Metabolic changes associated with antiretroviral therapy in HIV-positive patients

OBJECTIVE: To evaluate metabolic changes associated with highly active antiretroviral therapy (HAART) in HIV-positive patients, and to identify risk factors associated. METHODS: Retrospective study that included 110 HIV-positive patients who where on HAART in the city of Porto Alegre (Southern Brazil) between January 2003 and March 2004. Data on demographic variables, cigarette smoking, diabetes mellitus, cholesterol and triglyceride levels, stage of HIV infection, antiretroviral therapy and HCV coinfection were collected. General linear models procedure for repeated measures was used to test the interaction between HAART and HCV coinfection or protease inhibitor treatment. RESULTS: Total cholesterol, triglycerides, and glucose levels significantly increased after receiving HAART (p<0.001 for all variables), but no interaction with protease inhibitors was seen for total cholesterol, glucose and triglyceride levels (interaction treatment*protease inhibitors p=0.741, p=0.784, and p=0.081, respectively). An association between total cholesterol levels and HCV coinfection was found both at baseline and follow-up (effect of HCV coinfection, p=0.011). Glucose levels were increased by HAART (treatment effect, p=0.036), but the effect was associated to HCV coinfection (treatment*HCV effect, p=0.018). Gender, smoking habit, intravenous drug use and age were not significantly associated with cholesterol, triglyceride and glucose changes. CONCLUSIONS: HCV-infected patients at baseline were significantly less likely to develop hypercholesterolemia. The results provide further evidence of the role of HAART for the development of metabolic disturbances.

Ligand-Induced structural changes in TEM‑1 probed by molecular dynamics and relative binding free energy calculations

The TEM family of enzymes has had a crucial impact on the pharmaceutical industry due to their important role in antibiotic resistance. Even with the latest technologies in structural biology and genomics, no 3D structure of a TEM- 1/antibiotic complex is known previous to acylation. Therefore, the comprehension of their capability in acylate antibiotics is based on the protein macromolecular structure uncomplexed. In this work, molecular docking, molecular dynamic simulations, and relative free energy calculations were applied in order to get a comprehensive and thorough analysis of TEM-1/ampicillin and TEM-1/amoxicillin complexes. We described the complexes and analyzed the effect of ligand binding on the overall structure. We clearly demonstrate that the key residues involved in the stability of the ligand (hot-spots) vary with the nature of the ligand. Structural effects such as (i) the distances between interfacial residues (Ser70−Oγ and Lys73−Nζ, Lys73−Nζ and Ser130−Oγ, and Ser70−Oγ−Ser130−Oγ), (ii) side chain rotamer variation (Tyr105 and Glu240), and (iii) the presence of conserved waters can be also influenced by ligand binding. This study supports the hypothesis that TEM-1 suffers structural modifications upon ligand binding.

Structural stability of adenylate kinase from the sulfate-reducing bacteria Desulfovibrio gigas

Biophysical Chemistry 110 (2004) 83–92

Foresight methodologies to understand changes in the labour process. Experience from Portugal

The foresight and scenario building methods can be an interesting reference for social sciences, especially in terms of innovative methods for labour process analysis. A scenario – as a central concept for the prospective analysis – can be considered as a rich and detailed portrait of a plausible future world. It can be a useful tool for policy-makers to grasp problems clearly and comprehensively, and to better pinpoint challenges as well as opportunities in an overall framework. The features of the foresight methods are being used in some labour policy making experiences. Case studies developed in Portugal will be presented, and some conclusions will be drawn in order to organise a set of principles for foresight analysis applied to the European project WORKS on the work organisation re-structuring in the knowledge society, and on the work design methods for new management structures of virtual organisations.

The transformation of work? A quantitative evaluation of changes in work in Portugal

This report is made for the Work Package 15 of WORKS project and tries to develop more information on the Portuguese situation in the work structures changes in the recent years. It starts with an analysis of socio- economical indicators (Macro economical indicators, Employment indicators, Consumption, Technology at the workplace, Productivity), and then approaches the situation in terms of work flexibility in its dimensions of time use and New forms of work organisation. It traces employment in business functions with a sectoral and occupational approach, and analyses the occupational change in South Europe with particular relevance to Portugal (skill utilisation and job satisfaction, occupational and industrial mobility, quantitative evaluation of the shape of employment in Europe. Finaly are analysed the globalisation indicators.

Socioeconomic inequalities and changes in oral health behaviors among Brazilian adolescents from 2009 to 2012

OBJECTIVE To analyze oral health behaviors changes over time in Brazilian adolescents concerning maternal educational inequalities.METHODS Data from the Pesquisa Nacional de Saúde do Escolar(Brazilian National School Health Survey) were analyzed. The sample was composed of 60,973 and 61,145 students from 26 Brazilian state capitals and the Federal District in 2009 and 2012, respectively. The analyzed factors were oral health behaviors (toothbrushing frequency, sweets consumption, soft drink consumption, and cigarette experimentation) and sociodemographics (age, sex, race, type of school and maternal schooling). Oral health behaviors and sociodemographic factors in the two years were compared (Rao-Scott test) and relative and absolute measures of socioeconomic inequalities in health were estimated (slope index of inequality and relative concentration index), using maternal education as a socioeconomic indicator, expressed in number of years of study (> 11; 9-11; ≤ 8).RESULTS Results from 2012, when compared with those from 2009, for all maternal education categories, showed that the proportion of people with low toothbrushing frequency increased, and that consumption of sweets and soft drinks and cigarette experimentation decreased. In private schools, positive slope index of inequality and relative concentration index indicated higher soft drink consumption in 2012 and higher cigarette experimentation in both years among students who reported greater maternal schooling, with no significant change in inequalities. In public schools, negative slope index of inequality and relative concentration index indicated higher soft drink consumption among students who reported lower maternal schooling in both years, with no significant change overtime. The positive relative concentration index indicated inequality in 2009 for cigarette experimentation, with a higher prevalence among students who reported greater maternal schooling. There were no inequalities for toothbrushing frequency or sweets consumption.CONCLUSIONS There were changes in the prevalences of oral health behaviors during the analyzed period; however, these changes were not related to maternal education inequalities.

Spatio-temporal land use/land cover changes analysis and monitoring in the Valencia Municipality, Spain

Dissertation submitted in partial fulfilment of the requirements for the Degree of Master of Science in Geospatial Technologies

Protein folding, metal ions and conformational states: the case of a di-cluster ferredoxin

Dissertation presented to obtain the PhD degree in Biochemistry at the Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa

Study on the changes of soil chemical characteristics as result of prescribed fire

Every year, particularly during the summer period, the Portuguese forests are devastated by forest fire that destroys their ecosystems. So in order to prevent these forest fires, public and private authorities frequently use methods for the reduction of combustible mass as the prescribed fire and the mechanical vegetation pruning. All of these methods of prevention of forest fires alter the vegetation layer and/or soil [1-2]. This work aimed the study of the variation of some chemical characteristics of soil that suffered prescribed fire. The studied an area was located in the Serra of Cabreira (Figure 1) with 54.6 ha. Twenty sampling points were randomly selected and samples were collected with a shovel before, just after the prescribed fire, and 125 and 196 days after that event. The parameters that were studied were: pH, soil moisture, organic matter and iron, magnesium and potassium total concentration. All the analysis followed International Standard Methodologies. This work allowed to conclude that: a) after the prescribed fire; i) the pH remained practically equal to the the initial value; ii) occurred a slight increase of the average of the organic matter contents and iron total contents; b) at the end of the sampling period compared to the initial values; i) the pH didn´t change significantly; ii) the average of the contents of organic matter decreased; and iii) the average of the total contents of Fe, Mg and K increased.

Acquisition and data analysis related to changes in some forest soils properties after prescribed fire action

Controlled fires in forest areas are frequently used in most Mediterranean countries as a preventive technique to avoid severe wildfires in summer season. In Portugal, this forest management method of fuel mass availability is also used and has shown to be beneficial as annual statistical reports confirm that the decrease of wildfires occurrence have a direct relationship with the controlled fire practice. However prescribed fire can have serious side effects in some forest soil properties. This work shows the changes that occurred in some forest soils properties after a prescribed fire action. The experiments were carried out in soil cover over a natural site of Andaluzitic schist, in Gramelas, Caminha, Portugal, that had not been burn for four years. The composed soil samples were collected from five plots at three different layers (0-3cm, 3-6cm and 6-18cm) during a three-year monitoring period after the prescribed burning. Principal Component Analysis was used to reach the presented conclusions.

Liver morphology with emphasis on bile ducts changes and survival analysis in mice submitted to multiple Schistosoma mansoni infections and chemotherapy

In an attempt to be as close as possible to the infected and treated patients of the endemic areas of schistosomiasis (S. mansoni) and in order to achieve a long period of follow-up, mice were repeatedly infected with a low number of cercariae. Survival data and histological variables such as schistosomal granuloma, portal changes, hepatocellular necrosis, hepatocellular regeneration, schistosomotic pigment, periductal fibrosis and chiefly bile ducts changes were analysed in the infected treated and non treated mice. Oxamniquine chemotherapy in repeatedly infected mice prolonged survival significantly when compared to non-treated animals (chi-square 9.24, p = 0.0024), thus confirming previous results with a similar experimental model but with a shorter term follow-up. Furthermore, mortality decreased rapidly after treatment suggesting an abrupt reduction in the severity of hepatic lesions. A morphological and immunohistochemical study of the liver was carried out. Portal fibrosis, with a pattern resembling human Symmers fibrosis was present at a late phase in the infected animals. Bile duct lesions were quite close to those described in human Mansonian schistosomiasis. Schistosomal antigen was observed in one isolated altered bile duct cell. The pathogenesis of the bile duct changes and its relation to the parasite infection and/or their antigens are discussed.

Pliocene-quaternary upwelling in the SoutheasternAtlantic may reflect changes in water mass production

Proceedings of tile 1" R.C.A.N.S. Congress, Lisboa, October 1992

Coastal sedimentary environments and sea-level changes

A detailed knowledge of the 3-D arrangement and lateral facies relationships of the stacking patterns in coastal deposits is essential to approach many geological problems such as precise tracing of sea level changes, particularly during small scale fluctuations. These are useful data regarding the geodynamic evolution of basin margins and yield profit in oil exploration. Sediment supply, wave-and tidal processes, coastal morphology, and accommodation space generated by eustasy and tectonics govern the highly variable architecture of sedimentary bodies deposited in coastal settings. But these parameters change with time, and erosional surfaces may play a prominent role in areas located towards land. Besides, lateral shift of erosional or even depositional loci very often results in destruction of large parts of the sediment record. Several case studies illustrate some commonly found arrangements of facies and their distinguishing features. The final aim is to get the best results from the sedimentological analysis of coastal units.

Age-period-cohort effects in the incidence of hip fractures: political and economic events are coincident with changes in risk

Introduction: Healthcare improvements have allowed prevention but have also increased life expectancy, resulting in more people being at risk. Our aim was to analyse the separate effects of age, period and cohort on incidence rates by sex in Portugal, 2000–2008. Methods: From the National Hospital Discharge Register, we selected admissions (aged ≥49 years) with hip fractures (ICD9-CM, codes 820.x) caused by low/moderate trauma (falls from standing height or less), readmissions and bone cancer cases. We calculated person-years at risk using population data from Statistics Portugal. To identify period and cohort effects for all ages, we used an age–period–cohort model (1-year intervals) followed by generalised additive models with a negative binomial distribution of the observed incidence rates of hip fractures. Results: There were 77,083 hospital admissions (77.4 % women). Incidence rates increased exponentially with age for both sexes (age effect). Incidence rates fell after 2004 for women and were random for men (period effect). There was a general cohort effect similar in both sexes; risk of hip fracture altered from an increasing trend for those born before 1930 to a decreasing trend following that year. Risk alterations (not statistically significant) coincident with major political and economic change in the history of Portugal were observed around birth cohorts 1920 (stable–increasing), 1940 (decreasing–increasing) and 1950 (increasing–decreasing only among women). Conclusions: Hip fracture risk was higher for those born during major economically/politically unstable periods. Although bone quality reflects lifetime exposure, conditions at birth may determine future risk for hip fractures.

Molecular details of INH-C-10 binding to wt KatG and Its S315T mutant

Isoniazid (INH) is still one of the two most effective antitubercular drugs and is included in all recommended multitherapeutic regimens. Because of the increasing resistance of Mycobacterium tuberculosis to INH, mainly associated with mutations in the katG gene, new INH-based compounds have been proposed to circumvent this problem. In this work, we present a detailed comparative study of the molecular determinants of the interactions between wt KatG or its S315T mutant form and either INH or INH-C10, a new acylated INH derivative. MD simulations were used to explore the conformational space of both proteins, and results indicate that the S315T mutation did not have a significant impact on the average size of the access tunnel in the vicinity of these residues. Our simulations also indicate that the steric hindrance role assigned to Asp137 is transient and that electrostatic changes can be important in understanding the enzyme activity data of mutations in KatG. Additionally, molecular docking studies were used to determine the preferred modes of binding of the two substrates. Upon mutation, the apparently less favored docking solution for reaction became the most abundant, suggesting that S315T mutation favors less optimal binding modes. Moreover, the aliphatic tail in INH-C10 seems to bring the hydrazine group closer to the heme, thus favoring the apparent most reactive binding mode, regardless of the enzyme form. The ITC data is in agreement with our interpretation of the C10 alkyl chain role and helped to rationalize the significantly lower experimental MIC value observed for INH-C10. This compound seems to be able to counterbalance most of the conformational restrictions introduced by the mutation, which are thought to be responsible for the decrease in INH activity in the mutated strain. Therefore, INH-C10 appears to be a very promising lead compound for drug development.