Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 64
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Methods Mol Biol ; 2301: 235-258, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34415539

RESUMO

Fluorescence in situ hybridization and chromosome conformation capture methods point to the same conclusion: that chromosomes appear to the external observer as compact structures with a highly nonrandom three-dimensional organization. In this work, we recapitulate the efforts made by us and other groups to rationalize this behavior in terms of the mathematical language and tools of polymer physics. After a brief introduction dedicated to some crucial experiments dissecting the structure of interphase chromosomes, we discuss at a nonspecialistic level some fundamental aspects of theoretical and numerical polymer physics. Then, we inglobe biological and polymer aspects into a polymer model for interphase chromosomes which moves from the observation that mutual topological constraints, such as those typically present between polymer chains in ordinary melts, induce slow chain dynamics and "constraint" chromosomes to resemble double-folded randomly branched polymer conformations. By explicitly turning these ideas into a multi-scale numerical algorithm which is described here in full details, we can design accurate model polymer conformations for interphase chromosomes and offer them for systematic comparison to experiments. The review is concluded by discussing the limitations of our approach and pointing to promising perspectives for future work.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34694376

RESUMO

AIMS: There is little information about hypertrophic cardiomyopathy (HCM) with pathologic genetic mutations and concurrent hypertension (HTN). Hypertensive left ventricular hypertrophy (LVH) does not exclude an underlying genetic aetiology. METHODS AND RESULTS: This was a single-centre case-control study of 39 adults with pathologic HCM mutations, confirmed by genetic testing, compared to 39 age- and gender-matched patients with hypertensive LVH. The gene-positive HCM cohort was further stratified by the coexisting presence or absence of HTN. Clinical and echocardiographic characteristics were compared. Of 39 gene-positive HCM, 43.6% (17/39) had concurrent HTN. The gene-positive HCM cohort had larger left atrial (LA) area (22.1 cm2 vs. 18.9 cm2, P = 0.002), more diastolic predominant pulmonary vein flow (38.5% vs. 7.7%, P = 0.001), and more moderate diastolic dysfunction (33.3% vs. 12.8%, P = 0.032) when compared with the hypertensive LVH cohort. Greater left ventricular (LV) mass (277.7 g vs. 207.7 g, P = 0.025), increased frequency of severe LVH (58.8% vs. 27.3%, P = 0.047), and more abnormal global longitudinal strain (GLS) (-14.1% vs. -16.9%, P = 0.049) was observed in the gene-positive HCM cohort with concurrent HTN. CONCLUSION: Gene-positive HCM, compared to hypertensive LVH, is characterized by more advanced diastolic dysfunction and larger LA size. Gene-positive HCM patients with concomitant HTN had greater LV mass, more severe LVH, and more abnormal GLS, suggesting HTN may negatively affect the progression of myocardial dysfunction in genetic HCM. LVH out-of-proportion to pressure burden in HTN patients should raise suspicion of underlying genetic HCM.

3.
BMC Health Serv Res ; 21(1): 889, 2021 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-34454500

RESUMO

BACKGROUND: In the scientific literature, many studies describe the application of lean methodology in the hospital setting. Most of the articles focus on the results rather than on the approach adopted to introduce the lean methodology. In the absence of a clear view of the context and the introduction strategy, the first steps of the implementation process can take on an empirical, trial and error profile. Such implementation is time-consuming and resource-intensive and affects the adoption of the model at the organizational level. This research aims to outline the role contextual factors and introduction strategy play in supporting the operators introducing lean methodology in a hospital setting. METHODOLOGY: The methodology is revealed in a case study of an important hospital in Southern Italy, where lean has been successfully introduced through a pilot project in the pathway of cancer patients. The originality of the research is seen in the detailed description of the contextual elements and the introduction strategy. RESULTS: The results show significant process improvements and highlight the spontaneous dissemination of the culture of change in the organization and the streamlined adoption at the micro level. CONCLUSION: The case study shows the importance of the lean introduction strategy and contextual factors for successful lean implementation. Furthermore, it shows how both factors influence each other, underlining the dynamism of the organizational system.


Assuntos
Hospitais , Gestão da Qualidade Total , Humanos , Itália , Projetos Piloto
4.
Clin Transplant ; 35(11): e14451, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34365682

RESUMO

BACKGROUND: Adults with congenital heart disease (ACHD) may undergo heart transplantation (HTx) despite increased risk of poor short-term outcomes due to factors including surgical complexity and antibody sensitization. We assessed the clinical characteristics and outcomes of patients with ACHD in the current era referred for HTx at a single high-volume transplant center. METHODS: From 2010 to 2020, 37 ACHD patients were evaluated for HTx. ACHD HTx recipients were compared to non-ACHD HTx recipients matched for age, sex, listing status, and prior cardiac surgery. RESULTS: Of the 37 patients with ACHD, eight (21.6%) were declined for HTx. Of 29 ACHD patients listed, 19 (65.5%) underwent HTx. Compared with non-ACHD HTx controls, the ACHD HTx recipients had more treated cellular (21.1% vs. 15.8%, P = .010) and antibody-mediated (15.8% vs. 10.5%, P = .033) rejection. There was no difference in hospital readmission or allograft vasculopathy at 1 year. There was a nonsignificant higher 1-year mortality in ACHD HTx recipients (21.1% vs. 7.9%, P = .21). CONCLUSION: At a high-volume transplant center, ACHD patients undergoing HTx appear to have a marginally higher risk of rejection, but no significant increase in 1-year mortality. With careful selection and management, HTx for patients with ACHD may be feasible in the current era.

5.
Soft Matter ; 17(30): 7111-7117, 2021 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-34254620

RESUMO

We study the motion of dispersed nanoprobes in entangled active-passive polymer mixtures. By comparing the two architectures of linear vs. unconcatenated and unknotted circular polymers, we demonstrate that novel, rich physics emerge. For both polymer architectures, nanoprobes of size smaller than the entanglement threshold of the solution move faster as activity is increased and more energy is pumped in the system. For larger nanoprobes, a surprising phenomenon occurs: while in linear solutions they move qualitatively as before, in active-passive ring solutions nanoprobes decelerate with respect to the purely passive conditions. We rationalize this effect in terms of the non-equilibrium, topology-dependent association (clustering) of nanoprobes to the cold component of the ring mixture reminiscent of the recently discovered [Weber et al., Phys. Rev. Lett., 2016, 116, 058301] phase separation in scalar active-passive mixtures. We conclude with a potential connection to the microrheology of the chromatin in the nuclei of the cells.

6.
J Chem Phys ; 154(2): 024903, 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33445920

RESUMO

We propose a formalism for deriving force-elongation and elongation-force relations for flexible chain molecules from analytical expressions for their radial distribution function, which provides insight into the factors controlling the asymptotic behavior and finite chain length corrections. In particular, we apply this formalism to our previously developed interpolation formula for the wormlike chain end-to-end distance distribution. The resulting expression for the asymptotic limit of infinite chain length is of similar quality to the numerical evaluation of Marko and Siggia's variational theory and considerably more precise than their interpolation formula. A comparison to numerical data suggests that our analytical finite chain length corrections achieve a comparable accuracy. As an application of our results, we discuss the possibility of inferring the time-dependent number of nicks in single-molecule stretching experiments on double-stranded DNA from the accompanying changes in the effective chain length.


Assuntos
Simulação por Computador , DNA/química , Modelos Moleculares , Método de Monte Carlo , Conformação de Ácido Nucleico
7.
Clin Transplant ; 35(3): e14204, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33368675

RESUMO

BACKGROUND: Depression is prevalent in patients with heart failure and after heart transplant. We identified the prevalence of pre- and post-transplant depression and its association with clinical characteristics and post-transplant outcomes. METHODS: We reviewed 114 adults transplanted 1/1/2015 to 12/31/2015 and identified patients with pre- and post-transplant depression. Clinical characteristics and outcomes were compared. RESULTS: Of 114 patients, 35.1% had pre-transplant depression and 26.3% had post-transplant depression. Patients with post-transplant depression within the first year were significantly more likely to have acute rejection (10% vs 0%), longer intensive care unit (11.7 days vs 7.8 days) and hospital stay (31.7 days vs 16.3 days), and discharge to inpatient rehabilitation (26.7% vs 8.3%). Patients with post-transplant depression within the first year had significantly higher 5-year mortality (30% vs 9.5%, p = .009). However, after adjustment for total artificial heart/biventricular assist device, acute rejection, intensive care unit, and hospital length of stay, this relationship was no longer significant (HR 2.11; 95% CI 0.18-25.27; p = .556). CONCLUSIONS: Depression is common among heart transplant candidates and recipients. While pre-transplant depression did not impact outcomes, patients with post-transplant depression were more likely to have had a complicated course, suggesting the need for increased vigilance regarding depression in such patients.


Assuntos
Transplante de Coração , Coração Auxiliar , Adulto , Estudos de Coortes , Depressão/epidemiologia , Depressão/etiologia , Humanos , Estudos Retrospectivos , Resultado do Tratamento
8.
Curr Cardiol Rep ; 22(12): 175, 2020 10 10.
Artigo em Inglês | MEDLINE | ID: mdl-33040213

RESUMO

PURPOSE OF REVIEW: We review the prevalence; natural history; impact of subclinical clinical thrombosis on valve hemodynamics, clinical outcomes, and valve durability; and the role of anticoagulation after transcatheter aortic valve replacement (TAVR). RECENT FINDINGS: Subclinical leaflet thrombosis is a dynamic finding present in both transcatheter and surgical bioprosthetic aortic valves. This finding is less prevalent in patients on anticoagulation and resolves following initiation of anticoagulation. Routine anticoagulation after TAVR in high-surgical-risk patients was associated with increased mortality and thromboembolic complications. In the absence of a clinical indication for anticoagulation, there is no reason to initiate anticoagulation after TAVR for the prevention of subclinical leaflet thrombosis. In patients with an established indication for anticoagulation, for instance, atrial fibrillation, clinical or symptomatic valve thrombosis, or a clinical event related to valve thrombosis, anticoagulation should be initiated or continued after TAVR to treat the clinical indication.


Assuntos
Estenose da Valva Aórtica , Próteses Valvulares Cardíacas , Substituição da Valva Aórtica Transcateter , Anticoagulantes/uso terapêutico , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Próteses Valvulares Cardíacas/efeitos adversos , Humanos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Resultado do Tratamento
9.
J Electrocardiol ; 63: 12-16, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33017756

RESUMO

BACKGROUND: We examined the association between the absence ECG LVH and all-cause mortality in patients with severe AS undergoing TAVR. METHODS: We conducted a retrospective single center study on 399 TAVR patients from 2012 to 2016. ECGs were reviewed for LVH diagnosed by Sokolow-Lyon's voltage criteria. All patients met echocardiographic criteria for LVH. Logistic regression was used to examine the association between ECG LVH and covariates. Survival analysis was performed using Cox regression analysis and Kaplan Meier curves. RESULTS: Patients without ECG LVH were younger (81.0 ± 8.4 vs. 84.0 ± 7.7 years, p = 0.001) with a higher BMI (29.3 ± 7.0 vs. 27.1 ± 5.6 kg/m2, p = 0.006) and lower FEV1 (65.6 ± 22.8 vs. 74.1 ± 21.6%, p = 0.002). In multivariable analysis, increased BMI and decreased FEV1 remained predictive of the absence of ECG LVH. Over a mean follow-up time of 32 (± 17.0) months, the 5-year cumulative survival was 79% in the ECG LVH group and 58% in the group without ECG LVH (p = 0.039). Absence of ECG LVH remained predictive of all-cause mortality (HR 1.56, 95% CI 1.01-2.59, p = 0.045) in multivariable Cox regression analysis. When patients were grouped by comorbidities, patients with the highest mortality were those with increased BMI or decreased FEV1. CONCLUSIONS: Absence of LVH by ECG criteria in patients with severe AS undergoing TAVR was associated with increased all-cause mortality. Routinely performed, noninvasive and inexpensive ECG may aid in identification of high-risk patients that may not benefit from TAVR and warrant further evaluation of underlying comorbidities.


Assuntos
Estenose da Valva Aórtica , Substituição da Valva Aórtica Transcateter , Estenose da Valva Aórtica/cirurgia , Eletrocardiografia , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Estudos Retrospectivos
10.
Clin Transplant ; 34(11): e14075, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32916014

RESUMO

BACKGROUND: The incidence of recurrent laryngeal nerve injury (RLNI) after heart transplantation has not been well studied. This can manifest as vocal cord dysfunction causing dysphonia. Previous research is limited to aortic, coronary bypass, and valvular surgery. Identifying RLNI after heart transplantation is important in order to more accurately detail complications associated with this major surgery. METHODS: This is a retrospective study assessing 972 adult patients who underwent orthotopic heart transplantation between 2010-2019. Primary outcome was incidence of RLNI. Secondary outcomes were 1-year mortality and length of stay. Cardiology and otolaryngology notes were examined. Key word searches were used to identify possible RLNI in patients' health care record. RESULTS: 2.9% (29/972) of patients developed new RLNI confirmed by laryngoscopy during hospitalization. Patients with RLNI had a significantly increased risk of 1-year mortality (P = .015) and length of stay (P = .006) compared to those without RLNI. 68.9% (20/29) of RLNI was left-sided (68.9%). CONCLUSIONS: Recurrent laryngeal nerve injury is a recognizable adverse outcome following heart transplantation. This study supports that RLNI is associated with increased 1-year mortality and length of stay. Early otolaryngology evaluation may be warranted to evaluate vocal cord mobility and address potential management.


Assuntos
Transplante de Coração , Traumatismos do Nervo Laríngeo , Traumatismos do Nervo Laríngeo Recorrente , Adulto , Transplante de Coração/efeitos adversos , Humanos , Incidência , Traumatismos do Nervo Laríngeo Recorrente/etiologia , Estudos Retrospectivos
11.
J Chem Phys ; 152(11): 114903, 2020 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-32199437

RESUMO

Motivated by renewed interest in the physics of branched polymers, we present here a detailed characterization of the connectivity and spatial properties of 2- and 3-dimensional single-chain conformations of randomly branching polymers under θ-solvent conditions obtained by Monte Carlo computer simulations. The first part of the work focuses on polymer average properties, such as the average polymer spatial size as a function of the total tree mass and the typical length of the average path length on the polymer backbone. In the second part, we move beyond average chain behavior and we discuss the complete distribution functions for tree paths and tree spatial distances, which are shown to obey the classical Redner-des Cloizeaux functional form. Our results were rationalized first by the systematic comparison to a Flory theory for branching polymers and next by generalized Fisher-Pincus relationships between scaling exponents of distribution functions. For completeness, the properties of θ-polymers were compared to their ideal (i.e., no volume interactions) as well as good-solvent (i.e., above the θ-point) counterparts. The results presented here complement the recent work performed in our group [A. Rosa and R. Everaers, J. Phys. A: Math. Theor. 49, 345001 (2016); J. Chem. Phys. 145, 164906 (2016); and Phys. Rev. E 95, 012117 (2017)] in the context of the scaling properties of branching polymers.

12.
Biochim Biophys Acta Gene Regul Mech ; 1863(6): 194415, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-31672524

RESUMO

Genome organization in eukaryotes during interphase stems from the delicate balance between non-random correlations present in the DNA polynucleotide linear sequence and the physico/chemical reactions which shape continuously the form and structure of DNA and chromatin inside the nucleus of the cell. It is now clear that these mechanisms have a key role in important processes like gene regulation, yet the detailed ways they act simultaneously and, eventually, come to influence each other even across very different length-scales remain largely unexplored. In this paper, we recapitulate some of the main results concerning gene regulatory and physical mechanisms, in relation to the information encoded in the 1D sequence and the 3D folding structure of DNA. In particular, we stress how reciprocal crossfeeding between 1D and 3D models may provide original insight into how these complex processes work and influence each other. This article is part of a Special Issue entitled: Transcriptional Profiles and Regulatory Gene Networks edited by Dr. Dr. Federico Manuel Giorgi and Dr. Shaun Mahony.


Assuntos
Cromossomos , Genômica/métodos , Modelos Genéticos , Sequência de Bases , Cromatina/química , DNA/química , Eucariotos/genética
13.
ACS Macro Lett ; 9(5): 743-748, 2020 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-33828901

RESUMO

The relationship between polymer topology and bulk rheology remains a key question in soft matter physics. Architecture-specific constraints (or threadings) are thought to control the dynamics of ring polymers in ring-linear blends, which thus affects the viscosity to range between that of the pure rings and a value larger, but still comparable to, that of the pure linear melt. Here we consider qualitatively different systems of linear and ring polymers, fused together in "chimeric" architectures. The simplest example of this family is a "tadpole"-shaped polymer, a single ring fused to the end of a single linear chain. We show that polymers with this architecture display a threading-induced dynamical transition that substantially slows chain relaxation. Our findings shed light on how threadings control dynamics and may inform design principles for chimeric polymers with topologically tunable bulk rheological properties.

15.
Phys Biol ; 16(6): 066002, 2019 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-31394517

RESUMO

Chromatin fibers within the interior of the nucleus of the cell make stable interactions with the nucleoskeleton, an ensemble of 'extra-chromatin' structures which help ensuring genome stability. Although the role of these interactions appears crucial to the correct behavior of the cell, their impact on chromatin structure and dynamics remains to be elucidated. In order to tackle this important issue, in this work we introduce a simple polymer model for chromatin fibers in interphase which takes into account the two generic properties of chain-versus-chain mutual uncrossability and the presence of stable binding interactions to an extra-chromatin nuclear matrix. To study how these constraints affect chromatin structure from small to large scales, we employ extensive molecular dynamics computer simulations and we monitor the motion of nanoprobes of different sizes embedded within the polymer medium. Our results demonstrate that nanoprobes show hampered motion whenever their linear size becomes larger than chromatin stiffness. This transition is also displaying features which usually belong to the realm of glassy systems, namely long-tail correlations in the distribution functions of nanoprobe spatial displacements and heterogeneous behavior accompanied by ergodicity breaking.


Assuntos
Cromossomos/fisiologia , Interfase , Simulação de Dinâmica Molecular , Reologia
16.
Soft Matter ; 15(11): 2418-2429, 2019 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-30778466

RESUMO

The conformational statistics of ring polymers in melts or dense solutions is strongly affected by their quenched microscopic topological state. The effect is particularly strong for untangled (i.e. non-concatenated and unknotted) rings, which are known to crumple and segregate. Here we study these systems using a computationally efficient multi-scale approach, where we combine massive simulations on the fiber level with the explicit construction of untangled ring melt configurations based on theoretical ideas for their large scale structure. We find (i) that topological constraints may be neglected on scales below the standard entanglement length, Le, (ii) that rings with a size 1 ≤ Lr/Le ≤ 30 exhibit nearly ideal lattice tree behavior characterized by primitive paths which are randomly branched on the entanglement scale, and (iii) that larger rings are compact with gyration radii Rg2(Lr) ∝ Lr2/3. The detailed comparison between equilibrated and constructed ensembles allows us to perform a "Feynman test" of our understanding of untangled rings: can we convert ideas for the large scale ring structure into algorithms for constructing (nearly) equilibrated ring melt samples? We show that most structural observables are quantitatively reproduced by two different construction schemes: hierarchical crumpling and ring melts derived from the analogy to interacting branched polymers. However, the latter fail the "Feynman test" with respect to the magnetic radius, Rm, which we have defined based on an analogy to magnetostatics. While Rm is expected to vanish for double-folded structures, the observed values of Rm2(Lr) ∝ Rg2(Lr) provide a simple and computationally convenient measure of the presence of a non-negligible amount of local loop opening in crumpled rings.

17.
ACS Macro Lett ; 8(2): 155-160, 2019 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-30800531

RESUMO

Unconcatenated ring polymers in concentrated solutions and melt are remarkably well described as double-folded conformations on randomly branched primitive trees. This picture though contrasts recent evidence for extensive intermingling between close-by rings in the form of long-lived topological constraints or threadings. Here, we employ the concept of ring minimal surface to quantify the extent of threadings in polymer solutions of the double-folded rings vs rings in equilibrated molecular dynamics computer simulations. Our results show that the double-folded ring polymers are significantly less threaded compared to their counterparts at equilibrium. Second, threadings form through a slow process whose characteristic time-scale is of the same order of magnitude as that of the diffusion of the rings in solution. These findings are robust, being based on universal (model-independent) observables as the average fraction of threaded length or the total penetrations between close-by rings and the corresponding distribution functions.

18.
Eur Phys J E Soft Matter ; 42(1): 7, 2019 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-30659391

RESUMO

The conformations of topologically constrained double-folded ring polymers can be described as wrappings of randomly branched primitive trees. We extend previous work on the tree statistics under different (solvent) conditions to explore the conformational statistics of double-folded rings in the limit of tight wrapping. In particular, we relate the exponents characterizing the ring statistics to those describing the primitive trees and discuss the distribution functions [Formula: see text] and [Formula: see text] for the spatial distance, [Formula: see text], and tree contour distance, L, between monomers as a function of their ring contour distance, [Formula: see text].

19.
Eur Phys J E Soft Matter ; 41(12): 144, 2018 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-30552518

RESUMO

We study the properties of the classical Ising model with nearest-neighbor interaction for spins located at the monomers of long polymer chains in 2 and 3 dimensions. We compare results for two ensembles of polymers with very different single chain properties: 1) swollen, self-avoiding linear polymer chains in good solvent conditions and 2) compact, space-filling randomly branching polymers in melt. By employing a mean-field approach and Monte Carlo computer simulations, we show that swollen polymers cannot sustain an ordered phase. On the contrary, compact polymers may indeed produce an observable phase transition. Finally, we briefly consider the statistical properties of the ordered phase by comparing polymer chains within the same universality class but characterized by very different shapes.

20.
J Chem Phys ; 148(19): 194902, 2018 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-30307231

RESUMO

We employ large-scale molecular dynamics computer simulations to study the problem of nanoprobe diffusion in entangled solutions of linear polymers and unknotted and unconcatenated circular (ring) polymers. By tuning both the diameter of the nanoprobe and the density of the solution, we show that nanoprobes of diameter smaller than the entanglement distance (tube diameter) of the solution display the same (Rouse-like) behavior in solutions of both polymer architectures. Instead, nanoprobes with larger diameters appear to diffuse markedly faster in solutions of rings than in solutions of linear chains. Finally, by analysing the distribution functions of spatial displacements, we find that nanoprobe motion in rings' solutions shows both Gaussian and ergodic behaviors, in all regimes considered, while, in solutions of linear chains, nanoprobes exceeding the size of the tube diameter show a transition to non-Gaussian and non-ergodic motion. Our results emphasize the role of chain architecture in the motion of nanoprobes dispersed in polymer solutions.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...