Overcoming the heterologous bias: an in vivo functional analysis of multidrug efflux transporter, CgCdr1p in matched pair clinical isolates of Candida glabrata.

We have taken advantage of the natural milieu of matched pair of azole sensitive (AS) and azole resistant (AR) clinical isolates of Candida glabrata for expressing its major ABC multidrug transporter, CgCdr1p for structure and functional analysis. This was accomplished by tagging a green fluorescent protein (GFP) downstream of ORF of CgCDR1 and integrating the resultant fusion protein at its native chromosomal locus in AS and AR backgrounds. The characterization confirmed that in comparison to AS isolate, CgCdr1p-GFP was over-expressed in AR isolates due to its hyperactive native promoter and the GFP tag did not affect its functionality in either construct. We observed that in addition to Rhodamine 6 G (R6G) and Fluconazole (FLC), a recently identified fluorescent substrate of multidrug transporters Nile Red (NR) could also be expelled by CgCdr1p. Competition assays with these substrates revealed the presence of overlapping multiple drug binding sites in CgCdr1p. Point mutations employing site directed mutagenesis confirmed that the role played by unique amino acid residues critical to ATP catalysis and localization of ABC drug transporter proteins are well conserved in C. glabrata as in other yeasts. This study demonstrates a first in vivo novel system where over-expression of GFP tagged MDR transporter protein can be driven by its own hyperactive promoter of AR isolates. Taken together, this in vivo system can be exploited for the structure and functional analysis of CgCdr1p and similar proteins wherein the artefactual concerns encountered in using heterologous systems are totally excluded.

Clinical and radiographic findings in two brothers affected with a novel mutation in matrix metalloproteinase 2 gene.

The two well-described osteolysis syndromes associated with matrix metalloproteinase-2 deficiency and mutations in the metalloproteinase-2 gene are Torg-Winchester syndrome and nodulosis-arthropathy-osteolysis variant. They are characterized by carpal-tarsal destruction, subcutaneous nodules, and generalized osteoporosis and show autosomal recessive inheritance. Herein, we report two siblings affected with a novel mutation in matrix metalloproteinase 2 gene and discuss their clinical and radiographic findings.

Pressão social do grupo de pares na iniciação sexual de adolescentes

Dado que a literatura enfatiza a estreita relação entre o início da vida sexual e a pressão exercida pelos pares, o objetivo deste trabalho foi identificar a presença da pressão social na iniciação sexual de adolescentes, com base nos relacionamentos com o grupo de iguais. Participaram 363 pessoas, com idade entre 15 e 19 anos, compreendendo uma amostra representativa dos adolescentes cadastrados em uma unidade do Programa de Saúde da Família da cidade de São Paulo. Foi utilizado um questionário estruturado e auto-aplicado. Os resultados mostraram associação entre a iniciação sexual e idade, já ter ficado com alguém sem vontade, ter a maior parte dos amigos com experiência sexual e estar namorando, o que revelou indícios de que os pares parecem exercer certa influência na opção pela iniciação sexual.

POSSUM escore como preditor de mortalidade em pacientes cirúrgicos

O estudo avaliou a utilização do escore POSSUM (Physiological and Operative Severity Score for Enumeration of Mortality and Morbidity) para predizer a mortalidade na prática cirúrgica.Foram analisados 416 pacientes cirúrgicos com internação na UTI para cuidados de pós-operatório. Foram realizadas comparações entre as taxas de mortalidade predita e observada de acordo com 4 grupos de risco: 0-4%, 5-14%, 15-49%, 50% ou mais, e calculada a área sob a curva ROC do escore POSSUM e APACHE II para a mortalidade. A taxa de mortalidade foi de 22,4%. O escores POSSUM e APACHE II superestimaram o risco de morte, e a área sob a curva ROC do POSSUM foi de 0,762 e a do APACHE II de 0,737, sugerindo a utilização do POSSUM como ferramenta auxiliar na predição de risco de morte em pacientes cirúrgicos.

Sintomas de estresse e estratégias de coping em idosos saudáveis

Idosos podem manifestar sintomas de estresse em decorrência das mudanças biopsicossociais do envelhecimento. O objetivo deste estudo foi identificar sintomas de estresse em idosos e o estilo de coping utilizado por eles, verificando a relação entre estas variáveis. Foram aplicados a Lista de Sintomas de Stress (LSS) e o Inventário de Coping de Jalowiec, em 41 idosos saudáveis. Os idosos apresentaram sintomas de estresse, com intensidade média de 42.8 pontos. Observou-se predomínio do coping focado no problema, porém não houve diferença significativa entre as médias dos escores do LSS entre os indivíduos que utilizaram coping focado no problema ou na emoção (p=0.737). Neste estudo, embora os idosos tendessem a eleger o coping focado no problema, a intensidade dos sintomas de estresse independeu do tipo de coping utilizado, evidenciando que tanto o coping focado no problema como o focado na emoção estão associados a níveis semelhantes de estresse.

Aujourd'hui Cendrars : 1961-2011

Avec Cendrars, la vie et l'oeuvre se confondent en formant ce que Henry Miller a nommé « une masse poétique étincelante, dédiée à l'archipel de l'insomnie ». Voilà ce qui, aux yeux de son ami américain, faisait de lui rien de moins que l'écrivain du siècle. Un écrivain trop « distraitement reconnu », au dire de Malraux, qui déplorait que le poète ait été souvent négligé au profit du bourlingueur, dont Cendrars lui-même a largement contribué à sculpter la figure. Au miroir déformant de la légende, le romancier, le mémorialiste, le cinéaste ou encore l'homme de radio et le reporter se sont effacés, ne laissant trop longtemps persister de Cendrars qu'un cliché, celui de l'aventurier au visage buriné prêt à raconter ses voyages : sans doute la meilleure façon pour lui de prendre le large. Dès 1912 avec le poème Les Pâques et jusqu'en 1956 avec le roman baroque Emmène-moi au bout du monde !..., chaque publication ressemble à l'une des pièces d'un vaste puzzle où se dessine la modernité du XXe siècle. C'est peu dire que Cendrars fut un novateur de formes et de genres : son oeuvre, élaborée dans l'effervescence et le tumulte est hétiques, offre aujourd'hui plus que jamais des échos puissants à nos questionnements contemporains : elle ne cesse de commencer. Ce volume rassemble les contributions au colloque international « Aujourd'hui Cendrars. 1961-2011 » organisé, à l'occasion du cinquantenaire du décès de Blaise Cendrars, par l'Université de Lausanne, l'Université Paris Ouest Nanterre La Défense, le Centre d'Études Blaise Cendrars (CEBC) et l'Association internationale Blaise Cendrars (AIBC), qui s'est déroulé à Dorigny-Lausanne du 4 au 6 mai 2011.

The risk of subsequent cancer and arterial cardiovascular events in patients with superficial vein thrombosis in the legs.

Although it has been clearly demonstrated that venous thromboembolism is associated with an increased risk of subsequent overt cancer and arterial cardiovascular events in comparison with control populations, whether this association also applies to patients with isolated (ie, without concomitant involvement of the deep vein system) superficial vein thrombosis (SVT) in the legs is unknown. In 737 consecutive patients with isolated SVT not involving the sapheno-femoral junction, we conducted a retrospective investigation to assess the rate of cancer and that of arterial cardiovascular events occurring during follow-up. The event rates were compared with those occurring in 1438 controls having comparable characteristics. Both cases and controls were followed-up for an average period of 26 ± 8 months (range, 3-45). Malignancy was diagnosed in 26 cases (3.5%) and 56 controls (3.9%), leading to a hazard ratio of 0.86 (95% confidence interval, 0.55%-1.35%). Arterial cardiovascular events occurred in 32 cases (4.3%) and 63 controls (4.4%), leading to a hazard ratio of 0.97 (95% confidence interval, 0.63%-1.50%). We conclude that the occurrence of isolated SVT in the legs does not place patients at an increased risk of malignancies or arterial cardiovascular events. Whether this conclusion also applies to patients whose thrombosis involves the sapheno-femoral junction remains to be demonstrated.

Os Sino-moçambicanos da Beira. Mestiçagens Várias

Entre 1858 – data da chegada à Ilha de Moçambique dos primeiros «coolies»2 – e 1975 – data da Independência de Moçambique –, os imigrantes chineses e seus descendentes locais passaram a estar presentes nas relações que se foram tecendo entre os diferentes grupos étnicos e raciais de cada uma das regiões da colónia onde se instalaram, locais de encontro de culturas e de processos complexos de aculturação. Mas nesses encontros e desencontros, as diferenças de cor e de cultura foram quase sempre vividas por preconceitos raciais e étnicos, com frequência expressos nas próprias leis coloniais. Apesar disto, as diferenças foram também matizadas por um multiculturalismo vivido, sem a celebração, contudo, de uma sociedade multicolor. No caso particular da Beira, a sociedade local foi efectivamente caracterizada por um desenvolvimento separado das culturas3 sob o domínio da Companhia de Moçambique e do Estado português subsequente

NEWSPAPERS FOLHA DE SÃO PAULO E CORREIO BRAZILIENSE: WHAT THEY SAY ABOUT THE PROGRAM MORE DOCTORS?

Analyzes publications related More Medical Program from July to September of 2013 and its impact on Correio Braziliense and Folha de São Paulo. This is a descriptive study using a qualitative-quantitative methodology. The analyzed and related data represent what the program takes in print. 363 publications were found, 262 in Folha de São Paulo and 101 in Correio. The word "Doctor" appeared in more titles, and Folha de São Paulo were 110 negative titles; to Correio neutral character was in 50 publications. In the character of news, 178 of these are pessimistic. The "neutral" and 101 representing "optimistic" 83. Was found that the media is critical to the impact of the program, but the truth is not apparent, but the opinion of journalists who wrote the stories related to the theme.

Clustering of cardiovascular risk factors mimicking the human metabolic syndrome X in eNOS null mice.

AIMS/HYPOTHESIS: The metabolic syndrome comprises a clustering of cardiovascular risk factors but the underlying mechanism is not known. Mice with targeted disruption of endothelial nitric oxide synthase (eNOS) are hypertensive and insulin resistant. We wondered, whether eNOS deficiency in mice is associated with a phenotype mimicking the human metabolic syndrome. METHODS AND RESULTS: In addition to arterial pressure and insulin sensitivity (euglycaemic hyperinsulinaemic clamp), we measured the plasma concentration of leptin, insulin, cholesterol, triglycerides, free fatty acids, fibrinogen and uric acid in 10 to 12 week old eNOS-/- and wild type mice. We also assessed glucose tolerance under basal conditions and following a metabolic stress with a high fat diet. As expected eNOS-/- mice were hypertensive and insulin resistant, as evidenced by fasting hyperinsulinaemia and a roughly 30 percent lower steady state glucose infusion rate during the clamp. eNOS-/- mice had a 1.5 to 2-fold elevation of the cholesterol, triglyceride and free fatty acid plasma concentration. Even though body weight was comparable, the leptin plasma level was 30% higher in eNOS-/- than in wild type mice. Finally, uric acid and fibrinogen were elevated in the eNOS-/- mice. Whereas under basal conditions, glucose tolerance was comparable in knock out and control mice, on a high fat diet, knock out mice became significantly more glucose intolerant than control mice. CONCLUSIONS: A single gene defect, eNOS deficiency, causes a clustering of cardiovascular risk factors in young mice. We speculate that defective nitric oxide synthesis could trigger many of the abnormalities making up the metabolic syndrome in humans.

Identification of a new oncofoetal antigen associated with several types of human carcinomas.

In experimental animals, oncofoetal antigens1 have been found to be associated with both chemical-2 and virus-induced tumours3. In man the two best known oncofoetal antigens are the α-foetoprotein (AFP) described by both Abelev4 and Tatarinov5 and the carcinoembryonic antigen (CEA) of the human digestive system identified by Gold and Freedman6. We describe here a different human oncofoetal antigen, common to several types of carcinomas and various foetal organs. This antigen has been identified by rabbit antisera raised against semipurified fractions of colon carcinoma soluble extracts. Because of its β-immunoelectrophoretic mobility, this antigen will be referred to as β-oncofoetal antigen (BOFA).

Oxidative and glycogenolytic cCapacities within the developing chick heart.

Cardiac morphogenesis and function are known to depend on both aerobic and anaerobic energy-producing pathways. However, the relative contribution of mitochondrial oxidation and glycogenolysis, as well as the determining factors of oxygen demand in the distinct chambers of the embryonic heart, remains to be investigated. Spontaneously beating hearts isolated from stage 11, 20, and 24HH chick embryos were maintained in vitro under controlled metabolic conditions. O(2) uptake and glycogenolytic rate were determined in atrium, ventricle, and conotruncus in the absence or presence of glucose. Oxidative capacity ranged from 0.2 to 0.5 nmol O(2)/(h.microg protein), did not depend on exogenous glucose, and was the highest in atria at stage 20HH. However, the highest reserves of oxidative capacity, assessed by mitochondrial uncoupling, were found at the youngest stage and in conotruncus, representing 75 to 130% of the control values. At stage 24HH, glycogenolysis in glucose-free medium was 0.22, 0.17, and 0.04 nmol glucose U(h.microg protein) in atrium, ventricle, and conotruncus, respectively. Mechanical loading of the ventricle increased its oxidative capacity by 62% without altering glycogenolysis or lactate production. Blockade of glycolysis by iodoacetate suppressed lactate production but modified neither O(2) nor glycogen consumption in substrate-free medium. These findings indicate that atrium is the cardiac chamber that best utilizes its oxidative and glycogenolytic capacities and that ventricular wall stretch represents an early and major determinant of the O(2) uptake. Moreover, the fact that O(2) and glycogen consumptions were not affected by inhibition of glyceraldehyde-3-phosphate dehydrogenase provides indirect evidence for an active glycerol-phosphate shuttle in the embryonic cardiomyocytes.