Coronary CT angiography (CTA) is currently considered a reliable method to exclude obstructive coronary artery disease (CAD) before valvular heart surgery in patients with low pretest probability. ...However, its role in excluding obstructive CAD before transcatheter aortic valve implantation (TAVI) is less well established. Single-center retrospective study where patients with severe symptomatic aortic stenosis underwent both CTA and invasive coronary angiography (ICA) as part of TAVI planning. CTA exams were conducted on a 64-slice dual source scanner, with a median interval of 45 days to ICA (IQR 25-75 13-82). In both tests, obstructive CAD was defined as a ≥50% stenosis in an epicardial vessel ≥2 mm diameter. Per-patient, per-vessel and per-proximal segment analyses were conducted, excluding and including non-evaluable segments. The study included 200 patients (120 women, mean age 83 ± 6 years). The prevalence of obstructive CAD on ICA was 35.5% (n = 71). On a per-patient analysis (assuming non-evaluable segments as stenotic), CTA showed sensitivity of 100% (95% CI, 95-100%), specificity of 42% (95% CI, 33-51%), and positive and negative predictive values of 48% (95% CI, 44-51%) and 100% (95% CI, 92-100%), respectively. CTA was able to exclude obstructive CAD in 54 patients (27%), in whom ICA could have been safely withheld. Despite the high rate of inconclusive tests, pre-procedural CTA is able to safely exclude obstructive CAD in a significant proportion of patients undergoing TAVI, possibly avoiding the need for ICA in roughly one quarter of the cases.
Genetic variability in humans can explain many differences in disease risk factors. Polymorphism-related studies focus mainly on the single nucleotide polymorphisms (SNPs) of coding regions of the ...genes. SNPs on DNA binding motifs of the promoter region have been less explored. On a recent study of SNPs in patients with non-Hodgkin lymphomas we faced the problem of SNP selection from promoter regions and developed a practical methodology for clinical studies. The process consists in identifying SNPs in the coding and promoter regions of the antigen-processing system using the 'dbSNP' database. With the 'HapMap' program, we select SNPs with frequencies >20% in Caucasian populations. For coding regions, we sought biologically and clinically relevant SNPs described in the literature. For the promoter regions, we determined their chromosomal location on 'QiagenSABioscience' site database. The nucleotide sequence of ancestral and variant alleles is available in the 'dbSNP'. These sequences were used in 'Promoter TESS' to determine binding differences of transcription factors. Each sequence may have affinity to different TFs. Thus, SNP selection on the promoter regions was based in the differences on TF binding pattern between the old and the new allele. The potential clinical relevance of the new TFs was also evaluated before the final selection. With this approach, we found that almost half of the relevant SNP fall within the promoter region. In conclusion, we were able to develop a methodology of oriented selection of promoter regions of human genes, comparing the TF with affinity to the ancestral allele with the TF to a variant allele. We selected those SNPs that change the TF's affinity to a pattern with functional significance.
A Box–Behnken factorial design coupled with surface response methodology was used to evaluate the effects of temperature, pH and initial concentration in the Cu(II) sorption process onto the marine ...macro-algae
Ascophyllum nodosum. The effect of the operating variables on metal uptake capacity was studied in a batch system and a mathematical model showing the influence of each variable and their interactions was obtained. Study ranges were 10–40
°C for temperature, 3.0–5.0 for pH and 50–150
mg
L
−1 for initial Cu(II) concentration. Within these ranges, the biosorption capacity is slightly dependent on temperature but markedly increases with pH and initial concentration of Cu(II). The uptake capacities predicted by the model are in good agreement with the experimental values. Maximum biosorption capacity of Cu(II) by
A. nodosum is 70
mg
g
−1 and corresponds to the following values of those variables: temperature
=
40
°C, pH
=
5.0 and initial Cu(II) concentration
=
150
mg
L
−1.
Compared to bare-metal stents (BMS), drug-eluting stents reduce stent restenosis and improve subsequent revascularization rates. The impact on patients’ survival has been the subject of debate.
To ...assess the long-term (10-year) survival of patients undergoing percutaneous coronary intervention (PCI) with first-generation sirolimus-eluting stents (SES) in comparison with BMS.
In a single-center registry, 600 consecutive patients who underwent successful PCI with SES between April 2002 and February 2003 were compared to 594 patients who underwent PCI with BMS between January 2002 and April 2002, just before the introduction of SES. Clinical and procedural data were collected at the time of intervention and 10-year survival status was assessed via the national life status database.
All baseline characteristics were similar between groups except for smaller stent diameter (2.84±0.38 vs. 3.19±0.49 mm; p<0.001), greater stent length (18.50±8.2 vs. 15.96±6.10 mm; p<0.001) and higher number of stents per patient (1.95 vs. 1.46, p<0.001) in the SES group. Overall five- and 10-year all-cause mortality was 9.6% (n=110) and 22.7% (n=272), respectively. The adjusted HR for 10-year mortality in patients undergoing PCI with SES was 0.74 (95% CI 0.58-0.94; p=0.013), corresponding to a relative risk reduction of 19.8%. Other than PCI with BMS, older age, chronic kidney disease, chronic obstructive pulmonary disease and lower ejection fraction were independent predictors of 10-year mortality.
To date, this is the longest follow-up study ever showing a potential survival benefit of first-generation sirolimus-eluting stents versus bare-metal stents, supporting prior observations on their sustained efficacy and safety relative to contemporary BMS.
Em comparação com os stents de metal nulo (BMS), os stents com efeito de droga reduzem a restenose do stent e melhoram as taxas de revascularização subsequente. O impacto na sobrevivência dos pacientes tem sido objecto de debate.
Avaliar a sobrevivência a longo prazo (10 anos) de pacientes submetidos a intervenção coronária percutânea (ICP) com stents sirolimus-eluting de primeira geração (SES) em comparação com a BMS.
Num registo de um único centro, 600 pacientes consecutivos submetidos a ICP com SES entre Abril de 2002 e Fevereiro de 2003 foram comparados com 594 pacientes submetidos a ICP com BMS entre Janeiro de 2002 e Abril de 2002, imediatamente antes da introdução da SES. Os dados clínicos e processuais foram recolhidos no momento da intervenção e o estado de sobrevivência de 10 anos foi avaliado através da base de dados nacional do estado de vida.
Todas as características de linha de base foram semelhantes entre os grupos, excepto para stents de menor diâmetro (2,84±0,38 vs. 3,19±0,49 mm; p<0,001), maior comprimento do stent (18,50±8,2 vs. 15,96±6,10 mm; p<0,001) e maior número de stents por paciente (1,95 vs. 1,46, p<0,001) no grupo SES. A mortalidade global de cinco e 10 anos por todas as causas foi de 9,6% (n=110) e 22,7% (n=272), respectivamente. A FC ajustada para mortalidade de 10 anos em pacientes submetidos a ICP com SES foi de 0,74 (95% CI 0,58-0,94; p=0,013), correspondendo a uma redução relativa do risco de 19,8%. Para além da ICP com SES, a idade avançada, doença renal crónica, doença pulmonar obstrutiva crónica e a fracção de ejecção inferior foram preditores independentes da mortalidade de 10 anos.
Até à data, este é o estudo de seguimento mais longo a demonstrar um potencial benefício de sobrevida dos stents farmacológicos de primeira geração versus stents metálicos, em linha com estudos prévios que demonstram a sua eficácia e segurança quando comparados com SC contemporâneos.
The widespread use of agrochemicals is detrimental to the environment and may exert harmful effects on human health. The consumer demand for organic food plants has been increasing. There is thus a ...rising need for alternatives to agrochemicals that can foster sustainable plant production. The aim of this study was to evaluate the potential use of an arbuscular mycorrhizal (AM) fungus as an alternative to application of chemical fertilizer for improving growth performance of the medicinal and aromatic plant Coriandrum sativum. Plants were inoculated with the AM fungus Rhizophagus irregularis BEG163 and/or supplemented with a commercial chemical fertilizer (Plant Marvel, Nutriculture Bent Special) in agricultural soil. Plant growth, nutrition, and development of AM fungus were assessed. Plants inoculated with R. irregularis and those supplemented with chemical fertilizer displayed significantly improved growth performances when compared with controls. There were no significant differences in total fresh weight between plants inoculated with R. irregularis or those supplemented with chemical fertilizer. Leaf chlorophyll a + b (82%), shoot nitrogen (44%), phosphorus (254%), and potassium (27%) concentrations increased in plants inoculated with R. irregularis compared to controls. Application of chemical fertilizer inhibited root mycorrhizal colonization and the length of the extraradical mycelium of R. irregularis. Inoculation with R. irregularis was equally or more efficient than application of chemical fertilizer in promoting growth and nutrition of C. sativum. AM fungi may thus contribute to improve biologically based production of food plants and reduce the dependence on agrochemicals in agriculture.
There is an ever-growing need of human tissues and organs for transplantation. However, the availability of such tissues and organs is insufficient by a large margin, which is a huge medical and ...societal problem. Tissue engineering and regenerative medicine (TERM) represent potential solutions to this issue and have therefore been attracting increased interest from researchers and clinicians alike. But the successful large-scale clinical deployment of TERM products critically depends on the development of efficient preservation methodologies. The existing preservation approaches such as slow freezing, vitrification, dry state preservation, and hypothermic and normothermic storage all have issues that somehow limit the biomedical applications of TERM products. In this review, the principles and application of these approaches will be summarized, highlighting their advantages and limitations in the context of TERM products preservation.
Several cetacean species exhibit fine-scale population structure despite their high dispersal capacities and the apparent continuity of the marine environment. In dolphins, most studies have focused ...on coastal areas and continental margins, and they revealed differentiated populations within relatively small geographic areas, sometimes in conjunction with a specialisation for different habitats (ecotypes). We analysed the population genetic structure of short-beaked common dolphins (Delphinus delphis) and Atlantic spotted dolphins (Stenella frontalis) in the Azores and Madeira, the two most isolated archipelagos of the North Atlantic. The archipelago of the Azores is divided into three groups of islands and stands 900 km away from Madeira. It is not known whether individuals migrate between groups of islands and archipelagos, nor whether distinct ecotypes are present. These questions were investigated by genetic analyses of 343 biopsy samples collected on free-ranging dolphins. The analyses consisted in sequencing part of the mitochondrial hyper-variable region, screening up to 14 microsatellite loci, and molecular sexing. Results did not unravel any population structure at the scale of the study area. Lack of differentiation matches expectations for spotted dolphins, which are transient in both archipelagos, but not for common dolphins, which are present year-round in the Azores and potentially resident. Absence of genetic structure over hundreds and even thousands of kilometres implies the existence of gene flow over much larger distances than usually documented in small delphinids, which could be achieved through individual movements. This finding indicates that population structure in oceanic habitat differs from that observed in coastal habitat.
While N‐acetyl azaaurones have already been disclosed for their potential against tuberculosis (TB), their low metabolic stability remains an unaddressed liability. We now report a study designed to ...improve the metabolic stability and solubility of the azaaurone scaffold and to identify the structural requirements for antimycobacterial activity. Replacing the N‐acetyl moiety for a N‐carbamoyl group led to analogues with sub‐ and nanomolar potencies against M. tuberculosis H37Rv, as well as equipotent against drug‐susceptible and drug‐resistant M. tuberculosis isolates. The new N‐carbamoyl azaaurones exhibited improved microsomal stability, compared to their N‐acetylated counterparts, with several compounds displaying moderate to high kinetic solubility. The frequency of spontaneous resistance to azaaurones was observed to be in the range of 10−8, a value that is comparable to current TB drugs in the market. Overall, these results reveal that azaaurones are amenable to structural modifications to improve metabolic and solubility liabilities, and highlight their potential as antimycobacterial agents.
Azaaurones are potent agents against M.tb. This new family of compounds improved the overall metabolic stability and solubility of the scaffold, with 24 compounds with submicromolar activities and 4 compounds in the nanomolar range. Furthermore, all tested derivatives were equipotent among susceptible and drug‐resistant tuberculosis, with activity against multidrug‐resistant (MDR) and extensively drug‐resistant (XDR) clinical M.tb isolates.
Coastal overwash is one of the most important hazards affecting the coastal zone and therefore has been the focus of several studies related to the establishment of setback lines. However, studies of ...extreme overwash (EO) events along urban beaches backed by a seawall or structure are scarce, and reveal the difficulties associated with its assessment, measurement and validation. The Nazaré coastal urban area (located on the west coast of Portugal) is developed adjacent to an embayed reflective beach and is subject to frequent and localized inundation due to EO events capable of overtopping the protection seawall. The current work develops a methodological approach to simulate total water levels (TWL) and seawall overtopping occurrences in time and space, with the ultimate goal of identifying the factors that govern the extreme overwash regime. The method uses multi-decadal time series of site-specific wave and tide, and high-resolution topo-bathymetric data, and recreates the TWL time series for a 36-year period. The model is successfully validated against video imagery and maximum swash line data that provide information on the reach of the water levels measured during modal and extreme TWL conditions along the studied beach. This study establishes the importance of the interaction of the modal and extreme hydrodynamic processes with the beach and backshore morphology. The Nazaré embayment is in equilibrium with the alongshore-varying modal wave conditions, resulting in higher vulnerability of the most sheltered sector during extreme events.
•A model to simulate total water levels and overwash occurrences is presented.•The method is applied to an embayed reflective urban beach backed by a seawall.•Results provide high resolution time and space description of extreme overwash events.•Model results are successfully validated in storm and non-storm conditions.
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