RESUMO
TAVI devices are manufactured with cylindrical frames. However, the frames are rarely cylindrical post-deployment since deformation due to localised under expansion can be induced by calcified material on the native valve leaflets exerting irregular forces upon the frame. Consequently, the leaflets within a deformed TAVI device may undergo elevated stress during operation, which may lead to premature device failure. Using computational analysis a complete TAVI device model was simulated undergoing deployment into an aortic root model derived from CT data for a patient with severe calcific aortic stenosis, followed by a pressure simulated cardiac cycle. The complete analysis was performed eight times, each with the device at a different rotational orientation relative to the native valve, with an increment spacing of 15°. The TAVI device frames consistently featured significant distortions associated with bulky calcified material at the base of the non-coronary sinus. It was found that the average von Mises stress in the prosthetic valves was only increased in one of the cases relative to an idealised device. However, the maximum von Mises stress in the prosthetic valves was elevated in the majority of the cases. Furthermore, it was found that there were preferable orientations to deploy the prosthetic device, in this case, when the prosthetic leaflets were aligned with the native leaflets. As device orientation deviated from this orientation, the stresses in the valve increased because the distance between the prosthetic commissures decreased. This potentially could represent a sufficient increase in stress to induce variation in device lifespan.
Assuntos
Valva Aórtica/fisiologia , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Idoso de 80 Anos ou mais , Valva Aórtica/patologia , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Calcinose/cirurgia , Humanos , Estresse MecânicoRESUMO
Computational simulation of transcatheter aortic valve implantation (TAVI) device deployment presents a significant challenge over and above similar simulations for percutaneous coronary intervention due to the presence of prosthetic leaflets. In light of the complexity of these leaflets, simulations have been performed to assess the effect of including the leaflets in a complete model of a balloon-expandable TAVI device when deployed in a patient-specific aortic root. Using an average model discrepancy metric, the average frame positions (with and without the leaflets) are shown to vary by 0.236% of the expanded frame diameter (26 mm). This relatively small discrepancy leads to the conclusion that for a broad range of replacement valve studies, including new frame configurations and designs, patient-specific assessment of apposition, paravalvular leakage and tissue stress, modelling of the prosthetic leaflets is likely to have a marginal effect on the results
Assuntos
Valva Aórtica/cirurgia , Simulação por Computador , Substituição da Valva Aórtica Transcateter/métodos , Feminino , Humanos , Pessoa de Meia-Idade , Modelos CardiovascularesRESUMO
BACKGROUND: Elderly patients undergoing acute gastrointestinal (GI) surgery experience increased morbidity and mortality compared with younger and elective patients. Prognostic factors can be used to counsel patients of these risks and, if modifiable, to minimize them. We reviewed the literature on prognostic factors for adverse outcomes in elderly patients undergoing acute GI surgery. METHODS: We searched PubMed and Embase using a strategy developed in collaboration with an expert librarian. Studies examining independent associations between prognostic factors and morbidity or mortality in patients aged 65 and older undergoing acute GI surgery were selected. We extracted data using a standardized form and assessed study quality using the QUIPS tool. RESULTS: Nine cohort studies representing 2958 patients satisfied our selection criteria. All studies focused on postoperative mortality. Thirty-four prognostic factors were examined, with significant variability across studies. There was limited or conflicting evidence for most prognostic factors. Meta-analysis was only possible for the American Society of Anesthesiologists (ASA) score, which was found to be associated with mortality in 4 studies (pooled odds ratio 2.77, 95% confidence interval 0.92-8.41). CONCLUSION: While acute GI surgery in elderly patients is becoming increasingly common, the literature on prognostic factors for morbidity and mortality in this patient population lags behind. Further research is needed to help guide patient care and potentially improve outcomes.
CONTEXTE: On constate une morbidité et une mortalité accrues chez les patients âgés soumis à une chirurgie gastro-intestinale (GI) urgente, comparativement aux patients plus jeunes et ceux qui subissent une intervention non urgente. Certains facteurs pronostiques peuvent servir à conseiller les patients au sujet des risques et, s'ils sont modifiables, au sujet de leur atténuation. Nous avons passé en revue la littérature sur les facteurs pronostiques qui sous-tendent l'issue négative d'une chirurgie GI urgente chez des patients âgés. MÉTHODES: Nous avons interrogé les bases de données PubMed et Embase à l'aide d'une stratégie mise au point en collaboration avec un expert bibliothécaire. Nous avons sélectionné les études portant sur les liens indépendants entre facteurs pronostiques et morbidité ou mortalité chez les patients de 65 ans et plus soumis à une chirurgie GI urgente. Nous avons extrait les données à l'aide d'un formulaire standardisé et évalué la qualité des études au moyen de l'outil QUIPS. RÉSULTATS: Neuf études de cohorte regroupant 2958 patients répondaient à nos critères de sélection. Toutes les études faisaient état de la mortalité postopératoire. Trente-quatre facteurs pronostiques ont été analysés et la variabilité entre les études était significative. Les preuves se sont révélées limitées ou divergentes pour la plupart des facteurs pronostiques. Il n'a été possible d'effectuer une méta-analyse que pour le score ASA (American Society of Anesthesiologists), qui s'est révélé associé à la mortalité dans 4 études (rapport des cotes regroupées 2,77, intervalle de confiance de 95 % 0,928,41). CONCLUSION: La chirurgie GI urgente est de plus en plus courante chez les patients âgés, mais la littérature sur les facteurs pronostiques de morbidité et de mortalité chez cette population de patients a pris du retard. Il faudra approfondir la recherche pour orienter le soins des patients et améliorer les résultats.
Assuntos
Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/mortalidade , Fatores Etários , Idoso , Humanos , PrognósticoRESUMO
Human pharmaceuticals and personal care products (PPCPs) are routinely found in biosolids from wastewater treatment plants (WWTPs). Once land applied, the PPCPs in biosolids are potentially available for plant uptake and bioaccumulation. This study used a greenhouse model to investigate uptake of PPCPs commonly detected in biosolids by the agricultural plant Chinese cabbage (Brassica campestris). Two series of greenhouse experiments were conducted as part of this project. In the first set of experiments, four pharmaceuticals were added to an organic matter-rich soil in environmentally relevant concentrations based on typical biosolids application rates, resulting in final soil concentrations of 2.6 ng g(-1) carbamazepine, 3.1 ng g(-1) sulfamethoxazole, 5.4 ng g(-1) salbutamol, and 0.5 ng g(-1) trimethoprim. In the second set of experiments, the cabbage was grown in soil amended with an agronomic rate of biosolids from a local WWTP. The ambient concentration of PPCPs in the biosolids resulted in final soil concentrations of 93.1 ng g(-1) carbamazepine, 67.4 ng g(-1) sulfamethoxazole, 30.3 ng g(-1) salbutamol, 433.7 ng g(-1) triclosan, and 24.7 ng g(-1) trimethoprim. After growing to maturity, the aerials of the plants were separated from roots and the two tissue types were analyzed separately. All four human pharmaceuticals were detected in both tissues in the cabbage grown in the soil fortified with the four pharmaceuticals with median concentrations of 255.4 ng g(-1) aerials and 272.9 ng g(-1) roots carbamazepine; 222.8 ng g(-1) aerials and 260.3 ng g(-1) roots sulfamethoxazole; 108.3 ng g(-1) aerials and 140.6 ng g(-1) roots salbutamol; and 20.6 ng g(-1) aerials and 53.7 ng g(-1) roots trimethoprim. Although all study compounds were present in the biosolids-amended planting soil, only carbamazepine (317.6 ng g(-1) aerials and 416.2 ng g(-1) roots), salbutamol (21.2 ng g(-1) aerials and 187.6 ng g(-1) roots), and triclosan (22.9 ng g(-1) aerials and 1220.1 ng g(-1) roots) were detected in the aerials of the cabbage. In addition to the study compounds detected in the aerials, sulfamethoxazole was detected in the roots of one of the plants in the biosolid-amended soil. In comparison to many previous studies that have utilized PPCP concentration that exceed environmentally relevant concentrations, plants in this study were exposed to environmentally relevant concentrations of the PPCPs, yet resulted in uptake concentrations similar to or greater than those reported in comparable studies. We suggest that rhizosphere conditions, particularly the presence of dissolved organic matter in the planting matrix, might be one of the critical factors determining mobilization and bioavailability of xenobiotic compounds such as PPCPs.
Assuntos
Brassica/metabolismo , Produtos Domésticos/análise , Preparações Farmacêuticas/metabolismo , Poluentes do Solo/metabolismo , Eliminação de Resíduos Líquidos/métodos , Agricultura/métodos , Humanos , Preparações Farmacêuticas/análise , Solo/química , Poluentes do Solo/análiseRESUMO
Chromosome deletions in the mouse have proven invaluable in the dissection of gene function. The brown deletion complex comprises >28 independent genome rearrangements, which have been used to identify several functional loci on chromosome 4 required for normal embryonic and postnatal development. We have constructed a 172-bacterial artificial chromosome contig that spans this 22-megabase (Mb) interval and have produced a contiguous, finished, and manually annotated sequence from these clones. The deletion complex is strikingly gene-poor, containing only 52 protein-coding genes (of which only 39 are supported by human homologues) and has several further notable genomic features, including several segments of >1 Mb, apparently devoid of a coding sequence. We have used sequence polymorphisms to finely map the deletion breakpoints and identify strong candidate genes for the known phenotypes that map to this region, including three lethal loci (l4Rn1, l4Rn2, and l4Rn3) and the fitness mutant brown-associated fitness (baf). We have also characterized misexpression of the basonuclin homologue, Bnc2, associated with the inversion-mediated coat color mutant white-based brown (B(w)). This study provides a molecular insight into the basis of several characterized mouse mutants, which will allow further dissection of this region by targeted or chemical mutagenesis.
Assuntos
Deleção Cromossômica , Glicoproteínas de Membrana/genética , Oxirredutases/genética , Animais , Sequência de Bases , Evolução Biológica , Mapeamento Cromossômico , Cromossomos Artificiais Bacterianos/genética , Feminino , Morte Fetal/genética , Genes Letais , Cor de Cabelo/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Fenótipo , Polimorfismo de Nucleotídeo Único , GravidezRESUMO
The sequence of the mouse genome is a key informational tool for understanding the contents of the human genome and a key experimental tool for biomedical research. Here, we report the results of an international collaboration to produce a high-quality draft sequence of the mouse genome. We also present an initial comparative analysis of the mouse and human genomes, describing some of the insights that can be gleaned from the two sequences. We discuss topics including the analysis of the evolutionary forces shaping the size, structure and sequence of the genomes; the conservation of large-scale synteny across most of the genomes; the much lower extent of sequence orthology covering less than half of the genomes; the proportions of the genomes under selection; the number of protein-coding genes; the expansion of gene families related to reproduction and immunity; the evolution of proteins; and the identification of intraspecies polymorphism.