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1.
Phys Rev Lett ; 131(4): 048101, 2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37566871

RESUMO

Polymers confined in corrugated channels, i.e., channels of varying amplitude, display multiple local maxima and minima of the diffusion coefficient upon increasing their degree of polymerization N. We propose a theoretical effective free energy for linear polymers based on a Fick-Jacobs approach. We validate the predictions against numerical data, obtaining quantitative agreement for the effective free energy, the diffusion coefficient, and the mean first passage time. Finally, we employ the effective free energy to compute the polymer lengths N_{min} at which the diffusion coefficient presents a minimum: we find a scaling expression that we rationalize with a blob model. Our results could be useful to design porous adsorbers, that separate polymers of different sizes without the action of an external flow.

2.
J Chem Phys ; 158(7): 074902, 2023 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-36813707

RESUMO

Bacterial biofilms mechanically behave as viscoelastic media consisting of micron-sized bacteria cross-linked to a self-produced network of extracellular polymeric substances (EPSs) embedded in water. Structural principles for numerical modeling aim at describing mesoscopic viscoelasticity without losing details on the underlying interactions existing in wide regimes of deformation under hydrodynamic stress. Here, we approach the computational challenge to model bacterial biofilms for predictive mechanics in silico under variable stress conditions. Up-to-date models are not entirely satisfactory due to the plethora of parameters required to make them functioning under the effects of stress. As guided by the structural depiction gained in a previous work with Pseudomonas fluorescens [Jara et al., Front. Microbiol. 11, 588884 (2021)], we propose a mechanical modeling by means of Dissipative Particle Dynamics (DPD), which captures the essentials of topological and compositional interactions between bacterial particles and cross-linked EPS-embedding under imposed shear. The P. fluorescens biofilms have been modeled under mechanical stress mimicking shear stresses as undergone in vitro. The predictive capacity for mechanical features in DPD-simulated biofilms has been investigated by varying the externally imposed field of shear strain at variable amplitude and frequency. The parametric map of essential biofilm ingredients has been explored by making the rheological responses to emerge among conservative mesoscopic interactions and frictional dissipation in the underlying microscale. The proposed coarse grained DPD simulation qualitatively catches the rheology of the P. fluorescens biofilm over several decades of dynamic scaling.


Assuntos
Pseudomonas fluorescens , Pseudomonas fluorescens/fisiologia , Biofilmes , Reologia , Simulação por Computador , Hidrodinâmica
3.
J Cardiothorac Vasc Anesth ; 37(6): 927-932, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-36863985

RESUMO

OBJECTIVE: To determine the impact of diastolic dysfunction (DD) on survival after routine cardiac surgery. DESIGN: This was an observational study of consecutive cardiac surgeries from 2010 to 2021. SETTING: At a single institution. PARTICIPANTS: Patients undergoing isolated coronary, isolated valvular, and concomitant coronary and valvular surgery were included. Patients with a transthoracic echocardiogram (TTE) longer than 6 months prior to their index surgery were excluded from the analysis. INTERVENTIONS: Patients were categorized via preoperative TTE as having no DD, grade I DD, grade II DD, or grade III DD. MEASUREMENTS AND MAIN RESULTS: A total of 8,682 patients undergoing a coronary and/or valvular surgery were identified, of whom 4,375 (50.4%) had no DD, 3,034 (34.9%) had grade I DD, 1,066 (12.3%) had grade II DD, and 207 (2.4%) had grade III DD. The median (IQR) time of the TTE prior to the index surgery was 6 (2-29) days. Operative mortality was 5.8% in the grade III DD group v 2.4% for grade II DD, 1.9% for grade I DD, and 2.1% for no DD (p = 0.001). Atrial fibrillation, prolonged mechanical ventilation (>24 hours), acute kidney injury, any packed red blood cell transfusion, reexploration for bleeding, and length of stay were higher in the grade III DD group compared to the rest of the cohort. The median follow-up was 4.0 (IQR: 1.7-6.5) years. Kaplan-Meier survival estimates were lower in the grade III DD group than in the rest of the cohort. CONCLUSIONS: These findings suggested that DD may be associated with poor short-term and long-term outcomes.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Disfunção Ventricular Esquerda , Humanos , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/complicações , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Ecocardiografia , Coração , Estudos Retrospectivos , Resultado do Tratamento
4.
Rep Prog Phys ; 85(8)2022 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-35704983

RESUMO

Proteins are the workhorse of life. They are the building infrastructure of living systems; they are the most efficient molecular machines known, and their enzymatic activity is still unmatched in versatility by any artificial system. Perhaps proteins' most remarkable feature is their modularity. The large amount of information required to specify each protein's function is analogically encoded with an alphabet of just ∼20 letters. The protein folding problem is how to encode all such information in a sequence of 20 letters. In this review, we go through the last 30 years of research to summarize the state of the art and highlight some applications related to fundamental problems of protein evolution.


Assuntos
Dobramento de Proteína , Proteínas , Cinética , Proteínas/química , Análise de Sequência de Proteína
5.
J Card Surg ; 37(1): 29-38, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34796544

RESUMO

OBJECTIVE: Model for end-stage liver disease (MELD) likely has nonlinear effects on operative outcomes. We use machine learning to evaluate the nonlinear (dependent variable may not correlate one to one with an increased risk in the outcome) relationship between MELD and outcomes of cardiac surgery. METHODS: Society of Thoracic Surgery indexed elective cardiac operations between 2011 and 2018 were included. MELD was retrospectively calculated. Logistic regression models and an imbalanced random forest classifier were created on operative mortality. Cox regression models and random forest survival models evaluated survival. Variable importance analysis (VIMP) ranked variables by predictive power. Linear and machine-learned models were compared with receiver operator characteristic (ROC) and Brier score. RESULTS: We included 3872 patients. Operative mortality was 1.7% and 5-year survival was 82.1%. MELD was the fourth largest positive predictor on VIMP analysis for operative long-term survival and the strongest negative predictor for operative mortality. MELD was not a significant predictor for operative mortality or long-term survival in the logistic or Cox regressions. The logistic model ROC area was 0.762, compared to the random forest classifier ROC of 0.674. The Brier score of the random forest survival model was larger than the Cox regression starting at 2 years and continuing throughout the study period. Bootstrap estimation on linear regression demonstrated machine-learned models were superior. CONCLUSIONS: MELD and mortality are nonlinear. MELD was insignificant in the Cox multivariable regression but was strongly important in the random forest survival model and when using bootstrapping, the superior utility was demonstrated of the machine-learned models.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Doença Hepática Terminal , Cirurgia Torácica , Doença Hepática Terminal/cirurgia , Humanos , Aprendizado de Máquina , Prognóstico , Curva ROC , Estudos Retrospectivos , Índice de Gravidade de Doença
6.
J Card Surg ; 37(12): 4748-4754, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36352813

RESUMO

OBJECTIVE: To determine the impact of reoperative versus first-time sternotomy for emergent open repair of acute Type A aortic dissection (ATAAD). METHODS: This was an observational study of consecutive aortic surgeries from 2007 to 2021. Kaplan-Meier survival estimation and multivariable Cox regression analysis were performed to assess the impact of reoperative versus first-time sternotomy upon survival after ATAAD repair. RESULTS: A total of 601 patients with ATAAD were identified, of which 72 (12%) underwent reoperative sternotomy. The reoperative group had a higher prevalence of baseline comorbidities, including hypertension, diabetes, peripheral vascular disease, atrial fibrillation, and coronary artery disease. Central cannulation of the aorta was achieved at a similar rate across each group (81.9% vs. 81.5%, p = .923), and cardiopulmonary bypass (CPB) time was similar across each group (204 ± 84.8 vs. 203 ± 72.4 min, p = .923). Postoperative outcomes were similar across both groups, including in-hospital mortality, stroke, pulmonary complications, renal failure, and reexploration for excessive bleeding. Five-year survival was 74.5% (70.5, 78.3) for the first-time group and was 71.6% (60.0, 81.9) for the reoperative group. After multivariable Cox regression, reoperative sternotomy was not significantly associated with an increased hazard of death compared to first-time sternotomy (hazards ratio: 0.90, 95% confidence interval: 0.56, 1.43, p = .642). CONCLUSIONS: These findings suggest that re-sternotomy can be safely performed with similar outcomes as first-time sternotomy. Central initiation of CPB after sternal reentry limits CPB time and may therefore represent a protective strategy that enhances outcomes for patients presenting with ATAAD and prior cardiac surgery.


Assuntos
Dissecção Aórtica , Procedimentos Cirúrgicos Cardíacos , Humanos , Resultado do Tratamento , Estudos Retrospectivos , Dissecção Aórtica/cirurgia , Coração , Complicações Pós-Operatórias/cirurgia
7.
J Card Surg ; 37(12): 4342-4347, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36183385

RESUMO

BACKGROUND: While prior data have suggested worse outcomes in women after acute type A aortic dissection (ATAAD) repair when compared to men, results have been inconsistent across studies over time. This study sought to evaluate the impact of sex on short- and long-term outcomes after ATAAD repair. METHODS: This was a retrospective study utilizing an institutional database of ATAAD repairs from 2007 to 2021. Patients were stratified according to sex. Kaplan-Meier survival estimation and multivariable Cox regression were performed. Supplementary analysis using propensity score matching was also performed. RESULTS: Of the 601 patients who underwent ATAAD repair, 361 were males (60.1%) and 240 (39.9%) were females. Females were significantly older, more likely to have hypertension, and more likely to have chronic lung disease. Females were also significantly more likely than males to undergo hemiarch replacement, while males were significantly more likely than females to undergo total arch replacement and frozen elephant trunk. Operative mortality was 9.4% among males and 13.8% among females, though this was not a statistically significant difference (p = .098). Postoperative complications were comparable between groups. Kaplan-Meier survival estimates were similar for men and women, and, on multivariable Cox regression, sex was not significantly associated with long-term survival (hazard ratio: 1.00, 95% confidence interval: 0.73, 1.37, p = .986). Outcomes remained comparable after supplementary propensity score matched analysis. CONCLUSION: ATAAD repair can be performed with comparable short-term and long-term outcomes in both men and women.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Masculino , Humanos , Feminino , Estudos Retrospectivos , Implante de Prótese Vascular/métodos , Doença Aguda , Dissecção Aórtica/cirurgia , Estimativa de Kaplan-Meier , Aneurisma da Aorta Torácica/cirurgia , Resultado do Tratamento
8.
J Card Surg ; 37(10): 3313-3321, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35979682

RESUMO

INTRODUCTION: Connective tissue disorders predispose patients to earlier aortic dissections and aneurysms. However, there is limited large cohort data given its low incidence. METHODS: The National Inpatient Sample was searched for all adults with Marfans (MFS) and Ehlers Danlos (EDS) disease between 2010 and 2017. ICD codes were used to select those with a type A aortic dissection or aneurysm. RESULTS: There was a total of 19,567 cases, giving the estimated incidence of MFS and EDS of 18 and 22.4 per 100k people, respectively. After inclusion criteria, there were 2553 MF and 180 EDS patients. There was no statistical difference in mortality between the MFS and EDS cohorts (4.6% vs. 2.8%, p = .26). EDS patients were more likely to undergo a TEVAR procedure (2.8% vs. 1.0%, p = .03). MF patients were more likely to have a complication of acute kidney injury (p = .02). EDS patients were more likely older (50 vs. 42, p < .001) and female (47% vs. 33%, p < .001). MFS patients were more likely to have a type A aortic dissection (44% vs. 31%, p < .001). The majority (89%) of patients were treated at urban teaching hospitals. On univariable logistic regression, aortic dissection was a predictor for mortality (odds ratio 7.31, p < .001). The type of connective tissue disease was not a significant predictor. CONCLUSIONS: National level estimates show low mortality for patients with MF or ED presenting to the hospital with aortic dissection or aneurysm. The differences in age and gender can guide surveillance for these patient populations, leading to more elective admissions and reduced hospital mortality.


Assuntos
Aneurisma da Aorta Torácica , Dissecção Aórtica , Síndrome de Ehlers-Danlos , Procedimentos Endovasculares , Síndrome de Marfan , Adulto , Dissecção Aórtica/epidemiologia , Dissecção Aórtica/etiologia , Dissecção Aórtica/cirurgia , Aneurisma da Aorta Torácica/epidemiologia , Aneurisma da Aorta Torácica/etiologia , Aneurisma da Aorta Torácica/cirurgia , Síndrome de Ehlers-Danlos/complicações , Síndrome de Ehlers-Danlos/epidemiologia , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Pacientes Internados , Síndrome de Marfan/complicações , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
9.
J Card Surg ; 37(8): 2378-2385, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35582756

RESUMO

OBJECTIVE: To determine the long-term impact of developing acute renal failure (ARF) on survival after open aortic arch reconstruction for acute type A aortic dissection (ATAAD). METHODS: This was an observational study of consecutive aortic surgeries from 2007 to 2021. Patients with ATAAD were identified via a prospectively maintained institutional database and were stratified by the presence or absence of postoperative ARF (by RIFLE criteria). Kaplan-Meier survival estimation and multivariable Cox regression analysis were performed. RESULTS: A total of 601 patients undergoing open surgery for ATAAD were identified, of which 516 (85.9%) did not develop postoperative ARF, while 85 (14.1%) developed ARF, with a median follow-up time of 4.6 years (1.6, 7.9). Baseline characteristics were similar across each group, except for higher rates of branch vessel malperfusion and lower preoperative ejection fraction in the ARF group. Patients with ARF underwent more total arch replacement and elephant trunk procedures, with longer cardiopulmonary bypass and circulatory arrest times than patients without ARF. ARF was associated with worse short-term outcomes, including increased in-hospital mortality, prolonged mechanical ventilation, higher rates of sepsis, more blood transfusions, and longer length of hospital stay. Unadjusted Kaplan-Meier survival estimates were significantly lower in the ARF group, compared to the group without ARF (p < .001, log-rank test). After multivariable adjustment, the development of postoperative ARF was significantly associated with an increased hazard of death over the study's follow-up time-period (hazard ratio: 2.74, 95% confidence interval: 1.95, 3.86, p < .001). CONCLUSIONS: ARF is a highly morbid postoperative event that may adversely impact long-term survival after aortic surgery.


Assuntos
Injúria Renal Aguda , Aneurisma da Aorta Torácica , Dissecção Aórtica , Implante de Prótese Vascular , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/cirurgia , Dissecção Aórtica/cirurgia , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/métodos , Humanos , Estudos Retrospectivos , Resultado do Tratamento
10.
Phys Rev Lett ; 126(9): 097801, 2021 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-33750170

RESUMO

We investigate, using numerical simulations, the conformations of isolated active ring polymers. We find that their behavior depends crucially on their size: Short rings (N≲100) swell, whereas longer rings (N≳200) collapse, at sufficiently high activity. By investigating the nonequilibrium process leading to the steady state, we find a universal route driving both outcomes; we highlight the central role of steric interactions, at variance with linear chains, and of topology conservation. We further show that the collapsed rings are arrested by looking at different observables, all underlining the presence of an extremely long timescales at the steady state, associated with the internal dynamics of the collapsed section. Finally, we found that in some circumstances the collapsed state spins about its axis.

11.
Phys Rev Lett ; 126(1): 015704, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33480790

RESUMO

Ice nucleation is a phenomenon that, despite the relevant implications for life, atmospheric sciences, and technological applications, is far from being completely understood, especially under extreme thermodynamic conditions. In this work we present a computational investigation of the homogeneous ice nucleation at negative pressures. By means of the seeding technique we estimate the size of the ice critical nucleus N_{c} for the TIP4P/Ice water model. This is done along the isotherms 230, 240, and 250 K, from positive to negative pressures until reaching the liquid-gas kinetic stability limit (where cavitation cannot be avoided). We find that N_{c} is nonmonotonic upon depressurization, reaching a minimum at negative pressures in the doubly metastable region of water. According to classical nucleation theory we establish the nucleation rate J and the surface tension γ, revealing a retracing behavior of both when the liquid-gas kinetic stability limit is approached. We also predict a reentrant behavior of the homogeneous nucleation line. The reentrance of these properties is related to the reentrance of the coexistence line at negative pressure, revealing new anomalies of water. The results of this work suggest the possibility of having metastable samples of liquid water for long times at negative pressure provided that heterogeneous nucleation is suppressed.

12.
J Card Surg ; 36(10): 3631-3638, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34242433

RESUMO

INTRODUCTION: Coronary artery bypass grafting (CABG) continues to be the most commonly performed cardiac surgical procedure in the world. The use of multiarterial grafting may confer a long-term survival benefit over the use of vein grafts. However, there is a paucity of data comparing the use of in situ versus free right internal mammary artery (RIMA) in isolated CABG. METHODS: Patients that underwent isolated CABG between 2010 and 2018 where RIMA was used in addition to a left internal mammary artery graft. Patients with prior cardiac surgery or percutaneous coronary intervention were excluded. Propensity matching was used for subanalysis. Mortality and major adverse cardiac and cerebrovascular events (MACCE) were analyzed with Kaplan-Meier survival curves and Cox multivariable regression. Heart failure-specific readmissions were assessed with cumulative incidence curves with Fine and Gray competing risk regression. RESULTS: A total of 667 patients underwent isolated CABG. Of those, 422 had free RIMA and 245 had in situ RIMA utilized. Mortality was similar between cohorts (p = 0.199) with 5-year mortality rates of 6.6% (free) and 4.1% (in situ). MACCE was similar between cohorts, with 5-year event rates of 33.6% and 33.9% (p = 0.99). RIMA style was not a significant predictor of any outcome. CONCLUSION: There was no difference in long-term mortality, complications, MACCE, or heart failure readmissions when comparing a contemporary cohort of patients undergoing isolated CABG utilizing RIMA as a conduit. These data may allow surgeons to consider using RIMA either as an in situ or a free conduit.


Assuntos
Doença da Artéria Coronariana , Artéria Torácica Interna , Intervenção Coronária Percutânea , Ponte de Artéria Coronária , Doença da Artéria Coronariana/cirurgia , Humanos , Anastomose de Artéria Torácica Interna-Coronária , Estudos Retrospectivos , Resultado do Tratamento
13.
J Card Surg ; 36(10): 3599-3606, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34363420

RESUMO

BACKGROUND: Time of day for surgical procedures has been a topic of considerable controversy, with some suggesting that later operating times are associated with worse outcomes. METHODS: All patients who underwent open cardiac surgery from 2011 to 2018 were included. Patients that had ventricular assist devices, heart transplant, transcatheter aortic valves, aortic dissections, and emergent operations were excluded. Primary outcomes included postoperative mortality and survival; secondary outcomes included postoperative complications and readmission. RESULTS: The initial patient population consisted of 7883 patients who underwent index cardiac surgery. Following propensity matching (3:1), there were 2569 patients in the a.m. cohort (7-11 a.m.) and 860 patients in the p.m. cohort (3-11 p.m.). All baseline characteristics were matched to equivalent proportions. Total intensive care unit time following surgery was longer for the a.m. cohort (46.5 vs. 40.0 h; p<.001). Otherwise, there was no significant difference between cohorts including operative mortality (1.83% vs 2.21%; p= .48). On multivariable analysis, p.m. surgery was not significantly associated with 30 days mortality (hazard ratio [HR]: 0.96 [0.60, 1.53]; p= .86] or mortality over the study follow-up (HR: 0.87 [0.73, 1.03]; p= .10]. For propensity-matched cohorts, Kaplan-Meier survival at 30 days (97.9% vs. 97.4%; p= .44), 1 (93.4% vs 93.9%; p= .51), and 5 years (80.9% vs. 80.2%; p= .84) was not significantly different between cohorts. CONCLUSION: Short- and long-term mortality, hospital readmission, and postoperative complications were not significantly different between patients that underwent cardiac surgery starting in the a.m. versus patients who had cases that started in the afternoon.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Mortalidade Hospitalar , Humanos , Morbidade , Complicações Pós-Operatórias/epidemiologia , Pontuação de Propensão , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
14.
J Card Surg ; 36(1): 206-215, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33225474

RESUMO

BACKGROUND: The wide availability of transcatheter aortic valve replacement (TAVR) and broadening of its indications to most patients with aortic stenosis may increase its utilization in the urgent setting. However, a comparison of long-term outcomes of patients undergoing urgent TAVR when compared to elective TAVR have not been well studied. METHODS: All patients that underwent TAVR from 2011 to 2018 were included. Primary outcomes included operative (30-day), 1-, and 5-year survival and readmissions. RESULTS: The total patient population undergoing TAVR was divided into urgent (n = 247) and elective (n = 946) cohorts. Thirty days mortality (6.5% vs. 2.3%; p = .001), acute kidney injury (2.8% vs. 0.6%; p = .003), and length of stay (12 vs. 3 days; p < .001) were higher for the urgent cohort. There was no significant difference between cohorts for 30-day all-cause (14.6% vs. 10.8%; p = .097) readmissions. Freedom from readmission for heart failure at 1-year (73.6% vs. 83.4%; p < .001) was lower for the urgent cohort. One- (79.0% vs. 87.1%; p < .001) and five-year (39.6% vs. 43.5%; p = .005) survival was lower for the urgent cohort. This difference was eliminated after risk adjustment (hazard ratio [HR]: 1.3; p = .158 and HR: 1.1; p = .639, respectively). CONCLUSION: Unadjusted survival was significantly worse for the urgent cohort up to 1 year. This trend continued for 5-year survival, however, after risk adjustment there was no significant difference in survival between cohorts. Although urgent TAVR is associated with increased periprocedural risk due to more comorbid disease, outcomes and long-term survival are encouraging and support the consideration of urgent TAVR as a viable alternative for this patient population.


Assuntos
Estenose da Valva Aórtica , Implante de Prótese de Valva Cardíaca , Substituição da Valva Aórtica Transcateter , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Procedimentos Cirúrgicos Eletivos , Humanos , Fatores de Risco , Resultado do Tratamento
15.
Chemphyschem ; 21(5): 377-384, 2020 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-31721405

RESUMO

We present a computational study on the folding and aggregation of proteins in an aqueous environment, as a function of its concentration. We show how the increase of the concentration of individual protein species can induce a partial unfolding of the native conformation without the occurrence of aggregates. A further increment of the protein concentration results in the complete loss of the folded structures and induces the formation of protein aggregates. We discuss the effect of the protein interface on the water fluctuations in the protein hydration shell and their relevance in the protein-protein interaction.


Assuntos
Simulação de Dinâmica Molecular , Proteínas/química , Algoritmos , Interações Hidrofóbicas e Hidrofílicas , Agregados Proteicos , Conformação Proteica , Desdobramento de Proteína , Termodinâmica
16.
Chemphyschem ; 21(4): 335-347, 2020 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-31944517

RESUMO

Protein sequence stores the information relative to both functionality and stability, thus making it difficult to disentangle the two contributions. However, the identification of critical residues for function and stability has important implications for the mapping of the proteome interactions, as well as for many pharmaceutical applications, e. g. the identification of ligand binding regions for targeted pharmaceutical protein design. In this work, we propose a computational method to identify critical residues for protein functionality and stability and to further categorise them in strictly functional, structural and intermediate. We evaluate single site conservation and use Direct Coupling Analysis (DCA) to identify co-evolved residues both in natural and artificial evolution processes. We reproduce artificial evolution using protein design and base our approach on the hypothesis that artificial evolution in the absence of any functional constraint would exclusively lead to site conservation and co-evolution events of the structural type. Conversely, natural evolution intrinsically embeds both functional and structural information. By comparing the lists of conserved and co-evolved residues, outcomes of the analysis on natural and artificial evolution, we identify the functional residues without the need of any a priori knowledge of the biological role of the analysed protein.


Assuntos
Biologia Computacional , Proteínas/análise , Sequência de Aminoácidos , Modelos Moleculares , Conformação Proteica , Proteínas/metabolismo
17.
J Chem Phys ; 153(9): 091102, 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32891082

RESUMO

Antifreeze proteins (AFPs) are biopolymers capable of interfering with ice growth. Their antifreeze action is commonly understood considering that the AFPs, by pinning the ice surface, force the crystal-liquid interface to bend forming an ice meniscus, causing an increase in the surface free energy and resulting in a decrease in the freezing point ΔTmax. Here, we present an extensive computational study for a model protein adsorbed on a TIP4P/Ice crystal, computing ΔTmax as a function of the average distance d between AFPs, with simulations spanning over 1 µs. First, we show that the lower the d, the larger the ΔTmax. Then, we find that the water-ice-protein contact angle along the line ΔTmax(d) is always larger than 0°, and we provide a theoretical interpretation. We compute the curvature radius of the stable solid-liquid interface at a given supercooling ΔT ≤ ΔTmax, connecting it with the critical ice nucleus at ΔT. Finally, we discuss the antifreeze capability of AFPs in terms of the protein-water and protein-ice interactions. Our findings establish a unified description of the AFPs in the contest of homogeneous ice nucleation, elucidating key aspects of the antifreeze mechanisms and paving the way for the design of novel ice-controlling materials.


Assuntos
Proteínas Anticongelantes/química , Gelo , Adsorção , Cristalização , Propriedades de Superfície , Termodinâmica , Temperatura de Transição
18.
J Cardiothorac Vasc Anesth ; 34(1): 258-266, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31151860

RESUMO

Cardiopulmonary bypass (CPB) has been one of the most important additions to the field of heart surgery in the past century. However, significant morbidity associated with CPB has led to the increasing implementation of off-pump coronary artery bypass (OPCAB). The use of OPCAB has broadened surgical revascularization for patient populations at high risk for undergoing CPB, including the very elderly and patients with impending end-organ failure. Intraoperative hemodynamic instability requires expeditious correction of hypotension with various medical and surgical techniques that require the close attention and skill of both the anesthesia and surgical teams. Technical skill at performing and interpreting transesophageal echocardiography is essential to help differentiate regional wall motion abnormalities from coronary ischemia and external compression from manipulation of the heart, which require different management strategies to resolve hemodynamic collapse. Flawless communication between the anesthesiologist and surgeons, with frequent intraoperative adjustments, is paramount for the completion of successful OPCAB.


Assuntos
Ponte de Artéria Coronária sem Circulação Extracorpórea , Idoso , Ponte Cardiopulmonar , Comunicação , Ponte de Artéria Coronária , Éter , Humanos , Resultado do Tratamento
19.
J Card Surg ; 35(11): 2950-2956, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32789931

RESUMO

INTRODUCTION: Stentless porcine xenografts are versatile bioprosthetic valves with the advantage of improved hemodynamics that mimic the function of the native aortic valve. However, these bioprostheses are challenging to implant in the subcoronary position. METHODS: All consecutive patients who underwent a bioprosthetic aortic valve replacement (AVR) were included from our institutional database. Cox regression analysis was preformed to determine significant predictors for mid term mortality as well as all cause, cardiac, and heart failure readmission. RESULTS: Patients in the subcoronary stentless group were older and more likely to be female and were likely to have a higher Society of Thoracic Surgery risk of mortality. Survival was superior in the stented AVR cohort at 30-days (96.4% vs 90.5%; P < .001), 1-year (90.5% vs 71.6%; P < .001), and 5-year (74.5% vs 56.9%; P < .001) follow up. Acute kidney injury (16.22% vs 5.22%; P < .001) and blood product transfusion (70.27% vs 44.0%; P < .001) were higher in the stentless group. Multivariable analysis revealed subcoronary stentless implantation as a significant independent risk factor for mortality (hazards ratio: 1.92 [1.35,2.72]; P < .001). CONCLUSION: Stentless porcine xenograft implantation with the Freestyle bioprosthetic in the subcoronary position can be successfully performed in select patients, but its use is associated with increased perioperative morbidity and mortality affecting midterm outcomes. Individual patient selection and surgeon experience are important to ensure favorable outcomes.


Assuntos
Valva Aórtica/cirurgia , Bioprótese , Implante de Prótese de Valva Cardíaca/métodos , Próteses Valvulares Cardíacas , Stents , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Valva Aórtica/fisiopatologia , Competência Clínica , Estudos de Coortes , Feminino , Implante de Prótese de Valva Cardíaca/mortalidade , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Cirurgiões , Suínos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
20.
J Card Surg ; 35(8): 1920-1926, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32652793

RESUMO

BACKGROUND: Redo cardiac surgery carries an inherent risk for adverse short-term outcomes and worse long-term survival. Strategies to mitigate these risks have been numerous, including initiation of cardiopulmonary bypass via peripheral cannulation before resternotomy. This study evaluated the impact of central versus peripheral cannulation on long-term survival after redo cardiac surgery. METHODS: This was an observational study of open cardiac surgeries between 2010 and 2018. Patients undergoing open cardiac surgery that utilized cardiopulmonary bypass, who also had more than equal to 1 prior cardiac surgery, were identified. Kaplan-Meier survival estimation and multivariable Cox regression analysis were performed to assess the impact of peripheral cannulation on survival. To isolate long-term survival, patients with operative mortality were excluded and survival time was counted from the date of discharge until the date of death. RESULTS: Of the 1660 patients with more than equal to 1 prior cardiac surgery, 91 (5.5%) received peripheral cannulation. After excluding patients with operative mortality and after multivariable risk-adjustment, the peripheral cannulation group had significantly increased hazard of death, as compared to the central cannulation group (HR 1.53, 95% CI: 1.01, 2.30, P = .044). Yet, there were no relevant differences for other postoperative outcomes, including blood product requirement, prolonged ventilation (>24 hours), pneumonia, reoperation for bleeding, stroke, sepsis, and new dialysis requirement. CONCLUSIONS: This is the first study reporting the long-term impact of peripheral cannulation for redo cardiac surgery after excluding patients with operative mortality. These data suggest that central cannulation may to be the preferred approach to redo cardiac surgery whenever safe and possible.


Assuntos
Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/mortalidade , Procedimentos Cirúrgicos Cardíacos/métodos , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/mortalidade , Reoperação/efeitos adversos , Reoperação/mortalidade , Idoso , Ponte Cardiopulmonar/efeitos adversos , Ponte Cardiopulmonar/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Risco , Segurança , Taxa de Sobrevida , Fatores de Tempo
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