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1.
J Biol Chem ; 299(12): 105408, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-38229397

RESUMEN

Increased endothelial cell (EC) permeability is a cardinal feature of acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Tyrosine phosphorylation of VE-cadherin is a key determinant of EC barrier disruption. However, the identity and role of tyrosine kinases in this context are incompletely understood. Here we report that Spleen Tyrosine Kinase (Syk) is a key mediator of EC barrier disruption and lung vascular leak in sepsis. Inhibition of Syk by pharmacological or genetic approaches, each reduced thrombin-induced EC permeability. Mechanistically, Syk associates with and phosphorylates VE-cadherin to cause EC permeability. To study the causal role of endothelial Syk in sepsis-induced ALI, we used a remarkably efficient and cost-effective approach based on gene transfer to generate EC-ablated Syk mice. These mice were protected against sepsis-induced loss of VE-cadherin and inflammatory lung injury. Notably, the administration of Syk inhibitor R788 (fostamatinib); currently in phase II clinical trial for the treatment of COVID-19, mitigated lung injury and mortality in mice with sepsis. These data identify Syk as a novel kinase for VE-cadherin and a druggable target against ALI in sepsis.


Asunto(s)
Lesión Pulmonar Aguda , Antígenos CD , Cadherinas , Síndrome de Dificultad Respiratoria , Sepsis , Quinasa Syk , Animales , Ratones , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/patología , Antígenos CD/metabolismo , Cadherinas/metabolismo , Permeabilidad Capilar , Pulmón/metabolismo , Sepsis/complicaciones , Quinasa Syk/metabolismo , Fosforilación
2.
J Cutan Pathol ; 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38769706

RESUMEN

Cytophagic histiocytic panniculitis (CHP) is associated with a number of systemic conditions and is characterized by the presence of benign phagocytic histiocytes ("bean bag cells"), including phagocytosed erythrocytes, leukocytes, and platelets. We describe a case of a 72-year-old female who presented with a papular eruption that clinically mimicked pityriasis lichenoides et varioliformis acuta (PLEVA). Given that her skin biopsy had multiple features concerning PLEVA, this diagnosis was classified as a superficial pityriasis lichenoides-like variant of CHP. The histopathologic presence of cytophagic histiocytosis prompted workup for a systemic malignancy, leading to a diagnosis of underlying acute monocytic leukemia of myeloid lineage.

3.
Phys Rev Lett ; 130(3): 038201, 2023 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-36763385

RESUMEN

The dispersive spreading of microscopic particles in shear flows is influenced both by advection and thermal motion. At the nanoscale, interactions between such particles and their confining boundaries become unavoidable. We address the roles of electrostatic repulsion and absorption on the spatial distribution and dispersion of charged nanoparticles in near-surface shear flows, observed under evanescent illumination. The electrostatic repulsion between particles and the lower charged surface is tuned by varying electrolyte concentrations. Particles leaving the field of vision can be neglected from further analysis, such that the experimental ensemble is equivalent to that of Taylor dispersion with absorption. These two ingredients modify the particle distribution, deviating strongly from the Gibbs-Boltzmann form at the nanoscale studied here. The overall effect is to restrain the accessible space available to particles, which leads to a striking, tenfold reduction in the spreading dynamics as compared to the noninteracting case.

4.
Phys Rev Lett ; 130(7): 077101, 2023 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-36867824

RESUMEN

We study the diffusion of particles confined close to a single wall and in double-wall planar channel geometries where the local diffusivities depend on the distance to the boundaries. Displacement parallel to the walls is Brownian as characterized by its variance, but it is non-Gaussian having a nonzero fourth cumulant. Establishing a link with Taylor dispersion, we calculate the fourth cumulant and the tails of the displacement distribution for general diffusivity tensors along with potentials generated by either the walls or externally, for instance, gravity. Experimental and numerical studies of the motion of a colloid in the direction parallel to the wall give measured fourth cumulants which are correctly predicted by our theory. Interestingly, contrary to models of Brownian-yet-non-Gaussian diffusion, the tails of the displacement distribution are shown to be Gaussian rather than exponential. All together, our results provide additional tests and constraints for the inference of force maps and local transport properties near surfaces.

5.
Mol Pharm ; 20(12): 6090-6103, 2023 Dec 04.
Artículo en Inglés | MEDLINE | ID: mdl-37963105

RESUMEN

Short-interfering RNA (siRNA) oligonucleotide therapeutics that modify gene expression by accessing RNA-interference (RNAi) pathways have great promise for the treatment of a range of disorders; however, their application in clinical settings has been limited by significant challenges in cellular delivery. Herein, we report a structure-function study using a series of modified cyclic amphipathic cell-penetrating peptides (CAPs) to determine the impact of peptide sequence on (1) siRNA-binding efficiency, (2) cellular delivery and knockdown efficiency, and (3) the endocytic uptake mechanism. Nine cyclic peptides of the general sequence Ac-C[XZ]4CG-NH2 in which X residues are hydrophobic/aromatic (Phe, Tyr, Trp, or Leu) and Z residues are charged/hydrophilic (Arg, Lys, Ser, or Glu) are assessed along with one acyclic peptide, Ac-(WR)4G-NH2. Cyclization is enforced by intramolecular disulfide bond formation between the flanking Cys residues. Binding analyses indicate that strong cationic character and the presence of aromatic residues that are competent to participate in CH-π interactions lead to CAP sequences that most effectively interact with siRNA. CAP-siRNA binding increases in the following order as a function of CAP hydrophobic/aromatic content: His < Phe < Tyr < Trp. Both cationic charge and disulfide-constrained cyclization of CAPs improve uptake of siRNA in vitro. Net neutral CAPs and an acyclic peptide demonstrate less-efficient siRNA translocation compared to the cyclic, cationic CAPs tested. All CAPs tested facilitated efficient siRNA target gene knockdown of at least 50% (as effective as a lipofectamine control), with the best CAPs enabling >80% knockdown. Significantly, gene knockdown efficiency does not strongly correlate with CAP-siRNA internalization efficiency but moderately correlates with CAP-siRNA-binding affinity. Finally, utilization of small-molecule inhibitors and targeted knockdown of essential endocytic pathway proteins indicate that most CAP-siRNA nanoparticles facilitate siRNA delivery through clathrin- and caveolin-mediated endocytosis. These results provide insight into the design principles for CAPs to facilitate siRNA delivery and the mechanisms by which these peptides translocate siRNA into cells. These studies also demonstrate the nature of the relationships between peptide-siRNA binding, cellular delivery of siRNA cargo, and functional gene knockdown. Strong correlations between these properties are not always observed, which illustrates the complexity in the design of optimal next-generation materials for oligonucleotide delivery.


Asunto(s)
Péptidos de Penetración Celular , Péptidos Cíclicos , Péptidos Cíclicos/química , ARN Interferente Pequeño/química , Técnicas de Silenciamiento del Gen , Péptidos de Penetración Celular/química , Oligonucleótidos , Disulfuros
6.
Oral Dis ; 2023 Aug 31.
Artículo en Inglés | MEDLINE | ID: mdl-37650229

RESUMEN

INTRODUCTION: Dental examination and stabilization are performed prior to allogeneic hematopoietic cell transplantation to decrease infection risk during neutropenia. Burden of dental disease and treatment need is not well characterized in this population. OBJECTIVES: This report describes the dental status of a cohort of patients within the Chronic Graft-versus-Host Disease Consortium and treatment rendered prior to transplant. METHODS: The cohort included 486 subjects (Fred Hutchinson: n = 245; Dana-Farber: n = 241). Both centers have institutional-based dental clearance programs. Data were retrospectively abstracted from medical records by calibrated oral health specialists. RESULTS: The median age at transplant was 55.9 years, 62.1% were male, and 88% were white. Thirteen patients were edentulous (2.7%). The mean teeth among dentate patients before clearance was 26.0 (SD, 4.6). Dental findings included untreated caries (31.2%), restorations (91.6%), endodontically treated teeth (48.1%), and dental implants (5.7%). Pretransplant procedures during clearance included endodontic therapy (3.6%; mean = 0.1 teeth), restorations (25.1%; mean = 0.7), dental prophylaxis (59.2%), scaling/root planing (5.1%), and extraction (13.2%; mean = 0.3). The mean teeth after clearance was 25.6 (SD, 5.0). CONCLUSIONS: Retrospective analysis of pre-AlloHCT dental data in subjects at two large transplant centers identified low levels of dental need. Findings suggest high access to care.

7.
N Engl J Med ; 380(17): 1618-1627, 2019 04 25.
Artículo en Inglés | MEDLINE | ID: mdl-30883052

RESUMEN

BACKGROUND: In two interim analyses of this trial, patients with advanced heart failure who were treated with a fully magnetically levitated centrifugal-flow left ventricular assist device were less likely to have pump thrombosis or nondisabling stroke than were patients treated with a mechanical-bearing axial-flow left ventricular assist device. METHODS: We randomly assigned patients with advanced heart failure to receive either the centrifugal-flow pump or the axial-flow pump irrespective of the intended goal of use (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke or reoperation to replace or remove a malfunctioning device. The principal secondary end point was pump replacement at 2 years. RESULTS: This final analysis included 1028 enrolled patients: 516 in the centrifugal-flow pump group and 512 in the axial-flow pump group. In the analysis of the primary end point, 397 patients (76.9%) in the centrifugal-flow pump group, as compared with 332 (64.8%) in the axial-flow pump group, remained alive and free of disabling stroke or reoperation to replace or remove a malfunctioning device at 2 years (relative risk, 0.84; 95% confidence interval [CI], 0.78 to 0.91; P<0.001 for superiority). Pump replacement was less common in the centrifugal-flow pump group than in the axial-flow pump group (12 patients [2.3%] vs. 57 patients [11.3%]; relative risk, 0.21; 95% CI, 0.11 to 0.38; P<0.001). The numbers of events per patient-year for stroke of any severity, major bleeding, and gastrointestinal hemorrhage were lower in the centrifugal-flow pump group than in the axial-flow pump group. CONCLUSIONS: Among patients with advanced heart failure, a fully magnetically levitated centrifugal-flow left ventricular assist device was associated with less frequent need for pump replacement than an axial-flow device and was superior with respect to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755.).


Asunto(s)
Insuficiencia Cardíaca/terapia , Corazón Auxiliar , Diseño de Prótesis , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Corazón Auxiliar/efectos adversos , Humanos , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Falla de Prótesis , Reoperación/estadística & datos numéricos , Accidente Cerebrovascular/etiología
8.
Support Care Cancer ; 30(11): 8761-8773, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35717462

RESUMEN

PURPOSE: The Palliative Care Study Group in conjunction with the Oral Care Study Group of the Multinational Association for Supportive Care in Cancer (MASCC) formed a sub-group to develop evidence-based guidance on the management of common oral problems in patients with advanced cancer. METHODS: This guidance was developed in accordance with the MASCC Guidelines Policy. A search strategy for Medline was developed, and the Cochrane Database of Systematic Reviews and the Cochrane Central Register of Controlled Trials were explored for relevant reviews and trials, respectively. Guidance was categorised by the level of evidence, and "category of guideline" (i.e., "recommendation", "suggestion" or "no guideline possible"). RESULTS: Twelve generic suggestions (level of evidence - 5), three problem-specific recommendations and 14 problem-specific suggestions were generated. The generic suggestions relate to oral hygiene measures, assessment of problems, principles of management, re-assessment of problems and the role of dental/oral medicine professionals. CONCLUSIONS: This guidance provides a framework for the management of common oral problems in patients with advanced cancer, although every patient requires individualised management.


Asunto(s)
Neoplasias , Estomatitis , Humanos , Testimonio de Experto , Neoplasias/complicaciones , Cuidados Paliativos , Revisiones Sistemáticas como Asunto
9.
Appetite ; 179: 106307, 2022 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-36089124

RESUMEN

Cultured meat is a relatively new product, enjoying consumer appreciation as a more sustainable meat option. The present study builds on a sample from a diverse set of countries and continents, including China, the US, the UK, France, Spain, Netherlands, New Zealand, Brazil, and the Dominican Republic and uses partial least square structural equation modelling. The proposed conceptual model identified key factors driving and inhibiting consumer willingness to try, buy, and pay a price premium for cultured meat. Results relate to the overall sample of 3091 respondents and two sub-sample comparisons based on gender and meat consumption behaviour. Food neophobia, having food allergies, being a locavore, and having concerns about food technology were found to be inhibiting factors towards willingness to try, buy, and pay a price premium for cultured meat. Food curiosity, meat importance, and a consumer's perception of cultured meat as a realistic alternative to regular meat were found to be important drivers that positively impacted consumers' willingness to try, buy and pay more. Best practice recommendations address issues facing marketing managers in food retail and gastronomy.


Asunto(s)
Comportamiento del Consumidor , Carne , Tecnología de Alimentos/métodos , Humanos , Mercadotecnía , Encuestas y Cuestionarios
10.
N Engl J Med ; 378(15): 1386-1395, 2018 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-29526139

RESUMEN

BACKGROUND: In an early analysis of this trial, use of a magnetically levitated centrifugal continuous-flow circulatory pump was found to improve clinical outcomes, as compared with a mechanical-bearing axial continuous-flow pump, at 6 months in patients with advanced heart failure. METHODS: In a randomized noninferiority and superiority trial, we compared the centrifugal-flow pump with the axial-flow pump in patients with advanced heart failure, irrespective of the intended goal of support (bridge to transplantation or destination therapy). The composite primary end point was survival at 2 years free of disabling stroke (with disabling stroke indicated by a modified Rankin score of >3; scores range from 0 to 6, with higher scores indicating more severe disability) or survival free of reoperation to replace or remove a malfunctioning device. The noninferiority margin for the risk difference (centrifugal-flow pump group minus axial-flow pump group) was -10 percentage points. RESULTS: Of 366 patients, 190 were assigned to the centrifugal-flow pump group and 176 to the axial-flow pump group. In the intention-to-treat population, the primary end point occurred in 151 patients (79.5%) in the centrifugal-flow pump group, as compared with 106 (60.2%) in the axial-flow pump group (absolute difference, 19.2 percentage points; 95% lower confidence boundary, 9.8 percentage points [P<0.001 for noninferiority]; hazard ratio, 0.46; 95% confidence interval [CI], 0.31 to 0.69 [P<0.001 for superiority]). Reoperation for pump malfunction was less frequent in the centrifugal-flow pump group than in the axial-flow pump group (3 patients [1.6%] vs. 30 patients [17.0%]; hazard ratio, 0.08; 95% CI, 0.03 to 0.27; P<0.001). The rates of death and disabling stroke were similar in the two groups, but the overall rate of stroke was lower in the centrifugal-flow pump group than in the axial-flow pump group (10.1% vs. 19.2%; hazard ratio, 0.47; 95% CI, 0.27 to 0.84, P=0.02). CONCLUSIONS: In patients with advanced heart failure, a fully magnetically levitated centrifugal-flow pump was superior to a mechanical-bearing axial-flow pump with regard to survival free of disabling stroke or reoperation to replace or remove a malfunctioning device. (Funded by Abbott; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755 .).


Asunto(s)
Insuficiencia Cardíaca/terapia , Corazón Auxiliar , Diseño de Prótesis , Adulto , Anciano , Anciano de 80 o más Años , Presión Sanguínea , Femenino , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Corazón Auxiliar/efectos adversos , Humanos , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Calidad de Vida , Reoperación/estadística & datos numéricos , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/mortalidad , Trombosis/etiología , Resultado del Tratamiento , Prueba de Paso
11.
FASEB J ; 34(6): 8044-8056, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32307751

RESUMEN

Islet transplantation in man is limited by multiple factors including islet availability, islet cell damage caused by collagenase during isolation, maintenance of islet function between isolation and transplantation, and allograft rejection. In this study, we describe a new approach for preparing islets that enhances islet function in vitro and reduces immunogenicity. The approach involves culture on native decellularized 3D bone marrow-derived extracellular matrix (3D-ECM), which contains many of the matrix components present in pancreas, prior to islet transplantation. Compared to islets cultured on tissue culture plastic (TCP), islets cultured on 3D-ECM exhibited greater attachment, higher survival rate, increased insulin content, and enhanced glucose-stimulated insulin secretion. In addition, culture of islets on 3D-ECM promoted recovery of vascular endothelial cells within the islets and restored basement membrane-related proteins (eg, fibronectin and collagen type VI). More interestingly, culture on 3D-ECM also selectively decontaminated islets of "passenger" cells (co-isolated with the islets) and restored basement membrane-associated type VI collagen, which were associated with an attenuation in islet immunogenicity. These results demonstrate that this novel approach has promise for overcoming two major issues in human islet transplantation: (a) poor yield of islets from donated pancreas tissue and (b) the need for life-long immunosuppression.


Asunto(s)
Membrana Basal/fisiología , Médula Ósea/fisiología , Matriz Extracelular/fisiología , Tolerancia Inmunológica/fisiología , Islotes Pancreáticos/inmunología , Islotes Pancreáticos/fisiología , Animales , Membrana Basal/inmunología , Membrana Basal/metabolismo , Médula Ósea/inmunología , Médula Ósea/metabolismo , Colágeno Tipo VI/inmunología , Colágeno Tipo VI/metabolismo , Matriz Extracelular/inmunología , Matriz Extracelular/metabolismo , Fibronectinas/inmunología , Fibronectinas/metabolismo , Glucosa/inmunología , Glucosa/metabolismo , Tolerancia Inmunológica/inmunología , Insulina/inmunología , Insulina/metabolismo , Secreción de Insulina/inmunología , Secreción de Insulina/fisiología , Islotes Pancreáticos/metabolismo , Trasplante de Islotes Pancreáticos/métodos , Masculino , Ratas , Ratas Endogámicas F344 , Ratas Endogámicas Lew , Ratas Endogámicas WF
12.
J Med Genet ; 57(5): 296-300, 2020 05.
Artículo en Inglés | MEDLINE | ID: mdl-31662342

RESUMEN

BACKGROUND: Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACDMPV) is a lethal disorder of lung development. ACDMPV is associated with haploinsufficiency of the transcription factor FOXF1, which plays an important role in the development of the lung and intestine. CNVs upstream of the FOXF1 gene have also been associated with an ACDMPV phenotype, but mechanism(s) by which these deletions disrupt lung development are not well understood. The objective of our study is to gain insights into the mechanisms by which CNVs contribute to an ACDMPV phenotype. METHODS: We analysed primary lung tissue from an infant with classic clinical and histological findings of ACDMPV and harboured a 340 kb deletion on chromosome 16q24.1 located 250 kb upstream of FOXF1. RESULTS: In RNA generated from paraffin-fixed lung sections, our patient had lower expression of FOXF1 than age-matched controls. He also had an abnormal pattern of FOXF1 protein expression, with a dramatic loss of FOXF1 expression in the lung. To gain insights into the mechanisms underlying these changes, we assessed the epigenetic landscape using chromatin immunoprecipitation, which demonstrated loss of histone H3 lysine 27 acetylation (H3K27Ac), an epigenetic mark of active enhancers, in the region of the deletion. CONCLUSIONS: Together, these data suggest that the deletion disrupts an enhancer responsible for directing FOXF1 expression in the developing lung and provide novel insights into the mechanisms underlying a fatal developmental lung disorder.


Asunto(s)
Factores de Transcripción Forkhead/genética , Predisposición Genética a la Enfermedad , Pulmón/metabolismo , Síndrome de Circulación Fetal Persistente/genética , Cromosomas Humanos Par 16/genética , Elementos de Facilitación Genéticos/genética , Eliminación de Gen , Regulación de la Expresión Génica/genética , Haploinsuficiencia/genética , Humanos , Lactante , Recién Nacido , Pulmón/crecimiento & desarrollo , Pulmón/patología , Síndrome de Circulación Fetal Persistente/patología
13.
Int J Mol Sci ; 22(24)2021 Dec 08.
Artículo en Inglés | MEDLINE | ID: mdl-34948005

RESUMEN

In this work, NiTi alloy parts were fabricated using laser powder bed fusion (LBPF) from pre-alloyed NiTi powder and in situ alloyed pure Ni and Ti powders. Comparative research on the corrosive and biological properties of both studied materials was performed. Electrochemical corrosion tests were carried out in phosphate buffered saline at 37 °C, and the degradation rate of the materials was described based on Ni ion release measurements. Cytotoxicity, bacterial growth, and adhesion to the surface of the fabricated coupons were evaluated using L929 cells and spherical Escherichia coli (E. coli) bacteria, respectively. The in situ alloyed NiTi parts exhibit slightly lower corrosion resistance in phosphate buffered saline solution than pre-alloyed NiTi. Moreover, the passive layer formed on in situ alloyed NiTi is weaker than the one formed on the NiTi fabricated from pre-alloyed NiTi powder. Furthermore, in situ alloyed NiTi and NiTi made from pre-alloyed powders have comparable cytotoxicity and biological properties. Overall, the research has shown that nitinol sintered using in situ alloyed pure Ni and Ti is potentially useful for biomedical applications.


Asunto(s)
Aleaciones/farmacología , Escherichia coli/fisiología , Níquel/química , Titanio/química , Aleaciones/química , Animales , Adhesión Bacteriana/efectos de los fármacos , Línea Celular , Corrosión , Escherichia coli/efectos de los fármacos , Ensayo de Materiales , Ratones , Fosfatos/química , Polvos , Propiedades de Superficie
14.
Biol Blood Marrow Transplant ; 26(10): 1784-1802, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32653624

RESUMEN

Bone health disturbances commonly occur after hematopoietic cell transplantation (HCT) with loss of bone mineral density (BMD) and avascular necrosis (AVN) foremost among them. BMD loss is related to pretransplantation chemotherapy and radiation exposure and immunosuppressive therapy for graft-versus-host-disease (GVHD) and results from deficiencies in growth or gonadal hormones, disturbances in calcium and vitamin D homeostasis, as well as osteoblast and osteoclast dysfunction. Although the pathophysiology of AVN remains unclear, high-dose glucocorticoid exposure is the most frequent association. Various societal treatment guidelines for osteoporosis exist, but the focus is mainly on menopausal-associated osteoporosis. HCT survivors comprise a distinct population with unique comorbidities, making general approaches to bone health management inappropriate in some cases. To address a core set of 16 frequently asked questions (FAQs) relevant to bone health in HCT, the American Society of Transplant and Cellular Therapy Committee on Practice Guidelines convened a panel of experts in HCT, adult and pediatric endocrinology, orthopedics, and oral medicine. Owing to a lack of relevant prospective controlled clinical trials that specifically address bone health in HCT, the answers to the FAQs rely on evidence derived from retrospective HCT studies, results extrapolated from prospective studies in non-HCT settings, relevant societal guidelines, and expert panel opinion. Given the heterogenous comorbidities and needs of individual HCT recipients, answers to FAQs in this article should be considered general recommendations, with good medical practice and judgment ultimately dictating care of individual patients. Readers are referred to the Supplementary Material for answers to additional FAQs that did not make the core set.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Densidad Ósea , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Estudios Prospectivos , Estudios Retrospectivos , Estados Unidos
15.
N Engl J Med ; 376(5): 440-450, 2017 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-27959709

RESUMEN

BACKGROUND: Continuous-flow left ventricular assist systems increase the rate of survival among patients with advanced heart failure but are associated with the development of pump thrombosis. We investigated the effects of a new magnetically levitated centrifugal continuous-flow pump that was engineered to avert thrombosis. METHODS: We randomly assigned patients with advanced heart failure to receive either the new centrifugal continuous-flow pump or a commercially available axial continuous-flow pump. Patients could be enrolled irrespective of the intended goal of pump support (bridge to transplantation or destination therapy). The primary end point was a composite of survival free of disabling stroke (with disabling stroke indicated by a modified Rankin score >3; scores range from 0 to 6, with higher scores indicating more severe disability) or survival free of reoperation to replace or remove the device at 6 months after implantation. The trial was powered for noninferiority testing of the primary end point (noninferiority margin, -10 percentage points). RESULTS: Of 294 patients, 152 were assigned to the centrifugal-flow pump group and 142 to the axial-flow pump group. In the intention-to-treat population, the primary end point occurred in 131 patients (86.2%) in the centrifugal-flow pump group and in 109 (76.8%) in the axial-flow pump group (absolute difference, 9.4 percentage points; 95% lower confidence boundary, -2.1 [P<0.001 for noninferiority]; hazard ratio, 0.55; 95% confidence interval [CI], 0.32 to 0.95 [two-tailed P=0.04 for superiority]). There were no significant between-group differences in the rates of death or disabling stroke, but reoperation for pump malfunction was less frequent in the centrifugal-flow pump group than in the axial-flow pump group (1 [0.7%] vs. 11 [7.7%]; hazard ratio, 0.08; 95% CI, 0.01 to 0.60; P=0.002). Suspected or confirmed pump thrombosis occurred in no patients in the centrifugal-flow pump group and in 14 patients (10.1%) in the axial-flow pump group. CONCLUSIONS: Among patients with advanced heart failure, implantation of a fully magnetically levitated centrifugal-flow pump was associated with better outcomes at 6 months than was implantation of an axial-flow pump, primarily because of the lower rate of reoperation for pump malfunction. (Funded by St. Jude Medical; MOMENTUM 3 ClinicalTrials.gov number, NCT02224755 .).


Asunto(s)
Insuficiencia Cardíaca/terapia , Corazón Auxiliar , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Insuficiencia Cardíaca/mortalidad , Corazón Auxiliar/efectos adversos , Humanos , Análisis de Intención de Tratar , Estimación de Kaplan-Meier , Persona de Mediana Edad , Diseño de Prótesis , Falla de Prótesis , Accidente Cerebrovascular/etiología , Trombosis/etiología , Adulto Joven
16.
Phys Rev Lett ; 122(18): 183901, 2019 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-31144892

RESUMEN

The forces acting on optically trapped particles are commonly assumed to be conservative. Nonconservative scattering forces induce toroidal currents in overdamped liquid environments, with negligible effects on position fluctuations. However, their impact in the underdamped regime remains unexplored. Here, we study the effect of nonconservative scattering forces on the underdamped nonlinear dynamics of trapped nanoparticles at various air pressures. These forces induce significant low-frequency position fluctuations along the optical axis and the emergence of toroidal currents in both position and velocity variables. Our experimental and theoretical results provide fundamental insights into the functioning of optical tweezers and a means for investigating nonequilibrium steady states induced by nonconservative forces.

17.
Biomacromolecules ; 20(4): 1699-1708, 2019 04 08.
Artículo en Inglés | MEDLINE | ID: mdl-30807696

RESUMEN

Complex three-dimensional (3D) pore geometries, useful for tissue engineering scaffolds, can be fabricated via photo-crosslinking of resorbable poly(propylene fumarate) (PPF) resins using stereolithography (SLA) and/or continuous digital light processing (cDLP) methods. Physico-chemical parameters inherent to 3D printable resin design, include viscosity, polymer concentration, degree of polymerization, and resin printing temperature. We report here on our study of these parameters and their influence the cDLP 3D printing process and the resulting mechanical properties. A series of PPF oligomers were synthesized by the ring-opening copolymerization (ROCOP) of maleic anhydride and propylene oxide followed by a base-catalyzed isomerization. The resin viscosities were measured as a function of number-average molecular mass ([Formula: see text]) of the PPF oligomers (1.1, 1.7 and 2.0 kDa), concentrations of PPF in the reactive diluent diethyl fumarate (DEF) (50 and 75 wt %) and resin temperature (25 to 55 °C). The zero-shear viscosity (η0) of the resins was found to be temperature-dependent and follow a linear Arrhenius relationship. Tensile tests demonstrated mechanical properties within the range of trabecular bone, with the ultimate strength at break above 15 MPa and elastic moduli between 178 and 199 MPa.


Asunto(s)
Materiales Biocompatibles/química , Fumaratos/química , Anhídridos Maleicos/química , Polimerizacion , Polipropilenos/química , Impresión Tridimensional , Viscosidad
18.
Biomacromolecules ; 20(12): 4345-4352, 2019 12 09.
Artículo en Inglés | MEDLINE | ID: mdl-31661252

RESUMEN

Poly(propylene fumarate) (PPF) has shown potential for the treatment of bone defects as it can be 3D printed into scaffolds to suit patient-specific needs with strength comparable to that of bone. However, the lack of specific cell attachment and osteogenic signaling moieties have limited their utility as it is necessary to provide these signals to aid in bone tissue formation. To address this issue and provide a platform for functionalization, Bioglass (∼1-2 µm) microparticles have been incorporated into PPF to create a 3D printable resin with concentrations ranging from 0 to 10 wt %. The zero-shear viscosity of PPF-Bioglass resins increased proportionally from 0 to 2.5 wt % Bioglass, with values of 0.22 and 0.34 Pa·s, respectively. At higher Bioglass concentrations, 5 and 10 wt %, the resin viscosity increased to 0.44 and 1.31 Pa·s, exhibiting a 2- and 6-fold increase from the 0 wt % Bioglass resin. Despite this increase in viscosity, all resins remained printable with no print failures. In addition, the surface available Bioglass can tether catechol containing molecules for postprinting functionalization. Analysis of PPF-Bioglass functionalization using a catechol dye analyte shows functionalization increases with Bioglass concentration, up to 157 nmol/cm2, and demonstrates it is possible to modulate functionalization. This presents a versatile and highly translationally relevant strategy to functionalize 3D printed scaffolds post printing with a diverse array of functional species.


Asunto(s)
Cerámica/química , Fumaratos/química , Polipropilenos/química , Impresión Tridimensional , Andamios del Tejido/química
19.
Oral Dis ; 25 Suppl 1: 193-203, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31034120

RESUMEN

OBJECTIVE: To detail a scoping review on the global and regional relative frequencies of oral mucosal disorders in the children based on both clinical studies and those reported from biopsy records. MATERIALS AND METHODS: A literature search was completed from 1 January 1990 to 31 December 2018 using PubMed and EMBASE. RESULTS: Twenty clinical studies (sample size: 85,976) and 34 studies from biopsy services (40,522 biopsies) were included. Clinically, the most frequent conditions were aphthous ulcerations (1.82%), trauma-associated lesions (1.33%) and herpes simplex virus (HSV)-associated lesions (1.33%). Overall, the most commonly biopsied lesions were mucoceles (17.12%), fibrous lesions (9.06%) and pyogenic granuloma (4.87%). By WHO geographic region, the pooled relative frequencies of the most common oral lesions were similar between regions in both clinical and biopsy studies. Across regions, geographic tongue (migratory glossitis), HSV lesions, fissured tongue and trauma-associated ulcers were the most commonly reported paediatric oral mucosal lesions in clinical studies, while mucoceles, fibrous lesions and pyogenic granuloma were the most commonly biopsied lesions. CONCLUSIONS: The scoping review suggests data from the clinical studies and biopsy records shared similarities in the most commonly observed mucosal lesions in children across regions. In addition, the majority of lesions were benign in nature.


Asunto(s)
Enfermedades de la Boca/epidemiología , Úlceras Bucales/epidemiología , Estomatitis Aftosa/epidemiología , Biopsia , Niño , Congresos como Asunto , Humanos , Enfermedades de la Boca/diagnóstico , Mucosa Bucal/patología , Medicina Oral , Úlceras Bucales/diagnóstico , Estomatitis Aftosa/patología
20.
J Chem Phys ; 148(8): 084503, 2018 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-29495772

RESUMEN

Starting from the stochastic equation for the density operator, we formulate the exact (instantaneous) stress tensor for interacting Brownian particles and show that its average value agrees with expressions derived previously. We analyze the relation between the stress tensor and forces due to external potentials and observe that, out of equilibrium, particle currents give rise to extra forces. Next, we derive the stress tensor for a Landau-Ginzburg theory in generic, non-equilibrium situations, finding an expression analogous to that of the exact microscopic stress tensor, and discuss the computation of out-of-equilibrium (classical) Casimir forces. Subsequently, we give a general form for the stress tensor which is valid for a large variety of energy functionals and which reproduces the two mentioned cases. We then use these relations to study the spatio-temporal correlations of the stress tensor in a Brownian fluid, which we compute to leading order in the interaction potential strength. We observe that, after integration over time, the spatial correlations generally decay as power laws in space. These are expected to be of importance for driven confined systems. We also show that divergence-free parts of the stress tensor do not contribute to the Green-Kubo relation for the viscosity.

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