomers of the bicyclic vinyl aziridine can be performed by taking advantage of an enzymatic methodology for the resolution of racemic secondary alcohols. Both enantiomers would be highly valuable as precursors in the synthesis of enantiomerically pure molecules, as no other method is currently reported for their separation.

Synthesis and antibiotic activity of some β-Carboline alkaloids

Nine β-carboline alkaloids were synthetized and screened for antibiotic activity. Six of the compounds testes showed inhibitory activity against one or more of the microorganisms assayed.