MFS transporters required for multidrug/multixenobiotic (MD/MX) resistance in the model yeast: understanding their physiological function through post-genomic approaches

Multidrug/Multixenobiotic resistance (MDR/MXR) is a widespread phenomenon with clinical, agricultural and biotechnological implications, where MDR/MXR transporters that are presumably able to catalyze the efflux of multiple cytotoxic compounds play a key role in the acquisition of resistance. However, although these proteins have been traditionally considered drug exporters, the physiological function of MDR/MXR transporters and the exact mechanism of their involvement in resistance to cytotoxic compounds are still open to debate. In fact, the wide range of structurally and functionally unrelated substrates that these transporters are presumably able to export has puzzled researchers for years. The discussion has now shifted towards the possibility of at least some MDR/MXR transporters exerting their effect as the result of a natural physiological role in the cell, rather than through the direct export of cytotoxic compounds, and the hypothesis that MDR/MXR transporters may have evolved in nature for other purposes than conferring chemoprotection has been gaining momentum in recent years. This review focuses on the drug transporters of the Major Facilitator Superfamily (MFS; drug:H+ antiporters) in the model yeast Saccharomyces cerevisiae. New insights into the natural roles of these transporters are described and discussed here, focusing on the knowledge obtained or suggested by post-genomic research. The new information reviewed here provides clues into the unexpectedly complex roles of these transporters, including a proposed indirect regulation of the stress response machinery and control of membrane potential and/or internal pH, with a special emphasis on a genome-wide view of the regulation and evolution of MDR/MXR-MFS transporters

ALCOHOL- AND DRUG-RELATED CONTENTS IN THE NURSING PROGRAM AT ESPÍRITO SANTO FEDERAL UNIVERSITY: A CRITICAL ANALYSIS

The study was based on the project sponsored by the Organization of American States which wasdeveloped by São Paulo Federal University College of Nursing aiming at analyzing the alcohol- and drug-relatedcourse contents taught in undergraduate nursing programs in Brazil. Its purpose was to evaluate teachingconditions concerning this theme in the undergraduate nursing program at Espírito Santo Federal Universitythrough a descriptive survey applied to 86 nursing students. To 95% of the students, the problem related to theconsumption of alcohol and drugs is a theme of great interest. The inclusion of these themes in nursing programsis a facilitating condition for the education of nurses in this area

Visual contrast sensitivity in tonic-clonic epileptic patients

We measured the effects of epilepsy on visual contrast sensitivity to linear and vertical sine-wave gratings. Sixteen female adults, aged 21 to 50 years, comprised the sample in this study, including eight adults with generalized tonic-clonic seizure-type epilepsy and eight age-matched controls without epilepsy. Contrast threshold was measured using a temporal two-alternative forced-choice binocular psychophysical method at a distance of 150 cm from the stimuli, with a mean luminance of 40.1 cd/m². A one-way analysis of variance (ANOVA) applied to the linear contrast threshold showed significant differences between groups (F[3,188] = 14.829; p < .05). Adults with epilepsy had higher contrast thresholds (1.45, 1.04, and 1.18 times for frequencies of 0.25, 2.0, and 8.0 cycles per degree of visual angle, respectively). The Tukey Honestly Significant Difference post hoc test showed significant differences (p < .05) for all of the tested spatial frequencies. The largest difference between groups was in the lowest spatial frequency. Therefore, epilepsy may cause more damage to the neural pathways that process low spatial frequencies. However, epilepsy probably alters both the magnocellular visual pathway, which processes low spatial frequencies, and the parvocellular visual pathway, which processes high spatial frequencies. The experimental group had lower visual contrast sensitivity to all tested spatial frequencies

Comparative evolutionary patterns of Burkholderia cenocepacia and B. multivorans during chronic co-infection of a cystic fibrosis patient lung

During chronic respiratory infections of cystic fibrosis (CF) patients, bacteria adaptively evolve in response to the nutritional and immune environment as well as influence other infecting microbes. The present study was designed to gain insights into the genetic mechanisms underlying adaptation and diversification by the two most prevalent pathogenic species of the Burkholderia cepacia complex (Bcc), B. cenocepacia and B. multivorans. Herein, we study the evolution of both of these species during coinfection of a CF patient for 4.4 years using genome sequences of 9 B. multivorans and 11 B. cenocepacia. This co-infection spanned at least 3 years following initial infection by B. multivorans and ultimately ended in the patient’s death by cepacia syndrome. Both species acquired several mutations with accumulation rates of 2.08 (B. cenocepacia) and 2.27 (B. multivorans) SNPs/year. Many of the mutated genes are associated with oxidative stress response, transition metal metabolism, defense mechanisms against antibiotics, and other metabolic alterations consistent with the idea that positive selection might be driven by the action of the host immune system, antibiotic therapy and low oxygen and iron concentrations. Two orthologous genes shared by B. cenocepacia and B. multivorans were found to be under strong selection and accumulated mutations associated with lineage diversification. One gene encodes a nucleotide sugar dehydratase involved in lipopolysaccharide O-antigen (OAg) biosynthesis (wbiI). The other gene encodes a putative two-component regulatory sensor kinase protein required to sense and adapt to oxidative- and heavy metal- inducing stresses. This study contributes to understanding of shared and species-specific evolutionary patterns of B. cenocepacia and B. multivorans evolving in the same CF lung environment

Higiene, saúde e segurança no trabalho: enquadramento legal e análise de riscos na António & Manuel Coelho, Lda

O presente trabalho tem como pano de fundo o estudo da problemática ligada à área da Higiene e Segurança no Trabalho e o seu enquadramento legal na empresa António & Manuel Coelho, Lda. Encontra-se estruturado em quatro capítulos onde são abordadas várias temáticas, desde a higiene e segurança nas organizações, o enquadramento legal desde o licenciamento até à organização da higiene e segurança, os riscos profissionais, a avaliação e a prevenção de riscos profissionais, entre outras. A opção por este tema tem como impulso maior a fiscalização exercida neste âmbito por parte das entidades competentes, assim como se chegar à conclusão ser uma necessidade intrínseca à empresa. A metodologia adoptada passa pela identificação dos riscos através da lida diária com as actividades desenvolvidas na empresa, visto desempenhar cargo nesta, para além da verificação através de uma check-list apresentada durante o projecto desenvolvido. Um facto a ter em conta é que a empresa em análise não possui qualquer “organização” interna a nível de Saúde, Higiene e Segurança no Trabalho, sendo que o obrigatório por lei é cumprido por uma entidade externa que presta serviços à António & Manuel Coelho, Lda. Sendo que ainda não foi efectuada qualquer medição de ruído e sendo isso um risco patente na empresa, esta está em vias de efectuar essas medições para além de já fornecer auriculares aos trabalhadores. Neste sentido, muita coisa há ainda a fazer neste âmbito, tais como, o fornecimento de mais equipamento de protecção individual, formação e sensibilização dos trabalhadores, mais fiscalização e limpeza no local de trabalho. Em suma, podemos concluir que a Higiene e a Segurança no Trabalho são importantes para o bem-estar dos trabalhadores no seu ambiente de trabalho, pois contribuem para minimizar as condições de insalubridade e de periculosidade, dado que afectam, directa ou indirectamente, a produtividade do trabalhador, conduzindo a um maior ou menor desempenho e motivação no trabalho

Severe imported malaria in an intensive care unit: a review of 59 cases

<p>Abstract</p> <p>Background</p> <p>In view of the close relationship of Portugal with African countries, particularly former Portuguese colonies, the diagnosis of malaria is not a rare thing. When a traveller returns ill from endemic areas, malaria should be the number one suspect. World Health Organization treatment guidelines recommend that adults with severe malaria should be admitted to an intensive care unit (ICU).</p> <p>Methods</p> <p>Severe cases of malaria in patients admitted to an ICU were reviewed retrospectively (1990-2011) and identification of variables associated with in-ICU mortality performed. Malaria prediction score (MPS), malaria score for adults (MSA), simplified acute physiology score (SAPSII) and a score based on WHO's malaria severe criteria were applied. Statistical analysis was performed using StataV12.</p> <p>Results</p> <p>Fifty nine patients were included in the study, all but three were adults; 47 (79,6%) were male; parasitaemia on admission, quantified in 48/59 (81.3%) patients, was equal or greater than 2% in 47 of them (97.9%); the most common complications were thrombocytopaenia in 54 (91.5%) patients, associated with disseminated intravascular coagulation (DIC) in seven (11.8%), renal failure in 31 (52.5%) patients, 18 of which (30.5%) oliguric, shock in 29 (49.1%) patients, liver dysfunction in 27 (45.7%) patients, acidaemia in 23 (38.9%) patients, cerebral dysfunction in 22 (37.2%) patients, 11 of whom with unrousable coma, pulmonary oedema/ARDS in 22 (37.2%) patients, hypoglycaemia in 18 (30.5%) patients; 29 (49.1%) patients presented five or more dysfunctions. The case fatality rate was 15.2%. Comparing the four scores, the SAPS II and the WHO score were the most sensitive to death prediction. In the univariate analysis, death was associated with the SAPS II score, cerebral malaria, acute renal and respiratory failure, DIC, spontaneous bleeding, acidosis and hypoglycaemia. Age, partial immunity to malaria, delay in malaria diagnosis and the level of parasitaemia were not associated with death in this cohort.</p> <p>Conclusion</p> <p>Severe malaria cases should be continued monitored in the ICUs. SAPS II and the WHO score are good predictors of mortality in malaria patients, but other specific scores deserve to be studied prospectively.</p

Ability of Different Measures of Adiposity to Identify High Metabolic Risk in Adolescents

Introduction. This study aimed to evaluate the screening performance of different measures of adiposity: body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) for high metabolic risk in a sample of adolescents. Methods. A cross-sectional school-based study was conducted on 517 adolescents aged 15–18, from the Azorean Islands, Portugal. We measured fasting glucose, insulin, total cholesterol (TC), HDL-cholesterol, triglycerides, and systolic blood pressure. HOMA and TC/HDL-C ratio were calculated. For each of these variables, a Z-score was computed by age and sex. A metabolic risk score (MRS) was constructed by summing the Z-scores of all individual risk factors. High risk was considered when the individual had ≥1SD of this score. Receiver-operating characteristics (ROC) were used. Results. Linear regression analyses showed that, after adjusting for age and pubertal stage, all different measures of adiposity are positively and significantly associated with MRS in both sexes, with exception of WHtR for boys. BMI, WC, and WHtR performed well in detecting high MRS, indicated by areas under the curve (AUC), with slightly greater AUC for BMI than for WC and WHtR in both sexes. Conclusion. All measures of adiposity were significantly associated with metabolic risk factors in a sample of Portuguese adolescents

Water and wastewater monitoring of Guia Submarine Outfall: an 11 year survey

SANEST is a public sanitation company that manages a wastewater treatment plant located at Guia, on the west coast of Lisbon, Portugal. This company collects and treats the sewage of four municipalities with an estimated 750 000 population equivalent, thus being one of the biggest sanitation companies in Portugal. A Decision of the Commission 2001/720/CE conceded SANEST derogation, exempting it to apply less than secondary treatment to wastewaters discharged into the Atlantic Ocean from the four agglomerations. This decision was supported on a large monitoring program, presented to the EU, and set up by SANEST. It surveys the impact of the effluent disposal and includes measurements of physical, chemical, biological and microbiological properties in the effluent and in the receiving waters. This paper presents methods and results for the effluent chemical and microbiological quality as well as for the receiving waters and an ichthyofauna survey, and resumes an eleven year situation, with the preliminary wastewater treatment before effluent disposal. The WWTP results correspond to medium load urban effluents without treatment with temporal variability related to flood fluctuations. In the receiving waters almost legal values are respected and the plume of the outfall is only identifiable by faecal bacteria in the vicinity of the discharge. The fish community, in particular benthic species, has revealed a slight degradation probably due to the fact that pollutants tend preferentially to accumulate on sediment. The treatment plant is being upgraded to fulfil, by May 2009, an advanced primary treatment level that includes disinfection during the bathing season to fully observe the European Commission Decision 2001/720/EC

The reality of acoustic power emitted by therapeutic ultrasound equipment: a revision

The safety and efficiency of ultrasonic therapy may be compromised if the outlet power on the tranducer differs considerably from the value indicated on the equipment panel. This fact may be seen in the various publications which approach the referenced theme, where various studies determine that over 50% of equipment in routine use in clinics and physiotherapy departments are out of the specifications recommended by the International Electrotechinical Commission (IEC). This occurs as a result of the non regulation of technical production standards, the wear of the equipment itself in use and by the non adoption of routine metrological procedures on the part of the physiotherapist. The precision of the acoustic intensity would enable a more efficient therapy, besides the reproduction of protocols already defined in literature. Another important factor to be pointed out is the material used for coupling the ultrasonic transducer, where of the various means utilized, some propiciate the atenuation of irradiated energy. This revision intends to update the professional therapeutic ultrasound user, as well as make him aware of the need for adopting metrological measures for the equipment in use as routine practice.A segurança e a eficiência da terapia ultra-sônica poderá ser comprometida se a potência de saída no transdutor diferir consideravelmente do valor indicado no painel do equipamento. Este fato pode ser evidenciado nas várias publicações que abordam o referido tema, onde diversos estudos determinam que mais de 50% dos equipamentos, em uso rotineiro, nas clínicas e departamentos de fisioterapia estão fora das especificações postuladas pela International Eletrotechinical Commission (IEC) . Isso ocorre em função da não regulamentação das normas técnicas de produção, do próprio desgaste do equipamento em uso e pela não adoção de procedimentos metrológicos de rotina por parte do fisioterapeuta. A precisão da intensidade acústica irá possibilitar uma terapia mais eficiente, além da reprodução de protocolos já definidos na literatura. Outro importante fator a ser destacado é o material utilizado para o acoplamento do transdutor ultra-sônico, onde evidencia-se que dos vários meios utilizados, alguns propiciam a atenuação da energia irradiada. Esta revisão pretende atualizar o profissional usuário do ultra-som terapêutico, bem como conscientizá-lo da necessidade de adoção de medidas metrológicas como prática de rotina para os equipamentos em uso