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| 3. |
- Bravo, L, et al.
(author)
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- 2021
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swepub:Mat__t
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| 4. |
- Tabiri, S, et al.
(author)
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- 2021
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swepub:Mat__t
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| 5. |
- Glasbey, JC, et al.
(author)
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- 2021
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swepub:Mat__t
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| 7. |
- Khatri, C, et al.
(author)
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Outcomes after perioperative SARS-CoV-2 infection in patients with proximal femoral fractures: an international cohort study
- 2021
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In: BMJ open. - : BMJ. - 2044-6055. ; 11:11, s. e050830-
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Journal article (peer-reviewed)abstract
- Studies have demonstrated high rates of mortality in people with proximal femoral fracture and SARS-CoV-2, but there is limited published data on the factors that influence mortality for clinicians to make informed treatment decisions. This study aims to report the 30-day mortality associated with perioperative infection of patients undergoing surgery for proximal femoral fractures and to examine the factors that influence mortality in a multivariate analysis.SettingProspective, international, multicentre, observational cohort study.ParticipantsPatients undergoing any operation for a proximal femoral fracture from 1 February to 30 April 2020 and with perioperative SARS-CoV-2 infection (either 7 days prior or 30-day postoperative).Primary outcome30-day mortality. Multivariate modelling was performed to identify factors associated with 30-day mortality.ResultsThis study reports included 1063 patients from 174 hospitals in 19 countries. Overall 30-day mortality was 29.4% (313/1063). In an adjusted model, 30-day mortality was associated with male gender (OR 2.29, 95% CI 1.68 to 3.13, p<0.001), age >80 years (OR 1.60, 95% CI 1.1 to 2.31, p=0.013), preoperative diagnosis of dementia (OR 1.57, 95% CI 1.15 to 2.16, p=0.005), kidney disease (OR 1.73, 95% CI 1.18 to 2.55, p=0.005) and congestive heart failure (OR 1.62, 95% CI 1.06 to 2.48, p=0.025). Mortality at 30 days was lower in patients with a preoperative diagnosis of SARS-CoV-2 (OR 0.6, 95% CI 0.6 (0.42 to 0.85), p=0.004). There was no difference in mortality in patients with an increase to delay in surgery (p=0.220) or type of anaesthetic given (p=0.787).ConclusionsPatients undergoing surgery for a proximal femoral fracture with a perioperative infection of SARS-CoV-2 have a high rate of mortality. This study would support the need for providing these patients with individualised medical and anaesthetic care, including medical optimisation before theatre. Careful preoperative counselling is needed for those with a proximal femoral fracture and SARS-CoV-2, especially those in the highest risk groups.Trial registration numberNCT04323644
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| 10. |
- McCrae, Cristopher, et al.
(author)
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Lanosterol Synthase Regulates Human Rhinovirus Replication in Human Bronchial Epithelial Cells
- 2018
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In: American Journal of Respiratory Cell and Molecular Biology. - 1044-1549. ; 59:6, s. 713-722
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Journal article (peer-reviewed)abstract
- Human rhinovirus (RV) infections are a significant risk factor for exacerbations of asthma and chronic obstructive pulmonary disease. Thus, approaches to prevent RV infection in such patients would give significant benefit. Through RNA interference library screening, we identified lanosterol synthase (LSS), a component of the cholesterol biosynthetic pathway, as a novel regulator of RV replication in primary normal human bronchial epithelial cells. Selective knock down of LSS mRNA with short interfering RNA inhibited RV2 replication in normal human bronchial epithelial cells. Small molecule inhibitors of LSS mimicked the effect of LSS mRNA knockdown in a concentration-dependent manner. We further demonstrated that the antiviral effect is not dependent on a reduction in total cellular cholesterol but requires a 24-hour preincubation with the LSS inhibitor. The rank order of antiviral potency of the LSS inhibitors used was consistent with LSS inhibition potency; however, all compounds showed remarkably higher potency against RV compared with the LSS enzyme potency. We showed that LSS inhibition led to an induction of 24(S),25 epoxycholesterol, an important regulator of the sterol pathway. We also demonstrated that LSS inhibition led to a profound increase in expression of the innate antiviral defense protein, IFN-beta. We found LSS to be a novel regulator of RV replication and innate antiviral immunity and identified a potential molecular mechanism for this effect, via induction of 24(S),25 epoxycholesterol. Inhibition of LSS could therefore be a novel therapeutic target for prevention of RV-induced exacerbations.
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| 18. |
- Filippi, M, et al.
(author)
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Author Correction: Multiple sclerosis
- 2018
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In: Nature reviews. Disease primers. - : Springer Science and Business Media LLC. - 2056-676X. ; 4:1, s. 49-
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Journal article (other academic/artistic)
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| 19. |
- Filippi, M, et al.
(author)
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Multiple sclerosis
- 2018
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In: Nature reviews. Disease primers. - : Springer Science and Business Media LLC. - 2056-676X. ; 4:1, s. 43-
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Journal article (peer-reviewed)
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| 20. |
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| 21. |
- Bes, R., et al.
(author)
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New insight in the uranium valence state determination in UyNd1-yO2 +/- x
- 2018
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In: Journal of Nuclear Materials. - : ELSEVIER SCIENCE BV. - 0022-3115 .- 1873-4820. ; 507, s. 145-150
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Journal article (peer-reviewed)abstract
- The charge compensation mechanisms in UyNd1-yO2 +/- x, and its consequence on the overall O stoichiometry (or O/M ratio where M = Nd + U) have been studied through the uranium valence state mixture evolution as a function of Nd content up to y = 0.62 by means of high energy resolution fluorescence detection X-ray absorption spectroscopy (HERFD-XAS) at the U M-4-edge. Our results clearly demonstrate the formation of U5+ at low Nd content (y < 0.15). Upon increasing the Nd content, oxygen vacancies and the formation of U6+ appear as competing mechanisms for intermediate Nd concentrations, leading to the co-existence of U4+/U5+/U6+ mixed valence and an overall hypostoichiometry (O/M < 2.00). Finally, the formation of U6+ associated with strongly distorted U local environment is observed for high Nd concentrations (y = 0.62), leading to an overall hyperstoichiometry (O/M < 2.00).
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| 22. |
- Henriksson, J, et al.
(author)
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Chromosomal size variation in Trypanosoma cruzi is mainly progressive andis evolutionarily informative
- 2002
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In: Parasitology. - 0031-1820 .- 1469-8161. ; 124:Pt3, s. 277-286
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Journal article (peer-reviewed)abstract
- The evolutionary significance of chromosome size polymorphism was explored in a representative panel of 26 Trypanosoma cruzi stocks. We tested a progressive model (aCSDI) assuming that the larger the size difference between homologous chromosomes, the more divergent the parasites are. This was contrasted with a non-progressive model (Jaccard's distance), in which any chromosome size difference has the same weight. ACSDI-based dendrograms were very similar to those built-up from multilocus enzyme electrophoresis (MLEE) and random amplified polymorphic DNA (RAPD) data: structuring in 2 major lineages (T. cruzi I and T. cruz II) and 5 small subdivisions within T. cruzi II was identical, and branching was very similar. Furthermore, a significant correlation (P < 0.001) was observed between aCSDI and phenetic distances calculated from MLEE and RAPD data. In contrast, analysis of chromosome size polymorphism with Jaccard's distance generated dendrograms with relatively long branches, causing most branching points to cluster close together, which generates statistically uncertain branching points. Our results thus support a model of progressive chromosome size-variation and show that despite an extensive polymorphism, chromosomal sizes constitute valuable characters for evolutionary analyses. Furthermore, our data are consistent with the clonal evolution model previously proposed for T. cruzi.
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| 23. |
- Natiello, Mario A., et al.
(author)
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Modelling population dynamics based on experimental trials with genetically modified (RIDL) mosquitoes
- 2020
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In: Ecological Modelling. - : Elsevier BV. - 0304-3800. ; 424
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Journal article (peer-reviewed)abstract
- Recently, the RIDL-SIT technology has been field-tested for control of Aedes aegypti. The technique consists of releasing genetically modified mosquitoes carrying a “lethal gene”. In 2016 the World Health Organization (WHO) and the Pan-American Health Organization (PAHO) recommended to their constituent countries to test the new technologies proposed to control Aedes aegypti populations. However, issues concerning effectiveness and ecological impact have not been thoroughly studied so far. In order to study these issues, we develop an ecological model. It presents interdependent dynamics of mosquito populations and food in a homogeneous setting. Mosquito populations are described in a stochastic compartmental setup, in terms of reaction norms depending on the available food in the environment. The development of the model allows us to indicate some critical biological knowledge that is missing and could (should) be produced. Hybridisation levels, release numbers during and after intervention and population recovery time after the intervention as a function of intervention duration and target are calculated under different hypotheses with regard to the fitness of hybrids and compared with two field studies of actual interventions. This minimal model should serve as a basis for detailed models when the necessary information to construct them is produced. For the time being, the model shows that nature will not clean non-lethal introgressed genes.
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| 24. |
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| 25. |
- Solari, H. G., et al.
(author)
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A Constructivist View of Newton’s Mechanics
- 2019
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In: Foundations of Science. - : Springer Science and Business Media LLC. - 1233-1821 .- 1572-8471. ; 24:2, s. 307-341
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Journal article (peer-reviewed)abstract
- In the present essay we attempt to reconstruct Newtonian mechanics under the guidance of logical principles and of a constructive approach related to the genetic epistemology of Piaget and García (Psychogenesis and the history of science, Columbia University Press, New York, 1989). Instead of addressing Newton’s equations as a set of axioms, ultimately given by the revelation of a prodigious mind, we search for the fundamental knowledge, beliefs and provisional assumptions that can produce classical mechanics. We start by developing our main tool: the no arbitrariness principle, that we present in a form that is apt for a mathematical theory as classical mechanics. Subsequently, we introduce the presence of the observer, analysing then the relation objective–subjective and seeking objectivity going across subjectivity. We take special care of establishing the precedence among all contributions to mechanics, something that can be better appreciated by considering the consequences of removing them: (a) the consequence of renouncing logic and the laws of understanding is not being able to understand the world, (b) renouncing the early elaborations of primary concepts such as time and space leads to a dissociation between everyday life and physics, the latter becoming entirely pragmatic and justified a-posteriori (because it is convenient), (c) changing our temporary beliefs has no real cost other than effort. Finally, we exemplify the present approach by reconsidering the constancy of the velocity of light. It is shown that it is a result of Newtonian mechanics, rather than being in contradiction with it. We also indicate the hidden assumption that leads to the (apparent) contradiction.
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| 26. |
- Solari, N, et al.
(author)
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Understanding cognitive deficits in Parkinson's disease: lessons from preclinical animal models
- 2013
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In: Learning & memory (Cold Spring Harbor, N.Y.). - : Cold Spring Harbor Laboratory. - 1549-5485. ; 20:10, s. 592-600
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Journal article (peer-reviewed)abstract
- Parkinson’s disease (PD) has been, until recently, mainly defined by the presence of characteristic motor symptoms, such as rigidity, tremor, bradykinesia/akinesia, and postural instability. Accordingly, pharmacological and surgical treatments have so far addressed these motor disturbances, leaving nonmotor, cognitive deficits an unmet clinical condition. At the preclinical level, the large majority of studies aiming at defining mechanisms and testing novel therapies have similarly focused on the motor aspects of PD. Unfortunately, deterioration of the executive functions, such as attention, recognition, working memory, and problem solving, often appear in an early, premotor phase of the disease and progressively increase in intensity, negatively affecting the quality of life of ∼50%–60% of PD patients. At present, the cellular mechanisms underlying cognitive impairments in PD patients are largely unknown and an adequate treatment is still missing. The preclinical research has recently developed new animal models that may open new perspectives for a more integrated approach to the treatment of both motor and cognitive symptoms of the disease. This review will provide an overview on the cognitive symptoms occurring in early PD patients and then focus on the rodent and nonhuman primate models so far available for the study of discriminative and spatial memory attention and learning abilities related to this pathological condition.
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| 27. |
- Venegas, Juan A., et al.
(author)
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Cloning and characterization of a DNA polymerase beta gene from Trypanosoma cruzi
- 2009
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In: Parasitology international. - : Elsevier BV. - 1383-5769 .- 1873-0329. ; 58:2, s. 187-192
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Journal article (peer-reviewed)abstract
- A gene coding for a DNA polymerase beta from the Trypanosoma cruzi Miranda clone, belonging to the TcI lineage, was cloned (Miranda Tcpol beta), using the information from eight peptides of the T. cruzi beta-like DNA polymerase purified previously. The gene encodes for a protein of 403 amino acids which is very similar to the two T. cruzi CL Brener (TcIIe lineage) sequences published, but has three different residues in highly conserved segments. At the amino acid level, the identity of TcI-pol beta with mitochondrial pol beta and pol beta-PAK from other trypanosomatids was between 68-80% and 22-30%, respectively. Miranda Tc-pol beta protein has an N-terminal sequence similar to that described in the mitochondrial Crithidia fasciculata pol beta, which suggests that the TcI-pol beta plays a role in the organelle. Northern and Western analyses showed that this T. cruzi gene is highly expressed both in proliferative and non-proliferative developmental forms. These results suggest that, in addition to replication of kDNA in proliferative cells, this enzyme may have another function in non-proliferative cells, such as DNA repair role similar to that which has extensively been described in a vast spectrum of eukaryotic cells.
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