Quality assessment of cardiovascular magnetic resonance in the setting of the European CMR registry: description and validation of standardized criteria.

BACKGROUND: Cardiovascular magnetic resonance (CMR) has become an important diagnostic imaging modality in cardiovascular medicine. However, insufficient image quality may compromise its diagnostic accuracy. We aimed to describe and validate standardized criteria to evaluate a) cine steady-state free precession (SSFP), b) late gadolinium enhancement (LGE), and c) stress first-pass perfusion images. These criteria will serve for quality assessment in the setting of the Euro-CMR registry. METHODS: Thirty-five qualitative criteria were defined (scores 0-3) with lower scores indicating better image quality. In addition, quantitative parameters were measured yielding 2 additional quality criteria, i.e. signal-to-noise ratio (SNR) of non-infarcted myocardium (as a measure of correct signal nulling of healthy myocardium) for LGE and % signal increase during contrast medium first-pass for perfusion images. These qualitative and quantitative criteria were assessed in a total of 90 patients (60 patients scanned at our own institution at 1.5T (n=30) and 3T (n=30) and in 30 patients randomly chosen from the Euro-CMR registry examined at 1.5T). Analyses were performed by 2 SCMR level-3 experts, 1 trained study nurse, and 1 trained medical student. RESULTS: The global quality score was 6.7±4.6 (n=90, mean of 4 observers, maximum possible score 64), range 6.4-6.9 (p=0.76 between observers). It ranged from 4.0-4.3 for 1.5T (p=0.96 between observers), from 5.9-6.9 for 3T (p=0.33 between observers), and from 8.6-10.3 for the Euro-CMR cases (p=0.40 between observers). The inter- (n=4) and intra-observer (n=2) agreement for the global quality score, i.e. the percentage of assignments to the same quality tertile ranged from 80% to 88% and from 90% to 98%, respectively. The agreement for the quantitative assessment for LGE images (scores 0-2 for SNR <2, 2-5, >5, respectively) ranged from 78-84% for the entire population, and 70-93% at 1.5T, 64-88% at 3T, and 72-90% for the Euro-CMR cases. The agreement for perfusion images (scores 0-2 for %SI increase >200%, 100%-200%,<100%, respectively) ranged from 81-91% for the entire population, and 76-100% at 1.5T, 67-96% at 3T, and 62-90% for the Euro-CMR registry cases. The intra-class correlation coefficient for the global quality score was 0.83. CONCLUSIONS: The described criteria for the assessment of CMR image quality are robust with a good inter- and intra-observer agreement. Further research is needed to define the impact of image quality on the diagnostic and prognostic yield of CMR studies.

Acute ischemic stroke in children versus young adults.

Objective: The aim of this study was to compare children and young adults with acute ischemic stroke (AIS) in 2 large registries.Methods: We compared clinical characteristics, stroke etiology, workup, and outcome (modified Rankin scale score [mRS] at 3-6 months) in children (1 month-16 years) and young adults (16.1-45 years) with AIS. Data of children were collected prospectively in the nationwide Swiss NeuroPediatric Stroke Registry, young adults in the Bernese stroke database. Outcome (mRS) and stroke severity (pediatric adaptation of the National Institutes of Health stroke scale [PedNIHSS]) in children were calculated retrospectively.Results: From January 2000 to December 2008, 128 children and 199 young adults suffered from an AIS. Children were more likely to be male than young adults (62%/49%, p = 0.023) and less frequently had hypertension (p = 0.001), hypercholesterolemia (p = 0.003), and a family history of stroke (p = 0.048). Stroke severity was similar in children and young adults (median PedNIHSS/NIHSS 5/6; p = 0.102). Stroke etiology (original TOAST classification) was more likely to be "other determined cause" in children than in young adults (51%/29%; p < .001). Cervicocerebral artery dissections were less frequent in children than in young adults (10%/23%; p = 0.005). Outcome at 3 to 6 months did not differ between children and young adults (p = 0.907); 59% of children and 60% of young adults had a favorable outcome (mRS 0-1). Mortality was similar among children and young adults (4%/6%; p = 0.436). In multivariate analysis, low PedNIHSS/NIHSS was the most important predictor of favorable outcome (p < 0.001).Interpretation: Although stroke etiology and risk factors in children and young adults are different, stroke severity and clinical outcome were similar in both groups. ANN NEUROL 2011;70:245-254

Connexin26 is regulated in rat urothelium by the scaffold protein IB1/JIP-1.

Proper function of the wall of bladder requires gap junctional communication for coordinating the responses of smooth muscle (SMC) and urothelial cells exposed to urine pressure. In the rat bladder, Cx43 is expressed by SMC and urothelial cells, whereas Cx26 expression is restricted to the epithelium. We used a model of bladder outlet obstruction, in which a ligature is placed around the urethra to increase voiding pressure. Increased fluid pressure was associated with increased Cx43 and Cx26 mRNA expression and with the activation of a signaling cascade including the transcription factor c-Jun, which is a component of the AP-1 complex. The signaling pathway of the c-Jun NH2 terminal kinase (JNK) requires the presence of the scaffold protein Islet-Brain1/c-Jun amino-terminal kinase Interacting Protein-1 (IB1/JIP-1). Under stress conditions resulting from urine retention, we have found a reduced content of IB1/JIP-1 in urothelial cells, which in turn induced a drastic increase of JNK and AP-1 binding activities. The stress-induced activation of JNK was prevented by overexpressing IB1/JIP-1, using a viral gene transfer approach, a condition which also resulted in a decrease in Cx26 mRNA. The data show that: 1) mechanical stress of urothelial cells activates in vivo JNK, as a consequence of a regulated expression of IB1/JIP-1 and 2) that urothelial Cx26 may be directly regulated by the AP-1 complex.

Reference Cluster Normalization Improves Detection of Frontotemporal Lobar Degeneration by Means of FDG-PET.

Positron emission tomography with [18F] fluorodeoxyglucose (FDG-PET) plays a well-established role in assisting early detection of frontotemporal lobar degeneration (FTLD). Here, we examined the impact of intensity normalization to different reference areas on accuracy of FDG-PET to discriminate between patients with mild FTLD and healthy elderly subjects. FDG-PET was conducted at two centers using different acquisition protocols: 41 FTLD patients and 42 controls were studied at center 1, 11 FTLD patients and 13 controls were studied at center 2. All PET images were intensity normalized to the cerebellum, primary sensorimotor cortex (SMC), cerebral global mean (CGM), and a reference cluster with most preserved FDG uptake in the aforementioned patients group of center 1. Metabolic deficits in the patient group at center 1 appeared 1.5, 3.6, and 4.6 times greater in spatial extent, when tracer uptake was normalized to the reference cluster rather than to the cerebellum, SMC, and CGM, respectively. Logistic regression analyses based on normalized values from FTLD-typical regions showed that at center 1, cerebellar, SMC, CGM, and cluster normalizations differentiated patients from controls with accuracies of 86%, 76%, 75% and 90%, respectively. A similar order of effects was found at center 2. Cluster normalization leads to a significant increase of statistical power in detecting early FTLD-associated metabolic deficits. The established FTLD-specific cluster can be used to improve detection of FTLD on a single case basis at independent centers - a decisive step towards early diagnosis and prediction of FTLD syndromes enabling specific therapies in the future.

Caracterização mineralógica, potencial de reserva e sustentabilidade agrícola de alguns sítios florestais de eucalipto da região do Vale do Rio Doce (MG)

Foram estudados alguns solos da região do Vale do Rio Doce (MG) em 1991, nos municípios de Ipatinga, Nova Era e Guanhães, provenientes de áreas de reflorestamento de Eucalyptus grandis. Selecionaram-se oito sítios florestais com solos de diferentes classes taxonômicas, e uma detalhada caracterização mineralógica e avaliação do potencial de reserva de nutrientes foram desenvolvidas. Os solos estudados foram mineralogicamente classificados como: caulinítico não-sesquioxídicos (2 e 5); caulinítico-sesquioxídico (1); gibbsítico-sesquioxídicos (4, 6 e 7); hematítico (3) e gibbsítico (8). Os principais argilominerais e óxidos de ferro e alumínio presentes nesses solos são caulinita, gibbsita, hematita, goethita e maghemita. A reserva mineral de médio a longo prazo para potássio é praticamente inexistente, estando presente, embora com baixa magnitude, nos solos 2 e 5, na forma de micas e feldspatos. As relações Ca-trocável/Ca-total e Mg-trocável/Mg-total exprimem baixa capacidade de reposição desses nutrientes nos solos estudados. Sugere-se a adição de nutrientes de acordo com os níveis críticos exigidos na implantação e manutenção do ciclo do eucalipto, em virtude da ausência de sustentabilidade desses sítios florestais em termos de reserva de nutrientes a curto, médio e longo prazos.

Isoquantas de produtividade de soja e sorgo para níveis de calagem e molibdênio

A calagem tem sido considerada uma prática suficiente para o suprimento de molibdênio (Mo) para as culturas, pelo aumento do pH que o torna mais disponível no solo. A cultura da soja exige doses elevadas de calcário para a otimização da produtividade, o que também está relacionado com a demanda adicional de Mo para o complexo da nitrogenase, atuante na fixação do nitrogênio. Assim, o presente trabalho foi planejado para estudar as interações entre calagem e Mo, nas culturas de soja e sorgo, em um Podzólico Vermelho-Amarelo da Estação Experimental de Mococa (IAC), de 1985 a 1989. Os tratamentos foram arranjados no delineamento experimental de blocos ao acaso, com parcelas subdivididas e quatro repetições. Nas parcelas principais, foram aplicadas as doses de calcário 0, 2, 4, 6, e 8 t ha-1 (PRNT = 126%) e, nas subparcelas, as doses de Mo de 0, 50 e 100 g ha-1, aplicadas às sementes, na forma de molibdato de amônio. Foram realizados três cultivos de soja, cultivar IAC 11, e um de sorgo granífero, híbrido DK 64. Em todos os cultivos, as respostas à calagem foram acentuadas, porém reduzidas com a aplicação de molibdênio, tanto para a soja como para o sorgo. Tais resultados demonstraram a relação de substituição de calcário por Mo. A resposta da soja ao Mo foi mais acentuada na ausência do calcário, enquanto a do sorgo, mais sensível à acidez do solo, foi mais acentuada nas doses intermediárias de calcário. De modo geral, as respostas ao Mo ocorreram até o valor de pH (CaCl2 ) do solo igual a 5,2. Concluiu-se que altas produtividades de soja exigem níveis mais elevados de correção de acidez de solo, e que é possível reduzir a necessidade de calagem, para atingir a produtividade máxima, mediante a aplicação de Mo nas sementes, para ambas as culturas, principalmente num solo ácido com pouco alumínio e manganês trocáveis.

Escherchia coli ribose binding protein based bioreporters revisited.

Bioreporter bacteria, i.e., strains engineered to respond to chemical exposure by production of reporter proteins, have attracted wide interest because of their potential to offer cheap and simple alternative analytics for specified compounds or conditions. Bioreporter construction has mostly exploited the natural variation of sensory proteins, but it has been proposed that computational design of new substrate binding properties could lead to completely novel detection specificities at very low affinities. Here we reconstruct a bioreporter system based on the native Escherichia coli ribose binding protein RbsB and one of its computationally designed variants, reported to be capable of binding 2,4,6-trinitrotoluene (TNT). Our results show in vivo reporter induction at 50 nM ribose, and a 125 nM affinity constant for in vitro ribose binding to RbsB. In contrast, the purified published TNT-binding variant did not bind TNT nor did TNT cause induction of the E. coli reporter system.

Libtech International 96 : networked periodical services

Annikki Hyvärinen

Efeitos da calagem, cobalto e molibdênio sobre a concentração de clorofila nas folhas de amendoim

Para avaliar os efeitos da calagem e da aplicação de cobalto e molibdênio nas sementes sobre a concentração de clorofila em folhas de plantas de amendoim, foram instalados experimentos, no período "das águas", nos anos agrícolas 1990/91 e 1991/92, em área de ocorrência de Latossolo Vermelho-Escuro distrófico textura média. Foram utilizadas quatro doses de calcário dolomítico calcinado: 0, 4, 6 e 8 t ha-1; dois cultivares de amendoim: "Tatu" e "Tupã", e quatro tratamentos de sementes: não tratadas, tratadas com cobalto, com molibdênio e com cobalto mais molibdênio. Verificou-se que, em condições de elevada acidez do solo, a aplicação de molibdênio nas sementes aumentou a concentração de clorofila nas folhas do amendoim, com efeito semelhante ao da calagem na ausência de molibdênio. A concentração de clorofila correlacionou-se positivamente com o teor de nitrogênio nas folhas, indicando que os efeitos da calagem e da aplicação de molibdênio sobre a concentração de clorofila foram basicamente ocasionados pela melhoria do processo de fixação simbiótica do nitrogênio por maior atividade da nitrogenase. Houve aumento linear da produção de vagens e grãos do cultivar "Tatu" com o aumento da concentração de clorofila nas folhas e, no caso do cultivar "Tupã", a máxima produção de vagens e grãos foi obtida para concentração de clorofila nas folhas de 4,6 mg dm-2.

Social and medical vulnerability factors of emergency department frequent users in a universal health insurance system

Objectifs - Identifier les facteurs de vulnérabilité sociaux et médicaux associés au recours multiple aux consultations des urgences. - Déterminer si les patients à recours multiple sont plus à même de combiner ces facteurs dans un système d'assurance universelle. Méthode Il s'agit d'une étude cas-contrôle rétrospective basée sur l'étude de dossiers médico-administratifs comparant des échantillons randomisés de patients à recours multiple à des patients n'appartenant pas à cette catégorie, au sein des urgences du Centre Hospitalier Universitaire Vaudois et de la Policlinique Médicale Universitaire de Lausanne. Les auteurs ont défini les patients à recours multiple comme comptabilisant au moins quatre consultations aux urgences durant les douze mois précédents. Les patients adultes (>18 ans) ayant consulté les urgences entre avril 2008 et mars 2009 (période d'étude) étaient inclus ; ceux quittant les urgences sans décharge médicale étaient exclus. Pour chaque patient, le premier dossier d'urgence informatisé inclus dans la période d'étude était sélectionné pour l'extraction des données. Outre les variables démographiques de base, les variables d'intérêt comprennent des caractéristiques sociales (emploi, type de résidence) et médicales (diagnostic principal aux urgences). Les facteurs sociaux et médicaux significatifs ont été utilisés dans la construction d'un modèle de régression logistique, afin de déterminer les facteurs associés avec le recours multiple aux urgences. De plus, la combinaison des facteurs sociaux et médicaux a été étudiée. Résultats Au total, 359/Γ591 patients à recours multiple et 360/34'263 contrôles ont été sélectionnés. Les patients à recours multiple représentaient moins d'un vingtième de tous les patients des urgences (4.4%), mais engendraient 12.1% de toutes les consultations (5'813/48'117), avec un record de 73 consultations. Aucune différence en termes d'âge ou de genre n'est apparue, mais davantage de patients à recours multiples étaient d'une nationalité autre que suisse ou européenne (n=117 [32.6%] vs n=83 [23.1%], p=0.003). L'analyse multivariée a montré que les facteurs de vulnérabilité sociaux et médicaux les plus fortement associés au recours multiple aux urgences étaient : être sous tutelle (Odds ratio [OR] ajusté = 15.8; intervalle de confiance [IC] à 95% = 1.7 à 147.3), habiter plus proche des urgences (OR ajusté = 4.6; IC95% = 2.8 à 7.6), être non assuré (OR ajusté = 2.5; IC95% = 1.1 à 5.8), être sans emploi ou dépendant de l'aide sociale (OR ajusté = 2.1; IC95% = 1.3 à 3.4), le nombre d'hospitalisations psychiatriques (OR ajusté = 4.6; IC95% = 1.5 à 14.1), ainsi que le recours à au moins cinq départements cliniques différents durant une période de douze mois (OR ajusté = 4.5; IC95% = 2.5 à 8.1). Le fait de comptabiliser deux sur quatre facteurs sociaux augmente la vraisemblance du recours multiple aux urgences (OR ajusté = 5.4; IC95% = 2.9 à 9.9) ; des résultats similaires ont été trouvés pour les facteurs médicaux (OR ajusté = 7.9; IC95% = 4.6 à 13.4). La combinaison de facteurs sociaux et médicaux est fortement associée au recours multiple aux urgences, puisque les patients à recours multiple étaient dix fois plus à même d'en comptabiliser trois d'entre eux (sur un total de huit facteurs, IC95% = 5.1 à 19.6). Conclusion Les patients à recours multiple aux urgences représentent une proportion modérée des consultations aux urgences du Centre Hospitalier Universitaire Vaudois et de la Policlinique Médicale Universitaire de Lausanne. Les facteurs de vulnérabilité sociaux et médicaux sont associés au recours multiple aux urgences. En outre, les patients à recours multiple sont plus à même de combiner les vulnérabilités sociale et médicale que les autres. Des stratégies basées sur le case management pourraient améliorer la prise en charge des patients à recours multiple avec leurs vulnérabilités afin de prévenir les inégalités dans le système de soins ainsi que les coûts relatifs.

Crystal packing modifies ligand binding affinity: the case of aldose reductase.

The relationship between the structures of protein-ligand complexes existing in the crystal and in solution, essential in the case of fragment-based screening by X-ray crystallography (FBS-X), has been often an object of controversy. To address this question, simultaneous co-crystallization and soaking of two inhibitors with different ratios, Fidarestat (FID; K(d) = 6.5 nM) and IDD594 (594; K(d) = 61 nM), which bind to h-aldose reductase (AR), have been performed. The subatomic resolution of the crystal structures allows the differentiation of both inhibitors, even when the structures are almost superposed. We have determined the occupation ratio in solution by mass spectrometry (MS) Occ(FID)/Occ(594) = 2.7 and by X-ray crystallography Occ(FID)/Occ(594) = 0.6. The occupancies in the crystal and in solution differ 4.6 times, implying that ligand binding potency is influenced by crystal contacts. A structural analysis shows that the Loop A (residues 122-130), which is exposed to the solvent, is flexible in solution, and is involved in packing contacts within the crystal. Furthermore, inhibitor 594 contacts the base of Loop A, stabilizing it, while inhibitor FID does not. This is shown by the difference in B-factors of the Loop A between the AR-594 and AR-FID complexes. A stable loop diminishes the entropic energy barrier to binding, favoring 594 versus FID. Therefore, the effect of the crystal environment should be taken into consideration in the X-ray diffraction analysis of ligand binding to proteins. This conclusion highlights the need for additional methodologies in the case of FBS-X to validate this powerful screening technique, which is widely used.

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MMM:n tiedote

Intravenous thrombolysis in patients with stroke attributable to small artery occlusion.

BACKGROUND: Intravenous thrombolysis (IVT) for stroke seems to be beneficial independent of the underlying etiology. Recent observations raised concern that IVT might cause harm in patients with strokes attributable to small artery occlusion (SAO). OBJECTIVE: The safety of IVT in SAO-patients is addressed in this study. METHODS: We used the Swiss IVT databank to compare outcome and complications of IVT-treated SAO-patients with IVT-treated patients with other etiologies (non-SAO-patients). Main outcome and complication measures were independence (modified Rankin scale <or=2) at 3 months, intracranial hemorrhage (ICH), and recurrent ischaemic stroke. RESULTS: Sixty-five (6.2%) of 1048 IVT-treated patients had SAO. Amongst SAO-patients, 1.5% (1/65) patients died, compared to 11.2% (110/983) in the non-SAO-group (P = 0.014). SAO-patients reached independence more often than non-SAO-patients (75.4% versus 58.9%; OR 2.14 (95% CI 1.20-3.81; P = 0.001). This association became insignificant after adjustment for age, gender, and stroke severity (OR 1.41 95% CI 0.713-2.788; P = 0.32). Glucose level and (to some degree) stroke severity but not age predicted 3-month-independence in IVT-treated SAO-patients. ICHs (all/symptomatic) were similar in SAO- (12.3%/4.6%) and non-SAO-patients (13.4%/5.3%; P > 0.8). Fatal ICH occurred in 3.3% of the non-SAO-patients but none amongst SAO-patients. Ischaemic stroke within 3 months after IVT reoccurred in 1.5% of SAO-patients and in 2.3% of non-SAO-patients (P = 0.68). CONCLUSION: IVT-treated SAO-patients died less often and reached independence more often than IVT-treated non-SAO-patients. However, the variable 'SAO' was a dependent rather than an independent outcome predictor. The absence of an excess in ICH indicates that IVT seems not to be harmful in SAO-patients.