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1.
Nature ; 578(7794): 256-260, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-32051599

RESUMEN

Prussian blue analogues (PBAs) are a diverse family of microporous inorganic solids, known for their gas storage ability1, metal-ion immobilization2, proton conduction3, and stimuli-dependent magnetic4,5, electronic6 and optical7 properties. This family of materials includes the double-metal cyanide catalysts8,9 and the hexacyanoferrate/hexacyanomanganate battery materials10,11. Central to the various physical properties of PBAs is their ability to reversibly transport mass, a process enabled by structural vacancies. Conventionally presumed to be random12,13, vacancy arrangements are crucial because they control micropore-network characteristics, and hence the diffusivity and adsorption profiles14,15. The long-standing obstacle to characterizing the vacancy networks of PBAs is the inaccessibility of single crystals16. Here we report the growth of single crystals of various PBAs and the measurement and interpretation of their X-ray diffuse scattering patterns. We identify a diversity of non-random vacancy arrangements that is hidden from conventional crystallographic powder analysis. Moreover, we explain this unexpected phase complexity in terms of a simple microscopic model that is based on local rules of electroneutrality and centrosymmetry. The hidden phase boundaries that emerge demarcate vacancy-network polymorphs with very different micropore characteristics. Our results establish a foundation for correlated defect engineering in PBAs as a means of controlling storage capacity, anisotropy and transport efficiency.

2.
Nat Mater ; 2024 Jul 23.
Artículo en Inglés | MEDLINE | ID: mdl-39043928

RESUMEN

By virtue of their open network structures and low densities, metal-organic frameworks (MOFs) are soft materials that exhibit elastic instabilities at low applied stresses. The conventional strategy for improving elastic stability is to increase the connectivity of the underlying MOF network, which necessarily increases the material density and reduces the porosity. Here we demonstrate an alternative paradigm, whereby elastic stability is enhanced in a MOF with an aperiodic network topology. We use a combination of variable-pressure single-crystal X-ray diffraction measurements and coarse-grained lattice-dynamical calculations to interrogate the high-pressure behaviour of the topologically aperiodic system TRUMOF-1, which we compare against that of its ordered congener MOF-5. We show that the topology of the former quenches the elastic instability responsible for pressure-induced framework collapse in the latter, much as irregularity in the shapes and sizes of stones acts to prevent cooperative mechanical failure in drystone walls. Our results establish aperiodicity as a counter-intuitive design motif in engineering the mechanical properties of framework structures that is relevant to MOFs and larger-scale architectures alike.

3.
J Am Chem Soc ; 146(20): 13714-13718, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38723156

RESUMEN

We report the magnetic behavior of the hybrid perovskites [Gua]Mn1-xFe2x/3□x/3(HCOO)3 (0 ≤ x ≤ 0.88), showing that vacancy ordering drives bulk ferrimagnetism for x > 0.6. The behavior is rationalized in terms of a simple microscopic model of percolation-induced ferrimagnetism. Monte Carlo simulations driven by this model reproduce the experimental dependence of magnetic susceptibility on x and show that, at intermediate compositions, domains of short-range vacancy order lead to the emergence of local magnetization. Our results open up a new avenue for the design of multiferroic hybrid perovskites.

4.
CrystEngComm ; 26(5): 673-680, 2024 Jan 29.
Artículo en Inglés | MEDLINE | ID: mdl-38293003

RESUMEN

We explore the role and nature of torsional flexibility of carboxylate-benzene links in the structural chemistry of metal-organic frameworks (MOFs) based on Zn and benzenedicarboxlyate (bdc) linkers. A particular motivation is to understand the extent to which such flexibility is important in stabilising the unusual topologically aperiodic phase known as TRUMOF-1. We compare the torsion angle distributions of TRUMOF-1 models with those for crystalline Zn/1,3-bdc MOFs, including a number of new materials whose structures we report here. We find that both periodic and aperiodic Zn/1,3-bdc MOFs sample a similar range of torsion angles, and hence the formation of TRUMOF-1 does not require any additional flexibility beyond that already evident in chemically-related crystalline phases. Comparison with Zn/1,4-bdc MOFs does show, however, that the lower symmetry of the 1,3-bdc linker allows access to a broader range of torsion angles, reflecting a greater flexibility of this linker.

5.
Angew Chem Int Ed Engl ; 63(22): e202403842, 2024 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-38517212

RESUMEN

The structure of amorphous silicon (a-Si) is widely thought of as a fourfold-connected random network, and yet it is defective atoms, with fewer or more than four bonds, that make it particularly interesting. Despite many attempts to explain such "dangling-bond" and "floating-bond" defects, respectively, a unified understanding is still missing. Here, we use advanced computational chemistry methods to reveal the complex structural and energetic landscape of defects in a-Si. We study an ultra-large-scale, quantum-accurate structural model containing a million atoms, and thousands of individual defects, allowing reliable defect-related statistics to be obtained. We combine structural descriptors and machine-learned atomic energies to develop a classification of the different types of defects in a-Si. The results suggest a revision of the established floating-bond model by showing that fivefold-bonded atoms in a-Si exhibit a wide range of local environments-analogous to fivefold centers in coordination chemistry. Furthermore, it is shown that fivefold (but not threefold) coordination defects tend to cluster together. Our study provides new insights into one of the most widely studied amorphous solids, and has general implications for understanding defects in disordered materials beyond silicon alone.

6.
J Am Chem Soc ; 2023 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-37931061

RESUMEN

Based on simple electrostatic and harmonic potential considerations, we derive a straightforward expression linking the composition of a Prussian blue analogue (PBA) to its propensity to undergo collective structural distortions. We demonstrate the existence of a threshold value, below which PBAs are undistorted and above which PBAs distort by a degree that is controlled by a geometric tolerance factor. Our analysis rationalizes the presence, absence, and magnitude of distortions in a wide range of PBAs and distinguishes their structural chemistry from that of other hybrid perovskites.

7.
J Am Chem Soc ; 145(44): 24249-24259, 2023 Nov 08.
Artículo en Inglés | MEDLINE | ID: mdl-37879069

RESUMEN

We study the phenomenology of cooperative off-centering of K+ ions in potassiated Prussian blue analogues (PBAs). The principal distortion mechanism by which this off-centering occurs is termed a "K-ion slide", and its origin is shown to lie in the interaction between local electrostatic dipoles that couple through a combination of electrostatics and elastic strain. Using synchrotron powder X-ray diffraction measurements, we determine the crystal structures of a range of low-vacancy K2M[Fe(CN)6] PBAs (M = Ni, Co, Fe, Mn, Cd) and establish an empirical link between composition, temperature, and slide-distortion magnitude. Our results reflect the common underlying physics responsible for K-ion slides and their evolution with temperature and composition. Monte Carlo simulations driven by a simple model of dipolar interactions and strain coupling reproduce the general features of the experimental phase behavior. We discuss the implications of our study for optimizing the performance of PBA K-ion battery cathode materials and also its relevance to distortions in other, conceptually related, hybrid perovskites.

8.
Mol Ther ; 30(4): 1451-1464, 2022 04 06.
Artículo en Inglés | MEDLINE | ID: mdl-35038582

RESUMEN

Brain pericytes regulate cerebral blood flow, maintain the integrity of the blood-brain barrier (BBB), and facilitate the removal of amyloid ß (Aß), which is critical to healthy brain activity. Pericyte loss has been observed in brains from patients with Alzheimer's disease (AD) and animal models. Our previous data demonstrated that friend leukemia virus integration 1 (Fli-1), an erythroblast transformation-specific (ETS) transcription factor, governs pericyte viability in murine sepsis; however, the role of Fli-1 and its impact on pericyte loss in AD remain unknown. Here, we demonstrated that Fli-1 expression was up-regulated in postmortem brains from a cohort of human AD donors and in 5xFAD mice, which corresponded with a decreased pericyte number, elevated inflammatory mediators, and increased Aß accumulation compared with cognitively normal individuals and wild-type (WT) mice. Antisense oligonucleotide Fli-1 Gapmer administered via intrahippocampal injection decelerated pericyte loss, decreased inflammatory response, ameliorated cognitive deficits, improved BBB dysfunction, and reduced Aß deposition in 5xFAD mice. Fli-1 Gapmer-mediated inhibition of Fli-1 protected against Aß accumulation-induced human brain pericyte apoptosis in vitro. Overall, these studies indicate that Fli-1 contributes to pericyte loss, inflammatory response, Aß deposition, vascular dysfunction, and cognitive decline, and suggest that inhibition of Fli-1 may represent novel therapeutic strategies for AD.


Asunto(s)
Enfermedad de Alzheimer , Disfunción Cognitiva , Proteína Proto-Oncogénica c-fli-1/metabolismo , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/genética , Péptidos beta-Amiloides/metabolismo , Animales , Encéfalo/metabolismo , Cognición , Disfunción Cognitiva/genética , Disfunción Cognitiva/metabolismo , Humanos , Ratones , Ratones Transgénicos , Pericitos/metabolismo
9.
Mol Ther ; 30(7): 2618-2632, 2022 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-35331906

RESUMEN

Sepsis-associated encephalopathy (SAE) is characterized by acute and diffuse brain dysfunction and correlates with long-term cognitive impairments with no targeted therapy. We used a mouse model of sepsis-related cognitive impairment to examine the role of lncRNA nuclear enriched abundant transcript 1 (Neat1) in SAE. We observed that Neat1 expression was increased in neuronal cells from septic mice and that it directly interacts with hemoglobin subunit beta (Hbb), preventing its degradation. The Neat1/Hbb axis suppressed postsynaptic density protein 95 (PSD-95) levels and decreased dendritic spine density. Neat1 knockout mice exhibited decreased Hbb levels, which resulted in increased PSD-95 levels, increased neuronal dendritic spine density, and decreased anxiety and memory impairment. Neat1 silencing via the antisense oligonucleotide GapmeR ameliorated anxiety-like behavior and cognitive impairment post-sepsis. In conclusion, we uncovered a previously unknown mechanism of the Neat1/Hbb axis in regulating neuronal dysfunction, which may lead to a novel treatment strategy for SAE.


Asunto(s)
MicroARNs , ARN Largo no Codificante , Sepsis , Animales , Modelos Animales de Enfermedad , Subunidades de Hemoglobina , Ratones , Ratones Noqueados , MicroARNs/genética , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Sepsis/complicaciones , Sepsis/genética
10.
Regul Toxicol Pharmacol ; 138: 105327, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36586472

RESUMEN

The nonhuman primate (NHP) has always been a limited resource for pharmaceutical research with ongoing efforts to conserve. This is due to their inherent biological properties, the growth in biotherapeutics and other modalities, and their use in small molecule drug development. The SARS-CoV-2 pandemic has significantly impacted the availability of NHPs due to the immediate need for NHPs to develop COVID-19 vaccines and treatments and the China NHP export ban; thus, accelerating the need to further replace, reduce and refine (3Rs) NHP use. The impact of the NHP shortage on drug development led DruSafe, BioSafe, and the United States (U.S.) Food and Drug Administration (FDA) Center for Drug Evaluation and Research (CDER) to discuss this issue at their 2021 annual meeting. This meeting identified areas to further the 3Rs in NHP use within the current nonclinical safety evaluation regulatory framework and highlighted the need to continue advancing alternative methods towards the aspirational goal to replace use of NHPs in the long term. Alignment across global health authorities is necessary for implementation of approaches that fall outside existing guidelines. This article captures the proceedings from this meeting highlighting current best practices and areas for 3Rs in NHP use.


Asunto(s)
COVID-19 , Primates , Animales , Humanos , Estados Unidos , United States Food and Drug Administration , Vacunas contra la COVID-19 , COVID-19/prevención & control , SARS-CoV-2
11.
BMC Health Serv Res ; 23(1): 23, 2023 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-36627627

RESUMEN

BACKGROUND: Institutions or clinicians (units) are often compared according to a performance indicator such as in-hospital mortality. Several approaches have been proposed for the detection of outlying units, whose performance deviates from the overall performance. METHODS: We provide an overview of three approaches commonly used to monitor institutional performances for outlier detection. These are the common-mean model, the 'Normal-Poisson' random effects model and the 'Logistic' random effects model. For the latter we also propose a visualisation technique. The common-mean model assumes that the underlying true performance of all units is equal and that any observed variation between units is due to chance. Even after applying case-mix adjustment, this assumption is often violated due to overdispersion and a post-hoc correction may need to be applied. The random effects models relax this assumption and explicitly allow the true performance to differ between units, thus offering a more flexible approach. We discuss the strengths and weaknesses of each approach and illustrate their application using audit data from England and Wales on Adult Cardiac Surgery (ACS) and Percutaneous Coronary Intervention (PCI). RESULTS: In general, the overdispersion-corrected common-mean model and the random effects approaches produced similar p-values for the detection of outliers. For the ACS dataset (41 hospitals) three outliers were identified in total but only one was identified by all methods above. For the PCI dataset (88 hospitals), seven outliers were identified in total but only two were identified by all methods. The common-mean model uncorrected for overdispersion produced several more outliers. The reason for observing similar p-values for all three approaches could be attributed to the fact that the between-hospital variance was relatively small in both datasets, resulting only in a mild violation of the common-mean assumption; in this situation, the overdispersion correction worked well. CONCLUSION: If the common-mean assumption is likely to hold, all three methods are appropriate to use for outlier detection and their results should be similar. Random effect methods may be the preferred approach when the common-mean assumption is likely to be violated.


Asunto(s)
Intervención Coronaria Percutánea , Humanos , Hospitales , Ajuste de Riesgo , Modelos Logísticos , Inglaterra
12.
Angew Chem Int Ed Engl ; 62(51): e202314444, 2023 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-37902095

RESUMEN

The sodium-rich antiperovskites (NaRAPs) with composition Na3 OB (B=Br, Cl, I, BH4 , etc.) are a family of materials that has recently attracted great interest for application as solid electrolytes in sodium metal batteries. Non-Arrhenius ionic conductivities have been reported for these materials, the origin of which is poorly understood. In this work, we combined temperature-resolved bulk and local characterisation methods to gain an insight into the origin of this unusual behaviour using Na3 OBr as a model system. We first excluded crystallographic disorder on the anion sites as the cause of the change in activation energy; then identified the presence of a poorly crystalline impurities, not detectable by XRD, and elucidated their effect on ionic conductivity. These findings improve understanding of the processing-structure-properties relationships pertaining to NaRAPs and highlight the need to determine these relationships in other materials systems, which will accelerate the development of high-performance solid electrolytes.

13.
Nat Mater ; 20(6): 841-850, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-33479526

RESUMEN

Metal fluorides, promising lithium-ion battery cathode materials, have been classified as conversion materials due to the reconstructive phase transitions widely presumed to occur upon lithiation. We challenge this view by studying FeF3 using X-ray total scattering and electron diffraction techniques that measure structure over multiple length scales coupled with density functional theory calculations, and by revisiting prior experimental studies of FeF2 and CuF2. Metal fluoride lithiation is instead dominated by diffusion-controlled displacement mechanisms, and a clear topological relationship between the metal fluoride F- sublattices and that of LiF is established. Initial lithiation of FeF3 forms FeF2 on the particle's surface, along with a cation-ordered and stacking-disordered phase, A-LixFeyF3, which is structurally related to α-/ß-LiMn2+Fe3+F6 and which topotactically transforms to B- and then C-LixFeyF3, before forming LiF and Fe. Lithiation of FeF2 and CuF2 results in a buffer phase between FeF2/CuF2 and LiF. The resulting principles will aid future developments of a wider range of isomorphic metal fluorides.

14.
Acc Chem Res ; 54(5): 1288-1297, 2021 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-33600147

RESUMEN

ConspectusThe structural degrees of freedom of a solid material are the various distortions most straightforwardly activated by external stimuli such as temperature, pressure, or adsorption. One of the most successful design strategies in materials chemistry involves controlling these individual distortions to produce useful collective functional responses. In a ferroelectric such as lead titanate, for example, the key degree of freedom involves asymmetric displacements of Pb2+ and Ti4+ cations; it is by coupling these together that the system as a whole interacts with external electric fields. Collective rotations of the polyhedral units in oxide ceramics are another commonly exploited distortion, driving anomalous behavior such as negative thermal expansion-the counterintuitive phenomenon of volume contraction on heating. An exciting development in the field has been to take advantage of the interplay between different distortion types: generating polarization by combining two different polyhedral rotations, for example. In this way, degrees of freedom act as geometric "elements" that can themselves be combined to engineer materials with new and interesting properties. Just as the discovery of new chemical elements quite obviously diversified chemical space, we might expect that identifying new and different types of structural degrees of freedom to be an important strategy for developing new kinds of functional materials. In this context, the broad family of molecular frameworks is emerging as an extraordinarily fertile source of new and unanticipated distortion types, the vast majority of which have no parallel in the established families of conventional solid-state chemistry.Framework materials are solids whose structures are assembled from two fundamental components: nodes and linkers. Quite simply, linkers join the nodes together to form scaffolding-like networks that extend from the atomic to the macroscopic scale. These structures usually contain cavities, which can also accommodate additional ions for charge balance. In the well-established systems-such as lead titanate-node, linker, and extra-framework ions are all individual atoms (Ti, O, and Pb, respectively). But in molecular frameworks, at least one of these components is a molecule.In this Account, we survey the unconventional degrees of freedom introduced through the simple act of replacing atoms by molecules. Our motivation is to understand the role these new distortions play (or might be expected to play) in different materials properties. The various degrees of freedom themselves-unconventional rotational, translational, orientational, and conformational states-are summarized and described in the context of relevant experimental examples. The much-improved prospect for generating emergent functionalities by combining these new distortion types is then discussed. We highlight a number of directions for future research-including the design and application of hierarchically structured phases of matter intermediate to solids and liquid crystals-which serve to highlight the extraordinary possibilities for this nascent field.

15.
Phys Rev Lett ; 128(17): 177201, 2022 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-35570439

RESUMEN

In the dense metal-organic framework Na[Mn(HCOO)_{3}], Mn^{2+} ions (S=5/2) occupy the nodes of a "trillium" net. We show that the system is strongly magnetically frustrated: the Néel transition is suppressed well below the characteristic magnetic interaction strength; short-range magnetic order persists far above the Néel temperature; and the magnetic susceptibility exhibits a pseudo-plateau at 1/3-saturation magnetization. A simple model of nearest-neighbor Heisenberg antiferromagnetic and dipolar interactions accounts quantitatively for all observations, including an unusual 2-k magnetic ground state. We show that the relative strength of dipolar interactions is crucial to selecting this particular ground state. Geometric frustration within the classical spin liquid regime gives rise to a large magnetocaloric response at low applied fields that is degraded in powder samples as a consequence of the anisotropy of dipolar interactions.

16.
Biotechnol Bioeng ; 119(1): 187-198, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34676884

RESUMEN

Cellular quiescence is a reversible state of cell cycle arrest whereby cells are temporarily maintained in the nondividing phase. Inducing quiescence in cancer cells by targeting growth receptors is a treatment strategy to slow cell growth in certain aggressive tumors, which in turn increases the efficacy of treatments such as surgery or systemic chemotherapy. However, ligand interactions with cell receptors induce receptor-mediated endocytosis followed by proteolytic degradation, which limits the duration of cellular quiescence. Here, we report the effects of targeted covalent affibody photoconjugation to epidermal growth factor receptors (EGFR) on EGFR-positive MDA-MB-468 breast cancer cells. First, covalently conjugating affibodies to cells increased doubling time two-fold and reduced ERK activity by 30% as compared to cells treated with an FDA-approved anti-EGFR antibody Cetuximab, which binds to EGFR noncovalently. The distribution of cells in each phase of the cell cycle was determined, and cells conjugated with the affibody demonstrated an accumulation in the G1 phase, indicative of G1 cell cycle arrest. Finally, the proliferative capacity of the cells was determined by the incorporation of 5-ethynyl-2-deoxyuridine and Ki67 Elisa assay, which showed that the percentage of proliferative cells with photoconjugated affibody was half of that found for the untreated control.


Asunto(s)
Muerte Celular/efectos de los fármacos , Receptores ErbB , Procesos Fotoquímicos , Proteínas Recombinantes de Fusión , Neoplasias de la Mama/metabolismo , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Receptores ErbB/química , Receptores ErbB/metabolismo , Femenino , Humanos , Proteínas Recombinantes de Fusión/química , Proteínas Recombinantes de Fusión/metabolismo , Proteínas Recombinantes de Fusión/farmacología
17.
J Thromb Thrombolysis ; 53(2): 479-484, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34347201

RESUMEN

The cumulative incidence of symptomatic venous thromboembolism (VTE) among patients with malignant gliomas (MG) is estimated to be as high as 36% during the course of therapy. Development of VTE is associated with an increased risk of hospitalization, delays in cancer treatment, and an increased risk of complications including intracranial hemorrhage as well as VTE specific symptoms. Despite the high risk of VTE and associated morbidity, there is no standard recommendations regarding long term outpatient VTE prophylaxis in patients with MG due to the lack of clinical trial evidence in this patient population. In this study, we treated ten patients with newly diagnosed MG with apixaban, 2.5 mg twice daily beginning 2-21 days after craniotomy and continuing for up to 6 months. Unacceptable toxicity was defined by ≥ grade 2 CNS or non-CNS hemorrhage, a thromboembolic event (i.e. stroke) or cardiovascular event requiring anticoagulation or anti-platelet therapy. There were no unacceptable toxicities to report and no treatment-related adverse events. None of the patients on the study were diagnosed with a VTE while receiving apixaban. We conclude that apixaban can be given safely to patients with primary MG shortly after craniotomy and should be considered for VTE prevention in these high-risk patients.


Asunto(s)
Glioma , Tromboembolia Venosa , Anticoagulantes/uso terapéutico , Glioma/complicaciones , Glioma/tratamiento farmacológico , Glioma/cirugía , Humanos , Pirazoles , Piridonas/efectos adversos , Tromboembolia Venosa/epidemiología , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & control
18.
Eur Heart J ; 43(1): 44-52, 2021 12 28.
Artículo en Inglés | MEDLINE | ID: mdl-34468733

RESUMEN

AIMS: Operability of type A acute aortic dissections (TAAAD) is currently based on non-standardized decision-making process, and it lacks a disease-specific risk evaluation model that can predict mortality. We investigated patient, intraoperative data, surgeon, and centre-related variables for patients who underwent TAAAD in the UK. METHODS AND RESULTS: We identified 4203 patients undergoing TAAAD surgery in the UK (2009-18), who were enrolled into the UK National Adult Cardiac Surgical Audit dataset. The primary outcome was operative mortality. A multivariable logistic regression analysis was performed with fast backward elimination of variables and the bootstrap-based optimism-correction was adopted to assess model performance. Variation related to hospital or surgeon effects were quantified by a generalized mixed linear model and risk-adjusted funnel plots by displaying the individual standardized mortality ratio against expected deaths. Final variables retained in the model were: age [odds ratio (OR) 1.02, 95% confidence interval (CI) 1.02-1.03; P < 0.001]; malperfusion (OR 1.79, 95% CI 1.51-2.12; P < 0.001); left ventricular ejection fraction (moderate: OR 1.40, 95% CI 1.14-1.71; P = 0.001; poor: OR 2.83, 95% CI 1.90-4.21; P < 0.001); previous cardiac surgery (OR 2.29, 95% CI 1.71-3.07; P < 0.001); preoperative mechanical ventilation (OR 2.76, 95% CI 2.00-3.80; P < 0.001); preoperative resuscitation (OR 3.36, 95% CI 1.14-9.87; P = 0.028); and concomitant coronary artery bypass grafting (OR 2.29, 95% CI 1.86-2.83; P < 0.001). We found a significant inverse relationship between surgeons but not centre annual volume with outcomes. CONCLUSIONS: Patient characteristics, intraoperative factors, cardiac centre, and high-volume surgeons are strong determinants of outcomes following TAAAD surgery. These findings may help refining clinical decision-making, supporting patient counselling and be used by policy makers for quality assurance and service provision improvement.


Asunto(s)
Disección Aórtica , Procedimientos Quirúrgicos Cardíacos , Adulto , Disección Aórtica/cirugía , Mortalidad Hospitalaria , Humanos , Complicaciones Posoperatorias , Estudios Retrospectivos , Factores de Riesgo , Volumen Sistólico , Resultado del Tratamiento , Reino Unido/epidemiología , Función Ventricular Izquierda
19.
Aust Crit Care ; 35(4): 355-361, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-34321180

RESUMEN

BACKGROUND: Nonurban residential living is associated with adverse outcomes for a number of chronic health conditions. However, it is unclear what effect it has amongst survivors of critical illness. OBJECTIVES: The purpose of this study is to determine whether patients living greater than 50 km from the treating intensive care unit (ICU) have disability outcomes at 6 months that differ from people living within 50 km. METHODS: This was a multicentre, prospective cohort study conducted in five metropolitan ICUs. Participants were adults admitted to the ICU, who received >24 h of mechanical ventilation and survived to hospital discharge. In a secondary analysis of these data, the cohort was dichotomised based on residential distance from the treating ICU: <50 km and ≥50 km. The primary outcome was patient-reported disability using the 12-item World Health Organization's Disability Assessment Schedule (WHODAS 2.0). This was recorded at 6 months after ICU admission by telephone interview. Secondary outcomes included health status as measured by EQ-5D-5L return to work and psychological function as measured by the Hospital Anxiety and Depression Scale (HADS). Multivariable logistic regression was used to assess the association between distance from the ICU and moderate to severe disability, adjusted for potential confounders. Variables included in the multivariable model were deemed to be clinically relevant and had baseline imbalance between groups (p < 0.10). These included marital status and hours of mechanical ventilation. Sensitivity analysis was also conducted using distance in kilometres as a continuous variable. RESULTS: A total of 262 patients were enrolled, and 169 (65%) lived within 50 km of the treating ICU and 93 (35%) lived ≥50 km from the treating ICU (interquartile range [IQR] 10-664 km). There was no difference in patient-reported disability at 6 months between patients living <50 km and those living ≥50 km (WHODAS total disability % [IQR] 10.4 [2.08-25] v 14.6 [2.08-20.8], P = 0.74). There was also no difference between groups for the six major life domains of the WHODAS. There was no difference in rates of anxiety or depression as measured by HADS score (HADS anxiety median [IQR] 4 [1-7] v 3 [1-7], P = 0.60) (HADS depression median [IQR] 3 [1-6] v 3 [1-6], P = 0.62); health status as measured by EQ-5D (mean [SD] 66.7 [20] v 69.8 [22.2], P = 0.24); or health-related unemployment (% (N) 39 [26] v 25 [29.1], P = 0.61). After adjusting for confounders, living ≥50 km from the treating ICU was not associated with increased disability (odds ratio 0.61, 95% confidence interval: 0.33-1.16; P = 0.13) CONCLUSIONS: Survivors of intensive care in Victoria, Australia, who live at least 50 km from the treating ICU did not have greater disability than people living less than 50 km at 6 months after discharge. Living 50 km or more from the treating ICU was not associated with disability, nor was it associated with anxiety or depression, health status, or unemployment due to health.


Asunto(s)
Unidades de Cuidados Intensivos , Calidad de Vida , Adulto , Enfermedad Crítica/psicología , Humanos , Estudios Prospectivos , Victoria
20.
Lab Invest ; 101(5): 625-635, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33446892

RESUMEN

Pericytes apposed to the capillary endothelium are known to stabilize and promote endothelial integrity. Recent studies indicate that lung pericytes play a prominent role in lung physiology, and they are involved in the development of various lung diseases including lung injury in sepsis, pulmonary fibrosis, asthma, and pulmonary hypertension. Accordingly, human lung pericyte studies are important for understanding the mechanistic basis of lung physiology and pathophysiology; however, human lung pericytes can only be cultured for a few passages and no immortalized human lung pericyte cell line has been established so far. Thus, our study aims to establish an immortalized human lung pericyte cell line. Developed using SV40 large T antigen lentivirus, immortalized pericytes exhibit stable SV40T expression, sustained proliferation, and have significantly higher telomerase activity compared to normal human lung pericytes. In addition, these cells retained pericyte characteristics, marked by similar morphology, and expression of pericyte cell surface markers such as PDGFRß, NG2, CD44, CD146, CD90, and CD73. Furthermore, similar to that of primary pericytes, immortalized pericytes promoted endothelial cell tube formation and responded to different stimuli. Our previous data showed that friend leukemia virus integration 1 (Fli-1), a member of the ETS transcription factor family, is a key regulator that modulates inflammatory responses in mouse lung pericytes. We further demonstrated that Fli-1 regulates inflammatory responses in immortalized human lung pericytes. To summarize, we successfully established an immortalized human lung pericyte cell line, which serves as a promising tool for in vitro pericyte studies to understand human lung pericyte physiology and pathophysiology.


Asunto(s)
Línea Celular , Pulmón/citología , Pericitos , Proteínas de Microfilamentos/metabolismo , Transactivadores/metabolismo
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