The new automated daily mortality surveillance system

The experience reported in an earlier Eurosurveillance issue on a fast method to evaluate the impact of the 2003 heatwave on mortality in Portugal, generated a daily mortality surveillance system (VDM) that has been operating ever since jointly with the Portuguese Heat Health Watch Warning System. This work describes the VDM system and how it evolved to become an automated system operating year-round, and shows briefly its potential using mortality data from January 2006 to June 2009 collected by the system itself. The new system has important advantages such as: rapid information acquisition, completeness (the entire population is included), lightness (very little information is exchanged, date of death, age, sex, place of death registration). It allows rapid detection of impacts (within five days) and allows a quick preliminary quantification of impacts that usually took several years to be done. These characteristics make this system a powerful tool for public health action. The VDM system also represents an example of inter-institutional cooperation, bringing together organisations from two different ministries, Health and Justice, aiming at improving knowledge about the mortality in the population

Histological changes and impairment of liver mitochondrial bioenergetics after long-term treatment with alpha-naphthyl-isothiocyanate (ANIT)

This study was designed to evaluate the effects of long-term treatment with alpha-naphthyl-isothiocyanate (ANIT) on liver histology and at the mitochondrial bioenergetic level. Since, ANIT has been used as a cholestatic agent and it has been pointed out that an impairment of mitochondrial function is a cause of hepatocyte dysfunction leading to cholestatic liver injury, serum markers of liver injury were measured and liver sections were analyzed in ANIT-treated rats (i.p. 80 mg/kg/week x 16 weeks). Mitochondrial parameters such as transmembrane potential, respiration, calcium capacity, alterations in permeability transition susceptibility and ATPase activity were monitored. Histologically, the most important features were the marked ductular proliferation, proliferation of mast cells and the presence of iron deposits in ANIT-treated liver. Mitochondria isolated from ANIT-treated rats showed no alterations in state 4 respiration, respiratory control ratio and ADP/O ratio, while state 3 respiration was significantly decreased. No changes were observed on transmembrane potential, but the repolarization rate was decreased in treated rats. Consistently with these data, there was a significant decrease in the ATPase activity of treated mitochondria. Associated with these parameters, mitochondria from treated animals exhibited increased susceptibility to mitochondrial permeability transition pore opening (lower calcium capacity). Since, human cholestatic liver disease progress slowly overtime, these data provide further insight into the role of mitochondrial dysfunction in the process

Relationship between cardiac diffusion tensor imaging parameters and anthropometrics in healthy volunteers

Background: In vivo cardiac diffusion tensor imaging (cDTI) is uniquely capable of interrogating laminar myocardial dynamics non-invasively. A comprehensive dataset of quantative parameters and comparison with subject anthropometrics is required. Methods: cDTI was performed at 3T with a diffusion weighted STEAM sequence. Data was acquired from the mid left ventricle in 43 subjects during the systolic and diastolic pauses. Global and regional values were determined for fractional anisotropy (FA), mean diffusivity (MD), helix angle gradient (HAg, degrees/%depth) and the secondary eigenvector angulation (E2A). Regression analysis was performed between global values and subject anthropometrics. Results: All cDTI parameters displayed regional heterogeneity. The RR interval had a significant, but clinically small effect on systolic values for FA, HAg and E2A. Male sex and increasing left ventricular end diastolic volume were associated with increased systolic HAg. Diastolic HAg and systolic E2A were both directly related to left ventricular mass and body surface area. There was an inverse relationship between E2A mobility and both age and ejection fraction. Conclusions: Future interpretations of quantitative cDTI data should take into account anthropometric variations observed with patient age, body surface area and left ventricular measurements. Further work determining the impact of technical factors such as strain and SNR is required

Gold nanoparticles functionalised with fast water exchanging Gd3+ chelates: linker effects on the relaxivity.

This is the accepted manuscript. The final version is available at http://dx.doi.org/10.1039/C4DT03210AThe relaxivity displayed by Gd(3+) chelates immobilized onto gold nanoparticles is the result of the complex interplay between the nanoparticle size, the water exchange rate and the chelate structure. In this work we study the effect of the length of ω-thioalkyl linkers, anchoring fast water exchanging Gd(3+) chelates onto gold nanoparticles, on the relaxivity of the immobilized chelates. Gold nanoparticles functionalized with Gd(3+) chelates of mercaptoundecanoyl and lipoyl amide conjugates of the DO3A-N-(α-amino)propionate chelator were prepared and studied as potential CA for MRI. High relaxivities per chelate, of the order of magnitude 28-38 mM(-1) s(-1) (30 MHz, 25 °C), were attained thanks to simultaneous optimization of the rotational correlation time and of the water exchange rate. Fast local rotational motions of the immobilized chelates around connecting linkers (internal flexibility) still limit the attainable relaxivity. The degree of internal flexibility of the immobilized chelates seems not to be correlated with the length of the connecting linkers. Biodistribution and MRI studies in mice suggest that the in vivo behavior of the gold nanoparticles was determined mainly by size. Small nanoparticles (HD = 3.9 nm) undergo fast renal clearance and avoidance of the RES organs while larger nanoparticles (HD = 4.8 nm) undergo predominantly hepatobiliary excretion. High relaxivities, allied to chelate and nanoparticle stability and fast renal clearance in vivo suggest that functionalized gold nanoparticles hold great potential for further investigation as MRI contrast agents. This study contributes to a better understanding of the effect of linker length on the relaxivity of gold nanoparticles functionalized with Gd(3+) complexes. It is a relevant contribution towards "design rules" for nanostructures functionalized with Gd(3+) chelates as Contrast Agents for MRI and multimodal imaging.This work was financially supported by Fundação para a Ciência e a Tecnologia, Portugal: PhD grant SFRH/BD/63994/2009 to Miguel Ferreira and Sabbatical Grant SFRH/BSAB/1328/2013 to José Martins at Bath University, UK; and Rede Nacional de NMR (REDE/1517/RMN/2005) for the acquisition of the Varian VNMRS 600 NMR spectrometer in Coimbra. T.B.R. was supported by a Marie Curie Fellowship (FP/- PEOPLE-2009-IEF 254380) and an EMBO Fellowship (ALTF 1145-2009). Financial support from Ministerio de Ciencia e Innovación, Spain, projects SAF2011-23622 (S.C.) and CTQ2010-20960-C02-02 (P.L.-L.), and Comunidad de Madrid, Spain, project S2010/BMD-2349 (S.C. and P.L.-L), is also acknowledged. B. Mousavi and L. Helm acknowledge financial support by the Swiss National Science Foundation. This work was carried out in the frame of the COST D38 Action “Metal Based Systems for Molecular Imaging” and COST TD1004 Action “Theranostics Imaging and Therapy”

Optimization of K-edge subtraction imaging using a pixellated spectroscopic detector

Conventional K-edge subtraction imaging is based around the acquisition of two separate images at energies respectively below and above the K-edge of a contrast agent. This implies increased patient dose with respect to a conventional procedure and potentially incorrect image registration due to patient motion. © 2012 IEEE

Evaluation of the impact of strain correction on the orientation of cardiac diffusion tensors with in vivo and ex vivo porcine hearts

Purpose To evaluate the importance of strain-correcting stimulated echo acquisition mode echo-planar imaging cardiac diffusion tensor imaging. Methods Healthy pigs (n = 11) were successfully scanned with a 3D cine displacement-encoded imaging with stimulated echoes and a monopolar-stimulated echo-planar imaging diffusion tensor imaging sequence at 3 T during diastasis, peak systole, and strain sweet spots in a midventricular short-axis slice. The same diffusion tensor imaging sequence was repeated ex vivo after arresting the hearts in either a relaxed (KCl-induced) or contracted (BaCl2-induced) state. The displacement-encoded imaging with stimulated echoes data were used to strain-correct the in vivo cardiac diffusion tensor imaging in diastole and systole. The orientation of the primary (helix angles) and secondary (E2A) diffusion eigenvectors was compared with and without strain correction and to the strain-free ex vivo data. Results Strain correction reduces systolic E2A significantly when compared without strain correction and ex vivo (median absolute E2A = 34.3° versus E2A = 57.1° (P = 0.01), E2A = 60.5° (P = 0.006), respectively). The systolic distribution of E2A without strain correction is closer to the contracted ex vivo distribution than with strain correction, root mean square deviation of 0.027 versus 0.038. Conclusions The current strain-correction model amplifies the contribution of microscopic strain to diffusion resulting in an overcorrection of E2A. Results show that a new model that considers cellular rearrangement is required

Biological evaluation of hydroxynaphthoquinones as anti-malarials

Abstract\ud \ud \ud \ud Background\ud The hydroxynaphthoquinones have been extensively investigated over the past 50 years for their anti-malarial activity. One member of this class, atovaquone, is combined with proguanil in Malarone®, an important drug for the treatment and prevention of malaria.\ud \ud \ud \ud Methods\ud Anti-malarial activity was assessed in vitro for a series of 3-alkyl-2-hydroxy-1,4-naphthoquinones (N1-N5) evaluating the parasitaemia after 48 hours of incubation. Potential cytotoxicity in HEK293T cells was assessed using the MTT assay. Changes in mitochondrial membrane potential of Plasmodium were measured using the fluorescent dye Mitrotracker Red CMXROS.\ud \ud \ud \ud Results\ud Four compounds demonstrated IC50s in the mid-micromolar range, and the most active compound, N3, had an IC50 of 443 nM. N3 disrupted mitochondrial membrane potential, and after 1 hour presented an IC50ΔΨmit of 16 μM. In an in vitro cytotoxicity assay using HEK 293T cells N3 demonstrated no cytotoxicity at concentrations up to 16 μM.\ud \ud \ud \ud Conclusions\ud N3 was a potent inhibitor of mitochondrial electron transport, had nanomolar activity against cultured Plasmodium falciparum and showed minimal cytotoxicity. N3 may serve as a starting point for the design of new hydroxynaphthoquinone anti-malarials.This work was supported by FAPESP (Fundação de Amparo a Pesquisa de São Paulo) (07/52924-0), by Malaria Pronex, and by a INCT-INBqMed (Instituto Nacional de Ciência e Tecnologia- Instituto Nacional de Ciência e Tecnologia de Biotecnologia Estrutural e Química Medicinal em Doenças Infecciosa) grant. C.R.S. Garcia and V. Ferreira are CNPQ (Conselho Nacional de Pesquisa) fellows. D.S. received a CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) Fellowship. D.R. da Rocha thanks FAPERJ (Fundação de Amparo a Pesquisa do Rio De Janeiro) for their doctoral fellowship. LNC and MM received a FAPESP Fellowship. Thanks are due to the CNPQ, CAPES and FAPERJ for funding this work.This work was supported by FAPESP (Fundação de Amparo a Pesquisa de São Paulo) (07/529240), by Malaria Pronex, and by a INCTINBqMed (Instituto Nacional de Ciência e Tecnologia Instituto Nacional de Ciência e Tecnologia de Biotecnologia Estrutural e Química Medicinal em Doenças Infecciosa) grant. C.R.S. Garcia and V. Ferreira are CNPQ (Conselho Nacional de Pesquisa) fellows. D.S. received a CAPES (Coordenação de Aperfeiçoamento de Pessoal de Nível Superior) Fellowship. D.R. da Rocha thanks FAPERJ (Fundação de Amparo a Pesquisa do Rio De Janeiro) for their doctoral fellowship. LNC and MM received a FAPESP Fellowship. Thanks are due to the CNPQ, CAPES and FAPERJ for funding this work

Freshwater transport in the coupled ocean-atmosphere system: a passive ocean

Conservation of water demands that meridional ocean and atmosphere freshwater transports (FWT) are of equal magnitude but opposite in direction. This suggests that the atmospheric FWT and its associated latent heat (LH) transport could be thought of as a \textquotedblleft coupled ocean/atmosphere mode\textquotedblright. But what is the true nature of this coupling? Is the ocean passive or active? Here we analyze a series of simulations with a coupled ocean-atmosphere-sea ice model employing highly idealized geometries but with markedly different coupled climates and patterns of ocean circulation. Exploiting streamfunctions in specific humidity coordinates for the atmosphere and salt coordinates for the ocean to represent FWT in their respective medium, we find that atmospheric FWT/LH transport is essentially independent of the ocean state. Ocean circulation and salinity distribution adjust to achieve a return freshwater pathway demanded of them by the atmosphere. So, although ocean and atmosphere FWTs are indeed coupled by mass conservation, the ocean is a passive component acting as a reservoir of freshwater

One-step isolation and biochemical characterization of a highlyactive plant PSII monomeric core

We describe a one-step detergent solubilization protocol for isolating a highly active form of Photosystem II (PSII) from Pisum sativum L. Detailed characterization of the preparation showed that the complex was a monomer having no light harvesting proteins attached. This core reaction centre complex had, however, a range of low molecular mass intrinsic proteins as well as the chlorophyll binding proteins CP43 and CP47 and the reaction centre proteins D1 and D2. Of particular note was the presence of a stoichiometric level of PsbW, a low molecular weight protein not present in PSII of cyanobacteria. Despite the high oxygen evolution rate, the core complex did not retain the PsbQ extrinsic protein although there was close to a full complement of PsbO and PsbR and partial level of PsbP. However, reconstitution of PsbP and PsbPQ was possible. The presence of PsbP in absence of LHCII and other chlorophyll a/b binding proteins confirms that LHCII proteins are not a strict requirement for the assembly of this extrinsic polypeptide to the PSII core in contrast with the conclusion of Caffarri et al. (2009)