Radiometric studies on the oxidation of (U-14C) L-amino acids by drug-susceptible and drug-resistant mycobacteria

A radiometric assay system has been used to study oxidation patterns of (U-14C) L-amino acids by drug-susceptible and drug-resistant mycobacteria. Drug-susceptible M. tuberculosis (H37Rv TMC 102 and Erdman) along with the drug-resistant organism M. tuberculosis (H37 Rv TMC 303), M. bovis, M. avium, M. intracellulare, M. kansasii and M. chelonei were used. The organisms were inoculated into a sterile reaction system with liquid 7H9 medium and one of the (U-14C) L-amino acids. Each organism displayed a different pattern of amino acid oxidation, but these patterns were not distinctive enough for identification of the organism. Complex amino acids such as proline, phenylalanine and tyrosine were of no use in identification of mycobacteria, since virtually all organisms failed to oxidize them. There was no combination of substrates able to separate susceptible from resistant organisms.

Towards high-available and energy-efficient virtual computing environments in the cloud

Empowered by virtualisation technology, cloud infrastructures enable the construction of flexi- ble and elastic computing environments, providing an opportunity for energy and resource cost optimisation while enhancing system availability and achieving high performance. A crucial re- quirement for effective consolidation is the ability to efficiently utilise system resources for high- availability computing and energy-efficiency optimisation to reduce operational costs and carbon footprints in the environment. Additionally, failures in highly networked computing systems can negatively impact system performance substantially, prohibiting the system from achieving its initial objectives. In this paper, we propose algorithms to dynamically construct and readjust vir- tual clusters to enable the execution of users’ jobs. Allied with an energy optimising mechanism to detect and mitigate energy inefficiencies, our decision-making algorithms leverage virtuali- sation tools to provide proactive fault-tolerance and energy-efficiency to virtual clusters. We conducted simulations by injecting random synthetic jobs and jobs using the latest version of the Google cloud tracelogs. The results indicate that our strategy improves the work per Joule ratio by approximately 12.9% and the working efficiency by almost 15.9% compared with other state-of-the-art algorithms.

Herb-drug interactions among commonly used psychoactive substances by healthcare students

The concurrent use of herbs and/or nutritional supplements with psychoactive effect and prescription medications is common among college students. College students are a particularly vulnerable population, for they are under less social/familiar surveillance and seek greater independence, as well as under greater intellectual effort, stress, anxiety and depression, which predispose them to a higher consumption of psychoactive substances. Herbs, vitamins, and other dietary supplements may influence the effects of prescription and nonprescription drugs leading to adverse consequences, by increasing the potential for interactions. However, documented interactions between herbal medicinal products and prescribed drugs are rare. Objective: determine the prevalence of concomitant use of psychoactive substances among healthcare students in the Lisbon School of Health Technology, Portugal, in order to assess the risk of potential herb-drug interactions.

Plasmodium falciparum drug resistance in Angola

Facing chloroquine drug resistance, Angola promptly adopted artemisinin-based combination therapy as the first-line to treat malaria. Currently, the country aims to consolidate malaria control, while preparing for the elimination of the disease, along with others African countries in the region. However, the remarkable capacity of Plasmodium to develop drug resistance represents an alarming threat for those achievements. Herein, the available, but relatively scarce and dispersed, information on malaria drug resistance in Angola, is reviewed and discussed. The review aims to inform but also to encourage future research studies that monitor and update the information on anti-malarial drug efficacy and prevalence of molecular markers of drug resistance, key fields in the context and objectives of elimination.

Drug susceptibility of Plasmodium falciparum in the western Amazon region, state of Acre, Brazil

Field studies in the western Amazon region (state of Acre, Brazil) indicate that the 4-aminoquinolines, as well as the combined regimen with sulfadoxine-pyrimethamine, can no longer be recomended for the treatment and prophylaxis of P. falciparum infections in this region. Quinine remains an effective drug when used correctly. However, compliance problems arise due to the often occurring side-effects during a ten day regimen. Prospects of overcoming these constraints by combining a short course of quinine with other drugs are limited, because of the lack of suitable partner compounds. For this reason quinine/clindamycin appears to be a more practical therapy of P. falciparum malaria. In vitro data from this study suggest that mefloquine is another effective alternative for the treatment of falciparum malaria in this Amazon region.

Vigilância activa de eventos após vacinação

A vigilância de efeitos indesejáveis após a vacinação é complexa. Existem vários actores de confundimento que podem dar origem a associações espúrias, meramente temporais mas que podem provocar uma percepção do risco alterada e uma consequente desconfiança generalizada acerca do uso das vacinas. Com efeito as vacinas são medicamentos complexos com características únicas cuja vigilância necessita de abordagens metodológicas desenvolvidas para esse propósito. Do exposto se entende que, desde o desenvolvimento da farmacovigilância se tem procurado desenvolver novas metodologias que sejam concomitantes aos Sistemas de Notificação Espontânea que já existem. Neste trabalho propusemo-nos a desenvolver e testar um modelo de vigilância de reacções adversas a vacinas, baseado na auto-declaração pelo utente de eventos ocorridos após a vacinação e testar a capacidade de gerar sinais aplicando cálculos de desproporção a datamining. Para esse efeito foi constituída uma coorte não controlada de utentes vacinados em Centros de Saúde que foram seguidos durante quinze dias. A recolha de eventos adversos a vacinas foi efectuada pelos próprios utentes através de um diário de registo. Os dados recolhidos foram objecto de análise descritiva e análise de data-mining utilizando os cálculos Proportional Reporting Ratio e o Information Component. A metodologia utilizada permitiu gerar um corpo de evidência suficiente para a geração de sinais. Tendo sido gerados quatro sinais. No âmbito do data-mining a utilização do Information Component como método de geração de sinais parece aumentar a eficiência científica ao permitir reduzir o número de ocorrências até detecção de sinal. A informação reportada pelos utentes parece válida como indicador de sinais de reacções adversas não graves, o que permitiu o registo de eventos sem incluir o viés da avaliação da relação causal pelo notificador. Os principais eventos reportados foram eventos adversos locais (62,7%) e febre (31,4%).------------------------------------------ABSTRACT: The monitoring of undesirable effects following vaccination is complex. There are several confounding factors that can lead to merely temporal but spurious associations that can cause a change in the risk perception and a consequent generalized distrust about the safe use of vaccines. Indeed, vaccines are complex drugs with unique characteristics so that its monitoring requires specifically designed methodological approaches. From the above-cited it is understandable that since the development of Pharmacovigilance there has been a drive for the development of new methodologies that are concomitant with Spontaneous Reporting Systems already in place. We proposed to develop and test a new model for vaccine adverse reaction monitoring, based on self-report by users of events following vaccination and to test its capability to generate disproportionality signals applying quantitative methods of signal generation to data-mining. For that effect we set up an uncontrolled cohort of users vaccinated in Healthcare Centers,with a follow-up period of fifteen days. Adverse vaccine events we registered by the users themselves in a paper diary The data was analyzed using descriptive statistics and two quantitative methods of signal generation: Proportional Reporting Ratio and Information Component. themselves in a paper diary The data was analyzed using descriptive statistics and two quantitative methods of signal generation: Proportional Reporting Ratio and Information Component. The methodology we used allowed for the generation of a sufficient body of evidence for signal generation. Four signals were generated. Regarding the data-mining, the use of Information Component as a method for generating disproportionality signals seems to increase scientific efficiency by reducing the number of events needed to signal detection. The information reported by users seems valid as an indicator of non serious adverse vaccine reactions, allowing for the registry of events without the bias of the evaluation of the casual relation by the reporter. The main adverse events reported were injection site reactions (62,7%) and fever (31,4%).

Adapted Control Methods for Cerebral Palsy Users of an Intelligent Wheelchair

The development of an intelligent wheelchair (IW) platform that may be easily adapted to any commercial electric powered wheelchair and aid any person with special mobility needs is the main objective of this project. To be able to achieve this main objective, three distinct control methods were implemented in the IW: manual, shared and automatic. Several algorithms were developed for each of these control methods. This paper presents three of the most significant of those algorithms with emphasis on the shared control method. Experiments were performed by users suffering from cerebral palsy, using a realistic simulator, in order to validate the approach. The experiments revealed the importance of using shared (aided) controls for users with severe disabilities. The patients still felt having complete control over the wheelchair movement when using a shared control at a 50% level and thus this control type was very well accepted. Thus it may be used in intelligent wheelchairs since it is able to correct the direction in case of involuntary movements of the user but still gives him a sense of complete control over the IW movement.

Evolution of Drug Resistance: Insight on TEM -Lactamases Structure and Activity and Beta-Lactam Antibiotics

Extended-spectrum β-lactamases (ESBLs) prevalence was studied in the north of Portugal, among 193 clinical isolates belonging to citizens in a district in the boundaries between this country and Spain from a total of 7529 clinical strains. In the present study we recovered some members of Enterobacteriaceae family, producing ESBL enzymes, including Escherichia coli (67.9%), Klebsiella pneumoniae (30.6%), Klebsiella oxytoca (0.5%), Enterobacter aerogenes (0.5%), and Citrobacter freundii (0.5%). β-lactamases genes blaTEM, blaSHV, and blaCTX-M were screened by polymerase chain reaction (PCR) and sequencing approaches. TEM enzymes were among the most prevalent types (40.9%) followed by CTX-M (37.3%) and SHV (23.3%). Among our sample of 193 ESBL-producing strains 99.0% were resistant to the fourth-generation cephalosporin cefepime. Of the 193 isolates 81.3% presented transferable plasmids harboring genes. Clonal studies were performed by PCR for the enterobacterial repetitive intragenic consensus (ERIC) sequences. This study reports a high diversity of genetic patterns. Ten clusters were found for E. coli isolates and five clusters for K. pneumoniae strains by means of ERIC analysis. In conclusion, in this country, the most prevalent type is still the TEM-type, but CTX-M is growing rapidly.

Nonlinear dynamics of the patient’s response to drug effect during general anesthesia

In today’s healthcare paradigm, optimal sedation during anesthesia plays an important role both in patient welfare and in the socio-economic context. For the closed-loop control of general anesthesia, two drugs have proven to have stable, rapid onset times: propofol and remifentanil. These drugs are related to their effect in the bispectral index, a measure of EEG signal. In this paper wavelet time–frequency analysis is used to extract useful information from the clinical signals, since they are time-varying and mark important changes in patient’s response to drug dose. Model based predictive control algorithms are employed to regulate the depth of sedation by manipulating these two drugs. The results of identification from real data and the simulation of the closed loop control performance suggest that the proposed approach can bring an improvement of 9% in overall robustness and may be suitable for clinical practice.

Utilização de PAM's e Medicamentos e/ou Produtos à base de Plantas pela População do Concelho de Bragança

Introdução: Entende-se por fitoterapia a terapêutica caracterizada pelo uso de plantas medicinais nas diferentes formas farmacêuticas com finalidade terapêutica, usada assim para prevenir, atenuar ou curar um estado patológico. Objetivos: Caracterizar a utilização de plantas aromáticas e medicinais (PAM´s), medicamentos e produtos à base de plantas pela população do concelho de Bragança, conhecer a fonte de indicação deste tipo de produtos, apurar a relação entre a fonte de indicação e o estado de saúde após a utilização, verificar a sua correta utilização relativa à indicação terapêutica, modo e frequência de utilização, identificar potenciais interacções medicamentosas, averiguar se os utentes informam o médico do seu uso, investigar a ocorrência de efeitos adversos e apurar a relação entre os efeitos adversos ocorridos e o género dos inquiridos. Métodos: Trata-se de um estudo observacional analítico-transversal. Nele participaram 404 indivíduos de ambos os géneros e com idades compreendidas entre os 18 e os 89 anos. A recolha de dados foi realizada entre os meses de abril e junho de 2014, através de um questionário estruturado de autopreenchimento, formado por 30 perguntas. Após a recolha dos dados procedeu-se à leitura óptica dos questionários, sendo os dados posteriormente exportados para SPSS permitindo assim o tratamento dos mesmos. Para análise estatística utilizou-se o teste do qui-quadrado considerando o nível de significância p <0,05. Resultados: Verificou-se que 53,7% dos inquiridos recorre terapeuticamente a PAM´s que inclui principalmente o uso de cidreira e camomila enquanto 33,8% faz uso de medicamentos e/ou produtos àbase de plantas nomeadamente Valdispert e Daflon. A utilização de PAM,s é motivada por autoconhecimento e indicação de familiares, amigos e vizinhos. Já os medicamentos e/ou produtos à base de plantas são utilizados maioritariamente por prescrição médica e indicação na farmácia. A ocorrência de efeitos indesejáveis foi sentida unicamente com a utilização de PAM´s e em pequena escala. Conclusão: O recurso a este tipo de produtos é uma prática bastante comum entre os moradores do concelho de Bragança, que utilizam uma grande diversidade de plantas e produtos à base de plantas para um variado leque de indicações terapêuticas, apontando a percentagem de respostas para um conhecimento dos seus efeitos terapêuticos.

Drug resistance of M. Tuberculosis isolated from patients with HIV infection seen at an AIDS Reference Center in São Paulo, Brazil

M. tuberculosis-positive cultures were obtained from 228 patients seen in our service and drug sensitivity assays were carried out from January 1992 to December 1994. A survey of the medical records of these patients showed resistance to one or more drugs in 47 (20.6%), 25 of whom (10.9%), who reported previous treatment, were considered to have acquired resistance. Among the antecedents investigated, only previous treatment and alcoholism were the factors independently associated with the occurrence of resistance. The survival of patients with resistant strains was lower than that of patients attacked by non-resistant M. tuberculosis. We conclude that in the present series M. tuberculosis resistance to tuberculostatic agents was predominantly of the acquired type.

The need for information literacy skills among users of European Union information

The aim of this paper is the assessment of information literacy skills related to European topics, among a group of 234 users of 55 European Documentation Centres (EDCs), from 21 European Union Member- States. We will present the results of a survey European information. So we will analyse the answers given by the users of the EDCs relating to aspects like the best sources to access trustworthy and impartial Europe information. The factors determining access to information on the EU and the frequency of this access will equally be analysed. The reasons the users gave for the ease or difficulty in accessing European information are also included and pondered on. Parallel to this, we will evaluate the aspects most valued by the users of this kind of information. Our findings on the use of European information available on the Internet, especially the knowledge and making use of databases will be presented. Based on this analysis the paper will demonstrate the need to develop information literacy competencies to identify, use and access European information. Doing so, some potential components of information literacy skills adapted to European information will be introduced.

Etiological drug treatment of human infection by Trypanosoma cruzi

Forty-nine American Trypanosomiasis (Chagas' disease) patients, with xenodiagnosis proven parasitemia were treated by the authors. Forty-one of these patients were given benznidazole, at dosages ranging from 5mg/kg/day to 8mg/kg/day, during a pre-established period of 60 days. In this group, 17 patients had an undetermined form of the disease, whereas 22 had cardiologic disease and 4 had digestive disease (two patients had a mixed form of the disease). Side effects were frequent, and led to the discontinuation of treatment in 17 patients. The follow-up period ranged from 1 to 20 years (mean follow-up period of 6 yrs. 7 mo). 26 (63.4%) of the patients became parasitemia-negative. The other eight patients were treated with nifurtimox, during 120 days, following a variable dose regime of 5mg/kg/day (initial dose) to 17 mg/kg/day (final dose). Six of them had severe side effects, and only one patient remained parasitemia-negative throughout the observation period (ranging from 1 to 18 years). Benznidazole proved to be better tolerated and more effective in the management of parasitemia when compared to nifurtimox, although more effective and less toxic drugs are still desirable.

Evolution of Drug Resistance: Insight on TEM β-Lactamases Structure and Activity and β-Lactam Antibiotics

Since the discovery of the first penicillin bacterial resistance to β-lactam antibiotics has spread and evolved promoting new resistances to pathogens. The most common mechanism of resistance is the production of β-lactamases that have spread thorough nature and evolve to complex phenotypes like CMT type enzymes. New antibiotics have been introduced in clinical practice, and therefore it becomes necessary a concise summary about their molecular targets, specific use and other properties. β-lactamases are still a major medical concern and they have been extensively studied and described in the scientific literature. Several authors agree that Glu166 should be the general base and Ser70 should perform the nucleophilic attack to the carbon of the carbonyl group of the β-lactam ring. Nevertheless there still is controversy on their catalytic mechanism. TEMs evolve at incredible pace presenting more complex phenotypes due to their tolerance to mutations. These mutations lead to an increasing need of novel, stronger and more specific and stable antibiotics. The present review summarizes key structural, molecular and functional aspects of ESBL, IRT and CMT TEM β-lactamases properties and up to date diagrams of the TEM variants with defined phenotype. The activity and structural characteristics of several available TEMs in the NCBI-PDB are presented, as well as the relation of the various mutated residues and their specific properties and some previously proposed catalytic mechanisms.