Graduate entry to medical studies: thoughts from 'down under' (editorial)

This invited editorial, reflecting on expectations of changing to graduate entry, eg enhanced maturity in the student cohort with greater self-sufficiency and taking of responsibility for learning in the context of adoption of a problem-based learning model, examines experiences of early post-change years and raises questions for contemplation by medical schools considering graduate entry.

Quality of life assessment in the community-dwelling elderly: Validation of the Assessment of Quality of Life (AQoL) Instrument and comparison with the SF-36

Measurement of Health-Related Quality of Life (HRQoL) of the elderly requires instruments with demonstrated sensitivity, reliability, and validity, particularly with the increasing proportion of older people entering the health care system. This article reports the psychometric properties of the 12-item Assessment of Quality of Life (AQoL) instrument in chronically ill community-dwelling elderly people with an 18-month follow-up. Comparator instruments included the SF-36 and the OARS. Construct validity of the AQoL was strong when examined via factor analysis and convergent and divergent validity against other scales. Receiver Operator Characteristic (ROC) curve analyses and relative efficiency estimates indicated the AQoL is sensitive, responsive, and had the strongest predicative validity for nursing home entry. It was also sensitive to economic prediction over the follow-up. Given these robust psychometric properties and the brevity of the scale, AQoL appears to be a suitable instrument for epidemiologic studies where HRQoL and utility data are required from elderly populations. (C) 2003 Elsevier Science Inc. All rights reserved.

Turkey's Accession to the European Union in terms of impact on the EU's security and defense policies: potential and drawbacks

This study explores the impact of Turkey's likely entry in the European Union (EU) in terms of the EU's foreign, security and defense policies. It reviews Turkish capabilities, namely its military capabilities, which could provide the EU with valuable defense assets. There are differences related to Turkey's relations with the EU, which have increasingly spilled over into the NATO, hindering the development of cooperation over crisis management operations. The article then delves in the implications of Turkey's strategic geographical location to EU policies. It reviews how far the EU and Turkey may have convergent interests in some of the neighboring regions, especially in the Middle East.

Extraction of hemoglobin with calixarenes and biocatalysis in organic media of the complex with pseudoactivity of peroxidase

The present work involves the use of p-tert-butylcalix[4,6,8]arene carboxylic acid derivatives ((t)Butyl[4,6,8]CH2COOH) for selective extraction of hemoglobin. All three calixarenes extracted hemoglobin into the organic phase, exhibiting extraction parameters higher than 0.90. Evaluation of the solvent accessible positively charged amino acid side chains of hemoglobin (PDB entry 1XZ2) revealed that there are 8 arginine, 44 lysine and 30 histidine residues on the protein surface which may be involved in the interactions with the calixarene molecules. The hemoglobin-(t)Butyl[6]CH2COOH complex had pseudoperoxidase activity which catalysed the oxidation of syringaldazine in the presence of hydrogen peroxide in organic medium containing chloroform. The effect of pH, protein and substrate concentrations on biocatalysis was investigated using the hemoglobin-(t)Butyl[6]CH2COOH complex. This complex exhibited the highest specific activity of 9.92 x 10(-2) U mg protein(-1) at an initial pH of 7.5 in organic medium. Apparent kinetic parameters (V'(max), K'(m), k'(cat) and k'(cat)/K'(m)) for the pseudoperoxidase activity were determined in organic media for different pH values from a Michaelis-Menten plot. Furthermore, the stability of the protein-calixarene complex was investigated for different initial pH values and half-life (t(1/2)) values were obtained in the range of 1.96 and 2.64 days. Hemoglobin-calixarene complex present in organic medium was recovered in fresh aqueous solutions at alkaline pH, with a recovery of pseudoperoxidase activity of over 100%. These results strongly suggest that the use of calixarene derivatives is an alternative technique for protein extraction and solubilisation in organic media for biocatalysis.

Modern epidemiology and its discontents

The goal of this article is to present a snapshot of an ongoing debate within epidemiology, pitching opposing sides in the struggle to define the path it should follow in the years to come. The debate among epidemiologists in the mid-90s pitted those who defended the idea that epidemiology should necessarily deal with a wide context against those who believed that science and public health are better served by focusing on the individual level. Ian Hacking’s concept of styles of reasoning was used as a theoretical tool. The literature was reviewed using a core set of articles as an entry point, seeking articles that cited them, and then back-tracking the citations of the resulting set in the Scopus database. The main arguments are presented according to levels (ontological, epistemological, axiological and pragmatic), in order to show an even deeper disagreement, in the very conception of science and its relation to social issues and public policy.

Exposure to acellular blood products and risk of HIV infection in hemophiliacs from Belo Horizonte, Brazil

Results of a HIV prevalence study conducted in hemophiliacs from Belo Horizonte, Brazil are presented. History of exposure to acellular blood components was determined for the five year period prior to entry in the study, which occurred during 1986 and 1987. Patients with coagulations disorders (hemophilia A = 132, hemophilia B = 16 and coagulation disorders other than hemophilia = 16) were transfused with liquid cryoprecipitate, locally produced, lyophilized cryoprecipitate, imported from São Paulo (Brazil) and factor VIII and IX, imported from Rio de Janeiro (Brazil), Europe, and United States. Thirty six (22%) tested HIV seropositive. The univariate and multivariate analysis (logistic model) demonstrated that the risk of HIV infection during the study period was associated with the total units of acellular blood components transfused. In addition, the proportional contribution of the individual components to the total acellular units transfused, namely a increase in factor VIII/IX and lyophilized cryoprecipitate proportions, were found to be associated with HIV seropositivity. This analysis suggest that not only the total amount of units was an important determinant of HIV infection, but that the risk was also associated with the specific component of blood transfused

Estudo de delaminação em compósitos de matriz polimérica

A aplicação do material compósito é neste momento bastante vasta, graças à combinação das suas características específicas, tais como, maior resistência específica e módulos específicos e melhor resistência à fadiga, quando comparados com os metais convencionais. Tais características, quando requeridas, tornam este material ideal para aplicações estruturais. Esta caminhada de sucesso iniciou desde muito cedo, quando o material compósito já era utilizado para fabrico de armas pelos mongóis e na construção civil pelos hebreus e egípcios, contudo, só a partir dos meados do século XX é que despertou interesses para aplicações mais modernas. Atualmente os materiais compósitos são utilizados em equipamentos domésticos, componentes elétricos e eletrónicos, passando por materiais desportivos, pela indústria automóvel e construção civil, até indústrias de grande exigência e visibilidade tecnológica como a aeronáutica, espacial e de defesa. Apesar das boas características apresentadas pelos materiais compósitos, no entanto, estes materiais têm tendência a perderem as suas propriedades quando submetidas a algumas operações de acabamento como a furação. A furação surge da necessidade de ligação de peças de um mesmo mecanismo. Os furos obtidos por este processo devem ser precisos e sem danos para garantir ligações de alta resistência e também precisas. A furação nos materiais compósitos é bastante complexa devido à sua heterogeneidade, anisotropia, sensibilidade ao calor e pelo facto de os reforços serem extremamente abrasivos. A operação de furação pode causar grandes danos na peça, como a delaminação a entrada, defeitos de circularidade do furo, danos de origem térmica e a delaminação à saída que se apresenta como o mais frequente e indesejável. Com base nesses pressupostos é que este trabalho foi desenvolvido de forma a tentar obter processos simples para determinação e previsão de danos em polímeros reforçados com fibras (de carbono neste caso) de forma a precavê-los. De forma a conseguir estes objetivos, foram realizados ensaios de início de delaminação segundo a proposta de Lachaud et al. e ensaios de pin-bearing segundo a proposta de Khashaba et al. Foram também examinadas extensões de danos de acordo com o modelo de Fator de delaminação ajustado apresentado por Davim et al. A partir dos ensaios, de pin-bearing, realizados foram analisadas influências do material e geometria da broca, do avanço utilizado na furação e de diferentes orientações de empilhamentos de placas na delaminação de laminados compósitos e ainda a influências dessas variáveis na força de rutura por pin-bearing. As principais conclusões tiradas daqui são que a delaminação aumenta com o aumento do avanço, o que já era esperado, as brocas em carboneto de tungsténio são as mais recomendas para a furação do material em causa e que a delaminação é superior para a placa cross-ply quando comparada com placas unidirecionais. Para a situação de ensaios de início de delaminação foram analisadas as influências da variação da espessura não cortada por baixo da broca/punção, de diferentes geometrias de brocas, da alteração de velocidade de ensaio e diferentes orientações de empilhamentos de placas na força de início de delaminação. Deste ensaio as principais conclusões são que a força de início de delaminação aumenta com o aumenta da espessura não cortada e a influência da velocidade de ensaio altera com a variação das orientações de empilhamento.

Welfare effects of entry into international markets with licensing

We study the effects of entry of a foreign firm on domestic welfare in the presence of licensing, when the entrant is technologically inferior to the incumbent. We show that foreign entry increases domestic welfare for intermediate (respectively, sufficiently large) technological differences between the firms under licensing with fixed fee (respectively, output royalty).

Rat hepatocyte invasion by Listeria monocytogenes and analysis of TNF-alpha role in apoptosis

Listeria monocytogenes, etiological agent of severe human foodborne infection, uses sophisticated mechanisms of entry into host cytoplasm and manipulation of the cellular cytoskeleton, resulting in cell death. The host cells and bacteria interaction may result in cytokine production as Tumor Necrosis Factor (TNF) alpha. Hepatocytes have potential to produce pro-inflammatory cytokines as TNF-alpha when invaded by bacteria. In the present work we showed the behavior of hepatocytes invaded by L. monocytogenes by microscopic analysis, determination of TNF-alpha production by bioassay and analysis of the apoptosis through TUNEL technique. The presence of bacterium, in ratios that ranged from 5 to 50,000 bacteria per cell, induced the rupture of cellular monolayers. We observed the presence of internalized bacteria in the first hour of incubation by electronic microscopy. The levels of TNF-alpha increased from first hour of incubation to sixth hour, ranging from 0 to 3749 pg/mL. After seven and eight hours of incubation non-significant TNF-alpha levels decrease occurred, indicating possible saturation of cellular receptors. Thus, the quantity of TNF-alpha produced by hepatocytes was dependent of the incubation time, as well as of the proportion between bacteria and cells. The apoptosis rate increased in direct form with the incubation time (1 h to 8 + 24 h), ranging from 0 to 43%, as well as with the bacteria : cells ratio. These results show the ability of hepatocyte invasion by non-hemolytic L. monocytogenes, and the main consequences of this phenomenon were the release of TNF-alpha by hepatocytes and the induction of apoptosis. We speculate that hepatocytes use apoptosis induced by TNF-alpha for release bacteria to extracellular medium. This phenomenon may facilitate the bacteria destruction by the immune system.

Co-infection between influenza virus and flagellated bacteria

Trypsin is required in the hemagglutinin (HA) cleavage to in vitro influenza viruses activation. This HA cleavage is necessary for virus cell entry by receptor-mediated endocytosis. Bacteria in the respiratory tract are potential sources of proteases that could contribute to the cleavage of influenza virus in vivo. From 47 samples collected from horses, pigs, and from humans, influenza presence was confirmed in 13 and these samples demonstrated co-infection of influenza with flagellated bacteria, Stenotrophomonas maltophilia from the beginning of the experiments. Despite treatment with antibiotics, the bacteria remained resistant in several of the co-infected samples (48.39%). These bacteria, considered opportunistic invaders from environmental sources, are associated with viral infections in upper respiratory tract of hosts. The protease (elastase), secreted by Stenotrophomonas maltophilia plays a role in the potentiation of influenza virus infection. Proteolytic activity was detected by casein agar test. Positive samples from animals and humans had either a potentiated influenza infectivity or cytopathic effect (CPE) in MDCK and NCI H292 cells, Stenotrophomonas maltophilia were always present. Virus and bacteria were observed ultrastructurally. These in vitro findings show that microbial proteases could contribute to respiratory complications by host protease activity increasing inflammation or destroying endogenous cell protease inhibitors.

High prevalence and association of HIV-1 non-B subtype with specific sexual transmission risk among antiretroviral naïve patients in Porto Alegre, RS, Brazil

In South Brazil the circulation of two HIV-1 subtypes with different characteristics represents an important scenario for the study of the impact of HIV-1 diversity on the evolution of the HIV-1 epidemic and AIDS disease. HIV-1 B, the predominant variant in industrialized countries and HIV-1 C, the most prevalent subtype in areas with rapid epidemic growth, are implicated in most infections. We evaluated blood samples from 128 antiretroviral (ARV) naïve patients recruited at entry to the largest HIV outpatient service in Porto Alegre. Based on partial pol region sequencing, HIV-1 C was observed in 29%, HIV-1 B in 22.6% and, the recently identified CRF31_BC, in 23.4% of 128 volunteers. Other variants were HIV-1 F in 10% and other mosaics in 5.5%. In order to evaluate the association of socio-behavioral characteristics and HIV-1 subtypes, interviews and laboratory evaluation were performed at entry. Our data suggest an established epidemic of the three major variants, without any evidence of partitioning in either of the subgroups analyzed. However, anal sex practices were associated with subtype B, which could indicate a greater transmissibility of non-B variants by vaginal intercourse. This study provides baseline information for epidemiologic surveillance of the changes of the molecular characteristics of HIV-1 epidemics in this region.

PREVALENCE OF HERPES SIMPLEX VIRUS TYPE 2 AND RISK FACTORS ASSOCIATED WITH THIS INFECTION IN WOMEN IN SOUTHERN BRAZIL

SUMMARY The herpes simplex virus type 2 (HVS-2) is the most prevalent infection worldwide. It is a cofactor in the acquisition of human immunodeficiency virus (HIV) and the persistence of human papillomavirus (HPV). This study evaluated the prevalence of HSV-2, using the polymerase chain reaction (PCR), and associated factors in patients treated at the Federal University of Rio Grande (FURG) and Basic Health Units (BHU) in Rio Grande, Brazil. The observed prevalence of HSV-2 was 15.6%. Among the 302 women studied, 158 had received assistance in BHU and 144 were treated at FURG. The prevalence of HSV-2 in these groups was 10.8% and 20.8%, respectively, RR 1.9 and p = 0.012. Knowledge about the Pap smear, and the presence of lesions showed no association with HSV-2 infection. Multivariate analysis showed that the variable that most influenced the risk of HSV-2 infection was the presence of HIV infection, with a relative risk of 1.9 and p = 0.04. Discussion: Genital ulcers are an important entry point for HIV, and condom use is an important strategy to reduce transmission of HIV and HSV-2.

Coreceptor Usage by HIV-1 and HIV-2 Primary Isolates: The Relevance of CCR8 Chemokine Receptor as an Alternative Coreceptor

The human immunodeficiency virus replication cycle begins by sequential interactions between viral envelope glycoproteins with CD4 molecule and a member of the seven-transmembrane, G-protein-coupled, receptors' family (coreceptor). In this report we focused on the contribution of CCR8 as alternative coreceptor for HIV-1 and HIV-2 isolates. We found that this coreceptor was efficiently used not only by HIV-2 but particularly by HIV-1 isolates. We demonstrate that CXCR4 usage, either alone or together with CCR5 and/or CCR8, was more frequently observed in HIV-1 than in HIV-2 isolates. Directly related to this is the finding that the non-usage of CXCR4 is significantly more common in HIV-2 isolates; both features could be associated with the slower disease progression generally observed in HIV-2 infected patients. The ability of some viral isolates to use alternative coreceptors besides CCR5 and CXCR4 could further impact on the efficacy of entry inhibitor therapy and possibly also in HIV pathogenesis.

First Diabetic Retinopathy Prevalence Study in Portugal: RETINODIAB Study-Evaluation of the Screening Programme for Lisbon and Tagus Valley Region

BACKGROUND/AIMS: In Portugal, so far, there is no study or even accurate data on the prevalence of diabetic retinopathy (DR), based on a large representative sample and on a long-term follow-up. The objective of our study was to determine the prevalence of DR based on a national screening community-based programme. METHODS: A 5-year retrospective analysis of the RETINODIAB screening programme results was implemented in Lisbon and Tagus Valley area between July 2009 and October 2014. We estimated the prevalence of retinopathy for all patients with type 2 diabetes and studied the association between known risk factors and retinopathy emergence at their first screening. RESULTS: Throughout this period, from a total of 103 102 DR readable screening examinations, 52 739 corresponded to patients who attended RETINODIAB screening at entry. Globally, DR was detected in 8584 patients (16.3%). Of these, 5484 patients (10.4%) had mild non-proliferative (NP) DR, 1457 patients (2.8%) had moderate NPDR and 672 (1.3%) had severe NPDR. Finally, 971 patients (1.8%) had proliferative DR requiring urgent referral to an ophthalmologist. The presence of any DR, non-referable DR or referable DR was strongly associated with increasing duration of diabetes and earlier age at diagnosis. CONCLUSIONS: The prevalence rate of DR in our study (16.3%) was slightly lower than other published international data. The RETINODIAB network proved to be an effective screening programme as it improved DR screening in Lisbon and Tagus Valley surrounding area

Baseline Susceptibility of Primary HIV-2 to Entry Inhibitors

BACKGROUND: The baseline susceptibility of primary HIV-2 to maraviroc (MVC) and other entry inhibitors is currently unknown. METHODS: The susceptibility of 19 HIV-2 isolates obtained from asymptomatic and AIDS patients and seven HIV-1 clinical isolates to the fusion inhibitors enfuvirtide (ENF) and T-1249, and to the coreceptor antagonists AMD3100, TAK-779 and MVC, was measured using a TZM-bl cell-based assay. The 50% inhibitory concentration (IC(50)), 90% inhibitory concentration (IC(90)) and dose-response curve slopes were determined for each drug. RESULTS: ENF and T-1249 were significantly less active on HIV-2 than on HIV-1 (211- and 2-fold, respectively). AMD3100 and TAK-779 inhibited HIV-2 and HIV-1 CXCR4 tropic (X4) and CCR5 tropic (R5) variants with similar IC(50) and IC(90) values. MVC, however, inhibited the replication of R5 HIV-2 variants with significantly higher IC(90) values (42.7 versus 9.7 nM; P<0.0001) and lower slope values (0.7 versus 1.3; P<0.0001) than HIV-1. HIV-2 R5 variants derived from AIDS patients were significantly less sensitive to MVC than variants from asymptomatic patients, this being inversely correlated with the absolute number of CD4(+) T-cells. CONCLUSIONS: T-1249 is a potent inhibitor of HIV-2 replication indicating that new fusion inhibitors might be useful to treat HIV-2 infection. Coreceptor antagonists TAK-779 and AMD3100 are also potent inhibitors of HIV-2 replication. The reduced sensitivity of R5 variants to MVC, especially in severely immunodeficient patients, indicates that the treatment of HIV-2-infected patients with MVC might require higher dosages than those used in HIV-1 patients, and should be adjusted to the disease stage.