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1.
Plast Reconstr Surg ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38589990

RESUMO

PURPOSE: Merit-based incentive payment system (MIPS) is a payment model implemented to promote high-value care through performance-based adjustments of Medicare reimbursements. Higher scores indicate superior performance in healthcare quality, efficiency, and interoperability, which can result in financial advantages. Given the paucity of literature, we aimed to characterize plastic surgery performance in MIPS. METHOD: The Centers for Medicare and Medicaid Services (CMS) online data repository was queried for data on MIPS performance of plastic surgeons from 2019-2021. Descriptive analyses and multivariable logistic regression were conducted to identify predictors of receiving bonus payment for exceptional performance. RESULTS: Approximately 1400 surgeons were sampled in each year. The median number of Medicare beneficiaries and percent of dually eligible beneficiaries-eligible for Medicare and Medicaid-were higher in 2019 (p<0.001). Beneficiary median HCC risk score, which measures expected healthcare costs and needs based on health status, was lower in 2021 (p<0.001). The most common reporting schema was reporting as a group. Total MIPS score increased from 2019 to 2020 to 2021 (90.2 vs 96.4 vs 98.3, p<0.001), but quality score progressively decreased (98.8 vs 95.5 vs 89.90, p<0.001). Fewer physicians received positive adjustment and bonus payments in 2020 and 2021. Predictors of receiving bonus payments were reporting as an alternative payment model, practice size >24, and having 10-49% of dually eligible beneficiaries (p<0.05). CONCLUSION: Understanding performance of plastic surgeons in MIPS can guide future policy direction and ensure that high-quality care translates into improved patient outcomes across all fields and levels of social vulnerability.

4.
Prev Sci ; 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37728810

RESUMO

The stepped wedge design is often used to evaluate interventions as they are rolled out across schools, health clinics, communities, or other clusters. Most models used in the design and analysis of stepped wedge trials assume that the intervention effect is immediate and constant over time following implementation of the intervention (the "exposure time"). This is known as the IT (immediate treatment effect) assumption. However, recent research has shown that using methods based on the IT assumption when the treatment effect varies over exposure time can give extremely misleading results. In this manuscript, we discuss the need to carefully specify an appropriate measure of the treatment effect when the IT assumption is violated and we show how a stepped wedge trial can be powered when it is anticipated that the treatment effect will vary as a function of the exposure time. Specifically, we describe how to power a trial when the exposure time indicator (ETI) model of Kenny et al. (Statistics in Medicine, 41, 4311-4339, 2022) is used and the estimand of interest is a weighted average of the time-varying treatment effects. We apply these methods to the ADDRESS-BP trial, a type 3 hybrid implementation study designed to address racial disparities in health care by evaluating a practice-based implementation strategy to reduce hypertension in African American communities.

5.
Implement Sci Commun ; 3(1): 96, 2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068611

RESUMO

BACKGROUND: Hypertension (HTN) control among Blacks in the USA has become a major public health challenge. Barriers to HTN control exist at multiple levels including patient, physician, and the health system. Patients also encounter significant community-level barriers, such as poor linkage to social services that impact health (unstable housing, food access, transportation). We describe a multi-component needs assessment to inform the development, implementation, and evaluation of a program to improve HTN management within a large healthcare system in New York City (NYC). METHODS: Guided by the Community-Based Participatory Research (CBPR) and Consolidated Framework for Implementation Research (CFIR) frameworks, data will be collected from four main sources: (1) quantitative surveys with health systems leadership, providers, and staff and with community-based organizations (CBOs) and faith-based organizations (FBOs); (2) qualitative interviews and focus groups with health systems leadership, providers, and staff and with CBOs and FBOs; (3) NYC Community Health Survey (CHS); and (4) New York University (NYU) Health system Epic Electronic Health Record (EHR) system. The data sources will allow for triangulation and synthesis of findings. DISCUSSION: Findings from this comprehensive needs assessment will inform the development of a clinic-community-based practice facilitation program utilizing three multi-level evidence-based interventions (nurse case management, remote blood pressure (BP) monitoring, and social determinants of health (SDoH) support) integrated as a community-clinic linkage model for improved HTN control in Black patients. Integration of stakeholders' priorities, perspectives, and practices into the development of the program will improve adoption, sustainability, and the potential for scale-up. TRIAL REGISTRATION: NCT05208450; registered on January 26, 2022.

6.
Biomaterials ; 34(19): 4582-91, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23528228

RESUMO

Based on a porcine model with surgically created myocardial infarction (MI) as a pre-clinical scheme, this study investigates the clinical translation of cell sheet fragments of autologous mesenchymal stem cells (MSCs) for cellular cardiomyoplasty. MSC sheet fragments retaining endogenous extracellular matrices are fabricated using a thermo-responsive methylcellulose hydrogel system. Echocardiographic observations indicate that transplantation of MSC sheet fragments in infarcted hearts can markedly attenuate the adverse ventricular dilation and preserve the cardiac function post MI, which is in contrast to the controlled groups receiving saline or dissociated MSCs. Additionally, histological analyses suggest that administering MSC sheet fragments significantly prevents the scar expansion and left ventricle remodeling after MI. Immunohistochemistry results demonstrate that the engrafted MSCs can differentiate into endothelial cells and smooth muscle cells, implying that angiogenesis and the subsequent regional perfusion improvement is a promising mechanism for ameliorating post-infarcted cardiac function. However, according to the data recorded by an implantable loop recorder, the transplanted MSCs may provoke arrhythmia. Nevertheless, the proposed approach may potentially lead to the eventual translation of MSC-based therapy into practical and effective clinical treatments.


Assuntos
Cardiomioplastia/métodos , Transplante de Células-Tronco Mesenquimais/métodos , Infarto do Miocárdio/cirurgia , Miocárdio/patologia , Animais , Arritmias Cardíacas/etiologia , Células Cultivadas , Ecocardiografia , Hidrogéis/química , Transplante de Células-Tronco Mesenquimais/efeitos adversos , Células-Tronco Mesenquimais/citologia , Metilcelulose/química , Infarto do Miocárdio/patologia , Suínos , Engenharia Tecidual/métodos , Alicerces Teciduais/química
7.
Biomaterials ; 33(7): 2127-36, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22169824

RESUMO

Cell transplantation is a promising strategy for therapeutic treatment of ischemic heart diseases. In this study, cord blood mesenchymal stem cells (cbMSCs) and human umbilical vein endothelial cells (HUVECs) in the form of core-shell bodies (cbMSC/HUVEC bodies) were prepared to promote vascularization and restore heart functions in an experimentally-created myocardial infarction (MI) rat model. Saline, cbMSC bodies and HUVEC bodies were used as controls. In vitro results indicated that cbMSC/HUVEC bodies possessed the capability of heterotypic assembly of cbMSCs and HUVECs into robust and durable tubular networks on Matrigel. The up-regulated gene expressions of VEGF and IGF-1 reflected the robust expansion of tubular networks; in addition, the augmented levels of SMA and SM22 suggested smooth muscle differentiation of cbMSCs, possibly helping to improve the durability of networks. Moreover, according to the in vivo echocardiographic, magnetic resonance and computed-tomographic results, transplantation of cbMSC/HUVEC bodies benefited post-MI dysfunction. Furthermore, the vascularization analyses demonstrated the robust vasculogenic potential of cbMSC/HUVEC bodies in vivo, thus contributing to the greater viable myocardium and the less scar region, and ultimately restoring the cardiac function. The concept of core-shell bodies composed of perivascular cells and endothelial cells may serve as an attractive cell delivery vehicle for vasculogenesis, thus improving the cardiac function significantly.


Assuntos
Células Endoteliais da Veia Umbilical Humana/transplante , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Infarto do Miocárdio/terapia , Neovascularização Fisiológica/fisiologia , Animais , Células Cultivadas , Humanos , Imageamento por Ressonância Magnética , Células-Tronco Mesenquimais/citologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miocárdio/citologia , Miocárdio/metabolismo , Miocárdio/patologia , Ratos , Tomografia Computadorizada de Emissão de Fóton Único
8.
Biomaterials ; 32(33): 8446-55, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21871659

RESUMO

Rapid induction and creation of functional vascular networks is essential for the success of treating ischemic tissues. The formation of mature and functional vascular networks requires the cooperation of endothelial cells (ECs) and perivascular cells. In the study, we used a thermo-responsive hydrogel system to fabricate core-shell cell bodies composed of cord-blood mesenchymal stem cells (cbMSCs) and human umbilical vascular ECs (HUVECs) for functional vasculogenesis. When seeded on Matrigel, the shelled HUVECs attempted to interact and communicate vigorously with the cored cbMSCs initially. Subsequently, HUVECs migrated out and formed tubular structures; cbMSCs were observed to coalesce around the HUVEC-derived tubes. With time progressing, the tubular networks continued to expand without regression, indicating that cbMSCs might function as perivascular cells to stabilize the nascent networks. In the in vivo study, cbMSC/HUVEC bodies were embedded in Matrigel and implanted subcutaneously in nude mice. At day 7, visible blood-filled vessels were clearly identified within the implant containing cbMSC/HUVEC bodies, indicating that the formed vessels anastomosed with the host vasculature. The cored cbMSCs were stained positive for smooth muscle actin, suggesting that they underwent smooth muscle differentiation and formed microvessels with the shelled HUVECs, as the role of perivascular cells. These data confirm that the formation of mature vessels requires heterotypic cooperation of HUVECs and MSCs. This study provides a new strategy for therapeutic vasculogenesis, by showing the feasibility of using cbMSC/HUVEC bodies to create functional vascular networks.


Assuntos
Endotélio Vascular/citologia , Células-Tronco Mesenquimais/citologia , Animais , Sequência de Bases , Células Cultivadas , Primers do DNA , Sangue Fetal/citologia , Humanos , Camundongos , Camundongos Nus , Reação em Cadeia da Polimerase em Tempo Real , Cordão Umbilical/citologia
9.
Biomaterials ; 32(24): 5558-67, 2011 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-21555151

RESUMO

Stem cell transplantation may repair the infarcted heart. Despite the encouraging preliminary results, an optimal cell type used and low retention of the transplanted cells remain to be overcome. In this study, a multiwelled methylcellulose hydrogel system was used to cultivate human amniotic-fluid stem cells (hAFSCs) to form spherically symmetric cell bodies for cellular cardiomyoplasty. The grown hAFSC bodies enriched with extracellular matrices (ECM) were xenogenically transplanted in the peri-infarct area of an immune-suppressed rat, via direct intramyocardial injection. Results of bioluminescence imaging and real-time PCR revealed that hAFSC bodies could considerably enhance cell retention and engraftment in short-term and long-term observations, when compared with dissociated hAFSCs. Echocardiography and magnetic resonance imaging showed that the enhanced cell engraftment in the hAFSC-body group could significantly attenuate the progression of heart failure, improve the global function, and increase the regional wall motion. At the infarct, expressions of HGF, bFGF and VEGF were significantly up-regulated, an indication of the significantly increased vessel densities in the hearts treated with hAFSC bodies. The injected hAFSC bodies could undergo differentiation into angiogenic and cardiomyogenic lineages and contribute to functional benefits by direct regeneration. The aforementioned results demonstrate that hAFSC bodies can attenuate cell loss after intramuscular injection by providing an adequate physical size and offering an enriched ECM environment to retain the transplanted cells in the myocardium, thus improving heart function.


Assuntos
Líquido Amniótico/citologia , Terapia Baseada em Transplante de Células e Tecidos/métodos , Infarto do Miocárdio/terapia , Transplante de Células-Tronco/métodos , Animais , Células Cultivadas , Ecocardiografia , Matriz Extracelular/metabolismo , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Imageamento por Ressonância Magnética , Masculino , Metilcelulose/química , Infarto do Miocárdio/metabolismo , Reação em Cadeia da Polimerase , Ratos , Ratos Endogâmicos Lew
10.
Tissue Eng Part C Methods ; 17(6): 651-61, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21375393

RESUMO

Engineering three-dimensional (3D) cell-dense tissues with a well-organized structure remains a challenge in tissue engineering. In this study, highly oriented fibrous bundles, consisted of composite fibers of poly(L-lactide-co-glycolide)/superparamagnetic iron oxide nanoparticles, were fabricated using an electrospinning technique. The magnetic properties of the fabricated fibrous bundles were examined by a vibrating sample magnetometer and a superconducting quantum interference device; the results demonstrate that the fabricated fibrous bundles revealed superparamagnetic behavior without magnetic hysteresis. After seeding C2C12 myoblasts on the fibrous bundles, cells were grown along the direction of the underlying fibers (cell rods), an aligned pattern similar to those in native skeletal muscle tissues. When treated with the differentiation medium, myoblasts were fused together and formed multinucleated myotubes. As soon as applying an external magnetic field, the cell rods can spontaneously response to the magnetic control and self-assemble into 3D tissues with a highly ordered architecture. These findings demonstrate that the magnetically susceptible fibrous bundles not only can serve as a functional unit providing the topographic cue for cell orientation, but also can be magnetically manipulated for the creation of 3D cell-dense constructs. This technique may be applied to various cell types and scaffold configurations, thus advancing the design of engineered tissues that more closely replicate native tissues.


Assuntos
Mioblastos/citologia , Mioblastos/fisiologia , Engenharia Tecidual/instrumentação , Engenharia Tecidual/métodos , Animais , Diferenciação Celular/efeitos da radiação , Linhagem Celular , Movimento Celular/fisiologia , Eletroquímica/métodos , Campos Eletromagnéticos , Camundongos , Mioblastos/efeitos da radiação , Doses de Radiação , Rotação
11.
Biomaterials ; 31(25): 6444-53, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20621766

RESUMO

Direct intramyocardial injection of the desired cell types in a dissociated form is a common route of cell transplantation for repair of damaged myocardium. However, following injection of dissociated cells, a massive loss of transplanted cells has been reported. In this study, human amniotic fluid stem cells (hAFSCs) were used as the cell source for the fabrication of cell sheet fragments, using a thermo-responsive methylcellulose hydrogel system. The fabricated hAFSC sheet fragments preserved the endogenous extracellular matrices (ECM) and retained their cell phenotype. Test samples were xenogenically transplanted into the peri-ischemic area of an immune-suppressed rat model at 1 week after myocardial infarction (MI) induction. There were four treatment groups (n>=10): sham; saline; dissociated hAFSCs; and hAFSC sheet fragments. The results obtained in the echocardiography revealed that the group treated with hAFSC sheet fragments had a superior heart function to those treated with saline or dissociated hAFSCs. Due to their inherent ECM, hAFSC sheet fragments had a better ability of cell retention and proliferation than dissociated hAFSCs upon transplantation to the host myocardium. Additionally, transplantation of hAFSC sheet fragments stimulated a significant increase in vascular density, consequently contributing towards improved wall thickness and a reduction in the infarct size, when compared with dissociated hAFSCs. Our histological findings and qPCR analyses suggest that the transplanted hAFSCs can be differentiated into cardiomyocyte-like cells and cells of endothelial lineages and modulate expression of multiple angiogenic cytokines and cardiac protective factor with the potential to promote neo-vascularization, which evidently contributed to the improvement of ventricular function.


Assuntos
Líquido Amniótico/citologia , Coração/fisiopatologia , Metilcelulose , Infarto do Miocárdio/terapia , Transplante de Células-Tronco , Células-Tronco/citologia , Animais , Humanos , Hidrogel de Polietilenoglicol-Dimetacrilato/química , Terapia de Imunossupressão , Injeções , Metilcelulose/química , Infarto do Miocárdio/fisiopatologia , Miocárdio/patologia , Miócitos Cardíacos/citologia , Neovascularização Fisiológica , Ratos , Transplante de Células-Tronco/métodos
12.
Tissue Eng Part A ; 16(6): 1925-36, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20067384

RESUMO

Human amniotic fluid stem cells (hAFSCs) derived from second-trimester amniocentesis were evaluated for the therapeutic potential of cardiac repair. Whether hAFSCs can be differentiated into cardiomyogenic cells and toward the maturation of endothelial cell lineage was investigated in vitro using mimicking differentiation milieu. Employing an immune-suppressed rat model with experimental myocardial infarction, an intramyocardial injection was conducted with a needle directly into the peri-infarct areas. There were three treatment groups: sham, saline, and hAFSCs (n > or = 10). When cultured with rat neonatal cardiomyocytes or in endothelial growth medium-2 enriched with vascular endothelial growth factor, hAFSCs were differentiated into cardiomyocyte-like cells and cells of endothelial lineage, respectively. After 4 weeks, hAFSC-treated animals showed a preservation of the infarcted thickness, an attenuation of left ventricle remodeling, a higher vascular density, and thus an improvement in cardiac function, when compared with the saline injection group. Survival and proliferation of the transplanted hAFSCs were revealed by immunohistochemical staining. Expressions of the cardiac-specific markers such as Nkx2.5, alpha-actinin, and cardiac Troponin T were observed in the transplanted hAFSCs. Additionally, Cx43 was clearly expressed at the borders of the transplanted/transplanted and host/transplanted cells, an indication of enhancement of cell connection. The results demonstrated that hAFSCs induce angiogenesis, have cardiomyogenic potential, and may be used as a new cell source for cellular cardiomyoplasty.


Assuntos
Líquido Amniótico/citologia , Cardiomioplastia/métodos , Células Endoteliais/citologia , Miócitos Cardíacos/citologia , Células-Tronco/citologia , Actinina/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Células Endoteliais/metabolismo , Proteína Homeobox Nkx-2.5 , Proteínas de Homeodomínio/metabolismo , Humanos , Imuno-Histoquímica , Masculino , Infarto do Miocárdio/terapia , Miócitos Cardíacos/metabolismo , Ratos , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Fatores de Transcrição/metabolismo , Troponina T/metabolismo , Fator A de Crescimento do Endotélio Vascular/farmacologia , Remodelação Ventricular/efeitos dos fármacos , Remodelação Ventricular/fisiologia
13.
Biomaterials ; 30(29): 5505-13, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19631978

RESUMO

Typical cell transplantation techniques involve the administration of dissociated cells directly injected into muscular tissues; however, retention of the transplanted cells at the sites of the cell graft is frequently limited. An approach, using spherically symmetric aggregates of cells with a relatively uniform size self-assembled in a thermo-responsive methylcellulose hydrogel system, is reported in the study. The obtained cell aggregates preserved their endogenous extracellular matrices (ECM) and intercellular junctions because no proteolytic enzyme was used when harvesting the cell aggregates. Most of the cells within aggregates (with a radius of approximately 100 microm) were viable as indicated by the live/dead staining assay. After injection through a needle, the cell aggregates remained intact and the cells retained their activity upon transferring to another growth surface. The cell aggregates obtained under sterile conditions were transplanted into the skeletal muscle of rats via local injection. The dissociated cells were used as a control. It was found that the cell aggregates can provide an adequate physical size to entrap into the muscular interstices and offer a favorable ECM environment to enhance retention of the transplanted cells at the sites of the cell graft. These results indicated that the spherically symmetric cell aggregates developed in the study may serve as a cell delivery vehicle for therapeutic applications.


Assuntos
Células da Medula Óssea/citologia , Células da Medula Óssea/fisiologia , Transplante de Medula Óssea/métodos , Técnicas de Cultura de Células/métodos , Hidrogéis/química , Músculo Esquelético/citologia , Músculo Esquelético/cirurgia , Animais , Materiais Biocompatíveis/química , Agregação Celular , Células Cultivadas , Injeções , Teste de Materiais , Camundongos , Ratos , Ratos Endogâmicos Lew , Esferócitos , Temperatura
14.
Stem Cells ; 27(3): 724-32, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19259939

RESUMO

Cell transplantation via direct intramyocardial injection is a promising therapy for patients with myocardial infarction; however, retention of the transplanted cells at the injection sites remains a central issue following injection of dissociated cells. Using a thermoresponsive hydrogel system with a multiwell structure, we successfully developed an efficient technique to generate spherically symmetric bodies of mesenchymal stromal cells (MSCs) inherent with endogenous extracellular matrices (ECMs) for direct intramyocardial injection. After injection through a needle and upon transferring to another growth surface, the time required to attach, migrate, and proliferate was significantly shorter for the MSC bodies than the dissociated MSCs. Employing a syngeneic rat model with experimental myocardial infarction, an intramyocardial injection was conducted with a needle directly into the peri-infarct areas. There were four treatment groups (n = 10): sham, phosphate-buffered saline, dissociated MSCs, and MSC bodies. The results obtained in the echocardiography and catheterization measurements demonstrated that the MSC body group had a superior heart function to the dissociated MSC group. Histologically, it was found that MSC bodies could provide an adequate physical size to entrap into the interstices of muscular tissues and offer a favorable ECM environment to retain the transplanted cells intramuscularly. Additionally, transplantation of MSC bodies stimulated a significant increase in vascular density, thus improving the cardiac function. These results indicated that the spherically symmetric bodies of MSCs developed in the study may serve as a cell-delivery vehicle and improve the efficacy of therapeutic cell transplantation.


Assuntos
Cardiomioplastia/métodos , Matriz Extracelular/metabolismo , Transplante de Células-Tronco Mesenquimais/métodos , Infarto do Miocárdio/terapia , Animais , Células Cultivadas , Ecocardiografia , Masculino , Células-Tronco Mesenquimais/citologia , Ratos , Ratos Endogâmicos Lew , Células Estromais/transplante , Função Ventricular Esquerda
15.
Cardiovasc Res ; 80(1): 88-95, 2008 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-18539631

RESUMO

AIMS: To provide the basis for uniform cardiac tissue regeneration, a spatially uniform distribution of adhered cells within a scaffold is a prerequisite. To achieve this goal, a bioengineered tissue graft consisting of a porous tissue scaffold sandwiched with multilayered sheets of mesenchymal stromal cells was developed. METHODS AND RESULTS: This tissue graft (sandwiched patch) was used to replace the infarcted wall in a syngeneic Lewis rat model with an experimentally chronic myocardial infarction (MI). There were four treatment groups (n >/= 10): sham, MI, empty patch, and sandwiched patch. After a 7 day culture of the sandwiched patch, a tissue graft with relatively uniform cell concentrations was obtained. The cells were viable and tightly adhered to the tissue scaffold, as the endogenous extracellular matrix inherent with multilayered cell sheets can act as an adhesive agent for cell attachment and retention. At retrieval, the area of the empty patch was relatively enlarged, suggesting reduced structural support, while that of the sandwiched patch remained about the same (P = 0.56). In the immunofluorescent staining, host cells together with neo-microvessels were clearly observed in the empty patch; however, there were still a large number of unfilled pores within the patch. In the sandwiched patch, besides host cells, originally seeded cells were populated within the entire patch. No apparent evidence of apoptotic cell death was found in both studied patches. Thus, the sandwiched-patch-treated hearts demonstrated a better heart function to the empty-patch-treated hearts (P < 0.05). CONCLUSION: The results demonstrated that this novel bioengineered tissue graft can serve as a useful cardiac patch to restore the dilated left ventricle and stabilize heart functions after MI.


Assuntos
Regeneração Tecidual Guiada , Transplante de Células-Tronco Mesenquimais , Infarto do Miocárdio/terapia , Alicerces Teciduais , Animais , Bovinos , Masculino , Infarto do Miocárdio/patologia , Miocárdio/patologia , Pericárdio/transplante , Ratos , Ratos Endogâmicos Lew , Função Ventricular Esquerda
16.
Biomaterials ; 29(26): 3547-56, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18538386

RESUMO

Growing three-dimensional scaffolds that contain more than a few layers of seeded cells is crucial for the creation of thick and viable cardiac tissues. To achieve this goal, a bioengineered cardiac patch (the MSC patch) composed of a sliced porous biological scaffold inserted with multilayered mesenchymal stem cells (MSCs) was developed for myocardial repair in a syngeneic rat model. After culture, sliced layers of the scaffold were stuck together and seeded MSCs were redistributed throughout the scaffold. Immunofluorescence analyses indicated that cells were viable and tightly adhered to a robust fibronectin meshwork within the scaffold. Results of echocardiography and heart catheterization revealed that the MSC-patch group had a superior heart function to the infarct group. Cells together with neo-muscle fibers and neo-microvessels were clearly observed in the entire MSC patch to fill its original pores, indicating that the implanted patch became well integrated into the host. The thickness of the retrieved MSC patch increased significantly as compared to that before implantation. When compared with the infarct group, expressions of angiogenic cytokines (bFGF, vWF and PDGF-B) and cardioprotective factors (IGF-1 and HGF) were significantly increased in the MSC-patch group. The aforementioned results indicated that transplantation of the MSC patch could restore the dilated LV and preserve cardiac functions after infarction.


Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/fisiologia , Miocárdio/patologia , Engenharia Tecidual/métodos , Alicerces Teciduais , Animais , Materiais Biocompatíveis/metabolismo , Células Cultivadas , Coração/anatomia & histologia , Coração/fisiologia , Masculino , Teste de Materiais , Células-Tronco Mesenquimais/citologia , Miocárdio/citologia , Miocárdio/metabolismo , Ratos , Ratos Endogâmicos Lew
17.
J Biol Chem ; 283(4): 1882-92, 2008 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-18042541

RESUMO

Akt is a protein serine/threonine kinase that is involved in the regulation of diverse cellular processes. Phosphorylation of Akt at regulatory residues Thr-308 and Ser-473 leads to its full activation. The protein phosphatase 2A (PP2A) has long been known to negatively regulate Akt activity. The PP2A holoenzyme consists of the structural subunit (A), catalytic subunit (C), and a variable regulatory subunit (B). Here we report the identification of the specific B regulatory subunit that targets the PP2A holoenzyme to Akt. We found endogenous association of PP2A AB55C holoenzymes with Akt by co-immunoprecipitation analyses in pro-lymphoid FL5.12 cells. Akt was shown to associate with ectopically expressed B55alpha subunit in NIH3T3 cells. The direct interaction between B55alpha subunit and Akt was confirmed using in vitro pulldown analyses. Intriguingly, we found that overexpression of B55alpha subunit significantly impaired phosphorylation at Thr-308, but to a lesser extent at Ser-473 of Akt in both FL5.12 and NIH3T3 cells. Concomitantly, phosphorylation of a subset of Akt substrates, including FoxO3a, was substantially decreased by B55alpha overexpression in these cells. Silencing of B55alpha expression markedly increased phosphorylation at Thr-308 but not at Ser-473 in both FL5.12 cells and NIH3T3 cells. Consistently, PP2A AB55alphaC holoenzymes preferentially dephosphorylated phospho-Thr-308 rather than phospho-Ser-473 in in vitro dephosphorylation assays. Furthermore, B55alpha overexpression retarded proliferation of NIH3T3 cells, and knockdown of B55alpha expression increased survival of FL5.12 cells upon interleukin-3 deprivation. Together, our data demonstrate that B55alpha-dependent targeting of the PP2A holoenzyme to Akt selectively regulates Akt phosphorylation at Thr-308 to regulate cell proliferation and survival.


Assuntos
Proliferação de Células , Proteína Fosfatase 2/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Inativação Gênica , Holoenzimas/genética , Holoenzimas/metabolismo , Humanos , Interleucina-3/metabolismo , Interleucina-3/farmacologia , Camundongos , Células NIH 3T3 , Fosforilação/efeitos dos fármacos , Proteína Fosfatase 2/genética , Proteínas Proto-Oncogênicas c-akt/genética
18.
Gynecol Oncol ; 97(1): 68-73, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15790439

RESUMO

OBJECTIVE: Patients with stage I granulosa cell tumors (GCTs) may occasionally develop metastasis, which is hard to predict using pathologic criteria. It is interesting to elucidate whether certain chromosomal imbalances (CIs), detected by comparative genomic hybridization (CGH), could be useful prognostic markers. METHODS: CGH was used to identify CI(s) in 37 adult-type GCTs from 36 women. Nonrandom CIs were compared with clinical and pathological features to evaluate their significance as a prognostic marker. RESULTS: Twenty-two (61%) of the 36 primary tumors had CIs. One woman's tumor showed identical CIs to another tumor that occurred in contralateral ovary 2 years later, supporting a metastatic nature. The nonrandom CIs included losses of 22q (31%), 1p33-p36 (6%), 16p13.1 (6%), and 16q (6%) and gains of 14 (25%), 12 (14%), and 7p15-p21 (6%). No tumor exhibited high-level amplification. The associations between each CI and pathological features, including the growth pattern, tumor size, and mitotic activity, were not evident. The only CI repeatedly detected in tumors with metastasis was monosomy 22, which presented in 2 of the 4 cases with metastasis but also in 2 of the 5 cases without recurrence for more than 5 years. CONCLUSIONS: Monosomy 22 was the most common CI in GCTs, which often coexisted with trisomy 14 (in 55% cases). Deletion of 22q seems to be, albeit not very specific, associated with the risk of early metastases of stage I disease. The role of loss-of-function mutation(s) of certain putative tumor suppressor gene(s) on 22q is worthy of further investigations.


Assuntos
Aberrações Cromossômicas , Tumor de Células da Granulosa/genética , Neoplasias Ovarianas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Cromossomos Humanos Par 22/genética , Feminino , Tumor de Células da Granulosa/patologia , Humanos , Pessoa de Meia-Idade , Monossomia/genética , Monossomia/patologia , Estadiamento de Neoplasias , Hibridização de Ácido Nucleico , Neoplasias Ovarianas/patologia , Prognóstico
19.
J Formos Med Assoc ; 101(8): 588-92, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12440092

RESUMO

Advances in spiral computerized tomography (CT) have made rapid biphasic contrast-enhanced CT possible. This study evaluated the capability of biphasic contrast-enhanced spiral CT to detect hepatocellular carcinoma (HCC). A total of 125 patients (68 men and 57 women) with proven HCC underwent preliminary noncontrast (NC) scanning, followed by hepatic arterial phase (HAP) and portal venous phase (PVP) imaging. Contrast medium (80 mL, 300 mgI/mL) was administered routinely at a rate of 2 mL/second using an automated contrast injector under guidance software monitoring. Study of NC and PVP images without concurrent study of HAP images detected 131/171 (76.6%) cases of HCC. In contrast, combined study of NC, PVP, and HAP images detected 153/171 (89.5%) cases of HCC. Thus, combined study of NC and biphasic images was able to detect an additional 12.9% of HCC cases in comparison with conventional study of NC and PVP images only. All HCCs that were detectable only on HAP imaging were enhanced homogeneously with contrast medium during the arterial phase.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Meios de Contraste , Neoplasias Hepáticas/diagnóstico por imagem , Fígado/diagnóstico por imagem , Intensificação de Imagem Radiográfica/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
20.
J Am Med Inform Assoc ; 9(4): 311-9, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12087112

RESUMO

OBJECTIVE: User data and information about anatomy education were used to guide development of a learning environment that is efficient and effective. The research question focused on how to design instructional software suitable for the educational goals of different groups of users of the Visible Human data set. The ultimate goal of the study was to provide options for students and teachers to use different anatomy learning modules corresponding to key topics, for course work and professional training. DESIGN: The research used both qualitative and quantitative methods. It was driven by the belief that good instructional design must address learning context information and pedagogic content information. The data collection emphasized measurement of users' perspectives, experience, and demands in anatomy learning. MEASUREMENT: Users' requirements elicited from 12 focus groups were combined and rated by 11 researchers. Collective data were sorted and analyzed by use of multidimensional scaling and cluster analysis. RESULTS: A set of functions and features in high demand across all groups of users was suggested by the results. However, several subgroups of users shared distinct demands. The design of the learning modules will encompass both unified core components and user-specific applications. The design templates will allow sufficient flexibility for dynamic insertion of different learning applications for different users. CONCLUSION: This study describes how users' requirements, associated with users' learning experiences, were systematically collected and analyzed and then transformed into guidelines informing the iterative design of multiple learning modules. Information about learning challenges and processes was gathered to define essential anatomy teaching strategies. A prototype instrument to design and polish the Visible Human user interface system is currently being developed using ideas and feedback from users.


Assuntos
Anatomia Transversal , Anatomia/educação , Instrução por Computador/normas , Interface Usuário-Computador , Grupos Focais , Guias como Assunto , Humanos
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